Bilateral tension pneumothoraces leading to cardiac arrest after coronary artery bypass surgery.
Bilateral pneumothoraces are a very rare event. In clinical settings, inadvertent incursion into the pleural space resulting from diagnostic or therapeutic medical interventions such as bilateral venipunctures or damage to the lung parenchyma due to high pressure ventilation may be causative. Bilateral pneumothoraces postcardiac surgery are rarely reported. We present the case of bilateral tension pneumothoraces leading up to cardiorespiratory arrest in a 57-year-old male, weighing 130 kg, who underwent without any complications a coronary artery bypass surgery. Thoracic chest tubes (retrosternal and intrapericardial) and a left pleural tube were removed 24 hours prior to the incident. Diffuse sternal pain sensation accompanied by slow progressive respiratory distress and confusion shortly before the incident were all developed over a period of 12 hours. A prompt cardiopulmonary resuscitation and bilateral chest tube insertion had prevented a fatality in the patient.


Pulse-labeling Studies on Protein Synthesis in Developing Pea Seeds and Evidence of a Precursor Form of Legumin Small Subunit.
Intact cotyledons were taken from pea seeds at various stages during seed development and pulse-labeled with (14)C-amino acids. Salt-soluble proteins then were extracted and fractionated on Na dodecyl sulfate-polyacrylamide gels. Storage proteins in these extracts were identified by their binding to immunoaffinity columns. The labeling studies showed that the synthesis of storage protein polypeptides accounts for a major part of total protein synthesis of developing cotyledons between 10 and 22 days after flowering. The distribution of the incorporated radioactivity between individual storage protein polypeptides varied with stage of development. For example, the synthesis of the 50 kilodalton complex of vicilin subunits dominated the early stages of protein accumulation but was a negligible proportion of the total incorporation in the later stages. On the other hand, the 75 kilodalton vicilin subunit was synthesized throughout this entire period. The major small subunit of legumin (20 kilodaltons) was not detected by either Coomassie blue staining or by 2-hour labeling during this period. It was found to arise during the desiccation phase of seed maturation from a long-lived precursor with a relative electrophoretic mobility equivalent to 19 kilodaltons.


Clinical utility of viscoelastic tests of coagulation in patients with liver disease.
The prothrombin time (PT) and international normalised ratio (INR) are used in scoring systems (Child-Pugh, MELD, UKELD) in chronic liver disease and as a prognostic tool and for dynamic monitoring of hepatic function in acute liver disease. These tests are known to be poor predictors of bleeding risk in liver disease; however, they continue to influence clinical management decisions. Recent work on coagulation in liver disease, in particular thrombin generation studies, has led to a paradigm shift in our understanding and it is now recognised that haemostasis is relatively well preserved. Whole blood global viscoelastic tests (TEG(®) /ROTEM(®) ) produce a composite dynamic picture of the entire coagulation process and have the potential to provide more clinically relevant information in patients with liver disease. We performed a systematic review of all relevant studies that have used viscoelastic tests (VET) of coagulation in patients with liver disease. Although many studies are observational and small in size, it is clear that VET provide additional information that is in keeping with the new concepts of how coagulation is altered in these patients. This review provides the basis for large scale, prospective outcome studies to establish the clinical value of these tests.


Evaluation of tumor-size response metrics to predict overall survival in Western and Chinese patients with first-line metastatic colorectal cancer.
To assess new metrics of tumor-size response to predict overall survival (OS) in colorectal cancer (CRC) in Western and Chinese patients. Various metrics of tumor-size response were estimated using longitudinal tumor size models and data from two phase III studies that compared bevacizumab plus chemotherapy versus chemotherapy as first-line therapy in Western (n = 923) and Chinese (n = 203) patients with CRC. Baseline prognostic factors and tumor-size metrics estimates were assessed in multivariate models to predict OS. Predictive performances of the models were assessed by simulating multiple replicas of the phase III studies. Time to tumor growth (TTG) was the best metric to predict OS. TTG fully captured bevacizumab effect. Chinese ethnicity had no impact on OS or on the TTG-OS relationships. The model correctly predicted OS distributions in each arm as well as bevacizumab hazard ratio (model prediction, 0.75 v 0.68 observed in Western patients; 95% prediction interval, 0.62 to 0.91). TTG captured therapeutic benefit with bevacizumab in first-line CRC patients. Chinese ethnicity had no impact. Longitudinal tumor size data coupled with model-based approaches may offer a powerful alternative in the design and analysis of early clinical studies.


Predictors of High Psychosocial Functioning in Bipolar Disorder.
The aim of this study was to identify predictors of high psychosocial functioning in patients with bipolar disorder (BD). One hundred forty-five outpatients with BD and 50 healthy controls were included. Patients were categorized as having high psychosocial functioning if they concomitantly met three conditions: a) General Assessment of Functioning greater than 90, b) full-time employment, and c) full functional recovery. Clinical, demographical, and neurocognitive variables were assessed and considered as potential predictors of high functioning in regression models. We found that 22.8% (n = 33) of patients exhibited high psychosocial functioning. BD type II, higher educational level, and better performance in verbal memory, attention, and executive functions were independent predictors of high psychosocial functioning. Our results provide evidence that functional outcomes are heterogeneous in BD, including a percentage of patients who maintain good to excellent psychosocial functioning despite their illness. Neurocognitive functioning could be one of the most influential factors to explain this heterogeneity.


A novel folding intermediate state for apolipoprotein A-I: role of the amino and carboxy termini.
Intramolecular interactions between the amino and carboxy termini of apolipoprotein A-I (apoAI) are believed to stabilize the helix bundle conformation of the protein. During lipid assembly the protein undergoes conformational changes that result in an exposure of the carboxy terminus and its insertion into the lipid phase. To determine the role of the two termini in the energetics of unfolding, we studied the guanidine-hydrochloride-induced unfolding and refolding of apoAI as well as its N-terminal deletion (del[1-43]), C-terminal deletion (del[186-243]), and the double deletion containing only the central residues 44-185. Thermodynamic analysis of the equilibrium unfolding measured by fluorescence spectroscopy revealed the presence of an intermediate unfolded state (I(equil)) in addition to the native (N) and unfolded states. Refolding kinetics of apoAI, measured by stopped-flow circular dichroism, revealed two kinetic intermediates, I(burst) and I(recovery). Computer modeling suggested that the first resembles the partially unfolded protein, whereas the second overlaps with the native state of the protein. The free energy changes for the N --> I(equil) transition of the N-terminal and double deletions were lower then that of the full-length form, whereas that for the C-terminal deletion was higher. Our findings suggest that the N-terminus of apoAI stabilizes the native state of the protein by increasing the Eyring energy barrier for the N --> I(equil) unfolding transition; whereas the carboxyl terminus destabilizes that state.


The birth of protein electrochemistry.
The results from a final-year undergraduate project led to an $876M sale of a spin-out company 19 years later: the 1977 communication from Mark Eddowes and Allen Hill seeded the rich field of protein electrochemistry, the technology that underpins commercial glucose biosensors.


Photochemistry of 124 kilodalton Avena phytochrome in vitro.
The photochemical properties of purified 124 kilodalton (kD) Avena cv Garry phytochrome are examined and compared with those of the proteolytically degraded 118/114 kD species. The proportion of the chromoprotein in the far red absorbing form, Pfr, following saturating red irradiation is 0.86 for 124 kD phytochrome, substantially higher than the values of 0.79 determined here and 0.75 reported in the literature for 118/114 kD preparations. The ratio of the quantum yields for Pr to Pfr phototransformation and for Pfr to Pr phototransformation (phir/phifr) is 1.76 for the 124 kD molecule and 0.98 for the 118/114 kD species. Based on extinction coefficients determined using the Lowry assay as a measure of protein weight, the individual phototransformation quantum yields for 124 kD phytochrome are 0.17 for Pr --> Pfr (phir) and 0.10 for Pfr --> Pr (phifr). Comparison of these quantum yields with those of the 118/114 kD species (where phir = phifr = approximately 0.11) indicates that proteolytic degradation of the 124 kD molecule to the 118/114 kD species significantly affects only phir. Therefore, the lower proportion of Pfr at photoequilibrium observed for 118/114 kD preparations is explained mainly in terms of a reduced efficiency of Pr --> Pfr phototransformation. The absolute Pfr absorbance spectrum for 124 kD phytochrome obtained by correcting the measured spectrum for residual Pr exhibits a maximum at 730 nm and differs from previous absolute Pfr spectra for both ;120' kD and 60 kD phytochrome in that it lacks a shoulder in the red region of the spectrum.


Inactivation of UCP1 and the glycerol phosphate cycle synergistically increases energy expenditure to resist diet-induced obesity.
Our current paradigm for obesity assumes that reduced thermogenic capacity increases susceptibility to obesity, whereas enhanced thermogenic capacity protects against obesity. Here we report that elimination of two major thermogenic pathways encoded by the mitochondrial uncoupling protein (Ucp1) and mitochondrial glycerol-3-phosphate dehydrogenase (Gdm) result in mice with increased resistance to diet-induced obesity when housed at 28 degrees C, provided prior adaptation occurred at 20 degrees C. Obesity resistant Gdm(-/-).Ucp1(-/-) mice maintained at 28 degrees C have increased energy expenditure, in part through conversion of white to brown adipocytes in inguinal fat. Increased oxygen consumption in inguinal fat cell suspensions and the up-regulation of genes of mitochondrial function and fat metabolism indicated increased thermogenic activity, despite the absence of UCP1, whereas liver and skeletal muscle showed no changes in gene expression. Additionally, comparisons of energy expenditure in UCP1-deficient and wild type mice fed an obesogenic diet indicates that UCP1-based brown fat-based thermogenesis plays no role in so-called diet-induced thermogenesis. Accordingly, a new paradigm for obesity emerges in which the inactivation of major thermogenic pathways force the induction of alternative pathways that increase metabolic inefficiency.


