Chemically Modified Hyaluronic Acid for Prevention of Post-Surgical Adhesions: New Aspects of Gel Barriers Physical Profiles.
This study was conducted to provide information regarding the chemistry-including structure, synthesis, formulation, and mechanical properties-of two types of chemically modified anti-adhesion gels made of hyaluronic acid. Gel A (Hyalobarrier®) and gels B and C (HyaRegen® and MetaRegen®) that are used in postsurgical adhesion prevention. To date, little information is available on their physicochemical attributes. This information is necessary in order to understand the differences in their in vivo behavior. Comparative analyses were conducted under laboratory-controlled conditions, including measuring the shear viscosity, storage modulus G', peel strength, and extrusion forces. All polymers exhibited viscoelastic behavior. Polymer A showed a shear viscosity approximately three times larger than both polymers B and C (114 Pa.s-1 vs. 36-38 Pa.s-1) over the shear-rate range measured, indicating a possible better ability to resist flows and potentially remain in place at the site of application in vivo. The results of storage modulus (G') measurements showed 100 Pa for polymer A and 16 Pa and 20 Pa for polymers B and C, respectively. This translated into a weaker elastic behavior for gels B and C, and a lower ability to resist sudden deformation. The peel test results showed a rupture strength of 72 mN (0.016 lbf) for polymer A, 39.6 mN (0.0089 lbf) for polymer B, and 38.3 mN (0.0086 lbf) for polymers C, indicating possible higher adhesive properties for polymer A. Tests measuring the extrudability of the hyaluronic acid gels in their commercial syringes showed an average extrusion force of 20 N (4.5 lbf) for polymer A, 28 N (6.33 lbf) for polymer B, and 17 N (3.79 lbf) for polymer C. Modified anti-adhesion gels made of hyaluronic acid differed in mechanical properties and concentration. Further clinical studies are needed to confirm whether these differences make one polymer easier to apply during surgery and more likely to stay in place longer after in vivo application, and to determine which is potentially superior in terms of preventing adhesions.


Socio-ecological trajectories in a rural Austrian region from 1961 to 2011: comparing the theories of Malthus and Boserup via systemic-dynamic modelling.
This paper investigates to what extent the theories of Thomas Robert Malthus and Ester Boserup are still useful to analyse population and land-use trajectories in an industrial society at a regional scale. Following a model-based approach toward long-term socio-ecological research, we built two system dynamic models, each representing one theory, and calculated socio-ecological trajectories from 1961 to 2011 for a study region located within the Eisenwurzen region in Austria. Comparing the model trajectories with empirical data reveals opposing results for the fit of the dynamics of 'population and technology' compared to 'land use and technology'. Technology strongly influenced population development, whereas its impact on land-use intensity faded over time. Although these theories are usually seen as opposing, both models identify population development as a main driver for land-use changes, mainly population decreases that contributed to farmland abandonment. We find out-migration to be essential when applying the investigated theories to contemporary societies.


Distribution of globin genes in chicken reticulocyte chromatin fractionated on urografin gradients.
Buoyant density centrifugation in Urografin solutions resolved French Pressure Cell-sheared, and micrococcal nuclease-digested avian reticulocyte chromatin into a broad profile of two peaks. Hybridization experiments using a globin cDNA probe suggested minimal fractionation of transcriptionally active and inactive components with chromatin sheared at 6000 psi, while no evidence was obtained for any fractionation with chromatin sheared at lower or higher pressures, or with chromatin digested to various extents with micrococcal nuclease, despite a considerable spread of chromatin material across gradients.


Association between dihydrotestosterone and long-term risk for prostate cancer mortality: A prospective cohort study.
The androgen metabolism plays an important role in the progression of prostate cancer. Contradictory to what one might assume given the androgenic potency of dihydrotestosterone (DHT) there are indications that high DHT levels protect from prostate cancer. We want to determine whether there is a long-term association between baseline levels of DHT and death from prostate cancer. During the years 1988 and 1989, 1782 men out of 2400 invited were screened for prostate cancer. The invited men were randomly selected from a background population of more than 27 000 men. Serum levels of DHT were analyzed for all 65 men diagnosed in the trial and 130 controls from the same cohort without any signs of prostate cancer. In this study we evaluate outcomes for the whole cohort (n = 195), the men without clinical signs of prostate cancer at beginning of follow up (n = 130) and men with screening detected cancer (n = 65). The cohort was followed up after 30 years and data from the Swedish Cause of Death Registry and the Swedish Cancer Registry were extracted. Hazard ratios (HRs) were calculated using Cox regression models. High DHT levels were positively correlated to a lower risk for prostate cancer death in the entire cohort: HR = 0.44 (0.25-0.77 95% confidence interval [CI]). The positive correlation remained significant for the subgroup analysis. HR for the men enrolled in the study without any clinical signs of prostate cancer was 0.25 (0.07-0.88 95% CI) and for the men with a prostate cancer diagnosis at time of inclusion: HR = 0.50 (0.26-0.94 95% CI). DHT is negatively associated with long-term prostate cancer death regardless of clinical presentation at time of inclusion.


Radioactive technetium phosphate bone scanning in preoperative assessment and follow-up study of patients with primary cancer of the breast.
Seventy-five female patients with early primary cancer of the breast were studied by bone scanning with 99mTc labeled phosphate at the time of initial presentation and serially during follow-up examination. Eleven patients had an abnormal bone scan at the time of presentation. During follow-up periods, which have ranged from three to 34 months with a mean of 16 months, abnormal bone scans have developed in a further 13 patients. To date, nine of the 24 patients with an abnormal bone scan have died, while only one of the 51 with a persistently normal scan has died. It is concluded that an abnormal bone scan carries a significant risk of earlier death due to metastatic disease.


Production of a monoclonal antibody specific to sablefish (Anoplopoma fimbria) IgM and its application in ELISA, western blotting, and immunofluorescent staining.
Sablefish (Anoplopoma fimbria) are an emerging aquaculture species native to the continental shelf of the northern Pacific Ocean. There is limited information on both innate and adaptive immunity for this species and new tools are needed to determine antibody response following vaccination or disease outbreaks. In this paper, a monoclonal antibody, UI-25A, specific to sablefish IgM was produced in mice. Western blotting confirmed UI-25A recognizes the heavy chain of IgM and does not cross react to proteins or carbohydrates in serum of four other teleost species. An ELISA was developed to measure Aeromonas salmonicida specific IgM in the plasma of sablefish from a previous experiment where fish were immunized with a proprietary A. salmonicida vaccine. UI-25A was used in Western blot analyses to identify immunogenic regions of A. salmonicida recognized by this specific IgM from vaccinated sablefish. Immunofluorescent staining also demonstrated the ability of UI-25A to recognize membrane-bound IgM and identify IgM + cells in the head kidney. These results demonstrate the usefulness of UI-25A as a tool to improve the understanding of antibody-mediated immunity in sablefish as well as to provide valuable information for vaccine development and expansion of aquaculture efforts for this fish species.


Isolation and initial characterization of glial fibrillary acidic protein from chicken, turtle, frog and fish central nervous systems.
The purification procedure for mammalian glial fibrillary acidic protein allowed the isolation of related proteins from the brain and spinal cord of the chicken, turtle, frog and fish. With the exception of the turtle, the proteins so isolated were homogeneous and migrated as a single band on sodium dodecyl sulfate-acrylamide gel electrophoresis, displaying the same mobility as bovine glial fibrillary acidic protein, 54 000 mol. wt. In the turtle an additional slower migrating band was constantly present, together with the main species. Mammalian and submammalian proteins were similar in amino acid composition and appeared to be susceptible to the same type of in situ proteolysis, with degradation of the major species into multiple polypeptides ranging down to 40 500 mol. wt. Unless degraded, the proteins isolated from submammalian vertebrates were excluded from sodium dodecyl sulfate-acrylamide gels if a reducing agent was not added to the electrophoretic sample, thus suggesting the existance of disulfide bridges between polypeptide chains, as demonstrated for the mammalian protein. The purified submammalian antigens cross-reacted with antisera to human glial fibrillary acidic protein with formation of spurs not only at the junction between mammalian and submammalian precipitation lines, but also between submammalian lines. The antisera produced against chicken antigen did not react with the human antigen and the antichicken sera could not be absorbed with human antigen. An immunologically active cyanogen bromide peptide in the myoglobin range (17 200 mol. wt.) characteristic of the mammalian protein, degraded and nondegraded, was not present in the digest of the submammalian proteins.


Experience of using tocilizumab for treatment in Indonesian patients with severe COVID-19.
COVID-19 is a public health emergency of international concern with millions confirmed cases globally including in Indonesia with more than two hundred thousand confirmed cases to date COVID-19. (1) COVID-19 has wide clinical manifestation ranging from asymptomatic, acute respiratory illness, respiratory failure that necessitates mechanical ventilation and support in an ICU, to MODS. (2) Several comorbidities have been demonstrated to be associated with the development of severe outcomes from COVID-19 infection, such as hypertension, diabetes, cardiovascular disease, dyslipidemia, thyroid disease, and pulmonary disease. (3)-(5) Severe COVID-19 is associated with increased plasma concentrations of IL-6, resulting in cytokine storm. (6) Tocilizumab, an interleukin-6 inhibitor, might alleviates the cytokine storm, prevents significant lungs and organs damage, thus improving clinical outcomes. (7) Therefore, tocilizumab, might be one of the promising therapies for severe COVID-19. (8) However there were limited studies regarding the efficacy in COVID-19 patients, especially with control group. We would like to report our experience in using tocilizumab as treatment in severe COVID-19 patients in Indonesia, which is the first in Indonesia to the best of our knowledge.


Efficient PCR-based gene targeting with a recyclable marker for Aspergillus nidulans.
The rapid accumulation of genomic sequences from a large number of eukaryotes, including numerous filamentous fungi, has created a tremendous scientific potential, which can only be realized if precise site-directed genome modifications, like gene deletions, promoter replacements, in-frame GFP fusions and specific point mutations can be made rapidly and reliably. The development of gene-targeting techniques in filamentous fungi and other higher eukaryotes has been hampered because foreign DNA is predominantly integrated randomly into the genome. For Aspergillus nidulans, we have developed a flexible method for gene-targeting employing a bipartite gene-targeting substrate. This substrate is made solely by PCR, which obviates the need for bacterial subcloning steps. The method reduces the number of false positives and can be used to produce virtually any genome alteration. A major advance of the method is that it allows multiple subsequent genome manipulations to be performed as the selectable marker is recycled.


