Leukocyte rolling and extravasation in surgical inflammation after mechanical and laser-induced trauma in human patients.
Acute inflammations main characteristics are exudation of fluid and plasma proteins and emigration of leukocytes, predominantly neutrophils into inflamed tissue. We have previously demonstrated that leukocyte extravasation can be directly monitored in human patients in vivo after tunnel cataract operation, but at the same time we noticed that only certain manipulations trigger also leukocyte extravasation. To define the type of surgical manipulations triggering leukocyte extravasation, we tested a set of surgical manipulations affecting distinct anatomical components of the conjunctiva. This set included various combinations of epithelial, nerve, and/or blood vessel damage. Manipulations tested here were surgical conjunctival biopsy, low-energy Argon laser treatment (80 mJ) closing a venule temporarily, high-energy argon laser treatment (480 mJ) to occlude a venule firmly, and 193 nm eximer laser-based conjunctival phototherapeutic keratectomy (160 mJ). These manipulations were compared to previous findings on conjunctival inflammation following the standard cataract operation. In mechanical trauma models (cataract operation and conjunctival biopsy) clinical signs of inflammation, number of leukocytes rolling, and number of tissue emigrated leukocytes were notably higher compared to pre-operative levels on one day after the operation. No specific anatomical triggering component for inflammation, including epithelial, nerve, and/or blood vessel damage, was indentified, but rather the trauma mechanism itself appeared to be an essential factor. Surprisingly, in laser-induced traumas no increase in number of rolling cells, rolling velocity slowing, or elevation of tissue emigrated leukocytes took place compared to pre-operative levels. These findings suggest that laser-induced traumas differ fundamentally from the mechanical traumas at all levels of leukocyte extravasation cascade, and at least in our setup, inflammatory reaction can be avoided or triggered depending on surgical method used.


Exosomal microRNA-16-5p from macrophage exacerbates atherosclerosis via modulating mothers against decapentaplegic homolog 7.
Studies have probed the function of microRNA (miR)-16-5p in the progression of atherosclerosis (AS), while the regulatory function of exosomal miR-16-5p from macrophage on AS remains largely unknown. This study commits to exploring the efficiency of exosomal miR-16-5p from macrophage on AS via modulating mothers against decapentaplegic homolog 7 (SMAD7). Macrophages were cultured and transfected with miR-16-5p antagomir, then, the exosomes from macrophages were extracted. The AS mouse model was established, and miR-16-5p or SMAD7 expression in AS mice was detected. Thereafter, the effects of macrophage-derived exosomes, miR-16-5p or SMAD7 on serum inflammatory response, oxidative stress response, pathological changes and apoptosis in AS mice were observed by immunohistochemical and biochemical analysis. Finally, the binding relation between miR-16-5p and SMAD7 was examined. MiR-16-5p was elevated while SMAD7 was depleted in AS mice. Macrophage-derived exosomes aggravated AS progression via facilitating inflammatory response and oxidative stress, exacerbating pathological changes and increasing cell apoptosis in AS mice; while downregulation of miR-16-5p reversed the exacerbation of AS progression by macrophage-derived exosomes in AS mice. MiR-16-5p targeted SMAD7, and the down-regulated SMAD7 reversed the impacts of depleted miR-16-5p on AS progression. Exosomal miR-16-5p from macrophages aggravates AS progression via downregulating SMAD7 expression. This study provides novel therapeutic targets for AS treatment from the animal level.


Brain muscarinic receptor subtypes are differently affected in Alzheimer's disease and Parkinson's disease.
The muscarinic receptor subtypes determined by displacing [3H]quinuclidinyl benzylate by carbachol showed distinct profiles in Alzheimer's disease (AD) and in Parkinson's disease (PD). A decrease in the M2-receptor count was seen in the hippocampus in AD as compared to controls, while PD patients had unaltered binding. By contrast, PD patients had increased M2-binding in the frontal and temporal cortex, whereas unchanged binding was seen in AD. In PD the total number of cortical muscarinic receptors was negatively associated with the activity of ChAT, but had a positive correlation with the degree of dementia of the patients.


COVID-19 patients presenting with gangrenous acalculous cholecystitis: Report of two cases.
COVID-19 virus is thought to complicate underlying conditions, including acalculous cholecystitis. Two COVID-19 patients with gangrenous gallbladder are reported who were not involved with severe pneumonia. We present two non-critically ill patients with COVID-19 presenting with acalculous cholecystitis. Both patients had gangrenous gallbladder and had to undergo cholecystectomy. Upon surgery, one of the patients showed patchy gangrene on gallbladder and the other, a fully gangrenous gallbladder. There may be a possibility for COVID-19 patients with cholecystitis to develop ischemic gallbladder.


Regulation of TRAIL-induced apoptosis by XIAP in pancreatic carcinoma cells.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapy because of its relative tumor selectivity. However, many cancers including pancreatic cancer remain resistant towards TRAIL. To develop TRAIL for cancer therapy of pancreatic carcinoma, it will therefore be pivotal to elucidate the molecular mechanisms of TRAIL resistance. Here, we identify X-linked inhibitor of apoptosis (XIAP) as a regulator of TRAIL sensitivity in pancreatic carcinoma cells. Full activation of effector caspases, loss of mitochondrial membrane potential and cytochrome c release following TRAIL treatment were markedly impaired in pancreatic carcinoma cell lines, which poorly responded to TRAIL (PaTuII, PancTu1, ASPC1, DanG), compared to TRAIL-sensitive Colo357 pancreatic carcinoma cells. Stable downregulation of XIAP by RNA interference significantly reduced survival and enhanced TRAIL-induced apoptosis in pancreatic carcinoma cells. Also, downregulation of XIAP significantly increased CD95-induced cell death. Importantly, knockdown of XIAP strongly inhibited clonogenicity of pancreatic cancer cells treated with TRAIL indicating that XIAP promotes clonogenic survival of pancreatic carcinoma cells. Thus, our findings for the first time indicate that targeting XIAP represents a promising strategy to enhance the antitumor activity of TRAIL in pancreatic cancer, which has important clinical implications.


Reducing the suicide rate among veterinary surgeons: how the profession can help.
A short communication on page 415 of this issue of The Veterinary Record draws attention to the high suicide rate among members of the veterinary profession. In this article, Professor Richard Halliwell, who has recently chaired a series of meetings on this matter at the Royal College of Veterinary Surgeons, and Mr Brian Hoskin, chairman of the Veterinary Benevolent Fund, describe some of the support mechanisms available to veterinary surgeons and discuss what more might be done.


Pituitary regulation of sex-specific forms of cytochrome P-450 in liver microsomes of rats.
Effects of hypophysectomy and treatment with testosterone or estradiol on the sex-specific forms of cytochrome P-450, P-450-male and P-450-female, were examined. The amounts of P-450-male as well as drug oxidation activities were decreased by hypophysectomy of male rats. In female rats, drug oxidation activities were increased by hypophysectomy, which was associated with the disappearance of P-450-female and the appearance of P-450-male. Treatment of hypophysectomized female rats with testosterone or estrodiol effected minor changes in the amounts of P-450-male.


Orexin-A stimulates the expression of GLUT4 in a glucose dependent manner in the liver of orange-spotted grouper (Epinephelus coioides).
Orexins are hypothalamic neuropeptides involved in the central regulation of feeding behavior, sleep-wake cycle and other physiological functions. Orexin-A can regulate energy metabolism and increase glucose uptake, suggesting a role in glucose metabolism. In this study, we investigated the effects of orexin-A on GLUT4 mRNA and protein levels and the intracellular signaling mechanisms mediating orexin-A activity in the hepatocytes of grouper. Our results demonstrate that intraperitoneal injection of orexin-A increased the expression of GLUT4 in the liver, and this effect was significantly enhanced by co-injection of glucose. Treatment of primary cultured hepatocytes with either orexin-A or glucose alone had no effect on the expression of GLUT4, while co-treatment with orexin-A and glucose significantly increased the expression of GLUT4. This stimulatory effect was partially blocked by inhibitors to ERK1/2, JNK or p38 MAPK and was further blocked by an orexin receptor antagonist, which indicates that orexin-A could stimulate the expression of GLUT4 in a glucose dependent manner in primary hepatocytes via ERK1/2, JNK and p38 signaling. Our results suggest that orexin-A could play a pivotal role in stimulating glucose utilization in grouper, for a long-term goal, which might be useful in reducing costs in the aquaculture industry.


Ionic liquid-modified materials for solid-phase extraction and separation: a review.
In recent years, materials science has propelled to the research forefront. Ionic liquids with unique and fascinating properties have also left their footprints to the developments of materials science during the last years. In this review we highlight some of their recent advances and provide an overview at the current status of ionic liquid-modified materials applied in solid-phase extraction, liquid and gas chromatography and capillary electrochromatography with reference to recent applications. In addition, the potential of ionic liquids in the modification of capillary inner wall in capillary electrophoresis is demonstrated. The main target material modified with ionic liquids is silica, but polymers and monoliths have recently joined the studies. Although imidazolium is still clearly the most commonly used ionic liquid for the covalently modification of materials, the exploitation of pyridinium and phosphonium will most probably increase in the future.


Chromatographic separation of two heterogeneous forms of the catalytic subunit of cyclic AMP-dependent protein kinase holoenzyme type I and type II from striated muscle of different mammalian species.
Electrophoretically homogeneous preparations of catalytic subunit (C) of cAMP-dependent protein kinase isolated according to two different procedures from holoenzyme type I and type II from rabbit and from holoenzyme type II from rat skeletal muscle and from bovine cardiac muscle can be separated on carboxymethyl cellulose or on a Mono S column (Pharmacia) by salt gradient elution into two enzymatically active peaks called A and B, which do not interconvert on rechromatography. Cochromatography of peak A fractions or of peak B fractions derived from both holoenzymes respectively yields single enzyme peaks in each case, thus indicating that both represent different entities, which were named CA and CB. The separate character of both enzyme forms is supported by the fact that CB under all conditions is degraded faster by the C-specific protease (E. Alhanaty et al. (1981) Proc. Natl. Acad. Sci. USA 78, 3492-3495) than CA, a phenomenon which is enhanced in both enzyme forms by substrate (Kemptide). The separation of both subtypes from each other is probably based on differences in isoelectric values (delta pH less than or equal to 0.5 units). The reason for the charge difference is not presently known. CA and CB do not differ significantly in their phosphate content. No differences between CA and CB have been detectable so far with respect to their migration in SDS gels, kinetic behavior regarding both substrates and cosubstrate, pH dependence, inhibition by regulatory subunits of holoenzyme type I (rabbit skeletal muscle) and of type II (bovine cardiac muscle), and inhibition by specific-heat and acid-stable inhibitor-modulator. The peptide pattern of both forms after limited proteolysis exhibits small differences.