Detection of pseudouridine and other modifications in tRNA by cyanoethylation and MALDI mass spectrometry.
Mass spectrometry plays a central role in the characterisation of modified nucleotides, but pseudouridine is a mass-silent post-transcriptional modification and hence not detectable by direct mass spectrometric analysis. We show by the use of matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry that pseudouridines in tRNA can be specifically cyanoethylated by acrylonitrile without affecting the uridines. The tRNA was cyanoethylated and then subjected to digestion with either RNase A or RNase T1. Cyanoethylated digestion fragments were identified by mass spectrometric comparison of untreated and acrylonitrile-treated samples, where the addition of one acrylonitrile resulted in a mass increment of 53.0 Da. The exact modified nucleotide could be identified by tandem mass spectrometry on the cyanoethylated digestion fragment. The methodology was used to identify additional one 4-thiouridine and one pseudouridine in tRNA(TyrII) from Escherichia coli. Furthermore, we observed that RNase A is highly tolerant towards nucleotide modifications, only being inhibited by 2'-O-methylation, whereas RNase T1 cleavage is affected by most nucleotide modifications.


Transfusion-related acute lung injury prevention measures and their impact at Canadian Blood Services.
Blood operators have taken measures to reduce transfusion-related acute lung injury (TRALI). We classified suspected TRALI cases reported to Canadian Blood Services from 2001 to 2009 and assessed the impact of TRALI reduction measures. Using Canadian Consensus Conference definitions, cases were reviewed by two experts or, from 2006 to 2009, a TRALI Medical Review Group (TMRG). Detection of HLA antibodies was performed using the Luminex system starting in 2008. Measures implemented from 2007 to 2009 included use of predominantly male plasma, suspension of buffy coat platelets in male plasma, and deferral of females with a pregnancy history from plateletpheresis. The buffy coat production method was implemented from 2005 to 2008. Reporting of all suspected TRALI cases, as well as cases classified as definite or possible, increased from 2001 to 2004, was stable from 2004 to 2007, and declined in 2008 to 2009. The decline was most marked for plasma-associated cases, but occurred for all components. TMRG consensus on classification was achieved in 56% of cases. Cases identified as definitive or possible TRALI were significantly more likely to have donor antibody against a corresponding recipient antigen, compared to other cases. Hemovigilance data demonstrated an initial increase in TRALI cases, likely due to increased adverse event reporting and awareness of TRALI, followed by a decrease in cases related to all components. TRALI prevention measures and possibly the switch to the buffy coat production method may have contributed to the decline. Classification of cases remains challenging.


Effect of patient weight on the anticoagulant response to adjusted therapeutic dosage of low-molecular- weight heparin for the treatment of venous thromboembolism.
Data evaluating the safety of using weight-based dosing of low-molecular-weight heparin (LMWH) in obese patients are limited. Some manufacturers have recommended a maximum daily dose of LMWH not to be exceeded. The purpose of this study was to determine if body weight influenced the anticoagulant response to a weight-based dose of LMWH for the treatment of venous thromboembolism. Patients with serum creatinine levels < 150 micromol/l receiving the LMWH, dalteparin 200 anti-Xa IU/kg based on actual body weight subcutaneously once daily for the treatment of deep vein thrombosis or pulmonary embolism, were eligible for the study. Patients received a minimum of 5 days LMWH treatment. Patients had peak anti-Xa levels (IL Test Chromogenic assay) measured 3-4 h following their day 3 injection and trough anti-Xa levels measured immediately prior to injections on day 3 and 5. No dose adjustments were made on the basis of the anti-Xa levels. Patients were a priori stratified into three weight classes: (A) within 20% of ideal body weight (IBW) (n = 13); (B) 20-40% of IBW (n = 14), and (C) greater than 40% of IBW (n = 10). The largest patient weighed 190 kg and had a body mass index of 58. Mean daily LMWH doses were 14,030, 17,646 and 23, 565 IU for groups A, B and C, respectively. Mean (SD) trough anti-Xa levels on day 3 were 0.12 (0.05) anti-Xa IU/ml for group A, 0.11 (0.03) anti-Xa IU/ml for group B and 0.11 (0.03) anti-Xa IU/ml for group C (p > 0.2). Similar trough anti-Xa levels were observed on day 5. Mean (SD) peak anti-Xa levels on day 3 were 1.01 (0.20) anti-Xa IU/ml, 0.97 (0.21) anti-Xa IU/ml and 1.12 (0.22) anti-Xa IU/ml for groups A, B and C, respectively (p > 0.2). No thromboembolic or bleeding complications occurred during LMWH therapy in any patients. These findings suggest that body mass does not appear to have an important effect on the response to LMWH up to a weight of 190 kg in patients with normal or near normal renal function.


[Treatment of injuries of the cervical spine].
Injuries of the cervical spine are re-evaluated at present. New surgical procedures and research on the stability, when these procedures are used, caused that surgical treatment is used more frequently. Attention is draw to provisions in the field as well as in hospitals, on the diagnostic approach and classification of these injuries, on the procedure of conservative surgical treatment. The domain of conservative treatment are injuries of the upper cervical spine (C1 and C2); injuries of the lower cervical spine are frequently unstable, and therefore frequently indicated for operation. Attention is drawn to modern views on surgical treatment of comminuted fractures of the atlas and the dens axis. The authors analyzed their own material from 1986 to April 30, 1989 and in case-histories of three patients they draw attention to their therapeutic method. The authors demonstrate their own modified plates for the anterior stabilization of the cervical spine and their modification of the Halo device "Halo Vest". They discuss biomechanical properties of posterior and anterior stabilization methods.


Role and mechanism of action of butyrate in atherosclerotic diseases: a review.
Butyrate is a bioactive molecule produced by the intestinal flora and plays a major role in a variety of inflammatory diseases. Increasing evidence indicates that butyrate can regulate the occurrence and development of atherosclerosis (AS). Coincidentally, it reduces hyperlipidemia and hyperglycemia, which are major risk factors of AS. However, the mechanism by which butyrate regulates the development of AS remains unclear. In this article, we review the effect of butyrate treatment on AS with a focus on the mechanisms of butyrate-mediated modulation of several atherosclerotic processes. These include the improvement of monocyte-endothelial interactions, macrophage lipid accumulation, smooth muscle cell proliferation and migration, and lymphocyte differentiation and function. The existing research indicates that butyrate treatment may be a potentially effective strategy for the prevention of AS. Identity and underlying mechanisms of the molecular pathways of these interactions should be explored in the future to counter AS effectively.


[Helicobacter pylori eradication therapy in children].
Proton pump inhibitor-based triple therapies are performed worldwide for Helicobacter pylori-associated diseases in childhood. As the first-line therapy, the Japanese Pediatric Guideline in H. pylori Infection has recommended a triple regimen with amoxicillin and clarithromycin, because the Japanese national health care insurance system has permitted only this regimen. However, the primary resistance to clarithromycin in Japan is demonstrated in around 30% of the strains, leaving an urgent issue for the physicians. A triple regimen with amoxicillin and metronidazole is acceptable as the second-line therapy. In children with chronic H. pylori gastritis, eradication should be considered if they have gastric atrophy or a family history of gastric cancer. In children, however, a 'test and treat' strategy to prevent gastric cancer is not recommended.


Azole endothelin antagonists. 3. Using delta log P as a tool to improve absorption.
The oral absorption profile of a family of azole-based ET(A)-selective antagonists has been improved through a rational series of structural modifications which were suggested by analysis of the physicochemical parameter delta log P. Comparison of urea 2 with a series of well-absorbed compounds using delta log P analysis suggested that 2 has an excess capacity for forming hydrogen bonds with solvent. A series of urea modifications were explored as a means of reducing H-bonding capacity while maintaining affinity for the ET(A)-receptor. The correlation between delta log P values and absorption in an intraduodenal (id) bioavailability model was good; this strategy uncovered replacements for each of the urea NH groups which simultaneously improve both potency and drug absorption. A combination of these optimized modifications produces carbamate 16h, a highly-selective ET(A) antagonist with a potency/bioavailability profile consistent with an oral route of administration.


Preoperative proteinuria and clinical outcomes in type B aortic dissection after thoracic endovascular aortic repair.
Background Proteinuria is a marker of poor outcomes in several diseases; however, few studies have been conducted to explore the prognostic value of proteinuria, assessed by urine dipstick test, for clinical outcomes in patients with type B acute aortic dissection (TBAD) undergoing thoracic endovascular aortic repair (TEVAR). Methods Consecutive patients with TBAD undergoing TEVAR were enrolled from January 2010 to July 2015. Proteinuria was defined as trace or higher, according to the results of urine dipstick testing. Associations among proteinuria and adverse events were evaluated. Results In total, 671 patients with a mean age of 44±15 years were included in the analysis. Proteinuria was detected in 281 patients (41.9%) before TEVAR. Multivariate logistic regression analysis showed that C-reactive protein and impaired renal function were independent predictors for proteinuria. During hospitalization, 21 patients died. In-hospital mortality was higher in patients with proteinuria (1.5% vs. 5.3%, p=0.005). After a median 3.4 years follow up, the post-TEVAR death rate was 10.4% (85 patients were lost to follow-up). The long-term cumulative mortality was significantly higher in patients with proteinuria (17.2% vs. 8.2%, log-rank=11.36, p=0.001). Multivariate Cox survival modeling indicated that proteinuria was significantly associated with long-term death, after adjustment for potential confounding risk factors (HR=1.92, p=0.012). Conclusions Pre-TEVAR proteinuria was identified as a prognostic marker in patients with TBAD and has potential for application as a convenient and simple risk assessment method before TEVAR.


Psychometric properties of the Parental Feeding Behaviours Questionnaire for Indonesian parents of young children.
The objective of this study was to test the psychometric properties of the Parental Feeding Behaviours Questionnaire (PFBQ) to measure feeding behaviours of Indonesian parents of toddlers (young children). A total of 696 parents of toddlers were obtained by convenience sampling during September 2013 to April 2014. To validate the PFBQ, confirmatory factor analysis and the contrasted group technique were conducted. Reliability of this instrument was examined by construct reliability and test-retest reliability. Results showed that the regression coefficients of all 56 indicators were statistically significant (P < 0.001). The contrasted group technique showed significantly different parental feeding behaviours between parents of well-nourished and malnourished toddlers (P = 0.047). The test-retest reliability of the PFBQ was acceptable (Pearson correlation = 0.644), and the construct reliability ranged from 0.88 to 0.96. The PFBQ is a valid and reliable instrument; however, more studies are required to identify acceptable tools to measure more culturally diverse range of parental feeding behaviours.


