Radioisotope binding capacity of serum in folic acid, vitamin B12 and ferritin in haematologic and rheumatologic patients.
In addition to the usual parameters for haematologic an rheumatologic diseases folic acid, vitamin B12, and ferritin were investigated by radioisotope studies. In some groups folic acid was lower compared to controls, and it is possible that the disease causes the deficiency of folic acid absorption and distribution. Vitamin B12 was only slightly decreased, thus, the values may be assumed to be close to normals. Transferrin ankylosing spondylitis is similar to that of controls, however, transferrin increases in rheumatoid arthritis and in mixed groups containing patients various diseases. Finally, the deficiency of folic acid absorption can be assumed to be caused by the symptoms of the disease, whereas in the case of inflammatory diseases and in mixed group transferrin increased.


An unusual transverse sacral fracture treated with early decompression. Case report.
The authors describe the case of a patient who sustained a transverse sacral fracture (TSF) associated with a depressed laminar fracture in a personal watercraft accident. The patient underwent early surgery, which allowed a quick recovery. To the best of the authors' knowledge, the mechanism of injury and type of fracture have not been previously described or classified in cases of TSF.


Enantioselective, Palladium-Catalyzed Conjugate Additions of Arylboronic Acids to Form Bis-benzylic Quaternary Stereocenters.
We report enantioselective, palladium-catalyzed conjugate additions of arylboronic acids to β-aryl, β,β-disubstituted enones to generate ketones containing bis-benzylic quaternary stereocenters. A catalyst generated from palladium trifluoroacetate and (S)-4-tert-butyl-2-(2-pyridyl)oxazoline ligand ((S)-t-BuPyOx) promotes conjugate additions of a wide range of arylboronic acids to a variety of β-aryl, β,β-disubstituted enones. Iterative addition of the arylboronic acid to minimize undesired protodeboronation pathways leads to efficient formation of the corresponding ketones containing bis-benzylic quaternary stereocenters in up to 92% yield and up to 93% enantioselectivity.


Impaired postoperative hyperglycemic stress response associated with increased mortality in patients in the cardiothoracic surgery intensive care unit.
To describe the association of tight glycemic control with intensive insulin therapy and clinical outcome among patients in the cardiothoracic surgery intensive care unit. All patients who underwent cardiothoracic surgery and were admitted to the cardiothoracic surgery intensive care unit between September 13, 2007, and November 1, 2007, were enrolled. Clinical and metabolic data were prospectively collected. All patients received intensive insulin therapy using a nurse-driven dynamic protocol targeting blood glucose values of 80 to 110 mg/dL. Four stages of critical illness were defined as follows: acute critical illness (intensive care unit days 0-2), prolonged acute critical illness (intensive care unit 3 or more days), chronic critical illness (tracheotomy performed), and recovery (liberated from ventilator). One hundred fourteen patients were enrolled. Seventy-three (64%) recovered during acute critical illness, 26 (23%) recovered during prolonged acute critical illness, and 15 (13%) progressed to chronic critical illness. All 6 deaths were among patients in chronic critical illness. Admission blood glucose and average blood glucose values for the first 12 hours were lower in patients who developed chronic critical illness and died and were higher in patients who developed chronic critical illness and survived (P = .007 and P = .007, respectively). Severe hypoglycemia (blood glucose <40 mg/dL) occurred once (0.03% of all measurements). Lower initial blood glucose values, which reflect an impaired stress response immediately after surgery, were associated with increased mortality, and a significant delay in achieving tight glycemic control with intensive insulin therapy was associated with prolonged intensive care unit course, but no increase in mortality. The study findings suggest that acute postoperative hyperglycemia and its prompt correction with intensive insulin therapy are associated with favorable outcomes in patients in the cardiothoracic surgery intensive care unit.


Purification from guinea pig erythrocyte stroma of a decay-accelerating factor for the classical c3 convertase, C4b,2a.
A protein with decay-accelerating activity for the classical C3 convertase, C4b2a, has been isolated on the basis of this function from guinea pig erythrocyte stroma. The isolation procedure for decay-accelerating factor of stroma (DAF-S) utilizes butanol extraction and chromatography on DEAE-Sephacel, hydroxylapatite, and phenyl Sepharose. Purified DAF-S has a m.w. of 60,000 and 65,000 on reduced and unreduced SDS gels, respectively, and exhibits m.w. of 30,000 and 175,000 on alkaline gradient gels, suggesting multiples of a 60,000-65,000 subunit. Purified DAF-S elicited a monospecific antiserum whose IgG fraction neutralized the decay-accelerating activity for C4b,2a affixed to 10(7) sheep erythrocytes (EAC1,4,2) in a dose-response fashion. The monospecific antiserum diluted up to 1:5120 agglutinated 1 x 10(6) guinea pig erythrocytes, but not sheep or human erythrocytes, suggesting that DAF-S, an integral membrane protein, has species-specific antigens that are expressed on the surface of the guinea pig erythrocyte.


A population-based survey of the social and personal impact of headache.
To explore the social and personal impact of headache, we contributed questions on serious headache to a population-based telephone survey on health in Kentucky. A total of 647 persons aged 20 and older was assessed for serious headache. Migraine without aura was distinguished from non-migraine headache using a modification of the 1988 IHS criteria. The 12-month period prevalence for all serious headaches was 13.4%; for migraine, it was 8.5%. Demographically, there was a higher proportion of headache sufferers in the low income bracket (< $10,000/year) and a higher proportion of women reporting migraines. Of those with serious headaches, 73.6% stated that headaches adversely affected their lifestyle in at least one way. Migraineurs reported significantly more interference in family relations, work attendance, and work efficiency than non-migraineurs. Women said their family relationships and work productivity were impacted significantly more often than men. Of those reporting disability, 46.8% said they take only non-prescription medications. We conclude there is a significant number of serious headache sufferers in Kentucky who experience social as well as vocational impairment as a result of their illness. Further research is recommended to evaluate the extent of interpersonal and personal disability and to identify barriers to adequate health care for headache sufferers.


Thermoelectric Properties of Cu2SnSe3-SnS Composite.
Heavily doped degenerate semiconductors such as Cu2SnSe3 (CTSe) attracted attention in thermoelectric (TE) and optoelectronic fields, due to their high electrical conductivity and small band gap. The small Seebeck coefficient of undoped CTSe, however, is the major issue in achieving high TE performance (figure of merit, ZT). Here, we report that the Seebeck coefficient of CTSe can be controlled by adding SnS within a CTSe matrix. CTSe-SnS composite has not only high Seebeck coefficient in the range of 300-500 µVolt/K but thermal conductivity which is lower than that of pristine CTSe due to the scattering at the interface between the matrix and the SnS particles. A reasonable ZT of 0.18 is achieved at 570 K by adding a small amount (3 wt.%) of SnS to the CTSe matrix.


Haptoglobin types and unipolar depression.
Haptoglobin (Hp) has been used in association studies with unipolar depression and has led to investigations on the possible association of Hp genotypes with disease. Because of the reported association between the Hp-2 allele and depression we phenotyped 65 elderly patients with unipolar depression and 40 elderly individuals without mental disorders. We failed to find an association between either of the Hp alleles and unipolar depression. The Hp2 gene frequencies for the depressed patients and the comparison group were 0.585 and 0.550, respectively, and these values were not significantly different. Both values were within the gene frequency range reported for Caucasian populations.


Oral and parenteral nutrition with L-Valine: mode of action.
The intravenous application of the branched chain amino acid L-valine to patients with hepatic coma resulted in a specific drop of tryptophan, serotonin and 5-hydroxyindole acetic acid. Clinical improvement of hepatic encephalopathy and of the underlying neurotransmitter (serotonin) and ammonia derangements by administration of L-valine suggest a possible role of this competitive amino acid on intermediary metabolism and ammonia detoxification.


AraC interacts with p75NTR transmembrane domain to induce cell death of mature neurons.
Cytosine arabinoside (AraC) is one of the main therapeutic treatments for several types of cancer, including acute myeloid leukaemia. However, after a high-dose AraC chemotherapy regime, patients develop severe neurotoxicity and cell death in the central nervous system leading to cerebellar ataxia, dysarthria, nystagmus, somnolence and drowsiness. AraC induces apoptosis in dividing cells. However, the mechanism by which it leads to neurite degeneration and cell death in mature neurons remains unclear. We hypothesise that the upregulation of the death receptor p75NTR is responsible for AraC-mediated neurodegeneration and cell death in leukaemia patients undergoing AraC treatment. To determine the role of AraC-p75NTR signalling in the cell death of mature neurons, we used mature cerebellar granule neurons' primary cultures from p75NTR knockout and p75NTRCys259 mice. Evaluation of neurite degeneration, cell death and p75NTR signalling was done by immunohistochemistry and immunoblotting. To assess the interaction between AraC and p75NTR, we performed cellular thermal shift and AraTM assays as well as Homo-FRET anisotropy imaging. We show that AraC induces neurite degeneration and programmed cell death of mature cerebellar granule neurons in a p75NTR-dependent manner. Mechanistically, Proline 252 and Cysteine 256 residues facilitate AraC interaction with the transmembrane domain of p75NTR resulting in uncoupling of p75NTR from the NFκB survival pathway. This, in turn, exacerbates the activation of the cell death/JNK pathway by recruitment of TRAF6 to p75NTR. Our findings identify p75NTR as a novel molecular target to develop treatments for counteract AraC-mediated cell death of mature neurons.