Severe steroid-resistant anti-PD1 T-cell checkpoint inhibitor-induced hepatotoxicity driven by biliary injury.
Hepatotoxicity from T-cell checkpoint blockade is an increasingly common immune-related adverse event, but remains poorly characterised and can be challenging to manage. Such toxicity is generally considered to resemble autoimmune hepatitis, although this assumption is extrapolated from limited clinicopathological reports of anti-cytotoxic T-lymphocyte-associated protein 4-induced hepatotoxicity. Here we report, with full clinicopathological correlation, three cases of T-cell checkpoint inhibitor-induced hepatotoxicity associated with anti-programmed cell death protein 1 agents. We find that a major feature of these cases is biliary injury, including a unique case of vanishing bile duct syndrome, and that such toxicity was poorly responsive to long-term immunosuppression (corticosteroids and mycophenolate mofetil). Any potential benefits of long-term immunosuppression in these cases were outweighed by therapy-related complications. We discuss potential aetiologies and risk factors for immune-mediated biliary toxicity in the context of the limited literature in this field, and provide guidance for the investigation and supportive management of affected patients.


Is combination pharmacotherapy effective for patients with acute depression?
A systematic review and meta-analysis found that these combinations were superior to monotherapy and had comparable tolerability.


Review of surgical robotic systems for keyhole and endoscopic procedures: state of the art and perspectives.
Minimally invasive surgery, including laparoscopic and thoracoscopic procedures, benefits patients in terms of improved postoperative outcomes and short recovery time. The challenges in hand-eye coordination and manipulation dexterity during the aforementioned procedures have inspired an enormous wave of developments on surgical robotic systems to assist keyhole and endoscopic procedures in the past decades. This paper presents a systematic review of the state-of-the-art systems, picturing a detailed landscape of the system configurations, actuation schemes, and control approaches of the existing surgical robotic systems for keyhole and endoscopic procedures. The development challenges and future perspectives are discussed in depth to point out the need for new enabling technologies and inspire future researches.


Establishment of Rabbit Liver VX2 Tumor Model Using Percutaneous Puncture Inoculation of Tumor Fragment Guided and Evaluated by Ultrasonography.
The aim of the present study is to evaluate a method of establishing model of rabbit liver VX2 tumor using percutaneous puncture inoculation of tumor fragment guided by ultrasonography. VX2 tumor fragments were implanted into the liver of 13 New Zealand white rabbits flushed by 1 mL normal saline through percutaneous puncture needle guided by ultrasonography. Conventional ultrasonography and contrast-enhanced ultrasonography (CEUS) were performed 14 days after inoculation, and then the rabbits were sacrificed and pathologically examined. The success rate of inoculation was 100%. The average size of liver VX2 tumor was 1.7 cm×1.3 cm, CEUS of VX2 liver tumors showed the "rapid wash-in and wash-out" vascular pattern. There were significant differences between VX2 tumors and liver parenchyma in quantitative parameters of A, k and A × k (P<0.05), which meant that VX2 liver tumors were characterized by more blood flow volume and faster blood velocity than liver parenchyma. Tumor fragment flushed by normal saline into the liver through a needle may be a promising method for the induction of a hepatic tumor. And CEUS can be used for accurately assessing angiogenesis and blood perfusion of VX2 tumors.


Erector spinae plane block: the ultimate 'plan A' block?
The erector spinae plane block (ESPB) is one of seven 'Plan A' blocks proposed by Regional Anaesthesia UK, covering the key areas of commonly encountered surgeries and acute pain. Unlike the other six blocks, the ESPB can be performed at all levels of the spine and provides analgesia to most regions of the body, leading to the argument that the ESPB is the ultimate Plan A block. Current studies show a high level of evidence supporting use in thoracoabdominal surgery but a lack of benefit in upper and lower limb surgery compared with local infiltration and other Plan A blocks. Thus, there is insufficient evidence to support the claim that the erector spinae plane block is the ultimate Plan A block.


Formation of macromolecule complex with Bacillus thuringiensis Cry1A toxins and chlorophyllide binding 252-kDa lipocalin-like protein locating on Bombyx mori midgut membrane.
P252, a 252-kDa Bombyx mori protein located on the larval midgut membrane, has been shown to bind strongly with Bacillus thuringiensis Cry1A toxins (Hossain et al. Appl Environ Microbiol 70:4604-4612, 2004). P252 was also shown to bind chlorophyllide (Chlide) to form red fluorescence-emitting complex Bm252RFP with significant antimicrobial activity (Pandian et al. Appl Environ Microbiol 74:1324-1331, 2008). In this article, we show that Cry1A toxin bound with Bm252RFP and Bm252RFP-Cry1A macrocomplex, with both antimicrobial and insecticidal activities, was formed. The insecticidal activity of Bm252RFP-Cry1Ab was reduced from an LD₅₀ of 1.62 to 5.05 μg, but Bm252RFP-Cry1Aa and Bm252RFP-Cry1Ac did not show such reduction. On the other hand, the antimicrobial activity of Bm252RFP-Cry1Ab was shown to retain almost the same activity as Bm252RFP, while the other two complexes lost around 30% activity. The intensity of photo absorbance and fluorescence emission of Bm252RFP-Cry1Ab were significantly reduced compared to those of the other two complexes. Circular dichroism showed that the contents of Cry1Ab α-helix was significantly decreased in Bm252RFP-Cry1Ab but not in the other two toxins. These data suggested that the reduction of contents of α-helix in Cry1Ab affected the insecticidal activity of the macrocomplex but did not alter the antimicrobial moiety in the macrocomplex of Bm252RFP-Cry1Ab.


Evidence of oxidative imbalance in long-term liver transplant patients.
Oxidative stress in patients undergoing liver transplantation results both from the pre-existing cirrhosis and ischaemia-reperfusion injury related to surgery. Previous studies have provided information limited to the immediate post-operative period. It remains to be established whether this oxidative imbalance is reversed in a longer time. This study aimed to compare plasma concentrations of thiobarbituric acid-reactant substances and alpha-tocopherol in 20 cirrhotic patients before liver transplantation and 22 patients in whom transplant had been carried out at least 6 months previously. Thirty healthy age and sex-matched volunteers served as controls (cross-sectional study). Five patients were evaluated before and after liver transplantation (longitudinal study). Pre-transplant patients showed greater thiobarbituric acid-reactant substances and lower alpha-tocopherol levels than controls. Transplanted patients presented lower thiobarbituric acid-reactant substances and greater alpha-tocopherol levels than cirrhotic patients without reaching, however, the levels observed in controls. No correlations were found between oxidative parameters and liver tests. Hypertransaminasaemia, liver disease recurrence, and rejection episodes did not significantly influence the oxidative parameters. In the longitudinal study, transplantation induced a significant decrease in plasma thiobarbituric acid-reactant substances and a rise in alpha-tocopherol. Although a long-term improvement in the oxidative injury observed in cirrhotic patients occurs after liver transplantation, mild oxidative stress persists even in successfully transplanted patients.


A green solar photo-Fenton process for the degradation of carbamazepine using natural pyrite and organic acid with in-situ generated H2O2.
Pyrite is widely used in Fenton reaction for degradation of pollutants and exhibits great potential for environmental remediation, however, its efficiency is greatly compromised by extra H2O2 and pH adjustment. Herein, a pyrite based green solar photo-Fenton system for carbamazepine (CBZ) treatment is constructed, involving the use of simulated sunlight and natural organic acids with in situ-generated H2O2 and without extra pH adjustment. The addition of organic acids including tartaric acid (TA), citric acid (CA), and ascorbic acid (AA) can form complex with iron in pyrite, which promotes the Fe(II) dissolution. Upon irradiation, pyrite could be excited to produce photoelectrons, which would reduce oxygen to produce H2O2 through a two-step route assisted by organic acids. The simulated sunlight and organic acids promoted the in-situ production of H2O2 and Fe(II) species, sustaining an efficient Fenton reaction. This produced massive hydroxyl radical (OH), as demonstrated by the active species capture experiment. Compared with no degradation of CBZ under pure pyrite, the degradation efficiency of CBZ reached to 70%, 60%, and 53% in pyrite/TA, pyrite/CA, pyrite/AA within 30 min under simulated solar light irradiation, respectively. This work reports the first use of natural pyrite, a typical Fe-mineral semiconductor, to produce OH for CBZ degradation through natural additive assisted Fenton reaction excluding the adding extra H2O2 and pH adjustment.


Medical Comorbidities and Complications Associated with Poliomyelitis and Its Sequelae.
Survivors of poliomyelitis may experience long-term sequelae that put them at increased risk for injury, pain, cardiovascular deconditioning, and functional decline. Osteoporotic fractures and entrapment neuropathies, in particular, may result in greater impairments in one's mobility and ability to perform activities of daily living. Dysphagia may necessitate the use of compensatory swallow strategies to minimize aspiration risk. Comorbid conditions, including hypertension, dyslipidemia, obesity, and stroke, are also very prevalent in this population. Risk factor modification, including diet, exercise, and medication compliance, is essential to achieve optimal health and function among survivors of poliomyelitis.


Adaptive neural network asymptotic tracking control for nonstrict feedback stochastic nonlinear systems.
The adaptive neural network asymptotic tracking control issue of nonstrict feedback stochastic nonlinear systems is studied in our article by adopting backstepping algorithm. Compared with the existing research, the hypothesis about unknown virtual control coefficients (UVCC) is overcome in the control design. By using the bound estimation scheme and some smooth functions, associating with approximation-based neural network, the asymptotic tracking controller is recursively constructed. With the aid of Lyapunov function and beneficial inequalities, the asymptotic convergence character and stability with stochastic disturbance and unknown UVCC can be ensured. Finally, the theoretical finding is verified via a simulation example.


Benthic food web structures as an explanation for prolonged ecological half-life of 137Cs in flatfish species in the Fukushima coastal area.
After the accident at the Fukushima Daiichi Nuclear Power Plant (FDNPP), Japan, in March 2011, 137Cs in demersal fish had, between 2011 and 2015, a prolonged ecological half-life when compared to pelagic fish. Using stable isotope mixing models combined with gut content analysis and 137Cs activity concentrations, this study investigated the hypothesis that an unexplored food web structure could be a contributing factor explaining the ecological half-life of 137Cs in benthic flatfish. Benthic invertebrates and demersal fish species sampled in 2015 still showed 137Cs activity concentrations higher than pre-accident. The mixing models of stable N and C isotopes and gut content analysis identified deposit, suspension and filter feeders to be the main flatfish food items in the benthos. There was a significant correlation between 137Cs activity concentrations in specific flatfish species and benthos, and between 137Cs activity concentrations in benthos and surface sediment. The results of this study partially explained the 137Cs activity concentrations found in the analysed demersal fish, suggesting that the benthos can be a continuous source of 137Cs for the demersal fish during this period of time. Extending monitoring programmes to include invertebrates that are not food species for humans would greatly improve our ability to understand the role of trophic transfer pathways and take appropriate management actions.