Surface plasmon mediated strong exciton-photon coupling in semiconductor nanocrystals.
We present an experimental demonstration of strong coupling between a surface plasmon propagating on a planar silver thin film and the lowest excited state of CdSe nanocrystals. Attenuated total reflection measurements demonstrate the formation of plasmon-exciton mixed states, characterized by a Rabi splitting of approximately 112 meV at room temperature. Such a coherent interaction has the potential for the development of nonlinear plasmonic devices, and furthermore, this system is akin to those studied in cavity quantum electrodynamics, thus offering the possibility to study the regime of strong light-matter coupling in semiconductor nanocrystals under easily accessible experimental conditions.


Useful immunohistochemical markers of tumor differentiation.
Immunohistochemistry (IHC) has been somewhat underutilized in the practice of toxicological pathology but can be a valuable tool for the evaluation of rodent neoplasms, both in a diagnostic and an investigational role. Determining an exact tumor type using standard hematoxylin and eosin (H&E) staining of formalin-fixed tissues can be challenging, especially with metastatic and/or poorly differentiated tumors. Successful IHC is dependent on many factors, including species and tissue type, type and duration of fixation, quality fresh or frozen sectioning, and antibody specificity. The initial approach of most tumor diagnosis IHC applications is distinguishing epithelial from mesenchymal differentiation using vimentin and cytokeratin markers, although false-negative and/or false-positive results may occur. Experimentally, IHC can be employed to investigate the earliest changes in transformed tissues, identifying cellular changes not normally visible with H&E. Individual markers for proliferation, apoptosis, and specific tumor proteins can be used to help distinguish hyperplasia from neoplasia and determine specific tumor origin/type. IHC provides a relatively rapid and simple method to better determine the origin of neoplastic tissue or investigate the behavior or progression of a given neoplasm. Several experimental and diagnostic examples will be presented to illustrate the utility of IHC as a supplement to standard staining techniques.


Platelet activating factor (PAF). A review of its effects, antagonists and possible future clinical implications (Part I).
This review is an attempt to summarise recent data on platelet activating factor (PAF) and PAF antagonists from 1988 to the present. This period saw a burst in research activity focused predominantly on the effect of PAF in various organs. The effect of PAF and its antagonists was further intensively studied in vitro on isolated platelets, leucocytes, macrophages and endothelial cells. From these and earlier data, based on the catastrophe theory of Thom and Zeeman, a new concept on the interaction between PAF and various cytokines could be recognised as an important mechanism of action of the phospholipid mediator, suggesting the existence of an autocatalytic feedback network through which PAF can influence cellular function under certain pathophysiological conditions. This mechanism can be regarded as the culmination of our recent knowledge on the role of PAF, and may influence the possible clinical implications of PAF antagonists in the near future. It is recognised that PAF is released in shock and ischaemic states, and that PAF antagonists can protect the heart and brain against ischaemic injury. Therefore, in contrast to the previous period, which was predominantly devoted to the elucidation of the role of PAF in immediate hypersensitivity reactions, studies performed on cerebral, myocardial and intestinal ischaemia as well as in various shock conditions have concentrated on entirely new aspects of the effect of PAF antagonists, emphasising the significance of the inflammatory process and cell-to-cell interactions in these pathophysiological states. This has led to a re-evaluation of the experimental data previously accumulated. At the same time, these new trends in PAF and PAF antagonist research have explored further possibilities for the application of PAF antagonists in clinical practice. Attention has been focused on the physiological role of PAF as a signal molecule, especially between the neuroendocrine system and related sensory organs. The recognition of the significance of PAF in mammalian reproduction is fascinating and may lead to new clinical applications of PAF antagonists. It appears probable that, like eicosanoids, PAF is involved in a great variety of membrane-dependent processes that play a fundamental role in the maintenance of homeostasis. PAF research has provided several potent natural and synthetic antagonists which may facilitate the clinical application of these drugs in the near future.


Necrotising soft tissue infection of bilateral upper limb caused by the injection of oral bacteria: a case report.
Necrotising soft tissue infection is a rare and rapid process with devastating consequence. We report one case of necrotising soft tissue infection in a bilateral upper limb with uncommon oral bacteria. Radiological imaging revealed the presence of gas in upper limb soft tissues, and an MRI showed the localised signal changes in the biceps muscle of the right upper arm, and the subcutaneous tissue of the left elbow. The patient was treated with surgical resection of the infected muscle and wide debridement of the subcutaneous tissue. Antibiotics were initiated. The patient recovered immediately without functional deficit. The unique features of this patient were possible to observe in the progression of the necrotising soft tissue infection in the bilateral upper limb with intentional injection of oral bacteria, and the effect of biceps brachii resection in a prime age worker.


Body image and peer relationships: Unique associations of adolescents' social status and competence with peer- and self-reported appearance victimization.
Adolescents were asked to nominate peers who experience appearance-related victimization or engage in appearance-related aggression, in order to examine the peer social status and competency correlates of receiving more nominations. Moreover, the correlates of peer-report vs. self-report appearance-related victimization were considered. Participants were 371 young Australian adolescents (55% girls, Mage = 12.0 years) who completed surveys. Results showed that victimized adolescents were rated as less liked, prosocial, popular and good-looking, and perceived themselves to be less attractive, less competent at sport and more teased by peers about appearance. Aggressive adolescents were rated as more popular and better looking, but also less prosocial. Aggressive adolescents also perceived themselves to be less academically but more romantically competent, and reported more appearance anxiety symptoms. Findings from peer-report measures generally support previous research findings using self-report measures, but the significant correlates did appear to differ between peer- and self-report of appearance victimization.


Current trends in onychomycosis therapy: a literature review.
Problems with the use of griseofulvin and ketoconazole in the treatment of onychomycosis have led to studies of three new oral antifungal drugs to treat this disease: fluconazole, itraconazole, and terbinafine. These drugs have been superior in relation to a high rate of cure, shorter duration of treatment, minimal adverse effects, and prolonged duration of remission. Although both fluconazole and itraconazole are structurally related to ketoconazole, their triazole ring is more site-specific than the imidazole ring of ketoconazole, which makes these newer drugs less likely to cause liver toxicity. Terbinafine belongs to a new class of compounds called the allylamines, which are fungicidal rather than fungistatic. Terbinafine has become the first line of therapy in Europe and Canada for onychomycosis, and it has recently been approved in the United States in oral form. Itraconazole and fluconazole are available in the United States, but fluconazole is not yet approved for treatment of onychomycosis.


Hot-spot identification on a broad class of proteins and RNA suggest unifying principles of molecular recognition.
Chemically diverse fragments tend to collectively bind at localized sites on proteins, which is a cornerstone of fragment-based techniques. A central question is how general are these strategies for predicting a wide variety of molecular interactions such as small molecule-protein, protein-protein and protein-nucleic acid for both experimental and computational methods. To address this issue, we recently proposed three governing principles, (1) accurate prediction of fragment-macromolecule binding free energy, (2) accurate prediction of water-macromolecule binding free energy, and (3) locating sites on a macromolecule that have high affinity for a diversity of fragments and low affinity for water. To test the generality of these concepts we used the computational technique of Simulated Annealing of Chemical Potential to design one small fragment to break the RecA-RecA protein-protein interaction and three fragments that inhibit peptide-deformylase via water-mediated multi-body interactions. Experiments confirm the predictions that 6-hydroxydopamine potently inhibits RecA and that PDF inhibition quantitatively tracks the water-mediated binding predictions. Additionally, the principles correctly predict the essential bound waters in HIV Protease, the surprisingly extensive binding site of elastase, the pinpoint location of electron transfer in dihydrofolate reductase, the HIV TAT-TAR protein-RNA interactions, and the MDM2-MDM4 differential binding to p53. The experimental confirmations of highly non-obvious predictions combined with the precise characterization of a broad range of known phenomena lend strong support to the generality of fragment-based methods for characterizing molecular recognition.


cDNA cloning and gene expression of ascorbate oxidase in tobacco.
A cDNA clone for ascorbate oxidase (AAO) has been isolated from a cDNA library of tobacco (Nicotiana tabacum) cells. The identity of the amino acid sequence deduced from tobacco AAO cDNA to that from pumpkin AAO cDNA was 68%, which was much lower than the identity (80%) between pumpkin and cucumber AAO. AAO activity in tobacco cells was much lower than that in pumpkin cells, whereas the immunoreactive protein in tobacco cells was more abundant than that in pumpkin cells. We suppose that AAO protein in tobacco cells may be less active than that in pumpkin cells. Genomic Southern blotting suggested that AAO in tobacco was encoded by a single-copy gene. Nothern blotting revealed that mRNA of AAO was highly expressed in young and growing tissues of tobacco plant.


Implementation of Pre-Admission Caregiver Testing for COVID-19.
Caregivers are often at the bedside of hospitalized children posing an additional risk for coronavirus disease 2019 (COVID-19) transmission. We describe the implementation of caregiver COVID-19 testing before inpatient pediatric admissions and the effect on patient cohorting and bed capacity. We implemented an ordering pathway to facilitate COVID-19 testing of caregivers of patients admitted to the inpatient units from the pediatric emergency department, elective procedural admissions, or direct admissions at a tertiary children's hospital in the Northeastern United States in August 2021. Testing was expedited by the clinical laboratory, and caregiver results were used to inform cohorting, infection prevention, and bed management decisions. From August 2021 to January 2022, 2558 caregiver tests were ordered through this pathway, and 83 (3.2%) were positive. Of the positive tests, 72 (86.7%) occurred after December 18, 2021, coinciding with the local Omicron variant wave. Among positives, 67 caregiver or child pairs were identified, and 36 positive caregivers had a COVID-19 negative child leading to use of isolation precautions. Reintroduction of patient cohorting increased overall bed capacity from 74% to 100% of available beds. The overall incidence of COVID-19 among caregivers before admission correlated well with rates of COVID-19 positivity among asymptomatic adults in the community during the study period. Implementation of caregiver testing increased bed capacity by reintroducing cohorting of patients and identified patients needing isolation that would have been missed by patient testing alone. More research is necessary to determine the extent that routine caregiver testing mitigates the risk of nosocomial severe acute respiratory syndrome coronavirus 2 transmission.


Mitogenic response to TGF-beta in 3T3-F442A cells.
In 3T3-F442A cells, TGF-beta caused cellular proliferation in a time and dose-dependent manner. TGF-beta induced cyclin D1 and cdk2 proteins in 3T3-F442A cells. The mitogenic effect of TGF-beta was specific in nature. The antimitogenic agent, hGH, inhibited the mitogenic effect of TGF-beta and was associated with inhibition of cyclin D1 expression. The protein kinase c inhibitor, staurosporine, inhibited the mitogenic effect of TGF-beta. Taken together, these results suggest that TGF-beta affects expression levels of cell cycle-regulated proteins and its mitogenic effect is mediated through protein kinase C in 3T3-F442A cells.


