Comparison of patients' age receiving therapeutic services in a cleft care team in Isfahan.
Due to numerous difficulties in patients suffering from varieties of cleft lip and palate, their therapeutic management involves interdisciplinary teamwork. This study was conducted to compare the age of commencing treatments such as speech therapy, secondary palate and alveolar bone grafting and orthodontics between those who sought treatment early and late. In this retrospective study, 260 files of patients with cleft lip and palate based on their age at the time of admission to a cleft care team were divided into two groups: The early admission and late admission. Both groups compared based on four variables including the mean age of beginning speech therapy, palatal secondary surgery, alveolar bone grafting, and receiving orthodontics using t-test. Based on the results, among 134 patients admitted for speech therapy, the mean age of initiating speech therapy in early clients was 3.3 years, and in the late ones was 9 years. Among 47 patients with secondary surgery, the mean age in early clients was 3.88 years, and in the late clients was 15.7 years. Among 17 patients with alveolar bone grafting, the mean age in the first group was 9 years, and in the other was 16.69 years. Among 24 patients receiving orthodontic services, the mean age in early clients was 7.66 years, and in the second group was 17.05 years. There was a significant difference between the age of performing secondary surgery and alveolar bone grafting and the age of beginning speech therapy and receiving orthodontic services in early references and late references to the team.


Gene expression profile in fibroblast growth factor 2-transformed endothelial cells.
Fibroblast growth factor-2 (FGF2) exerts paracrine and autocrine functions on endothelial cells. FGF2-overexpressing murine aortic endothelial cells (FGF2-T-MAE cells) induce opportunistic hemangioendothelioma-like tumors when inoculated in immunodeficient mice. To evaluate the impact of FGF2-mediated activation on gene expression profile in transformed endothelial cells, we performed subtractive suppression hybridization analysis between FGF2-T-MAE cells and parental MAE cells. The two cell populations were compared for differential gene expression also by gene macroarray hybridization with 32P-labeled cDNAs. The two approaches allowed the identification of 27 transcripts whose expression was upregulated by FGF2 in endothelial cells. With the exception of one unknown gene, the differentially expressed transcripts encoded for proteins involved in the modulation of cell cycle, differentiation, and cell adhesion. Among them, the stress-inducible genes A170, GADD45 and GADD153 are upregulated by FGF2 transfection or recombinant growth factor treatment. Their expression was also induced in vascular tumors originated by parental or FGF2-transfected MAE cells in nude mice. This study extends the number of genes involved in tumor angiogenesis and/or endothelial cell transformation, a finding with possible implications for the discovery of novel targets for angiostatic therapy.


Unusual metallic foreign bodies in the larynx: two case reports.
Impaction of a foreign body (FB) in the larynx is a rare situation. It is more common in children then older age group. The authors report two cases of unusual foreign bodies in the larynx which presented with complaints of sudden onset of change of voice without any respiratory difficulty. One was of 9 y and other was a 7-y-old boy with foreign body in the glottis. In both cases there was accidental inhalation of the FB which was immediately followed by difficulty of speech. Metallic foreign bodies were removed successfully by direct laryngoscopy under general anesthesia (GA) which is followed by recovery of the symptoms.


Impact of material homogeneity assumption on cortical stiffness estimates by MR elastography.
Inversion algorithms used to convert acquired MR elastography wave data into material property estimates often assume that the underlying materials are locally homogeneous. Here we evaluate the impact of that assumption on stiffness estimates in gray-matter regions of interest in brain MR elastography. We describe an updated neural network inversion framework using finite-difference model-derived data to train convolutional neural network inversion algorithms. Neural network inversions trained on homogeneous simulations (homogeneous learned inversions [HLIs]) or inhomogeneous simulations (inhomogeneous learned inversions [ILIs]) are generated with a variety of kernel sizes. These inversions are evaluated in a brain MR elastography simulation experiment and in vivo in a test-retest repeatability experiment including 10 healthy volunteers. In simulation and in vivo, HLI and ILI with small kernels produce similar results. As kernel size increases, the assumption of homogeneity has a larger effect, and HLI and ILI stiffness estimates show larger differences. At each inversion's optimal kernel size in simulation (7 × 7 × 7 for HLI, 11 × 11 × 11 for ILI), ILI is more sensitive to true changes in stiffness in gray-matter regions of interest in simulation. In vivo, there is no difference in the region-level repeatability of stiffness estimates between the inversions, although ILI appears to better maintain the stiffness map structure as kernel size increases, while decreasing the spatial variance in stiffness estimates. This study suggests that inhomogeneous inversions provide small but significant benefits even when large stiffness gradients are absent.


Modulatory effect of bradykinin on the release of noradrenaline from rat isolated atria.
1. We investigated the modulation by bradykinin (BK) of electrically induced noradrenaline release in rat isolated atria preincubated with [3H]-noradrenaline. 2. BK (1-100 nM) enhanced significantly the stimulation-induced outflow of radioactivity in a concentration-dependent manner with a calculated EC50 of 0.58 nM. 3. Des-Arg9-BK (0.1-100 nM), a selective B1 receptor agonist, did not modify the stimulation-induced outflow of radioactivity. Hoe 140 (10 nM), a selective B2 receptor antagonist, but not [Leu8]-des-Arg9-BK (100 nM), a selective B1 receptor antagonist, blocked the facilitatory effect of BK. 4. The effect of BK was not affected by diclofenac (1 microM), a cyclo-oxygenase inhibitor. Bisindolylmaleimide (1 microM), a protein kinase C inhibitor, significantly reduced the facilitatory effect of BK (10 nM), angiotensin II (0.3 microM) and phorbol dibutyrate (0.1 and 1 microM) but not of fenoterol (1 microM). 5. The results suggest that BK enhances noradrenaline release via a prejunctional B2 kinin receptor in the rat atrium. The effect appears to involve protein kinase C as a second messenger.


Upgrading of bio-separation and bioanalysis using synthetic polymers: Molecularly imprinted polymers (MIPs), cryogels, stimuli-responsive polymers.
Bio-separation plays a crucial role in many areas. Different polymers are suitable for bio-separation and are useful for applications in applications in both science and technology. Besides biopolymers, there are a broad spectrum of synthetic polymers with tailor-made properties. The synthetic polymers are characterized by their charges, solubility, hydrophilicity/hydrophobicity, sensitivity to environmental conditions and stability. Furthermore, ongoing developments are of great interest on biodegradable polymers for the treatment of diseases. Smart polymers have gained great attention due to their unique characteristics especially emphasizing simultaneously changing their chemical and physical property upon exposure to changes in environmental conditions. In this review, methodologies applied in bio-separation using synthetic polymers are discussed and efficient candidates are focused for the construction of synthetic polymers.


A common myosin light chain is expressed in chicken embryonic skeletal, cardiac, and smooth muscles and in brain continuously from embryo to adult.
We have isolated cDNA clones of the mRNA for chick embryonic myosin light chain (MLC), L23, by cross-hybridization with chicken skeletal muscle MLC1 cDNA. The identification of the isolated cDNAs was carried out by in vitro translation of hybrid-selected mRNA. Sequence analysis of the cloned cDNAs revealed that the cDNA insert contained 832 nucleotides and predicted a polypeptide of 185 amino acids with a calculated molecular weight of 20,687. The deduced amino acid sequence for L23 showed high sequence similarities to those of adult alkali type MLCs from various tissues, indicating that L23 belongs to the alkali MLC group. Using the cloned cDNA as a hybridization probe, we have revealed by RNA blot analysis that the expression of L23 mRNA was regulated in temporal and tissue-specific manners. The L23 mRNA of 1.1 kilobases is transiently expressed in embryonic skeletal, cardiac, and smooth muscles of chickens. It is also found in the brain of chickens during all stages of development so far investigated. Only a single gene for L23 was detected by Southern blot of chick genomic DNA. We therefore suggest that L23 is expressed from a single gene in both embryonic muscles and brain.


Effect of non-steroidal anti-inflammatory drugs of Moloney sarcoma virus inoculated mice.
Chronic administration of phenylbutazone, flufenamic acid and a new, potent non-steroidal anti-inflammatory agent ITF (3-methyl-5-benzoyl-amino-isothiazole-4-carboxy-p-ethoxyphenylamine) to BALB/c mice inoculated with a Moloney sarcoma virus resulted in a stimulation of tumor growth and increased severity of disease. This treatment, however, had no effect on the spontaneous regression of tumors. Indomethacin in a dose of 5.0 or 2.5 mg per kg suppressed the MSV-induced tumor growth, but this effect was apparently connected with the high toxicity of this drug for mice.


The contribution of undiagnosed adrenal insufficiency to euvolaemic hyponatraemia: results of a large prospective single-centre study.
The syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of hyponatraemia. Data on SIAD are mainly derived from retrospective studies, often with poor ascertainment of the minimum criteria for the correct diagnosis. Reliable data on the incidence of adrenal failure in SIAD are therefore unavailable. The aim of the study was to describe the aetiology of SIAD and in particular to define the prevalence of undiagnosed adrenal insufficiency. Prospective, single centre, noninterventional, observational study of patients admitted to Beaumont Hospital with euvolaemic hyponatraemia (plasma sodium ≤ 130 mmol/l) between January 1st and October 1st 2015. A total of 1323 admissions with hyponatraemia were prospectively evaluated; 576 had euvolaemic hyponatraemia, with 573 (43·4%) initially classified as SIAD. (i) Aetiology of SIAD, defined by diagnostic criteria; (ii) Incidence of adrenal insufficiency. Central nervous system diseases were the commonest cause of SIAD (n = 148, 26%) followed by pulmonary diseases (n = 111, 19%), malignancy (n = 105, 18%) and drugs (n = 47, 8%). A total of 22 patients (3·8%), initially diagnosed as SIAD, were reclassified as secondary adrenal insufficiency on the basis of cortisol measurements and clinical presentation; 9/22 cases had undiagnosed hypopituitarism; 13/22 patients had secondary adrenal insufficiency due to exogenous steroid administration. In a large, prospective and well-defined cohort of euvolaemic hyponatraemia, undiagnosed secondary adrenal insufficiency co-occurred in 3·8% of cases initially diagnosed as SIAD. Undiagnosed pituitary disease was responsible for 1·5% of cases presenting as euvolaemic hyponatraemia.


Onychomycosis Associated with Exophiala oligosperma in Taiwan.
A fungus was isolated from a nail of a 54-year-old female patient with onychomycosis in Taiwan. Based on ITS rDNA as well as beta tubulin gene sequences and microscopic analyses, this fungus was identified as Exophiala oligosperma. This is the first record of E. oligosperma in Taiwan. Negative keratin azure test indicates that keratin degradation is not involved in cases of E. oligosperma associated with skin and nail diseases.


