Metaplastic carcinoma of the breast: fine-needle aspiration cytology of seven cases.
We describe the cytomorphology of seven cases of metaplastic carcinoma of the breast studied by fine-needle aspiration cytology and by histology. All seven cases contained foci of ductual adenocarcinoma. This finding was combined with heterologous mesenchymal elements in four cases, a spindle-cell pattern of growth in one case, and extensive squamous-cell metaplasia in two cases. Both carcinomatous and metaplastic components were present on smears in four cases (57%). Thus in three cases (43%), the diagnosis was not possible on smear material alone. Differential diagnostic considerations are discussed.


Pollutant gas and particulate material emissions in ethanol production in Brazil: social and environmental impacts.
The replacement of fossil-based fuels by renewable fuels (biofuels) was proposed in the IPCC report, as an alternative to reduce greenhouse gas emission and reach out to a low-carbon economy. On this perspective, the Brazilian government had implemented a renewable energy program based on the use of ethanol in the transport sector. This work evaluates the scenario of pollutant gas emissions and particulate material that comes from the biomass burning process involved in ethanol production cycle, in the city of Campos dos Goytacazes, Brazil. The gases and particulate material emitted by sugarcane and bagasse burning processes-the last one in energy co-generation mills-were analyzed. A laboratory-controlled burning of both samples was realized in an oven with temperature ramp from 250 to 400 °C, at a regular rate of 50 °C. The gas samples were collected directly from the oven's exhaust pipe. The particulates obtained were the residual material taken out of the burned samples: a powder with the aspect of soot. A photoacoustic spectroscopy system coupled with quantum cascade laser and electrochemical analyzers was used to measure the emission of polluting gases such as N2O, CO2, CO, NOx (NO, NO2), and SO2 in ppmv range. Fluorescent X-ray spectrometry was applied to evaluate the chemical composition of particulate material, enabling the identification of elements such as Si, Al, Ca, K, Fe, S, P, Ti, Mn, Cu, Zn, Sc, V, Cu, and Sr.


Cooper pair splitting in parallel quantum dot Josephson junctions.
Devices to generate on-demand non-local spin entangled electron pairs have potential application as solid-state analogues of the entangled photon sources used in quantum optics. Recently, Andreev entanglers that use two quantum dots as filters to adiabatically split and separate the quasi-particles of Cooper pairs have shown efficient splitting through measurements of the transport charge but the spin entanglement has not been directly confirmed. Here we report measurements on parallel quantum dot Josephson junction devices allowing a Josephson current to flow due to the adiabatic splitting and recombination of the Cooper pair between the dots. The evidence for this non-local transport is confirmed through study of the non-dissipative supercurrent while tuning independently the dots with local electrical gates. As the Josephson current arises only from processes that maintain the coherence, we can confirm that a current flows from the spatially separated entangled pair.


A new approach to zip-lignin: 3,4-dihydroxybenzoate is compatible with lignification.
Renewed interests in the development of bioenergy, biochemicals, and biomaterials have elicited new strategies for engineering the lignin of biomass feedstock plants. This study shows, for the first time, that 3,4-dihydroxybenzoate (DHB) is compatible with the radical coupling reactions that assemble polymeric lignin in plants. We introduced a bacterial 3-dehydroshikimate dehydratase into hybrid poplar (Populus alba × grandidentata) to divert carbon flux away from the shikimate pathway, which lies upstream of lignin biosynthesis. Transgenic poplar wood had up to 33% less lignin with p-hydroxyphenyl units comprising as much as 10% of the lignin. Mild alkaline hydrolysis of transgenic wood released fewer ester-linked p-hydroxybenzoate groups than control trees, and revealed the novel incorporation of cell-wall-bound DHB, as well as glycosides of 3,4-dihydroxybenzoic acid (DHBA). Two-dimensional nuclear magnetic resonance (2D-NMR) analysis uncovered DHBA-derived benzodioxane structures suggesting that DHB moieties were integrated into the lignin polymer backbone. In addition, up to 40% more glucose was released from transgenic wood following ionic liquid pretreatment and enzymatic hydrolysis. This work highlights the potential of diverting carbon flux from the shikimate pathway for lignin engineering and describes a new type of 'zip-lignin' derived from the incorporation of DHB into poplar lignin.


Thymosin β4 stabilizes hypoxia-inducible factor-1α protein in an oxygen-independent manner.
The small actin-binding protein thymosin β4 (Tβ4) is understood to stimulate angiogenesis. Previously, we reported that Tβ4 induces angiogenesis by increasing vascular endothelial growth factor (VEGF) expression, but the mechanism underlying how Tβ4 upregulates VEGF expression remain unknown. To identify the mechanism of VEGF induction by Tβ4, we measured VEGF promoter activity and analyzed the effect of Tβ4 on VEGF RNA stability. The Tβ4 peptide had no effect on either VEGF promoter activity or VEGF RNA stability. We focused on the possibility that Tβ4 may indirectly induce VEGF expression via hypoxia-inducible factor (HIF)-1α. We determined that Tβ4 increased the stability of HIF-1α protein under normoxic conditions. These data suggest that Tβ4 indirectly induces VEGF expression by increasing the protein stability of HIF-1α in an oxygen-independent manner.


In-situ electrodeposited Co0.85Se@Ni3S2 heterojunction with enhanced performance for supercapacitors.
Rational design of porous heterostructured electrode materials for high-performance supercapacitors remains a big challenge. Herein, we report the in situ synthesis of Co0.85Se@Ni3S2 hybrid nanosheet arrays supported on carbon cloth (CC) substrate though an efficient two-step electrodeposition method. Compared with pure Co0.85Se and Ni3S2, the well-defined Co0.85Se@Ni3S2 heterojunction possesses enriched active sites, improved electrical conductivity, and reduced ion diffusion resistance. Benefiting from its hierarchically porous nanostructure and the synergistic effect of Co0.85Se and Ni3S2, the as-synthesized Co0.85Se@Ni3S2 electrode delivers a gravimetric capacitance (Cg)/volumetric capacitance (Cv) of 1644.1F g-1/3161.7F cm-3 at 1 A g-1, outstanding rate capability of 60.7% capacitance retention at 20 A g-1, as well as good cycling performance of 87.8% capacitance retention after 5000 cycles. Additionally, a hybrid supercapacitor (HSC) device presents a maximum energy density (E) of 65.7 Wh kg-1 at 696.2 W kg-1 with 93.3% cyclic durability after 15,000 cycles. Thus, this work proposes a simple and effective strategy to fabricate porous heterojunctions as high-performance electrode materials for energy storage devices.


Radiologically-guided percutaneous catheter drainage of empyemas.
We describe our experience with the percutaneous drainage of empyemas in 20 patients, using fluoroscopic, computed tomographic or ultrasonic guidance for catheter placement. The patients were seen over a period of 17 months. Sixteen patients were successfully treated, with the empyema drained and the cavity closed. In four patients drainage was unsuccessful and surgery was required. In three of these patients there was a history of illness in excess of 4 weeks preceding treatment and in one a history of trauma. Two or more catheters were used in seven patients and positive microbiological culture of the pus was obtained in 12, although neither factor significantly altered prognosis. There were no complications of the procedure. We believe the percutaneous insertion of catheters using suitable imaging guidance should be the initial method of drainage of empyemas.


Predictive simulation of gait at low gravity reveals skipping as the preferred locomotion strategy.
The investigation of gait strategies at low gravity environments gained momentum recently as manned missions to the Moon and to Mars are reconsidered. Although reports by astronauts of the Apollo missions indicate alternative gait strategies might be favored on the Moon, computational simulations and experimental investigations have been almost exclusively limited to the study of either walking or running, the locomotion modes preferred under Earth's gravity. In order to investigate the gait strategies likely to be favored at low gravity a series of predictive, computational simulations of gait are performed using a physiological model of the musculoskeletal system, without assuming any particular type of gait. A computationally efficient optimization strategy is utilized allowing for multiple simulations. The results reveal skipping as more efficient and less fatiguing than walking or running and suggest the existence of a walk-skip rather than a walk-run transition at low gravity. The results are expected to serve as a background to the design of experimental investigations of gait under simulated low gravity.


Advances in the Treatment of Food Allergy: Sublingual and Epicutaneous Immunotherapy.
Food allergies continue to increase in prevalence. Standard care is a strict elimination diet, but life-threatening reactions still occur. Allergen immunotherapy has the most potential in treating food allergy. Subcutaneous immunotherapy has not been adopted into food allergy therapy. Oral immunotherapy has a high rate of adverse reactions. Sublingual immunotherapy (SLIT) uses the tolerogenic environment of the oral mucosa and epicutaneous immunotherapy (EPIT) uses the immune cells of the epidermis to transport antigens to afferent lymph nodes to activate immune responses. SLIT and EPIT can successfully desensitize patients. More research is needed to define optimal doses and administration protocols.


Simulation does not just inform choice, it changes choice.
Simulation - imagining future events - plays a role in decision-making. In Conviction Narrative Theory, people's emotional responses to their simulations inform their choices. Yet imagining one possible future also increases its plausibility and accessibility relative to other futures. We propose that the act of simulation, in addition to affective evaluation, drives people to choose in accordance with their simulations.


Biological actions of human and rat calcitonin and calcitonin gene-related peptide.
We assessed the central and peripheral biological actions of human and rat calcitonin and calcitonin gene-related peptide (CGRP). After intravenous administration, human and rat calcitonin, but neither human nor rat CGRP significantly decreased plasma calcium and phosphorus concentrations in awake, freely moving rats. After intracerebroventricular as well as after intravenous administration, human and rat calcitonin and human and rat CGRP significantly inhibited gastric acid secretion in conscious rats. Intracerebroventricular administration of rat calcitonin did not alter plasma calcium and phosphorus concentrations. Linear, partially protected CGRP and calcitonin did not exhibit any biological effects. These studies indicate that calcitonin, but not CGRP, affects calcium and phosphorus homeostasis while both peptides decrease gastric acid secretion similarly. Furthermore, these studies support the hypothesis that the calcium and phosphorus lowering effects of calcitonin are peripheral while the gastric inhibiting actions of the calcitonin and CGRP are mediated by the central nervous system.