Feasibility of Transoral Approach to Accessory Parotid Tumors.
Tumors of the accessory parotid gland are very rare. Surgical removal of an accessory parotid tumor is usually accomplished by superficial parotidectomy through an external neck incision. However, this procedure inevitably results in a neck scar. In this case, we performed complete excision of a parotid tumor via an endoscopic-assisted transoral approach. Resection of such benign tumors can be achieved with less morbidity by endoscope-assisted surgery with a nerve monitoring system. The field of transoral surgery will continue to expand with technological advancements.


Human papillomavirus and prostate cancer: The role of viral expressed proteins in the inhibition of anoikis and induction of metastasis.
The aim of this study is to address the role of HPV in prostate cancer (PCa) development through the inducement of resistance to anoikis. In this case-control study, prostate tissues and blood samples were collected from 116 individuals, including 72 cases with PCa and 44 non-malignant prostate tissue samples as a control group. The expression level of HPV genes (E2, E6, and E7) and cellular genes including anti-apoptotic mediators (Bcl-2 and survivin), tumor suppressor proteins (Rb and p53), and some mediators involved in anoikis resistance and invasiveness (E-cadherin, N-cadherin, Twist, PTPN13 and SLUG) were evaluated. HPV genome was identified in 36.1% cases and 15.9% control samples, additionally there was found to be a statistic significant association between the presence of HPV and PCa (OR = 1.64, 95% C.I = 0.8-1.8, P-value = 0.023). HPV genotype 16 and 18 were the most prevalent genotype in both in the PCa group and the control group. The expression level of the tumor suppressor proteins (Rb and p53) and anti-apoptotic mediators (Bcl-2 and Survivin) were significantly decreased and increased, respectively, in the HPV-positive specimens compared to the HPV-negative specimens. Furthermore, the mean expression level of N-cadherin, SLUG, and TWIST in the HPV-positive specimens was higher than HPV-negative specimens while the mean expression level of PTPN-13 and E-cadherin genes in the HPV-positive specimens was lower than HPV-negative specimens. Our study suggests that HPV infection may be involved in the development of PCa metastases by modulating anoikis resistance related genes.


[The Case of Fulminant Myocarditis].
Fulminant myocarditis (FM) is a severe form of inflammatory myocardial injury rapidly developing as acute heart failure, cardiogenic shock, or life-threatening disturbances of cardiac rhythm. FM requires intensive treatment including drug therapy, mechanical circulatory support, and in some cases - heart transplantation. Echocardiography can be used as a screening method of diagnostics. Magnetic resonance imaging of the heart often cannot be performed because of hemodynamic instability of a patient, therefore endomyocardial biopsy with histological and immunohistochemical studies as well as molecular-genetic analysis of obtained samples is required for final diagnosis. Prognosis of the disease is determined by histological picture. In most cases, after cessation of acute stage of the inflammatory process, FM has a favorable long-term prognosis. In this article we present a clinical case of FM and review of current literature on diagnosis and treatment of this disease.


Rayleigh-Bénard convection with rotation at small Prandtl numbers.
We present experimental and theoretical results near the onset of the Rayleigh-Bénard convection with rotation about a vertical axis in a fluid with a Prandtl number sigma close to 0.18. In the experiment we used a H2-Xe gas mixture with a separation ratio Psi=0.22 and a Lewis number L=1.22 at various pressures and dimensionless rotation rates Omega up to 400. On the basis of a standard weakly nonlinear stability analysis, we found a supercritical, stationary bifurcation for Omega < than approximately 13, which became subcritical over the range 13 < than approximately Omega < or approximately 160. For Omega > than approximately 160 a supercritical Hopf bifurcation precedes the stationary instability of the uniform state. Following the unstable straight-roll fixed point in the subcritical regime by Galerkin methods we determined the location of the saddlenode and the stability of the nonlinear two-dimensional straight-roll state. The rolls were found to be unstable to three-dimensional Küppers-Lortz perturbations for 3.8 < than approximately Omega < than approximately 160. Theoretical results for a pure fluid with the same sigma were qualitatively similar. Measurements using shadowgraph flow visualization yielded a bifurcation line and an Omega range of subcriticality, which agreed with the stability analysis. In the subcritical range the experiment revealed a discontinuity of the pattern amplitude at onset, but was unable to find any hysteresis. Patterns at onset fluctuated irregularly between the ground state and the finite-amplitude state. In this parameter range the convection pattern further above onset was chaotically time dependent. Investigation of the Hopf bifurcation line was difficult because of a wall mode that, for large Omega, preceded the bulk instability. For Omega approximately equal to 400, patterns were found in the sample interior only when the expected Hopf bifurcation was exceeded by about 10%. This is consistent with the convective nature of the bifurcation. However, the observed structure, although time periodic, was spatially disordered and had a frequency that was considerably larger than the expected Hopf frequency. In a separate sample cell with a radial ramp in the spacing no structure was observed at all in the cell interior until the expected stationary instability was reached.


Effectiveness of Nonoperative Management of Hip Microinstability
Hip microinstability has recently gained acceptance as a cause of hip pain. In this condition, the femoral head demonstrates increased motion relative to the acetabulum, which may lead to chondrolabral damage. Even though patients are initially prescribed a trial of nonoperative treatment, the success rates of rehabilitation are unknown. To determine the success rate of nonoperative treatment of hip microinstability. Case series; Level of evidence, 4. After institutional review board approval was obtained, a retrospective chart review was performed on patients at a university sports medicine practice between January 2013 and July 2016. All patients older than 18 years presenting with hip microinstability who were initially recommended for treatment with physical therapy were enrolled in this study. Formal physical therapy sessions focused on strengthening the hip and core muscles. These sessions took place twice a week for a minimum of 6 weeks in conjunction with a home exercise program. The number of patients who eventually underwent surgical treatment and the clinical scores for the cohort (modified Harris Hip Score [mHHS] and 33-item International Hip Outcome Tool) were recorded. A total of 64 patients (63 female, 1 male), with a mean ± SD age of 32.2 ± 10.5 years, were identified and studied. Onset of symptoms was insidious (n = 45; 70.3%), acute atraumatic (n = 12; 18.8%), and traumatic (n = 7; 10.9%). A total of 9 (14.1%) patients were high-level athletes. After a follow-up of 45.7 ± 14.6 months, 14 (29.8%) patients eventually underwent hip arthroscopy for persistent hip pain. Capsular plication was performed in all surgical cases. High-level athletes were not more likely to need surgery (50% vs 26.8%; P = .34). The mHHS was available in 24 patients who were treated nonoperatively, and it improved from 67.4 to 85.0 (P < .01). More than two-thirds of patients treated for hip microinstability were able to avoid surgery; they were successfully treated nonoperatively with physical therapy and a home exercise program and demonstrated improved clinical outcome scores.


Decreased expression of smooth muscle alpha-actin results in decreased contractile function of the mouse bladder.
Smooth muscle alpha-actin (SMalphaA) is an important actin isoform for functional contractility in the mouse bladder. Alterations in the expression of SMalphaA have been associated with a variety of bladder pathological conditions. Recently, a SMalphaA-null mouse was generated and differences in vascular tone and contractility were observed between wild-type and SMalphaA-null mice suggesting alterations in function of vascular smooth muscle. We used SMalphaA-null mice to explore the hypothesis that SMalphaA is necessary for normal bladder function. Reverse transcriptase polymerase chain reaction, Western blotting and immunohistochemical staining were used to confirm the absence of SMalphaA transcript and protein in the bladder of SMalphaA-null mice. In vitro bladder contractility compared between bladder rings harvested from wild-type and SMalphaA-null mice was determined by force measurement following electrical field stimulation (EFS), and exposure to chemical agonists and antagonists including KCl, carbachol, atropine and tetrodotoxin. Resulting force generation profiles for each tissue and agent were analyzed. There was no detectable SMalphaA transcript and protein expression in the bladder of SMalphaA-null mice. Nine wild-type and 9 SMalphaA-null mice were used in the contractility study. Bladders from SMalphaA-null mice generated significantly less force than wild-type mice in response to EFS after KCl. Similarly, bladders from SMalphaA-null mice generated less force than wild-type mice in response to pretreatment EFS, and EFS after carbachol and atropine, although the difference was not significant. Surprisingly, the bladders in SMalphaA-null mice appeared to function normally and showed no gross or histological abnormalities. SMalphaA appears to be necessary for the bladder to be able to generate normal levels of contractile force. No functional deficits were observed in the bladders of these animals but no stress was placed on these bladders. To our knowledge this study represents the first report to demonstrate the importance of expression of SMalphaA in force generation in the bladder.


Oxidative Stress-Related Genetic Variants May Modify Associations of Phthalate Exposures with Asthma.
Background: Phthalate exposure may increase the risk of asthma. Little is known about whether oxidative-stress related genes may alter this association. First, this motivated us to investigate whether genetic polymorphisms of the oxidative-stress related genes glutathione S-transferase Mu 1 (GSTM1), glutathione S-transferase pi 1 (GSTP1), superoxide dismutase 2 (SOD2), catalase (CAT), myeloperoxidase (MPO), and EPHX1 in children are associated with phthalate urine concentrations. Second, we addressed the question whether these genes may affect the influence of phthalates on asthma.Methods: In a case-control study composed of 126 asthmatic children and 327 controls, urine phthalate metabolites (monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono(2-ethyl-5-hydroxyhexyl)phthalate (MEHHP) were measured by UPLC-MS/MS at age 3. Genetic variants were analyzed by TaqMan assay. Information on asthma and environmental exposures was also collected. Analyses of variance and logistic regressions were performed. Results: Urine MEHHP levels were associated with asthma (adjusted OR 1.33, 95% CI (1.11-1.60). Children with the GSTP1 (rs1695) AA and SOD2 (rs5746136) TT genotypes had higher MEHHP levels as compared to GG and CC types, respectively. Since only SOD2 TT genotype was significantly associated with asthma (adjusted OR (95% CI): 2.78 (1.54-5.02)), we estimated whether SOD2 variants modify the association of MEHHP levels and asthma. As MEHHP concentrations were dependent on GSTP1 and SOD2, but the assessment of interaction requires independent variables, we estimated MEHHP residuals and assessed their interaction, showing that the OR for SOD2 TT was further elevated to 3.32 (1.75-6.32) when the residuals of MEHHP were high. Conclusions: Urine phthalate metabolite concentrations are associated with oxidative-stress related genetic variants. Genetic variants of SOD2, considered to be reflect oxidative stress metabolisms, might modify the association of phthalate exposure with asthma.