Ischemic Hepatitis as the Presenting Manifestation of Cardiac Amyloidosis.
An abrupt elevation in aminotransferases without clear etiology may be attributed to hypoxic hepatitis. Underlying cardiac dysfunction, an important clinical clue, is often overlooked as a cause of hypoxic hepatitis, and understanding the interdependence of the heart and liver is crucial in making this diagnosis. Causes of cardiac dysfunction may include any of many different diagnoses; infiltrative heart disease is a rare cause of cardiac dysfunction, with amyloidosis being the most common among this category of pathologies. More advanced imaging techniques have improved the ability to diagnose infiltrative heart disease, thus allowing quicker diagnosis of conditions such as amyloidosis.


Important role of endogenous hydrogen peroxide in pacing-induced metabolic coronary vasodilation in dogs in vivo.
We examined whether endogenous hydrogen peroxide (H2O2) is involved in pacing-induced metabolic vasodilation in vivo. We have previously demonstrated that endothelium-derived H2O2 is an endothelium-derived hyperpolarizing factor in canine coronary microcirculation in vivo. However, the role of endogenous H2O2 in metabolic coronary vasodilation in vivo remains to be examined. Canine subepicardial small coronary arteries (> or =100 microm) and arterioles (<100 microm) were continuously observed by a microscope under cyclooxygenase blockade (ibuprofen, 12.5 mg/kg intravenous [IV]) (n = 60). Experiments were performed during paired right ventricular pacing under the following 7 conditions: control, nitric oxide (NO) synthase inhibitor (N(G)-monomethyl-L-arginine [L-NMMA], 2 micromol/min for 20 min intracoronary [IC]), catalase (a decomposer of H2O2, 40,000 U/kg IV and 240,000 U/kg/min for 10 min IC), 8-sulfophenyltheophylline (SPT) (an adenosine receptor blocker, 25 mug/kg/min for 5 min IC), L-NMMA+catalase, L-NMMA+tetraethylammonium (TEA) (K(Ca)-channel blocker, 10 microg/kg/min for 10 min IC), and L-NMMA+catalase+8-SPT. Cardiac tachypacing (60 to 120 beats/min) caused coronary vasodilation in both-sized arteries under control conditions in response to the increase in myocardial oxygen consumption. The metabolic coronary vasodilation was decreased after L-NMMA in subepicardial small arteries with an increased fluorescent H2O2 production compared with catalase group, whereas catalase decreased the vasodilation of arterioles with an increased fluorescent NO production compared with the L-NMMA group, and 8-SPT also decreased the vasodilation of arterioles. Furthermore, the metabolic coronary vasodilation was markedly attenuated after L-NMMA+catalase, L-NMMA+TEA, and L-NMMA+catalase+8-SPT in both-sized arteries. These results indicate that endogenous H2O2 plays an important role in pacing-induced metabolic coronary vasodilation in vivo.


Urinary Diversion With vs Without Bowel Anastomosis in Patients With an Existing Colostomy: A Multi-institutional Study.
To describe the short-term outcomes with the bowel anastomosis (BA) approach vs the no-bowel anastomosis (NBA) approach in adult patients undergoing urinary diversion. A chart review was performed of adults undergoing urinary diversion from 2006 to 2015. Patients with a pre-existing colostomy were divided into NBA and BA groups. Postoperative complications were recorded per the Clavien-Dindo system. Variables were compared using the BA group as a control. A 2-tailed t test was used to compare means. A total of 43 patients were included: 33 in the BA group and 10 in the NBA. No significant differences were found between the 2 groups for the comorbidity index (P = .16), the body mass index (P = .54), or radiation history (P = .90). In the NBA and BA groups, the median blood loss was 250 and 300 mL (P = .11); the operative time was 550 and 480 minutes (P = .15); and the length of stay was 10 and 25 days (P = .38), respectively. The BA group had a higher rate of intraoperative (P = .04) and early (P = .02) overall complications. No significant difference was found in early bowel (P = .15) or ureteral obstruction (P = .08), in the overall stomal complications (P = .11), or in the rate of <90-day reoperation (P = .32). A lower rate of intraoperative and postoperative complications occurred in patients undergoing conversion of colostomy to a urinary diversion compared with patients with de novo urinary conduit creation. When possible, a BA should be avoided.


Base-resolution analysis of 5-hydroxymethylcytidine by selective oxidation and reverse transcription arrest.
While 5-hydroxymethylcytidine in RNA (hm5C) is associated with cellular development and differentiation, its distribution and biological function remain largely unexplored because suitable detection methods are lacking. Here, we report a base-resolution sequencing method for hm5C in RNA by applying peroxotungstate-mediated chemical conversion of hm5C to trihydroxylated thymine (thT). Reverse transcription by SuperScript III terminated at the thT site, probably because of its unnatural nucleobase structure producing truncated cDNA. Consequently, base-resolution analysis of the hm5C sites in RNA was achieved with both Sanger sequencing and Illumina sequencing analysis by comparing sequencing data before and after peroxotungstate treatment.


Recent developments in antimicrobial therapy with beta-lactam antibiotics.
There are three new penicillin and three new cephalosporin compounds available in the United States. All have been developed via biochemical manipulation of the beta-lactam ring and its adjacent chemical groups. The antibacterial spectrum of activity has been greatly expanded. Each of the six new agents has a unique antimicrobial profile which mandates independent evaluation. Therapeutic use of these drugs, particularly in treatment of gram-negative meningitis, has yielded success rates not previously witnessed. Application of these antibiotics as prophylactic agents for surgical procedures remains controversial. Guidelines are offered to distinguish one agent from another based on antimicrobial, pharmacokinetic and toxicologic properties.


The World Bank, the Monetary Fund, and poverty.
The debt crisis into which heavy borrowing, steeply rising interest rates, and a worldwide recession had plunged a number of developing countries in the late 1970s and 1980s was alleviated largely by policies and conditionalities imposed by the International Monetary Fund and the World Bank. These policies and conditions were meant to strengthen the export and financial markets of those countries, stabilize their currencies, and reduce the reach of their governments in their economies. However, they contributed to deepening poverty and structural crises, as the reports and data published by the international financial institutions themselves attest.


Panning using a phage-displayed random peptide library to identify peptides that antagonize the Helicobacter pylori ArsS acid-sensing domain.
Helicobacter pylori is an important etiological factor involved in chronic gastritis, peptic ulcer, and gastric cancer. There are currently no optimal preventive or therapeutic interventions for H. pylori infection. H. pylori survives in the stomach by sensing and adapting to the highly acidic environment by using the two-component signal transduction system that contains the most widely known gastric acid receptor, ArsRS (which is composed of ArsS and ArsR). This study aimed to identify peptides that antagonize the acid-sensing domain of H. pylori ArsS. These peptides could be used to block the acid-sensing signal and thereby hinder H. pylori adaption to acidic environments to prevent its survival. Using proSite, the functional domains (including the N-terminal acid-sensing domain) of H. pylori J99 ArsS were predicted. The purified recombinant ArsS N-terminal acid-sensing protein (P-ArsS-A) was used as the target in a panning protocol in which peptides from the Ph.D.-7 Phage Display Peptide Library that could bind to P-ArsS-A were identified. As a result, eight phage clones that could specifically bind to P-ArsS-A were obtained and five amino acid sequences were identified, including P03 (MMSYPKH) and P06 (LTPMPNW). An in vitro minimum inhibitory concentration (MIC) evaluation showed that P03 and P06 significantly inhibited the growth of H. pylori J99. The MIC of P03 was 8 μM, and the MIC of P06 was >16 μM, indicating that P03 is a stronger inhibitor compared to P06. This was confirmed by colony counting on blood agar plates after P03 and P06 administration. Using homology modeling and molecular docking analysis, it was shown that P03 and P06 could bind to the ArsS N-terminal domain, and there were four shared binding sites: TYR25, ASN39, ARG73, and GLU74. Additionally, one hydrogen bond was found between P03 and ArsS, which is more cohesive than other forms of bonding (van der Waals force, other non-covalent bonds).


[Feasibility of transcatheter closure of atrial septal defect under the guidance of transthoracic echocardiography].
To explore the feasibility of transcatheter closure of atrial septal defect (ASD) under transthoracic echocardiography (TTE) guidance. Retrospective analysis was performed in 65 patients with simple ASD who underwent transcatheter closure under echocardiography guidance in Fuwai hospital from February to August 2013. They were divided into TTE group (n = 30) and transesophageal echocardiography (TEE) group (n = 35). The TTE group patients who underwent localized anesthesia or basal anesthesia received transcatheter closure of ASD under the guidance of TTE. The TEE group patients who underwent tracheal intubation and general anesthesia received transcatheter closure of ASD under the guidance of TEE. The patients were followed up with TTE and electrocardiogram at one month after procedure at outpatient department. In the TTE group, 28 occluders were implanted successfully and 2 patients were subsequently switched to TEE guidance because of unclear TTE images, and the occluder implantation in these 2 patients was successful. There were no obvious differences in age, sex, body weight, ASD size, and time of hospital stay between the two groups (all P > 0.05) . Compared with TEE group, the TTE group had a significantly shorter operation time ((52.77 ± 9.00 ) min vs. (60.11 ± 9.15) min, P < 0.05), respirator ventilation duration ((0.25 ± 0.95) h vs. (3.17 ± 0.69) h, P < 0.05), and stay time in ICU ((1.50 ± 1.96) h vs. (16.43 ± 6.99) h, P < 0.05). The dose of propofol required was significantly lower in the TTE group compared to TEE group ((2.41 ± 2.97) mg/kg vs. (9.43 ± 3.70) mg/kg, P < 0.05). The patients in both groups had no complications such as residual shunt, peripheral vascular injury or cardiac perforation at the time of hospitalization.No complications, such as occluder dislocation, residual shunt, or pericardial effusion were seen during follow-up at one month post procedure in both groups. Transcatheter closure of ASD under TTE guidance is feasible and has a broad application prospects.