Clinical Decision-making for Continuous Positive Airway Pressure Mask Selection.
Continuous positive airway pressure is the gold standard treatment for obstructive sleep apnea. Different interfaces with distinct characteristics, advantages, and disadvantages are available, which may influence long-term adherence. Oronasal masks have been increasingly used. However, recent evidence suggest that nasal masks are more effective when continuous positive airway pressure is used to treat obstructive sleep apnea. The main objective of this review is to describe the basis for the selection of the interface for the treatment of obstructive sleep apnea with continuous positive airway pressure.


[Which treatments for infantile colics?].
Infantile colics or excessive crying represent a source of stress for parents and a frequent reason for encounter in primary care. To assess the effectiveness of treatments of this syndrome from a systematic review. Medline, Cochrane and Embase databases. We used the following inclusion criteria: therapeutic assessment of infant colics or excessive crying, randomized controlled trials or meta-analyses, published in English or French language. Thirty-one randomized controlled trials and one meta-analysis have been included. Allopathic drugs have not proved effectiveness (simethicone, lactase) and some of them can cause potentially serious adverse reactions (dicyclomine). Protein hydrolysate or soy formulas seem to be effective, but soy milk can induce allergies. Sucrose solutions provide some benefit in studies with low level of evidence. Effectiveness is likely for a probiotics (Lactobacillus reuteri) and for herbal mixtures containing fennel extracts. Evidence is lacking for manual (osteopathy, acupuncture) and behavioural therapies (decreased stimulations, reassurance of parents). The definition of infantile colics and the methods used for crying measurement changed across trials. The included trials were of variable quality, especially with no double-blind procedure in 17 trials. The most validated treatments for infantile colics are the substitution of cows' milk by a hydrolysed formula, the use of L. reuteri and of fennel extracts.


Hepatocellular apoptosis is mediated by TNFalpha-dependent Fas/FasLigand cytotoxicity in a murine model of acute liver failure.
There is increasing evidence that the active contribution of hepatocytes to liver disease is strongly dependent on local cytokine environment. It has been shown in vitro that TNFalpha can enhance hepatocyte FasLigand (FasL)-mediated cytotoxicity. Here, we demonstrate that TNFalpha-induced apoptosis was associated with Fas and FasL upregulation and that a FasL-neutralizing antibody prevented TNFalpha-induced apoptosis. We further examined in vivo the relevance of the Fas/FasL pathway to hepatocellular apoptosis in a TNFalpha-driven model of acute liver failure. Livers of galactosamine/lipopolysaccharide (Gal/LPS)-exposed Fas wild-type mice highly expressed both Fas and FasL and revealed marked hepatocellular apoptosis that was almost completely blocked by soluble TNFalpha-receptor; this was also almost absent in Gal/LPS-exposed Fas lymphoproliferation mutant mice. Our data provide evidence for a direct link between TNFalpha and Fas/FasL in mediating hepatocyte apoptosis. Fratricidal death by Fas-FasL interactions of neighbouring hepatocytes may actively contribute to acute liver failure.


Dynamics and thermodynamics of acid-alkaline transitions in metmyoglobins lacking the usual distal histidine residue.
The kinetics of the acid-alkaline transition in the ferric myoglobins from the gastropodic mollusc Dolabella auricularia and the shark Mustelus japonicus, which possess the distal Val E7 and Gln E7, respectively, has been investigated using the paramagnetic 1H-NMR saturation transfer measurements in order to gain insight into functional properties of these non-His distal residues. Both myoglobins possess the penta-coordinated heme below the pK of the transition (7.8 and 10.0 for Dolabella and Mustelus myoglobins, respectively) and bind OH- above the pK. The pH dependence of the transition rates and the relatively high activation barrier (58 +/- 9 kJ/mol) for the dissociation of the Fe-bound OH- in Dolabella myoglobin indicate a strong interaction between the bound ligand and the guanidino NH proton of the Arg E10 in Dolabella myoglobin. Such a strong interaction between Fe-bound OH- and the Arg E10 side-chain in Dolabella myoglobin is also manifested in the EPR spectra. For Mustelus myoglobin, the pH and temperature dependence studies on the kinetics strongly suggest that the distal Gln E7 in this myoglobin does not contribute significantly to stabilize the Fe-bound ligand.


Isoflurane and sevoflurane augment norepinephrine responses to surgical noxious stimulation in humans.
Suppression of hypertensive response to noxious stimulation by volatile anesthetics may be a result of suppression of the stimulation-induced norepinephrine response or that of the cardiovascular response to catecholamines, or both. The suppression of the cardiovascular response is established, but that of norepinephrine response has not been confirmed. The authors hypothesized that the suppression of cardiovascular response but not that of norepinephrine response plays a major role in suppressing the noxious stimulation-induced hypertensive response by volatile anesthetics. Forty healthy donors for living-related liver transplantation were allocated to four groups: receiving 1.2% (end-tidal) isoflurane in oxygen and nitrogen, 2.0% isoflurane, 1.7% sevoflurane, or 2.8% sevoflurane. The intraoperative plasma norepinephrine and epinephrine concentrations, arterial blood pressure and pulse rate were measured for the first 15 min of surgery and were compared with the preoperative values. Norepinephrine and epinephrine concentrations both increased intraoperatively in all four groups. The values of maximum increase and area under the concentration-versus-time curve of norepinephrine were greater in the high dose groups of both anesthetics. The intraoperative blood pressure did not differ by different doses of anesthetics, and the degree of increase of blood pressure was not proportional to the plasma catecholamine concentrations. The effects of isoflurane and sevoflurane on the surgical noxious stimulation-induced norepinephrine response were inversely proportional to the dose. The suppression of noxious stimulation-induced blood pressure response by anesthetics that were studied may be the result of suppression of the responses of vascular smooth muscle and myocardium to catecholamines.


Preventing in-stent restenosis using lipoprotein (a), lipid and cholesterol adsorbent materials.
Atherosclerosis is one of the major cause of mortality in developed countries. The characteristic lesion of atherosclerosis is the atheroma or plaque that forms through thickening of the inner layer of the vessel wall (called the intima). The development of stent in 1980s revolutionised treatment of cardiovascular diseases, including atherosclerosis. However the advent of stenting was hindered by the new problem of in-stent restenosis. It was demonstrated that in-stent restenosis was the result of a new pathology in the form of neointimal hyperplasia, which was a maladaptive healing response to bare-metal stent implantation. Recent evidence suggests that although drug-eluting stent (DES) have reduced restenosis rates, important concerns have been raised regarding increased late stent thrombosis, myocardial infarction and death. With advances in nanotechnology and smart materials, covered stents has been proposed to overcome this problem. This is due to in-stent late restenosis and thromboses are mainly caused by smooth muscle cells (SMC) proliferation. Studies showed that there is a relation between high low-density lipoprotein (LDL) and lipoprotein (a) [Lp(a)] level in blood stream and chance of in-stent restenosis, moreover studies show that Lp(a) could stimulate SMC proliferation. We hypothesis development of covered stent with novel design and use of smart materials which could adsorb cholesterol and prevent contact between Lp(a) and vessel wall to overcome problem indicated in DES. In addition cost of stents will significantly reduce by elimination of drugs as well as complex manufacturing of the drug incorporation.


Lack of evidence of an effect of direct-acting antivirals on the recurrence of hepatocellular carcinoma: Data from three ANRS cohorts.
Sustained virological response following interferon-based antiviral treatment of chronic hepatitis C is associated with decreased long-term risk of hepatocellular carcinoma (HCC) in advanced liver fibrosis. An unexpected high rate of HCC recurrence following antiviral treatment using direct-acting antiviral (DAA) has recently been reported. We analyzed data individually from three French prospective multicentre ANRS cohorts including more than 6000 patients treated with DAA and we focused on HCC patients who underwent curative procedures before DAA treatment. The aim was to assess the rates of HCC recurrence in these patients according to antiviral treatment regimen. In the ANRS CO22 "Therapeutic options for hepatitis B and C: a French cohort" (HEPATHER) cohort, 267 patients with chronic hepatitis C who were previously treated for HCC were analyzed, among whom 189 received DAA and 78 did not. The rates of recurrence were 0.73/100 and 0.66/100 person-months, respectively. In the ANRS CO12 "Cirrhose Virale" (CirVir) cohort, 79 cirrhotic patients in whom HCC was diagnosed and treated, 13 received DAA and 66 did not. The rates of recurrence were 1.11/100 and 1.73/100 person-months, respectively. In the ANRS CO23 "Compassionate use of Protease Inhibitors in viral C Liver Transplantation" (CUPILT) Cohort, 314 liver transplant recipients for HCC who were subsequently treated with DAA were analyzed. Seven HCC recurrences were reported after a median time of 70.3months after liver transplantation. The rate of recurrence was 2.2%. In three distinct prospective cohorts, we did not observe an increased risk of HCC recurrence after DAA treatment, notably in patients who underwent curative HCC treatment including liver transplantation. Since an unexpected high rate of hepatocellular carcinoma (HCC) recurrence after direct-acting antiviral (DAA) treatment has been suggested in a retrospective study, we analyzed data from three French prospective multicentre ANRS cohorts of >6000 DAA-treated patients who underwent curative HCC therapies. We did not observe an increased risk of HCC recurrence after DAA treatment: the rates of recurrence were similar in treated and untreated patients (0.73/100 and 0.66/100 person-months in in the ANRS CO22 HEPATHER cohort including 189 DAA+ and 78 DAA- and 1.11/100 in 13 DAA+ and 1.73/100 person-months in 66 DAA- in the ANRS CO12 CirVir cohort), respectively. Finally, in the ANRS CO23 CUPILT Cohort, HCC recurred in only 7 among 314 (2.2%) liver transplant recipients for HCC subsequently treated after 70months after liver transplantation.


An upset to the standard model.
Latest measurement of the W boson digs at the most important theory in particle physics.