[Tissue engineering of hyaline cartilage].
To study the new way to repair the defect of the articular cartilage. The articular-epiphyseal cartilage complexes from 8 newborn rabbits were enzymatically dissolved, and the chondrocytes were seeded onto the fibrous chitin mesh in a 96-well plate in DMEM medium. Cultured for 21 days, the "membrane-like cartilage" was strong enough to be transferred. At the 110th day, the semitransparent cartilage discs were 4.4 mm in diameter and 14.8 mg in weightness. Staining of SatranO showed that engineered "cartilage" was bound of GAGs and the chondrocytes expressed the mRNA of type II collagen by in situ hybridization, which is resemble to that of the normal hyaline cartilage beside the biodegraded fibrous chitin embedded in. The "membrane-like cartilage" cultured for 21 days was grafted into the articular cartilage defects of knee of adult rabbits. Seven of 9 defects healed with new cartilage and the structure was well organized in 16 weeks. The biodegradable fibrous chitin is a good "matrix" for cartilage tissue engineering. The engineered "cartilage" is true hyaline cartilage, which is a new "alive cartilage tissue" for the repairment of the defect of articular cartilage.


[Dislocation of the polyethylene in a patello-femoral replacement with a movable patella].
Patellofemoral arthroplasty is an infrequently used surgical technique because of its controversial results. In an attempt to improve the results, a design with a mobile-bearing poliethylene patellar component has been developed. We describe a clinical case with an unusual complication: the dislocation of poliethylene from the metal backing; and accordingly, we carried out a literature review of this complication.


Accelerated postoperative recovery programme after colonic resection improves physical performance, pulmonary function and body composition.
Postoperative organ dysfunction contributes to morbidity, hospital stay and convalescence. Multimodal rehabilitation with epidural analgesia, early oral feeding, mobilization and laxative use after colonic resection has reduced ileus and hospital stay. Fourteen patients receiving conventional care (group 1) and 14 patients who had multimodal rehabilitation (group 2) were studied before and 8 days after colonic resection. Outcome measures included postoperative mobilization, body composition by whole-body dual X-ray absorptiometry, cardiovascular response to treadmill exercise, pulmonary function and nocturnal oxygen saturation. Defaecation occurred earlier (median day 1 versus day 4) and hospital stay was shorter (median 2 versus 12 days) in patients who had multimodal treatment. Lean body and fat mass decreased in group 1 but not in group 2. Exercise performance decreased by 44 per cent in group 1 but was unchanged in group 2. A postoperative increase in heart rate (HR) response to exercise was avoided in group 2. Pulmonary function decreased in group 1 but not in group 2. There was less nocturnal postoperative hypoxaemia in group 2. Cardiac demand-supply (HR/oxygen saturation ratio) increased in group 1 but not in group 2. Multimodal rehabilitation prevents reduction in lean body mass, pulmonary function, oxygenation and cardiovascular response to exercise after colonic surgery.


Detection of remote myocardial infarction with quantitative real-time ultrasonic characterization.
We have previously shown that the intrinsic properties of myocardium can be characterized quantitatively by the assessment of ultrasonic integrated backscatter. In this study we utilized a novel, real-time, two-dimensional system capable of quantitative integrated backscatter imaging to determine whether zones of remote myocardial infarction in dogs could be delineated definitively by ultrasonic tissue characterization. Detection of such zones in patients is needed as a basis for management decisions related to thrombolysis, angioplasty, and coronary surgery. Integrated backscatter was measured through the closed chest from 25 myocardial sites. Zones of infarction exhibited time-averaged integrated backscatter values approximately 10 dB (9.5 +/- 0.5 dB, standard error of the mean) greater than those in normal regions (p less than 0.001). In addition, the physiologic cardiac cycle--dependent variation of integrated backscatter was blunted significantly in zones of infarction [0.8 dB +/- 0.3 vs. 3.8 +/- 0.6 (p less than 0.01) for normal regions]. Ultrasonic results matched the histopathologic features assessed directly. Thus quantitative ultrasonic tissue characterization can differentiate infarcted tissue from normal myocardium and offers promise for quantitative detection of histopathology in vivo.


Systemic immune inflammation index in patients with recurrent aphthous stomatitis.
Recurrent Aphthous Stomatitis (RAS) a chronic idiopathic oral mucosal disease. But yet the etiology and pathogenesis of RAS are not exactly known, it is thought that inflammation play an important role in the pathogenesis. The aim of this study is to demonstrate the role of systemic inflammation among the possible etiological factors of RAS and to find the possible diagnostic correlation between Systemic Immune Inflammation Index (SII). Patients who were consulted the otolaryngology outpatient clinic and diagnosed with RAS between 2019-2021 were retrospectively analyzed. Neutrophil/Lymphocyte Ratio (NLR), Platelet/Lymphocyte Ratio (PLR) and SII values were calculated based on the results of complete blood count. Demographic and hematological parameters between control and RAS groups were compared. The statistical significance level was considered as <0.05. There was no statistically significant difference between the control and RAS groups in terms of sex and age distributions (p = 0.566 and p = 0.173, respectively). SII, NLR and PLR values were significantly higher in the RAS group compared to the controls (p < 0.001, p < 0.001 and p = 0.001, respectively). A very strong correlation between SII and NLR, moderately strong correlation between SII and PLR and moderate correlation between NLR and PLR values were detected (respectively ρ: 0.813, 0.719, 0.532; p-values <0.001). SII, NLR and PLR has significantly higher levels in the RAS group compared to the control group, that it supports the role of systemic inflammation in the etiopathogenesis of RAS. In addition, the results show that SII is a valuable marker for inflammation.


Visualization and quantification of the degenerative pattern of the distal tibia and fibula in unilateral varus ankle osteoarthritis.
The present study aimed to quantify and visualize the degenerative patterns of the distal tibia and fibula due to ankle osteoarthritis (OA). We analyzed differences in tibial and fibular surface deviation between sides of patients with unilateral varus ankle OA (medial talar tilt > 4°) by registering each surface model to the mirror image of corresponding bone. Computed tomography images of both feet of 33 patients (OA: 22, control: 11) were examined. Statistically significant surface depression of approximately 2.5 mm on the anterior articular surface of the medial malleolus, and surface elevation of approximately 1 mm on the anterodistal edge of the tibiofibular joint and the lateral malleolus were observed in OA patients. These bone degenerations were found to be correlated with those on the other side of the ankle joint, the medial margin of the talar trochlea and the lateral articular surface of the talus, respectively. In contrast, the amount of bone depression on the plafond was smaller than previously anticipated. Such quantitative information about stereotypical patterns of bone degeneration in ankle OA would contribute to better understanding of the development of ankle OA and possible therapeutic interventions.


What is meant by telling the truth: Bonhoeffer on the ethics of disclosure.
This article explores Dietrich Bonhoeffer's writings on truth telling with reference to the problem of medical error in the US, the UK, and other developed nations, with particular attention to physicians' resistance to disclosing their own mistakes to injured patients and their families. The brief essay 'What is Meant by "Telling the Truth"?' and its historical context--Bonhoeffer's imprisonment and interrogation in 1943--is proposed as a text for medical ethicists and others seeking to overcome the barrier of the 'hidden curriculum' within the culture of medicine, which encourages medical students and physicians to conceal their errors and to fear disclosure.


Clonality profile in relapsed precursor-B-ALL children by GeneScan and sequencing analyses. Consequences on minimal residual disease monitoring.
Detection of minimal residual disease (MRD), using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements as clone-specific targets, represents the most recent development in diagnosis and treatment of acute lymphoblastic leukaemia (ALL). Nevertheless, risk of false-negative results, due to secondary or ongoing rearrangements of Ig/TCR genes during the disease course, might hamper MRD detection. Therefore, to gain extensive information on clonal stability, we performed PCR-GeneScan analysis of Ig/TCR gene rearrangements at diagnosis and subsequent relapse in bone marrow samples from 53 childhood precursor-B-ALL patients. In addition, sequencing analysis of junctional regions at diagnosis and relapse provided a detailed insight in the stability and changes of Ig/TCR gene rearrangements during the disease course. At least one stable clonal Ig/TCR target was found in 94% of patients. In three patients complete differences in Ig/TCR rearrangements between diagnosis and relapse were observed, suggesting relapse with a new clone. At relapse, 71% of diagnostic clonal PCR targets was conserved. Since the comparison of Ig/TCR gene rearrangements at diagnosis and relapse in our precursor-B-ALL patients did not show significant difference in the stability of different clonal PCR targets (IGH, 70%; IGK, 71%; TCRD, 67%; TCRG, 75%), we conclude that there is no 'preferential' clone-specific target for MRD monitoring.


Surgical treatment of intracystic carcinoma of the breast.
Intracystic carcinoma of the breast is a type of breast cancer with favorable prognosis where cancer arises from the cystic wall. However, it is a relatively rare disease, and no general consensus has been reached on its definition, including pathogenesis, extramural invasion, and lymph node metastasis. Six patients who underwent surgery at the Department of Surgery at Asahikawa Medical University are presented. In each patient, background factors, diagnosis, surgery, pathological diagnosis, and prognosis were investigated. Fine needle aspiration showed class V disease in three patients and class III disease in the other three, and lumpectomy was performed for class III patients. Three patients underwent breast-conserving surgery While extramural invasion was seen in three patients, lymph node metastasis was absent in all patients. When it is difficult to diagnose intracystic carcinoma of the breast by fine needle aspiration, active lumpectomy is necessary. Because extramural invasion and lymph node metastasis have been reported, it is necessary to carefully determine the range of excision and rationally perform lymph node dissection, such as sentinel node biopsy.


