[Treatment strategy in non-testicular malignant germ cell tumors in children and adolescents--concept of the MAKEI 83 cooperative therapeutic study of the Society for Pediatric Oncology].
In December 1982 the German Society of Pediatric Oncology (GPO) has initiated a cooperative study for non-testicular malignant germ cell tumors with initial vinblastine, bleomycin and cisplatinum chemotherapy depending on stage and histological grading, followed by ifosfamide, cisplatinum and VP 16 chemotherapy. Dysgerminoma patients with advanced disease are also treated with primary chemotherapy including vinblastine, bleomycin and cisplatinum; radiotherapy is limited to current disease. Patients with more differentiated teratomas receive combination chemotherapy with vinblastine, actinomycin D and cyclophosphamide.


Triggered activity in atrial fibres of canine coronary sinus: role of extracellular potassium accumulation and depletion.
1. Bursts of triggered activity can be induced in atrial fibres of the canine coronary sinus exposed to catecholamines. During a triggered burst there is an initial acceleration of rate accompanied by depolarization of the maximum diastolic potential (m.d.p.) followed by slowing of the rate and termination accompanied by hyperpolarization. 2. We have used extracellular K+-sensitive micro-electrodes (potassium ISE) to monitor extracellular K+ concentration ([K+]o) during and following triggered activity, while simultaneously measuring membrane potential with conventional intracellular micro-electrodes. 3. We found that the initial increase in rate during triggered activity is accompanied by increased [K+]o and depolarization. Later rate slowing and m.d.p. hyperpolarization is accompanied by decline of extracellular K+ accumulation. Following termination of triggered activity, extracellular K+ depletion occurred. 4. The decline of [K+]o and slowing of rate are known responses to enhanced Na+-K+ pump activation, as is the post-triggering depletion of extracellular K+. 5. Strophanthidin, which blocks the Na+-K+ pump, also blocks the [K+]o decline, the slowing of rate seen towards the end of the triggered episode, and the post-triggering depletion of extracellular K+. 6. Separate experiments studying the effects of elevated bath K+ and depolarizing current on triggering rate and delayed after-depolarization amplitude support our hypothesis that the rate profile of the triggered episode is to a large extent controlled by variations in m.d.p. subsequent to extracellular K+ accumulation and Na+-K+ pump activation.


Efficacy of leflunomide addition in relation to prognostic factors for patients with active early rheumatoid arthritis failing to methotrexate in daily practice.
The recommendations of the European League Against Rheumatism (EULAR) for the management of rheumatoid arthritis (RA) suggest a different therapeutic approach to methotrexate (MTX) resistance according to the presence or absence of poor prognostic factors. Retrospectively, in our patients with active early RA (disease activity score in 28 joints (DAS28) > 3.2) that failed to respond to initial MTX monotherapy, we investigated whether leflunomide (LEF) addition had a different efficacy when associated with the presence or absence of poor prognostic factors. Of the 20 patients who received LEF, 15 (2 males and 13 females) tolerated the combination. Five patients had no poor prognostic factors, and 4 (80%) of those patients achieved remission or low disease activity (LDA) according to DAS28 and also a good response with the EULAR criteria. Of the 10 patients with at least one poor prognostic factor, remission or LDA occurred in 4 (40%) of the patients, and a good EULAR response was obtained in 3 (30%) of the patients. By Fisher's exact test, no significant difference was found between the two groups of patients in remission or LDA (p = 0.28) according to DAS28 and a good response (p = 0.12) with the EULAR criteria. In all patients with an inadequate response to the LEF+MTX combination, the substitution of a TNF inhibitor for LEF or the addition of a TNF inhibitor to the combination led to remission or LDA. Large studies are required to investigate the efficacy of LEF addition in relation to prognostic factors in patients with active early RA that did not respond to the initial therapy with MTX alone.


Ulnar nerve inoculation of poliovirus in bonnet monkey: a new primate model to investigate neurovirulence.
A new monkey model of poliovirus neurovirulence has been developed avoiding the currently used intraspinal injection route which traumatizes the spinal cord. Poliovirus type 1 (0.1 ml) was inoculated into the ulnar nerve of bonnet monkeys (Macaca radiata) at the right elbow. Five monkeys were inoculated with 10(7) TCID of LSc/2ab (Sabin vaccine strain); none developed any illness. Limb paralysis, clinically resembling spinal poliomyelitis in children, developed in all four monkeys given greater than or equal to 10(5) TCID50 of Mahoney strain, and in three of four monkeys given 10(4) or 10(3) TCID50. Higher functions and cranial nerves were not affected. Paralysis occurred more frequently in the lower limbs (11 limbs in seven monkeys) than in upper limbs (six limbs in seven monkeys). The incubation period, from inoculation to onset of paralysis, ranged from 5 to 12 days. Further progression of paralysis to other limbs occurred within 2 to 6 days. No illness developed in two monkeys given 10(2) TCID50 of Mahoney virus. All monkeys given LSc/2ab and those given greater than 10(2) TCID50 Mahoney virus developed humoral antibody response; however, infection of the gastrointestinal tract was detected by virus isolation from throat swabs and stools only in monkeys given Mahoney virus, but not in those given LSc/2ab. Thus, intraneural spread of Mahoney virus to the spinal cord, neurovirulence of Mahoney but not of LSc/2ab and retrograde gastrointestinal infection with Mahoney but not with LSc/2ab are the features of this experimental model.


Clinicopathologic profile of normocomplementemic and hypocomplementemic urticarial vasculitis: a study from South India.
This study aims to study the clinical and histopathological characteristics of hypocomplementemic and normocomplementemic urticarial vasculitis (HUVS and NUV) among dermatology clinic attendees in a tertiary care hospital in South India. A prospective study was conducted in the dermatology department from February 2003 to May 2004. Seventy-five patients met the inclusion criteria for UV. Sixty-eight patients in whom complement levels were available were classified into either NUV or HUVS groups. Clinical features, laboratory parameters and histological features were compared, and the significance of differences was established using Pearson's Chi-squared test. There was a female preponderance among patients with HUVS. Wheals > 24 h were seen in 90% of patients, and in 54.4% of patients, the wheals were partially blanching or non-blanching. Angioedema was more prevalent in patients with NUV than HUVS (44.4% vs. 21.4%). Systemic involvement was seen in 64.3% of patients with HUVS and 44.4% of patients with NUV. Fever, ANA positivity and systemic lupus erythematosus (SLE) were significantly associated with HUVS. In most cases of UV, a provoking factor could not be identified. Neutrophilic small vessel vasculitis was seen in 42.9% of patients with HUVS and 16.6% patients with NUV. Direct immunofluorescence test showing immunoreactants at the dermo-epidermal junction were present in 60% of patients with HUVS and 33.3% patients with NUV. The clinical features of Indian patients with UV were similar to those reported from the West. Fever, ANA positivity and SLE were significantly associated with HUVS.


An in situ FTIR step-scan photoacoustic investigation of kerogen and minerals in oil shale.
Step-scan photoacoustic infrared spectroscopy experiments were performed on Green River oil shale samples obtained from the Piceance Basin located in Colorado, USA. We have investigated the molecular nature of light and dark colored areas of the oil shale core using FTIR photoacoustic step-scan spectroscopy. This technique provided us with the means to analyze the oil shale in its original in situ form with the kerogen-mineral interactions intact. All vibrational bands characteristic of kerogen were found in the dark and light colored oil shale samples confirming that kerogen is present throughout the depth of the core. Depth profiling experiments indicated that there are changes between layers in the oil shale molecular structure at a length scale of micron. Comparisons of spectra from the light and dark colored oil shale core samples suggest that the light colored regions have high kerogen content, with spectra similar to that from isolated kerogen, whereas, the dark colored areas contain more mineral components which include clay minerals, dolomite, calcite, and pyrite. The mineral components of the oil shale are important in understanding how the kerogen is "trapped" in the oil shale. Comparing in situ kerogen spectra with spectra from isolated kerogen indicate significant band shifts suggesting important nonbonded molecular interactions between the kerogen and minerals.


Caco-2 cell metabolism of oxygen-derived radicals.
Reactive oxygen metabolites have been associated with gastrointestinal injury and may play a role as mediators of inflammation. The effect of oxygen metabolites on Caco-2 cell viability (trypan blue exclusion and 51Cr release), hexose monophosphate shunt activity, and glutathione was assessed. Caco-2 cells were incubated with amino acid oxidase, xanthine oxidase, menadione, and t-butylhydroperoxide in the presence and absence of superoxide dismutase, catalase, mannitol, and butylated hydroxytoluene. With amino acid oxidase, trypan blue exclusion decreased (P < 0.01) and 51Cr release, oxidized glutathione, and shunt activity increased (P < 0.05). The addition of catalase attenuated these changes. Trypan blue exclusion decreased (P < 0.005) and 51Cr release, oxidized glutathione, and shunt activity increased (P < 0.01) with xanthine oxidase. The addition of superoxide dismutase caused a further increase in 51Cr release, oxidized glutathione, and shunt activity (P < 0.01), which was prevented by the addition of catalase or mannitol. t-Butylhydroperoxide did not effect 51Cr release or trypan blue exclusion, but oxidized glutathione and shunt activity increased (P < 0.01). The increase in shunt activity was prevented by preincubation with butylated hydroxytoluene (P < 0.01). Menadione did not alter trypan blue exclusion or 51Cr release, but caused an increase in oxidized glutathione and shunt activity (P < 0.001). The increase in shunt activity was attenuated by preincubation with butylated hydroxytoluene (P < 0.001). Menadione also caused a depletion of total glutathione.(ABSTRACT TRUNCATED AT 250 WORDS)


Defective energy coupling in delta-subunit mutants of Escherichia coli F1F0-ATP synthase.
Membrane vesicles from 13 strains carrying mutations in the C-terminal region of the delta-subunit of Escherichia coli F1F0-ATP synthase were characterized in respect to ATPase activity, ATP-driven proton-pumping, dicyclohexylcarbodiimide sensitivity of ATPase, and oxidative phosphorylation. The salient finding was that energy-coupling between F1 and F0 sectors of the enzyme is impaired by several of the mutations. The delta G150N mutant appeared completely uncoupled in vitro. The data emphasize the role of the C-terminal region of delta-subunit in integration of the proton conduction machinery in F0 with the three F1 catalytic sites. It is suggested that the C-terminal region of delta-subunit, speculatively located in the central region of the alpha 3 beta 3 hexagon, acts functionally at the interface between the helical domain of the stalk and the F1 subunits to relay conformational signals which alter the affinities of the catalytic sites for substrates and products.