The fragility of freedom of speech.
Freedom of speech is a fundamental liberty that imposes a stringent duty of tolerance. Tolerance is limited by direct incitements to violence. False notions and bad laws on speech have obscured our view of this freedom. Hence, perhaps, the self-righteous intolerance, incitements and threats in response to Giubilini and Minerva. Those who disagree have the right to argue back but their attempts to shut us up are morally wrong.


Real-time chemical composition of ambient fine aerosols and related cytotoxic effects in human lung epithelial cells in an urban area.
Particulate matter with aerodynamic diameters ≤1 μm (PM1) in the atmosphere, especially that which is emitted from anthropogenic sources, can induce considerable negative effects on the cardiopulmonary system. To investigate the chemical emission characteristics and organic sources in Yuen Long (Hong Kong), both offline and online approaches for PM1 samples were applied by filter-based samplers and a Quadrupole Aerosol Chemical Speciation Monitor (Q-ACSM), respectively. The toxicological effects on human A549 lung alveolar epithelial cells were investigated, and associations between cytotoxicity and organic sources and compositions were evaluated. The organics from the Q-ACSM measurement were the largest contributor to submicron aerosols in both seasons of our study, and the mass fraction was higher in winter (60%) than it was in autumn (46%). Regarding organic sources, the mass fraction of hydrocarbon-like organics (HOA) increased from 7% in autumn to 38% in winter, whereas cooking organics (COA) decreased from 30% in autumn to 18% in winter, and oxygenated organics (OOA) decreased from 63% to 45%. Organic compounds contributed more during pollution episodes, and more secondary ions were formed by means of the oxidation process. Oxidative and inflammatory responses in A549 cells were found with PM1 exposures; the differences in chemical compositions resulted in the higher cytotoxicity in winter than autumn. The cooking organic aerosol in residential area was significantly correlated with cell inflammation. Both elemental carbon and specific inorganic ions (SO42- and Mg2+) contributed to the intracellular cytotoxicity. This study demonstrated that specific atmospheric particulate matter chemical properties and sources can trigger distinct cell reactions; the inorganic ions from cooking emissions cannot be disregarded in terms of their pulmonary health risks in residential areas.


Benefit of Early Initiation of Neuraminidase Inhibitor Treatment to Hospitalized Patients With Avian Influenza A(H7N9) Virus.
The significance of early neuraminidase inhibitor (NAI) therapy for treating influenza A(H7N9) is currently unknown. The duration of viral shedding was monitored by reverse-transcription polymerase chain reaction after patients with confirmed H7N9 infection were admitted to the First Affiliated Hospital, Zhejiang University, during April 2013-April 2017. Indices such as the length of hospitalization and mortality were collected, and the correlation between the time of administration of NAI and the severity of disease was systematically analyzed. One hundred sixty patients with confirmed H7N9 infection were divided into 3 groups according to NAI starting time. Three of 20 (15%) patients for whom NAI was administered within 2 days died compared with 12 of 52 (23.1%) patients who received treatment within 2-5 days and 33 of 88 (37.5%) patients who were treated after 5 days (P < .05). The median durations of viral shedding from NAI therapy initiation was 4.5 days (interquartile range [IQR], 3-9 days) for patients who took antiviral medication within 2 days, which was significantly different from that for patients who took medication within 2-5 days (7.5 days [IQR, 4.25-12.75 days]) or after 5 days (7 days [IQR, 5-10 days]) (P < .05). We found that the duration of viral shedding from NAI therapy was the shortest in spring 2013 (5.5 days) and the longest in winter-spring 2016-2017 (8.5 days) (P < .05), showing a prolonged trend. Early NAI therapy within 2 days of illness shortened the duration of viral shedding and improved survival in patients with H7N9 viral infection.


Motives for health plan-academic health center relationships: journal review of the first quarter century.
Motives for health plan (HP)-academic health center (AHC) relationships, including both deterrents and inducements, are explored through a review of 153 articles, published from 1970 through 1997, in academic and health care industry journals about HP-AHC relationships. Every article that met inclusion criteria was coded for year, journal, author, audience, type of article, organization of focus, purposes, priorities, affiliation motives, and issues. Peak years were 1973 (the passage of HMO legislation) and the most recent years from 1994 through 1997. The motives to affiliate were found to be different for AHCs and HPs (e.g., physician attitudes, a deterrent for AHCs and inducement for HPs; resources, a deterrent for HPs and inducement for AHCs). Increases in size of HPs and decreases in political power of AHCs have resulted in changes to motives to form relationships. Motives must be acknowledged to move from competitive to collaborative relationships.


Economy in track runners and orienteers during path and terrain running.
The aims of the present study were to assess running economy in track runners and orienteers and to identify the factors responsible for any differences. The participants were 11 orienteers and 10 track runners of similar age, body mass, maximal oxygen uptake and training background. However, the orienteers included heavy terrain running in their daily training, whereas the track runners ran almost entirely on the roads and tracks. Maximal oxygen uptake and running economy were calculated during horizontal path running and during cross-country running in rough terrain with steep hills, using a telemetric system (K2, Cosmed, Italy). Running economy during path running was 217+/-12 and 212+/-14 ml x kg(-1) x km(-1) (mean +/- s) in the orienteers and the track runners, respectively. Running economy was impaired by 41-52% in heavy terrain (P < 0.05), and was less pronounced in the orienteers than in the track runners (88+/-18 vs 109+/-26 ml x kg(-1) x km(-1); P < 0.05). In conclusion, the better running economy of orienteers when changing from horizontal path to heavy terrain running could be an innate ability, or it could be speculated that specific training may improve running economy, indicating the importance of specific training for orienteers.


Sequestration of p-nitrophenol from liquid phase by poly(acrylonitrile-co-acrylic acid) containing thioamide group.
In this paper, the adsorptive performance of synthesized thiourea (TU) modified poly(acrylonitrile-co-acrylic acid) (TU-P(AN-co-AA)) polymeric adsorbent for capturing p-nitrophenol (PNP) from aqueous solution was investigated. TU-P(AN-co-AA) was synthesized via the redox polymerization method with acrylonitrile (AN) and acrylic acid (AA) as the monomers, then modified chemically with thiourea (TU). Characterization analysis with Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), elemental microanalysis for CHNS, zeta potential measurement, Brunauer-Emmett-Teller (BET) surface analysis and thermal analyses were carried out to determine the morphology and physico-chemical properties of the synthesized polymer. The characterization results indicated successful surface modification of polymer with TU. The performance of TU-P(AN-co-AA) for the removal of PNP was investigated under various experimental parameters (adsorbent dosage, initial adsorbate concentration, contact time and temperature). The results demonstrated that the Freundlich isotherm model and pseudo-second-order kinetic model best described the equilibrium and kinetic data, respectively. Thermodynamic studies showed that the uptake of PNP by TU-P(AN-co-AA) was spontaneous and exothermic in nature. The results of the regeneration studies suggested that the TU-P(AN-co-AA) polymer is a reusable adsorbent with great potential for removing PNP from wastewater.


A relative-entropy algorithm for genomic fingerprinting captures host-phage similarities.
The degeneracy of codons allows a multitude of possible sequences to code for the same protein. Hidden within the particular choice of sequence for each organism are over 100 previously undiscovered biologically significant, short oligonucleotides (length, 2 to 7 nucleotides). We present an information-theoretic algorithm that finds these novel signals. Applying this algorithm to the 209 sequenced bacterial genomes in the NCBI database, we determine a set of oligonucleotides for each bacterium which uniquely characterizes the organism. Some of these signals have known biological functions, like restriction enzyme binding sites, but most are new. An accompanying scoring algorithm is introduced that accurately (92%) places sequences of 100 kb with their correct species among the choice of hundreds. This algorithm also does far better than previous methods at relating phage genomes to their bacterial hosts, suggesting that the lists of oligonucleotides are "genomic fingerprints" that encode information about the effects of the cellular environment on DNA sequence. Our approach provides a novel basis for phylogeny and is potentially ideally suited for classifying the short DNA fragments obtained by environmental shotgun sequencing. The methods developed here can be readily extended to other problems in bioinformatics.


Treatment of femoral neck nonunions with a sliding compression screw: comparison with and without subtrochanteric valgus osteotomy.
The aim of this prospective study was to investigate and compare the results of treatment of femoral neck nonunions using a sliding compression screw (SCS) with and without subtrochanteric valgus osteotomy (SVO). Thirty-two consecutive patients with femoral neck nonunions, which sustained no osteonecrosis of the femoral head based on bone scan study, were prospectively treated with SCS with (21 patients) or without (11 patients) SVO. The indication for SCS with SVO was a femoral neck nonunion with leg shortening of more than 1.5 cm. SCS without SVO was for leg shortening of less than 1.5 cm. Seventeen patients with osteotomy and nine patients without osteotomy were followed for at least 2 years (range, 2-8 years). All femoral neck fractures healed, with a union period of 4.6+/-1.0 months (95% confidence interval, 4.1-5.1 months) for osteotomy cases and 4.6+/-1.1 months (95% confidence interval, 3.8-5.4 months) for nonosteotomy cases (p = 0.83). However, in the osteotomy group, two patients sustained osteonecrosis of the femoral head, and nonunion remained in 1 patient at the osteotomy site (complication rate, 18%; 3 of 17 patients). There were no complications in the nonosteotomy group (p = 0.26). The average lengthening achieved from osteotomy was 1.0 to 1.5 cm (p < 0.001). Using SCS without SVO to treat femoral neck nonunions can result in a very satisfactory outcome. It is thus preferred for indicated patients. SCS without SVO, however, cannot concomitantly correct a femoral neck shortening; furthermore, shortening may deteriorate because of a telescoping effect. For patients with evident shortening, therefore, combined SVO with SCS is more suitable.