[Infection in Joint Prosthesis. When Should it Be Suspected?].
Joint prosthesis constitute one of the major advances of medicine in the treatment of patients with osteoarticular disease. Infections of prosthetic material, though having a low frequency (1%-3% according to the series and type of prosthesis) constitute one of the larger complications of this surgery and a diagnostic challenge for the physician. The concept of prosthesis infection includes colonization due to germs in periprosthetic material that also leads to clinical manifestations. There are diverse classifications of the prosthetic infections, most of which are based in the form of clinical presentation which largely depends on the germ which is responsible for the infection. In this sense, late forms are generally caused by poorly virulent germs (plasma coagulase negative staphilococcus is the most frequent) and are the most difficult to diagnose. Diagnostic suspicion must be established in relation to the clinical manifestations and a series of accompanying clinical signs. In this sense, in the abscense of baseline inflammatory rheumatism, the persistent elevation of CRP (which normalizes 1-2 weeks after the surgery), or the presence of inflammatory joint fluid (with cell counts over 1700 cells/μL and especially with a predominance of PMN>68%) are signs that strenghten the diagnostic suspicion of bacterial infection. The definitive diagnosis is established by the isolation of the causal germ in culture and, in this sense, the biopsy of periprosthetic material and its study by the pathology department as well as its culture, allow for a trustworthy diagnosis in 80%-90% of cases.


Metabolism of intratesticular spermatozoa of a tropical teleost fish (Clarias gariepinus).
Sperm metabolism of a tropical fish species, the African catfish, Clarias gariepinus, was studied by measurements of sperm enzyme activity and metabolite levels. We also analysed the effect of metabolites, co-enzymes and enzymatic blockers on sperm motility behaviour and viability. Similar to other teleostean species, African catfish spermatozoa have the capacity for glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, lipid catabolism, beta-oxidation and osmoregulation. In immotile spermatozoa, lipid catabolism, beta-oxidation, the tricarboxylic acid cycle and oxidative phosphorylation were important primary energy-delivering pathways; sperm oxygen consumption was 0.39-0.85 microg O(2)/min/ ml of testicular semen. During motility, glycolysis, lipid catabolism and beta-oxidation of fatty acids occurred simultaneously, which is atypical for teleosts, and the spermatozoal respiration rate increased drastically by 15-25-fold. Also in contrast to other teleostean sperm cells, ATP levels remained stable during motility and immotile storage. The sperm cell status was unstable in the African catfish. Although the spermatozoa have osmoregulation ability, and even though balanced physiological saline solutions were used for sperm motility activation and sperm incubation, the motility and viability of spermatozoa quickly decreased at 28 degrees C, the spawning temperature of the African catfish. Cyclic AMP and inhibition of phosphodiesterase activity could not prolong sperm motility and viability. In contrast, at 6-10 degrees C motility was prolonged from approximately 30 s to >5 min, probably due to decreased metabolic rates.


Expression of nitric oxide synthases and in vitro migration of eosinophils from allergic rhinitis subjects.
The expression of nitric oxide (NO) synthases and the role of the NO cyclic GMP pathway on the migration of eosinophils from untreated patients with allergic rhinitis were investigated. Inducible NO synthase was strongly expressed in eosinophils from healthy individuals, but not in eosinophils from allergic rhinitis patients. The neuronal isoform was observed in eosinophils from each group studied, whereas no staining for the endothelial isoform was detected in either group. The chemotaxis to N-formyl-methionyl-leucyl-phenylalanine (fMLP, 5 x 10(-7) M) and eotaxin (100 ng/ml) was significantly potentiated in allergic rhinitis eosinophils. In both groups, N(omega)-nitro-L-arginine methyl ester (L-NAME, 1.0 mM) or 1H(1,2,4)-oxadiazolo(4,3,-a)quinoxalin-1-one (ODQ, 0.2 mM) markedly reduced the chemotaxis. The selective iNOS inhibitor N-(3-(aminomethyl)benzyl)acetamidine (1400 W, 0.1-1.0 mM) significantly reduced the chemotaxis of eosinophils from healthy but not from allergic rhinitis subjects. The inhibition by L-NAME was restored by 3-morpholinosydnonimine (SIN-1) and S-nitroso-N-acetyl-penicillamine, whereas the inhibition by ODQ was restored by dibutyryl cyclic GMP. In conclusion, both endothelial and inducible NO synthase isoforms are absent in allergic rhinitis eosinophils, suggesting that the NO cyclic GMP pathway in this cell type is maintained through the activity of a neuronal isoform.


The role of CXC chemokines in the regulation of angiogenesis in non-small cell lung cancer.
Angiogenesis is a critical component of tumor biology. In recent years newer techniques of cell and molecular biology have led to important advances in our understanding of this process. The regulation of angiogenesis depends on a balance between the activity of local factors that promote (angiogenic factors) or inhibit (angiostatic factors) neovascularization. Nowhere is this paradigm of a balance more apparent than in the study of tumor-associated angiogenesis. Tumors promote angiogenesis through a combination of overexpression of angiogenic factors and local inhibition of angiostatic factors. This strategy leads to an angiogenic environment that promotes tumor growth and metastases. Our laboratory has focused studies on the role of the CXC chemokine family in the regulation of angiogenesis by non-small cell lung cancer (NSCLC). In this article, we review our findings that the CXC chemokine family is composed of members that are either angiogenic or angiostatic. We have found that in NSCLC an imbalance exists in the expression of these factors that favors tumor-derived angiogenesis, and therefore tumor growth and metastases. Furthermore, when this imbalance is corrected to reduce the presence of angiogenic factors or increase the presence of angiostatic factors, tumor growth and metastases are reduced.


Biological nitrogen and carbon removal in a gravity flow biomass concentrator reactor for municipal sewage treatment.
A novel membrane system, the Biomass Concentrator Reactor (BCR), was evaluated as an alternative technology for the treatment of municipal wastewater. Because the BCR is equipped with a membrane whose average poresize is 20 μm (18-28 μm), the reactor requires low-pressure differential to operate (gravity). The effectiveness of this system was evaluated for the removal of carbon and nitrogen using two identical BCRs, identified as conventional and hybrid, that were operated in parallel. The conventional reactor was operated under full aerobic conditions (i.e., organic carbon and ammonia oxidation), while the hybrid reactor incorporated an anoxic zone for nitrate reduction as well as an aerobic zone for organic carbon and ammonia oxidation. Both reactors were fed synthetic wastewater at a flow rate of 71 L d(-1), which resulted in a hydraulic retention time of 9 h. In the case of the hybrid reactor, the recycle flow from the aerobic zone to the anoxic zone was twice the feed flow rate. Reactor performance was evaluated under two solids retention times (6 and 15 d). Under these conditions, the BCRs achieved nearly 100% mixed liquor solids separation with a hydraulic head differential of less than 2.5 cm. The COD removal efficiency was over 90%. Essentially complete nitrification was achieved in both systems, and nitrogen removal in the hybrid reactor was close to the expected value (67%).


Electric-double-layer p-i-n junctions in WSe2.
While p-n homojunctions in two-dimensional transition metal dichalcogenide materials have been widely reported, few show an ideality factor that is constant over more than a decade in current. In this paper, electric double layer p-i-n junctions in WSe2 are shown with substantially constant ideality factors (2-3) over more than 3 orders of magnitude in current. These lateral junctions use the solid polymer, polyethylene oxide: cesium perchlorate (PEO:CsClO4), to induce degenerate electron and hole carrier densities at the device contacts to form the junction. These high carrier densities aid in reducing the contact resistance and enable the exponential current dependence on voltage to be measured at higher currents than prior reports. Transport measurements of these WSe2 p-i-n homojunctions in combination with COMSOL multiphysics simulations are used to quantify the ion distributions, the semiconductor charge distributions, and the simulated band diagram of these junctions, to allow applications to be more clearly considered.


Intraoperative Ultrasound-Guided Posterior Cervical Laminectomy for Degenerative Cervical Myelopathy.
We present our experience with routine intraoperative ultrasound (IOUS)-guided posterior cervical laminectomy (PCL) in patients with degenerative cervical myelopathy (DCM), describe the technique used, and describe relevant IOUS findings that may impact the surgical procedure. Three illustrative cases are presented of patients (age range, 67-79 years) who underwent PCL with IOUS guidance and instrumented fusion for DCM. Intraoperative standard B-mode images were obtained with a linear array 6.6- to 13.3-MHz transducer. Excellent high-resolution IOUS view of the spinal cord and nerve roots was obtained in every case after laminectomy. IOUS had a relevant intraoperative impact in all cases, leading to extended decompression of focal residual compression, confirmation of posterior shift of the spinal cord from anteriorly located structures, and final confirmation of sufficient decompression by visualization of symmetric and rhythmic cord pulsations. IOUS is a poorly described yet easy-to-use and very effective tool for guidance and confirmation of adequate posterior decompression of the cervical spinal cord and nerve roots during PCL. Routinely using IOUS-guided decompression for PCL in patients with myelopathy will help avoid residual compression of neural elements and might be beneficial for functional outcome.


Acute and long-term gastrointestinal consequences of chemotherapy.
There are many anti-neoplastic agents in cancer treatment. Combination regimens are often the main standard treatment, particularly for gastrointestinal malignancies. The introduction of new regimens that combine fluoropyrimidines with irinotecan or oxaliplatin and recently also with antibodies against the Epidermal Growth Factor Receptor (EGFR) (cetuximab and panitumumab) and against the Vascular Endothelial Growth Factor (VEGF) (bevacizumab) pathways, has dramatically improved the progression free survival and survival of patients with metastatic colorectal cancer. This rapid extension of available anti-neoplastic drugs has, however, also highlighted the urgent need for clinicians to better understand and identify the spectrum of acute and late toxicities of these drugs. Acute and long-term adverse effects are inherent to non-surgical cancer treatment using chemotherapy and/or radiation therapy, which can profoundly affect the gastrointestinal tract leading to a wide spectrum of acute and late toxicities. An improved knowledge of the aetiology, incidence, supportive measures and of the prevention of these toxicities is warranted to improve patient care. We herein review and discuss the main acute and late gastrointestinal toxicities of chemotherapy and/or radiotherapy for patients with gastrointestinal malignancies.


Response specific temporal expectancy: evidence from a variable foreperiod paradigm.
When a stimulus-response event is frequently paired with a specific foreperiod, response performance for this event is improved after this foreperiod. This phenomenon is referred to as specific temporal expectancy. In four experiments, we investigated whether stimulus- or response-related processing benefits from specific temporal expectancy. In a speeded choice reaction task, different features of the imperative stimuli were frequently paired with foreperiods in such a way that only in some experiments were the responses also frequently paired with foreperiods. Participants revealed evidence for specific temporal expectancy when responses were frequently paired with foreperiods, but not when only the stimuli were frequently paired with foreperiods. We concluded that specific temporal expectancy affects response-related processing.