Remarkably Efficient Microwave-Assisted Cross-Metathesis of Lipids under Solvent-Free Conditions.
Catalytic transformation of renewable feedstocks into fine chemicals is in high demands and olefin metathesis is a sophisticated tool for biomass conversion. Nevertheless, the large-scale viability of such processes depends on the conversion efficiency, energy efficiency, catalytic activity, selective conversion into desired products, and environmental footprint of the process. Therefore, conversions of renewables by using simple, swift, and efficient methods are desirable. A microwave-assisted ethenolysis and alkenolysis (using 1,5-hexadiene) of canola oil and methyl esters derived from canola oil (COME) and waste/recycled cooking oil (WOME) was carried out by using ruthenium-based catalytic systems. A systematic study using 1st and 2nd generation Grubbs and Hoveyda-Grubbs catalysts was carried out. Among all ruthenium catalysts, 2nd generation Hoveyda-Grubbs catalyst was found to be highly active in the range of 0.002-0.1 mol % loading. The conversions proved to be rapid providing unprecedented turnover frequencies (TOFs). High TOFs were achieved for ethenolysis of COME (21 450 min-1 ), direct ethenolysis of canola oil (19 110 min-1 ), for WOME (15 840 min-1 ) and for cross-metathesis of 1,5-hexadiene with COME (10 920 min-1 ). The ethenolysis of commercial methyl oleate was also performed with a TOF of 8000 min-1 under microwave conditions.


Regulation of low molecular weight insulin-like growth factor binding proteins in experimental diabetes mellitus.
Circulating insulin-like growth factor (IGF) bioactivity is reduced in animals and patients with diabetes mellitus. We sought to determine whether the availability and levels of specific IGF binding proteins (BPs) are altered in animals with experimental diabetes, and might contribute to changes in circulating IGF bioactivity in experimental diabetes. Female Sprague-Dawley rats were administered streptozotocin or citrate buffer iv, and then killed either 3 days later, or else after 4-day insulin treatment (7.5 U/kg human NPH twice daily), or 2 days after insulin was discontinued. Serum [125I]IGF-I binding activity was markedly increased in diabetic animals compared to controls when analyzed by Sephacryl S-200 chromatography, dot blot, and affinity labeling techniques, due to increased binding to low mol wt BPs (81 +/- 4% of ligand eluting with low mol wt BPs in diabetic serum vs. 22 +/- 3% in control, P less than 0.001). In contrast, activated charcoal removed ligand from these BPs and underestimated the availability of BPs in diabetes. Serum binding activity fell toward control levels during insulin therapy, then rose again after insulin was withdrawn, corresponding to changes in metabolic status. To distinguish changes in specific BPs, serum proteins were separated by 13% sodium dodecyl sulfate-polyacrylamide gel electrophoresis, then transferred to nitrocellulose. Ligand blotting with [125I]IGF-I demonstrated that serum levels of a 32 K mol wt IGF BP are markedly increased in diabetic rats and decline during insulin therapy. Levels of this 32 K IGF BP rose again after insulin was discontinued, demonstrating regulation in accordance with changes in insulin and metabolic status. Western analysis and affinity labeling with immunoprecipitation revealed that this 32 K protein is distinct from the 34 K fetal rat BP, and is immunologically related to the type 1 human IGF BP. We conclude that circulating [125I]IGF-I binding activity is markedly increased in animals with acute streptozotocin-induced diabetes, due to changes in low mol wt proteins, including a 32 K type 1 IGF BP that is regulated by changes in insulin and/or metabolic status. Regulation of low mol wt IGF BPs by insulin, and perhaps other factors, may play an important role in the modulation of tissue growth factor bioactivity in metabolic disease.


Effects of riluzole on respiratory rhythm generation in the brainstem-spinal cord preparation from newborn rat.
The persistent sodium channel is an important pacemaker component in rhythm generation. In the present study, we examined the effects of a persistent sodium channel blocker, riluzole on pre-inspiratory (Pre-I) and inspiratory neurons in the rostral medulla as well as on 4th cervical ventral root (C4)-inspiratory activity in brainstem-spinal cord preparations. Preparations were isolated from postnatal day 0-3 Wistar rats and were superfused with artificial cerebrospinal fluid, equilibrated with 95% O2 and 5% CO2, pH 7.4, at 25-26 °C. The C4 inspiratory burst rate decreased in a dose-dependent manner (50-200 μM) after 15 min application of riluzole. Riluzole caused a strong reduction in the drive potential of Pre-I neurons but not of inspiratory neurons. After washout, C4 inspiratory burst gradually changed into an episodic pattern, in which one burst consisted of 3-9 short separate bursts. Riluzole also depressed the induction of repetitive firing induced by depolarizing stimulation. Under voltage clamp conditions, riluzole suppressed the negative-slope component of Pre-I neurons. Riluzole also depressed the intrinsic burst generation of Pre-I neurons in low calcium and high magnesium solution. Our findings indicate that the burst generation of Pre-I neurons is more sensitive than inspiratory burst generation to riluzole and thus suggested that persistent sodium channels have an important role in the burst generation of Pre-I neurons and are involved in the primary respiratory rhythm generation.


Evaluation of potential anti-toxoplasmosis efficiency of combined traditional herbs in a mouse model.
Toxoplasma gondii is a worldwide spread protozoan and is able to infect almost all warm-blood animals. No effective drugs are available clinically on toxoplasmosis. Chinese traditional herbal medicines have provided remedies for many health problems. There exists a possibility that Chinese herbs may provide protection against T. gondii. This work aims to assess the protective efficacy of combined Chinese herbs against T. gondii. We screened five herbal medicines that have different pharmacological effects and combined them into a prescription according to the traditional Chinese medicine compatibility principle. The drug potential and protective efficacy were evaluated through a mouse model by determining the survival time, the parasite load in blood and tissues, the change of cell proportions in blood and histological detection. The results showed that the survival time of mice in the 500 mg Chinese herbs group and sulfadiazine group was significantly longer than that of the PBS control group. Also the parasite load in blood and tissues of 500 mg Chinese herbs and sulfadiazine groups was significantly lower than that of PBS group at 7 days post infection (dpi), which was in accordance with the result of histological detection. Monocyte and neutrophil of infected mice were remarkably increased while lymphocyte was dramatically decreased compared to that of blank group at 7 dpi. The results demonstrated that the 500 mg dosage of our Chinese herbs could slow down the replication of T. gondii and prolong the survival time of mice and could be considered as possible candidate drug against toxoplasmosis.


Small cell carcinoma of ovary: a rare pathology.
A 15-year-old girl presented with rapidly developing ascites and bilateral tender pelvic masses, diagnosed as small cell carcinoma of the ovary, based on histopathological and immunohistochemical features. The case is being presented because of its rare occurrence.


Protection of liver ischemia due to inflow occlusion using prior perfusion with hepatic protective solution in dogs.
Temporary occlusion of hepatic inflow is a useful maneuver to reduce hemorrhage from liver trauma and difficult hepatic resections. The liver can be protected with a hepatic protective solution before inflow occlusion, just as the stopped heart is protected by a cardioplegic solution during open heart surgery. Twenty dogs were divided into two groups. The portal inflow of group A was infused via the mesenteric venous branch with a hepatic protective solution composed of 250 mg of hydrocortisone, 15 mEq of KC1, 6 mL of 0.1 N HC1, 5 mL of 10% magnesium sulfate and 250 mg of dextrose in one liter of cold lactated Ringer's solution. Group B was infused with cold lactated Ringer's solution as a control. The hepatic artery and portal vein were isolated and then clamped for 30 minutes. The elevation of serum GOT and GPT after release of the clamps was significantly greater in group B, especially during the first 48 hours. The levels of alkaline phosphatase and total bilirubin were also higher in group B until the 7th day. The results liver biopsies 3 hours after release of the clamps revealed marked congestion and destruction of hepatocytes in group B. We conclude that liver perfusion with a hepatic protective solution before inflow occlusion results in less damage to liver tissue and less impairment of liver function. Such protection is important in liver surgery.


Targeting an acid labile aspartyl-prolyl amide bond as a viable alternative to trypsin digestion to generate a surrogate peptide for LC-MS/MS analysis.
FGF21-AdPKE is a fusion protein and functionally inactivated in vivo by cleavage around the C-terminus. It is important to quantify the intact active protein in serum. Taking advantage of a uniquely acid-labile aspartyl-prolyl amide bond, we developed an acid hydrolysis procedure based on heating FGF21-AdPKE in dilute formic acid to generate a surrogate peptide encompassing the last 17 amino acids at the C-terminus. The monkey serum samples were extracted with an immunocapture procedure with an antibody specific for AdPKE. The calibration range was 200-50000 ng/ml. The assay accuracy and precision were between 92.8-99.8% and 3.9-14.5%, respectively. The method was applied to analyze incurred serum samples from a cynomolgus monkey toxicokinetic study involving administration of FGF21-AdPKE. A method of combining immunocapture and acid hydrolysis to quantify a therapeutic protein in biological fluids was developed.


[Advances in studies on accumulation and leaching of nitrate in farming soil].
Nitrate leaching in farming soil is the main reason resulting in ground water pollution of nitrate. The main factors, which can affect nitrate accumulation and leaching greatly, include fertilization, precipitation, irrigation, soil characteristics, and cultivation system. Superfluous nitrogen in soil caused either by using chemical fertilizer and manure solely or compost will result in nitrate accumulation. Cultivation and plow systems also can affect the process of nitrate accumulating and leaching. Down flows due to irrigation or precipitation are the necessary condition and carrier for transference and leaching of accumulated nitrate in soil. Great pores are the main channels for down flows. These factors always work corporately. Mathematical model, which has been developed quickly and used widely, may be a good method to study and predict nitrate leaching in farming land.