A comparative study of enol aldehyde formation from betamethasone, dexamethasone, beclomethasone and related compounds under acidic and alkaline conditions.
Enol aldehydes are one type of key degradation and metabolic intermediates from a group of corticosteroids containing the 1,3-dihydroxyacetone side chain on their D-rings, such as betamethasone, dexamethasone, beclomethasone, and related compounds. The formation of enol aldehydes from these corticosteroids is via acid-catalyzed beta-elimination of water from the side chain, a process known as Mattox rearrangement. It was recently reported by our group that enol aldehydes could also be formed directly from the corresponding 17,21-diesters of these corticosteroids but only under alkaline condition, which was proposed to follow a variation pathway of the original Mattox rearrangement. In this paper, we report the results of a comparative study of enol aldehyde formation from these structurally similar corticosteroids (under the original acidic Mattox condition) and their 17,21-diesters (under the alkaline Mattox variation condition), respectively. In general, enol aldehydes were found to be formed under both conditions; however, the ratios of the E- and Z-isomers of the enol aldehyde were different in each case. The only exception was beclomethasone 17,21-diester under the alkaline condition, where a competing elimination of HCl from the 9,11-positions became predominant. These results can be explained by their structural differences with regard to the Mattox mechanism and its variation pathway. Lastly, solvent effect under acidic condition was studied between an aprotic and a protic solvent and the result suggests that enol aldehyde formation is greatly favored in an aprotic environment.


Ear infections: otitis externa and otitis media.
This article reviews the diagnosis and treatment of acute otitis externa and acute otitis media, and will be helpful to primary care physicians who diagnose and treat these common diseases in the clinic. The pathophysiology, microbiology, clinical features, diagnosis, treatment, prognosis, and complications are discussed.


Efficacy of pentoxifylline in prevention of contrast-induced nephropathy in angioplasty patients.
Contrast-induced nephropathy (CIN) is an adverse consequence of contrast media use that results in significant morbidity and mortality and adds significant costs to diagnostic and interventional cardiology procedures. Various pathophysiological mechanisms have been proposed for CIN and various agents have been tested for its prevention. There is currently a general agreement that adequate pre-procedure hydration constitutes the cornerstone of prevention, yet there are reports of the use of some other agents with various efficacies. We prospectively tested pentoxifylline (PTX), an antioxidant, anti-inflammatory drug, for CIN prevention in patients undergoing coronary angioplasty. In this prospective, randomized, single-blind, single-center clinical trial, 286 consecutive patients were randomly assigned to the control group (n = 146), with routine treatment and no PTX, or the study group (n = 140), with routine treatment and PTX, 400 mg/tid from 24 h before to 24 h after coronary angioplasty. Serum creatinine was measured before and 2 days after the procedure. The primary end point was the occurrence of CIN within 48 h. The control and PTX groups were comparable in the overall predicted risk of CIN. Also, the type and volume of the contrast agent were not significantly different between the two groups. Following angioplasty, CIN occurred in 20 (13.69%) patients in the control group and in 12 (8.5%) patients in the study group; the difference was not statistically significant (P = 0.17). Additionally, there was no mortality and need for hemodialysis in either group. In angioplasty patients, the prophylactic oral use of PTX could be recommended for CIN prevention, although no statistically significant protective effect was documented.


Synthesis of the Hexasaccharide Related to the Exopolysaccharide from Lactobacillus mucosae VG1 through Regioselective Glycosylation.
Chemical synthesis of the hexasaccharide repeating unit associated with the exopolysaccharide of Lactobacillus mucosae VG1 is reported. The total synthesis is accomplished through a convergent [2 + 2 + 2] strategy using rationally protected monosaccharide derivatives. Chemoselective activation of the glycosyl donors and regioselective nucleophilicity of the acceptors were successfully employed throughout the chemical synthesis.


Nesiritide use for critically ill children awaiting cardiac transplantation.
This study aimed to explore the effects of nesiritide in children awaiting cardiac transplantation. At the discretion of the attending physician, nesiritide was added to standard therapy for seven children (median age, 11 months) and continued until clinical improvement or transplantation. Blood pressure and urine output data were compared with data from the day before nesiritide institution. Safety parameters were assessed throughout the study. Urine output increased from 2.6 to 3.6 ml/kg/h (p = 0.04). No significant blood pressure changes or adverse effects related to nesiritide were noted. Nesiritide may be safe and effective for children with severe heart failure.


Distinct transcriptome profiles identified in normal human bronchial epithelial cells after exposure to γ-rays and different elemental particles of high Z and energy.
Ionizing radiation composed of accelerated ions of high atomic number (Z) and energy (HZE) deposits energy and creates damage in cells in a discrete manner as compared to the random deposition of energy and damage seen with low energy radiations such as γ- or x-rays. Such radiations can be highly effective at cell killing, transformation, and oncogenesis, all of which are concerns for the manned space program and for the burgeoning field of HZE particle radiotherapy for cancer. Furthermore, there are differences in the extent to which cells or tissues respond to such exposures that may be unrelated to absorbed dose. Therefore, we asked whether the energy deposition patterns produced by different radiation types would cause different molecular responses. We performed transcriptome profiling using human bronchial epithelial cells (HBECs) after exposure to γ-rays and to two different HZE particles (28Si and 56Fe) with different energy transfer properties to characterize the molecular response to HZE particles and γ-rays as a function of dose, energy deposition pattern, and time post-irradiation. Clonogenic assay indicated that the relative biological effectiveness (RBE) for 56Fe was 3.91 and for 28Si was 1.38 at 34% cell survival. Unsupervised clustering analysis of gene expression segregated samples according to the radiation species followed by the time after irradiation, whereas dose was not a significant parameter for segregation of radiation response. While a subset of genes associated with p53-signaling, such as CDKN1A, TRIM22 and BTG2 showed very similar responses to all radiation qualities, distinct expression changes were associated with the different radiation species. Gene enrichment analysis categorized the differentially expressed genes into functional groups related to cell death and cell cycle regulation for all radiation types, while gene pathway analysis revealed that the pro-inflammatory Acute Phase Response Signaling was specifically induced after HZE particle irradiation. A 73 gene signature capable of predicting with 96% accuracy the radiation species to which cells were exposed, was developed. These data suggest that the molecular response to the radiation species used here is a function of the energy deposition characteristics of the radiation species. This novel molecular response to HZE particles may have implications for radiotherapy including particle selection for therapy and risk for second cancers, risk for cancers from diagnostic radiation exposures, as well as NASA's efforts to develop more accurate lung cancer risk estimates for astronaut safety. Lastly, irrespective of the source of radiation, the gene expression changes observed set the stage for functional studies of initiation or progression of radiation-induced lung carcinogenesis.


The survival of engrafted neural stem cells within hyaluronic acid hydrogels.
Successful cell-based therapy of neurological disorders is highly dependent on the survival of transplanted stem cells, with the overall graft survival of naked, unprotected cells in general remaining poor. We investigated the use of an injectable hyaluronic acid (HA) hydrogel for enhancement of survival of transplanted mouse C17.2 cells, human neural progenitor cells (ReNcells), and human glial-restricted precursors (GRPs). The gelation properties of the HA hydrogel were first characterized and optimized for intracerebral injection, resulting in a 25 min delayed-injection after mixing of the hydrogel components. Using bioluminescence imaging (BLI) as a non-invasive readout of cell survival, we found that the hydrogel can protect xenografted cells as evidenced by the prolonged survival of C17.2 cells implanted in immunocompetent rats (p < 0.01 at day 12). The survival of human ReNcells and human GRPs implanted in the brain of immunocompetent or immunodeficient mice was also significantly improved after hydrogel scaffolding (ReNcells, p < 0.05 at day 5; GRPs, p < 0.05 at day 7). However, an inflammatory response could be noted two weeks after injection of hydrogel into immunocompetent mice brains. We conclude that hydrogel scaffolding increases the survival of engrafted neural stem cells, justifying further optimization of hydrogel compositions.


[Pseudothrombosis of the inferior vena cava].
Flow phenomena can cause artifacts that may simulate thrombosis. The differentiation between thrombus and flow phenomenon can be made by delayed scans and certain CT-findings in thrombosis that may not be found in pseudothrombosis.


The remodeling of the primitive human biliary system.
From 12 weeks of gestation on, a progressive remodeling of the human primitive biliary structure or ductal plate occurs. A few parts of the primitive biliary structure (peripheral tubular or ductular structures) dilate, migrate toward the center of the portal tract, and transform into mature bile ducts, while most of them gradually disappear. To the best of our knowledge, quantitative studies have been performed only to evaluate the ratio between the number of remodeled bile ducts and portal tracts during human fetal development. We studied the remodeling of the intrahepatic fetal biliary structures as well as the bile duct to portal tract ratio in the developing human liver by immunohistochemistry with monoclonal antibodies anti-bile duct type cytokeratins and using a computer-based image-analysis system. We found that the surface and the perimeter of the portal tracts, the longest axis of the migrating peripheral tubular structures, and the maturation of bile ducts follow a process continuous and active up to term, but they slow between the 20th and the 32nd week of gestation, when intraportal granulopoiesis of the liver is active.


The facial nerve axotomy model.
Experimental models such as the facial nerve axotomy paradigm in rodents allow the systematic and detailed study of the response of neurones and their microenvironment to various types of challenges. Well-studied experimental examples include peripheral nerve trauma, the retrograde axonal transport of neurotoxins and locally enhanced inflammation following the induction of experimental autoimmune encephalomyelitis in combination with axotomy. These studies have led to novel insights into the regeneration programme of the motoneurone, the role of microglia and astrocytes in synaptic plasticity and the biology of glial cells. Importantly, many of the findings obtained have proven to be valid in other functional systems and even across species barriers. In particular, microglial expression of major histocompatibility complex molecules has been found to occur in response to various types of neuronal damage and is now regarded as a characteristic component of "glial inflammation". It is found in the context of numerous neurodegenerative disorders including Parkinson's and Alzheimer's disease. The detachment of afferent axonal endings from the surface membrane of regenerating motoneurones and their subsequent displacement by microglia ("synaptic stripping") and long-lasting insulation by astrocytes have also been confirmed in humans. The medical implications of these findings are significant. Also, the facial nerve system of rats and mice has become the best studied and most widely used test system for the evaluation of neurotrophic factors.