Antitorsadogenic effects of ({+/-})-N-(2,6-dimethyl-phenyl)-(4[2-hydroxy-3-(2-methoxyphenoxy)propyl]-1-piperazine (ranolazine) in anesthetized rabbits.
Ranolazine [Ranexa; (+/-)-N-(2,6-dimethyl-phenyl)-(4[2-hydroxy-3-(2-methoxyphenoxy)propyl]-1-piperazine] is novel anti-ischemic agent that has been shown to inhibit late I(Na) and I(Kr) and to have antiarrhythmic effects in various preclinical in vitro models. This study was undertaken to investigate the effects of ranolazine on drug-induced Torsade de Pointes (TdP) in vivo. TdP was induced by an I(Kr) blocker, clofilium, in anesthetized, alpha(1)-agonist-sensitized rabbits. Clofilium prolonged QT interval corrected for heart rate (QTc) (52 +/- 9%) and monophasic action potential duration (MAPD)(90) (56 +/- 9%) and caused TdP in eight of eight rabbits. Pretreatment with ranolazine (480 microg/kg/min) or lidocaine (200 microg/kg/min) reduced the clofilium-induced prolongation of QTc (15 +/- 3 and 19 +/- 3%, respectively, p < 0.001 versus vehicle) and MAPD(90) (21 +/- 4 and 20 +/- 2%, respectively, p < 0.001 versus vehicle) and prevented the occurrence of TdP (zero of eight and zero of eight, respectively). Administration of ranolazine after the first episode of TdP terminated TdP and prevented its recurrence (zero of four versus vehicle, four of four). To rule out an alpha(1)-adrenoceptor antagonistic activity of ranolazine, we compared the effects of ranolazine on blood pressure with those of the alpha(1)-antagonist, prazosin. Although prazosin (10 microg/kg/min) markedly shifted the phenylephrine (alpha(1)-agonist) dose-response curve to the right, it did not have any effect on clofilium-induced prolongation of QTc and MAPD(90) (43 +/- 7 and 53 +/- 9%, respectively) or the occurrence of TdP (seven of eight). In contrast, ranolazine completely suppressed TdP but did not cause any shift in the phenylephrine dose-response curve at the highest dose tested (480 microg/kg/min). We conclude that ranolazine antagonizes the ventricular repolarization changes caused by clofilium and suppresses clofilium-induced TdP in rabbits.


In vitro biodurability of the product of thermal transformation of cement-asbestos.
To safely recycle the product of the thermal transformation of cement-asbestos as secondary raw material, its toxicity potential should be assessed by in vitro biodurability tests. In this work, the acellular in vitro biodurability of the products of transformation of cement-asbestos at 1200 °C (named KRY·AS) was tested using both inorganic and organic simulated lung fluids at pH 4.5. The dissolution kinetics were followed using chemical, mineralogical and microstructural analyses. The total dissolution time estimated from the experiments with inorganic HCl diluted solution is one order of magnitude higher than that determined from the experiments with buffered Gamble solution (253 days vs. 20 days). The key parameter determining the difference in dissolution rate turns out to be the solidus/liquidus ratio which prompts a fast saturation of the solution with monosilicic acid. The calculated dissolution rate constants showed that the biodurability in vitro of KRY·AS is much lower with respect to that of standard chrysotile asbestos (total estimated dissolution time of 20 days vs. 298 days, respectively). This proves a low potential toxicity of this secondary raw material.


A new method for obtaining viable cells from dermal infiltrates. A study on 2,4 dinitrochlorobenzene induced contact dermatitis.
Experimental contact dermatitis has been induced in 2,4 dinitrochlorobenzene (DNCB) sensitized guinea pigs. The developing dermal infiltrate was excised and the infiltrating cells were obtained by mechanical extraction alone as well as by the combination with collagenase and elastase treatment. The most viable cells appeared in the elastase and mechanically extracted samples and the least in those subjected to mechanical treatment alone. The most cells in the enzyme-treated samples were present 24 h after re-exposure of the sensitized animals to DNCB consisting mainly of lymphocytes and of polymorphonuclear granulocytes. The optimum conditions for the action of enzymes including optimum duration of the treatment, buffer milieu, aspecific proteolytic effect on foreign substrate and action on T and B cell receptors have been elaborated. It was concluded that 80 min of collagenase treatment with gentle mechanical extraction under specified conditions does not affect any measurable immunologic properties of the liberated cells resulting in the second best yield. A comparison of these data with earlier reports and their significance is being discussed.


Renal progenitors in non-diabetic and diabetic nephropathies.
Chronic kidney disease represents a major health problem worldwide. Although the kidney has the ability to repopulate structures that have sustained some degree of injury, the mechanisms underlying its regenerative capacity have been unclear. Recent evidence now supports the existence of a renal progenitor system able to replace podocytes and tubular cells, localized within the urinary pole of Bowman's capsule and along the tubule. Altered growth or differentiation of renal progenitors has been reported in several renal disorders including diabetic nephropathy. Pharmacological modulation of renal progenitor growth or differentiation can enhance kidney regeneration, suggesting that treatments aimed at reversing kidney injury are possible. Renal progenitors may represent a novel target in diabetic nephropathy and other kidney disorders.


The UNILINK system for mechanical microvascular anastomosis in hand surgery.
A new mechanical anastomotic device--the UNILINK system--for small vessels, designed for work under the operating microscope was used in four patients for microvascular, hand surgical operations. All procedures were successful with regard to tissue survival and wound healing. Basal skin temperature and systolic blood pressure distal to the mechanical anastomoses were normal 12 to 26 months after the operation. Doppler investigation also confirmed that all mechanical anastomoses were patent. At the time of this report, 32 to 45 months after the operations, no adverse effects of the method have been found. The device offers increased safety and speed in microvascular operations.


Physical activity in midlife and telomere length measured in old age.
Physical activity has been associated with alterations in telomere length, a potential indicator of biological aging, but several inconsistencies exist. Our aim was to investigate the associations between physical activity in midlife and leukocyte telomere length (LTL) measured in old age in the Helsinki Businessmen Study, Finland. At entry, in 1974, 782 men (mean age 47) completed a questionnaire about their physical activity and this was collapsed into 3 categories: low (n=148), moderate (n=398) and high physical activity (n=236, 7 of whom had a competitive activity level). After 29-year follow-up in 2003, mean LTL and the proportion of short (<5 kB) telomeres were measured from DNA samples of a random subcohort of survivors (n=204, mean age 76) using the Southern blot technique. Adjusted for age, body mass index (BMI), cholesterol and smoking in 1974, the moderate physical activity group had longer mean LTL (8.27 kB, SE 0.05) than the low (8.10 kB, SE 0.07), or high (8.10 kB, SE 0.05) physical activity groups (P=0.03 between groups). Conversely, the proportion of short telomeres was lowest in the moderate physical activity group (11.35%, SE 0.25), and higher in the high (12.39%, SE 0.29), and the low physical activity (12.21%, SE 0.39) groups (P=0.02 between groups). We conclude that the results of this observational cohort study give support to the idea that both low and high physical activity is in the long-term associated with factors shortening LTL.


Osteoporosis treatment: focus on safety.
Osteoporosis results in approximately one-half of older white women and one-third of men sustaining fractures, which cause significant disability and increased mortality. Interventions are now available which reduce fracture risk by about one-half, and there is evidence that they also reduce mortality in frail elderly by about 10%. The mechanism of this reduced mortality is unclear but it has the potential to substantially impact on the cost-benefit of osteoporosis treatment. Available treatments are generally well-tolerated. Bisphosphonates cause gastrointestinal side-effects when administered orally, and acute phase responses when given intravenously. Osteonecrosis of the jaw is overwhelmingly a problem of cancer sufferers rather than those with osteoporosis, but atypical patterns of fracture in the upper femoral shaft sometimes occur in users of these drugs, though they are very rare in comparison with the other osteoporotic fractures which these drugs prevent. Thus, the cost-benefit of bisphosphonate use is clearly positive in those with osteoporosis. In contrast, calcium supplements probably increase the risk of myocardial infarction, admissions to hospital with acute gastrointestinal complaints and risk of renal calculi, whereas their impact on fracture is marginal (about a 10% reduction). Thus, they are not cost-effective, and a balanced diet is a safer way of obtaining one's calcium requirements.


Effects of acupuncture on mental health of migraine patients: a systematic review and meta-analysis.
Migraine is a neurological disease characterized by moderate to severe headache and various neurological symptoms. It is often cause mood and anxiety disorders that can seriously affect quality of life. Acupuncture has been claimed to have a role in treating neuropsychiatric disorders and is becoming increasingly popular. However, it remains unclear whether current evidence is sufficient to support acupuncture in improving mental health in migraine patients. This systematic review and meta-analysis aimed to investigate the effect of acupuncture on the management of pain and mood disorders in patients with migraine. We searched PubMed, Cochrane Library, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI) and Wan Fang Data Knowledge Service Platform for reports, conferences and academic papers published before January 1, 2022. Randomized controlled trials (RCTs) including acupuncture, sham acupuncture and medication for migraine were included. Stata 16.0 software and Cochrane RoB2.0 were used for data processing and migration risk analysis. Thirteen randomized controlled trials containing 1766 migraine patients were included in the present study, the results showed that compared with sham acupuncture and medication, acupuncture seemed to have advantage in improving SAS (WMD: -5.64;95% CI: -10.89, -0.39; p = 0.035) and SDS (WMD: -4.65; 95% CI: -9.25, -0.05; p = 0.048) in migraine patients. And it seems to be more effective in improving MH (SMD: 0.77; 95% CI: 0.19, 1.35; p = 0.009), VAS (SMD: -1.06; 95% CI: -1.73, -0.4; p = 0.002;) and MSQ (WMD: 4.76; 95% CI: 2.36, 7.15; p < 0.001) than sham acupuncture and medication. The present results suggest that, compared with Western medicine and sham acupuncture, acupuncture seems to be able to effectively improve anxiety and depression in migraine patients.And it may be more effective in improving SF36-mental health, VAS and MSQ than shame acupuncture or Western medicine. The results of this study need to be verified by higher quality RCTs.


Terminalia chebula extracts ameliorate methamphetamine-induced memory deficits via activating the ERK and Nrf2 pathway.
As a psychoactive substance abused worldwide, methamphetamine (METH) abuse leads to multiple neurodegenerative symptoms including memory deficits. Terminalia chebula retzius extracts (TREs) isolated by our lab have great antioxidant activity and its effect on METH-induced memory deficits has not been investigated yet. The present study was designed to investigate the protective effect of TREs on METH induced cell apoptosis in vitro and memory deficits in vivo. The results showed that TREs treatment attenuated free radical release and improved cell survival of primary hippocampal neurons after METH injury. In the Morris water maze task, TREs treatment reversed METH-induced learning and memory deficits in acquisition and retention. Moreover, TREs reduced oxidative stress in the serum and hippocampus of mice. Additionally, extracellular regulated protein kinases (ERK1/2) pathway and the nuclear factor E2-related factor 2 (Nrf2) pathway were inactivated after METH treatment, and were significantly activated after TREs pretreatment. These findings suggest that TREs may exert potent neuroprotective effect via activation of both ERK and Nrf2 pathways, thus providing a basis for its potential use for ameliorating memory deficits induced by METH.