7, 8-diacetoxy-4-methylcoumarin induced cell death in human tumor cells is influenced by calreticulin.
Calreticulin (CRT), an endoplasmic reticulum resident protein demonstrates transacetylase activity in presence of 7, 8 diacetoxy-4-methyl coumarin (DAMC) in vitro. To investigate the possible role of CRT and DAMC mediated protein acetylation in cells, we investigated the effects of DAMC in tumor cells with different levels of CRT. DAMC was more toxic (clonogenicity, metabolic viability and proliferation) to human glioma cells (BMG-1) expressing low endogenous CRT level as compared to head and neck carcinoma cells (KB) with a high CRT level. The cytotoxicity was accompanied by loss of mitochondrial membrane potential in both the cells, which correlated with corresponding changes in the levels of pro-apoptotic (Bax) and anti-apoptotic (NFkB) regulators. Manipulation of CRT protein level in KB cells by application of small RNA interference enhanced the sensitivity by four folds while over expression of CRT in BMG-1 cells reduced their sensitivity to DAMC by ~20% strongly suggesting the influence of CRT on DAMC induced cytotoxicity. The partial rescue of CROE cells from DAMC induced toxicity was accompanied by changes in NFkB levels and over all protein acetylation status, besides increase in the NADPH-cytochrome c reductase activity related to its well known antioxidant property. Since CRT is over-expressed in cancer cells, which are generally resistant to radio- and chemotherapy; targeting CRT transacetylase system, may be an attractive approach for increasing the efficacy of anticancer therapies.


Human IgE synthesis in vitro. Detection with monoclonal antibodies.
Using monoclonal anti-human IgE antibodies recognizing the D epsilon 1 or D epsilon 2 epitope, we have developed a sandwich radioimmunoassay (RIA) to determine IgE in human cell cultures. With the help of this assay, various methods of measuring an actual de novo IgE synthesis were compared. It was necessary to subtract performed IgE from released IgE in the culture supernatant and the IgE associated to the cultured cells, in order to determine a net IgE synthesis which would reflect de novo synthesized IgE. Using this differential in vitro IgE assessment, no net IgE synthesis could be demonstrated in culture conditions which lead to strong IgG synthesis. Actual net in vitro IgE antibody production was only found in approximately 30% of cell cultures from atopic donors. This spontaneous IgE synthesis did not correlate to the serum IgE levels of the patients. However, correlations were found between serum IgE levels and amount of performed, released or cell-associated IgE of the cultures.


Design, synthesis and evaluation of novel enzalutamide analogues as potential anticancer agents.
The androgen receptor inhibitor, Enzalutamide, proved effective against castration resistance prostate cancer, has demonstrated clinical benefits and increased survival rate in men. However, AR mutation (F876L) converts Enzalutamide from antagonist to agonist indicating a rapid evolution of resistance. Hence, our goal is to overcome this resistance mechanism by designing and developing novel Enzalutamide analogues. We designed a dataset of Enzalutamide derivatives using Enzalutamide's shape and electrostatic features to match with pharmacophoric features essential for tight binding with the androgen receptor. Based on this design strategy ten novel derivatives were selected including 5,5-dimethyl-3-(6-substituted benzo[d]thia/oxazol-2-yl)-2-thioxo-1-(4-(trifluoromethyl)pyridin-2-yl)imidazolidin-4-one (6a-j) for synthesis. All the compounds were evaluated in-vitro on prostate cancer cell lines DU-145, LNCaP and PC3. Interestingly, two compounds 3-(6-hydroxybenzo[d]thiazol-2-yl)-5,5-dimethyl-2-thioxo-1-(4-(trifluoromethyl)pyridin-2-yl) imidazolidin-4-one (6c, IC50 - 18.26 to 20.31μM) and 3-(6-hydroxybenzo[d]oxazol-2-yl)-5,5-dimethyl -2-thioxo- 1- (4-(trifluoromethyl) pyridin-2-yl)imidazolidin-4-one (6h, IC50 - 18.26 to 20.31μM) were successful with promising in-vitro antiproliferative activity against prostate cancer cell lines. The binding mechanism of potential androgen receptor inhibitors was further studied by molecular docking, molecular dynamics simulations and MM-GBSA binding free energy calculations and found in agreement with the in vitro studies. It provided strong theoretical support to our hypothesis.


Autoantibodies Present in Hidradenitis Suppurativa Correlate with Disease Severity and Promote the Release of Proinflammatory Cytokines in Macrophages.
Hidradenitis suppurativa (HS), also known as acne inversa, is a debilitating inflammatory skin disorder that is characterized by nodules that lead to the development of connected tunnels and scars as it progresses from Hurley stages I to III. HS has been associated with several autoimmune diseases, including inflammatory bowel disease and spondyloarthritis. We previously reported dysregulation of humoral immune responses in HS, characterized by elevated serum total IgG, B-cell activation, and antibodies recognizing citrullinated proteins. In this study, we characterized IgG autoreactivity in HS sera and lesional skin compared with those in normal healthy controls using an array-based high-throughput autoantibody screening. The Cy3-labeled anti-human assay showed the presence of autoantibodies against nuclear antigens, cytokines, cytoplasmic proteins, extracellular matrix proteins, neutrophil proteins, and citrullinated antigens. Most of these autoantibodies were significantly elevated in stages II‒III in HS sera and stage III in HS skin lesions compared with those of healthy controls. Furthermore, immune complexes containing both native and citrullinated versions of antigens can activate M1 and M2 macrophages to release proinflammatory cytokines such as TNF-α, IL-8, IL-6, and IL-12. Taken together, the identification of specific IgG autoantibodies that recognize circulating and tissue antigens in HS suggests an autoimmune mechanism and uncovers putative therapeutic targets.


Isoelectric focusing of alkaline phosphatases in agarose gel.
An isoelectric focusing technique in agarose gel is presented which is suitable for alkaline phosphatases from both serum and tissue sources. An anomaly in the literature about isoelectric focusing of serum alkaline phosphatase from liver origin is discussed and a possible explanation is proposed. The presented technique is used to demonstrate some differences in behaviour of serum liver and bone isoenzymes towards neuraminidase treatment.


Novel Screening and Monitoring Techniques for Deformational Plagiocephaly: A Systematic Review.
This article summarizes the current state of diagnostic modalities for infant craniofacial deformities and highlights capable diagnostic tools available currently to pediatricians.


Unraveling inner ear induction by gene manipulation using Pax2-Cre BAC transgenic mice.
One of the biggest drawbacks of conventional mouse knockout techniques in the study of the inner ear is that loss of a gene of interest may cause embryonic lethality before the inner ear develops. Thus, there is a need for an inner ear-specific gene manipulation system for loss- and gain-of-function analysis in the mouse inner ear. We generated a Pax2-Cre BAC transgenic line in which Cre recombinase expression recapitulates Pax2 expression in the presumptive otic ectoderm. Here, we present a brief summary of a recent model of inner ear induction suggested by the results of inner ear-specific gene modification using Pax2-Cre mice.


The effect of osteoporosis management on proximal humeral fracture.
Proximal humeral fractures comprise 10% of fractures in the Medicare population. The effect, if any, of treating osteoporosis to prevent these fractures has not been determined. The primary objective is to determine the effectiveness of a systematic osteoporosis screening and treatment program on the hazard of developing a fracture over the treatment period. The secondary aim is to determine demographic risk factors. This is a retrospective cohort study in a health care organization serving 3.3 million members. Individuals selected for dual-energy x-ray absorptiometry screening were (1) women aged 65 years or older; (2) men aged 70 years or older; and (3) individuals aged 50 years or older who have a history of fragility fracture, use glucocorticoids, have a parental history of hip fracture, have rheumatoid arthritis, use alcohol at a high rate, or are cigarette smokers. Treatment consisted primarily of pharmacologic intervention with bisphosphonates. Individuals diagnosed with osteoporosis had a hazard ratio of 7.43 for sustaining a fracture over the study period. Patients screened with dual-energy x-ray absorptiometry had a hazard ratio of 0.17 whereas those treated medically had a hazard ratio of 0.55 versus untreated controls. Risk factors that significantly increased the risk of a fracture developing included age, female gender, white race, diabetes mellitus, and history of a distal radius fracture. Over the study period, screening and treatment for osteoporosis significantly decreased the hazard ratio for proximal humeral fracture. This information broadens the impact of such programs because current best practices are primarily based on prevention of spine and hip fractures.


Adsorption of Amyloidogenic Peptides to Functionalized Surfaces Is Biased by Charge and Hydrophilicity.
Surfaces are abundant in living systems, such as in the form of cellular membranes, and govern many biological processes. In this study, the adsorption of the amyloidogenic model peptides GNNQQNY, NNFGAIL, and VQIVYK as well as the amyloid-forming antimicrobial peptide uperin 3.5 (U3.5) were studied at low concentrations (100 μM) to different surfaces. The technique of a quartz crystal microbalance with dissipation monitoring (QCM-D) was applied as it enables the monitoring of mass binding to sensors at nanogram sensitivity. Gold-coated quartz sensors were used as unmodified gold surfaces or functionalized with self-assembled monolayers (SAMs) of alkanethiols (terminated as methyl, amino, carboxyl, and hydroxyl) resulting in different adsorption affinities of the peptides. Our objective was to evaluate the underlying role of the nature and feature of interfaces in biological systems which could concentrate peptides and impact or trigger peptide aggregation processes. In overall, the largely hydrophobic peptides adsorbed with preference to hydrophobic or countercharged surfaces. Further, the glycoprotein lubricin (LUB) was tested as an antiadhesive coating. Despite its hydrophilicity, the adsorption of peptides to LUB coated sensors was similar to the adsorption to unmodified gold surfaces, which indicates that some peptides diffused through the LUB layer to reach the underlying gold sensor surface. The LUB protein-antiadhesive is thus more effective as a biomaterial coating against larger biomolecules than small peptides under the conditions used here. This study provides directions toward a better understanding of amyloid peptide adsorption to biologically relevant interfaces, such as cellular membranes.