Return to Sport After Hip and Knee Arthroplasty: Counseling the Patient on Resuming an Active Lifestyle.
The purpose of this review is to summarize the available literature on the epidemiology, biomechanics, clinical outcomes, and complications of return to sport after TJA, as well as provide guidelines for patients' safe return to athletic activity. As volume and indications for total joint arthroplasty (TJA) expand, arthroplasty candidates today are demographically younger, more physically active, and have higher expectations for postoperative function. Many TJA patients wish to resume sports activity that may theoretically place their reconstruction under more biomechanical stress and risk for early wear or failure. Recommendations for postoperative patient activity following TJA have historically largely been surgeon-dependent and in the context of evolving prosthetic design and surgical techniques. We endorse a three-tiered framework for return to sporting activities: (1) low-impact sports are generally recommended, (2) intermediate-impact sports are generally recommended with experience, and (3) high-impact sports are generally not recommended though activity-specific joint decisions between patient and surgeon can be made.


Peripheral nerve grafts to the frog optic tectum: a morphological study of the axon reaction in trigeminal motor and sensory neurons.
The mandibular branch of the trigeminal nerve was severed and the proximal stump was grafted onto the optic tectum in adult Rana pipiens. The resultant changes occurring in the cell bodies of origin in the ipsilateral trigeminal motor and mesencephalic nuclei were studied qualitatively and quantitatively. Nucleolar, nuclear, and somal cross-sectional areas increased in size significantly approximately 3 days after surgery and peaked at 6 weeks postsurgery. This swelling, in which the nucleolus was most severely affected, gradually reversed itself and disappeared by 24 weeks after surgery. Despite the cell enlargement, cytoplasmic basophilia was maintained or even slightly increased. These morphologic changes suggest a strong anabolic reaction. Two differences were found between the motoneurons and the sensory neurons. First, the morphometric cell changes occurred at a faster rate in neurons of the trigeminal motor nucleus than in those of the mesencephalic nucleus. The time course of the motoneuron response correlated well with that of axonal regeneration from the nerve graft. Second, there was a delayed loss of mesencephalic nucleus cells between 12 and 24 weeks after surgery, whereas cells of the trigeminal motor nucleus were maintained at all survival times studied. Taken together with sensory cell loss in the trigeminal ganglion, this suggests a greater viability of regenerating motoneurons.


Stable and transport indices applied to winter air pollution over the Yangtze River Delta, China.
Previous studies have developed a stable weather index (SWI) based on meteorological elements that adequately represent PM2.5 pollution over the North China Plain (NCP). However, the SWI performs poorly over the Yangtze River Delta (YRD) region because air pollution over this region is affected not only by stagnant weather (STAG) but also by transport (TRANS). For example, air pollutants can be transported from the NCP to the YRD by cold fronts. In this study, an obliquely rotated principal component analysis in the T-model is applied to classify the synoptic patterns of winter weather over the YRD region from 2013 to 2018. Among the four identified synoptic patterns, two of which cause TRANS, one pattern is most likely to cause STAG, and one pattern can lead to either STAG or TRANS depending on the location of high pressure around Shandong province. Due to the large contribution (63%) of TRANS to the total PM2.5 pollution events, a transport pollution index (TPI) is constructed to describe the transport features of PM2.5 pollution over the YRD region. Our results show that, when considering the SWI alone, the correlation coefficients between the SWI and ln(PM2.5) range from 0.50 to 0.57 in the main cities of the YRD. Excitingly, when considering both the TPI and SWI (TPI+SWI), the correlation coefficients increase significantly to 0.63-0.78, suggesting that TPI+SWI better reflects the wintertime PM2.5 pollution level over the YRD region. In addition, satisfactory performance in validation also suggests that TPI+SWI can increase the accuracy of evaluating and forecasting of PM2.5 pollution episodes over regions downstream of source emissions.


Nucleotide sequence of nuclear 5.4 S RNA of mouse cells.
The nucleotide sequence of nuclear 5.4 S RNA, a new species of small nuclear RNA (snRNA) of mouse cells, was determined. The 5.4 S RNA consists of 138 nucleotide residues containing 1 mol each of 2,2,7- trimethylguanosine (m3(2,2,7) G), 2'-O-methyladenosine (Am), 2'-O-methyluridine (Um) and pseudouridine as modified nucleosides. This RNA has a cap structure, m3(2,2,7) ++GpppAm -, at its 5'-terminus and sequences complementary to the terminal consensus sequences of introns. The sequence complementary to the 5'-splice junction, A-U-C-C-psi-U-A-C-C-U-G, is very similar to the 5'-terminal sequence of U1 RNA.


Proliferation of human aortic vascular smooth muscle cells in culture is modulated by active TGF beta.
Human vascular smooth muscle cells (VSMC) prepared by enzyme dispersal have been reported to proliferate more slowly and remain more differentiated than VSMC derived by explant culture. The aim of this study was to investigate whether these differences are attributable to the production of transforming growth factor beta (TGF beta), a major modulator of VSMC properties in culture, by enzyme dispersal, but not explant, cultures. Human aortic VSMC cultures were prepared by enzymatic dissociation of aortic media or by outgrowth of cells from explants derived from the vessel media. Properties, including rate of proliferation and differentiation, of the two different types of culture obtained from 10 donors (age 3-54 years, of either sex) were compared. The role of TGF beta as mediator of these differences was investigated. VSMC from enzyme dispersal cultures proliferated with a long doubling time in 20% fetal calf serum of 68(SEM 2) h, reaching a low saturation density with no "hills and valleys", and the cells were predominantly of stellate morphology. VSMC from explant cultures proliferated with a shorter doubling time of 35(2) h, reached a higher saturation density with "hills and valleys", and showed a spindle shaped morphology. The enzyme dispersed cells, but not the explant cells, released TGF beta into the medium. Addition of exogenous TGF beta to the explant cells extended the doubling time, while addition of a neutralising antibody to the enzyme dispersed cells decreased the doubling time. Tamoxifen, an anti-oestrogenic drug, decreased the rate of proliferation of the explant cells (ED50 = 50 nM; n = 3) but not enzyme dispersed cells by stimulating production of TGF beta. The explant and enzyme dispersal cultures also differed in response to growth factors. The explant cultures stimulated DNA synthesis in response to platelet derived growth factor (PDGF) AA and BB. Enzyme dispersal cultures stimulated DNA synthesis in response to PDGF-BB but response to AA was weaker and also variable. Human explant derived VSMC systematically differ from enzyme dispersed VSMC obtained from the same donor tissue. Wherever the potential role of TGF beta was investigated, the differences between enzyme dispersal and explant cultures were due to autocrine production of TGF beta by the enzyme dispersal, but not explant cultures.


Kinetics of CMV seroconversion in a Swiss pregnant women population.
Retrospective evaluation of the kinetics of cytomegalovirus (CMV) seroconversion with CMV IgM, IgG, and IgG avidity assays, in a Swiss pregnant women population, has shown that the current published CMV serologic diagnostic algorithms were valid and fit for use. In 19% of the cases analyzed, CMV-specific IgM was detected before IgG.


Influence of extra-intestinal inflammation on the in vitro absorption of 14C-glucose and the effects of anti-inflammatory drugs in the jejunum of rats.
Inflammation was induced in the hind legs of rats by formalin injection and the in vitro jejunal absorption of 14C-glucose was studied. Treatment of rats with formalin caused a reduction in the in vitro absorption of glucose from the jejunum. Oral administration of oxyphenbutazone or a herbal anti-inflammatory drug (Withania somnifera) prior to formalin injection, resulted in no alteration in the jejunal absorption of glucose.


Localization of apolipoprotein E in normal and atherosclerotic human aorta.
To elucidate the role of apolipoprotein E (apo E) in atherogenesis, we have investigated the localization of apo E in normal and atherosclerotic aortas as well as in other tissues of 32 post-mortem individuals. Using double immunofluorescence it has been found that normal intima of individuals older than 20 years and some adolescents contained immunoreactive material that reacted with poly- and monoclonal antibodies to apo E. A staining pattern of apo E differed from that of apolipoprotein B, the latter being seen in normal intima of each child older than 7 years. Apo E was present extracellularly in lipid streaks and atheromatous plaques, where its staining was particularly intensive around the necrotic zone of plaques. Some macrophages in the plaques of 4 aortas exhibited apo E-positive staining, while aortic endothelial and smooth muscle cells never contained apo E. Apo E-positive staining was not found in the majority of vessel cells, it was always, however, observed in other types of cells including hepatocytes. Kupffer cells, spleen macrophages and cerebral astrocytes. Our findings indicate that only some macrophages in human aorta may be responsible for the production of apo E that can participate in reverse cholesterol transport. At the same time, apo E accumulation in the aortic wall may promote the development of atherosclerosis.


Review article: pathophysiology and management of primary biliary cholangitis.
Primary biliary cholangitis (PBC), an immune-mediated disease characterised by destruction of intrahepatic bile ducts, results in progressive damage to the biliary tree, cholestasis and ultimately advanced liver disease. In the last decade, advances in practice have improved clinical care, driven novel therapeutic options and improved risk stratification tools. To provide an overview of the disease characteristics of PBC and review a patient-centred management approach for the clinical team caring for those with PBC. We reviewed the current literature and guidelines on PBC with a focus on management and therapies. A confident diagnosis of PBC is usually made based on serum liver tests and immune serology. Management of PBC should focus on three main 'process' pillars: (a) treat and risk-stratify through use of biochemical and prognostic criteria; (b) manage concurrent symptoms and other associated diseases; and (c) stage disease, monitor progression and prevent complications. With ongoing complexities in management, including a newly licensed therapy (obeticholic acid) and alternative non-licensed treatments and ongoing clinical trials, discussion with PBC expert centres is encouraged. PBC is a dynamic disease wherein current treatment goals have become appropriately ambitious. Goals of care should prioritise prevention of end-stage liver disease and amelioration of patient symptom burden for all.


