The metabolism of fatty acids in human Bietti crystalline dystrophy.
To investigate the role of abnormal lipid metabolism in Bietti crystalline dystrophy. Cultured human lymphocytes and fibroblasts from patients with Bietti crystalline dystrophy (BCD) were incubated in the presence of [(14)C]18:3n-3 or [(14)C]18:2n-6. Incorporation into the cellular lipid pools and further metabolism by desaturation or elongation were monitored by thin-layer chromatography and HPLC. Results were compared with those in normal control subjects and patients with Wolman disease (WD). Pulse-chase experiments with labeled fatty acids in all groups showed that, after 1 hour, radioactivity was largely confined to the triacylglyceride (TG) and choline phosphoglyceride (CPG) pools. However, after several hours, radioactivity was transferred from the TG and CPG pools, some going to the serine and ethanolamine phosphoglyceride (SPG and EPG) pools. Fibroblasts from all groups showed direct transfer of fatty acids (FAs) into CPG and EPG. Incorporation of labeled FAs into the EPG pool paralleled extensive desaturation and elongation of 18:2n-6 to 22:5n-6 and 18:3n-3 to 22:6n-3. Fibroblasts from patients with WD (a lysosomal acid lipase deficiency characterized by excessive lipid accumulation), showed higher incorporation of 18:2n-6 into TGs than did normal or BCD fibroblasts. Conversely, fibroblasts from patients with BCD showed lower conversion of 18:3n-3, but not of 18:2n-6, into polyunsaturated FAs (PUFAs) than those of normal subjects or patients with WD. This was true for total FAs, CPGs, and EPGs. Similar results were found in both fibroblasts and lymphocytes; however, unlike fibroblasts, lymphocytes from normal subjects showed similar levels of incorporation of FAs into EPGs and CPGs. In contrast, incorporation of 18:3n-3 into EPGs was decreased in lymphocytes from patients with BCD. BCD is characterized by a lower than normal conversion of FA precursors into n-3 PUFA, whereas there is a higher than normal level of n-6 and n-3 FAs incorporation into TGs in cells from patients with WD. These findings raise the possibility that abnormal lipid metabolism associated with BCD is the result of deficient lipid binding, elongation, or desaturation in contrast to the lysosomal acid lipase deficiency found in Wolman disease.


Ultrafast ranging lidar based on real-time Fourier transformation.
Real-time Fourier-transformation-based ranging lidar using a mode-locked femtosecond fiber laser is demonstrated. The object signal and the reference signal are guided from a fiber Mach-Zehnder interferometer into a dispersive element. The two optical pulses extend and overlap with each other temporally, which yields a microwave pulse on the photodetector with its frequency proportional to the time delay between the two signals. The temporal interferograms are transformed from the time domain into the frequency domain using a time-to-frequency conversion function obtained in the calibration process. The Fourier transform is used in the data processing. A range resolution of 334 nm at a sampling rate of 48.6 MHz over a distance of 16 cm is demonstrated in the laboratory.


Evaluation of patient selection guidelines for endoluminal AAA repair with the Zenith Stent-Graft: the Australasian experience.
To review the patient selection guidelines for endovascular repair of abdominal aortic aneurysms (AAA) using the Zenith Endovascular Graft and establish an order of importance for each criterion. The Zenith Endovascular Graft Research Database was interrogated for information on 238 patients (209 men; mean age 74.9 +/- 0.9 years, range 50-94) treated with a Zenith bifurcated graft from 1994 to 1998. The common complications of endoluminal AAA repair (endoleak, migration, graft occlusion, graft kinking, conversion, and deployment failure) were analyzed to determine any associations with selection criteria. By 1998, 69% of endograft patients did not meet the recommended guidelines; however, primary and secondary aneurysm exclusion rates were 87% and 94%, respectively. Over a median follow-up of 13.4 months (interquartile range 2.8-24.0), 38 (16%) patients developed 28 (74%) early and 10 (26%) late type-I endoleaks. The endoleak rate in necks < or = 10 mm long was 57% (8/14). Endoleak was associated with a neck contour change >3 mm (p = 0.003) and neck length <20 mm (p = 0.045). The risk of proximal endoleak was 4 times greater if at least one of the proximal neck guidelines was breached; combined guideline deviations of "contour change and large diameter" (p = 0.0004), "contour change and short length" (p = 0.006), "large diameter and short length" (p = 0.01), and "contour change and angle" (p = 0.03) also increased the risk of endoleak. Endograft migration was seen in 10 (4.2%) cases; only neck diameter >28 mm (p = 0.0024) was associated with this complication. Proximal neck contour, length, and diameter are the most important criteria in terms of endoleak development. Breaching the proximal neck length criterion resulted in a 4-fold increase in endoleak, and combined deviations from the guidelines multiplied the effect. Necks < or = 10 mm long are unsuitable for the standard Zenith graft.


Source-enhanced coalescence of trees in a random forest.
The time evolution of a random graph with varying number of edges and vertices is considered. The edges and vertices are assumed to be added at random by one at a time with different rates. A fresh edge connects either two linked components and forms a new component of larger order g (coalescence of graphs) or increases (by one) the number of edges in a given linked component (cycling). Assuming the vertices to have a finite valence (the number of edges connected with a given vertex is limited) the kinetic equation for the distribution of linked components of the graph over their orders and valences is formulated and solved exactly by applying the generating function method for the case of coalescence of trees. The evolution process is shown to reveal a phase transition: the emergence of a giant linked component whose order is comparable to the total order of the graph. The time dependencies of the moments of the distribution of linked components over their orders and valences are found explicitly for the pregelation period and the critical behavior of the spectrum is analyzed. It is found that the linked components are γ distributed over g with the algebraic prefactor g-5/2. The coalescence process is shown to terminate by the formation of the steady-state γ spectrum with the same algebraic prefactor.


[Combination therapy with ofloxacin and chloramphenicol against typhoid fever].
Recently we experienced two male typhoid patients who required additional treatment with CP sodium succinate (CP succinate) to OFLX therapy. Although both of the cases were administered 900 mg/day of OFLX orally for three and four days, respectively, the clinical efficacies were not sufficient. We added 2.0 g/day of CP succinate intravenously for six days, although a lasting high fever returned to normal level in a few days. The administration of OFLX was continued up to 14 days. The daily doses of OFLX during the co-medication with CP succinate were 600 mg in one case and 900 mg in the other case. In both cases no recurrence was observed clinically and bacteriologically for six months after their discharge. No adverse reaction was observed throughout the therapy.


PB1 domain-dependent signaling complex is required for extracellular signal-regulated kinase 5 activation.
MEKK2, MEK5, and extracellular signal-regulated kinase 5 (ERK5) are members of a three-kinase cascade for the activation of ERK5. MEK5 is the only MAP2K to express a PB1 domain, and we have shown that it heterodimerizes with the PB1 domain of MEKK2. Here we demonstrate the MEK5 PB1 domain is a scaffold that also binds ERK5, functionally forming a MEKK2-MEK5-ERK5 complex. Reconstitution assays and CFP/YFP imaging (fluorescence resonance energy transfer [FRET]) measuring YFP-MEKK2/CFP-MEK5 and CFP-MEK5/YFP-ERK5 interactions define distinct MEK5 PB1 domain binding sites for MEKK2 and ERK5, with a C-terminal extension of the PB1 domain contributing to ERK5 binding. Stimulus-dependent CFP/YFP FRET in combination with mutational analysis was used to define MEK5 PB1 domain residues critical for the interaction of MEKK2/MEK5 and MEK5/ERK5 required for activation of the ERK5 pathway in living cells. Fusion of the MEK5 PB1 domain to the N terminus of MEK1 confers ERK5 regulation by a MAP2K normally regulating only ERK1/2. The MEK5 PB1 domain confers stringent MAP3K regulation of ERK5 relative to more promiscuous MAP3K control of ERK1/2, JNK, and p38.


SR146131, a cholecystokinin-A receptor agonist, antagonizes prepulse inhibition deficits produced by dizocilpine and DOI.
Converging evidence has demonstrated that cholecystokinin (CCK) inhibits mesolimbic brain dopamine (DA) function via activation of CCK-A (CCK-1) receptors. These effects of CCK have stimulated interest in the potential use of CCK agonists as antipsychotic drugs. Most research on the antipsychotic-like drug effects of CCK has used CCK or CCK analogues that nonselectively activate both CCK-A and CCK-B (CCK-2) receptors, which may produce opposite effects. SR146131, a CCK-A selective nonpeptide agonist, has recently been developed (Sanofi-Synthelabo). To determine whether SR146131 exhibits antipsychotic-like qualities in the prepulse inhibition (PPI) paradigm. We performed experiments to determine whether SR146131 (vehicle, 0.01, 0.1, 1.0 mg/kg) would attenuate PPI deficits induced by amphetamine (2.0 mg/kg), an indirect dopamine agonist, and dizocilpine (0.1 mg/kg), a noncompetitive N-methyl-D-aspartate (NMDA) antagonist. Since SR146131 demonstrated significant effects on PPI disrupted by the noncompetitive NMDA antagonist, an effect associated with drugs that inhibit serotonin (5HT)2A transmission, we also tested the effects of SR146131 on PPI disruption produced by 2,5-dimethoxy-4-iodoamphetamine (DOI, 0.5 mg/kg), a direct 5HT2A agonist. SR146131 did not significantly affect startle magnitude, baseline PPI, or amphetamine-induced PPI deficits. However, it dose-dependently antagonized dizocilpine and DOI-induced PPI deficits. The lack of an effect of SR146131 on amphetamine-induced disruption of PPI suggests that a selective nonpeptide CCK-A agonist may not produce antipsychotic-like effects on dopamine transmission. However, the unexpected effects of SR146131 on dizocilpine and DOI-induced PPI deficits are consistent with the effects of drugs that inhibit transmission in the 5HT2A receptor system, including atypical antipsychotic drugs. Possible mechanisms underlying these findings are discussed.