Hytrel-like Copolymers Based on Furan Polyester: The Effect of Poly(Butylene Furanoate) Segment on Microstructure and Mechanical/Elastic Performance.
This paper aims to compare the performance of two Hytrel-like segmented copolymers: "classic" PBT-b-PTMG and fully bio-based PBF-b-PTMG, containing poly(butylene furanoate) as the rigid segment. The idea behind this research is to assess whether the sustainable copolymers can successfully replace those "classic" once at the thermoplastic elastomers' market. Two series of copolymers were synthesized under the same process parameters, had the same compositions, but differed in aromatic ring structure in terephthalate/furanoate unit. Furthermore, the materials were processed by injection moulding as typical Hytrel products. Then, the samples were subjected to extensive characterisation including NMR, GPC, FTIR, DSC, WAXS, DMTA, TGA techniques and mechanical tests with particular interest in the microstructure formed during processing and its effect on the copolymers' mechanical and elastic behaviour. The detailed analysis proved that PBF-b-PTMG and PBT-b-PTMG copolymers represent two kinds of materials with similar chemical structure, some features of thermoplastic elastomers, but evident differences in their physical properties.


Measuring Change in Health Status Over Time (Responsiveness): A Meta-analysis of the SF-36 in Cardiac and Pulmonary Rehabilitation.
The purpose of this meta-analysis is to gather and investigate pooled information on the responsiveness of the main patient outcome measure in cardiac rehabilitation (CR) and pulmonary rehabilitation (PR). The main outcome measure in CR and PR has been found to be the Medical Outcomes Study Short Form-36 health survey (SF-36). A previous systematic effectiveness review of this literature was used as the basis of this statistical analysis, with the bulk of articles being observational studies. This meta-analysis assessed articles on CR that used SF-36 pre and post "within" (per interventional group) mean scores and in the PR literature that used the SF-36 and the Chronic Respiratory Questionnaire (CRQ) "within" change scores. Each group of patients in the chosen literature were taken to represent a single group, so that studies such as randomized controlled trials were listed twice. We undertook a correlation analysis between SF-36 pre and post "within" mean scores in the CR literature. In the PR literature, we undertook a correlation analysis between SF-36 and the CRQ "within" change scores; this involved Spearman correlation coefficients. The SF-36 Mental Composite Score domain is the most responsive of the composite SF-36 domains, with the Physical Composite Score showing less ability to discriminate in the higher SF-36 scores. In the individual domains, Role Emotional scored r=0.52, P≤.001 with only 27% of the variance explained, and Role Physical with r=0.49, P≤.005 had only 24% of the variance explained. In the PR literature Spearman rank correlation coefficient shows that SF-36 Physical Composite Score has a weaker correlation to the CRQ at 0.39 than the SF-36 Mental Composite Score, which was 0.63. This suggests that the SF-36 is not suited as a pre- to postprogram assessment tool for CR and PR. More studies, however, need to be conducted particularly in CR with regard to the responsiveness of the SF-36.


Phylo- and -ontogenetically determined local changes in the structure of the arterial wall of vertebrates. Macroscopical findings.
It has been shown, by means of comparative anatomical, phylo- and -ontogenetic studies, that the focal structural changes occuring at seven points in the wall of the aortic arch and brachiocephalic arteries of reptiles, birds, and mammals, and in human-beinmnants of certain vessels which have regressed during embryonic development. They are considered to be loci minoris resistentiae and might therefore represent a site of predilection for pathological lesions, such as atherosclerosis. The existence of these "scars" in human-beings and birds has already been described. This paper presents definitive proof of their occurrence in reptiles (sea-turtle and crocodile) and mammals (dog, calf, sheep and monkey). It is therefore concluded that the "scars" in the aortic arch and brachiocephalic arteries are of phylogenetic origin.


A comparison of Class II open bite correction by maxillary or mandibular surgery.
The purpose of this study was to compare treatment outcomes for anterior occlusion and vertical skeletal stability after maxillary or mandibular surgery for correction of Class II malocclusion with a mild to moderate open bite. The records of 57 consecutive patients were retrieved; 30 had undergone 1-piece Le Fort I osteotomy, and 27 had undergone a bilateral sagittal split osteotomy (BSSO), without additional surgery. Lateral cephalograms at 6 stages were available (pretreatment to 3 years postsurgery). After the surgery, 87% of the Le Fort I patients and 63% of the BSSO patients had a positive overbite, and at the 6-month follow-up, the percentages were 90% and 74%, respectively. At 3 years after surgery, 74% of the Le Fort I patients and 42% of the BSSO patients had a positive overbite. The anterior facial height decreased in the Le Fort I subsample and increased in the BSSO subsample, and the mandibular plane angle decreased in both. The Le Fort I subsample generally remained stable, whereas clinically significant relapse of the mandibular plane angle (≥2°) occurred in 80% of the BSSO subsample. When taking into account the limitations of retrospective clinical studies, several conclusions can be drawn. A significant improvement of the anterior occlusion can be expected in most patients when either maxillary or mandibular surgery is used for correction of Class II open bite. However, there will be individual patients in whom considerable posttreatment changes occur in both the anteroposterior and vertical dimensions. Although individual morphology needs to be taken into account, it seems that both short- and long-term stability are likely to be greater after Le Fort I surgery compared with BSSO.


[Ligase chain reaction (LCR)].
Ligase chain reaction (LCR) is a ligation-mediated amplification technique of a target DNA sequence using oligonucleotides and thermostable ligase. LCR is useful for the detection of known DNA sequences and point mutations in a limited amount of DNA. We introduce the principle, development, and protocol of this simple and convenient technique for DNA analysis.


Aortic regurgitation and left ventricle remodeling on cardiac magnetic resonance and transthoracic echocardiography.
Transthoracic echocardiography (TTE) is the first imaging modality used to assess aortic regurgitation (AR). However, it is not possible to provide precise quantification in all patients. Our aim was to compare TTE and cardiovascular magnetic resonance (CMR) measurements in grading AR and left ventricle (LV) remodeling. A total of 51 consecutive patients with AR in TTE (New York Heart Association I/II, 55%/38%) were enrolled into the study and 49 individuals (age, 57.1 [14]; 61% males) underwent a non-contrast CMR (2 patients excluded) obtained on 1.5 T system (GE Optima MR450w). The comprehensive quantitative grading with AR volume (AR vol) and regurgitant fraction (RF) were measurable in TTE in 24 cases and showed an association with CMR parameters (AR vol: r = 0.75; P <0.001 and RF: r = 0.55; P <0.01). CMR revealed larger LV end-diastolic volumes (EDV) (185.5 [61] vs 158.4 [61] ml; P = 0.03) and a trend towards higher left ventricular ejection fraction (59% [8] vs 56% [8]; P = 0.08). The association of AR vol and LV EDV was stronger in CMR (r = 0.85; P <0.0001) compared to TTE (r = 0.6; P = 0.001). The inter-modality agreement (TTE-CMR) in AR grading was low (κ = 0.15), with highly concordant grading in mild AR (91%). CMR provides a comprehensive assessment of AR severity and LV remodeling with a weak or a moderate agreement with TTE.


Boston Patient Navigation Research Program: the impact of navigation on time to diagnostic resolution after abnormal cancer screening.
There is a need for controlled studies to assess the impact of patient navigation in vulnerable cancer populations. Boston Patient Navigation Research Program conducted a quasi-experimental patient navigation intervention across six federally qualified inner-city community health centers, three assigned to a breast cancer navigation intervention and three assigned to a cervical cancer navigation intervention; each group then served as the control for the other. Eligible women had an abnormal breast or cervical cancer screening test conducted at one of the participating health centers during a baseline (2004-2005) or intervention period (2007-2008). Kaplan-Meier survival curves and proportional hazards regression examined the effect of patient navigation on time to definitive diagnosis, adjusting for covariates, clustering by clinic and differences between the baseline and intervention period. We enrolled 997 subjects in the baseline period and 3,041 subjects during the intervention period, of whom 1,497 were in the navigated arm, and 1,544 in the control arm. There was a significant decrease in time to diagnosis for subjects in the navigated group compared with controls among those with a cervical screening abnormality [aHR 1.46; 95% confidence interval (CI), 1.1-1.9]; and among those with a breast cancer screening abnormality that resolved after 60 days (aHR 1.40; 95% CI, 1.1-1.9), with no differences before 60 days. This study documents a benefit of patient navigation on time to diagnosis among a racially/ethnically diverse inner city population. Patient navigation may address cancer health disparities by reducing time to diagnosis following an abnormal cancer-screening event.


MRI for local staging of endometrial carcinoma: Is endovenous contrast medium administration still needed?
To compare the diagnostic performance of T2-weighted images (T2-WI)+contrast-enhanced T1-weighted images (CE T1-WI) with the one of T2-WI+diffusion-weighted images (DWI) in the assessment of myometrial and cervical stromal infiltration by endometrial carcinoma (EC). Institutional review board approved our retrospective study; requirement for informed consent was waived. 56 patients with histologically proven EC who underwent preoperative MRI and surgery at our Institution over a 34 months period were included. Two radiologists independently evaluated T2-WI+CE T1-WI and T2-WI+DWI of each patient. Confidence in imaging evaluation (0-3), depth of myometrial invasion (</≥50%) and presence of cervical stromal infiltration (Yes/No) were assessed. MRI findings were compared with pathological ones. Confidence in imaging evaluation was higher for T2-WI+CE T1-WI (2.83/3) than for T2-WI+DWI (2.62/3). T2-WI+DWI showed a better diagnostic performance than T2-WI+CE T1-WI in recognizing deep myometrial infiltration by EC (accuracy, sensitivity and specificity of 0.89, 0.89 and 0.89 vs. 0.86, 0.84, 0.86; p>0.05) whereas both imaging sequences combinations showed the same diagnostic performance in recognizing cervical stromal infiltration (accuracy, sensitivity and specificity of 0.95, 0.98 and 0.80, p>0.05). T2-WI+DWI can reliably replace the "classical" combination T2-WI+CE T1-WI for local staging of endometrial carcinoma.


[Interest of tricuspid annular displacement (TAD) in evaluation of right ventricular ejection fraction].
The ultrasound assessment of RV structure and function is often sub-optimal. The range of excursions of the mitral or tricuspid annulus measured in millimetre by 2D or TM-mode in centimetre per second by DTI-mode echocardiography has been shown to reflect the systolic function of both ventricles. We studied a new technique based on a tissue tracking algorithm that is ultrasound beam angle independent for automated detection of tricuspid annular displacement (TAD) (QLAB, Philips Medical Imaging). Twenty-six patients (pts) referred for magnetic resonance imaging (MRI) and 44 control subjects underwent a complete transthoracic echocardiography. MRI of the right ventricular ejection fraction (RVEF) was correlated by linear regression with TAD. Sixteen pts (61.5%) exhibited right ventricular systolic dysfunction (MRI RVEF<40%). The MRI RVEF was positively correlated with TAD (R(2)=0,65; p<0,0001). A value of TAD <14mm predicted right ventricular dysfunction with a sensitivity of 87.5% and a specificity of 90%. Most of (90%) healthy subjects exhibited TAD values exceeding this cut-off point (mean: 16.9+/-1.64mm; range: 13.3 to 24.8mm). Negative correlation was found between TAD and age (R(2)=0,36; p<0,0001). Our study is the first to correlate TAD with MRI RVEF. TAD is a simple, rapid, and non-invasive tool for right ventricular systolic function assessment.