Seasonal variation in dust mite and grass-pollen allergens in dust from the houses of patients with asthma.
In order to study seasonal variation in dust-mite allergen, we obtained dust samples from bedding, carpet, and/or sofas in 12 houses in central Virginia, monthly, for 1 year. The houses included those of nine patients with asthma of whom six were allergic to dust mites. Dust samples were assayed with an inhibition radioimmunoassay for mite allergen that detects cross-reacting determinants on Der f and Der p I from Dermatophagoides farinae and D. pteronyssinus, respectively. The results are expressed as micrograms of antigen P1 equivalent (AgP1Eq). The results demonstrate that large seasonal variations in allergen, i.e., more than twentyfold, can occur in dust from all sites and are not restricted to the houses of allergic patients. However, dust from some sites, particularly sofas, remained "high" (greater than 10 micrograms AgP1Eq per gram), whereas dust from other sites remained "low" (less than 1 microgram AgP1Eq per gram) throughout the year. Levels of mite allergen generally started to rise in July about 1 month after the rise in humidity. In August to December, the mean levels of AgP1Eq in house dust were highly significantly increased relative to April to May. In keeping with this finding, in 31 of 37 sites, the highest level for the year was observed in August through December. In four sites, mite bodies were counted, and the numbers increased sharply in June to July; however, they decreased in September in parallel with falls in humidity but several months before the fall in mite allergen. Ryegrass-pollen allergen in 12 sites was also assayed in house dust, and pollen-allergen levels demonstrated a sharp increase in May or June that fell back to preseason values within 2 months. Dust was also obtained from the houses of 50 patients with acute or severe asthma. The results on these samples suggest that mite-allergic patients are more likely to have attacks in the fall at a time when their houses have greater than 10 micrograms AgP1Eq per gram of dust. The magnitude of changes observed seasonally within individual houses and of differences between houses within a close geographic area suggests that interpretation of the relationship between allergic symptoms and mite-allergen exposure will require measurement of mite-allergen levels in individual houses.


Editorial: Measuring and Buffering the Mental Health Impact of the War in Ukraine in Young People.
The Russian invasion of Ukraine on February 24, 2022, has caused social, political, and financial instability worldwide. In Ukraine, the war has brought the greatest levels of violence, devastation, and disruption seen in Europe since World War II. Of course, the impact of war on the mental health of Ukrainian young people is likely substantial. Yet, more specific information about the prevalence and distribution of mental health disorders in young people is essential to document their needs, to select the best interventions, and to deliver these through international humanitarian efforts. The study by Osokina and Silwal et al.1 presents some of the best evidence to date about the mental health impact of the war in Ukraine on young people.


[Appraisal, diagnosis and therapy of chronic metabolic acidosis in Germany].
Data concerning chronic metabolic acidosis (CMA) has been sparse for a long time. This might be one reason why the diagnosis and therapy of this common complication in CKD patients has not received much attention. Emerging clinical data indicate that the treatment of metabolic acidosis, which is simple and cost-efficient, offers great therapeutic potential. Survey among German nephrologists to collect information about current appraisal, diagnostic and therapeutic routine in clinical practice, and to determine the need for recommendations by the medical society. In August 2012, all nephrologists in Germany (n = 2095) were asked to complete a standardized questionnaire regarding diagnosis, evaluation and therapy of CMA. 207 questionnaires (9.9 %) were returned and analysed. The CMA was rated as the second most important contributor for the progression of renal insufficiency, with the most important being hypertension. In addition, there was a high consensus concerning diagnosis and therapy of CMA. But estimates on prevalence were highly diverse. In this survey the CMA was rated as an important co-morbidity. Participating nephrologists mostly followed treatment guidelines. However, major differences in the perception of prevalence of CMA were observed, leaving the possibility that CMA is still underdiagnosed. Further recommendations of the German Society of Nephrology could improve the diagnosis and therapy.


Pediatric urology research in 2020: A bibliometric analysis of the top 100 most cited articles.
Pediatric Urology deals with genitourinary diseases. Present study aimed to collect the top-cited article in Pediatric Urology in order to define the most debated and studied topics. The journals reported in "Urology & Nephrology" category of the 2019 edition of Journal Citation Reports, together with the most relevant journals of "Transplantation," "Pediatrics," and "Surgery" categories, were browsed. The articles of interest in Pediatric Urology with more than 50 citations were collected. A bibliometric analysis was performed to collect the top 100 cited articles. The top-cited articles were published in 27 journals (23%), with a median impact factor of 2.676 (IQR 1.981-5.642). Seventeen of them (63%) belonged to "Urology and Nephrology" category. The median number of citations was 82 (IQR 64-113). The most productive journal, with 23 articles, was "The Journal of Urology." Forty-eight top-cited articles were Guidelines or Reviews of the literature and only four papers were randomized controlled trials. The most relevant topic was "congenital anomalies" with 18 articles. As to minimally invasive surgery, eight studies were identified. All of them dealt with robotic-assisted laparoscopic surgery. Two articles reported the current evidence about transitional care. The top-cited articles were dispersed among journals of different areas. Current scientific literature deal with congenital anomalies, more specifically with obstructive uropathies and hypospadias. In the last decade, one of the most relevant innovation in pediatric urology was the introduction of robotic surgery. Transitional care has become a timely topic.


The influence of body position on leg kinematics and muscle recruitment during cycling.
The effects of upper body orientation on neuromuscular control of the leg during cycling are not well understood. Our aim was to investigate the effects of upper body orientation on control of movement of distal leg segments during cycling. We compared three-dimensional leg and foot kinematics and muscle recruitment patterns between upright and aerodynamic riding positions. Comparisons were made between 10 elite cyclists, 10 elite triathletes and 10 novice cyclists. We found that upper body orientation did not influence kinematics of the leg and foot or primary muscle activity (i.e., the main bursts of muscle activity). The aerodynamic riding position was, however, associated with less modulation of muscle activity (i.e., less relaxation of the muscle during secondary muscle activity) and greater coactivity in elite triathletes and novice cyclists. Our results suggest that orientation of the upper body influences neuromuscular control of the leg during cycling in elite triathletes and novice cyclists. The change in muscle recruitment (i.e., the change in how the goal movement was achieved) implies that the ability of the central nervous system to execute the cycling movement in the most skilled manner was adversely influenced by upper body orientation in elite triathletes and novice cyclists. Less modulation of muscle activity and greater coactivation in elite triathletes when cycling in the aerodynamic position, and the similarity of changes shown in elite triathletes and novice cyclists, may be interpreted as further evidence of less skilled control of movement in elite triathletes when compared to cyclists matched for cycling training history.


Space-Time Patterns, Change, and Propagation of COVID-19 Risk Relative to the Intervention Scenarios in Bangladesh.
The novel coronavirus (COVID-19) pandemic continues to be a significant public health threat worldwide, particularly in densely populated countries such as Bangladesh with inadequate health care facilities. While early detection and isolation were identified as important non-pharmaceutical intervention (NPI) measures for containing the disease spread, this may not have been pragmatically implementable in developing countries due to social and economic reasons (i.e., poor education, less public awareness, massive unemployment). Hence, to elucidate COVID-19 transmission dynamics with respect to the NPI status-e.g., social distancing-this study conducted spatio-temporal analysis using the prospective scanning statistic at district and sub-district levels in Bangladesh and its capital, Dhaka city, respectively. Dhaka megacity has remained the highest-risk "active" cluster since early April. Lately, the central and south eastern regions in Bangladesh have been exhibiting a high risk of COVID-19 transmission. The detected space-time progression of COVID-19 infection suggests that Bangladesh has experienced a community-level transmission at the early phase (i.e., March, 2020), primarily introduced by Bangladeshi citizens returning from coronavirus epicenters in Europe and the Middle East. Potential linkages exist between the violation of NPIs and the emergence of new higher-risk clusters over the post-incubation periods around Bangladesh. Novel insights into the COVID-19 transmission dynamics derived in this study on Bangladesh provide important policy guidelines for early preparations and pragmatic NPI measures to effectively deal with infectious diseases in resource-scarce countries worldwide.


Stability and range of motion of Insall-Burstein condylar prostheses. A computer simulation study.
The Insall-Burstein Posterior Stabilized Prosthesis (Zimmer, Warsaw, IN) uses an articulation between a femoral cam and tibial spine to provide anteroposterior stability to the knee. Dislocation can occur if the femoral cam translocates anteriorly and over the tibial spine. A computer model was used to examine the effects of design changes made between the Insall-Burstein I (IB I), Insall-Burstein II (IB II), and revised Insall-Burstein II (IB IIR) knees. The effects of these design changes were determined from their influence on knee stability and maximum obtainable knee flexion. Knee stability was characterized by a dislocation safety factor, defined as the vertical distance from the top of the tibial spine to the bottom of the femoral cam. Our analysis showed that the dislocation safety factor is greatest at approximately 70 degrees of knee flexion for all IB knees. As knee flexion is increased from this angle, the dislocation safety factor decreases, reducing knee stability. The simulations highlighted a trade-off between improving knee flexion and improving knee stability. The geometry of the IB II knee allowed greater knee flexion. The maximum flexion achieved with the IB II knee was 125 degrees compared with 115 degrees and 117 degrees for the IB I and IB IIR knees, respectively. However, the simulations indicate that the IB I and IB IIR knees are less likely to dislocate because they have greater dislocation safety factors than the IB II knees.


Total anomalous pulmonary venous drainage in newborns with visceral heterotaxy.
Children with visceral heterotaxy often present with total anomalous pulmonary venous drainage (TAPVD) associated with univentricular congenital heart disease. We reviewed our experience with the primary surgical management of this lesion under these circumstances. Over a recent 10-year span, 38 patients within the first 3 days of life were admitted to our institution and underwent primary palliation. Twenty-one of them had TAPVD, 18 to a systemic vein. Twelve (67%) of these 18 were seen with obstruction of the anomalous connection and underwent emergency operation. In 7 patients, repair of TAPVD was combined with a systemic-pulmonary artery shunt because of additional obstruction of the pulmonary blood supply, with two deaths. One patient had primary shunting and then repair of TAPVD. Four patients underwent repair of TAPVD alone. Two of them then showed signs of insufficient pulmonary blood flow, received a shunt in a second procedure, and subsequently died. Early mortality in the group with obstructed TAPVD was thus 4 (33%) of 12 patients. Statistical analysis of all 38 patients (univariate analysis, chi 2 testing) showed that neither the presence of TAPVD (p = 0.7) nor TAPVD repair alone (p = 0.8) or with shunting (p = 0.8) was a definite risk factor for early death. The performance of a shunt during the first operation, however, was associated with lower early mortality (p = 0.03). Total anomalous pulmonary venous drainage is a common finding in newborns with visceral heterotaxy. Its presence and its subsequent early repair (requiring cardiopulmonary bypass) do not increase the mortality risk. The need of a concomitant shunt in obstructed TAPVD can initially be underestimated.