[Enhancement of immunogenicity of hCGbeta protein vaccine and the hCG neutralization capacity of anti-serum by using the molecular adjuvant C3d3].
To enhance the immunogenicity of hCGbeta protein vaccine and the hCG neutralization capacity of anti-serum by using the molecular adjuvant C3d3, the secreted 6his-hCGbeta-C3d3 fusion protein and 6his-hCGbeta were expressed in CHO cells and purified with Ni(2+)-chelating chromatography and Sephadex G-150 column. Then we investigated the potential of three copies of C3d as the molecular adjuvant of hCGbeta protein antigen. The antibody response to hCGbeta-C3d3 conjugates was compared with those resulting from immunization with hCGbeta alone and hCGbeta plus CFA/IFA in BALB/c mice. Our results showed that the antibody titer of hCGbeta-C3d3 was 1995-fold higher than that of hCGbeta alone and the anti-serum was capable effectively neutralizing the bioactivity of hCG. The immunity-enhancing action of C3d3 was 10-fold (primer) and 32-fold (booster) greater than CFA/IFA. These results indicated that C3d3 conjugates might be a better way to overcome the poor immunogenicity of hCGbeta contraceptive vaccine.


[Differences in the mechanisms of thermoregulation in rats in separate and combined adaptation to cold and heat].
Combined adaptation of rats to heat and cold increasing mechanisms of thermogenesis enhances resistance to both factors and heat dissipation. Adaptive changes in thermogenesis are mainly a result of activation of adrenergic mechanisms, while the separate cold adaptation is accompanied by hyperfunction of thyroid glands. Mechanisms of heat dissipation in rats of the "combined" group increase even more than those of "heat" group.


T-cell-dependent immunity and thrombocytopenia in rats infected with Plasmodium chabaudi.
Normal, splenectomized, and athymic Fischer rats were infected with Plasmodium chabaudi. In normal rat infections, acute-phase infection resolved rapidly and completely. In splenectomized rats, infection resulted in high parasitemia and ultimately death. In nude rats, parasite growth was reduced compared with normal rats, and a persistent parasitemia (between 20 and 45%) was observed for several months. Complete resolution of the infection was achieved after adoptive transfer of T lymphocytes, even when transfer occurred during the course of infection. These results indicated that an acquired, T-lymphocyte-dependent immunity was necessary for the complete recovery observed in normal rats. In normal rats, thrombocytopenia and splenomegaly occurred during infection. By contrast, in nude rats, both of these pathological manifestations were only observed after thymus grafting. Thrombocytopenia was also absent in the splenectomized animals. Despite an increase in platelet-associated immunoglobulin levels during the infection, thrombocytopenia was not transferred by injection of infected rat serum to normal recipients. It has been concluded that the nude rat infection can be regarded as a novel and useful model for studying the T-cell-dependent effector and pathological mechanisms and to investigate the anti-P. chabaudi immune response.


Multiview confocal super-resolution microscopy.
Confocal microscopy1 remains a major workhorse in biomedical optical microscopy owing to its reliability and flexibility in imaging various samples, but suffers from substantial point spread function anisotropy, diffraction-limited resolution, depth-dependent degradation in scattering samples and volumetric bleaching2. Here we address these problems, enhancing confocal microscopy performance from the sub-micrometre to millimetre spatial scale and the millisecond to hour temporal scale, improving both lateral and axial resolution more than twofold while simultaneously reducing phototoxicity. We achieve these gains using an integrated, four-pronged approach: (1) developing compact line scanners that enable sensitive, rapid, diffraction-limited imaging over large areas; (2) combining line-scanning with multiview imaging, developing reconstruction algorithms that improve resolution isotropy and recover signal otherwise lost to scattering; (3) adapting techniques from structured illumination microscopy, achieving super-resolution imaging in densely labelled, thick samples; (4) synergizing deep learning with these advances, further improving imaging speed, resolution and duration. We demonstrate these capabilities on more than 20 distinct fixed and live samples, including protein distributions in single cells; nuclei and developing neurons in Caenorhabditis elegans embryos, larvae and adults; myoblasts in imaginal disks of Drosophila wings; and mouse renal, oesophageal, cardiac and brain tissues.


Phonological learning and lexicality of treated stimuli.
The purpose was to evaluate the lexicality of treated stimuli relative to phonological learning by preschool children with functional phonological disorders. Four children were paired in a single-subject alternating treatments design that was overlaid on a multiple baseline across subjects design. Within each pair, one child was taught one sound in real words and a second sound in non-words; for the other child of the pair, lexicality was reversed and counterbalanced. The dependent variable was production accuracy of the treated sounds as measured during the session-by-session course of instruction. Results indicated that production accuracy of the treated sound was as good as or better using non-word as opposed to real word stimuli. The clinical implications are considered, along with potential accounts of the patterns of learning.


Mikania Micrantha Wilt Virus Alters Insect Vector's Host Preference to Enhance Its Own Spread.
As an invasive weed, Mikaniamicrantha Kunth has caused serious damage to natural forest ecosystems in South China in recent years. Mikania micrantha wilt virus (MMWV), an isolate of the Gentian mosaic virus (GeMV), is transmitted by Myzuspersicae (Sulzer) in a non-persistent manner and can effectively inhibit the growth of M. micrantha. To explore the MMWV-M. micrantha-M. persicae interaction and its impact on the invasion of M. micrantha, volatile compounds (VOCs) emitted from healthy, mock-inoculated, and MMWV-infected plants were collected, and effects on host preference of the apterous and alate aphids were assessed with Y-shaped olfactometers. Gas chromatography-mass spectrometry (GC-MS) analysis indicated that MMWV infection changed the VOC profiles, rendering plants more attractive to aphids. Clip-cages were used to document the population growth rate of M.persicae fed on healthy, mock-inoculated, or MMWV-infected plants. Compared to those reared on healthy plants, the population growth of M. persicae drastically decreased on the MMWV-infected plants. Plant host choice tests based on visual and contact cues were also conducted using alate M.persicae. Interestingly, the initial attractiveness of MMWV-infected plants diminished, and more alate M. persicae moved to healthy plants. Taken together, MMWV appeared to be able to manipulate its plant host to first attract insect vectors to infected plants but then repel viruliferous vectors to promote its own dispersal. Its potential application for invasive weed management is discussed.


On the mechanism of elasto-inertial turbulence.
Elasto-inertial turbulence (EIT) is a new state of turbulence found in inertial flows with polymer additives. The dynamics of turbulence generated and controlled by such additives is investigated from the perspective of the coupling between polymer dynamics and flow structures. Direct numerical simulations of channel flow with Reynolds numbers ranging from 1000 to 6000 (based on the bulk and the channel height) are used to study the formation and dynamics of elastic instabilities and their effects on the flow. The flow topology of EIT is found to differ significantly from Newtonian wall-turbulence. Structures identified by positive (rotational flow topology) and negative (extensional/compressional flow topology) second invariant Qa isosurfaces of the velocity gradient are cylindrical and aligned in the spanwise direction. Polymers are significantly stretched in sheet-like regions that extend in the streamwise direction with a small upward tilt. The Qa cylindrical structures emerge from the sheets of high polymer extension, in a mechanism of energy transfer from the fluctuations of the polymer stress work to the turbulent kinetic energy. At subcritical Reynolds numbers, EIT is observed at modest Weissenberg number (Wi, ratio polymer relaxation time to viscous time scale). For supercritical Reynolds numbers, flows approach EIT at large Wi. EIT provides new insights on the nature of the asymptotic state of polymer drag reduction (maximum drag reduction), and explains the phenomenon of early turbulence, or onset of turbulence at lower Reynolds numbers than for Newtonian flows observed in some polymeric flows.


The development of the concept of reactive psychoses.
Although reactive (psychogenic) psychoses have no doubt occurred throughout the history of mankind, it is only during the last century that the corresponding concept has been defined, beginning with Sommer's definition of the term 'psychogenic' and Jaspers' distinctions between 'reaction' and 'process', and between 'neurosis' and 'psychosis', respectively. A change in Kurt Schneider's nosological concepts induced the majority of German-speaking psychiatrists to avoid the concept of psychogenic psychoses. The very varying use of the concept of reactive psychoses in different countries is described and discussed, with special regard to implications for psychiatric epidemiology.


Locally acquired neurocysticercosis--North Carolina, Massachusetts, and South Carolina, 1989-1991.
From October 1989 through November 1991, three persons with neurocysticercosis acquired in the eastern United States (North Carolina, Massachusetts, and South Carolina) were reported to CDC. This report summarizes clinical and epidemiologic information for these cases.


Aqueous humor flow and flare in patients with myotonic dystrophy.
Myotonic dystrophy is an autosomal dominant form of muscular dystrophy associated with a mutation that affects a gene on chromosome 19. Extremely low intraocular pressure is one of a constellation of clinical signs that sometimes accompany this disorder. This study was performed to determine if the ocular hypotony can be explained by aqueous humor hyposecretion. Seventeen persons with myotonic dystrophy and seventeen age-matched controls were studied. Intraocular pressure, light scattering (flare), fluorescein clearance at various times of day, and the response of the eye to the topical timolol were measured. Intraocular pressure was 40% lower in the persons with myotonic dystrophy (8.4 mm Hg vs 14.0 mm Hg) and flare was 50% higher (55.8 mg/dl albumin equivalent vs 37.1 mg/dl albumin equivalent). Fluorescein clearance in persons with myotonic dystrophy was indistinguishable from normal at all times of day. Myotonic eyes responded normally to topical timolol. The physiological data of this study are most consistent with the conclusion that the rate of aqueous humor flow is reduced approximately 9%, and the rate of inward leakage of light scattering proteins is increased approximately 37% in well-established myotonic dystrophy with ocular hypotony. The reduced aqueous humor flow alone is insufficient to explain the ocular hypotony. We hypothesize that the hypotony is due primarily to atrophy of the ciliary muscle that increases fluid exchange between the anterior chamber and the anterior uvea with consequent enhancement of uveoscleral outflow.