[Smoking habits in a family physician's practice].
Poland is the one of the countries in the European Union with the highest prevalence of smokers. The involvement of family physicians in smoking cessation activity could improve this situation. The aim of this study was to estimate smoking habits, their intensity and nicotine dependence in a family physician's practice (urban and rural population). An additional aim was to estimate smoking habits in relation to the presence of smoking-related disease, gender, location and motivation to stop smoking. This study was part of an investigation into the prevalence and severity of chronic obstructive pulmonary disease (COPD) in the same population. Statistical analysis of questionnaires about smoking and history of respiratory diseases, Fagerström's nicotine dependence test and a motivation to quit test were performed. Questionnaires were filled in by 1960 subjects (87% of those eligible). There were 29.6% current smokers, 24.9% ex-smokers, and 45.5% never-smokers. There were 39.4% current smokers among men, and 23.3% among women. Current smokers were more numerous in the rural population. 54% of women urban dwellers and 73% of women from rural population never smoked. There were no significant differences in the motivation to stop smoking or in the nicotine dependence among smokers with and without COPD nor according to the severity of COPD. Smoking habits among the studied population were comparable with national and regional data. The intensity of smoking habits among female town dwellers is especially alarming.


Predictors of Increased Daytime Sleepiness in Patients with Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study.
Background. Patients with Chronic Obstructive Pulmonary Disease (COPD) suffer from increased daytime sleepiness. The aim of this study was to identify potential predictors of subjective daytime sleepiness with special regard to sleep-related breathing disorder and nocturnal activity. Methods. COPD patients were recruited at the University Hospital Basel, Switzerland. COPD risk groups A-D were determined according to spirometry and COPD Assessment Test (CAT). Breathing disorder evaluation was performed with the ApneaLink device. Nocturnal energy expenditure was measured with the SenseWear Mini Armband. Subjective daytime sleepiness was recorded using the Epworth Sleepiness Scale (ESS). Results. Twenty-two patients (36%) were in COPD risk group A, 28 patients (45%) in risk group B, and 12 patients (19%) in risk groups C + D (n = 62). Eleven patients (18%) had a pathological ESS ≥ 10/24. ESS correlated positively with CAT (r = 0.386, p < 0.01) and inversely with age (r = -0.347, p < 0.01). In multiple linear regression age (β = -0.254, p < 0.05), AHI (β = 0.287, p < 0.05) and CAT score (β = 0.380, p < 0.01) were independent predictors of ESS, while nocturnal energy expenditure showed no significant association (p = 0.619). Conclusion. These findings provide evidence that daytime sleepiness in COPD patients may partly be attributable to nocturnal respiratory disturbances and it seems to mostly affect younger patients with more severe COPD symptoms.


In vivo Antimalarial and Antitrypanosomal Activity of Strychnogucine B, a Bisindole Alkaloid from Strychnos icaja.
Strychnogucine B is a bisindole alkaloid previously isolated from Strychnos icaja that possesses promising in vitro antiplasmodial properties. This compound was synthesized in four steps from (-)-strychnine. As no acute toxicity was observed at the highest tested cumulative dose of 60 mg/kg, its in vivo antimalarial activity was determined intraperitoneally at 30 mg/kg/d in a Plasmodium berghei murine model. In the Peters's 4-d suppressive test, this alkaloid suppressed the parasitaemia by almost 36% on day 5 and 60% on day 7 compared to vehicle-treated mice. In addition to this interesting antimalarial activity, it showed moderate in vitro antitrypanosomal activity but no in vivo activity in an acute Trypanosoma brucei model. It was also inactive in vitro on Leishmania mexicana promastigotes. This highlights its selective antimalarial efficacy and leads to further investigation to assess its potential as new antimalarial lead compound.


The Immunoregulatory Activities of Activated Protein C in Inflammatory Disease.
Tissue injury prompts the initiation of host defense responses to limit blood loss, restrict pathogen entry, and promote repair. Biochemical and cellular pathways that lead to blood coagulation serve a fundamental role in generating a physical barrier at the wound site, but have also evolved to promote immune response to injury. Similarly, anticoagulant pathways that attenuate clot formation also regulate innate and adaptive immune responses. Of particular importance is activated protein C (APC) which serves as a principal regulator of thrombin generation, shapes the innate immune response to infection, and has been shown to contribute to the adaptive immune response in several preclinical models of autoimmune disease. APC controls blood coagulation by proteolytic degradation of procoagulant activated cofactors essential for fibrin clot development, but also cleaves multiple additional substrates and interacts with cell surface receptors to exert additional physiologically important roles. In this review, we focus on the molecular mechanisms utilized by APC to limit inflammation and, in particular, current understanding of the basis for APC anticoagulant and signaling activities. In particular, we provide an overview of established and emerging signaling pathways initiated by APC on endothelial cells, monocytes, neutrophils, dendritic cells, and T cells to control and regulate immune cell physiology. Finally, we consider the impact of APC activity in the context of both acute and chronic inflammatory disease, and the continuing efforts to harness the immunoregulatory properties of recombinant APC for therapeutic use.


Triterpenoid saponins from the roots of Aralia spinifolia.
Two new triterpenoid saponins named aralosides H[1] and J [2], along with four known triterpenoid saponins 3-6 were isolated from the roots of Aralia spinifolia. Their structures were determined as 3-O-beta-D-xylopyranosyl-(1-->2)-[beta-D-glucuronopyranosyl (1-->3)]-beta-D-glucopyranosyl-oleanolic acid [1], 3-O-alpha-L-arabinofuranosyl-(1-->4)-beta-D-glucuronopyranosyl- oleanolic acid 28-O-beta-D-galactopyranosyl ester [2], araloside A methyl ester [3], chikusetusaponin Ib [4], chikusetusaponin IV [5], and araloside A [6] on the basis of spectral and chemical data.


Rapid tryptophan depletion following cognitive behavioural therapy for panic disorder.
The aim of this study was to examine the effect of rapid tryptophan depletion (RTD) combined with a panicogenic challenge in patients with panic disorder who had responded to treatment with cognitive behavioural therapy (CBT). We hypothesised that RTD (compared with the control drink) would result in an increase in anxiety symptoms when provoked by a panicogenic challenge with the benzodiazepine antagonist, flumazenil. Nine patients with panic disorder who had responded to CBT received a tryptophan-free amino acid drink on one occasion and a control drink on the other in a double-blind crossover design. In addition, they received flumazenil and placebo infusions on each day. Our hypothesis regarding the effects of RTD was supported by findings of a significant interaction between RTD and flumazenil on measures from visual analogues scales (total) and the Spielberger State Anxiety inventory. A somewhat unexpected finding was that in this group of CBT responders, the panicogenic effect of flumazenil was not completely blocked by treatment. This meant that although four of the nine subjects (44%) reported a panicogenic effect of flumazenil on the RTD day, this was not significantly different from the rate of panic attacks in response to flumazenil on the control day. We suggest that the partial return of symptoms in response to flumazenil reflects a vulnerability to RTD in this group of panic disorder patients who had responded to treatment with CBT.


Proposal for a state health technology assessment program.
Evidence suggests that a significant number of medical technologies are of little or no benefit to patients. Under current budgetary pressures, state health care programs cannot afford continued spending on unnecessary medical care without further cuts in enrollment. Limiting coverage of high-tech care only to indications supported by good clinical evidence would help save state health care dollars. However, there is currently no public process to formally evaluate new medical interventions in Wisconsin. In fact, new therapies often are introduced into clinical practice, and covered by state health insurance programs, even when there is weak or questionable evidence of clinical effectiveness. This article proposes the creation of a state Health Technology Assessment program in Wisconsin to systematically evaluate new tests or treatments, and to promote evidence-based coverage decisions. Such a program would help limit wasteful spending on unnecessary technologies, reinforce good clinical practice, and protect patients from the risks of interventions that have not been proven effective.


[Biopsy and resection of skull base tumors using transorbital endoscopic approaches: primary results].
Transorbital neuroendoscopic surgery is a new skull base surgery technique that uses the orbit as an artificial corridor to the anterior and middle skull base. The space is created between the periorbita and orbital walls by their additional resection and gentle traction of the orbital contents. Skull base structures are reached using cosmetic incisions. The major advantages of transorbital endoscopic approaches include their variety, possibility of their combination, and access to the central and lateral skull base lesions. The aim of this study was to analyze the primary results of transorbital endoscopic biopsy and resection of skull base lesions, which were performed at the N.N. Burdenko National Medical Research Center for Neurosurgery (Moscow, Russia). In 2017-2018, the authors operated on 12 patients with skull base lesions using transorbital endoscopic approaches. The series included ten female and two male patients. The patient's age varied between 24 and 78 years. All patients were admitted for the first time. Half of them underwent biopsy, while the other half underwent tumor resection. The upper-lateral transorbital approach with an eyebrow incision was used in most (8/12) patients; the retrocaruncular approach was used in two cases; the lateral retrocanthal approach was applied in one case; the upper-medial approach with an eyebrow incision was used in one patient. The histological diagnosis was established in all six biopsies: 3 pseudotumors, 2 WHO Grade I meningiomas, and 1 clear-cell kidney cancer. Tumor resection was successful in 5 out of 6 patients; repeated surgery was required in one patient. In one case, the transorbital approach was combined with the transnasal one for treatment of supraorbital mucocele. One patient developed a persistent neurological deficit (dysfunction of the fifth and sixth nerves) after upper-lateral transorbital surgery. There were no poor cosmetic results in the series. Transorbital neuroendoscopic surgery needs an interdisciplinary approach and a sufficient amount of surgical experience. Surgical skills setting includes microsurgical and endoscopic tumor resection, harvesting and positioning of free and vascularized grafts for skull base reconstruction and prevention of postoperative enophthalmos, and facial incisions and their cosmetic closure. Implementation of new local vascularized flaps may significantly improve the results of transorbital endoscopic procedures and extend the spectrum of indications.


Stroke recurrence within 2 years after ischemic infarction.
We prospectively studied stroke recurrence in 1,273 patients with ischemic stroke who were entered into the Stroke Data Bank. Median follow-up was 13 months. The 2-year cumulative recurrence rate among these patients was 14.1%. Age, sex, race, history of hypertension, atrial fibrillation, or transient ischemic attacks, and stroke location were not associated with a higher risk of stroke recurrence. Patients with an elevated blood pressure, an abnormal initial computed tomogram, or a history of diabetes mellitus were at a higher risk of stroke recurrence. In contrast, patients with an infarct of unknown cause were at a lower risk of stroke recurrence than patients with a defined stroke mechanism, such as lacune, embolism, or atherosclerosis. A multivariate model suggests that patients at the lowest risk for stroke recurrence have a low diastolic blood pressure, no history of stroke, no history of diabetes mellitus, and an infarct of unknown cause.


