Generation of porcine induced pluripotent stem cells and evaluation of their major histocompatibility complex protein expression in vitro.
Induced pluripotent stem cells (iPSCs) are thought to be highly beneficial in the field of regenerative medicine and are believed to overcome immunogenic barriers to cell transplantation. However, issues remain regarding their safety and efficiency for medical use. Furthermore, some recent reports have suggested that iPSCs could be targeted by the autologous immune system. To promote practical applications of iPSCs, in depth research using appropriate animal models is needed and porcine species appear to provide an ideal model. Recent studies have focused on the generation of porcine iPSC cells, but no investigations of their immunological properties have been conducted to date. In the present study, we generated putative iPSCs from porcine somatic cells and measured major histocompatibility complex (MHC) expression on the iPSCs and their derivatives. Compact colonies that expressed pluripotent markers appeared 11 days after viral infection. Embryonic bodies (EB) were produced and differentiated into three germ layers in vitro. Karyotyping and swine leukocyte antigen (SLA) typing showed that the iPSCs were identical to parental somatic cells. Porcine iPSCs expressed only low levels of MHC class I and moderately increased levels on their differentiated derivatives, whereas MHC class II was rarely expressed. In the presence of interferon-gamma (IFN-γ), the expression of MHC class I was elevated on differentiated iPSCs, and gradually decreased after withdrawal of the cytokine. Our data suggest that porcine iPSCs could be useful for preclinical studies of the efficiency and viability of iPSCs, and for devising strategies to rescue transplanted cells from the autologous immune system.


Concurrent tonic pupil and trochlear nerve palsy in COVID-19.
Since COVID-19 was first reported, different neurological complications have been acknowledged, but their description is constantly evolving. We report a case of concurrent tonic pupil and trochlear nerve palsy in this context. A 62-year-old man reported a 5-day history of binocular vertical diplopia and blurred vision in his left eye, noticing that his left pupil was dilated. He had suffered a flu-like syndrome 2 weeks before. Clinical exam showed a right trochlear nerve palsy and a left mydriatic pupil. MRI, X chest ray, and analytical results were normal. Antibodies for SARS-CoV-2 were positive (low IgM and high IgG titers). Antiganglioside antibodies were negative. A 0.125% pilocarpine test confirmed Adie's pupil diagnosis. The patient was treated with a tapered prednisone dose with resolution of his diplopia but no change in Adie's pupil. This is the first case reporting Adie's pupil as a postinfectious manifestation of COVID-19. An immune-mediated mechanism is presumed.


Derivation of a size-independent variable for scaling of cardiac dimensions in a normal adult population.
Most current methods for normalizing cardiac dimensions for differences in body size assume a linear isometric relationship between variables. This approach may be flawed. We therefore compared the isometric and allometric modeling approach to assess the optimal scaling method (using the left atrial dimension [LAD] as an example) in a large group of adults with normal echocardiograms. We studied 15,667 consecutive echocardiographically normal adults. Their mean age was 40 +/- 14 years; LAD was 32 +/- 4 mm; body weight (BW) was 72 +/- 17 kg; height (HT) was 1.7 +/- 0.2 m; body surface area (BSA) was 1.8 +/- 0.2 m(2); and body mass index was 25 +/- 6 kg/m(2). The LAD in the anterior-posterior dimension was indexed by each size variable using both isometric and allometric methods. LAD correlated with all size variables (r = 0.20 to r = 0.45). Simple isometric indices (e.g., LAD/BSA), rather than removing, actually increased the correlation with all body size variables (r = -0.27 to -0.80). Normalization by the optimal allometric exponent (BW = 0.262; HT = 0.428; BSA = 0.449; body mass index = 0.266) eliminated the association of the indexed variable with body size. Indexation by BW best removed the influence of all measures of body size. The proportion of variance of LAD explained by BW was 21.4% compared with only 3.9% for HT. There were minor, but statistically significant, age-, gender-, and obesity-related differences in the indexed left atrial size (e.g., optimal allometric exponent for BW in male patients = 0.257 vs. in female patients = 0.253). The standard isometric corrections for body size fail to adequately account for the associations between LAD and body size, and in fact increase the relationship of the indexed parameter to all body size measures. Normalization using the optimal allometric exponent removes the effect of that variable, with BW best removing the effect of body size.


The efficacy of onabotulinumtoxinA in patients with previous failed augmentation cystoplasty: Cohort series and literature review.
To investigate the role of onabotulinumtoxinA (BTX-A) injections in patients with failed augmentation cystoplasty for neuropathic or idiopathic detrusor overactivity (NDO or IDO). A retrospective review of all cystoplasty patients who underwent onabotulinumtoxinA injection at a tertiary center between 2008 and 2019 was performed. Details including indications and time from cystoplasty, video-urodynamic parameters, onabotulinumtoxinA dose, and clinical outcomes were analyzed. Telephone interview was performed for patients that requested repeat onabotulinumtoxinA injections. The interview included a modified PGIC7 and UDI6 questionnaires. A positive clinical response was considered improvement of overactive symptoms sufficient to merit repeat onabotulinumtoxinA injection and a modified PGIC7 of four or above. Thirty patients were identified (11 men and 19 women). The indications for augmentation were IDO (n = 18) or NDO (n = 12). Mean age at the time of cystoplasty was 42 years (range, 10-61). Interval between cystoplasty and initial onabotulinumtoxinA was 98 months (range, 3-271). Video-urodynamics before onabotulinumtoxinA revealed low compliance in 13 patients, DO in 22 patients, and combined low compliance/DO in 10. The median maximum cystometric bladder capacity was 338 mL (range, 77-570 mL). Thirteen patients responded to onabotulinumtoxinA injections. Higher peak DO pressure was associated with a significantly higher chance that the patient would experience benefit from the injections P = .026). The patients that responded to onabotulinumtoxin A underwent a total of 115 procedures (mean, 8.8 injections) over a mean 88 months (range, 20-157 months). Forty-three percent of patients responded well to intra-detrusor onabotulinumtoxinA injections. This avoided the need for more invasive surgery and had a positive impact on their quality of life.


The impact of laryngeal disorders on work-related dysfunction.
To determine the short-term disability (STD) and lost work productivity related to laryngeal disorders. A retrospective analysis of a national database of work absence and STD claims was performed. Patients with 12 months of follow-up who had an STD claim specifically linked to a dysphonia diagnosis based on ICD-9 codes were identified during the period of January 1, 2004, to December 31, 2008. Patient age, sex, and diagnosis and the total number of work days absent were determined. Using the mean national hourly wage, productivity losses in terms of lost wages were calculated. Of the 18,466 unique patients with an STD claim, 386 (2.1%) had an STD claim due to a laryngeal disorder. The mean age was 45.9 years (standard deviation, 9.6) with 53.2% male. The mean number of work days absent was 39.2 days (95% confidence interval: 31.9-46.5). Total STD payments in 2008 dollars were $647,269.30 with a mean per person in 12 months of $3,406.68. Total and mean lost wages in 12 months were $843,198.72 and $4,437.89, respectively. Patients with laryngeal cancer had the most days absent and highest total STD payment. Laryngeal disorders lead to work-related disability with STD and productivity losses and represent a significant societal burden. Managing work limitations from laryngeal disorders is an important public health goal.


Sentinel health events as indicators of unmet needs.
It is vitally important to be able to assess the impact of the health care system on the populations it serves. This paper explores whether sentinel health events--negative health states, such as death, disability, and disease, that might have been avoided given current medical and public health knowledge and technology--can be used as sociomedical indicators to assess levels of unmet needs and to evaluate health system performance. Using hospital discharge data, the occurrence of sentinel health events in New York State and differences among population subgroups are examined. Among hospitalized residents of New York State in 1983, more than 17,000 deaths occurred that were possibly avoidable. More than 336,000 instances of disease were found that were potentially preventable. Significantly higher rates and ratios for many sentinel events were found among blacks, Medicaid recipients, and users of public hospitals than were found for comparison groups. The sentinel events approach proved to be useful and practical. However, refinements and adaptations of the sentinel events method are needed, including the development of one or more smaller sets of indicators--tracer sentinel events--that can be used to profile aspects of health status and the health system.


A novel nanogel loaded with chitosan decorated bilosomes for transdermal delivery of terbutaline sulfate: artificial neural network optimization, in vitro characterization and in vivo evaluation.
The objective of the present work was to formulate, optimize, and evaluate transdermal terbutaline sulfate (TBN)-loaded bilosomes (BLS) in gel, compared to conventional oral TBN solution and transdermal gel loaded with free TBN, aiming at evading the hepatic first-pass metabolism. A face-centered central composite design was adopted to observe the effects of different formulation variables on TBN-BLS, and artificial neural network (ANN) modeling was employed to optimize TBN-BLS. TBN-BLS were prepared by a thin film hydration method integrating soybean phosphatidylcholine and cholesterol as a lipid phase and sodium deoxycholate (SDC) as a surfactant with or without the coating of chitosan (CTS). After being subjected to physicochemical characterization, TBN-BLS were enrolled in a histopathological study and pharmacokinetic investigation in a rat model. The optimized TBN chitosan-coated bilosomes (TBN-CTS-BLS) were spherical vesicles (245.13 ± 10.23 nm) with adequate entrapment efficiency (65.25 ± 5.51%) and good permeation characteristics (340.11 ± 22.34 μg/cm2). The TBN-CTS-BLS gel formulation was well-tolerated with no inflammatory signs manifested upon histopathological evaluation. The pharmacokinetic study revealed that the optimized TBN-CTS-BLS formulation successively enhanced the bioavailability of TBN by about 2.33-fold and increased t1/2 to about 6.21 ± 0.24 h as compared to the oral solution. These findings support the prospect use of BLS as active and safe transdermal carrier for TBN in the treatment of asthma. Graphical Abstract.


Osteofibrous dysplasia: clinicopathologic study of 80 cases.
A thorough review of the clinical, radiologic, and histologic features of 80 cases of long bone osteofibrous dysplasia is presented. Of the six cases of osteofibrous dysplasia immunostained with a cytokeratin antibody, two were cytokeratin positive; however, the five cases of fibrous dysplasia that were stained were all negative. Follow-up (mean, 5.4 years; range, 1 month to 31 years) data were available for 41 cases (51%). From the consultation series nine of the 18 patients studied had recurrences, regardless of the different treatment regimens. The average recurrence interval in these patients was 2.7 years. Two patients had incomplete excision and six had biopsy only. All eight of these patients had residual tumors. Among the 16 Mayo Clinic patients, one had recurrence 5 years after the initial treatment. In two cases, 7-year-old and 6-year-old boys, histologic maturation to fibrous dysplasia was observed 4 and 10 years later, respectively. Adamantinoma has not developed in any of the 41 cases of osteofibrous dysplasia for which we have follow-up information. It seems clear that osteofibrous dysplasia does not progress to adamantinoma. Our study suggests that osteofibrous dysplasia is probably a variant of fibrous dysplasia, as demonstrated by the maturation of two lesions of osteofibrous dysplasia to fibrous dysplasia. Surgical treatment may be appropriate in cases with an extensive lesion, pseudoarthrosis, and accentuated tibial bowing. The overall prognosis is good, even with recurrence.