3-tert-Butyl-4-hydroxyanisole perturbs renal lipid metabolism in vitro by targeting androgen receptor-regulated de novo lipogenesis.
The widespread usage of 3-tert-butyl-4-hydroxyanisole (3-BHA) as an anthropogenic antioxidant has caused considerable environmental contamination and frequent detection in diverse human-derived samples. 3-BHA can promote adipogenesis and impair hepatic lipid metabolism, while its effects on renal lipid homeostasis remain to be uncertain. Herein, using the human kidney 2 (HK-2) cell experiments, 3-BHA was found to cause a significant reduction in lipid accumulation of the HK-2 cells in both exposure concentration- and duration-dependent manners. Exposure to 3-BHA lowered the transcriptional expressions of sterol regulatory element-binding protein 1 (SREBP1) and acetyl-CoA carboxylase (ACC), as well as ACC activity, indicating the inhibition in the process of de novo lipogenesis in HK-2 cells. On this basis, the mechanism study suggested that the reduced glucose absorption and accelerated glycolysis were concomitantly involved. The antagonism of 3-BHA on the transactivation of androgen receptor (AR) contributed to the lowered de novo lipogenesis and the consequent intracellular lipid reduction. The metabolomics data further confirmed the imbalance of lipid homeostasis and dysregulation of de novo lipogenesis. The new findings on the impaired renal lipid metabolism induced by 3-BHA warranted proper care about the usage of this chemical as a food additive.


Systematic review of measures and their concepts used in published studies focusing on rehabilitation in the acute hospital and in early post-acute rehabilitation facilities.
To identify outcome measures cited in published studies focusing on rehabilitation in the acute hospital and in early post-acute rehabilitation facilities, and to identify and quantify the concepts contained in these measures using the ICF as a reference. Electronic searches of Medline, Embase, CINAHL, Pedro and the Cochrane Library from 1997 to March 2002 were carried out. In a first step, abstracts of the retrieved studies were checked and data on the outcome measures and certain characteristics of the included studies were extracted. In a second step, the items of the questionnaires and their underlying concepts were specified. These concepts were then linked to ICF categories using standardized linkage rules. From the 1,657 abstracts retrieved, 259 studies met the inclusion criteria. In a second step, 277 formal assessment instruments and 351 single clinical measures were retrieved. A total of 1,353 concepts were extracted from the clinical and technical measures. Ninety-six percent of these concepts could be linked to ICF categories. Fifty-six second-level ICF categories representing the concepts contained in the measures. Twenty-six (46%) of the 56 categories belong to the component Body Functions, five (9%) to the component Body Structures, and 25 (45%) to the component Activities and Participation. The ICF provides a valuable reference to identify and quantify the concepts of outcome measures focusing on rehabilitation in the acute hospital and in early post-acute rehabilitation facilities. Our findings indicate a need to define and to agree on 'what should be measured' in rehabilitation care to allow for a comparison of patient populations.


The Characteristics of Clinical Studies Submitted to the Saudi Food and Drug Authority from 2009 until 2020.
Clinical trials are crucial in contemporary evidence-based medicine for discovering new treatments for diseases. Their registration in a registry increases the transparency in the dissemination of knowledge about clinical research. It is essential to understand the activity of clinical trials in a country, thus identifying research gaps. This study, therefore, aims to describe the clinical trial activity since the inception of clinical trials' administration and national clinical trials' registry within the Kingdom of Saudi Arabia (KSA). A descriptive study was conducted by reviewing all clinical studies that have been registered during 2009 and June 2020. The inclusion criterion was all phases of the clinical trials registered in the national registry during that period. Data analysis was done using descriptive statistics. Since 2009, 352 studies have been registered. However, a total of 333 studies with complete data was included in the analysis. A total of 80 sponsors funded the clinical studies in the KSA. The majority of the clinical studies are funded by multinational pharmaceutical companies. Oncology (13.81%) and diabetes (11.71%) were the most common therapeutic areas and constituted the largest proportion of the overall studies. 44% were phase 4 and 40% were phase 3 studies. With a population approaching 34 million, the number of clinical trials in the KSA is not sufficient. Since the inception of the clinical trial's administration and SCTR, the emphasis has been on phase 3 and phase 4 clinical studies. The most studied therapeutic areas were oncology and diabetes. Many clinical studies in the KSA were sponsored by multinational pharmaceutical companies.


Can Walmart make us healthier? Prescription drug prices and health care utilization.
This paper analyzes how prices in the retail pharmaceutical market affect health care utilization. Specifically, I study the impact of Walmart's $4 Prescription Drug Program on utilization of antihypertensive drugs and on hospitalizations for conditions amenable to drug therapy. Identification relies on the change in the availability of cheap drugs introduced by Walmart's program, exploiting variation in the distance to the nearest Walmart across ZIP codes in a difference-in-differences framework. I find that living close to a source of cheap drugs increases utilization of antihypertensive medications by 7 percent and decreases the probability of an avoidable hospitalization by 6.2 percent.


Genetics of serum lipids and lipoproteins. A study of twins at birth and 3-5 years of age.
The genetic influence on serum lipid and lipoprotein values was estimated in 12 monozygotic (MZ) and 8 dizygotic (DZ) twins at birth and 3-5 years of age. The intrapair variances for total cholesterol and high density lipoprotein (HDL) cholesterol were smaller in MZ than DZ twins thus indicating a significant genetic influence.


Some factors affecting the stability of interferon alpha 2b in solution.
In this paper we evaluated the influence of the protein concentration and a formulation vehicle on the stability of recombinant human Interferon alpha 2b (rhIFN-alpha2b) in solution. The effect of the protein content (from 1 to 100 MIU/ml) at 37 degrees C, showed that higher concentration of this cytokine protected against the loss of bioactivity (antiviral titration) better than the lower concentrations. In contrast, rhIFN-alpha2b at 50 and 100 MIU/ml decreased the SDS/PAGE- and RP-HPLC-determined purity faster than samples at 1 or 10 MIU/ml. According to these results, 10 MIU/ml rhIFN-alpha2b was the best choice to evaluate the influence of a formulation on the stability of this cytokine. Taking this into consideration, we studied the stability of a liquid and albumin-free formulation of this protein at the recommended storage temperature (5+/-3 degrees C) and under accelerated conditions (28+/-2 degrees C). Accelerated storage results showed an acceptable biochemical stability of the active ingredient throughout 2 months. Real-time storage data confirmed the good biochemical stability of this formulation for 30 months.


Comparative performance of precommercial cellulases hydrolyzing pretreated corn stover.
Cellulases and related hydrolytic enzymes represent a key cost factor for biochemical conversion of cellulosic biomass feedstocks to sugars for biofuels and chemicals production. The US Department of Energy (DOE) is cost sharing projects to decrease the cost of enzymes for biomass saccharification. The performance of benchmark cellulase preparations produced by Danisco, DSM, Novozymes and Verenium to convert pretreated corn stover (PCS) cellulose to glucose was evaluated under common experimental conditions and is reported here in a non-attributed manner. Two hydrolysis modes were examined, enzymatic hydrolysis (EH) of PCS whole slurry or washed PCS solids at pH 5 and 50°C, and simultaneous saccharification and fermentation (SSF) of washed PCS solids at pH 5 and 38°C. Enzymes were dosed on a total protein mass basis, with protein quantified using both the bicinchoninic acid (BCA) assay and the Bradford assay. Substantial differences were observed in absolute cellulose to glucose conversion performance levels under the conditions tested. Higher cellulose conversion yields were obtained using washed solids compared to whole slurry, and estimated enzyme protein dosages required to achieve a particular cellulose conversion to glucose yield were extremely dependent on the protein assay used. All four enzyme systems achieved glucose yields of 90% of theoretical or higher in SSF mode. Glucose yields were reduced in EH mode, with all enzymes achieving glucose yields of at least 85% of theoretical on washed PCS solids and 75% in PCS whole slurry. One of the enzyme systems ('enzyme B') exhibited the best overall performance. However in attaining high conversion yields at lower total enzyme protein loadings, the relative and rank ordered performance of the enzyme systems varied significantly depending upon which hydrolysis mode and protein assay were used as the basis for comparison. This study provides extensive information about the performance of four precommercial cellulase preparations. Though test conditions were not necessarily optimal for some of the enzymes, all were able to effectively saccharify PCS cellulose. Large differences in the estimated enzyme dosage requirements depending on the assay used to measure protein concentration highlight the need for better consensus methods to quantify enzyme protein.


Capillary glycaemia responses to strength exercises performed before or after high-intensity interval exercise in Type 1 diabetes under real-life settings.
This study investigated the influence of performing strength exercises before or after high-intensity interval exercise on glycaemia during and postexercise in T1DM patients. Nine physically active adults with T1DM executed 30 min of strength exercises (SE) (3 sets at 10 RM) before 30 min of high-intensity interval exercise (HIIE) (10 × 60-s bout at ∼90% HRmax interspersed with 60 s recovery) (SE + HIIE) or performed the reverse order (HIIE + SE) or rested in this period. Capillary glucose levels were measured each 15 min during and 60 min postexercise recovery. Significant lower glucose levels were observed in SE + HIIE at 60, 75 and 90 min, in comparison with REST. HIIE + SE lowered glycaemia at 30, 45 and 60 min compared with baseline concentrations, while SE + HIIE postponed this glucose decayment to 60 min, when compared with baseline levels. An increased glycaemia at 105 min compared with end-exercise levels were also observed in HIIE + SE. Carbohydrates ingested during exercise to correct hypoglycemia, insulin dosage at same day before and after protocols, and nocturnal hypoglycemia episodes were similar among the three conditions. It is concluded that the performance of HIIE before SE decreases glycaemia already at the end of first exercise modality, while the reverse order postpones it to the end of second exercise, although HIIE + SE improves glycemic stability throughout recovery. T1DM patients who tend to develop exercise-associated hypoglycemia may perform strength exercises before high-intensity interval exercise in a single session.


Effects of bile salts of human erythrocytes. Plasma membrane vesiculation, phospholipid solubilization and their possible relationships to bile secretion.
Glycocholate removed approximately 25% of the membrane acetylcholinesterase and 10% of the membrane phospholipid from intact human erythrocytes prior to the onset of cell lysis. At low concentrations (up to 6 mM), glycocholate caused human erythrocytes to become echinocytic and to pinch off microvesicles, whereas at higher concentrations glycocholate also specifically released components from the outer leaflet of the plasma membrane in a 'soluble' form (as defined by their presence in a 150 00 X g/60 min supernatant) and caused the cells to become stomatocytic. Whilst the phospholipdi profile of the 'soluble' material differed from that of the whole membrane, the profile of the microvesicle fraction was similar. The microvesicles were depleted in several membrane proteins with respect to phospholipids. These observations are discussed in relation to the possible role of bile salts in the origins of biliary phospholipid and protein.