Tissue-specific impacts of aging and genetics on gene expression patterns in humans.
Age is the primary risk factor for many common human diseases. Here, we quantify the relative contributions of genetics and aging to gene expression patterns across 27 tissues from 948 humans. We show that the predictive power of expression quantitative trait loci is impacted by age in many tissues. Jointly modelling the contributions of age and genetics to transcript level variation we find expression heritability (h2) is consistent among tissues while the contribution of aging varies by >20-fold with [Formula: see text] in 5 tissues. We find that while the force of purifying selection is stronger on genes expressed early versus late in life (Medawar's hypothesis), several highly proliferative tissues exhibit the opposite pattern. These non-Medawarian tissues exhibit high rates of cancer and age-of-expression-associated somatic mutations. In contrast, genes under genetic control are under relaxed constraint. Together, we demonstrate the distinct roles of aging and genetics on expression phenotypes.


Bypassing sluggishness: SWAP algorithm and glassiness in high dimensions.
The recent implementation of a swap Monte Carlo algorithm (SWAP) for polydisperse glass forming mixtures bypasses computational sluggishness and closes the gap between experimental and simulation timescales in physical dimensions d=2 and 3. Here, we consider suitably optimized systems in d=2,3,⋯,8 to obtain insights into the performance and underlying physics of SWAP. We show that the speedup obtained decays rapidly with increasing the dimension. SWAP nonetheless delays systematically the onset of the activated dynamics by an amount that remains seemingly finite in the limit d→∞. This shows that the glassy dynamics in high dimensions d>3 is now computationally accessible using SWAP, thus opening the door for the systematic consideration of finite-dimensional deviations from the mean-field description.


Intestinal Fatty Acid Binding Protein, a Biomarker of Intestinal Barrier, is Associated with Severity of Psoriasis.
Alterations of intestinal microbiota play a significant role in the pathogenesis of psoriasis. Dysbiosis may cause disruption of the intestinal barrier, which contributes to immune activation by translocation of microbial antigens and metabolites. Intestinal fatty acid binding protein (I-FABP) serves as a biomarker of enterocyte damage. The aim of this study was to investigate clinical and metabolic factors affecting plasma concentration of I-FABP in patients with psoriasis. Eighty patients with psoriasis and 40 control subjects were enrolled in the study. Serum I-FABP (243.00 (108.88-787.10) vs. 114.38 (51.60-241.60) pg/ml, p < 0.001) and neutrophil to lymphocyte ratio (NLR; 2.59 (1.96-3.09) vs. 1.72 (1.36-47 2.11), p < 0.01) were significantly increased in patients with psoriasis compared to controls. A significant positive correlation was found between I-FABP and body mass index (BMI) (r = 0.82, p < 0.001), Psoriasis Area Severity Index (PASI) (r = 0.78, p < 0.001) and neutrophil to lymphocyte ratio (NLR) (r = 0.24, p < 0.001). Rising quartiles of I-FABP were associated with increasing values of BMI, PASI and NLR. The results of the logistic regression model confirmed an increased risk of higher disease severity with I-FABP concentration - odds ratio 3.34 per 100 pg/mL I-FABP increase. In conclusion, intestinal integrity in patients with psoriasis is affected by obesity, severity of the disease and systemic inflammation. The modulation of gut barrier may represent a new therapeutic approach for psoriasis.


[Hepatopathy of the drug addict. Morphological data and incidence of serological markers of hepatitis B virus in 65 patients].
65 heroin addicts who had previously underwent liver biopsy for liver disease were studied retrospectively; the histological features of liver disease and hepatitis B serological markers were analyzed in detail. Alcohol abuse was rare in this group (6.1%), but moderate or occasional use of mild alcoholic beverages was common. The liver biopsy examination showed that 35 (54%) had chronic active hepatitis, 21 (32%) had non specific reactive hepatitis, 6 (9%) had acute hepatitis and 3 (5%) had chronic persistent hepatitis. Steatosis was present in 41% of all biopsies. 19 subjects were HBsAg positive, and in 60 (92.3%) at least one marker of HBV was found. Observation of liver biopsy specimen under polarized light did not disclose the presence of birefringent material consistent with talc or other inorganic material. These results suggest that HBV infection is responsible for liver disease in heroin addicts in the great majority of cases.


Flow cytometric microsphere-based immunoassay: analysis of secreted cytokines in whole-blood samples from asthmatics.
The ability of flow cytometry to resolve multiple parameters was used in a microsphere-based flow cytometric assay for the simultaneous determination of several cytokines in a sample. The flow cytometer microsphere-based assay (FMBA) for cytokines consists of reagents and dedicated software, specifically designed for the quantitative determination of cytokines. We have made several improvements in the multiplex assay: (i) dedicated software specific for the quantitative multiplex assay that processes data automatically, (ii) a stored master calibration curve with a two-point recalibration to adjust the stored curve periodically, and (iii) an internal standard to normalize the detection step in each sample. Overall analytical performance, including sensitivity, reproducibility, and dynamic range, was investigated for interleukin-4 (IL-4), IL-6, IL-10, IL-12, gamma interferon (IFN-gamma), and tumor necrosis factor alpha. These assays were found to be reproducible and accurate, with a sensitivity in the picograms-per-milliliter range. Results obtained with FMBA correlate well with commercial enzyme-linked immunosorbent assay data (r > 0.98) for all cytokines assayed. This multiplex assay was applied to the determination of cytokine profiles in whole blood from atopic and nonatopic patients. Our results show that atopic subjects' blood produces more IL-4 (P = 0.003) and less IFN-gamma (P = 0.04) than the blood of nonatopic subjects. However, atopic asthmatic subjects' blood produces significantly more IFN-gamma than that of atopic nonasthmatic subjects (P = 0.03). The results obtained indicate that the FMBA technology constitutes a powerful system for the quantitative, simultaneous determination of secreted cytokines in immune diseases.


MicroRNA-210 contributes to peripheral nerve regeneration through promoting the proliferation and migration of Schwann cells.
Peripheral nerve injury impacts the daily life of affected individuals. MicroRNA (miR)-210 is a multifunctional miR and has effects on the proliferation, migration and differentiation of cells. However, whether miR-210 has effects on peripheral nerve regeneration has remained elusive. In the present study, the miR-210 levels in a rat model of sciatic nerve injury were evaluated by reverse-transcription quantitative PCR and the effects of miR-210 on the proliferation and migration of Schwann cells were explored. Elevated miR-210 levels were discovered in the sciatic nerve injury rat model. miR-210 mimics were found to promote the proliferation and migration of Schwann cells, while miR-210 inhibitor was found to inhibit the proliferation and migration of Schwann cells. Further study showed that miR-210 had effects on the expression of growth-associated protein-43, myelin-associated glycoprotein and myelin basic protein. These results showed that miR-210 had effects on the proliferation and migration of Schwann cells and may be involved in the peripheral nerve regeneration.


Kaposi's sarcoma in transfusion-associated acquired immunodeficiency syndrome. A case report and review of the literature.
Kaposi's sarcoma in transfusion-associated acquired immunodeficiency syndrome is rare; to our knowledge, only four previous cases have been reported. We report a unique case of transfusion-associated acquired immunodeficiency syndrome in a 74-year-old woman. At autopsy, both lungs were extensively affected by Kaposi's sarcoma, Pneumocystis carinii, and cytomegalovirus infection. These three processes led to respiratory failure and accounted for her death.


Severe Acute Subdural Hematoma in a Child following a Minor Head Trauma in the Context of a Recent Antecedent Head Injury: A Case Report.
Knowledge of the force required to generate a subdural hematoma is important when considering the veracity of histories given by family members of young children. Traditional wisdom is that a substantial impact is required to cause an acute subdural hematoma. We present a case of acute subdural hematoma following a low-level fall in a 3-year-old patient. An antecedent head injury associated with normal CT scan might have had some bearing on this outcome.


Fluorescent DNA labeling by N-mustard analogues of S-adenosyl-L-methionine.
Azide and alkyne-functionalized N-mustard analogues of S-adenosyl-L-methionine have been synthesized and were demonstrated to undergo efficient methyltransferase-dependent DNA alkylation by M.TaqI and M.HhaI. Subsequent labeling of the DNA with a fluorophore was carried out using copper-catalyzed azide-alkyne cycloaddition chemistry and was visualized by fluorescence scanning. This work demonstrates the utility of functionalized N-mustard analogues as biochemical tools to study biological methylation and offers a facile way to site-selectively label substrates of DNA methyltransferases.


Salivary gland gene expression atlas identifies a new regulator of branching morphogenesis.
During organ development, local changes in gene expression govern morphogenesis and cell fate. We have generated a microanatomical atlas of epithelial gene expression of embryonic salivary glands. The mouse submandibular salivary gland first appears as a single mass of epithelial cells surrounded by mesenchyme, and it undergoes rapid branching morphogenesis to form a complex secretory organ with acini connected to an extensive ductal system. Using laser capture microdissection, we collected samples from 14 distinct epithelial locations at embryonic days 12.5, 13.5, 14, and 15, and characterized their gene expression by microarray analysis. These microarray results were evaluated by qPCR of biological replicates and by comparisons of the gene expression dataset with published expression data. Using this gene expression atlas to search for novel regulators of branching morphogenesis, we found a substantial reduction in mRNA levels of GSK3β at the base of forming clefts. This unexpected finding was confirmed by immunostaining, and inhibition of GSK3β activity enhanced salivary gland branching. This first microanatomical expression atlas of a developing gland characterizes changes in local gene expression during salivary gland development and differentiation, which should facilitate the identification of key genes involved in tissue morphogenesis.


Mapping critical sites in collagen II for rational design of gene-engineered proteins for cell-supporting materials.
Collagen II is the most abundant protein of cartilage and forms a network of fibrils extended by proteoglycans that enables cartilage to resist pressure. The surface of the collagen fibril serves as a platform for the attachment of collagen IX, growth factors, and cells. In this study we examined the mechanism of the interaction of chondrocytes with recombinant versions of procollagen II, in which one of the four blocks of 234 amino acids that define repeating D periods of the collagen triple helix has been deleted. Analysis of the attachment of chondrocytes to collagen II variants with deleted D periods indicated that the collagen II monomer contains randomly distributed sites critical for cell binding. However, as was shown by spreading and migration assays, the D4 period, which is between residues 703 to 936, contains amino acids critical for cell motility. We also showed that binding, spreading, and migration of chondrocytes through three-dimensional nanofibrillar collagenous matrices are controlled by an interaction of the collagen triple helix with beta1 integrins. The results of this study provide a basis for the rational design of a scaffold containing genetically engineered collagen with a high density of specific sites of interaction.