Prognosis of patients removed from a transplant waiting list for medical improvement: implications for organ allocation and transplantation for status 2 patients.
To address the present controversy regarding optimal management of status 2 heart transplant candidates, we studied the short- and long-term fate of medically improved patients removed from our transplant waiting list to assess return of heart failure and occurrence of sudden cardiac death, identify interventions to improve outcomes, and compare their survival with that of similar transplanted patients. From January 1985 to February 2004, 100 status 2 patients were delisted for medical improvement (median on-list duration, 314 days). Return of heart failure, sudden cardiac death, and all-cause mortality were determined from follow-up (mean, 7.7 +/- 3.9 years among survivors; 10% followed >12 years). Hazard function modeling, competing-risks analyses, simulation, and propensity matching to equivalent patients undergoing transplantation were used to analyze and compare outcomes and predict benefit of interventions. Freedom from return of heart failure was 77% at 5 years. The most common mode of death was sudden cardiac death, with risk peaking at 2.5 years after delisting but remaining at 3.5% per year thereafter. Event-free survival at 1, 5, and 10 years was 94%, 55%, and 28%, respectively; simulation demonstrated that implantable cardioverter-defibrillators could have improved this to 45% at 10 years. Overall survival after delisting was better than that of matched status 2 patients who underwent transplantation, but was demonstrably worse after 30 months. Status 2 patients, including those delisted, require vigilant surveillance and optimal medical management, implantable cardioverter-defibrillators, and a revised approach to transplantation timing, such that overall salvage is maximized while allocation of scarce organs is optimized.


Determination of glucose turnover in sea bass Dicentrarchus labrax. Comparative aspects of glucose utilization.
1. Parameters of in vivo glucose utilization by sea bass (132 +/- 6 g, mean +/- SEM) acclimated at 15 degrees C in sea-water were measured after single injection of labelled glucose. 2. Glucose turnover rate (RG; mumol . min-1 . kg-1) was found to be 0.55-065 (2-3H glucose) and 0.34 +/- 0.42 (U14C glucose). 3. Glucose transit time was 443-449 min, glucose mass 233-261 mumol . kg-1, and glucose recycling 37%. 4. Oxygen consumption (MO2) amounted to 94 +/- 6.2 mumol . min-1 . kg-1. 5. The comparison with other fish species, mammals and birds, taking into account body size, temperature, diet, exercise, in poikilotherms and homeotherms leads to the calculation of a glucose turnover index (RGI = RG x 6 x 100 x MO2(-1)). 6. Value of this, generally lower in ectotherm teleosts (2-9), than in endotherms: mammals, birds and thunidae (22-60), confirms the minor quantitative importance of glucose in the metabolism of most fish.


Abnormal functional connectivity in women with urgency urinary incontinence: Can we predict disease presence and severity in individual women using Rs-fcMRI/.
To identify atypical brain functional connectivity in women with UUI and detrusor overactivity (DO) and to predict the presence/severity of UUI in individual women using connectivity features. This is a cross-sectional study comparing brain functional connectivity in women with and without UUI. Validated symptom/quality of life questionnaires were used for phenotyping. Participants are females between ages 40 and 85 with daily UUI with DO (Cases, N = 16) and without UUI (Controls, N = 24). Functional MRI and Resting state connectivity MRI were obtained at empty/ full bladder. Multivariate pattern analysis (MVPA) was used to predict the presence and severity of UUI from connectivity data. There are significant differences in brain activation between cases and controls in eighteen brain regions irrespective of empty or full bladder. These include regions involved in attention (inferior partietal), decision making (inferior and superior frontal gyrus), primary motor and sensory (precentral and postcentral gyrus) functions. Women with UUI showed no change in connectivity with bladder filling in regions involved in interoception (insula), integration of afferent function (anterior cingulate), and decision making (middle frontal). MVPA of connectivity data showed robust classification of an individual woman as case or control (89% sensitivity, 83% specificity). Six connectivity features accurately predicted disease severity (R(2) = 0.81). We identified two mechanisms of abnormal bladder control, one involving atypical activation of brain regions, and another atypical functional integration across sensory, emotional, cognitive and motor regions. Connectivity information is robust enough to classify an individual as having UUI or not and to predict symptom severity. Neurourol. Urodynam. 35:564-573, 2016. © 2015 Wiley Periodicals, Inc.


Effects of extracellular vesicles derived from oral bacteria on osteoclast differentiation and activation.
Dysbiosis of the oral microbiota plays an important role in the progression of periodontitis, which is characterized by chronic inflammation and alveolar bone loss, and associated with systemic diseases. Bacterial extracellular vesicles (EVs) contain various bioactive molecules and show diverse effects on host environments depending on the bacterial species. Recently, we reported that EVs derived from Filifactor alocis, a Gram-positive periodontal pathogen, had osteoclastogenic activity. In the present study, we analysed the osteoclastogenic potency and immunostimulatory activity of EVs derived from the Gram-negative periodontal pathogens Porphyromonas gingivalis and Tannerella forsythia, the oral commensal bacterium Streptococcus oralis, and the gut probiotic strain Lactobacillus reuteri. Bacterial EVs were purified by density gradient ultracentrifugation using OptiPrep (iodixanol) reagent. EVs from P. gingivalis, T. forsythia, and S. oralis increased osteoclast differentiation and osteoclstogenic cytokine expression in osteoclast precursors, whereas EVs from L. reuteri did not. EVs from P. gingivalis, T. forsythia, and S. oralis preferentially activated Toll-like receptor 2 (TLR2) rather than TLR4 or TLR9, and induced osteoclastogenesis mainly through TLR2. The osteoclastogenic effects of EVs from P. gingivalis and T. forsythia were reduced by both lipoprotein lipase and polymyxin B, an inhibitor of lipopolysaccharide (LPS), while the osteoclastogenic effects of EVs from S. oralis were reduced by lipoprotein lipase alone. These results demonstrate that EVs from periodontal pathogens and oral commensal have osteoclastogenic activity through TLR2 activation by lipoproteins and/or LPS.


A comparison of skin prick tests, intradermal skin tests, and specific IgE in the diagnosis of mouse allergy.
Mouse sensitization is assessed by using skin testing and serum levels of mouse allergen-specific IgE (m-IgE). However, it is unknown whether a positive skin test response or m-IgE result accurately identifies those with clinically relevant mouse sensitization. We sought to compare skin testing and m-IgE measurement in the diagnosis of mouse allergy. Sixty-nine mouse laboratory workers underwent skin prick tests (SPTs), intradermal tests (IDTs), and serum IgE measurements to mouse allergen, followed by nasal challenge to increasing concentrations of mouse allergen. Challenge response was assessed by nasal symptom score. Thirty-eight women and 31 men with a mean age of 30 years were studied. Forty-nine workers reported mouse-related symptoms, of whom 10 had positive m-IgE results and 12 had positive SPT responses. Fifteen had negative SPT responses but positive IDT responses. Positive nasal challenges were observed in 70% of workers with positive m-IgE results, 83% of workers with positive SPT responses, 33% of workers with negative SPT responses/positive IDT responses, and 0% of workers with negative IDT responses. SPTs performed best, having the highest positive and negative predictive values. Among participants with a positive challenge result, those with a positive SPT response or m-IgE result had a significantly lower challenge threshold than those with a positive IDT response (P = .01). Workers with a positive challenge result were more likely to have an increase in nasal eosinophilia after the challenge compared with those with a negative challenge result (P = .03). SPTs perform best in discriminating patients with and without mouse allergy. Mouse-specific IgE and IDTs appear to be less useful than SPTs in the diagnosis of mouse allergy.


When to stop? Mammographic surveillance in breast cancer survivors aged 70 years and older.
To assess the rates of breast cancer detected in postoperative surveillance mammograms in women >70 Years and overall mortality in this age group. Four hundred and ninety-eight patients were identified retrospectively from a database from a single large UK hospital. Patients were included in the study if they were female, aged >70 years at diagnosis of either invasive breast cancer or ductal carcinoma in situ (DCIS), had surgical treatment between 1 January 2010 and 31 December 2014, and no previous diagnosis of breast cancer. Statistical analysis was performed using Excel, using the X2 test, with p ≤ 0.05 considered statistically significant. The mean age of women included in this study was 77 years. The mean number of postoperative surveillance mammograms performed per patient was 4.2. In the 5-year follow-up, there was a local recurrence rate of 1.9% (n=6) and a contralateral breast cancer rate of 1% (n=6). The 5-year overall mortality rate was 17.7% (n=88), and the 5-year breast cancer-specific mortality rate was 7.2% (n=36). This study demonstrated low local recurrence and contralateral breast cancer rates during the 5-year follow-up period. Clear discussions therefore need to be held with older patients about the value of postoperative mammographic surveillance. Further research is required regarding patient opinion and experience to help develop more consistent guidelines.


Unique microtubules in luteal cells from superovulated rats.
Luteal cells of immature female rats treated with gonadotropins contain microtubules with a number of interesting features. Many of the microtubules of these cells are arranged in bundles in which they are separated one from another by strands of material (i-MT bands) of unknown composition. The microtubules within the bundles assume a hexagonal packing pattern with i-MT bands between any two microtubules. The bundle microtubules and their i-MT bands are further connected via crosslinking filaments: pattern obtained from densitometer scans (measuring the arrangement of the crosslinking filaments) suggest that the filaments may represent microtubule-associated proteins. The complex arrangement of the microtubules within a bundle does not appear to extend for the entire length of the individual microtubules, and occasionally one sees profiles of single microtubules fanning out from the ends of the bundle: whether the same microtubules are regrouped at some other point in the cell is not known. Structures similar to the i-MT band and the crosslinking filaments have also been observed connecting microtubules to segments of the luteal cell plasma membrane: in these instances the i-MT-like band is found between the longitudinally sectioned microtubule and the membrane, with filaments connecting the two structures via the intermediate band. It is of interest that the microtubules of these luteal cells are not sensitive to treatment with antimicrotubule drugs and we suggest that the complex bundling arrangement provides their unusual stability.


Response of Salvinia molesta to insect damage: changes in nitrogen, phosphorus and potassium content.
When adults and larvae of the weevil Cyrtobagous salviniae destroyed buds and tunnelled through rhizomes of Salvinia molesta, the plant responded by producting new growth which contained higher concentrations of nitrogen than in undamaged plants or in the older parent tissue of the same plant. Damage to leaves by the moth, Samea multiplicalis did not induce the same response. C. salviniae fed on the new growth and the higher nitrogen intake would have increased its reproductive capacity and enhanced its action as a biological control agent.Damage by both insects resulted in potassium leaching from the plant but no change in concentrations of phosphorus. The results support earlier suggestions that damage by C. salviniae might improve the qualtity of the host plant for this herbivore.


Cell free translation of rat adrenal messenger RNA coding for an ACTH-induced protein.
Protein markers induced by hormones are the necessary probes to study hormone regulation of gene expression. We have previously shown that ACTH was able to induce one of these markers in the cytosol of the rat adrenal: protein E (Dazord et al, Biochem. J., 176, 233-239, 1978). In this paper by using adrenal mRNA from control and in vivo ACTH treated rats as well as protein E antibodies, we show that: 1) ACTH affects both the amount of adrenal mRNA and its translational activity; 2) the translation of protein E is increased by the hormone; 3) protein E is the major translational product following ACTH treatment.