Outcomes of hip arthroplasty in Parkinson's disease: a meta-analysis and systematic review.
Hip arthroplasty in Parkinson's disease (PD) is considered to be associated with higher mortality, perioperative complications, and worse clinical outcomes. The purpose of this study was to evaluate the outcomes of hip arthroplasty in PD. The PUBMED, EMBASE, and Cochrane Library databases were searched for all available studies comparing the outcomes of hip arthroplasty in PD and non-PD patients. The quality of the studies was scored using the Newcastle-Ottawa scale (NOS). Meta-analysis was performed using Stata 12.0 software. Six retrospective cohort studies with a total of 59,878 patients were included. Among them, there were 15,313 patients in the Parkinson's group and 44,565 in the non-Parkinson's group. Results showed that patients in the Parkinson's group were more likely to have periprosthetic fracture (OR = 7.93, 95% CI, 1.96-32.04; P = 0.004), revision surgery (OR = 2.33, 95% CI, 1.37-3.98; P = 0.002), deep vein thrombosis (OR = 2.34, 95% CI, 1.56-3.49; P < 0.01), and urinary tract infection (OR = 1.34, 95% CI, 1.20-1.49; P < 0.01) than those in the non-Parkinson's group. The Parkinson's group had a longer hospital stay (WMD = 0.38, 95% CI, 0.24-0.52; P < 0.01) and higher hospitalization costs (WMD = 2487.08, 95% CI, 225.99-4748.17; P = 0.03), but there was no significant difference in short-term postoperative mortality (OR = 1.07, 95% CI, 0.65-1.73; P = 0.80). Hip arthroplasty can significantly improve the function of patients with PD and reduce pain. Although hip arthroplasty in patients with PD is associated with a higher revision rate and potential risk, it does not increase short-term mortality and can reduce pain, improve function, and improve quality of life. The periprosthetic fracture risk and revision rate are significantly higher and should be accounted for when deciding on operative treatment and communicated to patient with PD.


Development of pentaplex PCR and genetic analysis of X chromosomal STRs in Punjabi population of Pakistan.
The X-STRs are important tools in forensic application, particularly in complex cases of kinship testing. In deficiency paternity testing when alleged father cannot be typed, investigation of X-STR markers yields the desired information. Blood samples were collected from unrelated individual (118 females and 94 males) and 84 trios families (father, mother and daughter). DNA extraction from whole blood was performed with Phenol chloroform method. Five X-linked STR markers DXS6800, DXS7133, DXS6797, DXS981 and GATA165B12 were selected. The amplicons were analyzed through ABI 3100 Genetic Analyzer. Pentaplex PCR system was developed for multilocus amplification at the same time. For each locus 4-9 alleles were noted. Altogether, 32 alleles were observed from five markers. Eighty-four trios families were analysed to check the mutation rate and no mutation was observed. Stutter peaks were observed maximum at locus DXS6797 (12.44%) while the minimum at locus DXS7133 (4.5%). For sensitivity study, amplification of X chromosomal short tandem repeats loci was successfully performed using 0.15 ng quantity of DNA as template. In conclusion; this pentaplex represents a convenient method to study X chromosome markers. It works with reasonable amounts of DNA and is suitable for paternity cases.


Use of life cycle assessment and water quality analysis to evaluate the environmental impacts of the bioremediation of polluted water.
The lakes along the Yangtze River are important source of pollutants that ultimately flow from the river into the East China Sea. Bioremediation is a green technology used to treat polluted water in lakes along the Yangtze River. Life cycle assessment and a comprehensive water quality index are used to evaluate the potential environmental impacts of constructed wetlands (CWs), ecological floating beds (EFBs), and combined ecological floating beds (CEFBs). The results showed that the raw material acquisition, construction, and operation of the CWs, EFBs, and CEFBs accounted for 24.1%, 35.3%, and 40.6%, respectively, of the total environmental impact. The acquisition of raw materials to construct the bioremediation system accounted for 51.6% of the total environmental impact. Among the nine impact categories considered, the system's global warming potential was the largest. Among the three stages of the project (raw material acquisition, construction, and operation), construction had the largest impact on eutrophication (the eutrophic potential of the construction stage was the largest). Furthermore, the operation of the project reduced the human eco-toxicity potential. The evaluation of the water quality before and after implementing the project revealed that CEFBs purified the water more effectively than CWs and EFBs did, particularly with respect to the removal of the total phosphorus.


Comparison of reactant and analyte ions for ⁶³Nickel, corona discharge, and secondary electrospray ionization sources with ion mobility-mass spectrometry.
(63)Nickel radioactive ionization ((63)Ni) is the most common and widely used ion source for ion mobility spectrometry (IMS). Regulatory, financial, and operational concerns with this source have promoted recent development of non-radioactive sources, such as corona discharge ionization (CD), for stand-alone IMS systems. However, there has been no comparison of the negative ion species produced by all three sources in the literature. This study compares the negative reactant and analyte ions produced by three sources on an ion mobility-mass spectrometer: conventional (63)Ni, CD, and secondary electrospray ionization (SESI). Results showed that (63)Ni and SESI produced the same reactant ion species while CD produced only the nitrate monomer and dimer ions. The analyte ions produced by each ion source were the same except for the CD source which produced a different ion species for the explosive RDX than either the (63)Ni or SESI source. Accurate and reproducible reduced mobility (K0) values, including several values reported here for the first time, were found for each explosive with each ion source. Overall, the SESI source most closely reproduced the reactant ion species and analyte ion species profiles for (63)Ni. This source may serve as a non-radioactive, robust, and flexible alternative for (63)Ni.


Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex.
Networks of actin filaments, controlled by the Arp2/3 complex, drive membrane protrusion during cell migration. How integrins signal to the Arp2/3 complex is not well understood. Here, we show that focal adhesion kinase (FAK) and the Arp2/3 complex associate and colocalize at transient structures formed early after adhesion. Nascent lamellipodia, which originate at these structures, do not form in FAK-deficient cells, or in cells in which FAK mutants cannot be autophosphorylated after integrin engagement. The FERM domain of FAK binds directly to Arp3 and can enhance Arp2/3-dependent actin polymerization. Critically, Arp2/3 is not bound when FAK is phosphorylated on Tyr 397. Interfering peptides and FERM-domain point mutants show that FAK binding to Arp2/3 controls protrusive lamellipodia formation and cell spreading. This establishes a new function for the FAK FERM domain in forming a phosphorylation-regulated complex with Arp2/3, linking integrin signalling directly with the actin polymerization machinery.


The Adult Monteggia Fracture: Patterns and Incidence of Annular Ligament Incarceration Among 121 Cases at a Single Institution Over 19 Years.
The purposes of this study were to identify the relative frequency of Monteggia fracture patterns and to investigate the required frequency of open reduction of the proximal radiocapitellar joint. We identified 121 Monteggia fractures at a Level I trauma center from 1996 to 2015 and included 119 in this study. These fractures were identified using a database search for the appropriate International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes as well as individual surgeons' logs. Two fellowship-trained hand surgeons reviewed the identified patients' x-rays and operative notes. Each fracture was classified using Bado's original description, excluding transolecranon and Monteggia variants. Bado I lesion represented 68% (81 of 119) of Monteggia fractures. Annular ligament incarceration preventing radial head reduction occurred in approximately 17% (14 of 81) of this Bado type. Revision fixation of the ulna was not necessary (none of 119 cases) and functional range of motion (average arc, 117°) was recovered in most patients. The reoperation rate of 20% (23 of 119) was related to the severity of the presenting injury and hardware prominence. Most radial head dislocations associated with Monteggia fractures occur anteriorly and will reduce with anatomic plating of the ulna. In cases where the radial head fails to reduce, entrapment of the annular ligament can be expected and open reduction is required. Revision fixation of the ulna to achieve reduction of the radial head is uncommon in our experience. Prognostic IV.


Protein-RNA interactions: new genomic technologies and perspectives.
RNA-binding proteins are key players in the regulation of gene expression. In this Progress article, we discuss state-of-the-art technologies that can be used to study individual RNA-binding proteins or large complexes such as the ribosome. We also describe how these approaches can be used to study interactions with different types of RNAs, including nascent transcripts, mRNAs, microRNAs and ribosomal RNAs, in order to investigate transcription, RNA processing and translation. Finally, we highlight current challenges in data analysis and the future steps that are needed to obtain a quantitative and high-resolution picture of protein-RNA interactions on a genome-wide scale.


Stable transfection and overexpression of metallothionein isoform 3 inhibits the growth of MCF-7 and Hs578T cells but not that of T-47D or MDA-MB-231 cells.
The third isoform of metallothionein (MT-3) is overexpressed in some breast cancers and its expression is associated with a poor disease outcome. In the PC-3 prostate cancer cell line, MT-3 expression has been shown to inhibit cell growth and increase drug resistance. The goal of the present study was to determine if MT-3 overexpression would influence the growth of human breast cancer cell lines. To determine this, the coding sequence of the MT-3 gene was stably transfected into two estrogen receptor positive (MCF-7 and T-47D) and two estrogen receptor negative cell lines (Hs578T and MDA-MB-231) having no basal expression of MT-3. Cell growth was determined by counting DAPI-stained nuclei, cadmium resistance by the colony formation assay, MT mRNA expression by RT-PCR, and MT protein by immuno-blot. It was demonstrated that MCF-7 and Hs578T cells that overexpress the MT-3 gene were growth inhibited compared to untransfected cells. In contrast, T-47D and MDA-MB-231 cells that overexpress MT-3 were not growth inhibited. Stable transfection of the MT-1E gene had no effect on the growth of any of the four cell lines. It was also demonstrated that the overexpression of both MT-3 and MT-1E only increased the resistance of MCF-7 cells to Cd(+2). In all instances, stable transfection of the MT-3 or MT-1E gene had no effect on the expression of the other MT isoforms. The study shows that MT-3 can influence the growth of some breast cancer cell lines.