Osteolytic lesions in idiopathic myelofibrosis.
A case of idiopathic myelofibrosis with the unusual finding of osteolytic lesions is presented. Biopsies from the lesions showed proliferation of fibroblasts, megakaryocytes and myeloid cells.


[Preliminary findings on 2 groups of diabetics with regard to platelet aggregation in relation to retinopathy and ultimate relation to antidiabetic therapy].
Platelet clumping was examined in untreated insulin-dependent and insulin-independent diabetics, with and without retinopathy. Hyperaggregation was noted, particularly in subjects with retinopathy and longstanding diabetes. Metformin normalised clumping in the course of mild diabetes.


Ultrasound in Arthritis.
Ultrasound is currently performed in everyday rheumatologic practice. It is used for early diagnosis, to monitor treatment results, and to diagnose remission. The spectrum of pathologies seen in arthritis with ultrasound includes early inflammatory features and associated complications. This article discusses the spectrum of ultrasound features of arthritides seen in rheumatoid arthritis and other connective tissue diseases in adults, such as Sjögren syndrome, lupus erythematosus, dermatomyositis, polymyositis, and juvenile idiopathic arthritis. Ultrasound findings in spondyloarthritis, osteoarthritis, and crystal-induced diseases are presented. Ultrasound-guided interventions in patients with arthritis are listed, and the advantages and disadvantages of ultrasound are discussed.


Structural and serological characterization of Hafnia alvei lipopolysaccharide core region.
The structures and serological activities of core oligosaccharide of Hafnia alvei strains have been investigated. Methylation analysis, NMR spectroscopy and various specific degradation procedures were the principal methods used. It is concluded that, core hexasaccharides are identical in the lipopolysaccharides tested and are built of two glucose, three heptose and one 2-keto-3-deoxyoctulosonic acid residues. The antiserum raised against the ATCC13337 oligosaccharide core-tetanus toxoid conjugate cross-reacted strongly with all lipopolysaccharides used as antigens in ELISA test, suggesting that this core region is the common structure in the Hafnia genus.


Demographics of benign parotid tumours: Warthin's tumour versus other benign salivary tumours.
Some variation from the 'classical' clinical picture for Warthin's tumours is evident in these patients. A predilection for the parotid tail and a propensity for multiplicity has been confirmed. This study sought to analyse demographic and clinical features of a Warthin's patient population. Retrospective review of patients presenting with a benign parotid tumour. The group of Warthin's tumours was compared with the group of patients with other benign parotid tumours. Of 170 primary parotid tumours, 41 (24%) were Warthin's tumour. Mean age of Warthins patients was significantly older (60 years vs 48 years, p = 0.001) and male gender more prevalent (61% vs 33%, p = 0.015) than in other benign tumours. Most (86%) Warthin's tumours were found in the parotid tail, compared with 61% of other benign tumours (p = 0.002). There was no significant ethnic predilection for Warthin's tumours. Bilaterality (30%) and multiplicity (27%) were common. Significance of gender differences disappeared with logistic regression analysis.


Urinary matrix metalloproteinases as a potential screening test for gynecologic malignancies.
This was a pilot study to determine the feasibility of using urinary matrix metalloproteinases (MMPs) as a screening test for gynecologic malignancies. Urine samples from ovarian (n = 29), cervical (n = 31), endometrial (n = 31), and vulvar (n = 5) cancer patients and 19 controls were collected. Substrate gel electrophoresis (zymography) was used to determine the presence of MMP-2 (72 kDa), MMP-9 (92 kDa) and two high-molecular-weight forms (130 and 220 kDa) of MMPs. The sensitivity, specificity, and positive and negative predictive values of the test for each tumor type were determined. No association was noted between malignancy and presence of urinary MMPs in ovarian, cervical, endometrial, or vulvar cancer patients. Sensitivity, specificity, negative and positive predictive values, and likelihood ratios were determined. Sensitivities ranged from 28.1 to 51.0% for individual MMPs, peaking at 69.8% when the presence of any of the four proteinases was considered a positive test. Specificities ranged from 42.1 to 68.4%. Our study suggests that the presence of MMPs in the urine of patients with a gynecologic malignancy is not an adequate screening test for disease. There was also little evidence of an association between urinary MMPs and stage or extent of disease. However, the limited number of patients in the various stages of each disease site, specifically advanced stage disease, make it difficult to state this definitively.


Poly-FISH: a technique of repeated hybridizations that improves cytogenetic analysis of fetal cells in maternal blood.
Prenatal diagnosis of fetal chromosomal abnormalities using interphase fetal nucleated erythrocytes (FNRBCs) separated from maternal peripheral blood can be technically challenging due to the limited number of FNRBCs available for analysis, the limited number of probes that can be used simultaneously, and low FISH efficiency on the formaldehyde-fixed and immunohistochemically stained interphase FNRBCs. We developed a technique of sequential FISH analysis that involves removal of the previous hybridized probe under denaturing conditions, and rehybridization with different probes to improve FISH efficiency. This technique facilitates the analysis of multiple chromosome-specific probes on the same nuclei. Results from our experiments show that FISH can be performed at least nine times on the same interphase nucleus and at least three different probes can be used simultaneously. Thus, theoretically, at least 24 different chromosomes can be analysed on a single interphase fetal cell isolated from maternal blood. We have termed this technique 'Poly-FISH', and have successfully diagnosed trisomy 21, triploidy, and other chromosome abnormalities in FNRBCs using this technique.


Demand outstrips supply of US pediatric dermatologists: results from a national survey.
The US pediatric dermatology workforce was last examined in 1986 when limited employment opportunity was found. We sought to re-examine pediatric dermatology workforce issues. US dermatology chairpersons and residency program directors were surveyed for: (1) agreement with pediatric dermatology workforce statements; and (2) pediatric dermatology faculty and fellow numbers. Respondents agreed that having a pediatric dermatologist or dermatologists on faculty is important, and that a shortage of pediatric dermatologists exists, but did not agree that increasing pediatric dermatology training requirements will increase this shortage. Almost half of the programs (45/94) employed a full-time pediatric dermatologist, and 24 programs had currently been recruiting a pediatric dermatologist for more than 1 year. Only 6 pediatric dermatology fellows were in training. Given that open pediatric dermatology faculty positions greatly exceed the number of fellows in training and that formal training requirements will be increasing, the shortage of pediatric dermatologists will likely continue.


Clinical effectiveness, quality of life and cost-effectiveness of Flaminal® versus Flamazine® in the treatment of partial thickness burns: study protocol for a randomized controlled trial.
Partial thickness burns are painful, difficult to manage and can have a negative effect on quality of life through scarring, permanent disfigurement and loss of function. The aim of burn treatment in partial thickness burns is to save lives, stimulate wound healing by creating an optimumly moist wound environment, to have debriding and analgesic effects, protect the wound from infection and be convenient for the patient and caregivers. However, there is no consensus on the optimal treatment of partial thickness wounds. Flaminal® and Flamazine® are two standard treatment options that provide the above mentioned properties in burn treatment. Nevertheless, no randomized controlled study has yet compared these two common treatment modalities in partial thickness burns. Thus, the aim of this study is to evaluate the clinical effectiveness, quality of life and cost-effectiveness of Flaminal® versus Flamazine® in the treatment of partial thickness burns. In this two-arm open multi-center randomized controlled trial, 90 patients will be randomized between Flaminal® and Flamazine® and followed for 12 months. The study population will consist of competent or temporarily non-competent (because of sedation and/or intubation) patients, 18 years of age or older, with acute partial thickness burns and a total body surface area (TBSA) of less than 30 %. The main study outcome is time to complete re-epithelialization (greater than 95 %). Secondary outcome measures include need for grafting, wound colonization/infection, number of dressing changes, pain and anxiety, scar formation, health-related quality of life (HRQoL), and costs. This study will contribute to the optimal treatment of patients with partial thickness burn wounds and will provide evidence on the (cost-)effectiveness and quality of life of Flaminal® versus Flamazine® in the treatment of partial thickness burns. Netherlands Trial Register NTR4486 , registered on 2 April 2014.


The treadmill effect in a fixed budget system.
We examine the interaction in the market for physician services when the total budget for reimbursement is fixed. Physicians obtain points for the services they render. At the end of the period the budget is divided by the sum of all points submitted, which determines the price per point. We show that this retrospective payment system involves -- compared to a fee-for-service remuneration system -- a severe coordination problem, which potentially leads to the "treadmill effect". We argue that when market entry is possible, a budget can be efficiency enhancing, if in addition a price floor is used.


Quantitative analysis of trace gases of breath during exercise using the new SIFT-MS technique.
We show how the concentration of the breath gases ammonia, acetone, and isoprene vary with time during exercise using the new selected ion flow tube mass spectrometry (SIFT-MS) technique. The expired breath concentrations of ammonia, acetone and isoprene were observed within the range of 50-500, 100-1400 and 5-400 ppb, respectively. Increasing acetone levels were observed for most subjects during the exercise period. However, isoprene levels decreased with time during exercise. Older subjects showed higher levels of isoprene compared with younger subjects. The ammonia time profile with exercise showed both decreasing and increasing patterns for different subjects.


Defining the limits of the anterior wall of the cavernous sinus through an endoscopic view: Cadaveric anatomical study.
The anterior wall of the cavernous sinus (CS) represents an important landmark for endoscopic surgery that although mentioned before, no precise anatomical boundaries have been described. We describe the anatomical landmarks that delimit the anterior wall of the CS, emphasizing its importance as a reference for accessing the CS through endoscopic approaches. Six adult cadaveric heads fixed with formaldehyde and injected with colored silicone were studied. In all the heads, an endonasal endoscopic approach to the sellar and parasellar regions was performed and the anatomy of the anterior wall of the CS was studied. Four consistent anatomical landmarks that mark the limits of the anterior wall of the CS were found in all the specimens: anterosuperiorly, the lateral opticocarotid recess; posterosuperiorly, the medial opticocarotid recess; anteroinferiorly, the inferior part of the maxillary strut; and posteroinferiorly, the superolateral angle of the clival recess. It is of paramount importance to recognize the anatomical landmarks that define the limits of the anterior wall of the CS to achieve a safe access to this so complex region.