Erich Fischer-brügge (28.12.1904-4.2.1951) -- founder of neurosurgery at the university of Münster.
In 1936, Erich Fischer-Brügge, who worked as a surgeon at the University Clinic of Münster, Westfalia, Germany, visited Wilhelm Tönnis in Würzburg, to receive neurosurgical training. He commenced his work in the field of neurosurgery in Münster from 1937. In 1938 he published a new classification of the anterior circulation of cerebral arteries in states of tumorous mass lesions. From 1939 through to the end of WW II, Tönnis and Fischer-Brügge worked closely together, mainly in the field of war surgery. After WW II, in 1949, Fischer-Brügge published another relevant clinical contribution on the "Clivuskantensyndom". He recognised the ipsilateral osseous compression of the oculomotor nerve at the sphenoidal ridge in raised intracranial pressure. Paul Sunder-Plassmann, successor of Hermann Coenen as chief of surgery at the University Clinic in 1946, inhibited Fischer-Brügge's neurosurgical work massively. After numerous unsuccessful applications for newly installed neurosurgical units, Fischer-Brügge died at the age of only 46 years.


[Depression, nonverbal intellectual impairment and quality of life following left-brain ischemic insult--results of a catamnestic study].
The purpose of the present study was to establish the relationship between persisting aphasia and the extent of overall disability in the long-term outcome following left hemisphere ischaemic stroke. 55 right-handed patients who had sustained an initial left-sided cerebral infarction, verified by CT scan, were investigated after a mean observation period of six years. 39 patients were categorized as being non-aphasic, and 16 as being aphasic (3 Global, 6 Broca's, 1 conduction, 1 transcortical motor and 5 anomic aphasics) at the end of the follow-up period. Regarding motor and sensory functions, a correlation between the presence of aphasia and the severity of deficits could be established at the end of the follow-up period. With respect to activities of daily living, a significantly larger number of aphasic stroke victims had to rely on help by others. Furthermore, the persistence of aphasia also negatively influenced the subsequent occupational capacity. With regard to social participation and leisure activities, a significant reduction was found in aphasic long-term stroke survivors as compared to non-aphasics. Concerning quality of life, both groups reported a marked decline at the end of the observation period; the presence of aphasia had an additional negative effect. However, as regards the long-term non-verbal cognitive impairment, statistical analysis revealed no significant differences between both groups. In addition, aphasic stroke survivors did not demonstrate a higher incidence of depressive states than those without language deficit. On the basis of our results it is concluded that the presence of aphasia in left-hemispheric ischaemic stroke survivors indicates a more severe stroke, resulting in greater physical disability and social handicap in the long-term outcome.(ABSTRACT TRUNCATED AT 250 WORDS)


Pyogenic ventriculitis complicating Aggregatibacter aphrophilus infective endocarditis: A case report and literature review.
Pyogenic ventriculitis (PV) is an uncommon, but frequently fatal infection that results from inflammation of the ventricular ependymal lining associated with a purulent ventricular system. PV has been rarely reported as a secondary complication of infective endocarditis. Prompt diagnosis and treatment with appropriate culture-directed antibiotics with adequate central nervous system penetration is crucial when managing patients who are suspected of having PV. The present study reports on a fatal case of a previously well 42-year-old alcoholic woman with infective endocarditis caused by Aggregatibacter aphrophilus, with secondary brain abscess and spontaneous rupture into the ventricles causing PV.


Histology and function: analyzing the uvular muscle.
Virtual surgery and virtual patients necessitate quantitative data on the area of interest. The study was conducted to exactly describe the embryonic and fetal uvular muscle (MU), relevant for clinical as well as virtual surgery and virtual patient generation. Serially sectioned viscerocrania of 10 aborted embryos and fetuses underwent three-dimensional reconstruction to obtain detailed anatomic data and perform finite element analyses. The MU was paired in 80% of cases, while 20% allowed no clear-cut distinction. The MU merged with the levator muscle beneath the palatal aponeurosis without a hard palate insertion. Superior longitudinal central fibers ran below the nasal mucosa, and few circular peripheral fibers crossed in the central third to the contralateral side. This was seen in 30% of the paired muscles and in all cases when no differentiation was possible; about 40% to 80% MU fibers crossed to the ipsilateral and contralateral palatopharyngeus muscle behind the levator loop. MU fibers inserted 60% nasal and 40% oral to the basal membrane at the middle third of the macroscopic uvula, made of loose connective tissue and salivary glands. The results of the finite element simulation of the uvula showed no distinct patterns or distributions of local stress. Detailed anatomical study supported the concept of mediocranial MU repositioning during corrective surgery, although the impact is minor to the levator muscle's action. Future mathematical models describing effects of such a maneuver should integrate surrounding structures.


A biobehavioral perspective of tumor biology.
Extract: The perspective that cancer may be causally linked to stress has a long history. In 200 AD, Galen proposed that melancholic women were more susceptible to cancer than women who were sanguine. Rigorous examinations of related observations have lagged over the ensuing centuries. More recently, epidemiologic studies have shown that psychologic and social characteristics (e.g., chronic stress and negative life events, social isolation and support, socioeconomic burden, and emotional processes) might be associated with differential cancer incidence, progression, and mortality. The biologic mechanisms (e.g., signaling pathways) that may account for such observations are being discovered through the convergence of relevant molecular, cellular, and clinical data. In this article, we review the clinical and experimental evidence regarding the effects of stress on tumor development, growth, and progression. Within this context, we define "stress" as an external event ("stressor") or perception of such events that engender psychologic and physiologic changes ("stress responses") designed to approach, avoid, or defend against the external event.


How Rhizobia Adapt to the Nodule Environment.
Rhizobia are a phylogenetically diverse group of soil bacteria that engage in mutualistic interactions with legume plants. Although specifics of the symbioses differ between strains and plants, all symbioses ultimately result in the formation of specialized root nodule organs that host the nitrogen-fixing microsymbionts called bacteroids. Inside nodules, bacteroids encounter unique conditions that necessitate the global reprogramming of physiological processes and the rerouting of their metabolism. Decades of research have addressed these questions using genetics, omics approaches, and, more recently, computational modeling. Here, we discuss the common adaptations of rhizobia to the nodule environment that define the core principles of bacteroid functioning. All bacteroids are growth arrested and perform energy-intensive nitrogen fixation fueled by plant-provided C4-dicarboxylates at nanomolar oxygen levels. At the same time, bacteroids are subject to host control and sanctioning that ultimately determine their fitness and have fundamental importance for the evolution of a stable mutualistic relationship.


Assessment of fracture risk.
Osteoporosis-related fractures (low-trauma, fragility fractures) are associated with significant morbidity, mortality, and health care expenditure worldwide. In the absence of a defining fracture, the diagnosis of osteoporosis is based on the World Health Organization's T-score criteria using central dual-energy x-ray absorptiometry (DXA). Paradoxically, the majority of those patients who will sustain a low-trauma fracture do not meet the T-score definition of osteoporosis. Conversely, younger individuals with bone density in the osteoporotic range but no other risk factors have relatively low fracture rates and yet are frequently considered candidates for osteoporosis therapies. The limited accuracy of bone density testing alone to predict fractures has led to the development of a variety of fracture assessment tools that utilize the combination of bone density and clinical risk factors to improve the prediction of low-trauma fractures. These fracture assessment tools quantitatively predict the 10-year fracture probability of hip and major osteoporosis-related fractures, and can be used to define cost-effective intervention strategies for primary and secondary fracture prevention.


Comparison between the timing of JNK activation, c-Jun phosphorylation, and onset of death commitment in sympathetic neurones.
We have investigated the relationship between c-Jun N-terminal kinase (JNK) activity, apoptosis, and the potential of survival factors to rescue primary rat sympathetic neurones deprived of trophic support. Incubation of sympathetic neurones in the absence of nerve growth factor (NGF) caused a time-dependent increase in JNK activity, which became apparent by 3 h and attained maximal levels that were three- to fourfold higher than activity measured in neurones maintained for the same periods with NGF. Continuous culture in the presence of either NGF or the cyclic AMP analogue 4-(8-chlorophenylthio) cyclic AMP (CPTcAMP) not only prevented JNK activation from occurring, but also suppressed JNK activity that had been elevated by prior culture of the neurones in the absence of trophic support. When either NGF or CPTcAMP was added to cultures that had been initially deprived of neurotrophic support for up to 10 h, this resulted in complete suppression of total JNK activity, arrest of apoptosis, and rescue of >90% of the neurones that did not display apoptotic morphology by this time. However, when either agent was added after more protracted periods of initial neurotrophin deprivation (> or = 14 h), although this also resulted in near-complete suppression of total JNK activity and short-term arrest of apoptosis, not all of the neurones that appeared to be nonapoptotic at the time of agent addition were rescued. The lack of death commitment after 10 h of maintained JNK activity was not due to a late induction of c-Jun expression, because the majority of newly isolated sympathetic neurones had already been expressing high levels of c-Jun in their nuclei for several hours, yet were capable of being rescued by NGF. Elevation of JNK activity as a result of neurotrophic-factor deprivation was also associated with enhanced phosphorylation of c-Jun, assessed by immunoblot analysis and immunocytochemistry, and addition of NGF to cultures previously deprived of neurotrophic support resulted in a reversion of the state of phospho-c-Jun to that observed in cultures that had been maintained in the continuous presence of trophic support. We conclude that activation of JNK and c-Jun phosphorylation are not necessarily rate-limiting for apoptosis induction. In some neurones undergoing prolonged NGF deprivation, suppression of JNK activity and c-Jun dephosphorylation by NGF may be insufficient to effect their rescue. Thus, if c-Jun mediates death by increasing the expression of "death" genes, these must become effective very close to the death commitment point.


Reversible and bidirectional signaling of notch ligands.
The Notch signaling pathway is a direct cell-cell communication system involved in a wide variety of biological processes, and its disruption is observed in several pathologies. The pathway is comprised of a ligand-expressing (sender) cell and a receptor-expressing (receiver) cell. The canonical ligands are members of the Delta/Serrate/Lag-1 (DSL) family of proteins. Their binding to a Notch receptor in a neighboring cell induces a conformational change in the receptor, which will undergo regulated intramembrane proteolysis (RIP), liberating the Notch intracellular domain (NICD). The NICD is translocated to the nucleus and promotes gene transcription. It has been demonstrated that the ligands can also undergo RIP and nuclear translocation, suggesting a function for the ligands in the sender cell and possible bidirectionality of the Notch pathway. Although the complete mechanism of ligand processing is not entirely understood, and its dependence on Notch receptors has not been ruled out. Also, ligands have autonomous functions beyond Notch activation. Here we review the concepts of reverse and bidirectional signalization of DSL proteins and discuss the characteristics that make them more than just ligands of the Notch pathway.