Epigallocatechin-3-gallate inhibits bacterial virulence and invasion of host cells.
Increasing antibiotic resistance and beneficial effects of host microbiota has motivated the search for anti-infective agents that attenuate bacterial virulence rather than growth. For example, we discovered that specific flavonoids such as baicalein and quercetin from traditional medicinal plant extracts could attenuate Salmonella enterica serovar Typhimurium type III protein secretion and invasion of host cells. Here, we show epigallocatechin-3-gallate from green tea extracts also inhibits the activity of S. Typhimurium type III protein effectors and significantly reduces bacterial invasion into host cells. These results reveal additional dietary plant metabolites that can attenuate bacterial virulence and infection of host cells.


Isolation and characterization of a retinal-binding protein from the squid retina.
A retinal-binding protein (RALBP) was isolated from the squid retina, and purified by anion-exchange and size-exclusion chromatography. The molecular weight was determined to be 51,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by gel filtration. The purified sample showed absorption maxima at about 330 and 400 nm in addition to a protein band, indicating the occurrence of retinol and retinal, respectively. The relative heights of these two peaks varied from preparation to preparation, depending on retinoid ligands. Irradiation of RALBP caused no marked change in absorption, but the amount of 11-cis-retinal decreased to form a photosteady state mixture with all-trans- and 13-cis-retinals. RALBP was fairly stable even in the presence of hydroxylamine (100 mM), but was affected by sodium borohydride (30 mM) or borane dimethylamine (400 mM), with the retinal reduced to retinol. When incubated with metaretinochrome-carrying membranes in the dark, RALBP specifically took up 11-cis-retinal and lost all-trans-retinol. Upon further incubation of this RALBP with opsin-containing membranes, rhodopsin was progressively formed in the dark. Squid RALBP may act as a shuttle in transferring the 11-cis-retinal from metaretinochrome to opsin in the visual cells.


Chitosan alleviated menopausal symptoms and modulated the gut microbiota in estrogen-deficient rats.
Menopause disturbs energy, glucose, and lipid metabolisms and changes the composition of the gut microbiota, but dietary fibers without phytoestrogens may ameliorate menopausal metabolic disorders. The objective of the present study was to assess whether consuming the prebiotics chitosan and citrus pectin can improve postmenopausal symptoms, possibly by modulating the gut microbiota in ovariectomized (OVX) rats, and the mechanism of action was examined. The OVX rats were given 4.5% cellulose (OVX-Control), chitosan (OVX-Chitosan), or citrus pectin (OVX-Pectin) in a 43% fat diet and the sham rats were given the same diet as the OVX-Control for 12 weeks. Sham-operated rats had the same diet as OVX-Control (Normal-Control). Body-weight, visceral fat mass, tail skin temperature, serum 17β-estradiol, glucose intolerance, and insulin tolerance were determined. Gut microbiota in the fecal samples was measured by NGS and analyzed with PICRUSt2. Short-chain fatty acids (SCFA) and metabolomic characteristics of serum were also measured with UPLC-mass spectrometry. Chitosan and citrus pectin were selected because the incubation of rat feces with these two prebiotics in vitro had shown increased butyrate production. OVX-Chitosan reduced the weight, visceral fat content, and tail skin temperature, and OVX-Chitosan and OVX-Pectin improved glucose tolerance, compared to the OVX-Control. Both alleviated dyslipidemia, compared to the OVX-Control. OVX-Chitosan and OVX-Pectin elevated serum propionate and butyrate concentrations but only OVX-Chitosan lowered serum acetate concentrations. In PICRUSt2, chitosan upregulated the functional genes of gut microbiota involved in valine, leucine, and isoleucine biosynthesis, whereas the OVX-Control exhibited significantly upregulated lipopolysaccharide biosynthesis. OVX-Pectin exhibited increased α-diversity in the fecal bacteria. Metabolomic analysis revealed higher serum urate concentrations in the OVX-Control group than the other groups, and serum arginine and leucine concentrations were higher in the OVX-Chitosan group (P < 0.05). Chitosan and citrus pectin consumptions improved menopausal symptoms by improving the diversity and composition of the gut microbiota, and serum metabolites and SCFA originating from fecal bacteria. Chitosan was more effective for improving menopausal symptoms than citrus pectin.


Sleep apnea, metabolic disease, and the cutting edge of therapy.
Obstructive sleep apnea (OSA) is common, and many cross-sectional and longitudinal studies have established OSA as an independent risk factor for the development of a variety of adverse metabolic disease states, including hypertension, insulin resistance, type 2 diabetes, nonalcoholic fatty liver disease, dyslipidemia, and atherosclerosis. Nasal continuous positive airway pressure (CPAP) has long been the mainstay of therapy for OSA, but definitive studies demonstrating the efficacy of CPAP in improving metabolic outcomes, or in reducing incident disease burden, are lacking; moreover, CPAP has variable rates of adherence. Therefore, the future of OSA management, particularly with respect to limiting OSA-related metabolic dysfunction, likely lies in a coming wave of alternative approaches to endophenotyping OSA patients, personalized care, and defining and targeting mechanisms of OSA-induced adverse health outcomes.


Comparison of cardiac autonomic activity between positional and nonpositional obstructive sleep apnea using heart rate variability.
Patients with obstructive sleep apnea (OSA) experience sympathetic hyperactivation during sleep, which is associated with increased cardiovascular risk factors. However, the difference in cardiac autonomic activity in OSA patients according to position dependency has not been evaluated. This study aimed to evaluate the differences between positional OSA (pOSA) and nonpositional OSA (npOSA) using heart rate variability (HRV) analysis. This was a single-center cross-sectional study. Twenty-eight patients with npOSA and 28 age-, sex-, and AHI-matched patients with pOSA underwent standard polysomnography. A five-minute R-R interval from stable waking conditions before bedtime was collected from each subject and analyzed for HRV. Patients with pOSA had lower body-mass index (BMI, 25.8 ± 2.9 vs 28.9 ± 3.7 kg/m2, p = 0.001), shorter apnea duration (24.1 ± 7.1 vs 30.3 ± 12.7 s, p = 0.028) and higher minimum oxygen saturation (78.2 ± 7.1 vs 71.5 ± 11.4%, p = 0.011) than those with npOSA. HRV analysis showed higher parasympathetic activity in pOSA patients than in npOSA patients, including a higher square root of the mean of the sum of the squares of differences between adjacent NN intervals (RMSSD, 31.3 ± 29.0 vs 18.6 ± 9.2, p = 0.032), percentage of pairs of adjacent NN intervals that differ by more than 50 ms (pNN50%, 10.7 ± 17.1 vs 3.3 ± 6.5, p = 0.024), and high-frequency (HF) power (534.7 ± 986.8 vs 146.7 ± 150.5, p = 0.026). The group difference was insignificant after adjusting for age and BMI. The log-transformed supine/nonsupine AHI ratio was the sole independent predictor of HRV parameters. The waking HRV was higher in pOSA patients than in npOSA patients due to the lower BMI of pOSA patients. The difference was especially apparent in parasympathetic indices. Higher parasympathetic activity in pOSA may suggest a lower risk for cardiovascular morbidity and mortality.


Study on molecular level toxicity of Sb(V) to soil springtails: using a combination of transcriptomics and metabolomics.
To date, numerous studies have focused on the toxicity of antimony (Sb) to soil-dwelling organisms at the individual level. However, little is known about Sb-caused molecular level toxicity. Here, an integrated transcriptomics and metabolomics approach was used to better reveal toxicity of Sb(V) to springtails Folsomia candida considering environmentally relevant speciation of Sb. No significant effects of Sb(V) on survival, reproduction and growth of springtails were observed using the ISO standard test. Transcriptomics analysis identified 1015 and 3367 differentially expressed genes (DEGs) after 2 and 7 d of exposure, indicating an increasing transcriptomal changes with time. Significantly enriched top GO (Gene Ontology) terms (chitin metabolic process, chitin binding and extracellular region) were shared between the two time exposure groups. However, no enriched KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway was shared, with fatty acid metabolism and apoptosis-fly being the most significant pathway, respectively. Metabolomics analysis identified 155 differential changed metabolites (DCMs) in springtails after 7 d of exposure. Antifolate resistance was the most significantly enriched pathway, in which dihydrofolic acid was up-regulated and three purine nucleotides (adenosine 5'-monophosphate, inosine 5'-monophosphate, guanosine 5'-monophosphate) were down-regulated. This indicated obvious repression of DNA replication, which was also observed by transcriptomics. Additionally, metabolites level related to chitin, oxidative stress, and protein metabolism significantly changed, and these metabolites could also support and confirm main transcriptomic results. Thus, the combination of multiomics facilitated better understanding of the molecular level of toxicity of Sb(V) in Collembola.


Gene Selection for the Discrimination of Colorectal Cancer.
Colorectal cancer (CRC) is the third most common cancer worldwide. Cancer discrimination is a typical application of gene expression analysis using a microarray technique. However, microarray data suffer from the curse of dimensionality and usual imbalanced class distribution between the majority (tumor samples) and minority (normal samples) classes. Feature gene selection is necessary and important for cancer discrimination. To select feature genes for the discrimination of CRC. We improve the feature selection algorithm based on differential evolution, DEFSw by using RUSBoost classifier and weight accuracy instead of the common classifier and evaluation measure for selecting feature genes from imbalance data. We firstly extract differently expressed genes (DEGs) from the CRC dataset of the TCGA and then select the feature genes from the DEGs using the improved DEFSw algorithm. Finally, we validate the selected feature gene sets using independent datasets and retrieve the cancer related information for these genes based on text mining through the Coremine Medical online database. We select out 16 single-gene feature sets for colorectal cancer discrimination and 19 single-gene feature sets only for colon cancer discrimination. In summary, we find a series of high potential candidate biomarkers or signatures, which can discriminate either or both of colon cancer and rectal cancer with high sensitivity and specificity.