Spatial and genetic clustering of Plasmodium falciparum and Plasmodium vivax infections in a low-transmission area of Ethiopia.
The distribution of malaria infections is heterogeneous in space and time, especially in low transmission settings. Understanding this clustering may allow identification and targeting of pockets of transmission. In Adama district, Ethiopia, Plasmodium falciparum and P. vivax malaria patients and controls were examined, together with household members and immediate neighbors. Rapid diagnostic test and quantitative PCR (qPCR) were used for the detection of infections that were genetically characterized by a panel of microsatellite loci for P. falciparum (26) and P. vivax (11), respectively. Individuals living in households of clinical P. falciparum patients were more likely to have qPCR detected P. falciparum infections (22.0%, 9/41) compared to individuals in control households (8.7%, 37/426; odds ratio, 2.9; 95% confidence interval, 1.3-6.4; P = .007). Genetically related P. falciparum, but not P. vivax infections showed strong clustering within households. Genotyping revealed a marked temporal cluster of P. falciparum infections, almost exclusively comprised of clinical cases. These findings uncover previously unappreciated transmission dynamics and support a rational approach to reactive case detection strategies for P. falciparum in Ethiopia.


Adipogenic progenitors in different organs: Pathophysiological implications.
In physiological conditions, the adipose organ resides in well-defined areas, where it acts providing an energy supply and as an endocrine organ involved in the control of whole-body energy metabolism. Adipose tissue adipokines connect the body's nutritional status to the regulation of energy balance. When it surrounds organs, it provides also for mechanical protection. Adipose tissue has a complex and heterogenous cellular composition that includes adipocytes, adipose tissue-derived stromal and stem cells (ASCs) which are mesenchymal stromal cells, and endothelial and immune cells, which signal to each other and to other tissues to maintain homeostasis. In obesity and in other nutrition related diseases, as well as in age-related diseases, biological and functional changes of adipose tissue give rise to several complications. Obesity triggers alterations of ASCs, impairing adipose tissue remodeling and adipose tissue function, which induces low-grade systemic inflammation, progressive insulin resistance and other metabolic disorders. Adipose tissue grows by hyperplasia recruiting new ASCs and by hypertrophy, up to its expandability limit. To overcome this limitation and to store the excess of nutrients, adipose tissue develops ectopically, involving organs such as muscle, bone marrow and the heart. The origin of ectopic adipose organ is not clearly elucidated, and a possible explanation lies in the stimulation of the adipogenic differentiation of mesenchymal precursor cells which normally differentiate toward a lineage specific for the organ in which they reside. The chronic exposition of these newly-formed adipose depots to the pathological environment, will confer to them all the phenotypic characteristics of a dysfunctional adipose tissue, perpetuating the organ alterations. Visceral fat, but also ectopic fat, either in the liver, muscle or heart, can increase the risk of developing insulin resistance, type 2 diabetes, and cardiovascular diseases. Being able to prevent and to target dysfunctional adipose tissue will avoid the progression towards the complications of obesity and other nutrition-related diseases. The aim of this review is to summarize some of the knowledge regarding the presence of adipose tissue in particular tissues (where it is not usually present), describing the composition of its adipogenic precursors, and the interactions responsible for the development of organ pathologies.


Heparin pharmacokinetics: increased requirements in pulmonary embolism.
Heparin disappearance after injection and plasma levels during continuous infusion were studied in normal subjects and patients with thrombophlebitis, pulmonary embolism, renal failure, and liver failure. Heparin removal in normal subjects after 75 u/kg was nearly linear with a clearance of 0.64 ml/min/kg, SD +/- 0.11. Clearance varied inversely with dose. Heparin clearance in pulmonary embolism (0.80 ml/min/kg +/- 0.23) was significantly accelerated compared both to normals (P less than 0.005) and to thrombophlebitis patients (0.55 ml/min/kg +/- 0.19, P less than 0.01); the disappearance was more curvilinear in thrombophlebitis and pulmonary embolism than in normal subjects (P less than 0.025). Continuous infusion heparin requirements were greater in pulmonary embolism than in thrombophlebitis, in accordance with pharmacokinetic predictions. The pattern and rate of disappearance in renal disease was similar to normal subjects; in liver disease clearance was accelerated (0.86 ml/min/kg +/- 0.28) and disappearance curvilinear. Because of accelerated clearance, the initial dose of heparin in pulmonary embolism should be greater (25 u/kg/h) than in thrombophlebitis (10-15 u/kg/h). Variability within patient groups necessitates some laboratory control of dosage.


The cost-effectiveness of a universal influenza vaccination program for adults aged 50-64 years in Australia.
Currently the Australian government funds universal influenza vaccine for all those aged > or =65 years under the National Immunisation Program (NIP). Annual vaccination rates in those aged 50-64 years are significantly lower than vaccination rates in those aged > or =65 years, and currently less than half those at high-risk of influenza-related complications aged 50-64 years are immunised. This study used a decision tree model to examine the cost-effectiveness of lowering the age threshold for the influenza NIP in Australia to include those aged 50-64 years. From a healthcare payer perspective, a new influenza vaccination policy would cost $8908/QALY gained. From a societal perspective, a new influenza vaccination policy would cost $8338/QALY gained. From a governmental perspective, a new influenza vaccination policy would cost $22,408/QALY gained. The most influential parameters in deterministic sensitivity analysis included: probability of death due to influenza, vaccine efficacy against mortality, vaccine uptake, vaccine cost, and vaccine administration cost. Influenza vaccination for people aged 50-64 years appears highly cost-effective, and should be a strong candidate for funding under the NIP.


Nimodipine accelerates reinnervation of denervated rat thyroarytenoid muscle following nerve-muscle pedicle implantation.
To determine whether nimodipine, an L-type voltage-operated calcium channel antagonist that is an accelerator of axonal regeneration following peripheral nerve injury, can expedite reinnervation of denervated rat thyroarytenoid (TA) muscle following nerve-muscle pedicle (NMP) flap implantation. A quantitative histologic and physiologic assessment of the TA muscle following NMP flap implantation, with or without nimodipine treatment. Using 72 Wistar rats, we performed a transection on the left recurrent laryngeal nerve, followed by NMP flap implantation. Thirty-six animals received nimodipine treatment (NIMO [+] group), and the remaining 36 animals received no nimodipine treatment (NIMO [-] group). As a control, 18 animals were subjected only to transection of the left recurrent laryngeal nerve. We performed a histologic assessment for muscle area, axon, nerve terminals (NTs), and acetylcholine receptors (AchRs) in the TA muscle and electromyography at 2, 4, and 10 weeks after surgery. Muscle area, ratio of the number of NTs to that of AchRs (NT/AchR ratio), and evoked action potential in the TA muscle were significantly greater in the NIMO (+) group than in the NIMO (-) group (P < .05) at 4 weeks. At 10 weeks, the NT/AchR ratio was significantly greater in the NIMO (+) group than in the NIMO (-) group (P < .05). We found that nimodipine accelerated reinnervation of the denervated TA muscle following NMP flap implantation.


Long-Term Visuo-Gustatory Appetitive and Aversive Conditioning Potentiate Human Visual Evoked Potentials.
Human recognition of foods and beverages are often based on visual cues associated with flavors. The dynamics of neurophysiological plasticity related to acquisition of such long-term associations has only recently become the target of investigation. In the present work, the effects of appetitive and aversive visuo-gustatory conditioning were studied with high density EEG-recordings focusing on late components in the visual evoked potentials (VEPs), specifically the N2-P3 waves. Unfamiliar images were paired with either a pleasant or an unpleasant juice and VEPs evoked by the images were compared before and 1 day after the pairings. In electrodes located over posterior visual cortex areas, the following changes were observed after conditioning: the amplitude from the N2-peak to the P3-peak increased and the N2 peak delay was reduced. The percentage increase of N2-to-P3 amplitudes was asymmetrically distributed over the posterior hemispheres despite the fact that the images were bilaterally symmetrical across the two visual hemifields. The percentage increases of N2-to-P3 amplitudes in each experimental subject correlated with the subject's evaluation of positive or negative hedonic valences of the two juices. The results from 118 scalp electrodes gave surface maps of theta power distributions showing increased power over posterior visual areas after the pairings. Source current distributions calculated from swLORETA revealed that visual evoked currents rose as a result of conditioning in five cortical regions-from primary visual areas and into the inferior temporal gyrus (ITG). These learning-induced changes were seen after both appetitive and aversive training while a sham trained control group showed no changes. It is concluded that long-term visuo-gustatory conditioning potentiated the N2-P3 complex, and it is suggested that the changes are regulated by the perceived hedonic valence of the US.


Structural characterisation of a rhamnan and a fucorhamnan, both present in the lipopolysaccharide of Burkholderia vietnamiensis strain LMG 10926.
The polymeric fraction isolated after mild acid hydrolysis of the lipopolysaccharide (LPS) from Burkholderia vietnamiensis strain LMG 10926 contained L-rhamnose (Rha) and D-fucose (Fuc). From NMR studies supported by the results of methylation analysis and Smith degradation, it could be inferred that the material was probably a mixture of two glycans. One component was a linear rhamnan with a trisaccharide repeating unit (1); the other was a branched fucorhamnan with a tetrasaccharide repeating unit (2). The presence of two distinct polymeric fractions in LPS is a common feature for Burkholderia species. [structures: see text]


Lactate dehydrogenase--X--separation of human spermatozoa isoenzymes by extraction with detergents.
Proteins with known enzymatic properties are attractive molecules as possible agents for immunological contraception. Therefore a new technique for the selective isolation of LDH-X from human spermatozoa is described. Applying the detergents hyamine 2389 and triton X-100 LDH-X is extracted from the sperm surface membrane without the other LDH-isoenzymes. Ultrasonification of spermatozoa yields all LDH-isoenzymes together. After cell disruption the separation of LDH-X and the isoenzymes is performed by discelectrophoresis. With lactate as substrate tetrazolium staining identifies all LDH-enzymes. The technique represents an attractive method for the selective isolation of LDH-X and opens further purification steps.


Targeted NGS meets expert clinical characterization: Efficient diagnosis of spastic paraplegia type 11.
Next generation sequencing (NGS) is transforming the diagnostic approach for neurological disorders, since it allows simultaneous analysis of hundreds of genes, even based on just a broad, syndromic patient categorization. However, such an approach bears a high risk of incidental and uncertain genetic findings. We report a patient with spastic paraplegia whose comprehensive neurological and imaging examination raised a high clinical suspicion of SPG11. Thus, although our NGS pipeline for this group of disorders includes gene panel and exome sequencing, in this sample only the spatacsin gene region was captured and subsequently searched for mutations. Two probably pathogenic variants were quickly and clearly identified, confirming the diagnosis of SPG11. This case illustrates how combination of expert clinical characterization with highly oriented NGS protocols leads to a fast, cost-efficient diagnosis, minimizing the risk of findings with unclear significance.