A brief assessment of frontal and subcortical functions in dementia.
A brief assessment of cognitive and motor functions associated with the frontal/subcortical system was evaluated for discriminant validity. Patients with dementia of Huntington's disease and Parkinson's disease performed as well as normal control subjects on the Mini-Mental State Exam (MMSE) but significantly worse on the Frontal/Subcortical Assessment Battery (FSAB). Discriminant function analyses yielded significantly higher rates of accurate classification with FSAB and MMSE combined than with MMSE alone. Patients with Alzheimer's disease scored significantly lower than other groups on both measures. The authors recommend the FSAB as an adjunct to the MMSE for brief assessments of patients with suspected frontal or subcortical pathology.


[Biological responses, ultrastructural changes and metabolism of estrone sulfate in line cells of human breast cancer: MCF-7].
The biological responses, the metabolism and the ultrastructural modifications provoked by estrone sulfate in the MCF-7 mammary cancer cell line are studied. The data indicate: 1) A fraction of estrone sulfate is hydrolyzed and the freed hormone is sufficient to elicit a biological response (progesterone receptor). 2) Using [3H]estrone sulfate, 24 h after culture, it is observed that the great part of the radioactive material in the cells is in the form of unconjugated estrogens. 3) The main transformation product of [3H]estrone sulfate is estradiol. This is found particularly in the nucleus. 4) Tamoxifen inhibits very significantly the conversion of estrone sulfate into estradiol. 5) Electronmicroscopic observations indicate that the estrone sulfate provokes an important development in the secretory system. In conclusion, it is suggested that the estrone sulfate can play an important role in the response to estrogens in human mammary cancer.


Efficacy of Acupuncture Treatment for Incidence of Poststroke Comorbidities: A Systematic Review and Meta-Analysis of Nationalized Cohort Studies.
Acupuncture has been applied as a complementary therapy in stroke survivors worldwide and approved to be beneficial to stroke recovery. However, there is little medical evidence regarding the association between acupuncture and the risk of poststroke comorbidities. We reviewed big data studies from the Taiwan National Health Insurance Research Database to investigate the risk of poststroke comorbidities after acupuncture treatment in a real-world situation. Ten English (PubMed, Embase, Medline, Cochrane, Alt HealthWatch, CINAHL, Health Source, PsycINFO, PsycARTICLES, and Psychology and Behavioral Sciences Collection) and two Chinese (AiritiLibray and Visualizing Health Data) electronic databases were searched from inception until December 2020 for nationalized cohort studies comparing the effects of acupuncture treatment with a nonacupuncture control group among stroke patients. Eight nationalized cohort studies were included. Six of eight studies showed a moderate overall risk of bias, while two studies showed a serious overall risk of bias. Included studies have investigated the effect of acupuncture in reducing the risk of seven medical conditions after stroke, including stroke recurrence, new-onset acute myocardial infarction (AMI), pneumonia, dementia, epilepsy, urinary tract infection (UTI), and depression. The meta-analysis showed clinically significant reductions in the risk of poststroke comorbidities in the acupuncture group compared to the nonacupuncture group (HR, 0.776; 95% CI, 0.719-0.838; p < 0.0001). In this systematic review and meta-analysis of nationalized cohort studies, acupuncture showed clinically relevant benefits in reducing the incidence of poststroke comorbidities, such as stroke recurrence, new-onset acute myocardial infarction (AMI), pneumonia, dementia, epilepsy, and UTI.


T-cell prolymphocytic leukemia frequently shows cutaneous involvement and is associated with gains of MYC, loss of ATM, and TCL1A rearrangement.
T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive mature T-cell leukemia with frequent cutaneous presentation, which has not been well characterized. Among the 25 T-PLLs diagnosed between 1990 and 2013 at our institution, 32% (8/25) showed cutaneous manifestations, presenting as rash, purpura, papules, and ulcers. The skin biopsies showed leukemia cutis with perivascular and periadnexal irregular, small to medium-sized lymphoid infiltrates without epidermotropism. The lymphoid infiltrates were composed of mature CD4+ T cells expressing other T-cell antigens, and a subset (48%) showed dual CD4+/CD8+ coexpression. Higher median absolute peripheral blood lymphocyte count (43.0 vs. 13.0 k/mm; P=0.031) and elevated lactate dehydrogenase levels (P=0.00018) at the time of diagnosis were significantly associated with T-PLLs with skin involvement compared with those without. The extent of bone marrow involvement (P=0.849) and overall survival (P=0.144) was similar in the 2 groups. Fluorescence in situ hybridization or karyotype revealed frequent gains of MYC (67%; n=9), loss of ATM (64%; n=11), and TCL1A rearrangement or inversion 14q (75%; n=12). Gains of TCL1A was also seen (78%; n=9), including in some cases that had concurrent TCL1A rearrangement, whereas TP53 loss was less common (30%; n=10). No correlation was seen between the immunophenotype and morphology versus the presence or absence of skin involvement. These data suggest that cutaneous involvement by T-PLL is relatively common and often associated with significant peripheral blood involvement. The frequent MYC, ATM, and TCL1A alterations identified support that these genes are integral to the pathogenesis of T-PLL.


A classification scheme for paradoxical vocal cord motion.
Paradoxical vocal cord motion (PVCM) is characterized by the inappropriate adduction of the true vocal cords during inspiration. Multiple causes have been proposed for this group of disorders, which share the common finding of mobile vocal cords that adduct inappropriately during inspiration and cause stridor by approximation. Management of this group of disorders has been complicated by the lack of a classification scheme to include all types of PVCM. We propose that PVCM be classified according to its underlying etiology and recognize the following causes of the disorder: 1. brainstem compression; 2. cortical or upper motor neuron injury; 3. nuclear or lower motor neuron injury; 4. movement disorder; 5. gastroesophageal reflux; 6. factitious or malingering disorder; 7. somatization/conversion disorder. Case reports are presented to illustrate the characteristic features and diagnostic evaluation used in assessing patients with PVCM. Management varies depending on the cause of PVCM and entails speech therapy, pharmacologic therapy, behavioral modification, and/or surgical intervention. Recognition of the multiple causes of PVCM allows otolaryngologists to formulate well-directed diagnostic evaluation and treatment.


Synthesis and evaluation of potential N pi and N sigma metal chelation sites within the beta-hydroxy-L-histidine subunit of bleomycin A2: functional characterization of imidazole N pi metal complexation.
The synthesis and evaluation of 4 and 5, fully functionalized deglycobleomycin A2 (2) analogues incorporating an oxazole and a pyrrole in place of the beta-hydroxy-L-histidine imidazole, are detailed. The oxazole agent is only capable of Npi metal complexation through a form related to the N1-H imidazole tautomer of bleomycin A2 (1) while the pyrrole agent may potentially mimic the Nsigma metal complexation capabilities of the imidazole N3-H tautomer. Metal complexes (Fe-II, Fe-III) of 4 and 5 were found to cleave duplex DNA in the presence of O2 (Fe-II) or H2O2 (Fe-III). The oxazole agent 4 which is incapable of Nsigma metal chelation was found to behave analogous to, albeit slightly less effectively than, deglycobleomycin A2 resulting in the characteristic 5'-GC/5'-GT sequence selective cleavage of duplex DNA directly confirming that imidazole/oxazole Npi metal chelation is sufficient for functional reactivity. Importantly, the effective substitution of the oxazole O-1 for the histidine N-1 further illustrates that this group does not require deprotonation upon metal complexation, oxygen activation, or the ensuing oxidation reactions, that the functional bleomycin A2 tautomer is the imidazole N'-H tautomer, and that the imidazole N'-H functionality is not contributing to the polynucleotide recognition through H-bonding to the phosphate backbone or nucleotide bases. In contrast, the pyrrole agent 5 which is incapable of Npi metal chelation, but possesses the capabilities of functioning as a Nsigma metal donor was also found to cleave duplex DNA, but does so in a nonsequence selective fashion with a significantly reduced efficiency and a diminished double to single strand cleavage ratio both only slightly above that of background iron itself. These observations are analogous to those made with 3 which lacks the imidazole altogether and further support the observations that Nsigma coordination, not Npi coordination, of the imidazole is required for the functional activity of bleomycin A2.


Non-pharmacological control of blood pressure and physical fitness in subjects with arterial hypertension.
In a group of 60 men and 17 women aged 54 +/- 9 yrs. suffering from mild and moderate arterial hypertension (i.e. 90 greater than DBP less than 120 mmHg), a five-week non-pharmacological intervention programme in spa led to a reduction in body weight by 5 kg, an increase in maximum tolerated workload by 4 W, a decrease in blood pressure at rest by 12/6 mmHg on average, and a decrease in heart rate during exercise and in the recovery phase. The training effect persisted in a certain degree for a long time (i.e. 14 months on average after spa treatment). The reduction in weight, heart rate and systolic blood pressure at rest persisted as well. The therapy resulted in a decrease in minute ventilation and there was no increase in aerobic capacity. No change in the number of pathological ECG changes at rest and during exercise was observed during spa treatment. The regimen and training measures enable to reduce pharmacological therapy in 60% of originally treated hypertensives. This kind of spa treatment constitutes a model of a rational lifestyle for persons with arterial hypertension.


Effects of low-dose dexamethasone on sleep EEG patterns, plasma cortisol, and the TSH response to TRH in major depression.
Dexamethasone (DEX) (0.5 mg, P.O.) and placebo were administered at 2300 h in randomized design to 19 patients with major depression and the effects on the sleep electroencephalogram (EEG) were studied. In addition, the thyroid stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH) and basal plasma cortisol concentrations were assessed the following morning. DEX did not affect sleep architecture or continuity variables, including rapid eye movement (REM) latency, REM activity and REM density. Similarly, DEX did not significantly influence the TSH response to TRH (delta max TSH). In contrast, plasma cortisol concentrations were significantly suppressed by DEX. The results indicate that, as opposed to higher dosages of glucocorticoids, 0.5 mg DEX had minimal effects on the sleep EEG or delta max TSH in depressed patients.


Facial Paresis After Mandibular Reconstruction.
Condylar neck fractures are common injuries that occur in the facial and mandibular regions. The proximity of this area to the vital neurovasculature creates the increased importance of proper surgical intervention to limit damage to the underlying structures. Here, we report a case of a condylar neck fracture that resulted in temporary paresis of the facial nerve. In addition, a review of the literature regarding condylar fracture treatment and its complications was conducted.