Large-scale population carrier screening for spinal muscular atrophy in Israel--effect of ethnicity on the false-negative rate.
The carrier frequency of spinal muscular atrophy varies from 1:168 to 1:35. We analyzed the carrier rate in a large population in Israel, evaluated the false-negative rate based on the number of alleles with duplication of exon 7, and analyzed the ethnic differences in both parameters. Data were collected from two centers that conduct carrier screening using the multiplex ligation-dependent probe amplification kit. We studied the number of copies of exons 7 and 8 in our population, which we divided into six different ethnic groups. Statistical analysis was conducted using chi-square test. A total of 7308 healthy individuals were tested in an organized community health maintenance organization (HMO) program, and 1729 in a large hospital setup. The carrier rate was 1:62 and was not statistically different between the ethnic groups. Duplication was found in one in nine individuals (false-negative rate 5.5%) with a significant difference in frequency between the ethnic groups: 13.5% among Ashkenazim, 6% among North-African Jews (p < 0.001). This difference was consistent in both centers and in exon 8 as well. There is, therefore, a higher prevalence of false negative results in some ethnic groups. The discrepancy between the rates of deletions versus duplications can be explained by the genetic disadvantage of deletions.


Case report: Curing a rare, unstable hemoglobin variant Hb Bristol-Alesha using haploidentical hematopoietic stem cell transplantation.
Unstable hemoglobinopathies are a rare, heterogeneous group of diseases that disrupt the stability of hemoglobin (Hb), leading to chronic hemolysis and anemia. Patients with severe phenotypes often require regular blood transfusions and iron chelation therapy. Although rare, studies have reported that hematopoietic stem cell transplantation (HSCT) seems to be an available curative approach in transfusion-dependent patients with unstable hemoglobinopathies. Here, we describe successful haploidentical HSCT for the treatment of an unstable Hb variant, Hb Bristol-Alesha, in a 6-year-old boy with severe anemia since early childhood. Two years after transplantation, he had a nearly normal hemoglobin level without evidence of hemolysis. DNA analysis showed complete chimerism of the donor cell origin, confirming full engraftment with normal erythropoiesis.


Two calcium-binding proteins associated with specific stages of myeloid cell differentiation are expressed by subsets of macrophages in inflammatory tissues.
Using a monoclonal antibody to macrophage migration inhibition factor (MIF), two proteins were isolated from supernatants of Concanavalin A-stimulated human peripheral blood mononuclear cells which seem to have complexed to a third component carrying the MIF activity. They are therefore designated MIF-related proteins or MRP-8 and MRP-14 according to their apparent molecular weights. Partial amino acid sequences have been determined and their cDNA have been cloned and expressed in Escherichia coli. Both are calcium-binding proteins and MRP-8 seems to be largely homologous to the cystic fibrosis antigen (Dorin et al., 1987). Antisera were raised in the rabbit against the recombinant proteins and their expression in cells and tissues studied using immunohistological techniques. The proteins are only found in blood granulocytes and monocytes. In culture the number of positive monocytes sharply increased and then declined with time, suggesting that their expression is associated with early stages of monocyte/macrophage differentiation and absent from resident macrophages in all tested tissues. In acute inflammatory reactions, e.g. gingivitis, MRP-8 is never seen in the tissue, whereas MRP-14 is expressed by intravascular monocytes and perivascular macrophages. In contrast, in chronic inflammation, e.g. rheumatoid arthritis, MRP-8 is also expressed by macrophages in the tissue. From this it is concluded that MRP-8 and MRP-14 are expressed sequentially at defined stages of monocyte/macrophage differentiation and that dysregulation of this process in chronic inflammation is mirrored by the presence of MRP-8-positive macrophages in the tissue.


Initiation at the third in-frame AUG codon of open reading frame 3 of the hepatitis E virus is essential for viral infectivity in vivo.
To determine the initiation strategy of the hepatitis E virus (HEV) open reading frame 3 (ORF3), we constructed five HEV mutants with desired mutations in the ORF1 and ORF2 junction region and tested their levels of in vivo infectivity in pigs. A mutant with a C-terminally truncated ORF3 is noninfectious in pigs, indicating that an intact ORF3 is required for in vivo infectivity. Mutations with substitutions in the first in-frame AUG in the junction region or with the same T insertion at the corresponding position of HEV genotype 4 did not affect the virus infectivity or rescue, although mutations with combinations of the two affected virus recovery efficiency, and a single mutation at the third in-frame AUG completely abolished virus infectivity in vivo, indicating that the third in-frame AUG in the junction region is required for virus infection and is likely the authentic initiation site for ORF3. A conserved double stem-loop RNA structure, which may be important for HEV replication, was identified in the junction region. This represents the first report of using a unique homologous pig model system to study the molecular mechanism of HEV replication and to systematically and definitively identify the authentic ORF3 initiation site.


Use of contrast enhancement for the assessment of left ventricular function.
Endocardial visualization is essential for accurate interpretation of regional wall thickening abnormalities, which constitute the diagnostic hallmark of coronary artery disease, and for reproducible assessment of left ventricular (LV) ejection fraction. Unfortunately, in many cardiac patients, poor image quality does not allow consistent visualization, let alone automated detection, of the endocardial boundary in all segments throughout the cardiac cycle. Continuing efforts directed towards improving endocardial visualization made by both echocardiographic imaging equipment manufacturers and researchers have recently produced new objective, quantitative approaches for the assessment of global and regional LV function. Although these developments have not been integrated into routine clinical practice, they may have a positive impact on endocardial visualization and, thus, eventually improve the ability to accurately and objectively evaluate LV performance. In this review, we discuss some of the latest developments in the use of contrast for the evaluation of LV function.


Morphological and Clinical Findings of Explanted Carpentier-Edwards Perimount Pericardial Valve in the Aortic Position.
Freedom from structural valve deterioration (SVD) at 15 years with the Carpentier-Edwards (CE) Perimount pericardial valve in the aortic position was 60% in patients aged <60 years compared to 90% and 99% in patients aged 60-70 years and >70 years, respectively. The study aim was to focus on the causes of SVD requiring valve explant according to three different age groups: <60 years, 60-70 years, and >70 years. The short- and longterm clinical results of the patient cohort, followed for 25 years, are presented. A retrospective review was made of 89 patients among 2,405 who had undergone elective aortic valve replacement (AVR) with CE pericardial valves between November 1981 and March 2011, and in whom the prosthesis explant was secondary to degeneration of the valve. Patients aged >70 years experienced more late complications such as endocarditis (p = 0.02) and mortality (p = 0.02). Following surgery for prosthesis explant and replacement, 39 of the 89 patients (44%) died. The average time to postoperative mortality in that population was 2.8 ± 3.6 years. On combining all causes of SVD, earlier dysfunction was noted in patients aged >60 years, and late dysfunction in patients aged <60 years (p = 0.003). However, there was no significant difference between groups in the process of degeneration (either calcification, pannus, tear, thrombus, endocarditis) (p = NS). No predictors were found of early and late dysfunction. Patients aged >60 years in whom a CE Perimount valve was implanted in the aortic position were more prone to early degeneration of their valve and related mortality. However, no predictors were found of early degeneration of the valve in that patient population.


Protecting Quantum Dot Fluorescence from Quenching to Achieve a Reliable Automated Multiplex Fluorescence In Situ Hybridization Assay.
Quantum dots (QD) are novel inorganic fluorochromes that are ultra-bright, photo-stable, and available in multiple, highly-resolvable colors. QDs represent an ideal detection material for in situ hybridization (ISH) because they may provide unprecedented resolution and strong signal intensities that are not attainable with traditional fluorophores. Unfortunately, lack of reliability has been an impediment to widespread adoption of QD-based fluorescence in situ hybridization (QD FISH) technology. By optimizing QD-to-target accessibility, we have developed a QD FISH staining procedure that dramatically improves the reliability of an automated ERG/PTEN QD FISH assay (91% 1st pass rate). Here, we report improvements to the assay that protects QD fluorescence from quenching due to trace amounts of heavy metals and minimizes QD background signals. When using this method, highly-consistent staining was observed with the ERG/PTEN QD FISH assay in prostate tissue. Successful staining of several other clinically-relevant genetic markers was also possible. We further demonstrated improved reliability for determining HER2 gene status in breast cancer, identifying anaplastic lymphoma kinase (ALK) gene break-apart in non-small cell lung cancer, and detecting human papillomavirus 16 (HPV16) in cervical intraepithelial neoplasia. The enhanced QD FISH assay allows for examining complicated genetic aberrances without use of enzymatic amplification. Our optimized methods now demonstrate reliability sufficient for QD FISH technology to be a diagnostic tool in a clinical setting.


[Critical care of Onco-hematology patients: new therapeutic targets, new complications and new admission policies].
Overall prognosis of cancer or haematological has dramatically decreased over the last decades. Thus advances regarding cancer or haematological treatment, improved knowledge of usual complications and of their pathophysiology and changes in ICU admission policy and management are among factors which participated to the overall prognostic changes. Tyrosine-Kinase inhibitors in patients with chronic myeloid leukemia and anti-CD20 antibodies in patients with non-hodgkin's lymphoma were among the first success of targeted therapies. These success stories have been followed by others and no less than 13 targeted therapies were available for cancer patients in December 2013. Additionally, pathophysiology of complication is better understood and prognostic impact of organ failure better apprehended. Standardized diagnostic criteria of tumor lysis syndrome along with improved understanding of short-term and long term influence of acute kidney injury (AK) in this setting have led to specific management strategiesfocusing on prevention. In non-malignant haematological diseases, pathophysiological processes leading to thrombotic thrombocytopenic purpura or atypical haemolytic and uremic syndrome are now better understood leading to additional therapeutic options. Last, diversification of ICU admission policies may help in taking into account uncertainties, therapeutic advances and patients' autonomy. This review will give an overview of these recent advances.