Bulked segregant RNA-sequencing (BSR-seq) identified a novel rare allele of eIF4E effective against multiple isolates of BaYMV/BaMMV.
A novel rare allele of the barley host factor gene eIF4E for BaMMV/BaYMV infection was identified in an Iranian landrace that showed broad resistance to barley yellow mosaic virus disease, and molecular markers facilitating efficient selection were developed. The soil-borne yellow mosaic virus disease caused by different strains of barley yellow mosaic virus (BaYMV) and barley mild mosaic virus (BaMMV) is a major threat to winter barley (Hordeum vulgare) production in Europe and East Asia. However, the exploration of resistant germplasm or casual genes for barley breeding is rather limited in relation to the rapid diversification of viral strains. Here, we identified an Iranian barley landrace 'HOR3298,' which represented complete resistance to BaYMV and BaMMV. In contrast to rym4 and rym5, which act as the predominant source in Europe and East Asia for breeding resistant cultivars over decades and which have been overcome by several virulent isolates, this landrace showed broad-spectrum resistance to multiple isolates of BaYMV/BaMMV in the fields of Germany and China. By employment of bulked segregant RNA sequencing, test for allelism, and haplotype analysis, a recessive resistance gene in 'HOR3298' was genetically mapped coincident with the host factor eukaryotic translation initiation factor 4E (eIF4E, causal gene of rym4 and rym5). The eIF4EHOR3298 allele encoded for a novel haplotype that contained an exclusive nucleotide mutation (G565A) in the coding sequence. The easily handled markers were developed based on the exclusively rare variation, providing precise selection of this allele. Thus, this work provided a novel reliable resistance source and the feasible marker-assisted selection assays that can be used in breeding for barley yellow mosaic virus disease resistance in cultivated barley.


Prevention of TNF-induced necrotic cell death by rottlerin through a Nox1 NADPH oxidase.
Previous studies have demonstrated that rottlerin, a specific PKCdelta inhibitor, potentiates death receptor- mediated apoptosis through a cytochrome c-dependent or -independent pathway. However, its ability to regulate necrotic cell death, as well as the underlying mechanism, remains unknown. We found that in murine fibrosarcoma L929 cells, treatment with rottlerin protected the cells against TNF-induced necrosis, whereas it sensitized the cells to apoptosis induced by co-treatment with Hsp90 inhibitor geldanamycin and TNF, in a manner independent of its ability to inhibit PKC-delta. TNF treatment induced rapid accumulation of mitochondrial superoxide (O2-) through the Nox1 NADPH oxidase when cells undergo necrosis. Moreover, pretreatment with rottlerin failed to induce the GTP-bound form of small GTPase Rac1 by TNF treatment, and subsequently suppressed mitochondrial O2- production and poly(ADP-ribose) polymerase activation, thus inhibiting necrotic cell death. Therefore, our study suggests that Nox1 NADPH oxidase is a new molecular target for anti-necrotic activity of rottlerin upon death-receptor ligation.


Test of association: which one is the most appropriate for my study?
Hypothesis tests are statistical tools widely used for assessing whether or not there is an association between two or more variables. These tests provide a probability of the type 1 error (p-value), which is used to accept or reject the null study hypothesis. To provide a practical guide to help researchers carefully select the most appropriate procedure to answer the research question. We discuss the logic of hypothesis testing and present the prerequisites of each procedure based on practical examples.


Induction of aldose reductase expression in rat kidney mesangial cells and Chinese hamster ovary cells under hypertonic conditions.
Rat kidney cortex mesangial cells (MES) and Chinese hamster ovary cells (CHO) responded to hypertonicity (600 mosmol/kg) in culture by accumulating sorbitol. The accumulation of sorbitol was due to increased aldose reductase (AR) activity, apparently brought about by increased levels of AR mRNA and protein. The levels of AR mRNA increased approximately 60-fold in MES cells and 30-fold in CHO cells by 24 h in culture media (300 mosmol/kg supplemented with 150 mM NaCl, 600 mosmol/kg total). AR activity also markedly increased (14- to 16-fold above control), but MES took 4 days and CHO 6 days to reach this maximum. Other osmolytes, raffinose and sorbitol (at concentrations of 250 to 300 mM) elicited the same response as that of 150 mM NaCl. These data show that AR expression is induced in MES and CHO cells under hypertonic conditions. Of special interest is the induction of large amounts of AR in rat kidney cortex mesangial cells, a target tissue of diabetes and a site where excessive accumulation of sorbitol is suspected to be a critical factor in diabetic nephropathy.


A comparative study of bio-inspired protective scales using 3D printing and mechanical testing.
Flexible natural armors from fish, alligators or armadillo are attracting an increasing amount of attention for their unique combinations of hardness, flexibility and light weight. The extreme contrast of stiffness between hard scales and surrounding soft tissues gives rise to unusual and attractive mechanisms, which now serve as models for the design of bio-inspired armors. Despite this growing interest, there is little guideline for the choice of materials, optimum thickness, size, shape and arrangement for the protective scales. In this work, we explore how the geometry and arrangement of hard scales can be tailored to promote scale-scale interactions. We use 3D printing to fabricate arrays of scales with increasingly complex geometries and arrangements, from simple squares with no overlap to complex ganoid-scales with overlaps and interlocking features. We performed puncture tests and flexural tests on each of the 3D printed materials, and we report the puncture resistance - compliance characteristics of each design on an Ashby chart. The interactions between the scales can significantly increase the resistance to puncture, and these interactions can be maximized by tuning the geometry and arrangement of the scales. Interestingly, the designs that offer the best combinations of puncture resistance and flexural compliance are similar to the geometry and arrangement of natural teleost and ganoid scales, which suggests that natural evolution has shaped these systems to maximize flexible protection. This study yields new insights into the mechanisms of natural dermal armor, and also suggests new designs for personal protective systems. Flexible natural armors from fishes, alligators or armadillos are attracting an increasing amount of attention for their unique and attractive combinations of hardness, flexibility and low weight. Despite a growing interest in bio-inspired flexible protection, there is still little guideline for the choice of materials, optimum thickness, size, shape and arrangement of the protective scales. In this work, we explore how the geometry and arrangement of hard scales affect puncture resistance and flexural compliance, using 3D printing and mechanical testing. Our main finding is that the performance of the scaled skin in terms of puncture resistance can be significantly improved by slight changes in their geometry and arrangement. Our results also suggest that natural evolution has shaped scaled skins to maximize flexible protection. This study yields new insights into the mechanics of natural dermal armors, and also suggests new designs for personal protective systems.


Teaching and learning birth: "help all to know".
This guest editorial explores the idea that our worldview, regardless of education, influences our childbirth practices, sometimes interfering with achieving the goals of our discipline. Over time, we have lost our ability to support women through the process of childbirth so that they emerge as strong, healthy women. The high road ahead is to teach everyone, including ourselves, that we need to provide optimal, evidence-based care. Pursuing this path will take courage and commitment.


Mortality from cancer and other causes in an Italian cohort of male rubber tire workers.
To investigate mortality among workers of an Italian rubber tire factory employed between 1954 and 2008. This cohort study included 6246 men, totaling 190,512 man-years of observation. Employment data were obtained from personnel records, whereas vital status and causes of death were ascertained from local authorities. We computed standardized mortality ratios (SMRs) using national and regional death certification rates. Mortality was significantly lower than expected for all cancers (SMR = 79) and all causes (SMR = 85). The SMRs were 99 for cancer of stomach, 78 for lung, 121 for urinary bladder, 116 for lymphoma, and 89 for leukemia, none being significant. Decreased mortality emerged for cancers of the oral cavity and pharynx (SMR = 45), esophagus (SMR = 29), colorectum (SMR = 71), liver (SMR = 57), and kidney (SMR = 33). This study shows no excess cancer risk among male rubber tire workers employed after 1954.


Hybrid liposomes affect cellular lipid constituents and caveolae structures.
We examined alterations of lipid constituents induced by hybrid liposomes (HLs) in cancer cells. As early as 1h after HL treatment, amounts of the raft/caveolae lipids sphingomyelin, ceramide, and ether-type PC were altered. In addition, the structures of caveolae on the cytoplasmic surface of the cell membrane were significantly changed. Our results suggest that alterations of lipid composition in caveolae mediate HL signaling for apoptosis.


Effects of sulphate and urea on the stability and reversible unfolding of beta-lactamase from Staphylococcus aureus. Implications for the folding pathway of beta-lactamase.
The reversible denaturation by urea of beta-lactamase from Staphylococcus aureus was followed in the presence and absence of ammonium sulphate by circular dichroism studies, difference absorption spectroscopy and measurement of enzyme activity. The multiple unfolding and refolding transitions demonstrate the existence of a thermodynamically stable state of intermediate conformation in equilibrium with the native (N) and fully unfolded (U) states. Its physical properties show that it is identical to the state H found on denaturation by guanidinium chloride. State H is 10.1 (+/-1.5) kJ mol-1 less stable than the native state and 10.1 (+/-1.6) kJ mol-1 more stable than the unfolded state. Ammonium sulphate shifts both the N in equilibrium H and H in equilibrium U transitions to concentrations of urea higher by 5.3 M per mole of sulphate. It has markedly different effects on the thermodynamic stabilities of states N and H, making delta G'N-H, O and delta G'H-U, O more negative by 41 kJ mol and 20 kJ mole, respectively, per mole of ammonium sulphate. The change in equilibrium constant for the N-H transition is reflected almost exclusively in a dramatic change of the unfolding rate constant, which is decreased by a factor of 10(11) on addition of 1.4 M-sulphate. The presence of the substrate benzyl penicillin has little effect on the equilibria or kinetics of the N-H transition. The results are discussed in terms of the nature of the N-H transition and of the ordering of intermediate states on the folding pathway.


Editorial Commentary: The Larger Holes or Larger Number of Holes We Drill in the Coracoid, the Weaker the Coracoid Becomes.
The larger holes or larger number of holes we drill in the coracoid, the weaker the coracoid becomes. Thus, minimizing bone holes (both size and number) is required to lower risk of coracoid process fracture, in patients in whom transosseous shoulder acromioclavicular joint reconstruction is indicated. A single 2.4-mm-diameter tunnel drilled through both the clavicle and the coracoid lowers the risk of fracture, but the risk cannot be entirely eliminated.