The impact of preconceptional exposure of F0 male mice to bisphenol A alone or in combination with X-rays on the intrauterine development of F2 progeny.
Bisphenol A (BPA) is used for the production of polycarbonates and epoxy resins. Exposure to chemical and physical environmental factors may influence the health of exposed individuals, and of the next generations. This paper describes the prenatal effects in the F2 generation of mice after exposure of F0 pubescent or mature males to BPA (5 mg/kg bw, 10 mg/kg bw, 20 mg/kg bw), X-rays (0.05 Gy) or a combination of both factors in low doses (0.05 Gy + 5 mg/kg bw BPA) for 8 weeks. F1 males were mated with females from the same group but from a different litter. The females were sacrificed before parturition and examined for the number of implantations, live foetuses, as well as early and late post-implantation deaths. The fertility of males and the percentage of pregnant females in each group were also assessed. Exposure of pubescent F0 males to 10 mg/kg bw of BPA decreased the frequency of fertile males. Following exposure of pubescent males, the frequency of pregnant females decreased in the groups of 10 mg/kg bw and 20 mg/kg bw of BPA, whereas after exposure of adult F0 males in the groups of 5 mg/kg bw and 20 mg/kg bw of BPA, no significant changes in the frequency of total, live and dead implantations in all the experimental groups were found. The results observed in regard to prenatal development of the F2 generation suggest that sperm of the sons of F0 pubescent males exposed to BPA contains genetic defects that affect the possibility of fertilization. The results of both pubescent and mature males exposed to BPA showed that fertilized eggs died before implantation, probably due to defects induced in the sperm. This confirmed that BPA induced transgenerational effects in male germ cells.


Determination of 15 human pharmaceutical residues in fish and shrimp tissues by high-performance liquid chromatography-tandem mass spectrometry.
An efficient, reliable, and sensitive multiclass analytical method has been expanded to simultaneously determine 15 human pharmaceutical residues in fish and shrimp tissue samples by ultra-high-performance liquid chromatography-tandem mass spectrometry. The investigated compounds comprise ten classes, namely, analgesic, antibacterial, anticonvulsant, cardiovascular, fluoroquinolones, macrolides, nonsteroidal anti-inflammatory, penicillins, stimulant, and sulfonamide. A simple liquid extraction procedure based on 0.1% formic acid in methanol was developed. Chromatographic conditions were optimized, and mobile phase A was 0.1% ammonium acetate, and mobile phase B was acetonitrile. The mobile phase's gradient program was as follows: 0-2 min, 15% B; 2-5 min, linear to 95% B; 5-10 min, 95% B; and 10-12 min. The limits of detection were from 0.017 to 1.371 μg/kg, while a quantification range was measured from 0.051 to 4.113 μg/kg. Finally, amoxicillin, azithromycin, caffeine, carbamazepine, ciprofloxacin, clarithromycin, diclofenac, erythromycin, furosemide, ibuprofen, ketoprofen, naproxen, sulfamethoxazole, tetracycline, and triclosan were quantifiable in fish and shrimp samples.


A comparison of tunnelled and nontunnelled subclavian vein catheters: a prospective study of complications during parenteral feeding.
Forty-four silastic catheters in 38 surgical patients, nursed in general surgical wards, were inserted under aseptic conditions by the infraclavicular subclavian route. The catheters were randomly allocated to non-tunnelled (NT) (n = 24) or tunnelled (T) (n = 20) groups. Catheters were removed on completion of intravenous feeding or clinical suspicion of catheter infection, and the catheter tip and blood samples taken through the catheter and from the peripheral vein were cultured. There was no significant difference between the two groups in terms of bacteriological infection (defined as two or more cultures of the same organism), clinical infection (defined by elevated temperature returning to normal after catheter removal) and combined infection (when both bacteriological and clinical infection co-existed). When the number of infected catheters was related to the duration of catheter insertion, the incidence of combined catheter related sepsis was reduced with tunnelling (NT: one infected catheter per 35 catheter days, T: one infected catheter per 89 catheter days). This study highlights the risks of subclavian vein catheterisation and emphasises the difficulties in defining catheter sepsis but suggests that its incidence may be reduced if skin tunnelling is employed.


Temporal trends and geographic variations in perioperative red blood cell transfusion in major surgical procedures from 2013 to 2018 in China.
Transfusion-related guidelines promote restrictive blood transfusion. However, whether these guidelines have been successfully translated into clinical practice in China is unknown. This study aimed to provide updated information about the temporal trends in the prevalence of perioperative red blood cell (RBC) transfusion in China. We analysed data from the Hospital Quality Monitoring System database (2013-2018) to investigate the prevalence of perioperative RBC transfusion in patients undergoing craniotomy for cerebral aneurysms or arteriovenous malformations, sternotomy for mitral valve replacement, open thoracotomy lobectomy, open gastrectomy and hip arthroplasty. Mixed-effects logistic regression models quantified the likelihood of RBC transfusions. The study included 438,183 patients, with 44,697 (10.20%) receiving perioperative RBC transfusions. Introducing transfusion-related guidelines in China markedly decreased the prevalence of RBC transfusion among patients who underwent major surgical procedures in the following years. The prevalence of RBC transfusion for hip arthroplasty was 17.34% in 2013 and 7.03% in 2018. After adjusting for patient risk factors, the odds ratio of RBC transfusion for hip arthroplasty was significantly lower in 2018 (0.74, 95% confidence intervals [CI] 0.53-1.02) than in 2013 (1.84, 95% CI 1.37-2.48). The prevalence of perioperative RBC transfusion decreased from 2013 to 2018 in China, supporting the potential beneficial effects of transfusion-related guidelines. Considering the geographic variations in RBC transfusion, reducing heterogeneity may impact public health by improving surgical outcomes.


Similarly low risk of hepatocellular carcinoma after either spontaneous or nucleos(t)ide analogue-induced hepatitis B surface antigen loss.
It is unknown whether patients with chronic hepatitis B (CHB) who achieved hepatitis B surface antigen (HBsAg) seroclearance spontaneously or following anti-viral therapy have similar clinical outcomes. To compare the risk of hepatocellular carcinoma (HCC) in patients with CHB who either cleared HBsAg spontaneously or following anti-viral therapy METHODS: Adult CHB-monoinfected patients who cleared HBsAg between January 2000 and March 2019 were identified from a territory-wide database in Hong Kong. Patients with liver transplantation and/or HCC before HBsAg loss were excluded. Patients' demographics, comorbidities, anti-viral treatment, laboratory parameters and HCC development were analysed. Of 7,124 identified patients with CHB who cleared HBsAg, mean age was 58.1 ± 13.8 years; 4,340 (60.9%) were male; 451 (6.3%) had cirrhosis; 5,917 (83.1%) and 1,207 (16.9%) had spontaneous and nucleos(t)ide analogue (NA)-induced HBsAg seroclearance, respectively. Most patients had normal liver function at HBsAg loss. Patients with NA-induced HBsAg seroclearance were younger, and more likely to be male and cirrhotic than patients with spontaneous HBsAg loss. At a median (interquartile range) follow-up of 4.3 (2.2-7.6) years, 97 (1.6%) and 16 (1.3%) patients with spontaneous and NA-induced HBsAg loss developed HCC, respectively. Patients who achieved NA-induced HBsAg loss had comparable HCC risk as those with spontaneous HBsAg loss (adjusted subdistribution hazard ratio 0.75, 95% CI 0.43-1.32, P = 0.323). The results remained robust in propensity score weighting and matching analyses. The HCC risk was similarly low after either spontaneous or NA-induced HBsAg seroclearance in a territory-wide cohort of patients with CHB who had cleared HBsAg.


Influence of varying titanium base abutment heights on retention of zirconia restorations: An in vitro study.
Implant manufacturers have introduced titanium base (Ti-Base) abutments with increased abutment heights, ostensibly, to increase the retention of the bonded restoration and to improve overall strength. However, evidence regarding the effects of increasing Ti-Base height on improving retention is lacking. The purpose of this in vitro study was to evaluate the effect of different Ti-Base abutment heights on the retention of zirconia implant-supported crowns. Thirty Ti-Base abutments of the same diameter and heights of 3.5 mm (n=10), 4.5 mm (n=10), and 5.5 mm (n=10), were used for testing. Zirconia restorations were cemented onto the Ti-Base abutments with a resin cement after treatment with a 10-methacryloyloxydecyl dihydrogen phosphate primer by a single operator using a positioning device. The zirconia-Ti-Base restorations were tightened to an implant analog embedded in an autopolymerizing resin block. The specimens were placed and tested in a universal testing machine for pull-out testing. Retention was measured by recording the force at load drop. Statistical analysis was performed using 1-way analysis of variance with the Tukey method for pairwise comparisons. The abutment height had a significant effect on retention (P=.010). Ti-Base abutments of 4.5 and 5.5 mm had significantly greater retention than Ti-Base abutments of 3.5 mm (P=.020, P=.040, respectively). However, Ti-Base abutments of 4.5 and 5.5 mm in height were statistically similar (P=.890). An increase in the height of Ti-Base abutments above the standard 3.5 mm height significantly improved the retention of the overlying restoration.


Cervical intra and extramedullary hemangioblastoma with associated syringomyelia: A case report and review of the literature.
Spinal hemangioblastoma (HB) is a highly vascularized tumor commonly presenting in the lower thoracic and lumbar segments. It typically causes spinal compression, extensive bleeding, and/or syringomyelia. A 32-year-old female presented with persistent headaches with a cervical MRI showing an intradural and extradural mass extending from the obex to C2. Following surgical tumor resection, the patient's symptoms resolved. Resection of spinal HB requires direct removal of the tumor mass as the accompanying cystic components typically spontaneously regress.


Primitive neuroectodermal tumor of the cervix: a case report.
Peripheral primitive neuroectodermal tumor of the cervix uteri is extremely rare. Between 1987 and 2010, there were only nine cases reported in the English literature, with considerably different management policies. A 45-year-old Iranian woman presented to our facility with a primitive neuroectodermal tumor of the cervix uteri. Her clinical stage IB2 tumor was treated successfully with chemotherapy. Our patient underwent radical hysterectomy. There was no trace of the tumor after four years of follow-up. According to current knowledge, primitive neuroectodermal tumors belong to the Ewing's sarcoma family, and the improvement of treatment outcome in our patient was due to dose-intensive neoadjuvant chemotherapy, surgery and consolidation chemotherapy in accordance with the protocol for bony Ewing's sarcoma.


Walking associated with public transit: moving toward increased physical activity in the United States.
We assessed changes in transit-associated walking in the United States from 2001 to 2009 and documented their importance to public health. We examined transit walk times using the National Household Travel Survey, a telephone survey administered by the US Department of Transportation to examine travel behavior in the United States. People are more likely to transit walk if they are from lower income households, are non-White, and live in large urban areas with access to rail systems. Transit walkers in large urban areas with a rail system were 72% more likely to transit walk 30 minutes or more per day than were those without a rail system. From 2001 to 2009, the estimated number of transit walkers rose from 7.5 million to 9.6 million (a 28% increase); those whose transit-associated walking time was 30 minutes or more increased from approximately 2.6 million to 3.4 million (a 31% increase). Transit walking contributes to meeting physical activity recommendations. Study results may contribute to transportation-related health impact assessment studies evaluating the impact of proposed transit systems on physical activity, potentially influencing transportation planning decisions.