Cardiac Strangulation Due to Partial Pericardial Defect Presenting as Acute Myocardial Infarction.
A 79-year-old man with chest pain and dyspnea underwent emergency percutaneous coronary intervention for acute myocardial infarction. However, he died 17 days later due to refractory heart failure. An autopsy revealed cardiac strangulation caused by herniation of the apical heart through a pericardial defect due to partial absence of the pericardium. (Level of Difficulty: Advanced.).


Transcatheter ablation of arrhythmias associated with congenital heart disease.
The improvement of surgical techniques resulted in significant life prolongation of many young patients with congenital heart disease (CHD). However, as these patients reach adulthood, their risk for late complications associated with surgery is also increased. One of the most difficult challenges associated with CHD is the high incidence of cardiac arrhythmias that arise from either the myocardial substrate created by abnormal physiology (pressure/volume changes, septal patches, and suture lines) or the presence of surgical scar. Catheter ablation is proven to be effective in treating atrial and ventricular arrhythmias in structurally normal hearts, and has also been used to treat arrhythmias in adults with congenital heart disease. In this review we provide an overview about diagnostic challenges, mapping and ablation techniques and outcome of patients undergoing transcatheter ablation procedures.


Scientific evidence of the association between oral intake of OMEGA-3 and OMEGA-6 fatty acids and the metabolic syndrome in adolescents: A systematic review.
To conduct a systematic review of the literature on the scientific evidence of the oral intake of omega-3 and omega-6 FAs and metabolic syndrome (MS) in adolescents. The study was registered in PROSPERO (number 42020185370). Studies were carried out with adolescents aged 10-19 years, who presented as intervention/exposure the oral intake of omega-3 and/or omega-6 fatty acids (FAs), in the databases PubMed, Scopus, Web of Science, LILACS, CENTRAL, and PQDT Global e BDTD. The tools used to assess the risk of bias were RoB 2.0, Agency for Healthcare Research and Quality (AHRQ), and Newcastle-Ottawa Scale. Fifteen papers retrieved published from 2010 to 2019 were included (n = 3534); nine were randomized studies and controlled clinical trials, four were cross-sectional studies, one was a retrospective cohort study, and one case-control study. No studies have evaluated the effect or association of omega-3 and/or of omega-6 FAs with actual MS, only with its components. The randomized clinical trials identified the effects of omega-3 FA on the decrease in blood pressure (n = 1 out of six), glycemia (n = 2 out of seven), and triglycerides (n = 5 out of eight), and the increase in HDL-c (n = 2 out of eight) considering the comparison between the group that received omega-3 FA and the control group. Scientific evidence is controversial on the association between oral intake of omega-3 FAs and MS in adolescents, due to the heterogeneity between studies and the divergence of results for the same MS component.


Expression of cardiac alpha-actin spares extraocular muscles in skeletal muscle alpha-actin diseases--quantification of striated alpha-actins by MRM-mass spectrometry.
As with many skeletal muscle diseases, the extraocular muscles (EOMs) are spared in skeletal muscle alpha-actin diseases, with no ophthalmoplegia even in severely affected patients. We hypothesised that the extraocular muscles sparing in these patients was due to significant expression of cardiac alpha-actin, the alpha-actin isoform expressed in heart and foetal skeletal muscle. We have shown by immunochemistry, Western blotting and a novel MRM-mass spectrometry technique, comparable levels of cardiac alpha-actin in the extraocular muscles of human, pig and sheep to those in the heart. The sparing of extraocular muscles in skeletal muscle alpha-actin disease is thus probably due to greater levels of cardiac alpha-actin, than the negligible amounts in skeletal muscles, diluting out the effects of the mutant skeletal muscle alpha-actin.


Local miRNA-Dependent Translational Control of GABAAR Synthesis during Inhibitory Long-Term Potentiation.
Molecular mechanisms underlying plasticity at brain inhibitory synapses remain poorly characterized. Increased postsynaptic clustering of GABAA receptors (GABAARs) rapidly strengthens inhibition during inhibitory long-term potentiation (iLTP). However, it is unclear how synaptic GABAAR clustering is maintained to sustain iLTP. Here, we identify a role for miR376c in regulating the translation of mRNAs encoding the synaptic α1 and γ2 GABAAR subunits, GABRA1 and GABRG2, respectively. Following iLTP induction, transcriptional repression of miR376c is induced through a calcineurin-NFAT-HDAC signaling pathway and promotes increased translation and clustering of synaptic GABAARs. This pathway is essential for the long-term expression of iLTP and is blocked by miR376c overexpression, specifically impairing inhibitory synaptic strength. Finally, we show that local de novo synthesis of synaptic GABAARs occurs exclusively in dendrites and in a miR376c-dependent manner following iLTP. Together, this work describes a local post-transcriptional mechanism that regulates inhibitory synaptic plasticity via miRNA control of dendritic protein synthesis.


Are Purple Finches (Haemorhous purpureus) the Next Host for a Mycoplasmal Conjunctivitis Epidemic?
Ever since 1994, when the bacterial pathogen Mycoplasma gallisepticum jumped from poultry to wild birds, it has been assumed that the primary host species of this pathogen in wild North American birds was the house finch (Haemorhous mexicanus), in which disease prevalence was higher than in any other bird species. Here we tested two hypotheses to explain a recent increase in disease prevalence in purple finches (Haemorhous purpureus) around Ithaca, New York. Hypothesis 1 is that, as M. gallisepticum evolved and became more virulent, it has also become better adapted to other finches. If this is correct, early isolates of M. gallisepticum should cause less-severe eye lesions in purple finches than in house finches, while more-recent isolates should cause eye lesions of similar severity in the two species. Hypothesis 2 is that, as house finch abundance declined following the M. gallisepticum epidemic, purple finches around Ithaca increased in abundance relative to house finches and purple finches are thus more frequently exposed to M. gallisepticum-infected house finches. This would then lead to an increase in M. gallisepticum prevalence in purple finches. Following an experimental infection with an early and a more-recent M. gallisepticum isolate, eye lesions in purple finches were more severe than in house finches. This did not a support Hypothesis 1; similarly, an analysis of Project Feeder Watch data collected around Ithaca did not show differences in changes in purple and house finches' abundance since 2006, a result which does not support Hypothesis 2. We conclude that purple finch populations will, unlike those of house finches, not suffer a severe decline because of a M. gallisepticum epidemic.


Quantitative detection of binding of PCNA protein to DNA strands on a 27 MHz quartz-crystal microbalance.
We report here binding kinetics of proliferating cell nuclear antigen (PCNA) to the dsDNA immobilized on a 27 MHz quartz-crystal microbalance. PCNA is a toroidal-shaped protein and encircles dsDNA sliding along the strand. The binding behavior of this sliding clamp protein was compared with those of other side binding proteins such as GCN4-bZIP and Zn-finger peptides.


Left atrial appendage occlusion device-related thrombus: a case report and review of the literature.
A 75-year-old male with persistent atrial fibrillation underwent implantation of a left atrial occlusion device. After 6 weeks, a scheduled trans-esophageal echocardiogram showed a 1.1-cm × 1.1-cm mass within the occluded left atrial appendage, suspected to be thrombus. He was continued on warfarin for an additional 6 weeks and a repeat trans-esophageal echocardiogram showed obliteration of the left atrial appendage. This report describes an uncommon observation detected at scheduled follow up by trans-esophageal echocardiogram, which sheds some light on the mechanism by which this device "matures" after it is implanted inside the left atrial appendage.


Quantum dots mediated fluorescent "turn-off-on" sensor for highly sensitive and selective sensing of protein.
We described a highly sensitive and selective strategy for sensing of human serum albumin (HSA) by constructing a reversible fluorescent "turn-off-on" sensor. Monodispersed cadmium telluride quantum dots (CdTe QDs) were synthesized by using a simple aqueous phase synthesis method, which exhibited strong green fluorescence. The CdTe QDs fluorescence was first quenched using resveratrol through dynamic quenching type, that is to say, excited states CdTe QDs collided with resveratrol. HSA can cooperate with resveratrol to dissociate CdTe QDs/resveratrol, leading to the recovered fluorescence of CdTe QDs. Therefore, a facile reversible fluorescent "turn-off-on" sensor can be developed for HSA detection. In a wide concentration range of HSA (0.0237-100 μg mL-1), the detection limit could reach 6.898 ng mL-1, which was much lower than previously reported values, indicating high sensitivity. Meanwhile, this strategy was successfully applied to the synthetic samples and demonstrated ideal selectivity. Moreover, the mechanisms of the interactions among QDs, resveratrol, and HSA were also investigated. The proposed strategy for HSA determination based on the constructed reversible fluorescent "turn-off-on" sensor suggests great promising in fluorescent sensing.


Schedule-induced defecation: a demonstration in pigeons exposed to fixed-time schedules of food delivery.
Previous studies have found that defecation increases in rats exposed to intermittent schedules of food delivery. In the present study, food-deprived pigeons were exposed to fixed-time 30-, 60-, 120-, and 240-s schedules of food delivery. For the subjects as a group, significantly more defecation (indexed by fecal weight) occurred under the fixed-time 60-s schedule than during massed-food control sessions in which an equivalent amount of food was presented. Thus, the present findings suggest that schedule-induced defecation occurs in pigeons.


Continuous glucose monitoring to assess glucose variability in type 3c diabetes.
The effectiveness of continuous glucose monitoring (CGM) in maintaining glycaemic control in type 1 diabetes mellitus and type 2 diabetes mellitus has been well demonstrated. However, the degree of glycaemic variability (GV) in people with type 3c diabetes mellitus has not been fully explored using CGM. This study aims to evaluate GV in type 3c diabetes mellitus participants and compare it to type 1 diabetes mellitus and type 2 diabetes mellitus. Participants were grouped according to type of diabetes. GV, defined as percentage coefficient of variation (%CV), and other glycaemic indices were obtained using CGM (FreeStyle Libre, Abbott, Australia) from 82 participants across all three cohorts over a 14-day period. Comparison of baseline characteristics and GV were performed across all groups. Correlation of GV with C-peptide values, and whether pancreatic supplementation had an effect on GV were also assessed in the type 3c diabetes mellitus cohort. GV of type 3c diabetes mellitus participants was within the recommended target of less than %CV 36% (p = 0.004). Type 3c diabetes mellitus participants had the lowest GV among the three groups (p = 0.001). There was a trend for lower C-peptide levels to be associated with higher GV in type 3c diabetes mellitus participants (p = 0.22). Pancreatic enzyme supplementation in type 3c diabetes mellitus participants did not have an effect on GV (p = 0.664). Although type 3c diabetes mellitus participants were the least variable, they had the highest mean glucose levels and estimated HbA1c , which suggests that the concept of 'brittle' diabetes in type 3c diabetes mellitus is not supported by the results of CGM in this study and may be leading to poorer glycaemic control.