The olive and central control of blood pressure.
This evidence, then, would suggest that the olive becomes active when, with a change in the motor task, the motor performance is required to adjust to the new circumstance. From Smith's experiments on blood pressure, it is extrapolated that the olive becomes active when there is a change in the physiological state, and the autonomic performance is required to adjust to the new circumstance. The important point is that the olive does have an experimental effect on blood pressure, and that it is a specific, though indirect, effect acting through the carotid sinus reflex. This effect appears similar to the effect on motor control which is specific for motor learning, and appears to act indirectly through the cerebellum. The hypothesis is being put forward because of the importance of blood pressure abnormalities, and the possible therpeutic benefits to be derived from an understanding of the central control of blood pressure. It is hoped that in pursuing this elusive control system one shall not overlook the olive.


Cholinergic and non-cholinergic components of the inotropism evoked by electric field stimulation in the isolated rat urinary bladder. Influence of some eicosanoids.
The present study explores whether some arachidonic acid (AA) metabolites formed via cyclo-oxygenase or lipoxygenase pathways influence the inotropism of isolated rat urinary bladders evoked by electric field stimulation (EFS), both in presence of or in absence of atropine. The EFS consisted in square wave pulses of 5 Hz, 5 msec duration and supramaximal voltage, applied every 3 min for a period of 10 sec. Acetylsalicylic acid (ASA) at 10(-4) M, decreased around 30% the magnitude of inotropic responses to EFS and prostaglandin E2 (PGE2, partially at 10(-9) M and fully at 10(-8) M), restored control inotropic levels. PGI2 was also active but only at 10(-7) M; whereas PGF2 alpha, at all concentrations tested (10(-9)-10(-7) M), failed to counteract the diminishing effect of ASA. Moreover, dose-response curves for added acetylcholine (ACh) were not modified by ASA. On the other hand, in presence of atropine (10(-5) M), a diminution of around 40% in the magnitude of control responses to EFS, was detected and when ASA (10(-4) M) was added to atropine-exposed preparations, the atropine resistant component of the EFS-evoked inotropism, was reduced around 30%. Although recovering effects of added PGs were again observed, they were not identical to those observed in absence of atropine. Indeed, PGE2 fully restored the magnitude of contractile responses but it did so only at concentrations 10 times higher than without the cholinergic receptor blocker. On the other hand, PGI2 as well as PGF2 alpha, even at 10(-7) M, were devoid of significant influence. In determining whether lipoxygenase products of AA were also able to modulate the EFS-evoked inotropism, tissue preparations were incubated with nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenases, and tested for contractile responses to electric stimulation. NDGA (10(-7) M), failed to alter rat urinary bladder inotropic response to EFS, both in presence of or in absence of atropine. Results suggest that the cholinergic, as well as the non-cholinergic components of the EFS-evoked contractions in isolated rat urinary bladders, are modulated by some cyclo-oxygenase formed AA metabolites, particularly certain PGs, like PGE2.


Catalytic oxidative treatment of diluted black liquor at mild conditions using copper oxide/cerium oxide catalyst.
Wet-air oxidation of diluted black liquor (chemical oxygen demand [COD] approximately 3250 to 14 500 mg/L) was performed at mild operating conditions (temperature = 388 to 423 K and total pressure = 0.6 MPa) in the presence of heterogeneous 60% copper oxide (CuO)/ 40% cerium oxide (CeO2) catalyst. Maximum COD reduction of 77.3% was obtained at 423 K at pH 3.0, which was marginally higher than that obtained at 413 K temperature (77.1%). In the acidic environment (pH < or = 3), most of the COD was removed in the form of settleable solids during the transient heating of the wastewater from room temperature to the desired one. The solid residue obtained after the reaction has a heating value of 20.1 MJ/kg, which is comparable with that of Indian coal. Thermal degradation kinetic determination suggested that thermal characteristics of the solid residue are well represented by a power law model with Agarwal and Sivasubramanian approximation (Safi et al., 2004).


Flavonoid and stilbene derivatives from Macaranga trichocarpa.
A new farnesylated flavonol (4'-O-methylmacagigantin) and a new geranylated stilbene (macatrichocarpin H), together with eight known phenolic compounds, have been isolated from the leaves of Macaranga trichocarpa. Structures of these compounds were determined based on NMR and mass spectrroscopic data. Cytotoxic properties of the isolated compounds were tested against P-388 cells showing that mactrichocarpin G was the most active compound with IC50 was 3.5μM.


Is anterior subcapital shortening osteotomy a reliable and reproducible technique in the treatment of severe slipped capital femoral epiphysis?
Proximal femoral shortening osteotomies are becoming the treatment of choice for severe slipped capital femoral epiphysis (SCFE) to reduce the risk of femoroacetabular impingement. The reported rates of complication seem reasonable, but these are single-operator series with surgeons highly experienced in this technique. The purpose of this study was to assess how surgeon experience impacted the outcomes of anterior subcapital shortening osteotomy (ASSO) in severe SCFE. The hypothesis was that ASSO is a reproducible technique that is accessible to junior surgeons. All ASSOs performed for severe SCFE (slipangle > 40°) between 2015 and 2019 were retrospectively reviewed. All osteotomies were performed by surgeons with less than 4 years' experience (senior residents), who were trained by a senior surgeon experienced in this technique (Group 1). The incidence of femoral head avascular necrosis (AVN) and complications were analyzed and compared to a historical control cohort (Group 2). A total of 62 SCFEs (37 unstable and 25 stable) were analyzed. Both groups had similar demographic data and SCFE characteristics. The mean operative times were statistically comparable in both groups. The rates of AVN in unstable SCFEs and in the overall series were comparable in both groups (18.9% vs. 13.3%, p=.55 and 12.9% vs. 9.7%, p=.6). These rates were comparable in the stable forms (4.0% vs. 5.4%; p=1). However, the preoperative MRI in Group 1 showed that 42.8% of unstable hips that developed AVN were already hypoperfused before surgery. The overall rate of complication showed no significant difference between the 2 groups (26% vs. 17%, p=.16). Although ASSO is a technically demanding procedure, it is reliable and reproducible. The main risk factor for developing AVN remains the unstable nature of SCFE and not the surgeon's experience. It can be performed by trained junior surgeons, but not in an emergency setting, with the possibility of assistance from a more experienced surgeon. IV; retrospective case study.


Treatment Patterns Among Patients with Bipolar Disorder in the United States: A Retrospective Claims Database Analysis.
Bipolar disorder is a chronic and complex disorder that can be difficult to treat. The objective of this retrospective study was to describe treatment patterns among patients with bipolar disorder. Adults newly diagnosed with bipolar disorder from 2016 to 2018 were identified using the IBM® MarketScan® Commercial claims database. Patients were enrolled for at least 12 months prior to and 6 months after initial diagnosis. Lines of therapy (LOTs) were continuous treatment periods based on filled prescriptions; medications, such as antidepressants, mood stabilizers, atypical antipsychotics, benzodiazepines, stimulants, and off-label prescriptions, were recorded. All data were analyzed descriptively. A total of 40,345 patients met criteria. The most common initial episode types were bipolar II (38.1%), and bipolar I depression (29.8%), mania (12.8%), and mixed features (12.0%). Among all episode types, approximately 90% of patients received treatment (LOT1) and approximately 80% of these patients received at least one additional LOT. Across all episode types, the most common medication classes in LOT1 (n = 36,587) were mood stabilizers (43.8%), antidepressants (42.3%; 12.9% as monotherapy), atypical antipsychotics (31.7%), and benzodiazepines (20.7%); with subsequent LOTs, antidepressant (51.4-53.8%) and benzodiazepine (26.9-27.4%) usage increased. Also in LOT1, there were 2067 different regimens. Treatment patterns were generally similar across episode type. Antidepressants and benzodiazepines were frequently prescribed to treat bipolar disorder despite guidelines recommending against use as frontline therapy. These results highlight the considerable heterogeneity in care and suggest that many clinicians treating bipolar disorder are not using evidence-based prescribing practices.


Preliminary findings of arterial embolization with balloon-occluded and flow-dependent histoacryl glue embolization in a swine model.
To evaluate the potential usefulness of the balloon-occluded histoacryl glue embolization (B-glue) technique. Both flow-dependent (no balloon occlusion) and B-glue techniques were used for 24 intercostal arteries of two female swine. N-butyl 2-cyanoacrylate (NBCA) was diluted with lipiodol to a 50 % solution, which was infused after occluding the arteries with microballoon catheters. The embolization range, fragmentation, reflux, adhesion, and glue particle attachment were compared between flow-dependent and B-glue techniques. The B-glue technique was performed in a controlled fashion resulting in successful arterial occlusion without fragmented migration of the injected glue cast. Reflux occurred less frequently with the B-glue technique and was significantly different (p = 0.039) [Corrected] from that for the flow-dependent technique. Catheters were safely removed from the arterial walls, although in one instance (8.3 %), large glue particles were found to be attached to the catheter tip on removal. Conversely, the flow-dependent technique was more difficult to control and resulted in several instances of higher rates of fragmentation. The B-glue technique can efficiently control NBCA delivery with lower rates of reflux.


Measurement of a helium tune-out frequency: an independent test of quantum electrodynamics.
Despite quantum electrodynamics (QED) being one of the most stringently tested theories underpinning modern physics, recent precision atomic spectroscopy measurements have uncovered several small discrepancies between experiment and theory. One particularly powerful experimental observable that tests QED independently of traditional energy level measurements is the "tune-out" frequency, where the dynamic polarizability vanishes and the atom does not interact with applied laser light. In this work, we measure the tune-out frequency for the 23S1 state of helium between transitions to the 23P and 33P manifolds and compare it with new theoretical QED calculations. The experimentally determined value of 725,736,700(260) megahertz differs from theory [725,736,252(9) megahertz] by 1.7 times the measurement uncertainty and resolves both the QED contributions and retardation corrections.


Case report. Mycotic aneurysm of the superior mesenteric artery: report of a successful repair.
A case of a patient with a mycotic superior mesenteric artery aneurysm that was successfully repaired by the technique of restorative endoaneurysmorrhaphy is presented. Principles of diagnosis and management are delineated.


[Chronic sciatic pain caused by sciatic nerve schwannoma].
Schwannomas are tumors with slowly progressive symptoms, more often painful than associated with neurologic deficits. Involvement of the sciatic nerve mimics chronic sciatic pain due to a herniated disk. If there is no lumbar pain and lumbar MRI is normal, the sciatic nerve must be clinically and radiologically examined all along its course. We report a patient with chronic sciatica in whom physical examination revealed a painful mass with a Tinel sign in her back thigh. MRI showed a multilobular mass along the sciatic nerve. Surgery of this plexiform schwannoma allowed a complete relief from pain.