Clinical evaluation of the DBR A-scan unit.
One hundred and eight eyes of 106 patients were evaluated preoperatively with the DBR-300 A-scan ultrasonic instrument. Intraocular lens power was then calculated using the formula supplied with the instrument, and the accuracy of the instrument was evaluated. It was found that 61.1% of the eyes were within +/- 1.00 D of the calculated refractive error and 81.5% of the eyes were within +/- 1.50 D of the calculated refractive error when using a standard 3.5-mm anterior chamber depth. Various factors were then analyzed to determine which factors contributed to the inaccuracy of the instrument. No single factor could be found to account for the slight tendency toward myopia, although several were found to contribute. No single factor was found to contribute to large errors.


Early life exposures and development of allergic disease in infants with familial risk: Results from ongoing probiotic intervention trials.
We search revision of risk determinants of the ongoing allergy epidemic. Children numbering 433 born to mothers with allergic disease or sensitisation were selected from the three ongoing probiotic intervention trials for this case-control study. Children who developed atopic eczema or food allergy, had positive skinprick test results or had been prescribed inhaled corticosteroids by the age of 2 years were identified as cases (n = 231), while children without allergic manifestations were the healthy controls (n = 202). The data on early environmental exposures were collected from prospectively documented study records. The statistical analyses were adjusted for potential confounders. Determinants associated with the increased risk of atopic eczema were lower maternal prepregnancy BMI (aOR 0.15, 95% CI: 0.037-0.54) and maternal intrapartum antibiotic treatment (aOR 2.21, 95% CI 1.20-4.10), the latter also linked to obstructive respiratory symptoms (aOR 3.87, 95% CI 1.07-14.06). The risk of allergic sensitisation was associated with lower maternal prepegnancy BMI (aOR 0.18, 95% CI 0.43-0.79) and intrapartum antibiotic treatment (aOR 2.13, 95% CI 1.07-4.22). Based on our demonstrations, interventions such as personalised diets, can be optimised for specific subgroups and definite risk periods.


The tumor therapeutic potential of long non-coding RNA delivery and targeting.
Long non-coding RNAs (lncRNAs) is a type of RNA over 200 nt long without any protein coding ability, which has been investigated relating to crucial biological function in cells. There are many key lncRNAs in tumor/normal cells that serve as a biological marker or a new target for tumor treatment. However, compared to some small non-coding RNA, lncRNA-based drugs are limited in clinical application. Different from other non-coding RNA, like microRNAs, most lncRNAs have a high molecular weight and conserved secondary structure, making the delivery of lncRNAs more complex than the small non-coding RNAs. Considering that lncRNAs constitute the most abundant part of the mammalian genome, it is critical to further explore lncRNA delivery and the subsequent functional studies for potential clinical application. In this review, we will discuss the function and mechanism of lncRNAs in diseases, especially cancer, and different approaches for lncRNA transfection using multiple biomaterials.


Therapy-related acute myeloid leukemia with t(8;16)(p11;p13) following anthracycline-based therapy for nonmetastatic osteosarcoma.
A case of therapy-related AML with t(8;16)(p11;p13) 14 months following the end of anthracycline-containing chemotherapy for a nonmetastatic osteosarcoma of the left tibia is presented. The patient was successfully treated with intensive remission-induction chemotherapy. Subsequently, he underwent an uncomplicated allogeneic bone marrow transplantation from his HLA-identical brother and is at present alive and disease-free 10 months after diagnosis of the secondary AML.


Antipeptide antibody to the insulin-like growth factor-I receptor sequence 1232-1246 inhibits the receptor kinase activity.
To approach the question of why insulin-like growth factor-I (IGF-I) and insulin have different physiological actions, we developed antibodies directed against cytoplasmic regions of the IGF-I receptor exhibiting a low degree of homology with the corresponding sequences of the insulin receptor. We found that an antipeptide antibody directed against the beta-subunit carboxyl-terminal sequence (1232-1246) of the IGF-I receptor significantly reduced the in vitro receptor autophosphorylation. The ability of the synthetic peptide corresponding to the IGF-I receptor sequence 1232-1246 to abolish this inhibitory effect reflects the specific nature of the antibody interaction with the targeted domain in the receptor. Antipeptide antibody to IGF-I receptor sequence 1232-1246 also decreased receptor phosphorylation activity toward the exogenous substrate poly(Glu/Tyr). The reduction in poly(Glu/Tyr) phosphorylation was seen even when the antibody was incubated with a receptor previously activated and phosphorylated. Therefore, the inhibitory action on substrate phosphorylation is likely to be unrelated to the antibody reduction of receptor autophosphorylation but rather results from a global decrease in receptor enzymatic activity. The effect of the antipeptide antibody on receptor tyrosine kinase cannot be accounted for by a lowering of the receptor Km for ATP or of its affinity for the substrate poly(Glu/Tyr). Moreover, the interaction of the antibody with the receptor had no repercussion on the ligand binding site as shown by the unaltered IGF-I binding. Taken together our data suggest that the beta-subunit carboxyl-terminal domain of the IGF-I receptor plays a key role in regulating its kinase activity and that the particular sequence recognized by our antipeptide antibody could be involved in negative regulation of receptor functioning.


Bioconjugation Methods for Coupling Targeting Ligands with Fluorescent Dyes.
Targeted molecular imaging probes are essential tools for visualization of specific molecular processes in cells and living systems. Among these, targeted fluorescent probes are widely used due to the high sensitivity and resolution of fluorescence imaging. The conventional strategy for developing targeted fluorescent probes is to couple targeting ligands with fluorescent dyes by covalent bond via bioconjugation. Here, we describe several commonly used bioconjugation methods, from traditional amide and thiol coupling, to metal-catalyzed coupling reaction and catalyst free cycloaddition.


Immune Checkpoint Inhibition in Non-metastatic Non-small Cell Lung Cancer: Chance for Cure?
Immune checkpoint inhibition of programmed-death receptor 1 (PD-1) or its ligand (PD-L1) has become a standard in the treatment of metastatic non-small cell lung cancer, either as monotherapy or in combination. Recently, it could be shown that immunotherapy works as consolidation after chemoradiotherapy in locally advanced disease if the tumours express PD-L1. A significant and meaningful survival benefit for consolidation with durvalumab after chemoradiotherapy compared to chemoradiotherapy alone was observed in the PACIFIC trial. In addition, there is a growing body of evidence that this treatment modality is also effective in a neoadjuvant setting in early stages, whereas the role as adjuvant treatment after surgery needs to be determined. The impact of combination therapies in non-metastatic stages-either neoadjuvant or adjuvant-needs to be evaluated in future trials. It is yet unclear whether PD-L1 and tumour mutational burden are predictive biomarkers as randomised trials are missing.


Outcomes of Salvage Therapy for Oropharyngeal Cancer Recurrence Following Upfront Radiation Therapy and Prognostic Factors.
This study aimed to investigate the oncologic outcomes and prognostic factors of salvage treatments in patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC) after radiotherapy (RT)-based treatment. A cancer registry was used to retrieve the records of 337 patients treated with definitive RT or concurrent chemoradiotherapy (CRT) from 2008 to 2018 at a single institution. The poor-responder group (PRG) was defined as patients with residual or recurrent disease after primary treatment, and the oncologic outcomes for each salvage treatment method were analyzed. In addition, prognostic indicators of recurrence-free survival (RFS) and overall survival (OS) were identified in patients who underwent salvage treatment. After initial (C)RT, the PRG comprised 71 of the 337 patients (21.1%): 18 patients had residual disease, and 53 had recurrence after primary treatment (mean time to recurrence 19.5 months). Of these, 63 patients received salvage treatment (surgery 57.2%, re-(C)RT 23.8%, and chemotherapy 19.0%), and the salvage success rate was 47.6% at the last follow-up. The overall 2-year OS for salvage treatments was 56.4% (60.8% for the salvage surgery group and 46.2% for the salvage re-(C)RT). Salvage surgery patients with negative resection margins had better oncologic outcomes than those with close/positive resection margins. Using multivariate analyses, locoregional recurrence and residual disease after primary surgery were associated with poor outcome after salvage treatment. In Kaplan-Meier analyses, p16 status was significantly associated with OS in the initial treatment setting but not in the salvage setting. In recurrent OPSCC after RT-based treatment, successful salvage was achieved in 56.4% patients who had undergone salvage surgery and radiation treatment. Salvage treatment methods should be selected carefully, given recurrence site as a prognostic factor for RFS.


Mindfulness, functioning and catastrophizing after multidisciplinary pain management for chronic low back pain.
We examined mindfulness in people with chronic low back pain who were attending a multidisciplinary pain management programme. Participants completed questionnaires at baseline (n=116) and after a 3-month cognitive-behaviourally informed multidisciplinary intervention (n=87). Self-reported mindfulness was measured before and after the intervention, and relationships were explored between mindfulness, disability, affect and pain catastrophizing. Mindfulness increased following participation in the intervention, and greater mindfulness was predictive of lower levels of disability, anxiety, depression and catastrophizing, even when pain severity was controlled. Mediator analyses suggested that the relationship between mindfulness and disability was mediated by catastrophizing. It is possible that cognitive-behavioural interventions and processes can affect both catastrophizing and mindfulness.


Interrogation of G-quadruplex-protein interactions.
The ability to accurately examine the interaction of G-quadruplex DNA with proteins is essential for revealing the biological roles of these unusual DNA structures. In this regard, there are four primary G-quadruplex-related activities of proteins that have been studied including simple equilibrium binding, promotion or catalysis of G-quadruplex formation, dissociation of G-quadruplex structures, and covalent modification of G-quadruplexes, which includes both nucleolytic cleavage and nucleotide addition. Here, assays used to examine the interactions of G-quadruplexes with proteins will be reviewed and specific methods to study the interactions of G-quadruplexes from telomeric DNA sequences with a variety of proteins will be described. Importantly, this review emphasizes the importance of evaluating the integrity of the G-quadruplex being studied as single sequences can often form a variety of folded structures.