YWHAE rearrangement identified by FISH and RT-PCR in endometrial stromal sarcomas: genetic and pathological correlations.
Endometrial stromal sarcomas represent the second most common mesenchymal uterine tumor. The 2003 WHO classification distinguishes low-grade and undifferentiated endometrial stromal sarcomas with different prognoses. Endometrial stromal sarcomas are a genetically heterogeneous group of sarcomas harboring different cytogenetic anomalies. Recently, a fusion between the YWHAE and FAM22A/B genes subsequent to a t(10;17) (q22;p13) has been described in endometrial sarcomas with high-grade histology. We examined YWHAE rearrangements by FISH break-apart and RT-PCR in a series of 27 undifferentiated uterine stromal sarcoma without JAZF1 rearrangements. Immunohistochemistry (IHC) was carried out with a panel of antibodies (estrogen (ER) and progesterone (PR) receptors, CD10, Cyclin D1, β-catenin, p53, and Ki-67). We identified a subgroup of endometrial sarcomas with high-grade histology and uniform morphology harboring YWHAE rearrangements. FISH break-apart was interpretable in 20 cases (74%). Twelve cases (60%) showed <10% of tumor cells with a YWHAE rearrangement, 4 cases (20%) showed between 10 and ≤20%, and 4 (20%) >20%. RT-PCR was tested on 24/27 cases (88%) and 19 cases were interpretable (79%). Five cases (26%) showed a specific fusion transcript YWHAE-FAM22A/B sequence. The best concordance rate between FISH and RT-PCR (94%) was obtained with the threshold of 20% of cells with a YWHAE rearrangement. The YWHAE-rearranged cases showed high-grade morphology with uniform appearance, spindle or round epithelioid cells, low ER and PR, CD10 expression, and a high and diffuse positivity for Cyclin D1, p53, and nuclear β-catenin negativity. Cyclin D1 was the most sensitive marker for high-grade endometrial sarcomas with YWHAE rearrangement. All undifferentiated uterine sarcomas with pleomorphic appearances did not harbor any YWHAE rearrangements, except for one case. Overall, for endometrial sarcoma cases with high-grade morphology we recommend to test for YWHAE rearrangements by FISH break-apart, a cost- and time-efficient method, and to complete the investigation by RT-PCR in borderline cases.


[Control of SARS-CoV-2 in prisons].
Review of control and management of SARS-CoV-2 infection in penitentiary institutions in Spain and other countries. A systematic review a comprehensive literature search in Global Health, SCOPUS, Medline and EMBASE was performed using relevant keywords and medical descriptors (MeSH) related to the coronavirus disease (COVID-19) and prisons. National and international recommendations and guides were examined as well as documents published by some countries. The key points of the guides are discussed. The vast majority of recommendations coincide with respect to the measures and procedures that should be used, except for some discrepancy regarding the population screening. Until now, most industrialized countries (except the US and some specific scenarios) have controlled successfully the epidemic in prisons. Less data is found as regards to socioeconomically more disadvantaged countries. Prisons are prone to a high risk of SARS-CoV-2 transmission due to their space limitations and sometimes poor environmental and hygienic conditions. The recommendations of the control and management of SARS-CoV-2 infection must be the same as those outside the prison, but must be adapted to the peculiarities of the prison. The recommendations must be issued by the health administration in coordination with the prison administration. Finally, must be abide by the Mandela Rules or by the Standard Minimum Rules for the treatment of United Nations prisoners.


Systemic Therapy for Oligoprogression in Patients with Metastatic NSCLC Harboring Activating EGFR Mutations.
After a variable period of activity of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment, patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations develop resistance to these TKIs. In some cases, an oligoprogression is diagnosed, and its management is still controversial. The oligoprogression represents an intermediate stage of metastatic NSCLC between localized and widely disseminated disease, and is characterized by a limited number and/or sites of metastases in which a disease progression appears, together with a more indolent tumor biology. Currently, the management of oligoprogressed NSCLC involves local treatment, including radiotherapy and/or surgery, to control the progressive lesions. Systemic therapy should also be a potential approach to boost the activity of EGFR-TKIs. However, considering the lack of large trials addressing this topic, the optimal therapeutic strategies remain undefined and should be evaluated on an individualized basis. In this paper, we review the most relevant scientific evidence of continuing the systemic therapy with the same EGFR-TKI for the management of patients with NSCLC harboring EGFR mutations and oligoprogressed to first-line EGFR-TKIs, also discussing the controversies and potential future directions.


Eradication of enterococci biofilms by lactic acid alone and combined with chlorhexidine and cetrimide.
The antimicrobial activity of lactic acid (LA) alone or in combination with chlorhexidine (CHX) and cetrimide (CTR) against three Enterococcus faecalis strains, E. faecalis ATCC 29212, E. faecalis EF-D1 and E. faecalis U-1765, one Enterococcus durans strain and one dual-species biofilm was investigated. The irrigating solutions tested were 20%, 15%, 10%, 5% and 2.5% LA, alone and in combination with 2% CHX and with 0.2% CTR. The biofilms were grown in the MBECTM high-throughput device for 24 hours and exposed to the solutions for 30 seconds and 1 minute. "Eradication" was defined as 100% bacterial kill. Twenty percent LA eradicated all enterococci biofilms after 30 seconds contact time. The association of LA+0.2% CTR achieved better results than LA alone, in contrast with the results obtained using LA+2% CHX. E. durans was eradicated by all the tested solutions at 1 minute. The dual-species biofilm, E. faecalis ATCC 29212+E. durans, gave intermediate values of the pure cultures. LA is capable of eradicating enterococci biofilm at a concentration of 20%. The combination of lower concentrations with 0.2% CTR achieved eradication after 1 minute.


A polysaccharide from Lycium barbarum L.: Structure and protective effects against oxidative stress and high-glucose-induced apoptosis in ARPE-19 cells.
Lycium barbarum polysaccharides (LBPs) are beneficial for vision; however, relevant research has mainly focused on entire crude polysaccharides, with the basis and exact structure of the polysaccharide rarely explored. In this study, LICP009-3F-2a, a novel polysaccharide from Lycium barbarum L., was separated and then purified using anion-exchange and size-exclusion chromatography. Structural characteristics were investigated using chemical and spectroscopic methods, which revealed that LICP009-3F-2a has an Mw of 13720 Da and is an acidic heteropolysaccharide composed of rhamnose (39.1%), arabinose (7.4%), galactose (22.5%), glucose (8.3%), galacturonic acid (13.7%), and glucuronic acid (4.0%). Linkage and NMR data revealed that LICP009-3F-2a has the following backbone: →2)-α-L-Rha-(1 → 2,4)-α-L-Rha-(1 → 4)-α-D-GalAp-(1 → 3,6)-β-D-Galp-(1 → 3,6)-β-D-Galp-(1 → 6)-β-D-Galp-(1→, with three main branches, including: α-L-Araf-(1 → 5)-α-L-Araf-(1 → 6)-β-D-Glcp-(1 → 2,4)-α-L-Rha-(1→, β-D-Glcp-(1 → 4)-β-D-Glcp-(1 → 3,6)-β-D-Galp-(1→, and β-D-Galp-(1 → 3)-β-D-Galp-(1 → 3,6)-β-D-Galp-(1 → . Differential scanning colorimetry and thermogravimetric analysis showed that LICP009-3F-2a is thermally stable, while X-ray diffractometry showed that LICP009-3F-2a has a semi-crystalline structure. In addition, LICP009-3F-2a protects ARPE-19 cells from H2O2-induced oxidative damage by regulating the expression of antioxidant SOD1 and CAT enzymes and down-regulating MMP2 expression. Moreover, LICP009-3F-2a promotes the proliferation of ARPE-19 cells in a concentration-dependent manner, and protects ARPE-19 cells from hyperglycemia by inhibiting apoptosis.


Encephalocele (cerebellocele) in the Goldenhar-Gorlin syndrome.
A patient with unilateral preauricular appendages and occipital mass is described who died on the fifth day of life. An autopsy demonstrated congenital megabladder and megaureters and dysplastic kidneys. The neuropathological examination revealed cranium bifidum in the occipital region, defective posterior arch of the C1 vertebral body, agenesis of vermis and a large cerebellocele. It is suggested that some patients with the Goldenhar-Gorlin syndrome may have prominent central nervous system involvement in spite of only relatively slight facial involvement.


[Cardiovascular assessment and management prior to non-cardiac surgery. Comment on the new 2014 ESC/ESA guidelines].
In 2014 the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA) published an update of the guidelines on "non-cardiac surgery: cardiovascular assessment and management". Epidemiological data underline the relevance of these guidelines: a total of 5.7 million surgical procedures are performed per year in patients with increased cardiac risk and approximately 167,000 cardiac complications occur per year in Europe of which 19,000 are life-threatening. This new version of the guidelines highlights the patient characteristics, such as functional capacity and comorbidities and procedure-specific aspects for perioperative risk stratification. Decision-making for preoperative stress tests and coronary angiography has been simplified, procedure-specific risks have been revised and the role of multidisciplinary teamwork for high risk procedures is emphasized. A standardized stepwise approach on how to stratify patient-specific and procedure-associated risks has been established. For the first time, the guidelines recommend perioperative regimens on dual antiplatelet therapy and the new oral anticoagulants (NOAC).


Truncated type IV pilin PilA(108) activates the intramembrane protease AlgW to cleave MucA and PilA(108) itself in vitro.
For alginate production in Pseudomonas aeruginosa, the intramembrane protease AlgW must be activated to cleave the periplasmic domain of anti-sigma factor MucA for release of the sequestered ECF sigma factor AlgU. Previously, we reported that three tandem point mutations in the pilA gene, resulting in a truncated type IV pilin termed PilA(108) with a C-terminal motif of phenylalanine-threonine-phenylalanine (FTF), induced mucoidy in strain PAO579. In this study, we purified PilA(108) protein and synthesized a peptide 'SGAGDITFTF' corresponding to C-terminus of PilA(108) and found they both caused the degradation of MucA by AlgW. Interestingly, AlgW could also cleave PilA(108) between alanine(62) and glycine(63) residues. Overexpression of the recombinant FTF motif-bearing MucE protein, originally a small periplasmic polypeptide with the C-terminal motif WVF, could induce mucoid conversion in the PAO1 strain. In all, our results provided a model of activation of AlgW by another protein ending with proper motifs. Our data suggest that in addition to MucA cleavage, AlgW may cleave other substrates.


First trial reactions and habituation rates over successive balance perturbations in Parkinson's disease.
Balance control in Parkinson's disease is often studied using dynamic posturography, typically with serial identical balance perturbations. Because subjects can learn from the first trial, the magnitude of balance reactions rapidly habituates during subsequent trials. Changes in this habituation rate might yield a clinically useful marker. We studied balance reactions in Parkinson's disease using posturography, specifically focusing on the responses to the first, fully unpractised balance disturbance, and on the subsequent habituation rates. Eight Parkinson patients and eight age- and gender-matched controls received eight consecutive toe-up rotations of a support-surface. Balance reactions were measured with a motion analysis system and converted to centre of mass displacements (primary outcome). Mean centre of mass displacement during the first trial was 51% greater in patients than controls (P=0.019), due to excessive trunk flexion and greater ankle plantar-flexion. However, habituated trials were comparable in both groups. Patients also habituated slower: controls were fully habituated at trial 2, whereas habituation in patients required up to five trials (P=0.004). The number of near-falls during the first trial was significantly correlated with centre of mass displacement during the first trial and with habituation rate. Higher first trial reactions and a slow habituation rate discriminated Parkinson's patients from controls, but habituated trials did not. Further work should demonstrate whether this also applies to clinical balance tests, such as the pull test, and whether repeated delivery of such tests offers better diagnostic value for evaluating fall risks in parkinsonian patients.