[Testicular metastasis of transitional cell carcinoma of the prostate].
This case illustrates in a 55 year old man a testicular metastasis from a prostatic TCC occurring fourteen years after a bladder localisation of the same type. To our knowledge no other similar observation has been reported in the literature so far. Metastatic disease should be considered in the differential diagnosis of testis tumours arising in patients with a history of urothelial TCC from bladder, ureter or even prostate as described here.


Mining clinical information in the utilization of social services: practitioners inform themselves.
When fully invested in applied studies regarding their own clinical and programmatic concerns, social work practitioners find that "mining" clinical information enriches their performance and services.


Standard of proof and intolerance of uncertainty in obsessive-compulsive disorder and social anxiety disorder.
Researchers have identified intolerance of uncertainty (IU) as a dysfunctional thought that contributes to OCD. Case examples of OCD suggest that uncertainty and anxiety persist despite low likelihoods of feared outcomes. In this study we examined how people with OCD react to minimal amounts of uncertainty relative to non-anxious individuals and a clinical comparison group of people with social anxiety disorder (SAD). We created a questionnaire to measure the distress people feel when there is only minimal uncertainty regarding a given outcome and if they prefer situations with the certainty of negative outcomes in the present versus living with uncertainty. Part two of our study tested whether IU is related to performance on neutral and idiographic versions of the Beads Task. OCD and SAD subjects reacted to hypothetical scenarios involving minimal risk with greater negative affect than did non-anxious subjects; however, after repeating analyses to account for comorbid disorders, OCD subjects' scores did not differ from those of non-anxious subjects. Only SAD subjects showed a preference for negative information in the present versus the uncertainty of a future outcome. Part two of our study revealed that self-reported IU was only marginally associated with performance on the neutral Beads Task. High rates of comorbidity made it difficult to identify the specific relationship of IU with other anxiety disorders. IU for general, non-OCD specific scenarios may not figure prominently in all individuals with OCD, but rather may play a larger, more consistent role in anxiety disorders such as SAD. Additionally, the number of beads or words viewed on Beads Task may be an inadequate behavioral measure of IU.


Preliminary Evidence-Based Method of Medical Kit Design for Wilderness Expeditions Modeled by a High-Altitude Expedition to Mount Kilimanjaro.
Wilderness expeditions require extensive planning and the correct medical supplies to ensure clinical care is possible in the event of illness or injury. There are gaps in the literature regarding evidence-based methods for medical kit design. This report describes a preliminary method for predicting medical events to determine medical supply requirements for a wilderness expedition. The performance of this method was evaluated using data from the 2017 Equal Playing Field (EPF) expedition to Mount Kilimanjaro. Eight reports documenting medical events during wilderness expeditions were reviewed. Incidence data were consolidated into a new dataset, and a subset of data from adventure race expeditions (ARS) was created. The cumulative incidence of medical events was then predicted for the 9-day EPF expedition. The medical supply list was determined based on indication. The effectiveness of the full dataset and ARS to predict the cumulative incidence of medical events by category during the EPF expedition was evaluated using regression analysis. The ARS predicted a higher incidence rate of medical events than the full dataset did but underestimated the EPF expedition incidence rate. The full dataset was a weak predictor of the cumulative incidence of medical events by category during the EPF expedition, while the ARS was a strong predictor. The finalized medical kit overestimated all nonreusable supplies. The medical kit created using this method managed all medical events in the field. This report demonstrates the potential utility of using a tailored, evidence-based approach to design a medical kit for wilderness expeditions.


Are Bacillus thuringiensis strains like any other Bacillus cereus strains? Phenotypic-based tools to locate Bacillus thuringiensis in the diversity of the Bacillus cereus sensu lato group.
Some Bacillus thuringiensis (Bt) strains are used as pesticide agent. This species belongs to Bacillus cereus (Bc) group which contains many species with a high phenotypic diversity, and could be pathogenic like B. cereus. The aim of this study was to characterize the phenotype of 90 strains belonging to Bc group, half of which were Bt. Knowing that Bt strains belong to different phylogenetic Bc groups, do Bt strains have the same phenotype than other Bc group strains? Five phenotypic parameters were estimated for 90 strains in the Bc group, of which 43 were Bt strains: minimal, maximal and optimal growth temperature, cytotoxicity on Caco-2 cells, heat resistance of spores. The dataset was processed by principal component analysis, showing that 53% of the variance of the profiles corresponded to factors linked to growth, heat resistance and cytotoxicity. The phenotype followed the phylogenetic groups based on panC. Bt strains showed similar behavior to other strains in the Bc group, in our experimental conditions. Commercial bio-insecticide strains were mesophilic with low heat resistance.


Antidepressants suppress neuropathic pain by a peripheral β2-adrenoceptor mediated anti-TNFα mechanism.
Neuropathic pain is pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. It is usually chronic and challenging to treat. Some antidepressants are first-line pharmacological treatments for neuropathic pain. The noradrenaline that is recruited by the action of the antidepressants on reuptake transporters has been proposed to act through β2-adrenoceptors (β2-ARs) to lead to the observed therapeutic effect. However, the complex downstream mechanism mediating this action remained to be identified. In this study, we demonstrate in a mouse model of neuropathic pain that an antidepressant's effect on neuropathic allodynia involves the peripheral nervous system and the inhibition of cytokine tumor necrosis factor α (TNFα) production. The antiallodynic action of nortriptyline is indeed lost after peripheral sympathectomy, but not after lesion of central descending noradrenergic pathways. More particularly, we report that antidepressant-recruited noradrenaline acts, within dorsal root ganglia, on β2-ARs expressed by non-neuronal satellite cells. This stimulation of β2-ARs decreases the neuropathy-induced production of membrane-bound TNFα, resulting in relief of neuropathic allodynia. This indirect anti-TNFα action was observed with the tricyclic antidepressant nortriptyline, the selective serotonin and noradrenaline reuptake inhibitor venlafaxine and the β2-AR agonist terbutaline. Our data revealed an original therapeutic mechanism that may open novel research avenues for the management of painful peripheral neuropathies.


Effect of freezing, long-term storage, and microwave thawing on the stability of ketorolac tromethamine.
Ketorolac tromethamine is a nonsteroidal agent with potent analgesic and moderate antiinflammatory activity. Advance preparation of intravenous solution could be useful to improve quality assurance, time management, and cost-savings of drug delivery. To investigate the effect of freezing, long-term storage, and microwave thawing on the stability of ketorolac tromethamine in dextrose 5% infusion. Five polyolefin bags of solution containing ketorolac tromethamine 20 mg per 100 mL of dextrose 5% were frozen for 3 months at -20 degrees C, thawed in a microwave oven with a validated cycle, and stored at 4 degrees C. The concentration of ketorolac was measured by HPLC. Visual inspection and pH measurement were also carried out. No color change or precipitation was observed. Ketorolac was stable for at least 60 days under refrigeration after freeze-thaw. Throughout this period, the lower confidence limit of the estimated regression line of the concentration-time profile remained >90% of the initial concentration, and the pH value decreased slightly without affecting chromatographic parameters. Within these limits, ketorolac tromethamine in dextrose 5% infusion may be prepared and frozen in advance by a centralized intravenous admixture service, then thawed before use in clinical units.


Isokinetic and functional shoulder outcomes after arthroscopic capsulolabral stabilization.
Shoulder stability is secured by dynamic and static stabilizers. Rotator cuff is responsible for dynamic stabilization. In cases of shoulder instability their activity is disturbed. Capsulolabral repair restores mainly static stabilization. This surgery treatment technique of shoulder instability was first described by Bankart in 1923. His idea, with further modifications, is commonly used up to this day. Evaluation of muscle shoulder recovery after stabilization should be one of the important criteria to allow patient to return to sport and work. However, not much isokinetic assessment after capsulolabral repair was described. The aim of this study were the following: the comparative assessment of the shoulder rotatory strength in patients following arthroscopic capsulolabral repair of unilateral anterior traumatic instability and clinical assessment with comparison of pre and post-operative results. Forty-five patients, 14 women and 31 men, with an average follow-up of 4.4 years were tested bilaterally for internal and external rotation strength at four angular velocities. ASES and UCLA tests were collected before and after surgery. The values of peak moment and muscle power parameters were slightly lower for an operated shoulder in comparison to a healthy shoulder for the external rotation. Total work parameter in external rotation was significantly lower for the operated shoulder in comparison to the non-operated side. The internal/external muscle group balance was lower for the operated shoulder in comparison to reference values in the women group. Furthermore, both ASES and UCLA scores were significantly higher after operation. After arthroscopic capsulolabral shoulder stabilization, slight differences in isokinetic evaluation, especially in external shoulder rotation, occur. It affects rotators muscle balance. In functional evaluation significant improvement in shoulder function occurs.


Subfractionation of cell populations by partitioning in dextran-poly (ethylene glycol) aqueous phases. "Discriminating" and "nondiscriminating" systems.
Partitioning of cells in dextran-poly(ethylene glycol) aqueous two-phase systems depends on the interaction between the surface properties of the cells and the physical properties of the phases. The latter can be manipulated to a considerable extent by selection of polymer concentrations and ionic composition and concentration. If salts (e.g., phosphate) are used that have an unequal affinity for the two phases, an electrostatic potential difference between the phases results and, at appropriately high polymer concentrations, the partition coefficient of cells is determined predominantly by membrane charge-associated properties. By "balancing" the magnitude of the electrostatic potential difference against that of the interfacial tension (primarily a function of polymer, but also phosphate, concentrations) one can obtain phase systems that give usable partition coefficients for most cell populations (1). In work under way in our laboratory on the effects of different chemical and enzymatic modifications on the relative surface properties of rat red blood cells of different ages, we have now found that certain phase compositions did not resolve such treated cell subpopulations while other phase compositions did. Thus not all charged phase systems in which cell populations as a whole have usable partition coefficients are equally capable of detecting or subfractionating cell subpopulations. It is therefore essential, before drawing conclusions on the nonseparability of cell subpopulations, to test cell separability in charged phase systems of different compositions if the system initially chosen does not afford a subfractionation.