Comparison of 6 DNA extraction methods for isolation of high yield of high molecular weight DNA suitable for shotgun metagenomics Nanopore sequencing to detect bacteria.
Oxford Nanopore Technologies (ONT) offers an accessible platform for long-read sequencing, which improves the reconstruction of genomes and helps to resolve complex genomic contexts, especially in the case of metagenome analysis. To take the best advantage of long-read sequencing, DNA extraction methods must be able to isolate pure high molecular weight (HMW) DNA from complex metagenomics samples, without introducing any bias. New methods released on the market, and protocols developed at the research level, were specifically designed for this application and need to be assessed. In this study, with different bacterial cocktail mixes, analyzed as pure or spiked in a synthetic fecal matrix, we evaluated the performances of 6 DNA extraction methods using various cells lysis and purification techniques, from quick and easy, to more time-consuming and gentle protocols, including a portable method for on-site application. In addition to the comparison of the quality, quantity and purity of the extracted DNA, the performance obtained when doing Nanopore sequencing on a MinION flow cell was also tested. From the obtained results, the Quick-DNA HMW MagBead Kit (Zymo Research) was selected as producing the best yield of pure HMW DNA. Furthermore, this kit allowed an accurate detection, by Nanopore sequencing, of almost all the bacterial species present in a complex mock community. Amongst the 6 tested methods, the Quick-DNA HMW MagBead Kit (Zymo Research) was considered as the most suitable for Nanopore sequencing and would be recommended for bacterial metagenomics studies using this technology.


Effects of treadmill exercise on cognitive functions and anxiety-related behaviors in ovariectomized diabetic rats.
Diabetes mellitus and ovarian hormone deficiency are associated with mood and cognition disorders. We aimed to study the possible beneficial effects of treadmill exercise on cognitive impairments and anxiety-related behaviors in ovariectomized diabetic rats. Fourteen days after bilateral ovariectomy or sham operation, adult female Wistar rats (n = 7 per group) received an intraperitoneal injection of streptozotocin (60 mg/kg) for induction of diabetes mellitus or citrate buffer. After 14 days, the animals were subjected to treadmill running or placed on the stationary treadmill for 4 weeks (5 days/week). The animals were then subjected to Morris water maze (MWM), elevated plus maze (EPM), and open field test to determine spatial learning and memory, anxiety-related behaviors, and locomotor activity, respectively. Spatial learning decreased in diabetic and ovariectomized + diabetic (Ovx + Dia) groups. Decreased spatial memory and increased anxiety levels were observed in the Ovx, Dia, and Ovx + Dia groups. Animals in the Ovx + Dia group showed reduced locomotor activity. Treadmill exercise improved spatial memory and anxiety levels in the Ovx and Dia groups, while had no significant effect on spatial learning and memory, anxiety levels, and locomotor activity in the Ovx + Dia group. Collectively, our results showed that physical exercise has beneficial effects on anxiety-related behaviors and spatial memory, but not of learning, in the ovariectomized and diabetic animals. Co-existence of ovariectomy and diabetes exacerbates anxiety-related behaviors, but not cognitive functions, compared to diabetes or ovariectomy alone; these complications could not be improved by exercise.


Age-related incidence and family history in frontotemporal dementia: data from the Swedish Dementia Registry.
Frontotemporal dementia (FTD) is considered to be a mainly early-onset neurodegenerative disorder with a strong hereditary component. The aim of the study was to investigate age-related incidence and family history in FTD compared to other dementia disorders, especially Alzheimer's disease (AD). The Swedish Dementia Registry (SveDem) registers all new cases of dementia diagnosed by the participating centres, including data on demographics, diagnosis, and investigations used. Data for the period 2008-2011 were extracted and compared with age-related population data on a regional and national level. There were 20 305 patients registered in SveDem during 2008-2011, whereof 352 received a diagnosis of FTD. Mean age at diagnosis for FTD was 69.6 years and almost 70% of FTD cases were 65 years or older at the time of diagnosis. Both FTD and AD showed an increased incidence with age, which reached a maximum in the age group 80-84 years at 6.04 and 202 cases per 100 000 person-years, respectively. The proportion of cases with a positive family history was significantly lower in FTD than in AD. Contrary to general opinion within the field, data from SveDem show that the incidence of FTD increases with age, and that the majority of cases are diagnosed after the age of 65 years. In addition, data from SveDem might suggest that the importance of hereditary factors in general is similar in FTD and AD. The recognition of these findings has important consequences for the diagnosis, treatment and care of patients with FTD.


Motivational Interviewing: moving from why to how with autonomy support.
Motivational Interviewing (MI), a counseling style initially used to treat addictions, increasingly has been used in health care and public health settings. This manuscript provides an overview of MI, including its theoretical origins and core clinical strategies. We also address similarities and differences with Self-Determination Theory. MI has been defined as person-centered method of guiding to elicit and strengthen personal motivation for change. Core clinical strategies include, e.g., reflective listening and eliciting change talk. MI encourages individuals to work through their ambivalence about behavior change and to explore discrepancy between their current behavior and broader life goals and values. A key challenge for MI practitioners is deciding when and how to transition from building motivation to the goal setting and planning phases of counseling. To address this, we present a new three-phase model that provides a framework for moving from WHY to HOW; from building motivation to more action oriented counseling, within a patient centered framework.


Older forests function as energetic and demographic refugia for a climate-sensitive species.
More frequent and extreme heat waves threaten climate-sensitive species. Structurally complex, older forests can buffer these effects by creating cool microclimates, although the mechanisms by which forest refugia mitigate physiological responses to heat exposure and subsequent population-level consequences remain relatively unexplored. We leveraged fine-scale movement data, doubly labeled water, and two decades of demographic data for the California spotted owl (Strix occidentalis occidentalis) to (1) assess the role of older forest characteristics as potential energetic buffers for individuals and (2) examine the subsequent value of older forests as refugia for a core population in the Sierra Nevada and a periphery population in the San Bernardino Mountains. Individuals spent less energy moving during warmer sampling periods and the presence of tall canopies facilitated energetic conservation during daytime roosting activities. In the core population, where tall-canopied forest was prevalent, temperature anomalies did not affect territory occupancy dynamics as warmer sites were both less likely to go extinct and less likely to become colonized, suggesting a trade-off between foraging opportunities and temperature exposure. In the peripheral population, sites were more likely to become unoccupied following warm summers, presumably because of less prevalent older forest conditions. While individuals avoided elevated energetic expenditure associated with temperature exposure, behavioral strategies to conserve energy may have diverted time and energy from reproduction or territory defense. Conserving older forests, which are threatened due to fire and drought, may benefit individuals from energetic consequences of exposure to stressful thermal conditions.


[Effects of Peroxisome Proliferator-Activated Receptor γ on Modulating Angiopoietin-Like Protein 4 Synthesis in Caco-2 Cells Exposed to Clostridium butyricum].
Angiopoietin-like protein 4 (ANGPTL4) is considered to be one of the important circulating mediators linking intestinal microorganisms and host lipid metabolism. The objective of this study was to assess the effects of peroxisome proliferator-activated receptor у (PPARγ) on modulating ANGPTL4 synthesis in Caco-2 cells exposed to Clostridium butyricum. The viability of Caco-2 cells and the expression of PPARγ and ANGPTL4 in Caco-2 cells were detected after the Caco-2 cells were co-cultured with C. butyricum at the concentration of 1 x 10^(6), 1 x 10^(7) and 1 x 10^(8) CFU/mL. The results showed that cell viability was enhanced by C. butyricum. Besides, PPARγ and ANGPTL4 expression and secretion in Caco-2 cells was significantly increased by 1 x 10^(7) and 1 x 10^(8) CFU/mL of C. butyricum. Furthermore, the effects of PPARγ on modulating ANGPTL4 synthesis in Caco-2 cells regulated by 1 x 10^(8) CFU/mL of C. butyricum was also be expounded in PPARγ activation/inhibition model based on Caco-2 cells and via ChIP technique. It was found that C. butyricum promoted the binding of PPARγ to the PPAR binding site (chr19: 8362157-8362357, located upstream of the transcriptional start site of angptl4) of the angptl4 gene in Caco-2 cells. However, the PPARγ was not the only way for C. butyricum to stimulate ANGPTL4 production. Taken together, PPARγ played a role in the regulation of ANGPTL4 synthesis by C. butyricum in Caco-2 cells.


MR-based temperature monitoring for hot saline injection therapy.
We applied magnetic resonance (MR) phase mapping methods to monitor the thermal frequency shift of water in order to study temperature changes from percutaneous hot saline injection therapy (PSIT) using in vitro swine livers and in vivo rabbit livers. The thermal coefficients calculated from the shifts of the water frequency with thermocouple based temperature measurements were -0.0085 +/- 0.0019 ppm/ degrees C for the in vitro studies and -0.0089 ppm/ degrees C for the in vivo studies. The error range was estimated to be +/- 3 degrees C and +/- 4.5 degrees C, respectively. Color-coded temperature maps were compared with macroscopic lesion sizes of the specimen. Regions defined using a 20 degrees C elevation in the initial images following hot saline injection (around 55 degrees C in absolute temperature) closely correlated with visible coagulation in size. We conclude that MR temperature monitoring of PSIT is quite feasible and may be helpful in expanding the clinical use of this thermal therapeutic tool for liver tumors.


Reuterin production by lactobacilli isolated from pig faeces and evaluation of probiotic traits.
To determine the production of reuterin by lactobacilli isolates from pig faeces and to evaluate their potential as probiotic bacteria. Twenty-eight of 165 lactobacilli isolates produced reuterin in the presence of glycerol. Six isolates yielding high levels of reuterin with respect to type strain Lactobacillus reuteri CECT 925T were identified as Lact. reuteri. They were able to survive at pH 3 and subsequent exposure to cholic acid or oxgall, and presented bile salt hydrolase and bacteriocin-like activities. Reuterin production is a frequently found trait among lactobacilli isolated from pig faeces. Selected Lact. reuteri isolates were able to survive at conditions likely to be encountered throughout the gastrointestinal tract. High yields of reuterin may be obtained from selected isolates of Lact. reuteri. Probiotic characteristics of isolates studied in the present work suggest their application in food and feed.


Inclusive Mentorship and Sponsorship.
Mentorship and sponsorship are part of academia because they are vital for professional and personal development. Inclusive mentorship is defined as mentoring across differences. It highlights the need of all mentors to be well-versed culturally and to recognize and circumvent bias and microaggressions. Inclusive mentorship can also elevate underrepresented populations in medicine and create intercultural relationships that also benefit the relationships we have with our diversifying patient populations. There are still several barriers prohibiting inclusive mentorship from being widely understood and employed. This article discusses the importance of and techniques for improving inclusive mentorship.