A double chain reversal loop and two diagonal loops define the architecture of a unimolecular DNA quadruplex containing a pair of stacked G(syn)-G(syn)-G(anti)-G(anti) tetrads flanked by a G-(T-T) Triad and a T-T-T triple.
The architecture of G-G-G-G tetrad-aligned DNA quadruplexes in monovalent cation solution is dependent on the directionality of the four strands, which in turn are defined by loop connectivities and the guanine syn/anti distribution along individual strands and within individual G-G-G-G tetrads. The smallest unimolecular G-quadruplex belongs to the d(G2NnG2NnG2NnG2) family, which has the potential to form two stacked G-tetrads linked by Nn loop connectivities. Previous studies have focused on the thrombin-binding DNA aptamer d(G2T2G2TGTG2T2G2), where Nn was T2 for the first and third connecting loops and TGT for the middle connecting loop. This DNA aptamer in K(+) cation solution forms a unimolecular G-quadruplex stabilized by two stacked G(syn)-G(anti)-G(syn)-G(anti) tetrads, adjacent strands which are antiparallel to each other and edge-wise connecting T2, TGT and T2 loops. We now report on the NMR-based solution structure of the d(G2T4G2CAG2GT4G2T) sequence, which differs from the thrombin-binding DNA aptamer sequence in having longer first (T4) and third (GT4) loops and a shorter (CA) middle loop. This d(G2T4G2CAG2GT4G2T) sequence in Na(+) cation solution forms a unimolecular G-quadruplex stabilized by two stacked G(syn)-G(syn)-G(anti)-G(anti) tetrads, adjacent strands which have one parallel and one antiparallel neighbors and distinct non-edge-wise loop connectivities. Specifically, the longer first (T4) and third (GT4) loops are of the diagonal type while the shorter middle loop is of the double chain reversal type. In addition, the pair of stacked G-G-G-G tetrads are flanked on one side by a G-(T-T) triad and on the other side by a T-T-T triple. The distinct differences in strand directionalities, loop connectivities and syn/anti distribution within G-G-G-G tetrads between the thrombin-binding DNA aptamer d(G2T2G2TGTG2T2G2) quadruplex reported previously, and the d(G2T4G2CAG2GT4G2T) quadruplex reported here, reinforces the polymorphic nature of higher-order DNA architectures. Further, these two small unimolecular G-quadruplexes, which are distinct from each other and from parallel-stranded G-quadruplexes, provide novel targets for ligand recognition. Our results demonstrate that the double chain reversal loop connectivity identified previously by our laboratory within the Tetrahymena telomere d(T2G4)4 quadruplex, is a robust folding topology, since it has now also been observed within the d(G2T4G2CAG2GT4G2T) quadruplex. The identification of a G-(T-T) triad and a T-T-T triple, expands on the available recognition alignments for base triads and triples.


Umbilical serum insulin-like growth factor 1 (IGF-1) in newborns: effects of gestational age, postnatal age, and nutrition.
The aim of this study was to determine the relationship between nutrition, gestational age, and birth weight, and serum insulin-like growth factor 1 (IGF-1) levels in newborns. The first study group consisted of sixty newborns: thirty were fed with human breast milk and the others were fed with infant formula. Serum samples were obtained from all the newborns on days one and seven of life. Seventy-two pregnant women and their neonatal cord blood serum samples were obtained in a labor ward in the study group. All the serum samples were analyzed for IGF-1 by immunoassay. Newborns fed with human milk had higher serum IGF-1 concentrations compared to formula-fed controls (p < 0.05). Cord IGF-1 levels showed a negative correlation with birthweight (p < 0.05) and a positive correlation with gestational age (p < 0.05). These findings suggest that IGF-1 levels during the neonatal period are influenced by gestational age, birth weight, and nutrition.


Catalytically active polymers obtained by molecular imprinting and their application in chemical reaction engineering.
Molecular imprinting is a way of creating polymers bearing artificial receptors. It allows the fabrication of highly selective plastics by polymerizing monomers in the presence of a template. This technique primarily had been developed for the generation of biomimetic materials to be used in chromatographic separation, in extraction approaches and in sensors and assays. Beyond these applications, in the past few years molecular imprinting has become a tool for producing new kinds of catalysts. For catalytic applications, the template must be chosen, so that it is structurally comparable with the transition state (a transition state analogue, TSA) of a reaction, or with the product or substrate. The advantage of using these polymeric catalysts is obvious: the backbone withstands more aggressive conditions than a bio material could ever survive. Results are presented showing the applicability of a molecularly imprinted catalyst in different kinds of chemical reactors. It is demonstrated that the catalysts can be utilized not only in batch but also in continuously driven reactors and that their performance can be improved by means of chemical reaction engineering.


[Prevention of venous thromboembolism in urologic neoplasms].
We report our past experience on a sample of patients who underwent pelvic surgery to treat infiltrating bladder tumours. We observed the highest incidence of TVP (33.3%, 3 out of 9) in those patients with higher risk due to anaesthesia and type of surgery. One of our patients died of pulmonary embolism. Abdominal pelvic surgery in tumour-bearing patients can be risky due to high incidence of distal and proximal venous thrombosis often resulting in fatal pulmonary embolism (EP). The general risk factors should be evaluated. The diagnosis of venous thrombosis can be difficult to achieve only by clinical examination. Heparin administration as well as surgical techniques and physiotherapy are used as prophylactic measures to reduce the risk of venous thrombosis and to speed up recovery. Nowadays, there is an increasing risk of running into legal problems if appropriate measures to minimise the thromboembolism are not taken.


Maxillary posterior intrusion mechanics with mini-implant anchorage evaluated with the finite element method.
The goal of this study was to evaluate the effects of 3 maxillary posterior intrusion mechanics with mini-implant anchorage by using the finite element method. Finite element models were generated by assembling the images obtained by computed tomography and a laser surface scanner. For each posterior dental segment, a 300-g force was applied and distributed to the mini-implants in proportion to their calculated root surface areas. The most balanced intrusion and the most uniform stress distribution were obtained by concurrent force applications from the vestibular and palatinal sides. In the models with transpalatal arches and buccal force application, vestibular tipping movement and overall stress values were prominent. In all models, increased stress values were identified at the apical region of the first premolar roots and at the apical region of the first molar mesial root. The results of this study suggest that the apical region of the first premolar roots and the apical region of the first molar mesial root should be considered to be prone to resorption during posterior intrusion treatment. Posterior intrusion systems with force application from counterbalancing sites lead to a more uniform stress distribution and balanced intrusion than the mechanics with a transpalatal arch. For a balanced intrusion, root surface areas should be considered when determining the appropriate forces.


Molecular cloning of the complement regulatory factor I isotypes from the common carp (Cyprinus carpio).
Factor I is a novel serine protease that regulates complement activation. Here we report the complete primary structure of two isotypic factor Is isolated from the common carp ( Cyprinus carpio), a pseudotetraploid teleost. A carp hepatopancreas cDNA library was screened using two RT-PCR-amplified cDNA fragments encoding part of the carp factor I-like serine protease domain. Two distinct cDNA clones, designated FI-A and FI-B, were isolated. Their deduced amino acid sequences share 75.2% identity with each other. FI-A has a typical factor I-like domain organization composed of two disulfide-linked polypeptides (H-chain and L-chain). On the other hand, FI-B contains a novel sequence of 115 amino acids inserted at the N-terminus of the H-chain. Genomic Southern hybridization suggests that FI-A and FI-B are encoded by distinct genes in the carp genome. Expression analysis by RT-PCR revealed that the major site of FI-A expression is the ovary, whereas FI-B expression is detected mainly in the hepatopancreas at a level higher than that of FI-A. The present data, taken together, suggest that carp have duplicated genes coding for factor I, and FI-B with the novel insertion plays a dominant role in the complement system. In addition, homology search of the fugu genome database using the carp FI-A and FI-B sequences identified a putative fugu factor I gene, which has an exon/intron organization different from that of the human orthologue.


Regulation of intracerebral arteriolar tone by K(v) channels: effects of glucose and PKC.
Voltage-gated potassium (K(v)) channels in vascular smooth muscle cells (VSMC) are critical regulators of membrane potential and vascular tone. These channels exert a hyperpolarizing influence to counteract the depolarizing effects of intraluminal pressure and vasoconstrictors. However, the contribution of K(v) channel activity to the functional regulation of cerebral (parenchymal) arterioles within the brain is not known. Thus K(v) channel properties in parenchymal arteriolar SMCs were characterized. Isolated, pressurized parenchymal arterioles and arterioles in cortical brain slices exhibited robust constriction in the presence of the K(v) channel inhibitor 4-aminopyridine (4-AP). 4-AP also decreased the amplitude of K(v) currents recorded from SMCs. The steady-state activation and inactivation properties of K(v) currents suggested that these channels are composed of K(v)1.2 and 1.5 subunits, which was confirmed by RT-PCR. K(v) channels can be regulated by extracellular glucose, which may be involved in the functional hyperemic response in the brain. Thus the effects of glucose on K(v) channel activity and arteriolar function were investigated. Elevation of glucose from 4 to 14 mM significantly decreased the peak K(v) current amplitude and constricted arterioles. Arteriolar constriction was prevented by inhibition of protein kinase C (PKC), consistent with previous studies showing enhanced PKC activity in the presence of elevated glucose. In cortical brain slices, the dilation generated by neuronal activity induced by electrical field stimulation was decreased by 54% in 14 mM glucose when compared with the dilation in 4 mM glucose. In anesthetized mice the whisker stimulation-induced increase in local cerebral blood flow was also significantly decreased in 14 mM glucose, and this effect was similarly prevented by PKC inhibition. These findings point to a critical role for K(v) channels in the regulation of intracerebral arteriolar function and suggest that changes in perivascular glucose levels could directly alter vascular diameter resulting in a modulation of local cerebral blood flow.