Applicability of superhelical model for regulation of gene expression.
The superhelical model for regulation of gene expression was tested in 41 structural genes of eukaryotes, viruses and plasmids, and in the primer RNA gene for DNA replication in five kinds of enteric bacteria and two kinds of plasmids. The model which was first proposed for regulation of transcription in simian virus 40 was based on the following observations: a stem-loop structure of low free energy was located 3' downstream from the transcriptional initiation site; sequences homologous to the loop were located at the symmetrical site with the stem-loop at the center; and the loop encountered any of these homologous sequences after one rotation of superhelix depending on the superhelical density. If the loop interacted with the complementary sequences in the opposite strand, DNA formed a specific cruciform or T-shaped structure. The superhelical model proposed that transcription was regulated by the conversion of the template DNA in the regular, the cruciform, and the T-shaped structures. The model was applicable to all the structural genes and the primer RNA genes tested so far, except histone genes. In eukaryotes, only one stem-loop structure which conformed to the superhelical model was constructed in most of the genes except the growth hormone genes, the globin genes of human, and the human interferon gamma gene. An average length of the stem-loop was 46 bases, and the 5' end of the stem loop was located at the 30th base downstream from the transcriptional initiation site on the average in eukaryotes. In some genes, a consensus sequence was detected in the loops of the same kind of gene in different species or of different kind of gene in the same species.


Influence of muscle traction on the primary stability of a reverse humeral prosthesis.
Currently, the influence of muscle traction on the postoperative stability of humeral prostheses is not adequately researched. This study analyzed the prosthesis' stability in vitro during muscle traction considering different bone defect sizes. The reverse humeral prosthesis "AEQUALIS™ ADJUSTABLE REVERSED" (Stryker) was implanted using press-fit into ten bones with a length of 200 mm and 160 mm. Subsequently, the models were torqued in 30 cycles using a universal testing machine (2 Nm - 6 Nm) and loaded axially to simulate muscle traction. The axial weight increased from 7.7 kg (pure muscle traction) over 40 kg (45-degree abduction) to 69.3 kg (90-degree abduction). The prosthesis' relative micromotion was simultaneously measured at three different measurement heights using high-sensitivity displacement transducers and compared to the relative micromotion without axial load. It was found that a larger torsional moment was associated with a larger relative micromotion in both bone defects studied. However, the influence became significant (P < 0.014) in bone models with predominantly larger defect.Furthermore, no significant influence of muscle traction on relative micromotion could be detected for the larger bone models at any of the measurement levels (P = 1.000). In contrast, smaller bones showed no significant differences in muscle traction until a torsional moment of 6 Nm (P < 0.028). In conclusion, a larger torsional moment is associated with a higher relative micromotion and muscle traction, conclusively, has no effect on the primary stability of the reverse prosthesis for a 200 mm bone in vitro.


Response to the "Comment on Chemical and Toxicological Investigations of a Previously Unknown Poisonous European Mushroom Tricholoma terreum".
Recently, Dr. Paolo Davoli and his colleagues stated that the conclusions drawn by us were misleading from a mycotoxicological perspective, as they cast doubts on the edibility of a mushroom species (Tricholoma terreum) that has been always recognized as safe. Unfortunately, they made a mistake, and seriously misinterpreted our data, which resulted in scepticism of our research. Saponaceolides B and M were tested for their stabilities heating directly on and boiling in water. It is undoubted that both saponaceolides B and M are capable of withstanding prolonged heating during cooking.


The future prospects of Lithuanian family physicians: a 10-year forecasting study.
When health care reform was started in 1991, the physician workforce in Lithuania was dominated by specialists, and the specialty of family physician (FP) did not exist at all. During fifteen years of Lithuania's independence this specialty evolved rapidly and over 1,900 FPs were trained or retrained. Since 2003, the Lithuanian health care sector has undergone restructuring to optimize the network of health care institutions as well as the delivery of services; specific attention has been paid to the development of services provided by FPs, with more health care services shifted from the hospital level to the primary health care level. In this paper we analyze if an adequate workforce of FPs will be available in the future to take over new emerging tasks. A computer spreadsheet simulation model was used to project the supply of FPs in 2006-2015. The supply was projected according to three scenarios, which took into account different rates of retirement, migration and drop out from training. In addition different population projections and enrollment numbers in residency programs were also considered. Three requirement scenarios were made using different approaches. In the first scenario we used the requirement estimated by a panel of experts using the Delphi technique. The second scenario was based on the number of visits to FPs in 2003 and took into account the goal to increase the number of visits. The third scenario was based on the determination that one FP should serve no more than 2,000 inhabitants. The three scenarios for the projection of supply were compared with the three requirement scenarios. The supply of family physicians will be higher in 2015 compared to 2005 according to all projection scenarios. The largest differences in the supply scenarios were caused by different migration rates, enrollment numbers to training programs and the retirement age. The second supply scenario, which took into account 1.1% annual migration rate, stable enrollment to residency programs and later retirement, appears to be the most probable. The first requirement scenario, which was based on the opinion of well-informed key experts in the field, appears to be the best reflection of FP requirements; however none of the supply scenarios considered would satisfy these requirements. Despite the rapid expansion of the FP workforce during the last fifteen years, ten-year forecasts of supply and requirement indicate that the number of FPs in 2015 will not be sufficient. The annual enrollment in residency training programs should be increased by at least 20% for the next three years. Accurate year-by-year monitoring of the workforce is crucial in order to prevent future shortages and to maintain the desired family physician workforce.


Lymph node extraction of radiopaque nanoparticulates in the rabbit as measured in vivo with CT.
The purpose of this study was to estimate in vivo extraction of lymphographic material in the popliteal node of the rabbit. Serial quantitative computed tomography (CT) of target tissues in four legs of two rabbits was performed after subcutaneous injection of an improved lymphographic contrast agent. Massage was used as a lymphotrophic intervention. At 15 minutes, the mean change in Hounsfield units measured 815 in the popliteal node, 219 in afferent lymphatic vessels, and 127 in efferent lymphatic vessels. The nodal extraction of nanoparticulates from the lymph was approximately 55%. Nodal massage allowed the amount of nanoparticulate remaining in sinusoidal lymph to be estimated. Functional CT performed with timed studies, proper radiopaque materials, and physiologic interventions can depict in vivo lymphatic physiology under minimally invasive conditions.


New phenoxazinone-related alkaloids from strain Streptomyces sp. KIB-H1318.
Chemical investigation of a strain Streptomyces sp. KIB-H1318 isolated from soil sample led to the discovery of three new phenoxazinone-related alkaloids 1-3, as well as two known analogs exfoliazone (4) and viridobrunnine A (5). Their structures were determined on the basis of extensive spectroscopic analysis. The antimicrobial activity and cytotoxicity of the isolates were assayed. Exfoliazone and viridobrunnine A exhibited minor antibacterial activity against Escherichia coli ATCC 8099, Bacillus subtilis ATCC 6633, and Staphylococcus aureus ATCC 6538. Compound 2 exhibited low cytotoxicity against two human cancer cell lines HeLa and SW480 with the IC50 values of 36.8 and 37.8 μM, respectively.


Ecological and evolutionary consequences of predator-prey role reversal: Allee effect and catastrophic predator extinction.
In many terrestrial, marine, and freshwater predator-prey communities, young predators can be vulnerable to attacks by large prey. Frequent prey counter-attacks may hinder the persistence of predators. Despite the commonness of such role reversals in nature, they have rarely been addressed in evolutionary modelling. To understand how role reversals affect ecological and evolutionary dynamics of a predator-prey community, we derived an ecological model from individual-level processes using ordinary differential equations. The model reveals complex ecological dynamics, with possible bistability between alternative coexistence states and an Allee effect for the predators. We find that when prey counter-attacks are frequent, cannibalism is necessary for predator persistence. Using numerical analysis, we also find that a sudden ecological shift from coexistence to predator extinction can occur through several catastrophic bifurcations, including 'saddle-node', 'homoclinic', and 'subcritical Hopf'. The analysis of single-species evolution reveals that predator selection towards increasing or decreasing cannibalism triggers a catastrophic shift towards an extinction state of the predators. Such an evolutionary extinction of the predators may also be caused by prey selection towards increasing foraging activity because it facilitates encounters with vulnerable, young predators. The analysis of predator-prey coevolution further demonstrates that predator's catastrophic extinction becomes an even more likely outcome than in single-species evolution. Our results suggest that when young predators are vulnerable to prey attacks, a sudden extinction of the predators may be more common than currently understood.


Meanings, motivations, and strategies for engaging in physical activity among women with multiple sclerosis.
The aim of the current study was to better understand the adoption and maintenance of physical activity from the perspective of women with multiple sclerosis (MS). Participants (N = 11) were women with MS who had low levels of disability and who engaged in varying levels of physical activity. Participants completed two semi-structured, audio taped interviews focusing on their beliefs, motivators, and experiences of physical activity. Across all activity levels participants reported similar beliefs and motivations related to being physically active including the desire to be "normal", savoring current health, enjoyment of the activity, "feeling good" after activity, weight control, and maintenance of physical function. Active and inactive participants differed in the practical strategies they reportedly used to adopt and maintain physical activity, such as prioritizing and scheduling physical activity, managing disease-specific barriers, and building social support networks. A consideration of these beliefs, motivations, and strategies may be useful for designing behavioral interventions to increase physical activity that are sensitive to the needs and preferences of women with MS.


Experimental and theoretical study of the hydration of phosphate groups in esters of biological interest.
We have studied the influence of different groups esterified to phosphates on the strength of the interaction of the PO bond with one water molecule. Experimental vibrational spectra of PO(4)3-, HPO4(2-), H2PO4-, phosphoenolpiruvate (PEP) and ortho-phosphocholamine (o-PC) were obtained by means of FTIR spectroscopy. Geometry calculations were performed using standard gradient techniques and the default convergence criteria as implemented in GAUSSIAN 98 Program. In order to assess the behaviour of such DFT theoretical calculations using B3LYP with 6-31G* and 6-311++G** basis sets, we carried out a comparative work for those compounds. The results were then used to predict the principal bands of the vibrational spectra and molecular parameters (geometrical parameters, stabilisation energies, electronic density). In this work, the relative stability and the nature of the PO bond in those compounds were systematically and quantitatively investigated by means of Natural Bond Order (NBO) analysis. The topological properties of electronic charge density are analysed employing Bader's Atoms in Molecules theory (AIM). The hydrogen bonding of phosphate groups with water is highly stable and the PO bond wavenumbers are shifted to lower experimental and calculated values (with the DFT/6-311++G** basis set). Accordingly, the predicted order of the relative stability of the hydrogen bonding of the water molecule to the PO bond of the investigated compounds is: PO(4)3->HPO4(2-)>H2PO4->phosphoenolpiruvate>phosphocholamine for the two basis sets used.