Adenoviruses as vectors for the transfer of genetic information and for the construction of new type vaccines.
At present many types of corpuscular nondefective, conditional-defective and helper-dependent expressing adenoviral vectors are available which can be used in constructing gene-engineered live or inactivated viral vaccines. In particular, promising results have been obtained with live recombinant human adenoviruses expressing the S antigen of hepatitis B virus, capsid protein of rotaviruses and gB protein of herpes virus. These recombinants are proper candidates for testing as corresponding vaccine strains, a good alternative to well-known recombinant vaccine virus.


Feminizing Leydig cell tumor: endocrine and incubation studies.
A 32-year-old patient with a history of surgery for left gynecomastia four years previously presented with right gynecomastia; a tumor in the left testis proved to be a Leydig cell tumor. Preoperative investigations showed elevated but variable levels of plasma estradiol (E2) and estrone (E1), and reduced serum LH and FSH and plasma testosterone (T). After hCG stimulation, E2 response was increased and abnormally prolonged; T reached normal values, which has predictive value for a return to normal of post-operative T level. After left orchiectomy, gynecomastia regressed within a few days, gonadotropins increased by day 2, estrogens dropped by day 2 and were normal at day 7, T and 5 alpha-dihydrotestosterone dropped at day 2 but reached normal levels at day 16. Pathophysiology of these hormonal data are discussed. An incubation procedure with 3H testosterone showed an aromatase activity 21 times greater in the tumor than in normal peritumoral tissue, while the percentage of the volume occupied by Leydig cells was 34 times higher. This suggests that the aromatase activity of a single tumor cell is very similar to that of a normal Leydig cell. Furthermore, evidence of juxtatumoral Leydig cell hyperplasia in areas where the tumor was well encapsulated suggests the existence of a factor stimulating Leydig cell multiplication.


Current practice patterns and knowledge among gynecologic surgeons of InterStim® programming after implantation.
The objective of this study was to describe surgeons' current practices in InterStim® programming after initial implantation and their knowledge of programming parameters. We hypothesized that surgeons performing their own reprogramming would have increased knowledge. We administered a written survey to attendees at the Society of Gynecologic Surgeons Scientific Meeting and analyzed those on which surgeons indicated they offer InterStim® care. The survey queried surgeon characteristics, experience with InterStim® implantation and programming, and clinical opinions regarding reprogramming and tested six knowledge-based questions about programming parameters. Correct response to all six questions was the primary outcome. One hundred and thirty-five of 407 (33%) attendees returned the survey, of which 99 met inclusion criteria. Most respondents (88 of 99; 89%) were between 36 and 60 years, 27 (73%) were women, 76 (77%) practiced in a university setting, and 76 (77%) were trained in Female Pelvic Medicine and Reconstructive Surgery (FPMRS). Surgeons who had InterStim® programming training were more likely to perform their own programming [15/46 (32%) vs 6/47 (13%), p = 0.03]. Most answered all knowledge-based questions correctly (62/90, 69%); no surgeon characteristics were significantly associated with this outcome. Most surgeons cited patient comfort (71/80, 89%) and symptom relief (64/80, 80%) as important factors when reprogramming, but no prevalent themes emerged on how and why surgeons change certain programming parameters. Surgeons who had formal InterStim® programming training are more likely to perform programming themselves. No surgeon characteristic was associated with improved programming knowledge. We found that surgeons prioritize patient comfort and symptoms when deciding to reprogram.


Conformation-opioid activity relationships of bicyclic guanidines from 3D similarity analysis.
Conformation of bicyclic guanidines with kappa-opioid receptor activity derived in our laboratory from a positional scanning synthetic combinatorial library is presented in this work. We propose a common bioactive conformation and putative pharmacophoric features by means of 3D similarity methods. Our 'Y' shape molecular binding model explains structure-activity relationships and suggests that the guanidine functionality and a 4-methoxybenzyl group may be involved in key interactions with the receptor. Comparison of our model with known opiates suggest a similar binding mode showing that the bicyclic guanidines presented in this work are suitable scaffolds for further development of new opioid receptors ligands.


Early case conferences shorten length of stay in children admitted to hospital with suspected child abuse.
To compare the outcomes of two models for the management of children admitted to hospital with suspected child abuse: routine early case conferencing versus standard evaluation. Between March 2001 and February 2002 professionals from the Royal Children's Hospital, Melbourne, Victoria Police and Child Protection services collaborated on a randomized controlled study involving children admitted to hospital with suspected child abuse. The intervention group (n = 13) received a case conference within 24 h of the child's admission to hospital. The control group (n = 12) were managed according to standard procedures whereby each organization conducted their own evaluation (and a case conference might or might not have been held). Patients were followed for 3 months with data collected from all three professional groups. The process of evaluation, the eventual diagnosis of child abuse and the confidence with which professionals made this diagnosis was not significantly different between the groups. Case conferences were judged to be useful regardless of their timing. Mean length of stay in the intervention group was significantly less than in controls (42.4 h vs 99.7 h, P = 0.01). Early case conferences appear to shorten the period of time children spend in hospital when child abuse is suspected. This has significant implications for reducing costs for all organizations involved in the evaluation of suspected child abuse.


Nosocomial infection with SARS-CoV-2 and main outcomes after surgery within an orthopaedic surgery department in a tertiary trauma centre in Spain.
The purpose of the present study is to analyse clinical data of a series of cases who developed nosocomial infection with SARS-CoV-2 in an orthopaedic and traumatology department. In this non-interventional retrospective study, carried out at a tertiary hospital within the Spanish National Health System, all adult patients who were admitted in the Orthopaedic Surgery and Traumatology Department between March 9th and May 4th, 2020, were included. Clinical, biological and radiological data, as well as mortality rates, were collected from hospital medical records. A total of 293 periods of hospitalization were analysed in 288 patients. Mean age was 66.1 years old and 57.3% were females. Nineteen patients (6.48%) met the inclusion criteria to be categorized as a nosocomial infection with SARS-CoV-2. In a comparison between patients with and without nosocomial infection, age, mortality and hospital length of stay were statistically significant (p < 0.05). The median time from admission to diagnosis of SARS-CoV-2 infection in our cohort was 16 days (6-86 days). No statistically significant differences were found in sex, living situation, reason of admission or period of admission (even if we observed that most of the nosocomial infections (78.9%) occurred in March). We have found a 6.48% of nosocomial infection with SARS-CoV-2, but with an important reduction of it after undergoing preventing protocols that included screening RT-PCR test for COVID-19. Age and hospital length stay were statistically significant risk factors for nosocomial infection with SARS-CoV-2. For the progressive restoration of the surgical activity, we recommend to correctly select the patients in elective surgery and to encourage fast-track programs and early discharge of patients with fractures.


Post-operative fatigue - a real phenomenon attributable to the metabolic effects of surgery on body nutritional stores.
Ambulatory monitoring of activity was undertaken in 97 patients before and at intervals following surgery employing a lightweight recorder and sensors to monitor posture and movement over 24h periods. A subjective assessment of fatigue, anthropometric measurements and clinical details were noted prior to each recording. Results were assessed using multiple regression analysis. Few patients exhibited any subjective feeling of fatigue. However, objective assessment did show a reduction in activity, several of the changes correlating with factors related to surgical stress and post-operative nutritional depletion. Reduction in time standing was related to both weight change at 2 weeks (p < 0.005) and duration of surgery (p < 0.05). Increase in time spent lying correlated with muscle loss at 2 weeks (p < 0.005). Number of steps walked was only influenced by weight change at 2 weeks (p < 0.05). Reduction in post-operative mobility may be related to the metabolic consequences of the surgery and its effects on depletion of nutritional stores. Manipulation of the response and aggressive nutritional support might well reduce post-operative fatigue.


Actual memory as a mediator of the amyloid-subjective cognitive decline relationship.
Amyloid pathology in cognitively normal adults is associated with subjective cognitive decline, potentially reflecting awareness of Alzheimer's-related memory deficits. To clarify the mechanism underlying this relationship, we used mediational analyses to determine the role of depression, anxiety, and actual memory performance. To assess amyloid deposition, we imaged 85 cognitively normal adults with florbetapir positron emission tomography imaging. Subjective cognitive decline was measured using a multidimensional instrument that assessed seven subjective memory domains. Mediational measures included assessments of actual memory performance (current and retrospective longitudinal change), depression, and anxiety. The relationship between amyloid and subjective cognitive decline was mediated by poorer memory performance and greater retrospective memory decline, not depression or anxiety. The mediational roles were significant for domains associated with memory function and memory-related anxiety. In individuals harboring amyloid, self-reported beliefs of declining memory likely indicate early self-awareness of actual worsening function rather than depression or anxiety.


Identification of key regions and residues controlling Aβ folding and assembly.
Amyloid β-protein (Aβ) assembly is hypothesized to be a seminal neuropathologic event in Alzheimer's disease (AD). We used an unbiased D-amino acid substitution strategy to determine structure-assembly relationships of 76 different Aβ40 and Aβ42 peptides. We determined the effects of the substitutions on peptide oligomerization, secondary structure dynamics, fibril assembly dynamics, and fibril morphology. Our experiments revealed that the assembly of Aβ42 was more sensitive to chiral substitutions than was Aβ40 assembly. Substitutions at identical positions in the two peptides often, but not always, produced the same effects on assembly. Sites causing substantial effects in both Aβ40 and Aβ42 include His14, Gln15, Ala30, Ile31, Met35, and Val36. Sites whose effects were unique to Aβ40 include Lys16, Leu17, and Asn 27, whereas sites unique to Aβ42 include Phe20 and Ala21. These sites may be appropriate targets for therapeutic agents that inhibit or potentiate, respectively, these effects.


Understanding why decision aids work: linking process with outcome.
Decision aids help patients make treatment choices. There is little empirical evidence to explain how they work. The results from this randomised controlled trial comparing routine with decision-aided consultations in the prenatal diagnosis for Down's syndrome context are used to describe the strategies employed during decision making, to assess the impact of a decision aid on decision processes, and to investigate decision process and outcome associations. Data were elicited from two content analyses of consultation transcripts and questionnaires assessing knowledge, anxiety, decisional conflict, reasons, and information usefulness. 68/106 women completed measures at consultation and follow-up. Decision-aided women employed more cognitive and emotional strategies during decision making. More negative evaluations during decision making were associated with better outcomes. Decision-aided consultations facilitated the employment of strategies associated with more effective choices. These consultations take longer and elicit greater expressions of negative affect, so may be less rewarding encounters for health professionals.