Molecular Rearrangement of Longifolene by Arthrobacter ilicis T(2).
Arthrobacter ilicis T(2) brings about a unique type of cometabolic structural rearrangement of longifolene, a sesquiterpene, resulting in the formation of an acid. Infrared, nuclear magnetic resonance, mass spectrometry, and decoupling studies indicate that the acid product has a sativenelike structure, which is confirmed by conversion of the acid to its methyl ester and hydrocarbon.


Antigenic and allergenic determinants of ovalbumin. I. Peptide mapping, cleavage at the methionyl peptide bonds and enzymic hydrolysis of native and carboxymethyl OA.
The effects of enzymic cleavage and perturbing the conformation of the allergenic and antigenic determinants of hens egg white albumin (OA) were examined. Hens egg white extract of a total protein concentration 8.43 g/l was prepared. Isoelectric focusing in sodium dodecyl sulfate and polyacrylamide gel peptide maps for the crude egg white extract showed 26 spots visualized by staining with Coomassie blue. The OA was purified using a TSK-2000 gel filtration chromatography column. The specific allergenic reactivity of the purified OA as measured by RAST inhibition and direct RAST was relatively high: 3 micrograms gave an inhibition of approximately 10%. The cleavage of OA with cyanogen bromide resulted in 4 fractions, all capable of binding specific IgE with the first peak showing the highest inhibition. Thermal denaturation of OA had no direct effect on the antigenic reactivity. RAST inhibition values for the denatured protein were similar to those of the native protein. Carboxymethylation of OA gave a product with only 20% of the inhibition reactivity. Further treatment with trypsin did not abolish the allergenic and antigenic reactivities as shown by RAST inhibition and by deflection of OA line in rocket line immunoelectrophoresis. On the other hand, limited pepsin hydrolysis destroyed the antigenic structure of the molecule. The reactivity of OA is thus relatively stable and could easily be retained making it possible to identify the allergenic determinants of enzymic hydrolysates used for elucidating the antigenic structure of the molecule.


[Surgical management of shoulderblade fractures].
Fractures of the scapula are a domain of conservative therapy. In the majority of cases early restoration of function produces good results. Nevertheless there are types of fractures which should be reduced in open procedures and treated by an osteosynthetic method stable enough to ensure early mobilisation. A report of 5 patients is presented, 2 of whom showing severe, 1 light and the remaining 2 no concomitant injuries. Indications, access, choice of procedure and results are described.


Mobility Dynamics amid COVID-19 with a Case Study in Tennessee.
The year 2020 has marked the spread of a global pandemic, COVID-19, challenging many aspects of our daily lives. Different organizations have been involved in controlling this outbreak. The social distancing intervention is deemed to be the most effective policy in reducing face-to-face contact and slowing down the rate of infections. Stay-at-home and shelter-in-place orders have been implemented in different states and cities, affecting daily traffic patterns. Social distancing interventions and fear of the disease resulted in a traffic decline in cities and counties. However, after stay-at-home orders ended and some public places reopened, traffic gradually started to revert to pre-pandemic levels. It can be shown that counties have diverse patterns in the decline and recovery phases. This study analyzes county-level mobility change after the pandemic, explores the contributing factors, and identifies possible spatial heterogeneity. To this end, 95 counties in Tennessee have been selected as the study area to perform geographically weighted regressions (GWR) models. The results show that density on non-freeway roads, median household income, percent of unemployment, population density, percent of people over age 65, percent of people under age 18, percent of work from home, and mean time to work are significantly correlated with vehicle miles traveled change magnitude in both decline and recovery phases. Also, the GWR estimation captures the spatial heterogeneity and local variation in coefficients among counties. Finally, the results imply that the recovery phase could be estimated depending on the identified spatial attributes. The proposed model can help agencies and researchers estimate and manage decline and recovery based on spatial factors in similar events in the future.


Cerebral blood flow network differences correlated with cognitive impairment in mild traumatic brain injury.
To examine whether the cerebral blood flow (CBF) and CBF connectivity differences are sex-specific and whether these differences are correlated with cognitive impairment in mTBI. Resting-state perfusion magnetic resonance imaging was performed in 40 patients with acute mTBI and 40 healthy controls by using pseudocontinuous arterial spin labeling within 14 days following injury. The differences in normalized CBF were first compared and CBF connectivity of the brain regions with significant CBF differences were compared next. The association between the normalized CBF and CBF connectivity differences and cognitive function were further investigated. Men patients had lower normalized CBF in the frontal gyrus, temporal gyrus and hippocampus and decreased negative CBF connectivity between brain regions including the hippocampus, temporal gyrus, postcentral gyrus and lenticular nucleus, putamen, compared with men controls. Women patients had lower normalized CBF in the frontal gyrus, however had higher normalized CBF in the temporal gyrus and hippocampus, compared with women controls. Additionally, women patients showed increased positive CBF connectivity between the seed region of interest (ROI) of the right inferior temporal gyrus and temporal gyrus and frontal gyrus, and had increased positive CBF connectivity between the seed ROI of the right hippocampus and the temporal gyrus. Furthermore, men patients had higher CBF in the right middle temporal gyrus and left precentral gyrus than women patients. This study provides evidence of sex differences in both decreased and increased CBF and CBF connectivity and association with cognitive outcome in the acute stage after mTBI.


Transport and bioavailability studies of astragaloside IV, an active ingredient in Radix Astragali.
Astragaloside IV is an important constituent of Radix Astragali, a herbal remedy widely used in traditional Chinese medicine. Radix Astragali is administered orally but little is known about the transport properties and bioavailability of astragaloside IV. In this paper we report studies of the absorption of astragaloside IV in the perfused rat intestinal model, transport and uptake in Caco-2 cell monolayers and in vivo bioavailability in rat after an oral dose. In the perfused rat intestinal model, absorption of astragaloside IV was low from an aqueous solution but was significantly higher from a solution of Radix Astragali. Absorption was not affected by bile duct ligation. Transport through Caco-2 cells gave a very low permeability value (mean P(app) of 6.7+/-1.0 x 10(-8) cm/sec.) and uptake was unaffected by P-glycoprotein inhibitors. The absolute bioavailability of astragaloside IV in rat was 2.2%. The correlation between low permeability in vitro and poor bioavailability in vivo indicates in vitro absorption studies are useful in the evaluation of traditional Chinese medicines.


[Production and implementation of predictive biological models].
The production and implementation of methodologies allowing the construction of coherent, precise and trustworthy predictive biological models has become an inescapable necessity. The financial stakes -attached to this reality are very high indeed, be it in the public or the private domains (health, research, pharma and foodstuffs industries, environment, etc.). Modelling biological systems is widely presented as a problem in computational sciences. While certainly very true for low complexity, practically continuous systems, this view cannot be upheld in the case of discontinuous, hyper-complex systems such as living entities. In these domains, modelling becomes a problem in biology assisted by computational sciences and certainly not the obverse. The following article will attempt to demonstrate why it is so, using concrete examples.


A pragmatic evaluation of university student experience of remote digital learning during the COVID-19 pandemic, focusing on lessons learned for future practice.
The Covid-19 pandemic and subsequent national lockdowns resulted in drastic changes to the way that higher education was delivered. A mixed-methods research study was conducted to explore university students' perceptions of online learning during the 2020/21 academic year. Students from across all Welsh higher education institutions were invited to participate. First, a series of focus groups (n = 13) were conducted to explore students' experiences of online learning during the pandemic. Two were conducted in Welsh, the remaining eleven in English. Thematic analysis led researchers to develop eight key themes: Seeking the positives, Facilitators to learning, Barriers to learning, Lost sense of community, Let down by University, Workload, Assessment, and Health and well-being. These themes informed the design of a quantitative survey which was completed by 759 students. It was found that students were largely satisfied with the quality of online learning, however there were specific challenges associated with a lack of community, wellbeing concerns, and challenges with loneliness and isolation. Data from the focus groups and survey informed recommendations for practice in three key categories; teaching practice, institutional level recommendations, and student health and wellbeing considerations.


Effect of chloroquine phosphate treatment on serum MMP-9 and TIMP-1 levels in patients with systemic lupus erythematosus.
Antimalarials are widely used for the treatment of systemic lupus erythematosus. However, their mechanisms of action have not been fully elucidated. Literature data indicate that matrix metalloproteinases may play a role in the immune response and tissue damage that occur in autoimmune skin diseases. The aim of this study was to determine the effect of 3 months of chloroquine treatment on serum levels of MMP-9 and TIMP-1 in patients with systemic lupus erythematosus. The study group consisted of 25 patients with systemic lupus erythematosus and 25 sex- and age-matched healthy volunteers. Before drug administration, serum levels of MMP-9 and TIMP-1 were determined by enzyme-linked immunosorbent assay. The same procedure was performed after chloroquine treatment. We found significantly higher median serum levels of MMP-9 in patients with systemic lupus erythematosus before therapy (57.20 ng/ml) when compared with controls (44.50 ng/ml) (p < 0.001). After chloroquine therapy the median MMP-9 serum level of systemic lupus erythematosus patients decreased significantly (43 ng/ml; p < 0.001). Before treatment the median TIMP-1 serum level in the patients with systemic lupus erythematosus was significantly higher than in the control group (500 vs. 200 ng/ml; p < 0.001), and after therapy it increased significantly (750 ng/ml TIMP-1; p < 0.001). The results suggest that chloroquine treatment may affect the matrix metalloproteinase network, and this effect may contribute to the immunoregulatory and anti-inflammatory properties of antimalarials.


[Laparoscopic ureteroneocystostomiya a modo Boari - hitch operative technique and results].
To present the first laparoscopsic ureteroneotsistostomies we have performed by the Boari methods - operative technique and results. We investigated 9 patients for a period of two years -from 2015 to 2016 year, 9 had had previous surgery, in 2 of them followed by radiotherapy (one man and one woman). The average age of the patients was 45 (29-61) years. Women in the study were 7, men - 2. We performed 9 laparoscopic operating procedures following the open operative technique of Boari. All patients we have operated and who have no previous radiotherapy had excellent results - no hydronephrosis, recovering the kidney parenchyma and absence of reflux. In two patients who had undergone radiotherapy we had to perform an open procedure because of severe adhesions. The experience we have gained with open operative technique and the development of laparoscopic techniques allow us to look for more - often and less invasive methods of surgery. We have best results when indications for operative technique are strictly followed.