Removal of COD from real oily wastewater by electrocoagulation using a new configuration of electrodes.
In order to bring the chemical oxygen demand (COD) concentration down to safe levels for widespread use, this study plans to use a state-of-the-art electrocoagulation reactor (ECR) to treat real oily wastewater discharged from the Al-Muthanna petroleum refinery. A one-side finned (1SF) cathode tube was positioned between two tubular anodes in the continuous ECR, where the active area of the cathode was much more than its submerged volume. Each of these electrodes was made of aluminum and joined in a monopolar parallel to a DC power supply. On COD elimination efficiency, the impacts of operational parameters such as electrolysis time (4-60 min), current density (0.630-5.000 mA/cm2), and flow rate (50-150 ml/min) were explored. In conclusion, Increasing current density and electrolysis duration increases COD removal efficiency, whereas increasing flow rate reduces it. COD removal efficiencies were 82% at optimal electrolysis times of 60 (min), 5 (mA/cm2) current density, and 50 (ml/min) flow rate, with energy consumption of 4.787 (kWh/kg COD) and electrode consumption of 0.544 (g). The investigation results demonstrated that the new reactor could treat oily wastewater within the specified operational limits. It might be used before other, more conventional treatments.


[How long can we wait at full dilatation. A study of maternal and neonatal morbidity related to the duration of the second stage of labour in nulliparous women].
To determine the statistical association, in nulliparous patients, between maternal and fetal morbidity and the length of the second stage of labour. To precise whether a prolongation of this period of more than 2h may results in a dramatic increase of this morbidity. Retrospective cohort study conducted in a level III referral centre between 1 April 2004 and 30 April 2005, including all nulliparous, term, cephalic, live singleton birth without fetal malformation in patients reaching the second stage of labour (n=1191). All deliveries were performed without restrictions in the length of the second stage of labour in the absence of fetal heart rate abnormalities. Maternal and neonatal morbidity were examined according to the duration of the second stage of labour with univariate analysis and after statistical adjustment with multivariate logistic regression for potential confounding variables. Global maternal morbidity ranged from 5.7% after 1h to 20.4% after more than 3h of full cervical dilatation. After a second stage duration of 2h, each additional completed hour resulted in a significant increase in global maternal morbidity (OR 1.78; IC 95% [1.59-1.97]), postpartum haemorrhage (OR 1.72; IC 95% [1.21-2.23]) and level three or four perineal lacerations (OR 1.24; IC 95% [1.7-1.41]). In the same time, caesarean section rate (OR 2.09; IC 95% [1.84-2.34]) and operative vaginal deliveries (OR 1.82; IC 95% [1.59-2.05]) increased significantly. Conversely, our study didn't demonstrate any significant association between neonatal morbidity and the length of the second stage of labour. Our study confirmed the association between the duration of the second stage of labour and the increase of maternal but not neonatal morbidity. Such an association, predominantly after 3h spend at full cervical dilatation, needs to be taken into account and, according to our experience, may justify caesarean section.


Impaired neutrophil function during anesthesia and surgery is due to serum factors.
Neutrophil function was assessed in patients undergoing anesthesia and surgery using a chemiluminescence (CL) assay. With the anesthetic agents enflurane and nitrous oxide, peroperative CL (99.1 mV; 13.8 SEM: postinduction but prior to surgery) was significantly lower than the preoperative value (146.5 mV; 14.1 SEM) with a mean fall of 30% (P less than 0.001). CL measurements taken 24 hr postoperatively were significantly increased (193.9 mV; 16.4 SEM) over the pre- and peroperative values, showing mean increases of 32 and 96%, respectively (P less than 0.001 in both cases). The inhibitory influence on CL appeared to be due to serum factors since peroperative patients' sera inhibited control neutrophils. Significantly depressed levels of the complement component C3 and IgG detected during the peroperative period (P less than 0.05) may explain this phenomenon. Postoperatively, C3 and IgG levels returned to normal. The transient decrease in peroperative neutrophil function may be a contributory factor to the establishment of postoperative sepsis in surgical patients.


Synthesis and cellular compatibility of biomineralized Fe3O4 nanoparticles in tumor cells targeting peptides.
Fe3O4 nanoparticles (NPs) coated with WSG-peptide were prepared via a facile biomineralization technique at room temperature. The concentration of the peptides and the mixing time could substantially influence the morphology of as-prepared particles. The saturation magnetization of WSG-coated Fe3O4 particles were 35.92 emu/g, slightly higher than that of Fe3O4 without WSG peptides. Cell viability assay revealed that WSG-coated Fe3O4 particles had a good cellular compatibility. In addition, compared with Fe3O4 NPs, the mineralized Fe3O4 NPs coated with WSG peptides could more easily assemble into the cancer cell, indicating that the WSG-Fe3O4 NPs possess cancer targeting property. Thus, the WSG-coated Fe3O4 NPs could be used in cancer diagnosis and treatment fields.


Reading protein modifications with interaction domains.
Proteins are controlled by a vast and dynamic array of post-translational modifications, many of which create binding sites for specific protein-interaction domains. We propose that these domains, working together, read the state of the proteome and therefore couple post-translational modifications to cellular organization. We also identify common strategies through which modification-dependent interactions synergize to regulate cell behaviour.


Determination of paraquat in tissue using ion-pair chromatography in conjunction with spectrophotometry.
Homogenized tissue was deproteinized with sulfuric acid. Paraquat in the supernatant was quantificated directly with the dithionite reagent (step 1) or concentrated by the XAD-2 column chromatographic technique before paraquat determination (step 2). Tissue paraquat levels in the range of 0.01-75 mg/kg could be quantificated by second-derivative or zero-order spectroscopy using 2.5 g of tissues. The sensitivity could be increased tenfold by using 25 g of tissue samples. The coefficients of variation of within-run and day-to-day precisions of spiked paraquat in tissue homogenates were below 5% at concentrations of 10.0, 1.0 and 0.1 mg/kg, respectively. The recoveries of the spiked paraquat in tissues ranging from 0.1-10 mg/kg were 91% by step 1 and 74% by step 2. Using these simple methods, steps 1 and 2, the paraquat concentrations in the psoas muscle, liver, lung and kidneys of a swine dosed with 0.16 g/kg of paraquat were investigated. The results were in close agreement with those of the TCA deproteinization method followed by cation-resin column chromatography. The proposed method offers the advantages of simplicity, rapidity, reasonable sensitivity and a wide range of concentrations.


Acyl pentapeptide lactone synthesis in actinomycin-producing streptomycetes by feeding with structural analogs of 4-methyl-3-hydroxyanthranilic acid.
Several structural analogs of 4-methyl-3-hydroxyanthranilic acid (4-MHA) that had been established as substrates of the 4-MHA-activating enzyme from Streptomyces chrysomallus (Keller, U., Kleinkauf, H., and Zocher, R. (1984) Biochemistry 23, 1479-1484) were fed in short term labeling experiments to cultures of two actinomycin-producing streptomycetes. Besides inhibition of actinomycin synthesis, the addition of 4-methyl-3-hydroxybenzoic acid, 3-hydroxybenzoic acid, 4-aminobenzoic acid, or 4-methyl-3-methoxy-benzoic acid induced the formation of novel compounds. The data indicate that these compounds are structural analogs of 4-MHA pentapeptide lactones, which are the most probable precursors of actinomycins (Katz, E. (1967) in Antibiotics II (Gottlieb, D., and Shaw, P. D., eds) pp. 276-341, Springer-Verlag, New York). Since the structural analogs of 4-MHA are missing the o-aminophenol configuration, the corresponding acyl pentapeptide lactones cannot react with each other to give phenoxazines. Therefore, they accumulate and thus become detectable. Feeding cultures with 4-MHA resulted in an inhibition of actinomycin synthesis apparently at the level of acyl pentapeptide lactone synthesis. In such experiments, the formation of pentapeptide lactones, which are most likely derived from 4-MHA pentapeptide lactones, could be detected. The results provide experimental evidence that the biosynthesis of actinomycins proceeds via the 4-MHA-pentapeptide lactones.


Silicon dioxide nanoparticles suppress copper toxicity in Mentha arvensis L. by adjusting ROS homeostasis and antioxidant defense system and improving essential oil production.
Copper (Cu) is an essential micronutrient for plants; however, the excessive accumulation of Cu due to various anthropogenic activities generates progressive pollution of agricultural land and that causes a major constraint for crop production. Excess Cu (80 mg kg-1) in the soil diminished growth and biomass, photosynthetic efficiency and essential oil (EO) content in Mentha arvensis L., while amplifying the antioxidant enzyme's function and reactive oxygen species (ROS) production. Therefore, there is a pressing need to explore effective approaches to overcome Cu toxicity in M. arvensis plants. Thus, the present study unveils the potential of foliar supplementation of two distinct forms of silicon dioxide nanoparticles (SiO2 NPs) i.e., Aerosil 200F and Aerosil 300 to confer Cu stress tolerance attributes to M. arvensis. The experiment demonstrated that applied forms of SiO2 NPs (120 mg L-1), enhanced plants' growth and augmented the photosynthetic efficiency along with the activities of CA (carbonic anhydrase) and NR (nitrate reductase), however, the effects were more accentuated by Aerosil 200F application. Supplementation of SiO2 NPs also exhibited a beneficial effect on the antioxidant machinery of Cu-disturbed plants by raising the level of proline and total phenol as well as the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), ascorbate peroxidase (APX) and glutathione reductase (GR), thereby lowering ROS and electrolytic leakage (EL). Interestingly, SiO2 NPs supplementation upscaled EO production in Cu-stressed plants with more pronounced effects received in the case of Aerosil 200F over Aerosil 300. We concluded that the nano form (Aerosil 200F) of SiO2 proved to be the best in improving the Cu-stress tolerance in plants.


Frequent fever episodes and the risk of febrile seizures: the Generation R study.
To examine the association between the number of fever episodes and the risk of febrile seizures. This study was embedded in a population-based prospective cohort study from early foetal life onwards. Information about the occurrence of febrile seizures and fever episodes was collected by questionnaires at the ages of 12, 24 and 36 months. Analyses were based on 3033 subjects. The risk of febrile seizures was compared between children with frequent fever episodes (>2 per year), and children with only 1 or 2 fever episodes per year. The frequency of fever episodes was not associated with the risk of febrile seizures in the age range of 6-12 months. In the second and third year of life, having more than 2 fever episodes was associated with an increased risk of febrile seizures (odds ratios 2.02 [95% confidence interval 1.13-3.62] and 2.29 [95% confidence interval 1.00-5.24], respectively). In the age range between 6 and 36 months, we observed a significant trend between the frequency of fever episodes (<2, 3-4 or >4 per year) and the risk of febrile seizures (p-value for trend < 0.001). The association between the number of fever episodes and the occurrence of febrile seizures was stronger for children with recurrent febrile seizures. Frequent fever episodes are associated with an increased risk of febrile seizures in the second and third years of life. Further studies are needed to identify the mechanisms underlying this association.