Association of Age to Mortality and Repeat Revascularization in End-Stage Renal Disease Patients: Implications for Clinicians and Future Health Policies.
The clinical effects of age occur over an age continuum, yet age as a primary predictor is often analyzed using arbitrary age cut-points. To assess whether transformation of a continuous variable such as age using a spline function can uncover nonlinear associations between age and cardiovascular outcomes. Observational retrospective cohort study in 1015 Kaiser Permanente Northern California patients with end-stage renal disease after index coronary revascularization. Age, the primary predictor, was modeled by 5 different techniques: 1) dichotomized at 65 years or older; 2) at 80 years or older (as a sensitivity analysis); 3) categorized as younger than 55 years (reference), 55 to 64, 65 to 74, and 75 years or older; 4) linear (every 5 years) variable; and 5) nonlinear by transformation into a cubic spline. Age categories were changed in a sensitivity analysis. Primary and secondary outcomes were all-cause mortality and repeat revascularization, respectively. Graphical assessment demonstrated that age dichotomized at either 65 years and older or 80 years and older led to loss of information. Categorized age underestimated or overestimated risk at the extremes of age. A sensitivity analysis demonstrated that an arbitrary change in the age category led to a different conclusion. Age modeled linearly adequately represented mortality risk but was suboptimal with repeat revascularization. Only the cubic spline demonstrated the nonlinear association between age and repeat revascularization. Employing the continuous variable age as a case study, we have demonstrated that the use of flexible transformations, such as spline functions, can unearth clinically meaningful associations that would not have been possible otherwise. Future research should determine whether incorporation of these methods can improve decision making at a population level.


Relevance of the Measles Virus Expression in Cancer - an Update.
Evidence of an association between classical Hodgkin lymphoma and the measles virus has previously been presented by our group. Arguments held against our thesis were reevaluated. Substantiation of a relationship between the measles virus and additional solid tumors was submitted. Moreover, a pathogenic pathway was suggested to support a possible contribution of the measles virus to the development of classical Hodgkin lymphoma. We have chosen to exclude a discussion of measles virotherapy, since this carries distinct implications. We now add new evidence regarding the expression of the measles virus phosphoprotein in a few cancers. We also suggest a role in this context for atypical measles syndrome in malignant tumors. Last, we propose a collaboration which may make the best, on the one hand of our cohort of classical Hodgkin lymphoma, half of which carry the measles virus expression in their tumor cells. The planned study will also look into the patients vaccination records and into a previous history of the measles disease. On the other hand, cohorts of patients diagnosed with late onset measles will be assessed for the eventual diagnosis of atypical measles syndrome and will be followed up for the subsequent development of a malignant tumor.


Dissipative Asynchronous T-S Fuzzy Control For Singular Semi-Markovian Jump Systems.
This article addresses the problems of the dissipative asynchronous Takagi-Sugeno-Kong fuzzy control for a kind of singular semi-Markov jump system. An adjustable quantized approach is presented to deal with the uncertainties, nonlinear disturbance, actuator faults, and time-varying delay of the system. To deal with the problem of the nonsynchronous between system modes and controller modes, an asynchronous method is utilized. Then, a novel asynchronous sliding-mode controller is designed with an output measurement quantizer that is adaptive to the actuator faults and has good performance in practical applications. By solving the linear matrix inequalities, the sufficient conditions are obtained to guarantee the closed system stochastically admissible and strictly (Q,R,S)-α- dissipative and ensure the reachability of the sliding-mode surface. Finally, two numerical examples and comparisons are provided to illustrate the effectiveness and the priority of the proposed technique.


Evaluating the Prognostic Implication of the Collins Histology Scoring System in a Pediatric Eastern Ontario Population With Eosinophilic Esophagitis.
Collins et al developed a histology scoring system (EoE HSS) to assess multiple pathologic features. The aim of this study is to identify if the EoE HSS can better detect endoscopic and symptom improvement vs the Peak Eosinophilic Count (PEC). A retrospective chart review was performed for patients during 2014-2016. All patients ≤18 years old with a diagnosis of EoE and whose records included initial and follow-up upper gastrointestinal endoscopies were included. Severity and extent of endoscopic features were scored using 8 parameters, from normal to maximum change for each location of the esophageal biopsy. Forty patients with EoE were included in the study, of which 35 (87.5%) patients demonstrated symptom and 25 (62.5%) endoscopic improvement at the time of follow-up. In the proximal esophagus, the EoE HSS outperformed the change in eosinophil count of the Children's Hospital of Eastern Ontario (CHEO) practice in predicting endoscopic improvement by 16.8% when examining the change in grade and 17.1% when examining the change in stage scores. At our institution, adoption of the EoE HSS in assessing biopsies of EoE patients might be warranted, compared to the traditional practice. However, a bigger sample size may give a more robust difference in all locations.


An immunoassay for the measurement of (1-->3)-beta-D-glucans in the indoor environment.
An inhibition enzyme immunoassay was developed for quantitation of (1-->3)-beta-D-glucans in the indoor environment. Immunospecific rabbit antibodies were produced by immunization with bovine serum albuminconjugated laminarin.The laminarin calibration curve ranged from 40 to 3000 ng/ml.Another (1-->3)-beta-D-glucan (curdlan) showed a similar inhibition curve, but was less reactive on a weight basis. Pustulan, presumed to be (1-->3)-beta-D-glucan, also showed immunoreactivity in the assay. Control experiments indicated that this was due to (1-->3)-beta-D-glucan structures. Other non-(1-->3)-beta-D-glucan polysaccharides did not react. (1-->3)-beta-Dglucan was detectable in dust from a variety of occupational and environmental settings. We conclude that the new assay offers a useful method for indoor (1-->3)-beta-Dglucan exposure assessment.


Diagnostic Value of Different Phenotype Circulating Tumor Cells in Hepatocellular Carcinoma.
A growing body of research indicates that the monitoring of circulating tumor cells (CTCs) may have great significance to the diagnosis of malignant tumors, assessment of condition, selection of treatment methods, and evaluation of prognosis and has a broad range of potential applications. However, the value of CTCs with different phenotypes in the diagnosis of hepatocellular carcinoma (HCC) and assessment of patient condition remains unclear. We collected 5 ml of peripheral blood from 176 patients who were found to have space-occupying lesions in the liver via B-ultrasound diagnosis at Zhujiang Hospital affiliated with Southern Medical University between August 2015 and October 2017 and used CanPatrol™ CTCs assay technology to isolate and count CTCs with different phenotypes in the patients' peripheral blood. This allowed analysis of the value of CTCs with different phenotypes in the diagnosis of HCC and assessment of BCLC stage. We used CanPatrol™ CTCs assay technology to isolate different types of CTCs: epithelial CTCs (only stained for epithelial markers), mesenchymal CTCs (only stained for mesenchymal markers), mixed CTCs (stained for epithelial markers and mesenchymal markers), and total CTCs (all of the foregoing CTC phenotypes). Of 176 observed patients, 6 patients were finally diagnosed as other malignant tumor liver metastasis, 113 were diagnosed as having hepatocellular carcinoma, and 57 were diagnosed as having nonmalignant liver diseases. Furthermore, we intend to evaluate the diagnostic value of different phenotype CTCs count in discrimination between hepatocellular carcinoma and nonmalignant liver diseases. We found that CTCs of all types were significantly more numerous in the peripheral blood of the HCC group patients than in the NLD group patients (P < 0.05). Furthermore, of the different types of CTCs, total CTCs had the greatest diagnostic value (AUC 0.774; 95% CI, 0.704-0.834). A further discovery was that the AUC values for total CTCs, AFP, and a combined model (combined use of total CTCs and AFP) were 0.774 (95%CI, 0.704-0.834), 0.669 (95%CI, 0.587-0.750), and 0.821 (95%CI, 0.756-0.886). Late-stage HCC patients (BCLC stage B-C) had a higher peripheral blood mesenchymal CTC count than early-stage patients (BCLC stage 0-A) (median:1 vs 0), and mesenchymal CTCs ≥ 1 was the cut-off value for the diagnosis of BCLC stage in HCC patients (sensitivity: 66.67%, specificity: 59.46%, Youden index: 0.26). Total CTCs are more effective than AFP in the diagnosis of HCC; combined use of total CTCs and AFP can enhance the sensitivity of HCC diagnosis.


CT of dens axis fractures.
The distinction between the different types of dens axis fracture is important. Fractures at the base of dens (Type II) may be overlooked if reformated images are not made. If the fracture extends downward into the body of the vertebra (Type III), the body fragment may rotate into the spinal canal. The rotation is difficult to see on plain films, but is easily seen at axial CT.


Inhibition of rat basal pancreatic secretion by intraduodenal bile.
The effect on basal exocrine pancreatic secretion of diversion from and reintroduction into the duodenum of bile has been studied on conscious rats provided with pancreatic, biliary and duodenal fistulae. Diversion of bile from the intestine augmented protein output by 30%. After an eight-hour diversion recirculation of bile into the duodenum reduced pancreatic protein output by 30%; volume being not significantly modified. When either bile was diverted or the main bile duct was ligated, a similar inhibition of protein secretion was observed after intraduodenal injections of 20 mM solutions of taurocholate, taurochenodeoxycholate, chenodeoxycholate, and cholate, and of synthetic mixed micelles (bile salts, lecithin). Inhibitory action of bile salts on pancreatic secretion was seen equally whether or not the bile salts were in free or conjugated form or pancreatic juice returned to the intestine. We conclude that unlike man and the dog, bile as well as pancreatic juice inhibits the basal pancreatic exocrine secretion of the rat.


Functional pathology of the ovaries and uteri of premature female piglets exposed to distinct amounts of zearalenone.
The objective of this study was to investigate the effects of four different concentrations (groups II-V) of orally administered zearalenone (ZON) over a feeding period of 35 days on parts of the genital tract of 75 day-old female piglets in comparison to a control group (I). In order to determine possible dose related characteristics for a ZON intoxication in ovaries and uteri, histomorphological (HE and Azan stained slides) and immunohistochemical methods [expression patterns of estrogen (ER) and progesterone (PR) receptor, proliferating cell nuclear antigen (PCNA)] were carried out. Using these methods, there were no obvious (immuno-) histomorphological differences within the treatment groups or in comparison to the control group. Nevertheless, compared to the group I, statistical analyses of all parameters investigated revealed significance only in the increased mitotic activity of muscle cells in the uterinelamina muscularis in treatment group V.