Quantitating the dynamics of NBD hexanoic acid in homogeneous solution and in solutions containing unilamellar vesicles.
We report here on the motional and fluorescence lifetime dynamics of the chromophore NBDHA (6-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoic acid) in neat solvents and in aqueous solutions containing unilamellar vesicles of varying composition. We measure the transient response of this chromophore by time-correlated single-photon counting, using one- and two-photon excitation to resolve the Cartesian components of the rotational diffusion constant, D. Our experimental data for NBDHA in selected solvents of varying viscosity demonstrate that one- and two-photon excitation probe different components of the rotational diffusion constant and that this chromophore reorients as a prolate rotor with an aspect ratio of approximately 2. For NBDHA in aqueous solutions containing unilamellar vesicles of varying composition, we recover the same reorientation behavior regardless of vesicle composition. Fluorescence lifetime and steady-state fluorescence data show the chromophore to reside in a polar environment that is different from neat water. We understand these data in the context of the chromophore residing in close proximity to the unilamellar vesicle polar headgroups in all cases.


Collective cancer invasion forms an integrin-dependent radioresistant niche.
Cancer fatalities result from metastatic dissemination and therapy resistance, both processes that depend on signals from the tumor microenvironment. To identify how invasion and resistance programs cooperate, we used intravital microscopy of orthotopic sarcoma and melanoma xenografts. We demonstrate that these tumors invade collectively and that, specifically, cells within the invasion zone acquire increased resistance to radiotherapy, rapidly normalize DNA damage, and preferentially survive. Using a candidate-based approach to identify effectors of invasion-associated resistance, we targeted β1 and αVβ3/β5 integrins, essential extracellular matrix receptors in mesenchymal tumors, which mediate cancer progression and resistance. Combining radiotherapy with β1 or αV integrin monotargeting in invading tumors led to relapse and metastasis in 40-60% of the cohort, in line with recently failed clinical trials individually targeting integrins. However, when combined, anti-β1/αV integrin dual targeting achieved relapse-free radiosensitization and prevented metastatic escape. Collectively, invading cancer cells thus withstand radiotherapy and DNA damage by β1/αVβ3/β5 integrin cross-talk, but efficient radiosensitization can be achieved by multiple integrin targeting.


Adherence to self-care and glycaemic control among people with insulin-dependent diabetes mellitus.
Factors associated with adherence to self-care and glycaemic control were studied in 213 people with insulin-dependent diabetes mellitus using a self-report questionnaire and a biochemical indicator (glycosylated haemoglobin). The data were collected in the Oulu Health Center and the Central Hospital of Lapland in Northern Finland. The response rate was 76%. In order to verify the reliability and validity of the instruments, we used correlation coefficients, factor analysis and item-total analysis. Internal consistency was checked by Cronbach's alpha. The connections between self-care and the background variables were examined by cross-tabulation. The majority of subjects accomplished their insulin treatment as scheduled, but had more difficulties with the other aspects of self-care. According to the findings, a fifth (19%) of the respondents were neglecting their self-care. The others undertook flexible (46%), regimen-adherent (16%) or self-planned self-care (19%). The subjects who were adherent to self-care had better metabolic control than those who neglected self-care. According to logistic regression analysis, poor metabolic control (P=0.003), smoking (P=0.009) and living alone (P=0.014) were associated with neglect of self-care. Gender, concurrent diseases and complications as a result of diabetes increased the risk, but had no significant association with adherence to or neglect of self-care. The findings demonstrated that adherence to self-care does not always lead to good metabolic control, but neglect of self-care is likely to lead to poor metabolic control.


[Change of ROCK1 Gene Expression Level in Patients with Acute Lymphoblastic Leukemia and Its Clinical Significance].
To investigate the expression change of ROCK1 gene in patients with acute lymphoblastic leukemia (ALL) and its prognostic significance. Sixty patients with ALL were selected in our hospital from April 2017 to April 2018, and 60 healthy persons subjected to physical examination were selected as control. The venous blood was taken from the subjects, and then the mononuclear cells were separated. The ROCK1 gene expression level in the samples was detected by RT-PCR, and the expression level of ROCK1 protein was detected by Western blot. The correlation between ROCK1 gene expression and clinical characteristics of ALL patients was analyzed by using statistical methots. The RT-PCR showed that the relative expression level of ROCK1 gene in ALL patients was 1.37 (1.28-1.46), which was significantly higher than that in the control group (P<0.05). Western blot showed that the protein expression level of ROCK1 in ALL patients was higher than that in the control group (P<0.05). The expression level of ROCK1 gene correlated with age, WBC count, lactate dehydrogenase (LDH) level, peripheral blood immature cell count, and risk stratification of ALL patients (P<0.05). The expression level of ROCK1 gene did not correlate with sex, hemoglobin (Hb) level, platelet count and immunophenotype in ALL patients (P>0.05). The standard risk ratio of B-ALL and T-ALL patients with low ROCK1 expression was significantly higher than that in patients with high ROCK1 expression (P<0.05). The high risk ratio of B-ALL and T-ALL patients with low ROCK1 expression was significantly lower than those with high ROCK1 expression (P<0.05). The ratio of CR in the group with low ROCK1 expression patients was significantly higher than that in patients with high ROCK1 expression (P<0.05). The Relapse rate of the group with low ROCK1 expression was significantly lower than that of the group with high ROCK1 expression (P<0.05). Kaplan-Meier survival analysis showed that OS and DFS in ALL patients with low ROCK1 expression were superior to those in ALL patients with high ROCK1 expression (P<0.05). Multiple factor Cox regression analysis showed that age and ROCK1 gene were independent influencing factors for OS (P<0.05); leukocyte count and ROCK1 gene were independent influencing factors for DFS (P<0.05). The expression level of ROCK1 gene in ALL patients is high, which may stimulate the genesis of ALL, and the down-regulation of ROCK1 gene expression may help improve the therapeutic effect for ALL patients.


[The erythrocyte sodium-proton exchanger activity in patient with primary hypertension].
A sodium-proton exchanger (NHE) is a membrane transport system taking part in intracellular sodium homeostasis. An increased NHE activity was observed in erythrocytes of primary hypertension (NTP) patients. Study group consisted of 25 NTP patients and 24 control (K). NTP patients were significantly heavier (p < 0.01) than control group (BMI 26.0 +/- 2.9 vs. 23.1 +/- 2.7, respectively). They also had significantly higher systolic, diastolic and mean arterial pressure than K (SBP 167 +/- 24.6 vs. 120 +/- 10.5; DBP 98 +/- 16.7 vs. 76 +/- 6.4; MAP 118.6 +/- 17.9 vs. 89 +/- 6.4, respectively). There was positive correlation between MAP and BMI (p < 0.02) in NTP patients. Mean NHE activity was significantly higher in NTP than in K group (9.6 +/- 3.6 vs. 8.2 +/- 2.6 mmol/L RBC/h) p = 0.05. A bimodal distribution of NHE activity in NTP group was observed. There was no correlation between NHE activity and BMI, MAP, SBP, DBP, age or positive family history of hypertension in NTP or K groups.


Enterovirus isolation from foetal and placental tissues.
Four spontaneous abortions and two stillbirth occurred during a prospective survey following the teratogenicity of echoviruses in 80 pregnant women selected at random from the Antenatal Care Service. Echovirus types 19, 27, and 33. Coxsackie B2 and B6 were isolated from placental and foetal tissues (brain, liver, kidney, heart, and spleen). The mothers also excreted the virus by faeces at least twenty days before abortion and responded serologically, indicating active virus infection. Almost all aborted children were anomalous with signs of viral infection.


Finite element evaluation of the newest ISO testing standard for polyethylene total knee replacement liners.
Current treatment for end-stage osteoarthritis is total knee replacement. Given that the number of total knee replacement surgeries is expected to approach 3.48 million by 2030, understanding long-term failure is important. One of the preclinical tests for total knee replacements is carried out using mechanical wear testing under generic walking conditions. Used for this purpose is the International Standards Organization's generic walking profile. Recently this standard was updated by reversing the direction of anterior/posterior translation and internal/external rotation. The effects of this change have not been investigated, and therefore, it is unknown if comparisons between wear tests utilizing the old and new version of the standard are valid. In this study, we used a finite element model along with a frictional energy-based wear model to compare the kinematic inputs, contact conditions, and wear from the older and newer versions of the ISO standard. Simulator-tested components were used to validate the computational model. We found that there were no visible similarities in the contact conditions between the old and new versions of the standard. The new version of the standard had a lower wear rate but covered a larger portion of the articular surface. Locations of wear also varied considerably. The results of the study suggest that major differences between the old and new standard exist, and therefore, historical wear results should be compared with caution to newly obtained results.


Surgical excision of meningiomas involving the clivus: preoperative and intraoperative features as predictors of postoperative functional deterioration.
Neurological deterioration is commonly seen after surgical excision of clival meningiomas; however, an understanding of the risk factors associated with postoperative deterioration can lead to improvements in outcome. In 75 patients with clival meningiomas operated on over a 7-year period, the following data were studied; preoperative variables such as presenting Karnofsky scale score, age, sex, and prior operations or radiation therapy. Radiological findings on magnetic resonance imaging or arteriography, such as the development of the arachnoidal cleavage plane between tumor and the brain stem, brainstem edema, tumor size, extent of compression on the brain stem, vascular encasement, and blood supply from the basilar artery were among other data studied. In addition, intraoperative findings such as development of the arachnoid plane, vascular encasement, and the difficulty of dissection were noted. Finally, each patient's neurological and functional statuses were recorded at 1 week postoperatively and at follow-up examinations. Early postoperative functional deterioration occurred in 45 patients (60%) and ranged from mild (30 patients) to severe (three patients). Significant improvement had occurred by the time of follow-up examination in all but four patients; however, permanent postoperative dysfunction was present in 12 patients. Statistical analysis revealed significant correlations between early functional deterioration and preoperative Karnofsky scale scores, male gender, radiological findings of the absence of an arachnoid plane, edema of the brain stem, and arteriographic supply from the basilar artery. Operative features included difficulty with dissection, an absent arachnoidal cleavage plane, and incomplete tumor resection. Permanent functional deterioration was statistically associated with the following: blood supply from the basilar artery, difficulty of dissection, incomplete tumor resection, and early postoperative dysfunction. Logistical regression analysis revealed that the most important risk factor for early postoperative deterioration was tumor size. Patients with large or giant tumors had a 6.7 to 13 times greater risk of functional deterioration, respectively, than patients with small- or medium-sized tumors. Excluding tumor size, the most important factor for permanent deterioration was blood supply from the basilar artery. Patients in this category had a 4.4 times greater risk of permanent functional deterioration. Three stages of tumor relationship to the brainstem arachnoid and pial membranes are proposed. Based on the results of this clinical study of clival meningiomas, suggestions are made for changes in the management strategy of these difficult lesions.