Opioid Use Disorder ECHO: A Program Evaluation of a Project That Provides Knowledge and Builds Capacity for Community Health Workers in Medically Underserved Areas of South Texas.
Opioid use disorder is a growing public health concern in South Texas. To assist in mitigating the effects of this epidemic, staff produced a program that focused on replicating, modifying, and evaluating the impact of the "Opioid Addiction Treatment ECHO™ (Extension of Community Health Outcomes) for CHWs (community health workers) program" on 26 CHWs practicing in rural and other medically underserved areas through teleconferencing technology. CHWs trained on the topic of substance use disorder concentrated on behavioral health integration with a focus on opioid prescription misuse. The analysis found that knowledge attainment was increased above the pretest means. The ECHO™ model proved to be effective at linking subject matter experts and specialists at an academic "hub" with CHWs in local communities.


What your hairy cell leukemia patients want you to know.
Hairy cell leukemia is different from most other hematologic malignancies because it is so rare. Patient concerns include finding a knowledgeable physician, confirming the diagnosis at the initial presentation, coping with treatment side effects and monitoring for potential relapse of this chronic disease.


Surveillance of deep vein thrombosis in asymptomatic total hip replacement patients. Impedance phlebography and fibrinogen scanning versus roentgenographic phlebography.
Nine hundred thirty-seven limbs in 537 patients over the age of 39 years who underwent total hip replacement were studied by roentgenographic phlebography, cuff-impedance phlebography, and iodine-125 fibrinogen scanning. Cuff-impedance phlebography had a sensitivity of only 12.3 percent for thigh thrombi. Fibrinogen scanning had a sensitivity of only 59.1 percent for calf thrombi and 13.7 percent for thigh thrombi. The combined use of the two methods resulted in only a 23.2 percent sensitivity for thigh thrombi and an overall sensitivity of 47.4 percent. We have concluded that in asymptomatic patients, in contrast with symptomatic patients, the combination of cuff-impedance phlebography and fibrinogen scanning is not an effective screening method.


Generation of cytotoxic T lymphocytes against modified self in the absence of antigen by interleukin 2-containing preparations.
Spleen cells obtained from normal mice were cultured with interleukin 2 (IL2); no antigen was added. After 4-5 days, these cultures contained effector cells which lysed autologous spleen target cells that were modified with 2,4,6-trinitrobenzene sulfonic acid or fluorescein isothiocyanate. No killing was seen on unmodified spleen target cells. These effector cells were Thy 1+, Lyt 1-, 2+ and were derived from Thy 1+ precursor cells. IL2 preparations induced the generation of such cytotoxic T lymphocytes (CTL) in a dose-dependent manner. IL2-induced CTL were shown to be different from the natural killer (NK) cells augmented by IL2 by virtue of their time of appearance in culture, by cold-target competition, and by different cell-surface markers. These results demonstrate that the IL2 signal may be sufficient for the induction of the differentiation of CTL precursors in the absence of an antigenic signal.


Assessing the competence of practicing physicians in New Zealand, Canada, and the United Kingdom: progress and problems.
Members of the public expect practicing physicians to be competent. They expect poorly performing physicians to be identified and either helped or removed from practice. "Maintenance of professional standards" by continuing education does not identify the poorly performing physician; assessment of clinical performance is necessary for that. Assessment may be responsive-ie, following a complaint- or periodic, either for all physicians or for an identified high-risk group. A thorough review using a range of tools is appropriate for a responsive assessment but is not practical for periodic assessment for all. A single, valid, reliable, and practical screening tool has yet to be devised to identify physicians whose practice is suboptimal. Further, articulate commentators are concerned about the harm that too-intensive scrutiny of professional performance may cause. We conclude that high performance by all physicians throughout their careers cannot be fully ensured, but it is nonetheless the responsibility of licensing bodies to use reasonable methods to determine whether performance remains acceptable. Such methods should be shown scientifically to be accurate, valid, and reliable for practicing physicians. Such an approach is likely to encourage the agreement and cooperation of the profession. To do less risks losing the trust of the public.


α-Labeling of J591, an Antibody Targeting Prostate-Specific Membrane Antigen: The Technique and Considerations from the First Dedicated Production Lab at an Academic Institution in the United States.
The protein expression of the prostate-specific membrane antigen correlates with unfavorable or aggressive histologic features of prostate cancer, resulting in use as a diagnostic PET imaging radiotracer and therapeutic target. Here, we discuss the methods to develop 225Ac-DOTA-J591, an α-labeled compound targeting an extracellular epitope of prostate-specific membrane antigen, which is currently being studied in early clinical trials. In addition, we review quality control, radiation safety measures, and clinical considerations before administration of this radioimmunotherapeutic agent.


Impact of COVID-19 on neurosurgical service: A one-year experience from a provincial countryside hospital in a rural area in north Egypt.
Globally, there is a shooting pandemic that affected many healthcare systems. Healthcare facilities had to set up strategies to avoid exhaustion while facing a catastrophic health problem. Vaccines or perfect therapies were not available over a long pandemic time and also no certified immunity against that disease is guaranteed. Therefore, it is probable that healthcare systems will face it for an exceptionally long period. That already had a grave effect on the strategy of daily practice of different specialties' services at healthcare centers. We tried simply to share a countryside hospital's expertise in managing neurosurgical cases amid a dreadful health crisis. Healthcare workers' safety and patient safety were typical priorities for neurosurgical service at Damietta Specialized Hospital. We expose the lines of management, triaging cases, the methods of handling confirmed and suspected neurosurgical patients, and strategies for discharging and following up patients. We identified hospital admission and discharge records starting from February 2020 till February 2021 to track the neurosurgical case burden, the state of service offered and the rate of infection among healthcare workers who participated in surgeries. At the peak time of the COVID‑19 pandemic in Egypt starting from February 2020 till February 2021, we have admitted about 500 neurosurgical patients. About 400 (80%) of them did surgeries according to the triaging protocol of the hospital. About 150 (30%) of those who did surgeries were urgent and the rest were borderline or semi‑urgent. About 20 (4%) were tested COVID-19 positive and six of them died due to acute respiratory distress syndrome. Only two mortality cases were reported due to post-operative complications and not related to SARS‑CoV‑2 infection. The rest of the cases (97.6%) were discharged for follow‑up without complications. No neurosurgeons but three anesthesia staff were infected with SARS‑CoV‑2. A successful undisturbed neurosurgical care was available for patients during COVID-19 time. Following the suggested strategies, a rural area-serving hospital managed to provide uninterrupted neurosurgical care amid COVID-19 pandemic in Egypt. Rural areas in developing countries are in need of strategies to deal with pandemics in the future without dismantling the normal health system, especially for life‑saving cases in a critical specialty as neurosurgery.


Connexin 43 hemichannels regulate mitochondrial ATP generation, mobilization, and mitochondrial homeostasis against oxidative stress.
Oxidative stress is a major risk factor that causes osteocyte cell death and bone loss. Prior studies primarily focus on the function of cell surface expressed Cx43 channels. Here, we reported a new role of mitochondrial Cx43 (mtCx43) and hemichannels (HCs) in modulating mitochondria homeostasis and function in bone osteocytes under oxidative stress. In murine long bone osteocyte-Y4 cells, the translocation of Cx43 to mitochondria was increased under H2O2-induced oxidative stress. H2O2 increased the mtCx43 level accompanied by elevated mtCx43 HC activity, determined by dye uptake assay. Cx43 knockdown (KD) by the CRISPR-Cas9 lentivirus system resulted in impairment of mitochondrial function, primarily manifested as decreased ATP production. Cx43 KD had reduced intracellular reactive oxidative species levels and mitochondrial membrane potential. Additionally, live-cell imaging results demonstrated that the proton flux was dependent on mtCx43 HCs because its activity was specifically inhibited by an antibody targeting Cx43 C-terminus. The co-localization and interaction of mtCx43 and ATP synthase subunit F (ATP5J2) were confirmed by Förster resonance energy transfer and a protein pull-down assay. Together, our study suggests that mtCx43 HCs regulate mitochondrial ATP generation by mediating K+, H+, and ATP transfer across the mitochondrial inner membrane and the interaction with mitochondrial ATP synthase, contributing to the maintenance of mitochondrial redox levels in response to oxidative stress.


Effect of some heavy metal salts on hepatic monooxygenases after subchronic exposure.
The effects of subchronic exposure of some heavy metal salts on the activity of the rat liver monooxygenases and NADPH-dependent lipid peroxidation have been studied. The salts of Co, Cd and Zn (when given repeatedly for one month in subtoxic doses) shortened the duration of hexobarbital sleeping time, increased the activities of Ethylmorphine-N-demethylase (EMD) and Benzphetamine-N-demethylase (BND), and the cytochrome P-450 and heme contents. The same metal salts increased the activity of delta-aminolevulinic acid synthetase (ALAS), decreased that of Heme-oxygenase and decreased NADPH-dependent lipid peroxidation. Whereas the salts of Co, Cd and Zn seem to exert an enzyme-inducing action on the mixed function oxidizing enzyme systems, the salts of Hg and Ni did not show such effects.


Sleeping and dreaming in Greek mythology.
This article aims to emphasize the major influence of Ancient Greek Mythology on modern sleep medicine. An analysis of Greek texts and medical literature using the MeSH terms Greek mythology, sleep, Greek Gods, and myths was conducted to identify mythological references related to sleep medicine. The findings are discussed concerning etymology, the early conceptualization of some disorders, and the developing characterization of sleep disorders in Greek mythology. The search found several observations in clinical sleep medicine concealed in ancient myths. Beyond the etymology of terms and reflective imaginations, these myths and their characters influence concepts that still tantalize our medical practice in modern days.