Higher efficacy of resveratrol against advanced breast cancer organoids: A comparison with that of clinically relevant drugs.
The lack of reliable drugs is a therapeutic challenge of advanced breast cancers (ABCs). Resveratrol (Res) exerts inhibitory effects on breast cancer cell lines and animal models, while its efficacy against individual breast cancer cases remains unknown. This study aims to use ABC-derived organoids (ABCOs) as the ex vivo therapeutic platform to clarify the effectiveness of resveratrol against different ABC subtypes. Immunohistochemical staining confirmed that the ABCOs maintained their original tumors' ER, PR, HER2, and Ki67 expression patterns. ABCO proliferation and viability tests showed >50% cell death rates in 79.2% (19/24) of Res-treated, 28.6% (2/7) fulvestrant-treated, 66.7% (4/6) paclitaxel-treated, and 66.7% (6/9) gemcitabine-treated ABCOs. pSTAT3 nuclear translocation was more frequent in Res-sensitive (17/19; 89.47%) than that (1/5; 20%) of Res-insensitive ABCOs, which were suppressed upon Res treatment. Statistical analysis revealed a close correlation of STAT3 activation with the efficacy of Res, but not related to tumor receptor expression patterns (ER, PR, HER2) and pathological classification. We demonstrate for the first time the higher efficacy and broader spectrum of Res against different subtypes of ABCOs in comparison with that of conventional antibreast cancer drugs, providing an alternative approach for better management of ABCs.


Tumour vaccine associated lymphadenopathy and false positive positron emission tomography scan changes.
A patient receiving intradermal injections of vaccine directed towards carcinoembryonic antigen-bearing metastases from colorectal cancer showed uptake of 18F-fluorodeoxyglucose in local draining lymph nodes during the course of treatment. This appearance should be considered as a possible false positive in patients undergoing such treatment who are being investigated with PET scans.


Use of oral glucose minimal model-derived index of insulin sensitivity in subjects with early type 1 diabetes mellitus.
Insulin resistance plays an important role during various stages of the type 1 diabetes mellitus disease process. Unfortunately, many of the techniques used to measure insulin sensitivity are experimentally laborious and time-consuming and are thus impractical for larger clinical and population studies. Therefore, in this study, we obtain estimates of insulin sensitivity from a simpler experiment, the oral glucose tolerance test (OGTT), and compare them with those from a frequently sampled intravenous glucose tolerance test (FSIGT) in a population of subjects defined as having early type 1 diabetes mellitus (abnormal 2-hour glucose on OGTT) and a group of healthy controls. A total of 19 subjects were studied. Eight antibody-positive first- or second-degree relatives of patients with type 1 diabetes mellitus and 11 healthy controls underwent both a 3-hour OGTT and an insulin-modified FSIGT on separate days. Indices of insulin sensitivity (SI) were estimated from the recently derived oral glucose minimal model and the original minimal model of glucose kinetics for the OGTT and FSIGT, respectively. Estimates of SI from the OGTT correlated closely with those from the FSIGT in both early type 1 diabetes mellitus (rs=0.76, P = .04) and healthy control (rs = 0.67, P = .03) populations. This preliminary study demonstrates the usefulness of OGTT-derived estimates of insulin sensitivity in an early type 1 diabetes mellitus population. Given the simplicity of the OGTT relative to the traditional methods of measuring SI, the oral glucose minimal model may be appropriate for large population studies and clinical trials.


Correlation of tumor size and axillary lymph node involvement with prognosis in patients with T1 breast carcinoma.
The prognosis of patients with T1 breast carcinoma remains controversial. Some studies have shown a low risk of lymph node metastasis and distant failure whereas others have not, possibly due to differences in the definition of tumor size. In this study, the authors assessed the relation between macroscopic tumor size, microscopic invasive tumor size, axillary lymph node involvement, and prognosis in a group of patients with clinically lymph node negative disease. Between 1968 and 1986, 1865 women with American Joint Committee on Cancer clinical Stage I or II infiltrating carcinoma of the breast were treated at the Joint Center for Radiation Therapy with conservative surgery and radiation therapy. The study population was limited to 118 patients with clinically negative axillary lymph nodes for whom the macroscopic pathologic tumor size was identified unambiguously as being < or = 2.0 cm, who underwent an axillary lymph node dissection with at least 6 lymph nodes sampled, and for whom the microscopic size of the invasive component could be determined. The median follow-up time for surviving patients was 134 months (range, 90-208 months). No patients with pathologically negative axillary lymph nodes received systemic therapy. Macroscopic and microscopic tumor sizes differed by > 5 mm in 17 patients (14%), by 3-5 mm in 24 patients (20%), and by < or = 2 mm in 77 patients (65%). The macroscopic tumor size was smaller than the microscopic size in 37 patients (31%), larger in 55 patients (47%), and equal in 26 patients (22%). Pathologic axillary lymph node involvement was present in 21% of all patients. The risk of lymph node involvement was not significantly different for those patients with tumors < or = 1 cm compared with patients with tumors > or = 1.1 cm, regardless of whether tumor size was measured by macroscopic or microscopic examination. The 10-year actuarial rate of freedom from distant recurrence (FFDR) was 91% for lymph node negative patients with macroscopic tumors measuring < or = 1.0 cm compared with 77% for patients with macroscopic tumors measuring > or = 1.1 cm (P = 0.07). When measured microscopically, the rates were 96% and 72%, respectively (P = 0.001). There often is a discrepancy between microscopic tumor size and macroscopic tumor size. T1 tumors have a substantial risk of axillary lymph node metastasis whether measured macroscopically or microscopically. Among those patients with pathologic lymph node negative tumors who are not treated with systemic adjuvant therapy, microscopic invasive tumor size is a better predictor of 10-year FFDR than macroscopic tumor size. There is a substantial risk of distant failure for patients with tumors whose invasive component microscopically measure > or = 1.1 cm, whereas the prognosis for patients with tumors that microscopically measured < or = 1 cm is excellent. These results suggest that the microscopic size of the invasive component of breast carcinomas < or = 2.0 cm routinely should be reported.


Factors related to seat belt use among fatally injured teenage drivers.
In the United States, teenage drivers have a higher crash risk and lower observed seat belt use than other age groups. Seat belt use was examined for teenage (16-19 years) drivers who were fatally injured in traffic crashes occurring in the United States during the years 1995-2000. Vehicle, driver, and crash factors potentially related to belt use were examined. State differences in belt use rates among fatally injured teenage drivers were related to states' observed belt use rates for all ages and other state-level variables. During 1995-2000, mean belt use was 36% among fatally injured teenage drivers and 23% among fatally injured teenage passengers. One of the strongest predictors of higher belt use for both drivers and passengers was whether the crash occurred in a state with a primary seat belt law. Belt use rates for 1995-2000 for fatally injured teenage drivers ranged from 20% or less in six states to more than 60% in two states. States with the highest use rates were those with strong primary belt use laws and those with high rates of observed belt use for all ages. Lower belt use among fatally injured teenage drivers was associated with increasing age; male drivers; drivers of SUVs, vans, or pickup trucks rather than cars; older vehicles; crashes occurring late at night; crashes occurring on rural roadways; single vehicle crashes; and drivers with BACs of 0.10 or higher. Teenage driver belt use declined as the number of teenage passengers increased, but increased in the presence of at least one passenger 30 years or older. It is suggested that to increase teenage belt use, states should enact strong primary belt use laws and mount highly publicized efforts to enforce these laws. Graduated driver licensing systems should incorporate strong provisions that require seat belt use by teenage drivers and passengers.


Challenging Regeneration to Transform Medicine.
The aging population in the U.S. and other developed countries has led to a large increase in the number of patients suffering from degenerative diseases. Transplantation surgery has been a successful therapeutic option for certain patients; however, the availability of suitable donor organs and tissues significantly limits the number of patients who can benefit from this approach. Regenerative medicine has witnessed numerous recent and spectacular advances, making the repair or replacement of dysfunctional organs and tissues an achievable goal. Public-private partnerships and government policies and incentives would further catalyze the development of universally available donor tissues, resulting in broad medical and economic benefits. This article describes a Regenerative Medicine Grand Challenge that the Alliance for Regenerative Medicine recently shared with the White House's Office of Science and Technology Policy in response to a White House call to action in scientific disciplines suggesting that the development of "universal donor tissues" should be designated as a Regenerative Medicine Grand Challenge. Such a designation would raise national awareness of the potential of regenerative medicine to address the unmet needs of many diseases and would stimulate the scientific partnerships and investments in technology needed to expedite this goal. Here we outline key policy changes and technological challenges that must be addressed to achieve the promise of a major breakthrough in the treatment of degenerative disease. A nationalized effort and commitment to develop universal donor tissues could realize this goal within 10 years and along the way result in significant innovation in manufacturing technologies. Regenerative therapies, in which dysfunctional or degenerating cells, tissues, or organs are repaired or replaced, have the potential to cure chronic degenerative diseases. Such treatments are limited by a shortage of donor organs and tissues and the need for immune suppression to prevent rejection. This article proposes a 21st Century Grand Challenge that would address this significant medical need by coordinating a national effort to convene the multidisciplinary expertise needed to manufacture functional and engraftable cells, tissues, or organs that could be made available to any patient without significant risk of rejection-so-called universal donor tissues.


Electrogenic uptake of D-imino acids by luminal membrane vesicles from rabbit kidney proximal tubule.
Some characteristics of electrogenic uptake of D-proline and hydroxy-D-proline by luminal membrane vesicles isolated either from pars convoluta or from pars recta of rabbit proximal tubule were indirectly studied by the spectrophotometric method. In vesicles from pars convoluta, the uptake of D-imino acids was mediated by both Na+-dependent and Na+-independent, but electrogenic processes. Indirect evidence for coupling between D-imino acids and H+ fluxes was obtained by the following observations: (1) Addition of the H+ ionophore (FCCP) to the vesicle-dye (3,3'-diethyloxadicarbocyanine iodide) suspension completely abolished the Na+-independent electrogenic uptake of D-proline and hydroxy-D-proline by membrane vesicles from pars convoluta. (2) Addition of a relatively low concentration of D-proline in the incubation system decreased the H+-gradient dependent renal uptake of radioactive L-proline to approx. 60% of the control value. By contrast, the uptake of D-proline in vesicles from pars recta was strictly Na+-dependent, since no transient depolarization of membrane vesicles was ever observed in the absence of Na+. A comparison between the transport characteristics of D-imino acids and their naturally occurring L-isomers indicated that these compounds probably share common transport systems located along the proximal tubule of rabbit kidney.


[Homologous lamellar central limbokeratoplasty in severe limbal stem cell deficiency].
It is the purpose of this case report to present a new surgical technique for treatment of severe limbal stem cell deficiency. In a 42-year-old female patient with conjunctivalization of the cornea in congenital aniridia a homologous lamellar central limbokeratoplasty was performed. Postoperatively systemic Ciclosporin A was administered in order to prevent the transplanted limbal stem cells from immunological destruction. During the follow-up period of 16 months no immune reaction against the transplanted limbal stem cells could be observed. Visual acuity was ameliorated considerably. Homologous lamellar central limbokeratoplasty is a promising surgical procedure in selected patients with severe limbal stem cell deficiency having less complications compared with penetrating central limbokeratoplasty.