Human mesenchymal stem cells protect human islets from pro-inflammatory cytokines.
Transplantation of human islets is an attractive alternative to daily insulin injections for patients with type 1 diabetes. However, the majority of islet recipients lose graft function within five years. Inflammation is a primary contributor to graft loss, and inhibiting pro-inflammatory cytokine activity can reverse inflammation mediated dysfunction of islet grafts. As mesenchymal stem cells (MSCs) possess numerous immunoregulatory properties, we hypothesized that MSCs could protect human islets from pro-inflammatory cytokines. Five hundred human islets were co-cultured with 0.5 or 1.0 × 10(6) human MSCs derived from bone marrow or pancreas for 24 hours followed by 48 hour exposure to interferon-γ, tumor necrosis factor-α and interleukin 1β. Controls include islets cultured alone (± cytokines) and with human dermal fibroblasts (± cytokines). For all conditions, glucose stimulated insulin secretion (GSIS), total islet cellular insulin content, islet β cell apoptosis, and potential cytoprotective factors secreted in the culture media were determined. Cytokine exposure disrupted human islet GSIS based on stimulation index and percentage insulin secretion. Conversely, culture with 1.0 × 10(6) bMSCs preserved GSIS from cytokine treated islets. Protective effects were not observed with fibroblasts, indicating that preservation of human islet GSIS after exposure to pro-inflammatory cytokines is MSC dependent. Islet β cell apoptosis was observed in the presence of cytokines; however, culture of bMSCs with islets prevented β cell apoptosis after cytokine treatment. Hepatocyte growth factor (HGF) as well as matrix metalloproteinases 2 and 9 were also identified as putative secreted cytoprotective factors; however, other secreted factors likely play a role in protection. This study, therefore, demonstrates that MSCs may be beneficial for islet engraftment by promoting cell survival and reduced inflammation.


[THE EFFECT OF METAL IONES AND SPECIFIC CHEMICAL REAGENTS ON THE ACTIVITY OF ASPERGILLUS FLAVUS VAR. ORYZAE AND BACILLUS SUBTILIS α-AMYLASES].
The effect of cations and anions on the activity of Aspergillus flavus var. oryzae and Bacillus subtilis α-amylases showed that the tested enzymes are sensitive to most of cations and resistant to anions. The most significant inhibitory effects on the activity of A. flavus var. oryzae α-amylase have been demonstrated by Al3+ and Fe3+ ions, while on the activity of B. subtilis α-amylase - Hg2+, Cu2+ and Fe3+ ions. Inactivation of A. flavus var. oryzae and B. subtilis α-amylases in the presence of EGTA is indicated on the presence within their structure of metal ions. An important role in the enzymatic catalysis of both enzymes play carboxyl groups as evidenced by their inhibition of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide methiodide. Inhibition of B. subtilis α-amylase by p-chloromercuribenzoate, N-ethylmaleimide and sodium sulfite is indicated on the probable involvement of the sulfhydryl groups in the functioning of the enzyme. Unlike most studied glycosidases the tested enzymes do not contain histidine imidazole group in the active center.


Impaired cardiac energy metabolism in embryos lacking adrenergic stimulation.
As development proceeds from the embryonic to fetal stages, cardiac energy demands increase substantially, and oxidative phosphorylation of ADP to ATP in mitochondria becomes vital. Relatively little, however, is known about the signaling mechanisms regulating the transition from anaerobic to aerobic metabolism that occurs during the embryonic period. The main objective of this study was to test the hypothesis that adrenergic hormones provide critical stimulation of energy metabolism during embryonic/fetal development. We examined ATP and ADP concentrations in mouse embryos lacking adrenergic hormones due to targeted disruption of the essential dopamine β-hydroxylase (Dbh) gene. Embryonic ATP concentrations decreased dramatically, whereas ADP concentrations rose such that the ATP/ADP ratio in the adrenergic-deficient group was nearly 50-fold less than that found in littermate controls by embryonic day 11.5. We also found that cardiac extracellular acidification and oxygen consumption rates were significantly decreased, and mitochondria were significantly larger and more branched in adrenergic-deficient hearts. Notably, however, the mitochondria were intact with well-formed cristae, and there was no significant difference observed in mitochondrial membrane potential. Maternal administration of the adrenergic receptor agonists isoproterenol or l-phenylephrine significantly ameliorated the decreases in ATP observed in Dbh-/- embryos, suggesting that α- and β-adrenergic receptors were effective modulators of ATP concentrations in mouse embryos in vivo. These data demonstrate that adrenergic hormones stimulate cardiac energy metabolism during a critical period of embryonic development.


[Sentinel lymph node biopsy in endometrial cancer - methods].
Endometrial canceris the most common gynaecological malignancy after brest cancer. The lymph node status is with great prognostic value and it is important for postoperative treatment and survival. That is why it is looking for methods giving information for the lymph node status and not increasing postoperative complications.


▼Dupilumab for atopic dermatitis.
▼Dupilumab (Dupixent - Sanofi-Aventis Groupe), a monoclonal antibody for the treatment of moderate-to-severe atopic dermatitis in adults who require systemic therapy, was licensed by the European Medicines Agency in September 2017. It is the first biological drug approved specifically for this condition. Here, we review the evidence for its efficacy and safety and consider its place in therapy.


Realizing cool and warm white-LEDs based on color controllable (Sr,Ba)2Al3O6F:Eu2+ phosphors obtained via a microwave-assisted diffusion method.
Globally, phosphor converted white-LEDs (W-LEDs) are among the most suitable sources to reduce energy consumption. Nevertheless, modernization of efficient broadband emitting phosphors is most crucial to improve the W-LED performance. Herein, we synthesized a series of novel broadband emitting Sr2-xAl3O6F:xEu2+ phosphors via a new microwave-assisted diffusion method. Rietveld refinement of the obtained X-ray diffraction results was performed to recognize the exact crystal phase and the various cationic sites. Oxygen vacancies (VO) formed under synthetic reducing conditions enabled Sr2Al3O6F to demonstrate bright self-activated bluish emission. Doping of Eu2+ ions unlocked the energy transfer process from the host to the activator ions, owing to which, the self-activated emission diminished and the Eu2+-doped sample showed amplified bluish-green emission. The gradual increase in Eu2+ concentrations regulated the controllable emissions from the bluish (0.34, 0.42) to the greenish (0.38, 0.43) zone under UV excitation. Because of the different absorption preferences of Eu2+ ions located at the different Sr2+ sites, Sr2-xAl3O6F:xEu2+ exhibited bluish-white emission under blue irradiation. A further enhancement in PL intensity had been observed by the cation substitution of Ba2+ for Sr2+ sites in the optimum Sr1.95Al3O6F:0.05Eu2+ phosphor. The as-fabricated W-LEDs utilizing the optimized Sr1.75Ba0.2Al3O6F:0.05Eu2+ phosphor exhibited a cool-white light emission along with a 372 nm NUV-LED and a 420 nm blue-LED with a moderate CRI of 70 and a CCT above 6000 K. Such cool white emission was controlled to natural white with the CCT close to 5000 K, and the CRI above 80 via utilizing a suitable red emitting phosphor. The W-LED performances of the optimized phosphor justified its applicability to produce white light for lighting applications.


Combined effect of enterocin AS-48 and high hydrostatic pressure to control food-borne pathogens inoculated in low acid fermented sausages.
The single and combined effects of enterocin AS-48 and high hydrostatic pressure (HHP) on Listeria monocytogenes, Salmonellaenterica, and Staphylococcus aureus was investigated in fuet (a low acid fermented sausage) during ripening and storage at 7 degrees C or at room temperature. AS-48 (148 AU g(-1)) caused a drastic 5.5 log cfu g(-1) decrease in L. monocytogenes (P<0.001) and a significant (P<0.01) inhibition (1.79 logs) for Salmonella at the end of ripening (10 d). After pressurization (400 MPa) and storage Listeria counts remained below 5 cfu g(-1) in all fuets containing AS-48 (pressurized or not). HHP alone had no anti-Listeria effect. HHP treatment significantly reduced Salmonella counts, with lowest levels in pressurized fuets with AS-48. S. aureus showed similar growth for all treatments and storage conditions. These results indicate that AS-48 can be applied alone to control L. monocytogenes and combined with HHP treatment to control Salmonella in fuets.