[Histopathological and immunohistochemical characteristics of cutaneous and oral mucosa lesions in disseminated histoplasmosis associated with acquired immunodeficiency syndrome (AIDS)].
Biopsy specimens of the skin and oral mucosa from twenty-five patients bearing the disseminated form of histoplasmosis (H. capsulatum) associated with AIDS (acquired immunodeficiency syndrome) were studied by histologic and immunohistochemistry techniques. Histologically, the skin lesions showed four different patterns: diffuse macrophage, granulomatous, vasculitic with leukocytoclastic and scarce inflammatory reaction. The cell markers for macrophages, lymphocytes B and T and H. capsulatum revealed CD68, UCHL-1 and L26 associated with variable amounts of fungi.


Fingerprint characteristics of refined oils and their traceability in the groundwater environment.
Chemical fingerprinting is essential for identifying the presence and responding to oil spills that frequently contaminate the groundwater environment of refineries. In this study, crude oil and oil products from the atmospheric and vacuum distillation units of a refinery were analyzed by gas chromatography-mass spectrometry (GC-MS) to evaluate their chemical variability before and after refinery. A series of experiments involving evaporation and soil column penetration were conducted to simulate refined oil spilling into groundwater and determine appropriate characteristic ratios (CRs) for principal component analysis (PCA) for oil source identification. The simulated study demonstrated that all products had bell-shaped n-alkane distributions, with dominant peaks that remained unchanged or shifted towards longer chain lengths compared to the source oil. Similarly, naphthalene and dibenzothiophene series remained the main PAH components like the source oil. Ten relatively stable CRs were selected for PCA to identify different oil products through the simulated experiments. The chosen CRs were then utilized to identify the sources for two groundwater oil spills recently occurred, one that occurred in an oil depot area, and another near a continuous catalytic reforming unit in a refinery. This study showed that the components with long-chain n-alkanes (n ≥ C18), pristane, phytane, and phenanthrene and dibenzothiophene series PAHs played an important role in the identification of refined oil products spilling into the groundwater environment. The selected CRs provide an effective tool for rapid and accurate identification of oil spills, especially for newly occurring spills in the groundwater environment, which can aid in developing appropriate response strategies.


Antioxidant properties and PC12 cell protective effects of APS-1, a polysaccharide from Aloe vera var. chinensis.
Through a combination of anion-exchange and repeated gel chromatographies, APS-1 was isolated from fresh leaves of Aloe vera L. var. chinensis (Haw.) Berger (an edible and medicinal plant widely cultivated and consumed in China) as a principal polysaccharide composed of mannose and glucose (ca. 18:5) with its molecular weight around 2.1 x 10(5). In a dose-dependent manner, APS-1 was demonstrated to be free radical scavenging in superoxide and hydroxyl radical assays, inhibitory to the copper-mediated oxidation of human low density lipoprotein (LDL), and protective against hydrogen peroxide (H(2)O(2))-induced lesion to rat PC12 cell (pheochromocytoma cell line). The result suggested that APS-1 could be of considerable preventive and therapeutic significance to some free radical associated health problems such as coronary heart ailments, Parkinson's and Alzheimer's diseases. Furthermore, the finding shed as well fresh light helpful for a better understanding of the health-benefiting potential of the edible plant consumed by the Chinese people for a couple of centuries.


Dialdehyde sodium alginate bonded dicyandiamide for formaldehyde-free leather production with enhanced properties.
Dialdehyde sodium alginate (DSA) is an eco-crosslinker attracting extensive interest while undergoing limited large-scale applications. Herein, we employed DSA to react with dicyandiamide (DA) for engineering a biomass-derived retanning agent (BDR) towards addressing the long-term toxicity of residual formaldehyde (FA) in leather caused by amino resins. Results confirmed that BDR reserved the structural features of DSA by grafting DA onto DSA molecules. Owing to the suitable molecular weight (main components, 1424-1462 g/mol) and abundant oxygen-containing groups of BDR endowed by DSA, BDR-treated chrome-free leather showed higher hydrothermal stability (82.4 °C), thickening ratio (13.93 %), mechanical strengths (17.2 N/mm2 for tensile strength and 120 N/mm for tear strength), and fullness compared with industrial dicyandiamide-FA-resin (DFR)-treated leather. The FA-free feature of DSA led to BDR-treated leather containing no FA, while FA in DFR-treated leather reached 591.5 mg/kg. This work provided new insights into broadening the large-scale application scopes of DSA.


Financial implications of plans to combat methicillin-resistant Staphylococcus aureus (MRSA) in an orthopaedic department.
The aim of this study was to calculate retrospectively the cost of MRSA infections in the elective and trauma orthopaedic population in Rotherham District General Hospital in a 3-month period during 2005. A total of 686 patients were admitted to the orthopaedic wards and the surgical wounds 10 patients became infected with MRSA. The cost of these infections when extrapolated over 12 months was pound384,000 excluding staff costs. The key in the fight against MRSA in the hospital setting is multifactorial and requires a combination of measures. Our solution is: cohort nursing; non-selective screening of all admissions to the orthopaedic wards; use of a polymerase chain reaction as a diagnostic tool; ring-fencing of beds; and separate wound dressing rooms for each ward. The total cost is projected to be pound301,000.


[Difference in transmissibility between bronchial and laryngeal tuberculosis--a retrospective epidemiological study of TB patients newly registered in recent 19 years in Aichi Prefecture, Japan].
To elucidate difference in transmissibility between bronchial and laryngeal TB. The subjects of this retrospective study were 147 patients with bronchial TB and 28 patients with laryngeal TB registered in Aichi Prefecture between 1985 and 2003. All recorded files were reviewed to identify multiple TB patients in the same transmission group. When multiple patients with a registration interval of less than 10 years were found in the same transmission group, the first patient was considered as the index case, and the other patients were regarded as secondary cases. Bronchial TB patients were found in 0.17 per 100,000 population, and laryngeal TB patients in 0.032 per 100,000. Bronchial TB patients occupied 0.55% of total TB patients, and laryngeal TB patients occupied 0.10%. Significant differences were found in patients' proportion between bronchial and laryngeal TB; as to patients with non-cavitary infiltration (73.5% vs 50.0%, p<0.05), female patients (75.4% vs 39.3%, p<0.001), patients aged twenties (13.6% vs 0%, p<0.05), cavitary lesions (7.5% vs 21.4%, p<0.05), male patients (24.5% vs 60.7%, p<0.001), and patients aged thirties (6.1% vs 17.9%, p<0.05). However, no significant difference was observed in the patients' proportion between bronchial and laryngeal TB patients as to positive smear (64.7% vs 53.6%). Three patients with bronchial TB and other three patients with laryngeal TB were found to be the index patients. The proportion of the index patients among overall bronchial and laryngeal TB patients was 2.0% and 10.7% (p<0.05), while they were 2.1% and 20.0% (p< 0.05), respectively, in smear-positive patients, and 0% and 20.0% (p=0.18, not significant) in those patients with no chest pathology. These findings suggest that bronchial TB is less infectious than laryngeal TB.


A preliminary open study of the tolerability and effectiveness of nefazodone in major depressive disorder: comparing patients who recently discontinued an SSRI with those on no recent antidepressant treatment.
Anecdotal evidence suggests that the recent discontinuation of an SSRI may confound the tolerability of the initiation of nefazodone treatment. We sought to determine whether recent discontinuation of an SSRI interferes with effectiveness and/or tolerability of nefazodone. Twenty-six depressed subjects, 21-63 years old, were recruited at the Massachusetts General Hospital. Thirteen subjects (50%) had discontinued an SSRI within 1-4 weeks due to ineffectiveness and/or side effects. Thirteen subjects (50%) had not taken antidepressants for the previous 6 months. Subjects were administered open nefazodone 50 mg p.o. b.i.d., and doses were increased as tolerated to a maximum of 600 mg/day. Subjects were followed for 12 weeks and were assessed for response and side effects using HAM-D-6 and clinical interviews. Both groups improved significantly on nefazodone; however, there was no statistically significant difference in response (>or=50% decrease in HAM-D-6) rates between completers with prior SSRI treatment (80%) and completers without recent exposure to antidepressants (67%). Response rates based on intent-to-treat (ITT) analysis were 31% for both groups. Association between prior SSRI treatment and discontinuation of nefazodone due to side effects or non-response was not statistically significant. Our study suggests that the rate of negative outcomes with nefazodone is no different whether patients have recently failed an SSRI.


Formation and maintenance of the Golgi apparatus in plant cells.
The Golgi apparatus plays essential roles in intracellular trafficking, protein and lipid modification, and polysaccharide synthesis in eukaryotic cells. It is well known for its unique stacked structure, which is conserved among most eukaryotes. However, the mechanisms of biogenesis and maintenance of the structure, which are deeply related to ER-Golgi and intra-Golgi transport systems, have long been mysterious. Now having extremely powerful microscopic technologies developed for live-cell imaging, the plant Golgi apparatus provides an ideal system to resolve the question. The plant Golgi apparatus has unique features that are not conserved in other kingdoms, which will also give new insights into the Golgi functions in plant life. In this review, we will summarize the features of the plant Golgi apparatus and transport mechanisms around it, with a focus on recent advances in Golgi biogenesis by live imaging of plants cells.


A survey on oral health status and treatment needs of life-imprisoned inmates in central jails of Karnataka, India.
The prison population is a unique and challenging one with many health problems, including poor oral health. In a developing country like India, oral health problems of the prisoners had received scant attention. To assess the oral health status and treatment needs of life imprisoned inmates and to know the existing oral health care facilities available in central jails of Karnataka. MATERIALS AND METHODOLOGY DESIGN: Cross sectional survey A systematically selected sample of 800 life imprisoned inmates, were interviewed and examined using modified WHO oral health assessment proforma (1997). The prevalence of caries was 97.5% mean Decayed Missing Filled Teeth(DMFT) was 5.26; Majority of the study population had Community Periodontal Index(CPI) score of 2, whereas 21.6% had at least one sextant with a CPI score of 4. 41.1% prisoners were severely affected with loss of attachment. 8.8% inmates had dentures. Oral sub mucous fibrosis was observed among 9.9% of prisoners. 97.4% of the subjects needed oral hygiene instruction, 87.6% needed restoration, 62.1% extraction of teeth and 32.2% needed prosthesis. Bangalore and Mysore central jail had oral health care facilities on regular basis. This study emphasises the need for special attention from government and voluntary organisations to improve the oral health of inmates.


Surgical treatment of solitary metastasis in the male breast from non-small cell lung cancer.
Detection of metastases in the breast from extramammary neoplasms is rare. We present a case of metastases in breast tissue from surgically treated non-small cell bronchogenic carcinoma. A histologic and immunohistologic study was essential for choosing the appropriate treatment for the patient. The patient is alive and disease-free 18 months after the breast surgery.