Comprehensive analysis of TCR repertoire of COVID-19 patients in different infected stage.
The current pandemic of coronavirus disease 2019 (COVID-19), transmitted person-to-person by the severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2), poses a threat to global public health. In this study, we performed the comprehensive analysis of the T cell receptor (TCR) repertoire may contribute to a more in-depth understanding of the pathogenesis of COVID-19. A comprehensive immunological analysis was performed to explore the features of the TCR repertoire and identified TCR sequences correlated with SARS-CoV-2 viral antigens. we analyzed the COVID-19 patients' TCR repertoires in peripheral blood mononuclear cells (PBMC) which obtained before (baseline), during (acute), and after rehabilitation (convalescent) by ImmunoSEQ-technology, and found that repertoire features of TCRβ-chain (TCRβ) complementary-determining region 3 (CDR3) in COVID-19 patients were remarkable difference, including decreased TCR diversity, abnormal CDR3 length, difference of TRBV/J gene usage and higher TCR sequence overlap. Besides, we identified some COVID-19 disease-associated TCRβ clones, and the abundance of them changed with the progression of the disease. Importantly, these disease-associated TCRβ clones could be used to distinguish COVID-19 patients from healthy controls with high accuracy. We provide a clear understanding of the TCR repertoire of COVID-19 patients, which lays the foundation for better diagnosis and treatment of COVID-19 patients.


Safety and immunogenicity of Haemophilus influenzae type b-polysaccharide diphtheria toxoid conjugate vaccine in infants 9 to 15 months of age.
Sixty 9- to 15-month-old infants were randomly assigned to receive two doses, 1 month apart, of a Haemophilus influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) or PRP vaccine, each containing 20 micrograms PRP. There were no significant local or systemic reactions. After one dose of PRP-D, 93% of the subjects attained levels of greater than or equal to 0.15 microgram/ml and 59% achieved greater than or equal to 1 microgram/ml antibody protein. These percentages rose to 100% and 86%, respectively, after the second dose, at which time the geometric mean titer of anti-PRP antibody was 4.8 micrograms/ml. IgG anti-PRP levels were 4.3 times higher than IgM. The proportion of IgG to IgM antibody induced by PRP-D increased with age. After two doses, 33% of the PRP recipients responded with a level of greater than or equal to 0.15 microgram/ml and only 19% responded to a level of greater than or equal to 1.0 microgram/ml. One year later, all of the PRP-D recipients tested still had greater than or equal to 0.15 microgram/ml and more than half had greater than or equal to 1.0 microgram/ml antibody protein.


Current Status of Endovascular Training for Cardiothoracic Surgery Residents in the United States.
Endovascular interventions for cardiovascular pathology are becoming increasingly relevant to cardiothoracic surgery. This study assessed the perceived prevalence and efficacy of endovascular skills training and identified differences among training paradigms. Trainee responses to questions in the 2016 In-Service Training Examination survey regarding endovascular training were analyzed based on the four different cardiothoracic surgery training pathways: traditional 2- and 3-year thoracic, integrated 6-year, and combined 4+3 general and thoracic residency programs. The duration of endovascular training was substantially different among programs, at a median of 17 weeks for integrated 6-year, 8.5 weeks for 3-year, 6 weeks for 4+3, and 4 weeks for 2-year residency (p < 0.0001). After adjusting for year of training and program type, the duration of endovascular rotations was significantly associated with self-assessed comfort with catheter-based skills (p < 0.0001). Eighty-two percent of residents rotated with trainees from other specialties, and 58% experienced competition for cases. Residents reported greater exposure to transcatheter aortic valve replacement than to thoracic endovascular aortic repair, cardiac catheterization, percutaneous closure of atrial septal defect, and transcatheter mitral valve surgery (p < 0.0001). A significant proportion of responders reported feeling uncomfortable performing key steps of transcatheter aortic valve replacement (52%) or thoracic endovascular aortic repair (49%). Considerable heterogeneity exists in endovascular training among cardiothoracic surgery training pathways, with a significant number of residents having minimal to no exposure to these emerging techniques. These findings highlight the need for a standardized curriculum to improve endovascular exposure and training.


Balloon kyphoplasty for vertebra plana with or without osteonecrosis.
To compare efficacy of balloon kyphoplasty in restoring vertebral height and correcting kyphosis in patients having vertebra plana with or without osteonecrosis. 12 women and 3 men (mean age, 76 years), who had a complete vertebra plana with or without osteonecrosis (n=8 vs n=7), underwent balloon kyphoplasty. No external manoeuvres were performed before or during balloon kyphoplasty, except for positioning the patients in a prone posture on the operating table. The anterior, middle, and posterior vertebral height and the kyphotic angle were measured pre- and post-operatively with a digital imaging system. The vertebral height was measured as a percentage of the adjacent normal vertebral height. Respectively in vertebra plana patients with or without osteonecrosis, the mean corrections of (1) kyphosis were 10 and 4 degrees (p=0.099), (2) anterior vertebral height were 33% and 5% (p<0.001), (3) middle vertebral height were 38% and 18% (p=0.004), and (4) posterior vertebral height were 19% and 2% (p=0.031). In patients with vertebra plana, it is important to identify any osteonecrosis, which is an indication for balloon kyphoplasty to restore vertebral height and correct kyphosis.


Peanut oral immunotherapy in adolescents: study protocol for a randomized controlled trial.
Peanut allergy is an increasingly common health problem. Current treatment guidelines are based on strict avoidance. However, in the last few years, oral immunotherapy protocols have shown promising results yielding increased tolerance to peanut in allergic children. Adolescence is particularly at risk. We have designed a randomized, double-blind, placebo-controlled, multicenter study to investigate the efficacy and safety of peanut oral escalating immunotherapy in a 12- to 18-year-old population with proved allergy to peanut. Patients are selected when the threshold of peanut intake is over 100 mg and 2 cumulated g on the first double-blind, placebo-controlled oral food challenge (DBPCOFC). During the build-up placebo-controlled blinded phase, doses containing peanut or placebo will be administered by gradual up-dosing from 10 mg to 2 g with 2-weekly increments. After this first randomized phase, the desensitized participants will continue to intake native peanut in an unblinded process during 13 or 37 weeks following a second randomization. Adverse events are picked up and managed throughout the entire protocol. The main endpoint is the percentage of patients with negative DBPCOFC at the threshold of 2 g of cumulative peanut at the end of the build-up phase of 24 weeks. Secondary endpoints include: (1) desensitization 6 weeks and 6 months after the end of the maintenance phase; (2) adverse effects during the build-up phase; (3) immunological profile confirming peanut desensitization. Immunologic assays will be carried out at every DBPCOFC and at the middle of the build-up phase to evaluate the peanut immunologic profile modifications. This double-blind, placebo-controlled study will be, to our knowledge, the first evaluation of a peanut oral immunotherapy protocol in teenagers in the purpose to reduce severe reactions after unexpected intake and to improve quality of life. ClinicalTrial.gov: NCT02046083 (23 January 2014).


Tuberculosis burden in immigrants and natives, adults and children, in Tuscany between 2000-2018.
Updated data on epidemiology of tuberculosis are needed in Italy. The aim of this study is to evaluate trends in incidence and associated lethality of tuberculosis in immigrants compared with Italians. All tuberculosis cases diagnosed from 2000 to 2018 in 31 Tuscan hospitals were retrospectively identified. In 10,827 tuberculosis cases 6715 were males (62%), 4312 (60%) were Italian-born. Hospitalization rate was 15.37/100,000 population/year. The most common comorbidity were liver disease (832/10,827; 7.7%), COPD (675/10,827; 6.2%), cancer (614/10,827; 5.7%). HIV was more frequent in the immigrants (p < 0.001). Extra-pulmonary tuberculosis cases (EPTB) were mainly localized in pleura (740/3,894, 19%) and lymph nodes (449/3,894, 11,5%). HIV was associated with an increased risk of EPTB (OR 3.51 95% CI 2.92-4.23, p < 0.0001). EPTB risk was increased in South Asian-born patients (OR 1.77, 95% CI 1.46-2.15, p < 0.0001) as well in African-born patients (OR 1.13, 95% CI 1.03-1.24, p = 0.0091), who were at risk for gastroenteric tuberculosis (OR 3.74, 95% CI 2.69-5.22, p < 0.0001). Overall mortality rate was 0.006 per 1000. Most of death cases (89%) were Italians (p < 0.02) and mainly affected by pulmonary tuberculosis (PTB). In Tuscany, tuberculosis is still a health concern in terms of both morbidity and mortality.


Breath analysis using electronic nose and gas chromatography-mass spectrometry: A pilot study on bronchial infections in bronchiectasis.
In this work, breath samples from clinically stable bronchiectasis patients with and without bronchial infections by Pseudomonas Aeruginosa- PA) were collected and chemically analysed to determine if they have clinical value in the monitoring of these patients. A cohort was recruited inviting bronchiectasis patients (25) and controls (9). Among the former group, 12 members were suffering PA infection. Breath samples were collected in Tedlar bags and analyzed by e-nose and Gas Chromatography-Mass Spectrometry (GC-MS). The obtained data were analyzed by chemometric methods to determine their discriminant power in regards to their health condition. Results were evaluated with blind samples. Breath analysis by electronic nose successfully separated the three groups with an overall classification rate of 84% for the three-class classification problem. The best discrimination was obtained between control and bronchiectasis with PA infection samples 100% (CI95%: 84-100%) on external validation and the results were confirmed by permutation tests. The discrimination analysis by GC-MS provided good results but did not reach proper statistical significance after a permutation test. Breath sample analysis by electronic nose followed by proper predictive models successfully differentiated between control, Bronchiectasis and Bronchiectasis PA samples.


Muscle high energy phosphates in chronic peripheral vascular disease.
There is little information available concerning the alterations in skeletal muscle energy metabolism which occur in response to chronic arterial occlusive disease. In addition, the effect of arterial reconstruction on skeletal muscle energy metabolism in patients with peripheral vascular disease has not been defined. Needle biopsies were obtained from the quadriceps femoris muscle of 7 patients with aortoiliac disease and 15 patients with femoropopliteal disease and from the gastrocnemius muscle of 9 patients with femoropopliteal disease. Muscle samples were analyzed for ATP, ADP, AMP, phosphocreatine, creatine, and lactate. Eleven patients were rebiopsied after vascular reconstruction. Patients with rest pain had decreased total adenine nucleotides, energy charge potential, and ATP/ADP ratios as compared to those of controls. ATP levels were significantly decreased in muscle samples obtained distal to the arterial occlusion (i.e., quadriceps/aortoiliac, gastrocnemius/femoropopliteal) in patients with rest pain (compared with controls). ATP levels did not differ significantly from those of controls in muscle samples obtained from patients with claudication. However, energy charge potential was significantly decreased in all patients with claudication regardless of biopsy site and location of arterial occlusive disease. Normalization of muscle energy metabolism was not demonstrated following arterial reconstruction. We conclude that resting skeletal muscle energy metabolism is abnormal in patients with chronic arterial insufficiency and that progression of disease toward more severe ischemia is associated with more marked derangement. Whether the possible beneficial effects of revascularization on muscle energy metabolism are masked by the concurrent effect of injury in the early postoperative period remains to be clarified.