Androgen Receptor Transcriptionally Inhibits Programmed Death Ligand-1 Expression and Influences Immune Escape in Bladder Cancer.
In multiple clinical trials, immune checkpoint blockade-based immunotherapy has shown significant therapeutic efficacy in bladder cancer (BCa). Sex is closely related to the incidence rate and prognosis of BCa. As one of the sex hormone receptors, the androgen receptor (AR) is a well-known key regulator that promotes the progression of BCa. However, the regulatory mechanism of AR in the immune response of BCa is still unclear. In this study, the expression of AR and programmed death ligand 1 (PD-L1) was negatively correlated in BCa cells, clinical tissues, and tumor data extracted from The Cancer Genome Atlas Bladder Urothelial Carcinoma cohort. A human BCa cell line was transfected to alter the expression of AR. The results show that AR negatively regulated PD-L1 expression by directly binding to AR response elements on the PD-L1 promoter region. In addition, AR overexpression in BCa cells significantly enhanced the antitumor activity of cocultured CD8+ T cells. Injection of anti-PD-L1 monoclonal antibodies into C3H/HeN mice significantly suppressed tumor growth, and stable expression of AR dramatically enhanced the antitumor activity in vivo. In conclusion, this study describes a novel role of AR in regulating the immune response to BCa by targeting PD-L1, thus providing potential therapeutic strategies for immunotherapy in BCa.


[Study of medical-legal consultations outside the health system in primary care].
To evaluate how consultations in order to obtain a medical/legal document, whose destination is other than the health service. A descriptive, crossover study, using a questionnaire filled in by the doctor at the time of the medical-legal consultation. All those users who attended in one year the clinics of the doctors taking part in the study, in order to seek a medical-legal document (MLD) whose destination was other than the health service. Between 1-9-93 and 31-8-94 there were 287 consultations for a MLD. Of the variables studied, most attendances were by the age group between 15 and 44, masculine, with schooling up to EGB level (basic) or lower and unemployed or pensioner. Average length of the consultation was 6.6 minutes. 42.5% had a clinical interview. 4.6% were referred to a specialist. In 77.7% of cases, a document belonging to the health service was issued. The reason for the procedure was: health certificate (40%), and a sick note (39%). The PC doctor normally receives a considerable number of visits to obtain this kind of document, which are required by official bodies to determine the health status of users or concede social benefits to them. There are gaps in the rules on what kind of document.


Clinical relevance of third permanent molars in relation to crowding after orthodontic treatment.
The purpose of this study was to determine the relationship between dental crowding and the clinical presence or absence of third permanent molar teeth. Ninety-nine patients were analysed before and after orthodontic treatment and at least three years after the end of retention. The sample consisted of four groups: subjects whose third permanent molar teeth had erupted into the mouth, were non-erupted, were extracted, and were congenitally absent. Arch Length Discrepancy, Irregularity Index and observer bias were examined. Multivariate analysis of variance with repeated measurements was used to analyse differences between the four groups. Significant differences in Arch Length Discrepancy during time were shown between the premolar segment and the frontal area. The group with third permanent molar teeth congenitally missing showed a significant higher positive Arch Length Discrepancy in the premolar segment of the upper jaw. No significant differences in Irregularity Index were found between the third molar groups. It can be concluded that there is no relation between crowding and the presence or absence of third permanent molar teeth.


Influence of cholesterol on cancer progression and therapy.
Cholesterol is a fundamental molecule necessary for the maintenance of cell structure and is vital to various normal biological functions. It is a key factor in lifestyle-related diseases including obesity, diabetes, cardiovascular disease, and cancer. Owing to its altered serum chemistry status under pathological states, it is now being investigated to unravel the mechanism by which it triggers various health complications. Numerous clinical studies in cancer patients indicate an alteration in blood cholesterol level (either decreased or increased) in comparison to normal healthy individuals. This article elaborates on our understanding as to how cholesterol is being hijacked in the malignancy for the development, survival, stemness, progression, and metastasis of cancerous cells. Also, it provides a glimpse of how cholesterol derived entities, alters the signaling pathway towards their advantage. Moreover, deregulation of the cholesterol metabolism pathway has been often reported to hamper various treatment strategies in different cancer. In this context, attempts have been made to bring forth its relevance in being targeted, in pre-clinical and clinical studies for various treatment modalities. Thus, understanding the role of cholesterol and deciphering associated molecular mechanisms in cancer progression and therapy are of relevance towards improvement in the management of various cancers.


Dissecting the contribution of actin and vimentin intermediate filaments to mechanical phenotype of suspended cells using high-throughput deformability measurements and computational modeling.
Mechanical cell properties play an important role in many basic biological functions, including motility, adhesion, proliferation and differentiation. There is a growing body of evidence that the mechanical cell phenotype can be used for detection and, possibly, treatment of various diseases, including cancer. Understanding of pathological mechanisms requires investigation of the relationship between constitutive properties and major structural components of cells, i.e., the nucleus and cytoskeleton. While the contribution of actin und microtubules to cellular rheology has been extensively studied in the past, the role of intermediate filaments has been scarcely investigated up to now. Here, for the first time we compare the effects of drug-induced disruption of actin and vimentin intermediate filaments on mechanical properties of suspended NK cells using high-throughput deformability measurements and computational modeling. Although, molecular mechanisms of actin and vimentin disruption by the applied cytoskeletal drugs, Cytochalasin-D and Withaferin-A, are different, cell softening in both cases can be attributed to reduction of the effective density and stiffness of filament networks. Our experimental data suggest that actin and vimentin deficient cells exhibit, in average, 41% and 20% higher deformability in comparison to untreated control. 3D Finite Element simulation is performed to quantify the contribution of cortical actin and perinuclear vimentin to mechanical phenotype of the whole cell. Our simulation provides quantitative estimates for decreased filament stiffness in drug-treated cells and predicts more than two-fold increase of the strain magnitude in the perinuclear vimentin layer of actin deficient cells relatively to untreated control. Thus, the mechanical function of vimentin becomes particularly essential in motile and proliferating cells that have to dynamically remodel the cortical actin network. These insights add functional cues to frequently observed overexpression of vimentin in diverse types of cancer and underline the role of vimentin targeting drugs, such as Withaferin-A, as a potent cancerostatic supplement.


Challenges in imaging in preclinical rheumatoid arthritis.
There exists a preclinical phase to the disease progression of rheumatoid arthritis, in which there is evidence of autoimmunity but no overt clinical arthritis. Identifying patients in this phase would allow for early treatment, to potentially halt manifestation of the disease. Imaging, because it is noninvasive, provides an appealing alternative to gold-standard synovial biopsies for identification of these preclinical patients. Ultrasonography, magnetic resonance imaging, and positron emission tomography all have their advantages and disadvantages as imaging modalities in this regard. Further research into alternative imaging modalities with larger cohorts is required to determine the most effective technique.


Stereotactic body radiation therapy is associated with improved overall survival compared to chemoradiation or radioembolization in the treatment of unresectable intrahepatic cholangiocarcinoma.
Intrahepatic cholangiocarcinoma (ICC) is a highly lethal malignancy. For patients with locally advanced, unresectable disease, numerous liver-directed therapy options exist, including chemoradiation (CRT), stereotactic body radiation therapy (SBRT), and transarterial radioembolization (TARE). There is no randomized data to inform clinicians regarding the optimal treatment modality. We used the National Cancer Database (NCDB) to study the overall survival (OS) of patients with ICC treated with CRT, SBRT, and TARE. We used Cox proportional hazards modeling and inverse probability of treatment weighting (IPTW) to account for confounding variables. We identified 170 patients with unresected ICC treated with SBRT (n = 37), CRT (n = 61), or TARE (n = 72). SBRT was associated with higher OS compared to CRT (hazard ratio [HR] = 0.37; 95% confidence interval [CI] 0.20-0.68; p = 0.001) and TARE (HR = 0.40; 95% CI 0.22-0.74; p = 0.003). On multivariable analysis, SBRT remained associated with higher OS compared to CRT (HR = 0.44; 95% CI 0.21-0.91; p = 0.028) and TARE (HR = 0.42; 95% CI 0.21-0.84; p = 0.014). After IPTW (Bonferroni-adjusted significance threshold, α = 0.017), SBRT again had a statistically significant association with higher OS compared to CRT (HR = 0.22; 95% CI 0.11-0.44; p < 0.0001) and was nominally associated TARE (HR = 0.58; 95% CI 0.37-0.91; p = 0.019). We found SBRT is associated with higher OS when compared to CRT or TARE for the treatment of unresectable ICC. Due to the retrospective nature of the study and potential selection bias, these findings should be evaluated prospectively.


Corticostriatal and thalamic regulation of amphetamine-induced ascorbate release in the neostriatum.
Lesions of cerebral cortex and ventromedial nucleus (VM) of the thalamus were made in rats to investigate the contribution of these structures to amphetamine (AMPH)-induced ascorbate (AA) release in the neostriatum as measured by in vivo voltammetry. Following a recovery period of at least one week, rats were anesthetized, and electrochemically modified, carbon-fiber electrodes were lowered into the neostriatum. Compared to data obtained from sham-operated and unoperated controls, bilateral aspiration lesions of cerebral cortex significantly lowered both the basal level of AA and the amount of AA released by AMPH in the neostriatum. Similar results were obtained after bilateral, but not unilateral electrolytic lesions of the VM thalamus. Collectively, these results suggest that the corticostriatal pathway and the VM thalamic nuclei participate in the regulation of basal and AMPH-induced AA release in the neostriatum.


Major neonatal surgery under local anesthesia: a cohort study from Bangladesh.
Surgeons and anesthetists must respond to the perioperative mortality associated with general anesthesia in developing countries. The safety of performing major neonatal surgery under local anesthesia is one pragmatic response. This study describes and evaluates such practice in a tertiary pediatric surgery center in Bangladesh. Seven hundred and twenty neonates were admitted for major surgery during a 3.5-year study period. Hundred and fifty two neonates died pre-operatively, and 568 underwent major neonatal surgery. 352 (62.0%) neonates were operated under general anesthesia, while the 216 most fragile neonates (38.0%) were operated with local infiltrative anesthesia alone. Medical files were reviewed; data were collected prospectively; mortality risk factors were assessed by univariate and multivariate analysis. Two hundred and sixteen procedures were performed under local anesthesia: sigmoid colostomies (37.5%), laparotomies with anastomosis (21.3%), anoplasties (18.1%), laparotomies with enterostomy (8.3%), closures of abdominal wall defects (6.9%), fixations of silastic bags (3.7%), peritoneal tube drainage (2.3%), and gastrostomies (1.9%). Median weight was 2,400 g (2,200-2,460), median gestational age was 37.0 weeks (36.0-38.0), and median age at surgery was 5.0 days (3.0-14.7). In-hospital postoperative mortality was 10.6% among those selected for local anesthesia, and 11.4% among neonates operated under general anesthesia. Low birth weight was an independent risk factor for mortality on multivariate analysis (OR 1.002 g(-1), 95% CI [1.000-1.004], p = 0.029). Local anesthesia is an established option for the most fragile neonates with major surgical disease. Safe anesthesia ought to be accessible to all children of the world. The global pandemic of perioperative mortality needs to be addressed.