Can Cochlear Nerve Size Assessment With Magnetic Resonance Enhance the Understanding of Idiopathic Sudden Sensorineural Hearing Loss?
: Idiopathic sudden sensorineural hearing loss (ISSHL) is a rapid loss of hearing, exceeding 30 dB in at least 3 consecutive frequencies within 3 days, without any identifiable cause despite thorough investigations. Currently, the etiology and pathogenesis of ISSHL have not been fully elucidated. This study aimed to assess the size of the cochlear nerve in patients with ISSHL and explore its relationship with pretreatment audiograms and treatment response. : A total of 125 patients (59 [47.2%] women; mean age 47.7±13.8 years [minimum-maximum: 21-76]) and 60 healthy participants (27 [45%] women; mean age 45.7±16.8 years [minimum-maximum: 20-76]) as a control group were included in this study. The size of the cochlear nerve was assessed on the affected side, compared to the control group, as well as on the unaffected side. Pretreatment and posttreatment audiological values were also analyzed. : The cross-sectional area (CSA), vertical diameter (VD), and horizontal diameter (HD) of the CN were found to be smaller on the affected side of ISSHL patients compared to the control group (p<0.01; p=0.04; p=0.02, respectively). In the study group (affected side of ISSHL patients), there were no significant differences in VD, HD, and CSA values between pretreatment audiogram types (p=0.23; p=0.53; p=0.39, respectively), and initial hearing levels (p=0.16; p=0.22; p=0.23, respectively). Furthermore, there were no significant differences in VD, HD, and CSA values between the recovery groups according to Furuhashi criteria (p=0.18; p=0.37; p=0.27, respectively). : The size of the CN may be a risk factor for ISSHL, but it does not affect the type of audiogram curves and was not prognostic in terms of treatment response.


Induction of Broad and Polyfunctional HIV-1-Specific T Cell Responses by the Multiepitopic Protein TMEP-B Vectored by MVA Virus.
A human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) vaccine able to induce long-lasting immunity remains a major challenge. We previously designed a T cell multiepitopic immunogen including protective conserved epitopes from HIV-1 Gag, Pol and Nef proteins (TMEP-B), that induced potent HIV-1-specific CD8 T cells when vectored by DNA and combined with the vaccine candidate modified vaccinia virus Ankara (MVA)-B. Here, we described the vectorization of TMEP-B in MVA (MVA-TMEP) and evaluated the T cell immunogenicity profile elicited in mice when administered in homologous (MVA/MVA) or heterologous (DNA/MVA) prime/boost vector regimens or using homologous or heterologous inserts. The heterologous vector regimen was superior to the homologous protocol in inducing T cell responses. DNA-TMEP-primed animals boosted with MVA-TMEP or MVA-B exhibited the highest magnitudes of HIV-1-specific CD8, CD4 and T follicular helper (Tfh) cells, with MVA-TMEP significantly expanding Gag-specific CD8 T cell responses. In the homologous vector regimen, all groups exhibited similar HIV-1-specific CD8 and CD4 T cell responses, but both MVA-B/MVA-B and MVA-TMEP/MVA-TMEP combinations elicited higher Gag-Pol-Nef (GPN)-specific CD8 T cell responses compared to MVA-TMEP/MVA-B. Our results revealed an enhanced induction of HIV-1-specific T cell responses by TMEP-B when vectored in both DNA and MVA, and supported their use in combined prime/boost strategies for HIV-1 prevention and/or therapy.


The needle component of the type III secreton of Shigella regulates the activity of the secretion apparatus.
Gram-negative bacteria commonly interact with eukaryotic host cells by using type III secretion systems (TTSSs or secretons). TTSSs serve to transfer bacterial proteins into host cells. Two translocators, IpaB and IpaC, are first inserted with the aid of IpaD by Shigella into the host cell membrane. Then at least two supplementary effectors of cell invasion, IpaA and IpgD, are transferred into the host cytoplasm. How TTSSs are induced to secrete is unknown, but their activation appears to require direct contact of the external distal tip of the apparatus with the host cell. The extracellular domain of the TTSS is a hollow needle protruding 60 nm beyond the bacterial surface. The monomeric unit of the Shigella flexneri needle, MxiH, forms a superhelical assembly. To probe the role of the needle in the activation of the TTSS for secretion, we examined the structure-function relationship of MxiH by mutagenesis. Most point mutations led to normal needle assembly, but some led to polymerization or possible length control defects. In other mutants, secretion was constitutively turned "on." In a further set, it was "constitutively on" but experimentally "uninducible." Finally, upon induction of secretion, some mutants released only the translocators and not the effectors. Most types of mutants were defective in interactions with host cells. Together, these data indicate that the needle directly controls the activity of the TTSS and suggest that it may be used to "sense" host cells.


Antiprotozoal Activity of Triazole Derivatives of Dehydroabietic Acid and Oleanolic Acid.
Tropical parasitic diseases such as Chagas disease and leishmaniasis are considered a major public health problem affecting hundreds of millions of people worldwide. As the drugs currently used to treat these diseases have several disadvantages and side effects, there is an urgent need for new drugs with better selectivity and less toxicity. Structural modifications of naturally occurring and synthetic compounds using click chemistry have enabled access to derivatives with promising antiparasitic activity. The antiprotozoal activity of the terpenes dehydroabietic acid, dehydroabietinol, oleanolic acid, and 34 synthetic derivatives were evaluated against epimastigote forms of Trypanosoma cruzi and promastigotes of Leishmaniabraziliensis and Leishmania infantum. The cytotoxicity of the compounds was assessed on NCTC-Clone 929 cells. The activity of the compounds was moderate and the antiparasitic effect was associated with the linker length between the diterpene and the triazole in dehydroabietinol derivatives. For the oleanolic acid derivatives, a free carboxylic acid function led to better antiparasitic activity.


Community intervention with the elderly: a social network approach.
A technique is described for using the advantages of a social systems approach when working with elderly persons in psychiatric distress. The technique is based on the assumption that the solution to a variety of human predicaments lies within the collective instrumental and affective resources of the client's social network. The vehicle for accomplishing this objective is the "Network Session" during which a mental health professional meets with the elderly person and members of his/her social network to help resolve the difficulty. A case report demonstrating use of the technique is included.


Vocalizations of South African mustelines.
Vocalizations of African weasels (Poecilogale albinucha) and polecats (Ictonyx striatus) were tape recorded and analysed sonagraphically. Calls are described in terms of function. Adult calls of both species are divided into the categories: threat, defence, and greeting. Female polecats also vocalized during copulation. Three calls peculiar to the young of both species were recorded. Basically similar tonal patterns of homologous vocalizations by both mustelines can be recognized. Calls of blind young could be recognized as primitive versions of adult calls. The limited vocal repertoire of the animals, with most sounds of a threatening or defensive nature, is typical of solitary species. Similarities between the languages of the two study species and other mustelines can be recognized.


Nitrogen-Carbon Bond Formation by Reactions of a Titanium-Potassium Dinitrogen Complex with Carbon Dioxide, tert-Butyl Isocyanate, and Phenylallene.
Nitrogen-carbon bond-forming reactions at coordinated dinitrogen in a bifunctional titanium-potassium system are reported. A titanium atrane complex with a tris(aryloxide)methyl ligand (1) was treated with two equivalents of potassium naphthalenide under N2 atmosphere to generate a bifunctional complex (2) in which N2 binds end-on to two titanium centers and side-on to three potassium cations. Dinitrogen complex 2 reacted with carbon dioxide, tert-butyl isocyanate, and phenylallene, forming nitrogen-carbon bonds and affording diverse N-functionalized products. The reaction of 2 with CO2 followed by addition of Me3 SiCl resulted in the formation of the starting complex 1 with concomitant release of silylated carboxyl hydrazines while the reaction with two equivalents of tert-butyl isocyanate proceeded by insertion into the Ti-N bonds. Treatment of 2 with phenylallene afforded vinyl-substituted hydrazido complexes.


Regulation of food intake by mechanosensory ion channels in enteric neurons.
Regulation of food intake is fundamental to energy homeostasis in animals. The contribution of non-nutritive and metabolic signals in regulating feeding is unclear. Here we show that enteric neurons play a major role in regulating feeding through specialized mechanosensory ion channels in Drosophila. Modulating activities of a specific subset of enteric neurons, the posterior enteric neurons (PENs), results in sixfold changes in food intake. Deficiency of the mechanosensory ion channel PPK1 gene or RNAi knockdown of its expression in the PENS result in a similar increase in food intake, which can be rescued by expression of wild-type PPK1 in the same neurons. Finally, pharmacological inhibition of the mechanosensory ion channel phenocopies the result of genetic interrogation. Together, our study provides the first molecular genetic evidence that mechanosensory ion channels in the enteric neurons are involved in regulating feeding, offering an enticing alternative to current therapeutic strategy for weight control.


Linear cutaneous lupus erythematosus with calcinosis cutis and milia.
Linear cutaneous lupus erythematosus (LCLE) is an unusual manifestation of cutaneous lupus erythematosus in which erythematous, atrophic, dyschromic lesions are located along the lines of Blaschko. Calcinosis cutis and secondary milia are very uncommon in lupus erythematosus. We present a rare case of LCLE with calcinosis cutis and milia.


Nonoperative management of secondary shoulder impingement syndrome.
Shoulder pain secondary to impingement of the rotator cuff tendons underneath the coracoacromial arch is a common problem seen in athletes who perform repetitive overhead activities. Shoulder impingement has been classified into primary and secondary types. Several factors contribute to impingement, including rotator cuff weakness, posterior capsule tightness, and subacromial crowding. Recently, it has been proposed that scapulothoracic muscle weakness could be a factor that contributes to impingement. Traditional rehabilitation protocols for shoulder impingement syndrome stress individualized rotator cuff strengthening. The authors propose that individualized scapulothoracic muscle strengthening should be a part of any protocol for nonoperative treatment of secondary shoulder impingement syndrome.