Neural precursor cells as a novel target for interferon-beta.
The immunomodulating agent interferon-beta (IFNbeta) is administered therapeutically in several autoimmune diseases and endogenously released by immune cells during diverse infections. As in recent years a variety of pro- and anti-inflammatory substances were shown to influence significantly neural precursor cells that are implicated in a variety of regenerative mechanisms but also in tumor growth, we studied a possible effect of IFNbeta on neural precursor cells derived from murine embryonic day 14 neurospheres. First, we demonstrated that interferon type-I receptors are expressed on neural precursor cells and that these cells respond to IFNbeta treatment by up-regulating IFNbeta inducible genes including Myxovirus 1 and viperin. Furthermore, we could show for the first time that IFNbeta treatment significantly inhibited the proliferation of neural precursor cells possibly through induction of p21, a cyclin-dependent kinase inhibitor. IFNbeta did not exert cytotoxic or neuroprotective effects and we could not see effects on the differentiation of neural precursor cells into total amounts of neurons, astrocytes or oligodendrocytes. However, we found that IFNbeta markedly diminished neurite outgrowth and neuronal maturation of neural precursor-derived neurons.


Computer-based child abuse alert system to be launched.
An online child protection information system intended to alert nurses and doctors in emergency departments is to be introduced in 2015.


A Panel of Circulating MicroRNAs Detects Uveal Melanoma With High Precision.
To determine if a circulating microRNA (miRNA) panel could be used to distinguish between uveal melanoma and uveal nevi. We report on a multicenter, cross-sectional study conducted between June 2012 and September 2015. The follow-up time was approximately 3 to 5 years. Blood was drawn from participants presenting with a uveal nevus (n = 10), localized uveal melanoma (n = 50), or metastatic uveal melanoma (n = 5). Levels of 17 miRNAs were measured in blood samples of study participants using a sensitive real-time PCR system. A panel of six miRNAs (miR-16, miR-145, miR-146a, miR-204, miR-211, and miR-363-3p) showed significant differences between participants with uveal nevi compared with patients with localized and metastatic uveal melanoma. Importantly, miR-211 was able to accurately distinguish metastatic disease from localized uveal melanoma (P < 0.0001; area under the curve = 0.96). When the six-miRNA panel was evaluated as a group it had the ability to identify uveal melanoma when four or more miRNAs (93% sensitivity and 100% specificity) reached or exceeded their cut-point. This miRNA panel, in tandem with clinical findings, may be suited to confirm benign lesions. In addition, due to the panel's high precision in identifying malignancy, it has the potential to augment melanoma detection in subsequent clinical follow-up of lesions with atypical clinical features. Uveal nevi mimic the appearance of uveal melanoma and their transformation potential cannot be definitively determined without a biopsy. This panel is most relevant at the nevus stage and in lesions with uncertain malignant potential as a companion diagnostic tool to assist in clinical decision-making.


Eye lens exposure to medical staff during endoscopic retrograde cholangiopancreatography.
The paper presents a study of the radiation doses to eye lens of medical staff during endoscopic retrograde cholangiopancreatography (ERCP) procedures performed in a busy gastroenterology department. For each procedure the dose equivalent to the eye, exposure time, dose rate, Kerma Area Product and fluoroscopy time were recorded. Measurements were performed for a period of two months in four main positions of the operating staff, and then extrapolated to estimate annual doses. The fluoroscopy time per ERCP procedure varied between 1.0 min and 28.8 min, with a mean value of 4.6 min. The calculated mean eye dose per procedure varied between 34.9 μSv and 93.3 μSv. The results demonstrated that if eye protection is not used, annual doses to the eye lens of the gastroenterologist performing the procedure and the anesthesiologist can exceed the dose limit of 20 mSv per year.


Continued challenges with the use of erythropoiesis-stimulating agents in patients with cancer: perspectives and issues on policy-guided health care.
Erythropoiesis-stimulating agents (ESAs) are approved as an alternative to blood transfusions for treating anemia secondary to chemotherapy in patients with cancer. Recently, ESAs have been a source of controversy and confusion in the oncology community. This began when two European trials-the Breast Cancer Erythropoietin Survival Trial (BEST) and the Advanced Head-and-Neck Cancer Treated with Radiotherapy (ENHANCE) Study-raised safety concerns about decreased overall survival and increased venous thromboembolic events. In 2004, the United States Food and Drug Administration (FDA) convened its Oncologic Drugs Advisory Committee (ODAC) to review the data and reassess the risks and benefits of ESAs in patients with cancer. On May 10, 2007, ODAC reconvened when five trials (BEST, ENHANCE, AMG-20010103, AMG-20000161, and EPO-CAN-20) showed decreased overall survival. The briefing document noted that studies demonstrating detrimental effects on survival and/or tumor outcomes used an unapproved treatment regimen designed to maintain hemoglobin levels above 12 g/dl. On May 14, 2007, just days after the ODAC reconvened, the Centers for Medicare and Medicaid Services (CMS) released a proposed decision memo for a national coverage determination (NCD) imposing restrictions on ESAs. For health care providers, aspects of the proposed NCD were markedly inconsistent with FDA-approved ESA use and generally were considered ambiguous and unclear. Over objections of several professional associations and members of Congress, on July 30, 2007, CMS posted the final NCD and declared it effective immediately. When compared with FDA-approved labeling and professional society guidelines, the NCD revealed differences in ESA initiation, dosage escalation, dosage reduction, and definition of response. These discrepancies have generated confusion among health care providers, who are struggling over whether they can feasibly provide a dual system of care-one for Medicare patients and another for non-Medicare patients-that is evidence based. With this supplement, we hope to educate health care providers on the issues and challenges associated with policy-guided health care when discrepancies exist between the policy and evidence-based practice; offer guidance on implementing the NCD; and highlight the important role of pharmacists in the process.


Application of GESPECOR software for the calculation of coincidence summing effects in special cases.
In this work, coincidence summing correction factors have been measured for 133Ba, 152Eu and 88Y point sources with a 50% relative efficiency p-type detector and a 25% relative efficiency n-type detector in two close-to-detector measurement geometries. The experimental data for 133Ba and 152Eu and the results obtained with the GESPECOR software reveal a complex structure of the conventional dead layer of the p-type detector. The high value of the coincidence summing correction factor for the 511 keV peak of 88Y, in agreement with the values computed by GESPECOR, in this case cautions against the application of the semiempirical method for evaluating coincidence summing effects.


Lymphatic mast cells in response to in vitro stimulation by non-specific T-cell mitogens.
Activation of lymph nodes by the T-cell mitogens PHA and Con A is correlated with a depletion of lymphatic mast cells. This result, and our earlier reports on the depletion of mast cells in lymph nodes stimulated by allogeneic and tumour cells, as well as on the elevation of mast cell number in thymus-less 'nude' mice, lead us to the conclusion that antigen- or mitogen-stimulated T lymphocytes produce lymphokine(s) which degranulates mast cells and/or is responsible for their negative chemotaxis.


Targeting Caveolin-1 and Claudin-5 with AY9944, Improve Blood-Brain Barrier Permeability; Computational Simulation and Experimental Study.
The current study aimed to determine the protective effect of AY9944 related to Caveolin-1 and Claudin-5 role in lipid raft, which can rescue the blood-brain barrier from enhanced permeability. Therefore, in vivo analyses were performed following ischemia in normal, ischemic, and AY9944-treated animal groups. The results revealed that AY9944 reduced the infarct size, edema, and brain water content. The extravasation of Alb-Alexa 594 and biocytin-TMR was minimum in the AY9944-treated animals. The results showed a significant decrease in the expression level of Caveolin-1 over 8 h and 48 h and a remarkable increase in the level of Claudin-5 over 48 h following ischemia in AY9944-treated animals. Molecular docking simulation demonstrated that AY9944 exerts a possible protective role via attenuating the interaction of the Caveolin-1 and cholesterol in lipid raft. These findings point out that AY9944 plays a protective role in stroke by means of blood-brain barrier preservation. Proper neural function essentially needs a constant homeostatic brain environment which is provided by the blood-brain barrier. Rescuing blood-brain barrier from enhanced permeability via inducing the protective effect of AY9944 related to caveolin-1 and claudin-5 role in lipid raft was the aim of the current study.


Quality of Quality Accounts: transparency of public reporting of Never Events in England. A semi-quantitative and qualitative review.
To describe the quality of reporting and investigation into surgical Never Events in public reports. Semi-quantitative and qualitative review of published Quality Accounts for three years (2011/2-2013/14). Data on Never Events were compared with previously collated Never Events rates. Quality of reported investigations was assessed using the London Protocol. English National Health Service. All English acute hospital trusts. Quality of Never Event reporting. Quality Accounts were available for all Trusts for all three years, of which 342 referred to years when a surgical Never Event had occurred. A total of 125 of 342 (37%) accounts failed to report any or all Never Events that had occurred; 13/342 (4%) provided full disclosure; 197 (58%) reported that some investigation had taken place. Of these 197, 61 (31%) were limited in scope; 61 (31%) were categorised as detailed reports. Task and Technology factors were the commonest factor (103/211 (49%)) Identified in investigations, followed by Individual factors (48/211 (23%)). Team and Work environment factors were identified in 29/211 (14%) and 23/211 (11%), respectively. Organisational and Management 5/211 (2%) factors were rarely identified, and the Institutional context was never discussed. Reporting of Never Events and their investigations by English NHS Trusts in their Quality Accounts is neither consistently transparent nor adequate. As with clinical error, the true root causes are likely to be organisational rather than individual.


The Autism-Spectrum Quotient in university students: pattern of changes in its scores and associated factors.
Support to university students with autism spectrum disorders (ASD) is becoming increasingly important. To determine the validity of the Autism-Spectrum Quotient (AQ) for ASD screening of university students, we conducted longitudinal measurements of the AQ in a large sample of university students and investigated the possibility of changes in the AQ and associated factors. The AQ, University Personality Inventory (UPI), and the willingness of the students to be interviewed were determined at admission in students from four departments of Kochi University; the AQ was determined again in the second year. Changes in the AQ and associated factors were analyzed statistically. The number of valid responses in the initial survey was 3427 (87.2%). The AQ was significantly higher in the group with high UPI scores (F = 156.08, P < 0.001). Of the 486 students interviewed at admission, 22 had suspected ASD. The sensitivity/specificity of the AQ for ASD was 81.8%/92.0%. A total of 319 (11.0%) students responded to the second-year survey, which revealed significant decrease of the AQ in the group with high AQ values at admission. The AQ measured at admission was correlated with the UPI score, regardless of the sex or department; in the second survey, the scores decreased significantly in those with high AQ values at admission, suggesting that an unstable mental state can produce a temporary increase of the AQ scores.