Epidemiology of benign eyelid lesions in patients presenting to a teaching hospital.
This study evaluates the relative frequency of benign eyelid lesions presented to a teaching hospital in Saudi population. Charts of patients with benign eyelid lesions were retrospectively reviewed from January 2003 to December 2008. Clinical details included demographic data, symptoms and signs, surgical findings, primary diagnosis, and indication for biopsy were analyzed in a histopathologically confirmed benign eyelid lesions. Eyelid lesions were arranged according to their order of frequencies. A total of 222 biopsies were evaluated from 181 patients (male 39.2% and female 60.8%). The age of the patient at the time of biopsy ranged from 2 to 87 years old. The most common benign eyelid lesion encountered in our practice was sweat gland hidrocystoma followed by chalazion, skin tag, epidermal cyst, nevus, seborrheic keratosis, xanthelasma, and molluscum contagiosum respectively. Histopathological studies confirmed the clinical diagnosis in 95.9% (213/222) of specimens and was different from the clinical diagnosis in 4.1% (9/222) of the lesions which included seborrheic keratosis (n = 3), pilomatrixoma, steatocystoma, hemangioendothelioma, juvenile xanthogranuloma, calcinosis cutis, and syringocystadenoma papilliferum. No malignant lesion was labeled as benign. Epidemiology of benign eyelid lesions in Saudi population is different from Far East or Western populations. Sweat gland hidrocystoma with classical clinical features and straightforward diagnosis is the most frequent lesion in our series which could be due to characteristic dry climate.


The F-box protein EST1 modulates salt tolerance in Arabidopsis by regulating plasma membrane Na+/H+ antiport activity.
F-box protein, one of the building blocks of the SCF complex, functions in substrate recognition of the SCF subtype of E3 ubiquitin ligase. However, the role of F-box protein in salt stress is largely elusive in plants. Here, we report the characterization of an Arabidopsis salt-tolerant mutant est1 with significantly reduced sodium content and higher Na+/H+ antiporter activity after NaCl treatment compared to the wild-type. Over-expression of EST1 resulted in increased sensitivity to salt stress, suggesting that EST1 may act as a negative regulator for salt tolerance in Arabidopsis. EST1 encodes an F-box protein, which interacts with ASK4, ASK14, and ASK18, and is likely targeted to the endoplasmic reticulum. In addition, EST1 interacts with MKK4 and negatively regulates MKK4 protein levels and the activity of the plasma membrane Na+/H+ antiporter. Our findings demonstrate the existence of an EST1-MKK4 module that mediates salt sensitivity by regulating the activity of the plasma membrane Na+/H+ antiporter. These results provide important information for engineering salt-tolerant crops.


Water content determination of superdisintegrants by means of ATR-FTIR spectroscopy.
Water contents of superdisintegrant pharmaceutical excipients were determined by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy using simple linear regression. Water contents of the investigated three common superdisintegrants (crospovidone, croscarmellose sodium, sodium starch glycolate) varied over a wide range (0-24%, w/w). In the case of crospovidone three different samples from two manufacturers were examined in order to study the effects of different grades on the calibration curves. Water content determinations were based on strong absorption of water between 3700 and 2800 cm⁻¹, other spectral changes associated with the different compaction of samples on the ATR crystal using the same pressure were followed by the infrared region between 1510 and 1050 cm⁻¹. The calibration curves were constructed using the ratio of absorbance intensities in the two investigated regions. Using appropriate baseline correction the linearity of the calibration curves was maintained over the entire investigated water content regions and the effect of particle size on the calibration was not significant in the case of crospovidones from the same manufacturer. The described method enables the water content determination of powdered hygroscopic materials containing homogeneously distributed water.


STRUCTURAL INEQUALITY AND SOCIAL SUPPORT FOR WOMEN PRISONERS RELEASED TO RURAL COMMUNITIES.
Incarceration and community reentry for rural women reflect gendered processes. We draw upon in-depth semi-structured interviews and focus groups to examine the return of women prisoners to underserved rural communities, while attending to the perspectives of their closest social supporters. Our findings underscore the complexity of the reentry process for rural women and its particular impact on their families. We challenge dominant discourses of personal responsibility that detract from the structura violence and injustice shaping reentry experiences for women and their social supporters. We also consider the policy implications of discharge and reentry planning for rural women and their families, as well as strategies to reduce recidivism.


NO-inducible nitrosothionein mediates NO removal in tandem with thioredoxin.
Nitric oxide (NO) is a toxic reactive nitrogen species that induces microbial adaption mechanisms. Screening a genomic DNA library identified a new gene, ntpA, that conferred growth tolerance upon Aspergillus nidulans against exogenous NO. The gene encoded a cysteine-rich 23-amino-acid peptide that reacted with NO and S-nitrosoglutathione to generate an S-nitrosated peptide. Disrupting ntpA increased amounts of cellular S-nitrosothiol and NO susceptibility. Thioredoxin and its reductase denitrosated the S-nitrosated peptide, decreased cellular S-nitrosothiol and conferred tolerance against NO, indicating peptide-mediated catalytic NO removal. The peptide binds copper(I) in vitro but is dispensable for metal tolerance in vivo. NO but not metal ions induced production of the peptide and ntpA transcripts. We discovered that the thionein family of peptides has NO-related functions and propose that the new peptide be named NO-inducible nitrosothionein (iNT). The ubiquitous distribution of iNT-like polypeptides constitutes a potent NO-detoxifying mechanism that is conserved among various organisms.


SSGF-I, a potent growth-promoting substance for mammalian cells from swine serum.
A small amount of swine serum markedly stimulated cell growth for high productivity subclones derived from a mouse human-human heterohybridoma, N12-16.63, secreting an anti-tetanus toxoid human monoclonal antibody in a polyethylene glycol (PEG)-containing serum-free medium, PEG-86-1. A growth promoting substance, SSGF-I, was isolated from the serum by ammonium sulfate fractionation, Cibacron blue F3A-G affinity chromatography, DEAE-agarose ion exchange chromatography, and gel filtrations on Trisacryl GF 2000 and Sephacryl S-300. SSGF-I was characterized as a low density lipoprotein (LDL) of swine serum by its physico-chemical properties. It promoted cell growth synergistically with PEG and its optimum concentration was 1 to 100μg/ml. Human LDL was less active, and human or swine high density lipoprotein (HDL) and very low density lipoprotein (VLDL) were inactive. Based on these results, we propose an improved serum-free medium, PEG-86-3, which contains all the ingredients of PEG-86-1 and 10μg/ml SSGF-I. This medium is useful for not only high productivity heterohybridomas but also for a variety of lymphoid cell lines.


Optimal approach to circumferential decompression and reconstruction for thoracic spine metastatic disease.
Circumferential decompression has been demonstrated to be the first-line therapy for patients with metastatic tumors in the thoracic spine requiring surgical intervention. However, there is significant debate regarding whether these tumors are best accessed anteriorly utilizing a thoracotomy or posteriorly. We used decision analysis to determine which approach yields greater health-related quality of life (QOL). We searched Medline, Embase, and the Cochrane Library for relevant articles published between 1990 and 2011 on anterior and posterior approaches to metastatic disease in the thoracic spine. QOL values for major treatment outcomes were determined using the existing literature. Separate models were created for ambulatory and nonambulatory patients. A Monte Carlo simulation and sensitivity analyses were used to determine which treatment strategy resulted in the highest QOL. For ambulatory patients, an anterior approach resulted in a slightly higher QOL, and for nonambulatory patients, a posterior approach was favored, but these differences were not statistically significant. Using a decision-analytic model, we found no significant difference in QOL resulting from anterior versus posterior approaches to metastatic lesions in the thoracic spine. Decisions should instead be based on surgeon comfort, tumor characteristics, anatomy of the lesion, patient-related factors, and goals of the operation.


Ultrasonication-induced amyloid fibril formation of beta2-microglobulin.
To obtain insight into the mechanism of fibril formation, we examined the effects of ultrasonication, a strong agitator, on beta2-microglobulin (beta2-m), a protein responsible for dialysis-related amyloidosis. Upon sonication of an acid-unfolded beta2-m solution at pH 2.5, thioflavin T fluorescence increased markedly after a lag time of 1-2 h with a simultaneous increase of light scattering. Atomic force microscopy images showed the formation of a large number of short fibrils 3 nm in diameter. When the sonication-induced fibrils were used as seeds in the next seeding experiment at pH 2.5, a rapid and intense formation of long fibrils 3 nm in diameter was observed demonstrating seed-dependent fibril growth. We then examined the effects of sonication on the native beta2-m at neutral pH, conditions under which amyloid deposits occur in patients. In the presence of 0.5 mm sodium dodecyl sulfate, a model compound of potential trigger and stabilizer of amyloid fibrils in patients, a marked increase of thioflavin T fluorescence was observed after 1 day of sonication at pH 7.0. The products of sonication caused the accelerated fibril formation at pH 7.0. Atomic force microscopy images showed that the fibrils formed at pH 7.0 have a diameter of more than 7 nm, thicker than those prepared at pH 2.5. These results indicate that ultrasonication is one form of agitation triggering the formation of amyloid fibrils of beta2-m, producing fibrils adapted to the respective pH.


Use of affinity capillary electrophoresis for characterizing pharmaceutical colloidal vehicle systems thermodynamically.
This review offers a detailed discussion of the interaction between pharmaceutical compounds and vehicles using the affinity capillary electrophoresis and the microemulsion electrokinetic chromatography. Partition coefficients of drugs were calculated between a micelle and an aqueous phases from the measurement of the migration time, provided the critical micelle concentration and the phase ratio are known. Thermodynamic quantities such as enthalpy and entropy changes of micellar solubilization were calculated from the temperature dependence of the partition coefficients. Partial specific volumes were measured using dynamic light scattering. The logarithm of the partition coefficients and the capacity factor in the micellar system were correlated with the logarithm of the n-octanol/water partition coefficients.