Relationship between baseline blood pressure and blood pressure decrease after calcium channel blockers in conscious rats.
To determine whether vasodilators produce a fall in mean blood pressure (MBP) that is directly proportional to baseline MBP. The effects on blood pressure of three calcium channel blockers, nitrendipine, nisoldipine and verapamil, were compared with sodium nitroprusside, a drug acting through a different mechanism. The drugs were infused in conscious, unrestrained rats and their effect on MBP was measured. Primary experimental. Animals were divided into three groups according to their baseline MBP: high (greater than 119 mmHg), moderate (91 to 119 mmHg) and normal (less than 91 mmHg). Five successive infusion rates for each drug were tested in each animal. MBP readings were taken at the end of each infusion period (usually 10 mins). At the maximal dose infused, nitrendipine (0.57 mg/kg.min) lowered MBP 13 +/- 6 mmHg in the low MBP rats, 51 +/- 4 mmHg in the rats with moderate MBP and 83 +/- 8 mmHg in the rats with high MBP (P < 0.05 within groups). Similar results (ie, the greater the baseline MBP, the greater the fall in MBP) were obtained with nisoldipine and verapamil. In the same groups, sodium nitroprusside (0.096 mg/kg.min) produced a fall of 52 +/- 3 mmHg, 56 +/- 5 mmHg and 54 +/- 13 mmHg, respectively (not significant). Nitrendipine, nisoldipine and verapamil behave as antihypertensives since their effect increased as a function of the initial MBP, while sodium nitroprusside showed no effect related to baseline MBP.


Xylem anatomy and hydraulic traits in Vitis grafted cuttings in view of their impact on the young grapevine decline.
Grapevine grafting is an essential practice in viticulture and over the years, various bench grafting techniques have been developed to mechanize the nursery process and to increase the yield in number of viable cuttings. Bench grafting is a fundamental nursery practice that can potentially affect the quality of propagation material also in young decline associated to grapevine trunk diseases and has been recently reported to influence leaf symptoms development associated with diseases of Esca complex. The study aimed to investigate how three bench grafting methods [i.e., (i) Omega graft as mechanical technique, (ii) Whip and Tongue graft as manual technique and (iii) Full Cleft graft as semi-mechanical technique] can influence these phenomena. Specifically, the different methods were compared for their effect on the anatomical development of the grafting point and the functionality of the xylem, also considering two factors: the grapevine cultivar (Cabernet Sauvignon, Glera and Teroldego) and the scion/rootstock diameter (thin and large). Observations by light microscopy on the anatomical evolution and measurements on the xylem morphology and hydraulic traits were correlated with the grafting methods and the investigated varieties. The anatomical observations revealed that the mechanical (Omega) and semi-mechanical (Full Cleft) grafting methods have a faster callusing response while the manual technique (Whip and Tongue) has a slower but greater vascularization of the differentiated callus. Significant differences between cultivars and/or grafting types were also detected in necrotic area on the grafted tissues. Statistical analysis of the grapevine vessels suggested differences in xylem parameters between cultivars, while grafting type had no significant effects. On the other hand, the grafting type significantly affected the intrinsic growth rate. The study confirms the potential incidence of lesions and dysfunctionalities correlated with the grafting method applied, which can potentially induce grafted vine declines in vineyards due to the necrotic area detected on the grafted tissues.


Resolution of ischemia with β-blocker in a patient with anomalous right coronary artery.
Anomalous origin of right coronary artery (RCA) has been associated with angina, myocardial infarction and sudden death. Often these patients are referred for surgery. However, long-term β-blocker therapy instead of surgery has been used in some cases with success. The authors report a case of anomalous RCA where resolution of ischemia with β-blocker was objectively demonstrated on serial stress testing.


Transport of potassium by the colon of normal and sodium-depleted rats.
1. Ascending and descending segments of colon of normal and Nadepleted rats were perfused with solutions of differing KCl concentration. Net K flux, electrical p.d. and, in some experiments, unidirectional K fluxes were measured.2. Variation of luminal K concentration over the range 0-40 mM did not affect p.d. or K efflux rate.3. K secretion rate fell about 30% when Na-free choline chloride solution was perfused.4. Net flux was a linear function of the luminal K concentration, and fell as the latter increased. Na depletion increased K secretion rate and passive permeability of the mucosa to K. Adrenalectomy had the reverse effect. The luminal K concentration, associated with zero net K flux was much greater than expected if the colonic mucosa behaved passively with respect to K.5. Unidirectional fluxes determined when 5 mM-KCl was in the lumen showed that the ratio influx/efflux was much less than predicted by Ussing's flux ratio equation.6. It was concluded that K influx was due to simple diffusion and K efflux to diffusion and active transport, both processes being increased by Na depletion.


An Investigation of Transient Severe Motion Related to Gadoxetic Acid-enhanced MR Imaging.
To investigate the cause of imaging artifacts observed during gadoxetic acid-enhanced arterial phase imaging of the liver. This HIPAA-compliant study was approved by the institutional review board. Data were collected prospectively at two sites (site A, United States; site B, Japan) from patients undergoing contrast material-enhanced MR imaging with gadoxetic acid (site A, n = 154, dose = 0.05 mmol/kg; site B, n = 130, 0.025 mmol/kg) or gadobenate dimeglumine (only site A, n = 1666) from January 2014 to September 2014 at site A and from November 2014 to January 2015 at site B. Detailed comparisons between the two agents were made in the patients with dynamic liver acquisitions (n = 372) and age-, sex-, and baseline oxygen saturation (Spo2)-matched pairs (n = 130) at site A. Acquired data included self-reported dyspnea after contrast agent injection, Spo2, and breath-hold fidelity monitored with respiratory bellows. Self-reported dyspnea was more frequent with gadoxetic acid than with gadobenate dimeglumine (site A, 6.5% [10 of 154] vs 0.1% [two of 1666], P < .001; site B, 1.5% [two of 130]). In the matched-pair comparison, gadoxetic acid, as compared with gadobenate dimeglumine, had higher breath-hold failure rates (site A, 34.6% [45 of 130] vs 11.7% [15 of 130], P < .0001; site B, 16.2% [21 of 130]) and more severe artifacts during arterial phase imaging (site A, 7.7% [10 of 130] vs 0% [none of 130], P < .001; site B, 2.3% [three of 130]). Severe imaging artifacts in patients who received gadoxetic acid were significantly associated with male sex (P = .023), body mass index (P = .021), and breath-hold failure (P < .001) but not with dyspnea or Spo2 decrease. Severe motion-related artifacts in the arterial phase of gadoxetic acid-enhanced liver MR imaging are associated with breath-hold failure but not with subjective feelings of dyspnea or a substantial decrease in blood Spo2. Subjective feelings of dyspnea are not necessarily associated with imaging artifacts. The phenomenon, albeit at a lower rate, was confirmed at a second site in Japan.


Simple synthesis of a hierarchical LiMn0.8Fe0.2PO4/C cathode by investigation of iron sources for lithium-ion batteries.
Iron (Fe) substitution is an effective strategy for improving the electrochemical performance of LiMnPO4 which has poor conductivity. Herein, we focus on investigating the effect of substitution of Mn with different iron sources, on the structure and electrochemical performances of the LiMnPO4 materials. The Fe-substituted LiMnPO4/C composites were synthesized via a simple and rational solid-state method, and will be of benefit for engineering applications. The characterization of the materials shows an obvious influence of the iron sources on structure and morphology. The N-LMFP material prepared using soluble FeNO3 as iron sources exhibits an excellent rate capacity of 122 mA h g-1 at 5C, and superior cyclability with a capacity retention of 98.9% after 400 cycles at 2C. The enhanced rate capability and cycling stability of N-LMFP are the result of the lowered electron/ion resistance and the improved reversibility of the reaction, that originates from the homogeneous fine particles and hierarchical structure with large mesopores. This research provides significant guidelines for designing an LiMnPO4 cathode with a high performance.


Unusual presentation of extranodal diffuse large B-cell lymphoma in a solid-organ recipient during long-term immunosuppressive treatment.
Posttransplant lymphoproliferative disorders (PTLDs) refer to a group of diseases, including diffuse large B-cell lymphoma (DLBCL), that develop after solid organ transplantation or hematopoietic stem cell transplantation. Extranodal involvement in PTLDs is common. Reports about exclusive bone marrow involvement are rare. A 70-year-old woman, who had undergone kidney transplantation in 2018, was diagnosed with exclusively extranodal, Epstein-Barr virus-negative DLBCL, with bone marrow and spleen involvement, during long-term immunosuppression. She achieved complete remission with combined immunochemotherapy and temporary hold of immunosuppression. This case shows an uncommon clinical presentation of DLBCL, which was challenging to diagnose, being entirely extranodal. The favorable clinical course relied on timely diagnosis and a multidisciplinary approach. Long-term consequences of posttransplant immunosuppression require a high level of suspicion for an appropriate management, aimed at preserving the graft while eradicating the lymphoproliferative disorder.


Whistle signal variations among three Indo-Pacific humpback dolphin populations in the South China Sea: a combined effect of the Qiongzhou Strait's geographical barrier function and local ambient noise?
Geographic variations in the dolphin whistles could be useful in assessing association and isolation among populations. Whistle of free-ranging Indo-Pacific humpback dolphins (Sousa chinensis) among the Pearl River Estuary (PRE), Leizhou Bei (LZB) and Sanniang Bay (SNB) populations were investigated. A total of 2850 whistles with legible fundamental contour were extracted and 15 acoustic parameters were measured. Contrary to SNB, PRE and LZB had the same relative proportion of tonal type compositions with flat and sine representing the most frequent types. The generalized linear model analysis showed significant acoustic difference among populations and tonal types. All frequency parameters in SNB were significantly higher than those in PRE and LZB, where no significant variation was observed in most of the parameters either at the population level or within each tonal type. Canonical discriminant functions analysis showed a smaller difference between PRE and LZB than between PRE and SNB and between LZB and SNB. Compared with previous recordings, recent recordings demonstrated a consistent pattern of becoming higher in whistle frequency parameters in both LZB and SNB populations, suggesting that noise pollution in LZB and SNB increasing with time according to the acoustic niche hypothesis. Dolphin whistle's geographic variations could be shaped by the combined function of the geographical barrier function of the Qiongzhou strait and local ambient noise. Considering the isolated condition and the relatively smaller population size of the humpback dolphin in the SNB, more effective and proactive conservation actions should be taken to prevent the extinction of small populations.