The Possible Damaged Mechanism and the Preventive Effect of Monosialotetrahexosylganglioside in a Rat Model of Cerebral Ischemia-Reperfusion Injury.
The pathogenesis of cerebral ischemia-reperfusion injury (CIRI) is not completely clear and therapies are limited now. Therefore, our study aimed to investigate the possible pathogenesis and preventive approach of CIRI through analyzing changes of aspartate (Asp), glutamate (Glu), mitochondrial calcium (MCa), calmodulin (CaM), and malondialdehyde (MDA) contents and ultramicropathology in hippocampus and cerebral cortex of ischemic susceptible injured regions and the effect of monosialotetrahexosylganglioside (GM1) in the rat model of CIRI. Contents of Asp, Glu, MCa, CaM, and MDA in hippocampus and cerebral cortex tissues were measured by a high-performance liquid chromatography, atomic absorption spectrophotometer, and ordinary spectrophotometer, respectively, changes of ultramicrostructure in neurons of the hippocampus CA1 region and frontal cerebral cortex were observed by a transmission electron microscope. Contents of Asp and Glu in hippocampus and cerebral cortex tissues of CIRI groups significantly decreased and contents of MCa, CaM, and MDA significantly increased than those in control groups, and the ultramicrostructure in neurons of the hippocampus CA1 region and frontal cerebral cortex revealed a significant damaged change, and GM1 significantly ameliorated changes of Asp, Glu, MCa, CaM, and MDA contents in hippocampus and ultrastructural changes in neurons of the hippocampus CA1 region and frontal cerebral cortex. Our findings further support that the abnormal release and/or reuptake of excitatory amino acid neurotransmitters, the disordered calcium homeostasis and the excessive production and/or reduced elimination of reactive oxygen species contribute to the pathogenesis of CIRI, and GM1 can partially prevent these pathogenesises to exert the protective effect on CIRI.


Taking a look accurately at the alteration of interfacial asphaltene film exposed to the ionic surfactants as demulsifiers.
The water droplets surrounded by a rigid interfacial asphaltene (ASP) film is one of the major setbacks in the petroleum industry. In this study, the properties of the interfacial ASP films around water droplets exposed to ionic surfactants as demulsifier were investigated. According to molecular dynamics (MD) simulation, the anionic surfactants are more effective than the cationic surfactant in the demulsification process since the anionic surfactants have the exact desire to localize not only near the ASP molecules but also near the water molecules. It has been found that it is likely to cause film changes and ruptures. Also, the MD simulation results for the desired surfactant, anionic surfactant, demonstrated that an increase in the surfactant concentration had an adverse effect on the system by hindering the change in the interfacial film. The increase in the temperature along with the enhancement in the adsorption rate of the surfactant results in the better performance of the demulsifier. Taking the MD and quantum results into account, the film deformation is a decisive factor in demulsification. The quantum computation has indicated that the electrostatic interactions play a significant role in selecting the attraction position and adsorption energy of the surfactant molecules.


Fatal Brazilian spotted fever in a healthy military man during field training in Rio de Janeiro city, southeastern Brazil.
Brazilian spotted fever, a zoonotic disease transmitted by ticks, is caused by Rickettsia rickettsii. We report a fulminant case of this zoonosis in a healthy 46-year-old military man in the urban region of Rio de Janeiro city, in October, 2021. Ticks and capybaras (Amblyomma sculptum, Hydrochoerus hydrochaeris, respectively) were identified in the military fields, pointing to the participation of this large synanthropic rodent, recognized as an efficient amplifier host of Rickettsia rickettsii in Brazil. As the military population is considered a risk group for spotted fever, it is necessary to alert health professionals to the importance of the early detection of the disease and its adequate management, mainly in populations that are particularly at risk of exposure to ticks, in order to avoid fatal outcomes.


3D segmentation of SBFSEM images of neuropil by a graphical model over supervoxel boundaries.
The segmentation of large volume images of neuropil acquired by serial sectioning electron microscopy is an important step toward the 3D reconstruction of neural circuits. The only cue provided by the data at hand is boundaries between otherwise indistinguishable objects. This indistinguishability, combined with the boundaries becoming very thin or faint in places, makes the large body of work on region-based segmentation methods inapplicable. On the other hand, boundary-based methods that exploit purely local evidence do not reach the extremely high accuracy required by the application domain that cannot tolerate the global topological errors arising from false local decisions. As a consequence, we propose a supervoxel merging method that arrives at its decisions in a non-local fashion, by posing and approximately solving a joint combinatorial optimization problem over all faces between supervoxels. The use of supervoxels allows the extraction of expressive geometric features. These are used by the higher-order potentials in a graphical model that assimilate knowledge about the geometry of neural surfaces by automated training on a gold standard. The scope of this improvement is demonstrated on the benchmark dataset E1088 (Helmstaedter et al., 2011) of 7.5billionvoxels from the inner plexiform layer of rabbit retina. We provide C++ source code for annotation, geometry extraction, training and inference.


Diagnostic Biomarkers in Eosinophilic Renal Neoplasms.
Incidental small renal masses identified on imaging are increasingly investigated via needle core or fine needle aspiration biopsies with limited material provided for rendering a diagnosis. Lesions with a prominent eosinophilic or oncocytic cell presence showing morphologic overlap between well-known eosinophilic neoplasms are challenging to diagnose. We review the range of known benign and malignant eosinophilic renal neoplasms and their immunoprofiles to elucidate a useful panel of stains that may assist the pathologist in making an accurate diagnosis.


Pilot Investigation of the Katie Brown Educational Program: A School-Community Partnership.
Schools in the United States are increasingly being urged to address the problem of adolescent dating violence (DV) with their students. Given the limited time available to implement prevention programming during the school day, brief programs are needed. The purpose of this study was to test the efficacy of a widely disseminated, brief community-based DV prevention program in partnership with a nonprofit community agency. We conducted a randomized waitlist control trial of a 5-session DV prevention program (active condition) compared to health class as usual (waitlist control condition). Participants were 225 10th-grade students with a recent dating history in a large public school in New England. Surveys were administered at baseline, end of program, and 3 months postintervention. After completing the program, students in the active condition reported significantly lower approval of aggression, healthier dating attitudes, and more DV knowledge. These effects were sustained at 3-month follow-up. In addition, students in the active condition reported significantly less emotional/verbal and total DV perpetration and victimization at 3-month follow-up. These findings suggest that a brief, community-based DV prevention curriculum can promote change in behaviors, attitudes, and knowledge among high school students.


Deletion of BCG_2432c from the Bacillus Calmette-Guérin vaccine enhances autophagy-mediated immunity against tuberculosis.
Mycobacterium bovis bacillus Calmette-Guérin (BCG) is an attenuated live vaccine that provides insufficient protection against tuberculosis (TB), the underlying mechanisms for which remain unknown. Assuming that the BCG vaccine inherits immune evasive strategies from virulent parent M. bovis strains, we aimed to identify the associated genes and assess their effects on the vaccine efficacy. Three genes, BCG_3174, BCG_1782, and BCG_2432c, associated with immune evasion were first identified via bioinformatics analysis and then confirmed in the genome of M. bovis and 12 commercial BCG vaccine substrains using Polymerase Chain Reaction (PCR) and DNA sequencing. These genes were disrupted to develop mutant strains, and their effects on autophagy and their protective efficacy were further compared with the BCG vaccine in vitro and in vivo. Of the three identified genes, only the disruption of BCG_2432c, namely ΔBCG_2432c, conferred stronger protection against intranasal TB in vaccinated mice, when compared with the BCG vaccine. ΔBCG_2432c showed a stronger ability to trigger intracellular ROS-mediated complete autophagic flux in infected THP-1 cells that resulted in higher antigen presentation. The improved protection could be attributed to early and increased IFN-γ+ CD4+ TEM and IL-2+ CD4+ TCM cells in the spleens and lungs of ΔBCG_2432c-vaccinated mice. The insufficient efficacy of the BCG vaccine is attributable to the important autophagy-inhibition gene BCG_2432c that blocks the autophagosome-lysosome pathway of antigen presentation. ΔBCG_2432c provides a promising platform to either replace the current BCG vaccine or develop vaccines that are more effective against TB.


Central nervous system control of interactions between vocalization and respiration in mammals.
The purpose of this review is to examine what is known regarding the competition and synergy between respiratory and airway protective systems with vocalization for speech. It was demonstrated that there are integrative neural mechanisms between vocalization for speech and upper airway protective mechanisms at both the brainstem levels and within cerebral networks. When there is competition between cortical control of learned volitional tasks, usually the upper airway protective systems predominate (eg, the laryngeal adductor response overrides laryngeal muscle control for voice and respiratory tasks). On the other hand, volitional swallowing overrides the laryngeal adductor response. Possible mechanisms for enhanced control of upper airway systems and rehabilitation of abnormal other upper airway systems was also examined. Recently, intensive clinical training using volitional breathing and swallowing tasks has been shown to modulate hyper-reactive sensory driven reflexes such as cough and paradoxical vocal fold movement disorder secondary to laryngeal hypersensitivity.


Diagnostic performance analysis for diabetic cardiovascular autonomic neuropathy based on short-term heart rate variability using Bayesian methods: preliminary analysis.
This study aimed to estimate the performance of diabetic cardiovascular autonomic neuropathy (DCAN) diagnostic tests in the absence of a gold standard. The DCAN prevalence is rapidly growing in all populations worldwide. No document has been reported about diagnostic performance for DCAN based on short-term HRV without a gold standard. We conducted a cross-sectional study to perform diagnostic test in Chinese diabetic patients. A dataset contained 56 subjects who completed both the short-term HRV test and Ewing's test. Simultaneous inferences about the population prevalence and the performance of each diagnostic test were possible using the Bayesian approach. The HRV test had a high sensitivity (0.837 and 0.821 for independence model) and specificity (0.838 and 0.797 for dependence model) to DCAN. In addition, the non-inferiority test rejected the hypothesis that the performance of the HRV test was inferior to that of Ewing's test (P < 0.05). The estimated DCAN prevalence in our study sample was more than 0.400. Our findings provided evidence that short-term HRV were used for the DCAN diagnostic test with a high sensitivity and specificity. ClinicalTrial.org ID: NCT02461381.