Modifying clopidogrel maintenance doses according to vasodilator-stimulated phosphoprotein phosphorylation index improves clinical outcome in patients with clopidogrel resistance.
Despite dual antiplatelet therapy, the rate of major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) remains high. Ex vivo tests of clopidogrel resistance can predict MACE after PCI. The purpose of this study is to evaluate the clinical impact of adjusting phosphorylation analysis in patients with clopidogrel resistance undergoing PCI. We hypothesized that VASP-guided clopidogrel maintenance doses, compared to fixed doses, improved clinical outcome. This monocentric, prospective, randomized study was performed on 306 patients undergoing PCI. Patients were randomized to a control group (n = 156) and to a vasodilator-stimulated phosphoprotein (VASP)-guided group (n = 150). In the VASP-guided group, patients received adjusted maintenance doses of clopidogrel to obtain platelet reactivity index (PRI) of <50% during 1 year after PCI. The primary endpoint was the rate of MACE. The secondary endpoints were major and minor bleeding. All patients completed the PCI procedure and 298 patients completed follow-up. The control and VASP-guided groups had similar demographic, clinical, and angiographic characteristics. In the VASP-guided group, PRI was significantly decreased (from 72.1% ± 11.4% to 27.7% ± 8.4%; P = 0.001) in 128 patients (87.1% of all participants). During the 1-year follow-up, 14 MACEs were recorded in the VASP-guided group and 30 MACEs were recorded in the control group (9.3% vs 20.4%, respectively; P = 0.008). There was no difference in the rate of major and minor bleeding in the VASP-guided group compared with the control group (12.9% vs 16.6%; P = 0.06). Modifying clopidogrel maintenance doses according to platelet reactivity monitoring decreases the rate of MACE after PCI without increasing bleeding in patients with clopidogrel resistance during 1-year follow-up.


Thermal requirement of indian mustard (Brassica juncea) at different phonological stages under late sown condition.
Indian mustard [Brassica juncea (L.) Czern & Coss.] is a long day plant, which requires fairly cool climatic condition during growth and development for obtaining better seed yield. Various workers have correlated crop growth and development with energy requirement parameters, such as growing degree days (GDD), photo-thermal unit (PTU), helios thermal unit (HTU), photo-thermal index (PTI) and heat use efficiency (HUE). Therefore, GDD requirement for different phenological stages of 22 newly developed Indian mustard varieties was studies during winter (rabi) seasons of 2009-10 and 2010-11 at student instructional farm of C.S. Azad University of Agriculture and Technology, Kanpur, (Utter Pradesh). Study revealed that RH-8814, NRCDR-02 and BPR-549-9 recorded higher GDD (1703.0, 1662.9 and 1648.0), PTU (19129.8, 18694.2 and 18379.8), HTU (11397.7, 11072.2 and 10876.0), PTI (13.25, 13.14 and 13.08) and HUE (4.11, 3.84 and 3.71) at physiological maturity, while higher HUE was recorded (9.62, 8.99 and 8.91 kg ha-1 degrees-day) at days after sowing (DAS) to 50 % flowering. On the basis of study mustard genotypes RH-8814, NRCDR-02 and BPR-549-9 were identified as most heat-tolerant, as they maintained higher values for energy related parameters. Seed yield was highly positively correlated with GDD (r = 0.61, 0.65 and 0.75), PTU (r = 0.66, 0.64 and 0.74), HTU(r = 0.79, 0.68 and 0.73) at the above these three phenological stages, while negatively correlated with PTI at anthesis and at maturity. Hence, these parents could be used in crossing programme for achieving further improvement.


Prevalence of Mollicutes among men who have sex with men and transgender women aged 15 to 19 years in Salvador, North-eastern Brazil.
Some species of Mollicutes have been associated with different pathologies of the urogenital tract in humans, with a high prevalence among adult men who have sex with men (MSM) and transgender women (TGW). However, few studies have been performed to investigate its prevalence among adolescents. In this study, we estimated the initial prevalence of Mycoplasma genitalium (MG), Mycoplasma hominis (MH), Ureaplasma urealyticum (UU), and Ureaplasma parvum (UP); the rate of misdiagnosis at different anatomical sites; and the associated factors with positive tests for Mollicutes among MSM and TGW aged 15 to 19 years enrolled in the PrEP1519 study. PrEP-1519 is the first study to investigate the effectiveness of pre-exposure prophylaxis for human immunodeficiency virus among adolescent MSM and TGW aged 15 to 19 in Latin America. Oral, anal, and urethral swabs were taken from 246 adolescents upon enrolment in the study to detect MG, MH, UU, and UP by quantitative polymerase chain reaction (qPCR). Bivariate and multivariate analyses were conducted by Poisson regression and 95% confidence intervals (95% CI) were estimated. The prevalence of Mollicutes was 32.1%. UU was the most prevalent species (20.7%), followed by MH (13.4%), MG (5.7%), and UP (3.2%); 67.3% of the positive samples would have been missed if only urethral samples had been taken. Receptive anal sex (prevalence ratio [PR] = 1.79; 95% CI = 1.07-3.01) and clinical suspicion of sexually transmitted infection (PR = 1.62; 95% CI = 1.01-2.61) were factors associated with the detection of Mollicutes in general. Group sex (PR = 1.98; 95% CI = 1.12-3.50) and receptive anal sex (PR = 2.36; 95% CI = 0.95-5.86) were associated with the detection of Mycoplasma spp. No sociodemographic, clinical, or behavioural variable was significantly associated with the detection of Ureaplasma spp. A high prevalence of Mollicutes was observed among adolescent MSM and TGW, especially at extragenital sites. Further research is required to understand the epidemiological profile of high-risk adolescents in different regions and contexts, and to investigate the pathogenesis of Mollicutes in the oral and anal mucosa before routine screening can be recommended in clinical practice.


Indirect and direct effects of the subprime crisis on the real sector: labor market migration.
The bursting of the US housing bubble in the second half of 2008 triggered an almost unprecedented systemic crisis in the world economy. The financial collapse quickly overflowed into the real economy and caused, among other effects, a sharp fall in the flow of world trade. Using export data from Brazilian municipalities, we show that the subprime crisis had a more significant effect on production and employment in exporting cities than municipalities more devoted to the domestic economy. We find that the manufacturing and construction sectors of exporting cities were the most affected during the crisis. However, exporting municipalities with a substantial share of services activities were more resilient to the external crisis. This difference is significant and sheds light on the debate on the effects of the crisis on Brazilian regions and cities. Using a unique business management dataset that contains firm-to-firm controls, we also find spillovers in the labor market from exporting to domestic-oriented cities through job reallocation. Our results suggest that workers migrate from exporting municipalities to other non-exporting municipalities within the same firm economic group.


Eccentric, but not concentric muscle contraction induce inflammation and impairs fibrinolysis in healthy young men.
Different types of muscle contraction can cause different damage to the musculature and differences in inflammatory responses. Acute increases in circulatory inflammation markers can influence the crosstalk between coagulation and fibrinolysis processes, increasing the risk of thrombus formation and detrimental cardiovascular events. The aim of this study was to analyze the effects of concentric and eccentric exercise on hemostasis markers, C-reactive protein (CRP), and the relationship between these variables. Eleven healthy subjects with a mean age of 25.4 ± 2.8, non-smokers, with no history of cardiovascular disease and blood type O, randomly performed an isokinetic exercise protocol consisting of 75 concentric (CP) or eccentric (EP) contractions of knee extension, divided into five sets of 15 repetitions combined with 30-s rest. Blood samples for analysis of FVIII, von Willebrand factor, tissue plasminogen activator (t-PA), plasminogen activator inhibitor type-1 (PAI-1), and CRP were collected pre, post, 24 h, and 48 h after each protocol. Increased levels of CRP at 48 h in EP versus CP (p = 0.002), increased PAI-1 activity 48 h in EP versus CP (p = 0.044), and a reduction in t-PA at 48 h when compared with post-protocol in both protocols (p = 0.001). A correlation was found between CRP and PAI-1 at 48 h of PE (r2 = 0.69; p = 0.02). This study showed that both EP and CP increase the clotting process, albeit only the exercise performed eccentrically induces inhibition of fibrinolysis. This is possibly due to the increase in PAI-1 48 h after the protocol, which correlates with the increase in inflammation as demonstrated by the CRP levels.


Implementation of Video Laryngoscope-Assisted Coaching Reduces Adverse Tracheal Intubation-Associated Events in the PICU.
To evaluate implementation of a video laryngoscope (VL) as a coaching device to reduce adverse tracheal intubation associated events (TIAEs). Prospective multicenter interventional quality improvement study. Ten PICUs in North America. Patients undergoing tracheal intubation in the PICU. VLs were implemented as coaching devices with standardized coaching language between 2016 and 2020. Laryngoscopists were encouraged to perform direct laryngoscopy with video images only available in real-time for experienced supervising clinician-coaches. The primary outcome was TIAEs. Secondary outcomes included severe TIAEs, severe hypoxemia (oxygen saturation < 80%), and first attempt success. Of 5,060 tracheal intubations, a VL was used in 3,580 (71%). VL use increased from baseline (29.7%) to implementation phase (89.4%; p < 0.001). VL use was associated with lower TIAEs (VL 336/3,580 [9.4%] vs standard laryngoscope [SL] 215/1,480 [14.5%]; absolute difference, 5.1%; 95% CI, 3.1-7.2%; p < 0.001). VL use was associated with lower severe TIAE rate (VL 3.9% vs SL 5.3%; p = 0.024), but not associated with a reduction in severe hypoxemia (VL 15.7% vs SL 16.4%; p = 0.58). VL use was associated with higher first attempt success (VL 71.8% vs SL 66.6%; p < 0.001). In the primary analysis after adjusting for site clustering, VL use was associated with lower adverse TIAEs (odds ratio [OR], 0.61; 95% CI, 0.46-0.81; p = 0.001). In secondary analyses, VL use was not significantly associated with severe TIAEs (OR, 0.72; 95% CI, 0.44-1.19; p = 0.20), severe hypoxemia (OR, 0.95; 95% CI, 0.73-1.25; p = 0.734), or first attempt success (OR, 1.28; 95% CI, 0.98-1.67; p = 0.073). After further controlling for patient and provider characteristics, VL use was independently associated with a lower TIAE rate (adjusted OR, 0.65; 95% CI, 0.49-0.86; p = 0.003). Implementation of VL-assisted coaching achieved a high level of adherence across the PICUs. VL use was associated with reduced adverse TIAEs.