Saccular aortic aneurysm causing complete distal esophageal obstruction.
We have reported a case of progressive dysphagia and complete esophageal occlusion due to a saccular aortic aneurysm. Aortic aneurysm should be an initial consideration in the differential diagnosis and investigation of dysphagia. Complete esophageal occlusion is a rare and late manifestation of a saccular thoracic aortic aneurysm and has been fatal in two of the three reported cases. Prompt preoperative diagnosis and aortic repair has not yet been reported.


A flow-calorimetric study of the binding of iodine to amylodextrin fractions.
Acid hydrolyzates of waxy-maize starch were separated to give Fractions I, II, and III [T. Watanabe, and D. French, Carbohydr. Res., 84 (1980) 115-123]. Watanabe and French suggested that Fraction II, which contains approximately 25 D-glucose residues including an alpha-D-(1----6)-linked branch, has a double helical structure. In the present study, the thermodynamics of binding of iodine to Fractions II and III, and debranched Fraction II (Fraction II') was measured by isothermal-flow calorimetry. If four binding sites for Fraction II and two for Fractions II' and III are assumed, the standard free-energy changes, delta Gb0, for the binding of I2 are -18.5, -18.8, and -18.4 kJ X (mol I2)-1, and the enthalpy changes, delta Hb, are -28.4, -24.7, and -26.9 kJ X (mol I2)-1, respectively. The similarity of these values for the three fractions indicates that the conformation of Fraction II is essentially the same as those of Fractions II' and III, and that Fraction II, therefore, does not have a double helical structure in solution. The values for delta Gb0 are approximately 15 kJ X mol-1 less negative, and those for delta Hb approximately 40 kJ X mol-1 less negative than published values for the starch-I2 complex. These differences are due to the relatively very short D-glucose chains in the amylodextrin fractions employed in the present work.


Estrogenic regulation of diamine oxidase activity in rat uterus.
Diamine oxidase activity was studied in female rat tissues during the estrous cycle and after 17 beta-estradiol administration. During the estrous cycle, uterine and hepatic enzyme activities were highest at proestrus and lowest at estrus, when estrogen plasma levels are known to be respectively high and low. The administration of 17 beta-estradiol to ovariectomized rats caused a rapid and prolonged increase in enzyme activity in uterus and only a transient increase in the liver. Such increases were prevented by cycloheximide and by actinomycin D administration. No changes were observed in renal enzyme activity during estrus or after hormone treatment. Our data suggest that estrogens regulate diamine oxidase activity in rat uterus by a mechanism of enzyme induction.


Retrograde left ventricular catheterization in patients with an aortic valve prosthesis.
Twenty-seven consecutive patients with an aortic valve prosthesis were evaluated with retrograde left ventricular catheterization. The prosthesis was successfully crossed, permitting hemodynamic and angiographic evaluation of function of the prosthetic valve, left ventricle and mitral valve in all 27 cases. No complications were encountered. In patients with active endocarditis or recent embolization, the retrograde technique was avoided when possible, and attempts were made to utilize other techniques for study. However, three such patients were evaluated with the retrograde technique without complication. Examination of pressure tracings and cineangiographic films suggested only minor interference with valve poppet movement induced by the catheter transversing the valve. In three cases, hemodynamic data were recorded with the catheter crossing the prosthesis at one time and a paraprosthetic valve defect at another time. Identical gradients were recorded. This series documents the safety and efficacy of the retrograde approach, which is proposed as an alternative to the transseptal technique and left ventricular puncture.


Formatively assessing prospective teachers' skills in leading mathematics discussions.
Mathematics discussions are important for helping students to develop conceptual understanding and to learn disciplinary norms and practices. In recent years, there has been increased attention to teaching prospective teachers to lead discussions with students. This paper examines the possibilities of designing a formative assessment that gathers information about prospective elementary teachers' skills with leading problem-based mathematics discussions and makes sense of such information. A decomposition of the practice of leading discussions was developed and used to design the assessment. Nine first-year teachers who graduated from a range of different teacher education programs participated in the study. The findings reveal that our formative assessment works to gather information about teachers' capabilities with leading discussions and that the associated tools support making sense of the information gathered. This suggests that such tools could be useful to support the formative assessment of the developing capabilities of prospective teachers.


Transcriptional response of giant reed (Arundo donax L.) low ecotype to long-term salt stress by unigene-based RNAseq.
The giant reed is a fast growing herbaceous non-food crop considered as eligible alternative energy source to reduce the usage of fossil fuels. Tolerance of this plant to abiotic stress has been demonstrated across a range of stressful conditions, thus allowing cultivation in marginal or poorly cultivated land in order not to compromise food security and to overcome land use controversies. In this work, we de novo sequenced, assembled and analyzed the A. donax low G34 ecotype leaf transcriptome (RNAseq analysis) subjected to severe long-term salt stress (256.67 mM NaCl corresponding to 32 dS m-1 electric conductibility). In order to shed light upon the response to high salinity of this non model plant, we analyzed clusters related to salt sensory and signaling transduction, transcription factors, hormone regulation, Reactive Oxygen Species (ROS) scavenging and osmolyte biosynthesis, all of them showing different regulation compared to untreated plants. The analysis of clusters related to ethylene biosynthesis and signaling indicated that gene transcription is modulated towards the minimization of ethylene negative effects upon plant growth. Certainly, the photosynthesis is strongly affected since genes involved in Rubisco biosynthesis and assembly are down-regulated. However, a shift towards C4 photosynthesis is likely to occur as gene regulation is aimed to activate the primary CO2 fixation to PEP (phosphoenolpyruvate). The analysis of "carbon metabolism" category revealed that G34 ecotype under salt stress induces the expression of glycolysis and Krebs cycle related genes, this being consistent with the hypothesis that some sort of salt avoidance might be occurred in A. donax G34 low ecotype. By comparing our results with findings obtained with other giant reed ecotype, we identified several differences in the response to salt that are in accordance with the possibility that heritable phenotypic differences among clones of A. donax might be accumulated especially in ecotypes originating from distant geographical areas, despite their asexual reproduction modality. Additionally, 26,838 simple sequence repeat (SSR) markers were identified and validated. This SSR dataset definitely expands the marker catalogue of A. donax facilitating the genotypic characterization of this species.


The achievement by proxy spectrum in youth sports. Historical perspective and clinical approach to pressured and high-achieving children and adolescents.
This article, with examples of the descriptively defined three stages of achievement by proxy distorted (ABPD) behavior, should increase awareness of this field by facilitating communication, enabling child psychiatrists and other professionals to identify the "red flags" that can lead to abuse and exploitation of children and adolescents, and further contributing toward psychoeducation of self-help skills in parents and other adults with the goal of understanding motivations for ABPD behaviors and risky rationalizations, in addition to creating prevention strategies.


Inhibition of macrophage migration in zebrafish larvae demonstrates in vivo efficacy of human CCR2 inhibitors.
The chemokine signaling axes CCR2-CCL2 and CXCR3-CXCL11 participate in the inflammatory response by recruiting leukocytes to damaged tissue or sites of infection and are, therefore, potential pharmacological targets to treat inflammatory disorders. Although multiple CCR2 orthosteric and allosteric inhibitors have been developed, none of these compounds has been approved for clinical use, highlighting the need for a fast, simple and robust preclinical test system to determine the in vivo efficacy of CCR2 inhibitors. Herein we show that human CCL2 and CXCL11 drive macrophage recruitment in zebrafish larvae and that CCR2 inhibitors designed for humans also limit macrophage recruitment in this model organism due to the high conservation of the chemokine system. We demonstrated anti-inflammatory activities of three orthosteric and two allosteric CCR2 inhibitors using macrophage recruitment to injury as a functional read-out of their efficiency, while simultaneously evaluating toxicity. These results provide proof-of-principle for screening CCR2 inhibitors in the zebrafish model.


Is renal cell (Grawitz) tumor a carcinosarcoma? Evidence from analysis of intermediate filament types.
The expression of intermediate filament type was determined in 13 renal cell (Grawitz) tumors (10 primary renal tumors and 3 lymph node metastases). All of the tumors except one lymph node metastasis contained cells expressing vimentin intermediate filaments, generally a marker of mesodermally-derived tissues and their tumors, the sarcomas. In addition, the 10 primary renal tumors and two lymph node metastases contained cells expressing keratin proteins. Using a monoclonal antibody to keratins, specific for glandular epithelial cells, it has been shown that some of the tumor cells resemble adenocarcinomas, at least in this respect. Double immunofluorescence labeling demonstrated that some of the vimentin-containing cells contained keratin while others did not. Only occasional cells were found to contain keratin but not vimentin. However, one of the lymph node metastases was positive only for vimentin. Thus Grawitz tumor cells express intermediate filament types which are generally biological markers of both sarcomatous and carcinomatous tumors.


A novel acute toxicity resulting from the administration of morphine and adriamycin to mice.
The toxic potential of the combination of morphine and Adriamycin (doxorubicin) has been evaluated in mice. Intravenous administration of 20 or 40 mg Adriamycin/kg resulted in a dose-related mortality beginning 4 days postdose. Increasing the dose of Adriamycin to 75 mg/kg caused a biphasic mortality pattern, with 30% of the animals dying within 30 min of drug treatment. Pretreatment with morphine (20 mg/kg) reduced by 80% the dose of Adriamycin required to induce a 30% mortality at 30 min post-Adriamycin administration. Morphine pretreatment also caused a dose-dependent increase in plasma Adriamycin, as measured by total plasma fluorescence. Morphine or Adriamycin administered alone resulted in a slight hematocrit increase. The combination of morphine and Adriamycin caused an increase in hematocrit to maximal levels of approximately 75% from basal levels of about 48%. The increase in hematocrit after morphine plus Adriamycin exceeded the rise caused by higher doses of Adriamycin which, without morphine, resulted in similar plasma Adriamycin levels. The temporal relationship between the elevated hematocrit and early (30 min) mortality suggest a cause/effect relationship between these two events following combined morphine plus Adriamycin treatment.


Congenital atresia of the colon combined with segmental dilatation of the ileum: a case report.
Atresia of the colon is a rare form of congenital intestinal atresia. Other gastrointestinal anomalies have been reported in these patients, but to our knowledge, the association between colonic atresia and segmental dilatation of the ileum has not been reported.