The activation by Ca2+ of platelet phospholipase A2. Effects of dibutyryl cyclic adenosine monophosphate and 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate.
Thrombin-induced release of arachidonic acid from human platelet phosphatidylcholine is found to be more than 90% impaired by incubation of platelets with 1 mM dibutyryl cyclic adenosine monophosphate (Bt2 cyclic AMP) or with 0.6 mM 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8), an intracellular calcium antagonist. Incorporation of arachidonic acid into platelet phospholipids is not enhanced by Bt2 cyclic AMP. The addition of external Ca2+ to thrombin-treated platelets incubated with Bt2 cyclic AMP or TMB-8 does not counteract the observed inhibition. However, when divalent cation ionophore A23187 is employed as an activating agent, much less inhibition is produced by Bt2 cyclic AMP or TMB-8. The inhibition which does result can be overcome by added Ca2+. Inhibition of arachidonic acid liberation by Bt2 cyclic AMP, but not by TMB-8, can be overcome by high concentrations of A23187. When Mg2+ is substituted for Ca2+, ionophore-induced release of arachidonic acid from phosphatidylcholine of inhibitor-free controls is depressed and inhibition by Bt2 cyclic AMP is slightly enhanced. The phospholipase A2 activity of platelet lysates is increased by the presence of added Ca2+, however, the addition of either A23187 or Bt2 cyclic AMP is without effect on this activity. We suggest that Bt2 cyclic AMP may promote a compartmentalization of Ca2+, thereby inhibiting phospholipase A activity. The compartmentalization may be overcome by ionophore. By contrast, TMB-8 may immobilize platelet Ca2+ stores in situ or restrict access of Ca2+ to phospholipase A in a manner not susceptible to reversal by high concentrations of ionophore.


Macrophage-derived IGF-1 protects the neonatal intestine against necrotizing enterocolitis by promoting microvascular development.
Necrotizing enterocolitis (NEC) is a deadly bowel necrotic disease of premature infants. Low levels of plasma IGF-1 predispose premature infants to NEC. While increasing evidence suggests that defective perinatal intestinal microvascular development plays a role in NEC, the involved mechanism remains incompletely understood. We report here that serum and intestinal IGF-1 are developmentally regulated during the perinatal period in mice and decrease during experimental NEC. Neonatal intestinal macrophages produce IGF-1 and promote endothelial cell sprouting in vitro via IGF-1 signaling. In vivo, in the neonatal intestine, macrophage-derived IGF-1 promotes VEGF expression and endothelial cell proliferation and protects against experimental NEC. Exogenous IGF-1 preserves intestinal microvascular density and protects against experimental NEC. In human NEC tissues, villous endothelial cell proliferation and IGF-1- producing macrophages are decreased compared to controls. Together, our results suggest that defective IGF-1-production by neonatal macrophages impairs neonatal intestinal microvascular development and predisposes the intestine to necrotizing enterocolitis.


Regulatory factors of medical care expenditures for older people in Japan--analysis based on secondary medical care areas in Hokkaido.
For the purpose of clarifying determinants of medical care expenditure for older people in Japan, we analyzed the data on medical care expenditure for older people in 21 secondary medical care areas in Hokkaido, the second largest island of Japan. The annual amount of medical expenditure per insured older person can be reduced into three components: annual number of medical care bills per insured older person days of hospitalization or visits per medical care bill and amount of medical expenditure per day and per insured older person. The 21 secondary medical care areas in Hokkaido showed large differences in per capita amount of both inpatient and outpatient medical expenditures for older people. Per capita inpatient medical expenditure for men and women correlated positively with the days of hospitalization per bill and the per capita number of inpatient medical care bills per year, but inversely with the per capita amount of expenditure per day of hospitalization. The same held true for outpatient medical expenditure for men, but for women outpatient medical expenditure correlated positively with all three components. Multiple regression analysis indicated the more powerful effects of medical care demand or supply on inpatient medical expenditure, on the other hand, not much powerful effects of every index were indicated on outpatient medical expenditure.


Predation influences the structure of biofilm developed on ultrafiltration membranes.
This study investigates the impact of predation by eukaryotes on the development of specific biofilm structures in gravity-driven dead-end ultrafiltration systems. Filtration systems were operated under ultra-low pressure conditions (65 mbar) without the control of biofilm formation. Three different levels of predation were evaluated: (1) inhibition of eukaryotic organisms, (2) addition of cultured protozoa (Tetrahymena pyriformis), and (3) no modification of microbial community as a control. The system performance was evaluated based on permeate flux and structures of the biofilm. It was found that predation had a significant influence on both the total amount and also the structure of the biofilm. An open and heterogeneous structure developed in systems with predation whereas a flat, compact, and thick structure that homogeneously covered the membrane surface developed in absence of predation. Permeate flux was correlated with the structure of the biofilm with increased fluxes for smaller membrane coverage. Permeate fluxes in the presence or absence of the predators was 10 and 5 L m(-2) h(-1), respectively. It was concluded that eukaryotic predation is a key factor influencing the performance of gravity-driven ultrafiltration systems.


Comparing the use of the Taiwanese Depression Questionnaire and Beck Depression Inventory for screening depression in patients with chronic pain.
Studies have shown that the validity of self-reported depression questionnaires may be influenced by somatic symptoms such as chronic pain. The purpose of this study was to compare the validity of two self-reported questionnaires, the Taiwanese Depression Questionnaire (TDQ) and the Beck Depression Inventory (BDI), for screening depression in patients with chronic pain. One hundred patients with chronic pain were enrolled and assessed using the TDQ, BDI, McGill Pain Questionnaire, and Structured Clinical Interview for DSM-III-R. Seventy-three of them were diagnosed with depressive disorders. Conventional validity indices of the TDQ and BDI were examined and compared. Both the TDQ and BDI had satisfactory sensitivity, specificity, positive predictive value, and negative predictive value. Our results showed a trend that the validity of the TDQ was better than that of the BDI, and the validity of the cognitive/affective components of the TDQ was significantly better than that of the BDI. Our results suggest that the TDQ is superior to the BDI in detecting depression in patients with chronic pain in Taiwan.


A gas chromatography full scan high resolution Orbitrap mass spectrometry method for separation and characterization of 3-hydroxymethyl pyridine ester of fatty acids at low levels.
Fatty acid methyl esters (FAMEs), which are commonly used to characterize lipids, have several limitations to conclude on many structures. 3-Pyridylcarbinol esters (3-PCE) are used to characterize fatty acid structures [1], in particular, to identify ring and double bond positions on the carbon chain. Chromatographic separation of these esters is complex due to their polarity and high boiling points. In this study, we used a column with high resolutive power based on ionic liquids to increase the separation quality in gas chromatography (GC). In addition, we used a high-resolution detector (Orbitrap) to limit non-specific signals and improve the detection limits. This detector could be used with a mass filter at 5 ppm for the rapid determination of 3-PCE from its characteristic ions (m/z = 108.0441 and 92.0495). This filter allowed the identification of derivative fatty acids with good sensibility. Thus, it was possible to characterize 3-PCE by measuring the exact fragment masses to confirm structures such as C19:2n12cycloΔ9.


Cervical cancer control in developing countries: memorandum from a WHO meeting.
This memorandum summarizes the report of a WHO Consultation on the Control of Cervical Cancer in Developing Countries, held on 6-7 November 1994, in New Delhi, India. Evaluated was the current situation with regard to cervical cancer and the relevance of current practices in screening. New pragmatic approaches to cervical cancer were proposed that are relevant for developing countries; this includes empowerment of women to come forward, and visual inspection-"downstaging".


Subfornical organ neurons act to enhance the activity of paraventricular vasopressin neurons in response to intravenous angiotensin II.
The effects of pretreatment of the angiotensin II (ANGII) antagonist, saralasin (Sar), in the subfornical organ (SFO) on intravenous ANGII-induced responses of the activity of phasically firing paraventricular nucleus (PVN) neurons (n = 23) antidromically identified as projecting to the posterior pituitary were examined in urethane-anesthetized rats. The activity of the majority (n = 18) of identified PVN neurons was excited by intravenously administered ANGII, whereas the remaining neurons (n = 5) were not affected. The excitatory responses (n = 13) to ANGII were prevented by pretreatment with Sar, but not by isotonic saline (n = 3), in the SFO. These results suggest that ANGII-sensitive SFO neurons may act to enhance the excitability of putative vasopressin (VP)-secreting neurons in the PVN in response to circulating ANGII.


Does social distinction contribute to socioeconomic inequalities in diet: the case of 'superfoods' consumption.
The key mechanisms underlying socioeconomic inequalities in dietary intake are still poorly understood, hampering the development of interventions. An important, but sparsely mentioned mechanism is that of 'social distinction', whereby those in a higher socioeconomic position adopt dietary patterns by which they can distinguish themselves from lower socioeconomic groups. We investigated the importance of distinction as a mechanism, by testing the socioeconomic gradient in the consumption of so-called 'superfoods' and the contribution of a well-established indicator of distinction, cultural participation. Data from participants (25-75 years) of the 2014 survey of the Dutch population-based GLOBE study were used (N = 2812). Multivariable regression models were used to analyse the association between education, income and cultural participation (e.g. visits to museums, opera, theatre, concerts) and the consumption of superfoods (spelt, quinoa and goji berries, chia seeds or wheatgrass). The consumption of superfoods is far more prevalent among higher socioeconomic groups. Adjusting for cultural participation strongly attenuated the educational and income gradient in superfoods consumption, whereas cultural participation remained strongly associated with superfoods consumption. Those in the highest quintile of cultural participation reported the highest consumption of spelt products (OR = 2.97, 95% CI = 2.10;4.18), quinoa (OR = 3.50, 95% CI = 2.12;5.79) and goji berries, chia seeds or wheatgrass (OR = 2.69, 95% CI = 1.73;4.17). The associations between socioeconomic position and the consumption of 'superfoods' seem to be partially driven by a process of social distinction. These findings suggest that distinction may be an important, but currently neglected mechanism in generating socioeconomic inequalities in dietary intake. It deserves a more prominent role in interventions to reduce these inequalities.


Determination and validation of a simple high-performance liquid chromatographic method for simultaneous assay of iprodione and vinclozolin in human urine.
A method based on solid-phase extraction (SPE) and high-performance liquid chromatography (HPLC) was developed for the simultaneous determination of 3-(3,5-diclorophenyl)-5-ethenyl-5-methyl-2,4-oxazolidinedione (vinclozolin) and 3-(3,5-diclorophenyl)-N-(1-methylethyl)-2,4-dioxo-1-imidazolidinecarboxamide (iprodione) in human urine. Urine samples containing vinclozolin and iprodione were collected by solid phase extraction using C(18) cartridges. The chromatographic separation was achieved on a Spherisorb ODS2 (250 mm x 4.6 mm, 5 microm) column with an isocratic mobile phase of acetonitrile-water (60:40, v/v). Detection was UV absorbance at 220 nm. The calibration graphs were linear from 30 to 1000 ng/mL for the two fungicides. Intra- and inter-day R.S.D. did not exceed 2.9%. The quantitation limit was 50 ng/mL for vinclozolin and 30 ng/mL for iprodione, respectively.