Quality Improvement Initiative Increasing Early Discharges From an Acute Care Cardiology Unit for Cardiac Surgery and Cardiology Patients-Associated With Reduced Hospital Length of Stay.
Discharging patients from the acute care setting is complex and requires orchestration of many clinical and technical processes. Focusing on timely discharges improves throughput by off-loading ICUs and coordinating safe outpatient transitions. Our data review demonstrated most discharges occurred later in the day. We sought to improve our discharge times for cardiology and cardiovascular surgery (CVS) patients in our 26-bed inpatient acute care cardiology unit (ACCU). We aimed to increase the number of discharges between 6 am and 12 pm for cardiology and CVS patients on ACCU from 5 to 10 patients per month over 6 months and sustain. We performed a simplified Failure Mode Effect Analysis on the discharge process and identified improvement opportunities. Our key drivers centered around education, documentation, and planning. Our interventions included: staff education, communication of discharge expectations, daily quality board rounds, hospital-wide collaboration emphasizing conditional discharges, and hospital information technology (IT) improvements. We utilized statistical process control charts to analyze the data. Discharges between 6 am, and 12 pm increased from a baseline of 5 (8%) to 12 (18%) patients per month with a centerline shift. Our process measures demonstrated appropriate conditional discharge usage linked to earlier discharges. Upgrades to our EMR, documentation further increased our timely discharges. Our efforts resulted in a 22% reduction in hospital length of stay from 11.2 to 8.7 days without increased readmission rates suggesting that improved efficiency did not impact care quality. We successfully show how multidisciplinary collaboration and systems-based improvement can increase the number of safe, early discharges.


Involvement of lymphatics in lymphangioleiomyomatosis.
Lymphangioleiomyomatosis (LAM), a rare multisystem disease, occurs primarily in women, with cystic destruction of the lungs, abdominal tumors, and involvement of the axial lymphatics in the thorax and abdomen. To understand the pathogenesis of LAM, we initiated a longitudinal study of patients with LAM; over 500 patients have been enrolled. LAM results from the proliferation of a neoplastic cell (LAM cell), which has mutations in the tuberous sclerosis complex (TSC) genes, TSC1 or TSC2. Consistent with their metastatic behavior, LAM cells were isolated from blood, urine, and chylous effusions. Surface proteins on LAM cells include those found on metastatic cells and those involved in cell migration. In the lung, LAM cells are found clustered in nodules, which appear in the walls of the cysts, and in the interstitium. LAM lung nodules are traversed by slit-like vascular structures, with lining cells showing reactivity with antibodies against components of lymphatic endothelial cells. The axial lymphatics appear to be infiltrated by LAM cells, which may result in obstruction and formation of chyle-filled lymphangioleiomyomas. LAM cell clusters have been isolated from chylous pleural effusions, and it is hypothesized that these clusters may be responsible for metastatic spread of LAM cells via lymphatic vessels. Consistent with a lymphangiogenic process, levels of VEGF-D, a lymphangiogenic factor, were higher in sera of patients with LAM and lymphatic involvement (i.e., lymphangioleiomyoma, adenopathy) than in healthy volunteers or LAM patients with cystic disease limited to the lung. These findings are consistent with an important function for lymphangiogenesis in LAM.


Clinical diagnosis and treatment of immune checkpoint inhibitors-related endocrine dysfunction.
As a new class of antitumor drugs, immune checkpoint inhibitors (ICIs) have shown remarkable efficacy toward the treatment of various malignant tumors. By virtue of their targets and mechanisms of action, ICIs can cause autoimmune and inflammatory effects, termed as immune-related adverse events (irAEs) and unlike the adverse reactions of traditional therapies, irAEs are occult and not fixed, with some serious adverse reactions forcing patients to stop treatment which might even affect their survival. Therefore, with the wide clinical application of ICIs, clinicians need to fully understand the possible adverse reactions of these drugs and devise reasonable treatment strategies to improve the survival rate and therapeutic effects of patients receiving ICIs. In this article, we review the incidence, clinical manifestations, diagnosis and treatment of immune-related endocrine events that may occur with the administration of ICIs.


Occlusal Concepts and Considerations in Fixed Prosthodontics.
The UK has an increasingly ageing population, many of whom are retaining more of their own teeth. This has led to an increase in the prevalence of tooth wear and the need to replace pre-existing failing restorations. In many cases this will be achieved by fixed prosthodontics. This paper provides a brief overview of important occlusal concepts that should be considered when providing non-implant fixed prosthodontics using either a conformative or reorganised approach. The aim is to give general dental practitioners the confidence to provide these types of restorations in primary care. Clinical cases demonstrate how the occlusion can be controlled to optimise clinical outcomes.


Concept of left atrial pressure estimation using its pulsatile amplitude in the helical flow total artificial heart.
The total artificial heart (TAH) requires physiological control to respond to the metabolic demand of the body. To date, 1/R control is a single physiological control method that can control venous pressure. To realize an implantable 1/R control system, we are developing a new pressure measuring method using absolute pressure sensor. To find a method for absolute pressure sensor, which went well without calibration, concept of left atrial pressure (LAP) estimation using its pulsatile amplitude was proposed. Its possibility was investigated with two long-term survived goats whose hearts were replaced with the helical flow TAHs. In manual control condition, there existed a positive relation between mean LAP (mLAP) and normalized pulsatile amplitude (NPA). Percent systole revealed not to affect the relationship between mLAP and NPA. Dispersion was observed between different pulse rates. As for cardiac output difference (QLD) that is the difference of flow rate between systolic and diastolic phases, similar results were obtained except in low QLDs. In the 1/R control condition, relatively high correlation between mLAP and NPA could be obtained. In estimation of mLAP using the correlating function of individual goat, fairly good correlation was obtained between measured mLAP and estimated mLAP. Despite that further studies are necessary, it was demonstrated that the concept of the LAP estimation could be possible.


[Assessment of the possibilities of application of the thermovision technique in medico-legal diagnosis. Theoretical basis].
The authors in their work wish to prove that technological advancement of modern thermovision technique opens for forensic medicine, as an applied science, new diagnostic possibilities, especially in the scope of the post-mortem examinations. In the past, some attempts were already undertaken to apply thermovision techniques in forensic medicine, those tests, however, were not put in the everyday medical-legal practice. Most of the factors which have an influence in decreasing the value of thermograph tests are not present while biological material is tested post-mortem, therefore, paradoxically, natural elimination of obstacles occurs in such cases, which allows for medical-legal post-mortem diagnostics based on thermograph images. In particular, the most promising is active dynamic thermography which is based on the analysis of thermograms' sequence registered during transitional thermal processes in the examined object (heating or cooling of the object), which is stimulated by an external heat source, and the object's response to this stimulation is a change of the temperature which function in time determines its internal structure. Pathological and injury changes and their results in the form of structural damages of tissues lead to thermal conductivity and capacity which can be noticeable in a thermovision test. There are, then, no theoretical obstacles to the use of active dynamic thermography in post-mortem tests of tissues to evaluate their structure. With today's technological progress, it should be expected that in the near future sensitivity of thermovision appliances will significantly influence the increase of the specificity of obtained images. It can not be excluded that thermography methods could become a back-up method or even an alternative for other imagining methods.


Gonadal and adrenal catheterization during adrenal suppression and gonadal stimulation in a patient with bilateral testicular tumors and congenital adrenal hyperplasia.
We report the case of a patient with bilateral testicular tumors and congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Catheterization of the left testicular and adrenal veins was performed. The presence of 11 beta-hydroxylated steroids in the spermatic veins confirmed the presence of testicular tumor secondary to adrenal rest cells. After adrenal suppression by dexamethasone combined with gonadal stimulation with hCG, a dramatic decrease in androgens and adrenal steroids was observed in the peripheral blood. Compared to the periphery, 21-deoxycortisol and 11 beta-hydroxy-delta 4-androstenedione levels remained higher than that of 21-deoxycorticosterone in the gonadal vein, but not in the adrenal vein, which seems to indicate that the nature of this ectopic tissue is unusual and that its sensitivity to dexamethasone depends on the adrenocortical zones. No rise in estradiol or testosterone was obtained after hCG stimulation, suggesting that all of the testicular tissue was inactive or destroyed. This finding was confirmed by histological examination.


[Modification of silicone oil removal via limbus of corneal with aphakia].
To introduce a simplified method to remove silicone oil via limbus of corneal after previous lensectomy-vitrectomy. Fifty-one eyes received the modified procedures to eliminate silicone oil via one pars plana or limbus incision after previous lensectomy-vitrectomy. Local anesthesia was performed with 25G syringe needle through pars plana or corneal limbus infusion and super limbus incisions to eliminate silicone oil. All operations were primarily successful in eliminating silicone oil. The complications occurred in all the patients with the early low intraocular pressure, in 4 (4/51, 7.8%) eyes with retinal detachment, and in 2 (2/51, 3.9%) eyes with less bleeding at the point of puncture. The visual acuity was significantly improved after the procedure (P < 0.05) in patients with stable retinal reattachment. The procedure via one pars plana and limbus or limbus incision after previous lensectomy-vitrectomy is useful in removing the silicone oil tamponade in aphakic eyes because of its simplicity, good curative effect, and fewer complications.


Out of Office Self Measurement of Blood Pressure.
Self measurement of blood pressure is increasingly common among hypertensive patients. These out of office measurements are clinically useful in avoiding misdiagnosis of hypertension, over treatment and under treatment of hypertension, and as a measure to increase compliance and reduce the cost of antihypertensive therapy. This paper will address the clinical relevance of out of office blood pressure measurement related to hypertension management, the instruments available to perform out of office blood pressure measurement, and the current problems of interpretation of these blood pressure values as they relate to subsequent development of hypertension derived cardiovascular disease. (c)1999 by Le Jacq Communications, Inc.