Identification and characterization of cryptic SHOX intragenic deletions in three Japanese patients with Léri-Weill dyschondrosteosis.
Although short-stature homeobox-containing gene (SHOX ) haploinsufficiency is responsible for Léri-Weill dyschondrosteosis (LWD), the molecular defect has not been identified in approximately 20% of Japanese LWD patients. Furthermore, although high prevalence of microdeletions affecting SHOX is primarily ascribed to the presence of repeat sequences such as Alu elements around SHOX, it remains to be determined whether microdeletions are actually mediated by repeat sequences. We performed multiple ligation probe amplification (MLPA) assay in six Japanese LWD patients with apparently normal SHOX, followed by fluorescent in situ hybridization (FISH) analysis and sequencing for polymerase chain reaction (PCR) products encompassing the deletion junctions in patients with abnormal MLPA patterns. Consequently, heterozygous intragenic deletions were identified in three cases, i.e., a 5,906-bp deletion involving exons 4-5 in case 1, a 5,594-bp deletion involving exons 4-6a in case 2, and a 50,199-bp deletion involving exons 4-6b in case 3. The deletion breakpoints of cases 1 and 2 were present in nonrepeat sequences, whereas those of case 3 resided within Alu elements. The results suggest that cryptic SHOX intragenic deletions account for a small fraction of LWD and that microdeletions affecting SHOX can be generated by repeat-sequence-mediated aberrant recombinations and by nonhomologous end joining.


Reconstruction of nongrowing hemifacial microsomia patient with custom-made unilateral temporomandibular joint total joint prosthesis and orthognathic surgery.
A case of hemifacial microsomia in a young male is presented. The ascending ramus and condyle was reconstructed utilizing virtual 3D planning with a custom-made total TMJ device (TMJ Concepts, USA) in combination with conventional orthognathic surgery. The alternative available reconstructive options are discussed and the advantages and disadvantages of the technique selected.


Chondrosarcoma of bone complicating Ollier's disease: report of a favourable response to radiotherapy.
Because chondrosarcoma of bone is traditionally thought to be a radioresistant malignancy, it is usually managed surgically. We report a case of multifocal chondrosarcoma arising in Ollier's disease for which the patient declined surgery. He was given a course of radical radiotherapy that resulted in symptom palliation and a radiologically confirmed response before he died of disseminated disease. In patients with inoperable chondrosarcoma, radiotherapy can provide palliative benefit.


Pharmacokinetic analysis of amikacin twice and single daily dosage in immunocompromised pediatric patients.
Ten children received amikacin twice daily and 13 were treated using the single daily protocol. All had fever and neutropenia on admission, and received a total daily dose of 20 mg/kg when included in the study. Individual pharmacokinetic parameters were calculated using a one-compartment model for two blood amikacin samples. The mean (+/- SD) of elimination half-life (h), amikacin clearance (l/h/kg), volume of distribution (l/kg), peak concentration (microgram/ml) and trough concentration (microgram/ml) were: 2.51 (0.74) and 2.85 (0.32) h; 0.26 (0.16) and 0.115 (0.02) l/h/kg; 0.74 (0.44) and 0.47 (0.11) l/kg; 19.1 (12.3) and 42.6 (12.6) micrograms/ml; 0.85 (0.74) and 0.18 (0.24) microgram/ml with twice and single daily dosage schedules, respectively. A single daily dose of amikacin had a significantly longer elimination half-life, lower clearance, higher peak concentration and lower trough concentration in comparison to the twice-daily schedule. The use of amikacin 20 mg/kg daily delivered in a single daily dose is recommended for immunocompromised pediatric patients with fever and neutropenia, in spite of the measured pharmacokinetic differences.


Diagnostic accuracy of nasal nitric oxide for establishing diagnosis of primary ciliary dyskinesia: a meta-analysis.
To date, diagnosis of Primary Ciliary Dyskinesia (PCD) remains difficult and challenging. We systematically evaluated the diagnostic performance of nasal Nitric Oxide (nNO) measurement for the detection of PCD, using either velum-closure (VC) or non-velum-closure (non-VC) techniques. All major electronic databases were searched from inception until March 2015 using appropriate terms. The sensitivity and specificity of nNO measurement was calculated in PCD patients diagnosed by transmission electron microscopy, high speed video-microscopy or genetic testing. Summary receiver operating characteristic (HSROC) curves were drawn using the parameters of the fitted models. Twelve studies provided data for 13 different populations, including nine case-control (n = 793) and four prospective cohorts (n = 392). The overall sensitivity of nNO measured by VC techniques was 0.95 (95 % CI 0.91-0.97), while specificity was 0.94 (95 % CI 0.88-0.97). The positive likelihood ratio (LR+) of the test was 15.8 (95 % CI 8.1-30.6), whereas the negative likelihood ratio (LR-) was 0.06 (95 % CI 0.04-0.09). For non-VC techniques, the overall sensitivity of nNO measurement was 0.93 (95 % CI 0.89-0.96) whereas specificity was 0.95 (95 % CI 0.82-0.99). The LR+ of the test was 18.5 (95 % CI 4.6-73.8) whereas the LR- was 0.07 (95 % CI 0.04-0.12). Diagnostic accuracy of nNO measurement both with VC and non-VC maneuvers is high and can be effectively employed in the clinical setting to detect PCD even in young children, thus potentiating early diagnosis. Measurement of nNO merits to be part of a revised diagnostic algorithm with the most efficacious combination of tests to achieve PCD diagnosis.


Vitamin D receptor gene polymorphisms among Emirati patients with type 2 diabetes mellitus.
At a prevalence rate close to 19.5%, the UAE has one of the highest rates of Type 2 Diabetes Mellitus (T2DM) in the world. Genome wide association studies (GWAS) have led to the identification of several genetic variants that are associated with T2DM. Recently, genes involved in vitamin D metabolism have gained interest because of the association between vitamin D deficiency (VDD) and increased risk for T2DM. Among these, the Vitamin D receptor (VDR) gene is a good candidate for T2DM susceptibility. The aim of this study was to investigate the association between VDR polymorphisms and T2DM among a representative sample of the Emirati population. In this cross sectional study, two hundred and sixty four patients with T2DM and ninety-one healthy controls were enrolled. The study population was genotyped for the three VDR gene mutations, TaqI (rs731236), FokI (rs2228570) and BsmI (rs1544410). VDR alleles and haplotypes were compared between patients and their healthy controls. The mean age of the T2DM cohort was 60±11.59years and 48.21±12.17years for the healthy controls. The G-allele and GG genotype of rs2228570 and T-allele and TT genotype of rs1544410 SNPs were associated with T2DM. In regards to T2DM-related metabolic complications, the AG and GG genotypes of rs731236 were significantly associated with higher total cholesterol (p=0.011) and LDL-cholesterol (p=0.009) levels in the patients with T2DM. In contrast, the CT genotype of rs1544410 was significantly associated with lower BMI (p=0.031) and the TT genotype was associated with lower LDL-cholesterol level (p=0.007). The frequency of AAT and GGC haplotypes was also different between groups (p=0.014; p=0.032, respectively), implying that these haplotypes of the VDR gene are associated with the susceptibility to T2DM in the Emirati population. To conclude, an association between SNPs in the VDR gene (except for rs731236) and T2DM per se was demonstrated. The rs731236 variant was shown to be associated with high cholesterol and LDL-cholesterol levels in T2DM patients, while rs1544410 was associated with lower BMI and lower LDL cholesterol levels. Our results imply that alleles and haploypes of the VDR gene are associated with the susceptibility to T2DM in the Emirati population.


Nesfatin-1 inhibits free fatty acid (FFA)-induced endothelial inflammation via Gfi1/NF-κB signaling.
Nesfatin-1 is a neuropeptide produced in the hypothalamus. It is known that Nesfatin-1 is involved in food uptake, fat storage, and other metabolic regulation. We hypothesized that Nesfatin-1 may play a role in cardiovascular tissue. Free fatty acids (FFAs) are known to be the risk factor for cardiovascular diseases. FFA-mediated endothelial dysfunction is the critical mechanism of many cardiovascular disorders. The present study explores the protective effects of Nesfatin-1 on FFA-induced endothelial inflammation and the underlying mechanism. We found that significantly increased lactate dehydrogenase release and production of inflammatory factors were observed in FFA-treated human aortic endothelial cells (HAECs), accompanied by the enhanced attachment of U937 monocytes to HAECs and upregulated cell adhesion molecule vascular cell adhesion molecule-1, which were dramatically reversed by the treatment with Nesfatin-1. In addition, the promoted level of nuclear regulator NF-κB p65 and transcriptional function of NF-κB in FFA-treated HAECs were greatly suppressed by HAECs. Growth Factor Independent 1 Transcriptional Repressor 1 (Gfi1), an important negative regulator of NF-κB activity, was significantly downregulated in HAECs by FFAs and was upregulated by Nesfatin-1. Lastly, the inhibitory effects of Nesfatin-1 against FFA-induced NF-κB activation and adhesion of U937 monocytes to HAECs were abolished by the knockdown of Gfi1. In conclusion, our data reveal that Nesfatin-1 inhibited FFA-induced endothelial inflammation mediated by the Gfi1/NF-κB signaling pathway.


c-Myc stimulates cell invasion by inhibiting FBX8 function.
c-Myc is a cellular onco-protein and a transcriptional activator important for cell growth, cell division, and tumorigenesis. Despite all that is known of its function, the mechanism of how c-Myc contributes to tumorigenesis is unclear. To gain insight into the mechanism through which c-Myc protein exerts its oncogenic activity, we performed large-scale, tandem repeat affinity purification and identified the F box only protein 8 (FBX8), an F-box- and Sec7 domain-containing protein, as a novel Myc-binding protein. The c-Myc/FBX8 interaction was mediated by the c-Myc box II (MBII) region. We also confirmed that Myc protein overexpression in 293T cells affected FBX8 cellular translocation and led to recovery from FBX8-mediated inhibition of ADP-ribosylation factor 6 (ARF6) function during cell invasion. Together, these results suggest that FBX8 is a novel c-Myc binding protein and that c-Myc induces cell invasive activity through the inhibition of FBX8 effects on ARF6 function during cell invasion.