Isolation of up- or down-regulated genes in PPARgamma-expressing NIH-3T3 cells during differentiation into adipocytes.
Adipocyte differentiation is a complex process in which the expression of many transcription factors and adipocyte-specific genes is regulated under a strict program. The peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the steroid/thyroid nuclear hormone receptor superfamily of ligand-activated transcription factors, is an important regulator of adipocyte gene expression and differentiation. In this study, we tried to identify downstream target genes of PPARgamma, by using PPARgamma-expressing cells and a subtractive cloning strategy, and isolated cDNA clones which were up-regulated or down-regulated by PPARgamma. Northern blot analyses revealed that the expression levels of the aldehyde dehydrogenase-2-like, type VI collagen alpha 3 subunit, cellular retinoic acid binding protein 1 and thrombospondin 1 are changed during the differentiation of mouse 3T3-L1 preadipocyte cells, indicating that these genes might be downstream targets of PPARgamma in adipocyte differentiation.


Low versus high cell turnover in diffusely growing non-Hodgkin's lymphomas.
Cell loss, perhaps as important as cell production in determining the size of an expanding cell population, has not usually been registered in quantitative cellular kinetic analyses of neoplastic disorders. The present retrospective study on various types and subtypes of non-Hodgkin's lymphomas (NHLs; n = 170) was designed to test the usefulness of a novel additional parameter, the 'turnover index' (TI), which is the sum per case of the mitotic index and the apoptotic index. Results document that TIs clearly distinguished between categories and subtypes of NHLs according to the Kiel classification. Cluster analysis of TIs plotted against the percentage of Ki-67-positive cells per case revealed that about one-third of the high-grade malignancy lymphomas actually belonged to the low-turnover lymphomas. Overall survival was longer in the low- than in the high-turnover group of lymphomas. Assessment of TIs can, for practical diagnostic purposes, be replaced by counting mitotic figures and apoptotic cells in several high-power fields. The TI concept may help to interpret the kinetics of NHLs in terms of accumulation vs. proliferation of cells.


Species differences in the pattern of eicosanoids produced by inflamed and non-inflamed tissue.
The synthesis of 14C labelled arachidonic acid metabolites was measured in colonic tissues obtained from mice, rats, guinea pigs, rabbits, piglets and in colonic biopsies from humans during colonoscopy. The main eicosanoids formed after stimulation with calcium ionophore A23187 were: in humans, 15-hydroxy-eicosatetraenoic acid (15-HETE); in mice, 12-HETE; in rats, 12-HETE, 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 6-keto-prostaglandin F1 alpha (6kPGF1 alpha); in guinea pigs, PGD2; in rabbits, 6kPGF1 alpha, PGE2 and 15-HETE; and in pigs PGE2 and 12-HETE. In inflamed 15-HETE production was increased in man, HHT and 12-HETE production in rats and overall eicosanoid production in mice.


Diabetes that impacts on routine activities predicts slower recovery after total knee arthroplasty: an observational study.
In the 6 months after total knee arthroplasty (TKA), what is the pattern of pain resolution and functional recovery in people without diabetes, with diabetes that does not impact on routine activities, and with diabetes that does impact on routine activities? Is diabetes that impacts on routine activities an independent predictor of slower resolution of pain and functional recovery after TKA? Community-based prospective observational study. A consecutive cohort of 405 people undergoing primary TKA, of whom 60 (15%) had diabetes. PARTICIPANTS with diabetes were also asked preoperatively whether diabetes impacted on their routine activities. PARTICIPANTS were categorised into three groups: no diabetes (n=345), diabetes with no impact on activities (n=41), and diabetes that impacted activities (n=19). Pain and function were measured using the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index within the month before surgery and 1, 3 and 6 months after surgery. Demographic, medical and surgical factors were also measured, along with depression, social support and health-related quality of life. No baseline differences in pain and function were seen among the three groups (p > 0.05). Adjusting for age, gender and contralateral joint involvement across the 6 postoperative months, participants with diabetes that impacted on routine activities had pain scores that were 8.3 points higher (indicating greater pain) and function scores that were 5.4 points higher (indicating lower function) than participants without diabetes. PARTICIPANTS with diabetes that doesn't impact on routine activities had similar recovery to those without diabetes. People undergoing TKA who report preoperatively that diabetes impacts on their routine activities have less recovery over 6 months than those without diabetes or those with diabetes that does not impact on routine activities. Physiotherapists could institute closer monitoring within the hospital and community settings for people undergoing TKA who perceive that diabetes impacts on their routine activities. [Amusat N, Beaupre L, Jhangri GS, Pohar SL, Simpson S, Warren S, Jones CA (2014) Diabetes that impacts on routine activities predicts slower recovery after total knee arthroplasty: an observational study.Journal of Physiotherapy60: 217-223].


The image of nursing among nursing and other healthcare professional university students: A mixed-method study.
This study had three objectives: (1) determining the image of nursing in the eyes of undergraduate health sciences students; (2) identifying factors affecting that image; and (3) evaluating students' views and experiences regarding that image. If healthcare students perceive nursing positively, it may result in directing future generations to nursing, and improving nursing, and reducing the need for nurses. This study adopted an explanatory sequential design with participant selection variant. The design involved data collection in two consecutive phases. A mixed-method design using quantitative data and qualitative interviews was used. In the quantitative phase, a descriptive and cross-sectional research method was used. The qualitative phase was based on phenomenological research. The quantitative portion was performed with 1556 participants in their second, third or fourth year during the 2019-2020 academic year. Students were from the nursing, emergency and disaster management, nutrition and dietetics, occupational health and safety, health management, and social work departments. The qualitative portion was performed with 29 participant volunteers. Participants were interviewed on the phone. The data were collected using an introductory information form, a nursing image scale, and semi-structured interviews. The quantitative data were analyzed using descriptive statistics and the independent-samples t-test, Mann-Whitney U test, one-way ANOVA, and stepwise linear regression. The quantitative data were analyzed using thematic analysis. There were significant relationships between participants' nursing image scale total scores and their department (p < 0.001), education year (p = 0.014), age (p = 0.032) and desire to recommend the nursing profession (p < 0.001). Nursing image scale total score was significantly higher in nursing departments than in other departments. Second-year participants and 18-20-year-olds had higher total scores than fourth-year participants and 21-23-year-olds, respectively, and those who would recommend the nursing profession had higher total scores than those who would not recommend it (p < 0.05). Analysis of the qualitative data produced six main themes: perceptions of the nursing profession, perceived nursing figure, nurse knowledge, relationship with healthcare professionals, reason for preference and job gender. This study employed a mixed-method design involving both quantitative and qualitative stages. The results highlighted the image of nursing and its significance in the eyes of prospective healthcare professionals. Detecting nursing image early can increase professional training and improve the professional image of nursing. We should take into account the factors that negatively affect the image of nursing to plan nursing education better in the future.


Analyses of recombinant stereotypic IGHV3-21-encoded antibodies expressed in chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) cells that use IgH encoded by IGHV3-21 and that have a particular stereotypic third CDR (HCDR3), DANGMDV (motif-1), almost invariably express Ig L chains (IgL) encoded by IGLV3-21, whereas CLL that use IGHV3-21-encoded IgH with another stereotypic HCDR3, DPSFYSSSWTLFDY (motif-2), invariably express κ-IgL encoded by IGKV3-20. This nonstochastic pairing could reflect steric factors that preclude these IgH from pairing with other IgL or selection for an Ig with a particular Ag-binding activity. We generated rIg with IGHV3-21-encoded IgH with HCDR3 motif-1 or -2 and IgL encoded by IGKV3-20 or IGLV3-21. Each IgH paired equally well with matched or mismatched κ- or λ-IgL to form functional Ig, which we screened for binding to an array of different Ags. Ig with IGLV3-21-encoded λ-IgL could bind with an affinity of ∼ 2 × 10(-6) M to protein L, a cell-wall protein of Peptostreptococcus magnus, independent of the IgH, indicating that protein L is a superantigen for IGLV3-21-encoded λ-IgL. We also detected Ig binding to cofilin, a highly conserved actin-binding protein. However, cofilin binding was independent of native pairing of IgH and IgL and was not specific for Ig with IgH encoded by IGHV3-21. We conclude that steric factors or the binding activity for protein L or cofilin cannot account for the nonstochastic pairing of IgH and IgL observed for the stereotypic Ig made by CLL cells that express IGHV3-21.


Apolipoprotein(a) size polymorphism is associated with coronary heart disease in polygenic hypercholesterolemia.
In addition to high serum cholesterol levels, various cardiovascular risk factors may be involved in the development of coronary heart disease (CHD) in hypercholesterolemic subjects. As the levels of lipoprotein(a) [Lp(a)], an important and independent cardiovascular risk factor, are high in polygenic hypercholesterolemia (PH), we investigated plasma Lp(a) levels and apolipoprotein(a) [apo(a)] phenotypes in relation to occurrence of CHD events in PH patients. Lp(a) levels and apo(a) isoforms were determined in 191 PH patients, 83 normocholesterolemic subjects with CHD, and 94 normocholesterolemic controls without CHD. Lp(a) levels were similar in the hypercholesterolemic subjects with (n=100) or without CHD (n=91): 21.4 (range 6.6-59.23) vs 18.5 (range 5.25-57.25) mg/dL (p=NS). Low molecular weight apo(a) isoforms were more prevalent (55%) in the PH patients with CHD, whereas high molecular weight apo(a) isoforms were more prevalent (62.6%) in those without CHD: this difference was significant (p<0.05). A stepwise multiple-discriminant analysis made in order to determine the independence of common cardiovascular risk factors, Lp(a) levels and low molecular weight apo(a) isoforms in predicting CHD among hypercholesterolemic subjects showed that the presence of a positive family history of CHD, smoking, age, and the presence of at least one apo(a) isoform of low molecular weight were independently associated with CHD. Despite high Lp(a) levels, our findings do not support the hypothesis that Lp(a) plays an independent role in determining clinical CHD in PH subjects. However, the presence of at least one low molecular weight apo(a) isoform is an independent genetic predictor of CHD in hypercholesterolemic subjects. Together with other cardiovascular risk factors, apo(a) phenotypes should be assessed to evaluate the overall CHD risk status of all subjects with high serum cholesterol levels.