Radix paeoniae alba polysaccharide attenuates lipopolysaccharide-induced intestinal injury by regulating gut microbiota.
Accumulating evidence indicated that oxidative stress is closely related to inflammation and the progression of multiple chronic diseases, which seriously threaten the host health. Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. Here, we investigated whether different doses of RPAP administration could alleviate lipopolysaccharide (LPS)-induced intestinal injury and gut microbial dysbiosis in mice. Results indicated that RPAP administration effectively alleviated LPS-induced intestinal damage in dose dependent. Additionally, amplicon sequencing showed that RPAP administration reversed the significant decrease in gut microbial diversity caused by LPS exposure and restored the alpha-diversity indices to normal levels. Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). However, RPAP administration, especially in high doses, could improve the composition of the gut microbiota by altering the abundance of some bacteria. Taken together, this study demonstrated that RPAP administration could ameliorate LPS-induced intestinal injury by regulating gut microbiota. Meanwhile, this also provides the basis for the popularization and application of RPAP and alleviating oxidative stress from the perspective of gut microbiota.


Induction of cytochrome P450 mRNA in porcine primary hepatocytes cultured under serum free conditions: Comparison of freshly isolated cells and cryopreserved.
Primary hepatocytes are widely used in the study of dynamic events like regulation of gene expression, as they are superior to most cell-lines. However, the culturing of the hepatocytes often results in loss of phenotype, e.g. the expression of the cytochrome p450s (CYP). The present study investigated the impact of serum in the culture medium of porcine primary hepatocytes (PPH) on markers of dedifferentiation as well as the impact on CYP induction. The effects were studied in both freshly isolated primary hepatocytes as well as cryopreserved. The exclusion of serum in the culturing media were not introducing significant dedifferentiation as judged by the gene expression of α-fetoprotein, albumin, glucose-6-phosphatase and the constitutive expression of selected transcription factors and CYP. The induction of CYP2B22 and CYP3A29 by phenobarbital and rifampicin, were greater in hepatocytes cultured without serum. The same were not observed for TCDD induced CYP1A2 expression. In conclusion, PPH cultured under serum free conditions results in little or no dedifferentiation, while being more responsive to known CYP inducers. Hence, it can be suggested that PPH cultured under serum free conditions provides a reliable hepatocyte model to investigate CYP gene regulation.


Spatial characteristics of aluminum uptake and translocation in roots of buckwheat (Fagopyrum esculentum).
The detoxification of aluminum (Al) in root tips of the Al accumulator buckwheat by exudation of oxalate leading to reduced Al uptake (Al resistance) is difficult to reconcile with the Al accumulation (Al tolerance). The objective of this study was to analyze resistance and tolerance mechanisms at the same time evaluating particularly possible stratification of Al uptake, Al transport and oxalate exudation along the root apex. The use of a minirhizotron made it possible to differentiate between spatial responses to Al along the root apex with regard to Al uptake and organic acid anion exudation, but also to measure at the same time Al and organic acid transport in the xylem. Al accumulates particularly in the 3-mm root apex. The study showed that Al taken up by the 10-mm root apex is rapidly transferred to the xylem which differentiates in the 10 to 15-mm root zone as revealed by a microscopic study. Al induces the release of oxalate from the root apex but particularly from the subapical 6-20 mm root zone even when Al was applied only to the 5-mm root apex suggesting a basipetal signal transduction. Citrate proved to be the most likely ligand for Al in the xylem because Al and citrate transport rates were positively correlated. In conclusion, the data presented show that the Al-induced release of oxalate, and Al uptake as well as Al accumulation are spatially not separated in the root apex.


[An evaluation on corrosion resistance of magnetic retainers].
The present study was to explore the corrosion resistance of three kinds of magnetic retainers which named neodymium-iron-boron magnet and encapsulated in stainless steel. Three kinds of magnetic retainers were exposed for 6 months to artificial saliva thermostated at 36.5 degrees C. This study included a electrochemical test as polarization curves and a chemical test as immersion test. In the electrochemical test, current density of the national keeper was 7.015 microA/cm2 and magnet was 0.119 microA/cm2. In the chemical test, corrosion rate of national keeper was 3.67 x 10(-5) mg/cm2.h and magnet was 1.77 x 10(-5) mg/cm2.h. The corrosion resistance of the national magnetic retainer had little difference with the imported ones. Transient exposure of stainless steel to artificial saliva environment is likely to significantly increase elemental release. It would affect the useful life span of magnets.


Fat attenuation lesions of the mediastinum.
The identification of fat within a focal or diffuse mediastinal lesion significantly narrows the differential diagnosis. In many cases, a specific diagnosis can be suggested on the basis of CT findings. In this article, we illustrate and review the characteristic CT features of common and uncommon fat attenuation lesions of the mediastinum, including focal masses and diffuse abnormalities.


Aortic arch aneurysm: short- and mid-term results comparing open arch surgery and the hybrid procedure†.
Open arch surgery for aortic arch aneurysm was historically associated with a high risk of postoperative morbi-mortality. Improved operative techniques have now lowered the incidence of these complications but in parallel, hybrid arch procedures have emerged. Nowadays, very little data are available about their mid-term results compared with open surgery. From January 2002 to January 2014, 46 patients had treatment for an exclusive aortic arch aneurysm including 25 open arch surgeries and 21 type I hybrid arch procedures in our institution. All cases involved arch aneurysms involving at least one carotid artery (Zone 0 and Zone 1). Aneurysms of the distal arch and descending aorta were excluded (Zone 2 and beyond). Results from a retrospective database are reported. There were no patients lost to the follow-up. There was no significant difference in preoperative comorbidities between the two groups. The incidence of in-hospital mortality was similar at 20% (5/25) for open surgery and 19% (4/21) for hybrid procedure (P = 0.830). The incidence of permanent cerebral neurological deficit was comparable at 17.4% (4/23) for open surgery and 21.1% (4/19) for hybrid procedure (P = 1). Median survival was 109.5 months for open surgery and 56.3 months for hybrid procedure. Freedom from all-cause mortality was 78, 63, 63 and 57% at 1, 3, 5 and 7 years, respectively in the open surgical group. Freedom from all-cause mortality was 74, 55, 46 and 28% at 1, 3, 5 and 7 years, respectively in the hybrid group. Survival rates and incidence of major adverse cardiac and cerebro-vascular event between open surgery and hybrid procedure were not statistically different (P = 0.530 and P = 0.325, respectively). However, incidence of reintervention was in favour of open surgery [14.5 vs 44.8% at 7 years, P = 0.045; 95% confidence interval: (0.06-0.97)]. The type I hybrid arch procedure fails to demonstrate better results compared with open surgery, regarding morbi-mortality at the short- and mid-term follow-up. Moreover, it increases the risk of reintervention. Patients treated by this technique must undergo a closer follow-up because of this risk. Larger randomized studies are needed to better define the exact indications of this therapy.


[18F-FDG PET cerebral imaging for localizing epileptogenic foci and its relation to predicting operative outcome].
To find out the relationship between FDG PET image pattern and epileptogenic focus localization and predict prognosis by comparing pre- and post-surgical FDG images with operative effects. 72 patients with epilepsy who underwent surgery (49M, 23F, aged 24.3 years on average) were studied with pre-surgical FDG PET cerebral imaging and followed up (av. 15 months, 3-24 months) for assessment of seizure control. 20 of them were studied with post-surgical FDG PET. The accuracy of localization of epileptogenic foci of FDG PET was compared with that of VEEG and MRI. The relationship between pre- and post-surgical FDG metabolic image pattern and surgical outcome was evaluated. (1) 71 patients showed pre-surgical interictal focal hypometabolism. 1 patient with continuous seizure showed ictal hypermetabolic focus. (2) FDG PET could localize the seizure foci in patients whose EEG showed bilateral or no definite epileptoform discharge. The rate of detection of epileptogenic foci with FDG PET was much higher than that with MRI. Since hypometabolic foci were non-specific, not all hypometabolic foci were epileptogenic. The correlation between postoperative FDG PET and surgical effect could help determine the nature of metabolic focus. (3) Hypometabolism of ipsilateral thalamus and/or contralateral cerebellum with temporal lobe lesion was secondary functional change. (4) The patternization of cerebral images was helpful to surgical planning and helped predict operative outcome. Comparison of pre-surgical with post-surgical FDG PET images help determine the nature of hypometabolic foci. The patternization of FDG PET images help the surgeon select patients, plan type of operation and predict surgical effect.


Detection and quantification of Spirocerca lupi by HRM qPCR in fecal samples from dogs with spirocercosis.
Spirocerca lupi, the dog oesophageal nematode, causes a potentially fatal disease in domestic dogs, and is currently clinically diagnosed by coproscopy and oesophagoscopy. To date, a single molecular method, a semi-nested PCR, targeting the cox1 gene, has been developed to aid in the diagnosis of spirocercosis. The present study describes three novel high-resolution melt (HRM) quantitative PCR (qPCR) assays targeting fragments of the ITS1, 18S and cytb loci of S. lupi. The performance of these molecular assays in feces was compared to fecal flotation and to the previously described cox1 gene semi-nested PCR in 18 fecal samples from dogs with clinical oesophageal spirocercosis diagnosed by oesophagoscopy. The HRM qPCR for ITS1 and 18S were both able to detect 0.2 S. lupi eggs per gram (epg), while the HRM qPCR for the cytb and the semi-nested PCR for the cox1 detected 6 epg and 526 epg, respectively. Spirocerca lupi was detected in 61.1%, 44.4%, 27.8%, 11.1% and 5.6% of the fecal samples of dogs diagnosed with spirocercosis by using the ITS1 and 18S HRM qPCR assays, fecal flotation, cytb HRM qPCR and cox1 semi-nested PCR, respectively. All dogs positive by fecal flotation were also positive by ITS1 and 18S HRM qPCRs. Quantification of S. lupi eggs was successfully achieved in the HRM qPCRs and compared to the fecal flotation with no significant difference in the calculated concentrations between the HRM qPCRs that detected the 18S and ITS1 loci and the fecal flotation. The HRM qPCR for the 18S cross-amplified DNA from Toxocara canis and Toxascaris leonina. In contrast, the HRM qPCR for ITS1 did not cross-amplify DNA from other canine gastrointestinal parasites. This study presents two new molecular assays with significantly increased sensitivity for confirming and quantifying fecal S. lupi eggs. Of these, the HRM qPCR for ITS1 showed the best performance in terms of the limit of detection and absence of cross-amplification with other parasites. These assays will be useful in detecting infection and for follow-up during therapy.