The impact of pelvic balance, physical activity, and fear-avoidance on the outcome after decompression and instrumented fusion for degenerative lumbar stenosis.
To evaluate the impact of pelvic balance, physical activity, and fear-avoidance in a cohort of patients undergoing decompression and instrumented fusion for degenerative lumbar stenosis. This study includes consecutive patients undergoing decompression and instrumented fusion for degenerative lumbar stenosis by one main surgeon from January 2014 to January 2015. Patients were interviewed by a psychologist and underwent standing whole spine X-ray. Lumbar and pelvic parameters (PI, SS, PT, iPT, LL) were measured by an independent spinal surgeon. Physical activity was measured with the International Physical Activity Questionnaire (IPAQ). The "fear-avoidance" was measured with the Tampa Scale for Kinesiophobia (TSK). Back pain was assessed by the Graphic Rating Scale (GRS). The disability was assessed by the Roland-Morris Low Back Pain and Disability Questionnaire. Statistical interpretation of the data was performed using SPSS v19 software (SPSS Inc, Chicago, Illinois). The sample included 51 patients underwent standard posterior laminectomy and instrumented fusion. Surgery has a positive global impact on the perceived low back pain. No significant (Spearman) correlations emerged among pelvic parameters and the pre- and post-surgical GSR. Patients were divided into three groups according to the IPAQ scores after the operation: "inactive" (I), "minimally inactive" (m-I), and "HEPA". Significant differences emerged between IPAQ and Roland-Morris scores (F(2, 48) = 5.48, p = 0.007): the "inactive" (M(R-M) = 11.3) or "minimally active" (M(R-M) = 9.8) groups scored significantly higher than the "HEPA" group (M(R-M) = 4.7). Tampa scores correlated with gender (rho = -0.408, p = 0.003) and with BMI (rho = -0.369, p = 0.008). Females and obese patients reported higher levels of Tampa scores. Significant relationship was found between Tampa scores and pre-GSR (rho(pre) = 0.250, p = 0.08) and significant with post-surgical GSR (rho(post) = 0.275, p = 0.05) and with post-Roland-Morris score (rho(post) = 0.599, p < 0.01). The fear-avoidance and the physical inactivity are related to the highest levels of low back pain, more than pelvic imbalance. "Inactive" and "fear-avoidant" patients have also the worst outcome after surgery and the worst level of disability.


SIRT3 protects against early brain injury following subarachnoid hemorrhage via promoting mitochondrial fusion in an AMPK dependent manner.
Subarachnoid hemorrhage (SAH), an acute cerebrovascular accident, features with its high death and disability rate. Sirtuin3 (SIRT3) is a NAD+ dependent deacetylase which mainly located in mitochondria. Reduced SIRT3 function was indicated to involve in many disorders of central nervous system. Herein, we aimed to explore the neuroprotective effects of SIRT3 on SAH and to furtherly explore the underlying mechanisms. Adult C57BL/6 J male mice (8-10 weeks) were used to establish SAH models. The pharmacological agonist of SIRT3, Honokiol (HKL), was injected in an intraperitoneal manner (10 mg/kg) immediately after the operation. Brain edema and neurobehavioral score were assessed. Nissl staining and FJC staining were used to evaluate the extent of neuronal damage. The changes of mitochondria morphology were observed with transmission electron microscopy. Western blot was used for analyzing the protein level of SIRT3 and the downstream signaling molecules. SIRT3 was downregulated after SAH, and additional treatment of SIRT3 agonist HKL alleviated brain edema and neurobehavioral deficits after SAH. Additionally, electron microscopy showed that HKL significantly alleviated the morphological damage of mitochondria induced by SAH. Further studies showed that HKL could increase the level of mitochondrial fusion protein Mfn1 and Mfn2, thus maintaining (mitochondrial morphology), protecting mitochondrial function and promoting neural survival. While, additional Compound C (CC) treatment, a selective AMPK inhibitor, abolished these protective effects. Activation of SIRT3 protects against SAH injury through improving mitochondrial fusion in an AMPK dependent manner.


Digeda-4 decoction and its disassembled prescriptions improve dyslipidemia and apoptosis by regulating AMPK/SIRT1 pathway on tyloxapol-induced nonalcoholic fatty liver disease in mice.
Nonalcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome in the liver and the leading cause of chronic liver disease worldwide. Digeda-4 decoction (DGD-4) is a commonly prescribed Mongolian herbal drug for treating acute and chronic liver injury and fatty liver. However, the mechanisms underlying the improvement of dislipidemia and liver injury via treatment with DGD-4 remain unclear. Disassembling a prescription is an effective approach to studying the effects and mechanisms underlying Mongolian medicine prescriptions. By disassembling a prescription, it is feasible to discover effective combinations of individual herbs to optimize a given prescription. Accordingly, we disassembled DGD-4 into two groups: the single Lomatogonium rotatum (L.) Fries ex Nym (LR) (DGD-1) and non-LR (DGD-3). To study whether DGD-4 and its disassembled prescriptions have protective effects against tyloxapol (TY)-induced NAFLD and to explore the underlying mechanisms of action and compatibility of prescriptions. NAFLD mice were developed by TY induction. Biochemical horizontal analyses, enzyme-linked immunosorbent assay, and liver histological staining were performed to explore the protective effects of DGD-4 and its disassembled prescriptions DGD-3 and DGD-1. Furthermore, we performed immunohistochemical analyses and Western blotting to further explore the expression of target proteins. DGD-4 and its disassembled prescriptions could inhibit TY-induced dislipidemia and liver injury. In addition, DGD-4 and its disassembled prescriptions increased the levels of p-AMPKα and p-ACC, but decreased the levels of SREBP1c, SCD-1, SREBP-2, and HMGCS1 proteins. The activation of lipid metabolic pathways SIRT1, PGC-1α, and PPARα improved lipid accumulation in the liver. Moreover, DGD-4 could inhibit hepatocyte apoptosis and treat TY-induced liver injury by upregulating the Bcl-2 expression, downregulating the expression of Bax, caspase-3, caspase-8, and the ratio of Bax/Bcl-2, and positively regulating the imbalance of oxidative stress (OxS) markers (such as superoxide dismutase [SOD], catalase [CAT], malondialdehyde [MDA], and myeloperoxidase [MPO]). DGD-1 was superior to DGD-3 in regulating lipid synthesis-related proteins such as SREBP1c, SCD-1, SREBP-2, and HMGCS1. DGD-3 significantly affected the expression of lipid metabolic proteins SIRT1, PGC-1α, PPARα, apoptotic proteins Bcl-2, Bax, caspase-3, caspase-8, and the regulation of Bax/Bcl-2 ratio. However, DGD-1 showed no regulatory effects on Bax and Bcl-2 proteins. This study demonstrates the protective effects of DGD-4 in the TY-induced NAFLD mice through a mechanism involving improvement of dyslipidemia and apoptosis by regulating the AMPK/SIRT1 pathway. Although the Monarch drug DGD-1 reduces lipid accumulation and DGD-3 inhibits apoptosis and protects the liver from injury, DGD-4 can be more effective overall as a therapy when compared to DGD-1 and DGD-3.


Inverse relationship between plasma von Willebrand factor and soluble P selectin in patients with type 1 but not type 2 von Willebrand disease.
P selectin is a component of endothelial Wiebel-Palade body membrane and platelet alpha granule membrane. Patients with von Willebrand disease (VWD) have low plasma von Willebrand factor (VWF). To examine the relationship between plasma P selectin and VWF, both were measured by ELISA in 38 patients with VWD and 40 controls. The patient had lower VWF (P < 0.001) but similar P selectin levels (P = 0.458). In 24 type 1 VWD patients, VWF and P selectin correlated inversely (P = 0.005) but in 14 type 2 VWD patients there was no correlation (P = 0.997). These data imply major differences in VWF/P-selectin regulation between types 1 and 2 VWD.


Spermatozoon ultrastructure of the pseudophyllidean cestode Paraechinophallus japonicus, a parasite of deep-sea fish Psenopsis anomala (Perciformes, Centrolophidae).
This paper provides the first ultrastructural data on the spermatozoon of a pseudophyllidean cestode belonging to the family Echinophallidae, Paraechinophallus japonicus, parasitizing deep-sea fish Psenopsis anomala from Japan. The mature spermatozoon contains two axonemes of the 9+"1" trepaxonematan pattern, nucleus, cortical microtubules, and electron-dense granules. Its anterior extremity exhibits a single electron-dense crested body. One of the most interesting features of the mature spermatozoon is the presence of a ring of tubular structures encircling the axoneme. This character, previously reported in species of the families Bothriocephalidae and Triaenophoridae, may be unique to pseudophyllideans of the group "Bothriocephalidea", thus supporting the assumption that the order Pseudophyllidea is formed in fact by two unrelated clades; "Bothriocephalidea" and "Diphyllobothriidea". The posterior extremity contains the posterior part of the nucleus and the disorganized axoneme--a character previously not described in the Eucestoda.


Barriers and facilitators to deprescribing before surgery: A qualitative study of providers and older adults.
Deprescribing, the collaborative process between providers and patients to streamline medication regimen, may reduce the risk of adverse events following surgery among older adults with multimorbidity. However, barriers and facilitators to deprescribing for surgery has not been explored. We conducted a qualitative study of Primary Care Providers (PCP) and patients aged 65 and older who were scheduled for surgery. We used the Theoretical Domains Framework, which informed the interview guide and analysis. A total of 16 participants (n=8 providers, n=8 patients) were included. Themes were regarding: 1) attitudes towards deprescribing before surgery, 2) perceived benefits of deprescribing before surgery, 3) patient-provider relationship and shared decision-making, 4) hope for surgery, 5) barriers to deprescribing before surgery, and 6) preferences for deprescribing follow-up. Our study findings regarding provider- and patient-related barriers and facilitators for deprescribing and desired processes before surgery may inform future deprescribing intervention targets before surgery.


Hepatocyte specific long lasting inhibition of protein N-glycosylation by D-galactosamine.
The effect of D-galactosamine on protein N-glycosylation was studied in rat hepatocyte primary cultures for alpha 1-antitrypsin (three complex type oligosaccharide chains) and alpha 1-acid glycoprotein (six complex type oligosaccharide chains). D-Galactosamine at a concentration of 4 mM inhibited partially de novo N-glycosylation leading to the formation of alpha 1-antitrypsin lacking one to two and of alpha 1-acid glycoprotein lacking one to five of its carbohydrate side chains. In addition D-galactosamine interfered with oligosaccharide processing, leading to the formation of some carbohydrate side chains remaining in an endoglucosaminidase H sensitive, i.e., not completely processed, form. D-Galactosamine impaired the secretion of alpha 1-antitrypsin and of alpha 1-acid glycoprotein but did not inhibit the secretion of the unglycosylated albumin. The inhibitory effect of D-galactosamine on de novo glycosylation as well as on oligosaccharide processing lasted for at least 24 h after it had been removed from the cells. D-Galactosamine impaired the glycosylation of alpha 1-antitrypsin only in hepatocytes, but not in human monocytes. Furthermore, D-galactosamine did not impair the N- and O-glycosylation of interleukin-6 in human monocytes and in MRC 5 fibroblasts. The results indicate that the effect of D-galactosamine on protein glycosylation is restricted to D-galactosamine metabolizing hepatocytes and is not exerted by the drug itself but by its metabolites.