Outpatient management of sickle cell pain with chronic opioid pharmacotherapy.
We report our experience of providing chronic opioid pharmacotherapy on an outpatient basis to selected patients with frequent episodes of moderate-to-severe pain from sickle cell disease (SCD). Three cases illustrate our clinical experience in approximately 40 patients with sickle cell pain. Patients were seen at our sickle cell pain clinic at Beth Israel Hospital once each month for a three-hour visit. Visits included group music therapy and individual medical care, including comprehensive blood work and scheduling of medical tests when appropriate. Between visits, the pain and palliative care physicians followed patients on an as-needed basis. The SCD pain opioid pharmacotherapy protocol was modeled on a regimen used to treat malignant pain-typically a long-acting opioid in combination with a short-acting opioid, such as oral transmucosal fentanyl citrate (OTFC; Actiq) for breakthrough pain (BTP). Emergency department (ED) visits and hospital admissions were dramatically reduced in the three patients whose pain was managed by adapting the cancer pain model. During the year before their first visit to our pain clinic, the patients each had between six and 18 ED visits, which resulted in six- to 13 hospital admissions amounting to 32-182 inpatient days per patient. Each of the patients was prescribed a long-acting opioid (methadone, control-release oxycodone, or transdermal fentanyl) with a short-acting opioid for BTP from crises (oral transmucosal fentanyl citrate for two patients; short-acting oxycodone for one patient). Pain was well controlled. For each patient, hospital admissions were reduced to < or = 1 visit per year. These reduced levels of ED visits and hospital admissions have remained constant for more than three years.


Increased recruitment of cognitive control in the presence of traumatic stimuli in complex PTSD.
A neurocircuitry model of post-traumatic stress disorder (PTSD) suggests increased amygdala responses to emotional stimuli, coupled with hypoactivation of prefrontal regions associated with cognitive control. However, results are heterogenous across different subsamples of PTSD as well as different paradigms. We investigated cognitive control in a classic and emotional Stroop task in 28 female patients with complex PTSD (cPTSD), 28 female trauma-exposed healthy controls (TCs) and 28 female non-trauma-exposed healthy controls (HCs) using functional neuroimaging. Afterwards, we assessed memory function in a spontaneous free recall and recognition task. Patients with cPTSD displayed significantly greater Stroop interference with trauma-related words (as reflected in slower reaction times and increased errors) compared to the other conditions and compared to the TC and HC groups. Moreover, patients with cPTSD showed increased activation in the context of trauma-related words in brain regions associated with cognitive control (dlPFC, vmPFC, dACC) compared to both control groups, and a trend for increased activation in the insula compared to the HC group. Increased recruitment of regions contributing to cognitive control in patients with cPTSD, together with a lack of amygdala response may point to efforts to compensate for emotional distraction caused by the trauma-related words.


Comparative pilot study about HPV test with partial genotyping in primary screening versus other strategies for cervical cancer population screening, CRYGEN 16/18 study.
The early detection of cervical cancer requires the implementation of molecular screening programs for human papillomavirus (HPV). However, there are discrepancies in the optimization of screening protocols. The performance of 10 primary screening strategies based on molecular, cytological or combined techniques is now evaluated. A blind, prospective, and interventional study was designed in 1977 35-year-old women. The molecular determination was carried out by the Cobas 4800 HPV platform. Cytological analysis was performed on the same samples without knowledge of the result of the molecular assay. All women in whom HPV-16/HPV-18 was detected or presented cytological alteration together with detection of other high-risk genotypes (HPVhr) were referred to colposcopy. The molecular assay detected the presence of HPVhr genotypes in 12.5% of the women, while only 8.1% of the cytologies were pathological. Among the patients referred to colposcopy, in 19.5% high-grade lesions were observed, being HPV-16 present in 65.3% of them. In six of these high-grade lesions (associated with HPV-16 in all cases), cytology was reported as normal. The follow-up one year later, of women with normal cytology and HPVhr detection a HSIL/CIN2+ lesion was detected (associated to HPV-33). In the comparative study with other strategies, the protocol called CRYGEN 16/18 yielded the best balance of sensitivity and specificity with the least referral to colposcopy. Performing molecular detection of HPVhr with partial first-line genotyping of at least HPV-16, with direct referral to colposcopy, increases the detection rate of HSIL/CIN2+ lesions.


Evaluation of AT-752, a Double Prodrug of a Guanosine Nucleotide Analog with In Vitro and In Vivo Activity against Dengue and Other Flaviviruses.
Every year, millions of people worldwide are infected with dengue virus (DENV), with a significant number developing severe life-threatening disease. There are currently no broadly indicated vaccines or therapeutics available for treatment of DENV infection. Here, we show that AT-281, the free base of AT-752, an orally available double prodrug of a guanosine nucleotide analog, was a potent inhibitor of DENV serotypes 2 and 3 in vitro, requiring concentrations of 0.48 and 0.77 μM, respectively, to inhibit viral replication by 50% (EC50) in Huh-7 cells. AT-281 was also a potent inhibitor of all other flaviviruses tested, with EC50 values ranging from 0.19 to 1.41 μM. Little to no cytotoxicity was observed for AT-281 at concentrations up to 170 μM. After oral administration of AT-752, substantial levels of the active triphosphate metabolite AT-9010 were formed in vivo in peripheral blood mononuclear cells of mice, rats, and monkeys. Furthermore, AT-9010 competed with GTP in RNA template-primer elongation assays with DENV2 RNA polymerase, which is essential for viral replication, with incorporation of AT-9010 resulting in termination of RNA synthesis. In AG129 mice infected with DENV D2Y98P, treatment with AT-752 significantly reduced viremia and morbidity and increased survival. The demonstrated in vitro and in vivo activity of AT-752 suggests that it is a promising compound for the treatment of dengue virus infection and is currently under evaluation in clinical studies.


P21-activated kinase 4 regulates the cyclin-dependent kinase inhibitor p57(kip2) in human breast cancer.
The p21-activated kinases have been implicated in the control of cell cycle progression. However, the biological mechanism underlying the role of p21-activated kinase 4 (PAK4) in cell cycle control remains unknown. Here, by using quantitative RT-PCR and immunoblot analyses, we discovered that over-expression of PAK4 could suppress cyclin-dependent kinase inhibitor 1C (p57(Kip2) ) expression in the MCF-7 human breast cancer cell line, whereas lentiviral vector-mediated small interfering RNA (siRNA) knockdown of PAK4 markedly promoted p57(Kip2) expression in MCF-7 cells. Furthermore, PAK4-mediated down-regulation of p57(Kip2) was reversed by MG132, a specific proteasome inhibitor. The ubiquitination assay confirmed that the activity of PAK4 attenuated p57(Kip2) protein stability through the ubiquitin-proteasome pathway in MCF-7 cells. Moreover, a significant inverse correlation between PAK4 and p57(Kip2) protein levels was observed in breast cancer tissues by immunohistochemical analysis. Taken together, our data demonstrate a novel function for PAK4 in regulating the stability of p57(Kip2) , possibly through the ubiquitin-proteasome pathway, leading to increased proliferation of breast cancer cells. Thus, PAK4 may be used as a potential diagnostic and therapeutic target for human breast cancer.


[Localization and registration of the hinge axis in black Africans].
The study of the cinematic method using "SAM" and "Quick Axis of FAG" added to mandibular condyle palpation for the hinge axis limited points, show that the Black Africans mandibular condyle rotation axis position is higher (3.5 mm) and backer (2 mm) than the Caucasians. The axial points are located to between 11 and 12 mm in front of the tragus and between 7 and 8 mm below on the perpendicular line to the furrow defining the tragus superior side to the Ectocanthus.


The Efficacy of Vitamin D Supplementation against Nonalcoholic Fatty Liver Disease: A Meta-Analysis.
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. If this disease is not appropriately controlled, it can eventually cause chronic liver damage, including cirrhosis and hepatocellular carcinoma. Accordingly, the adoption of appropriate interventions to control NAFLD is important for any healthcare system. The aim of the present systematic review and meta-analysis was to clarify the effect of vitamin D supplementation on NAFLD. PubMed, Scopus, Science Direct, ISI Web of Science, and Google Scholar were systematically searched up to March 2019 to find clinical trials that examined the effects of vitamin D supplementation on liver enzyme levels in NAFLD patients. Means for liver enzymes and potential sources of heterogeneity were extracted. A subgroup analysis was performed to detect potential sources of interstudy heterogeneity. Nine trials (10 arms) comprising 467 participants were eligible for meta-analysis. The results from a pooled analysis did not reveal a significant effect of vitamin D intake on alanine aminotransferase (-2.88 U/L; 95% CI, -6.03 to 0.27; I2 = 85%), aspartate aminotransferase (-0.10 U/L; 95% CI, -1.18 to 0.97; I2 = 26%), and γ-glutamyltransferase levels (0.12 U/L; 95% CI, -5.94 to 6.18; I2 = 38%). The meta-analysis suggested a significant reduction in alkaline phosphatase (-13.79 U/L; 95% CI, -22.13 to -5.45; I2 = 72%) following vitamin D supplementation. This effect was robust in the subgroup in which > 3,000 IU/day vitamin D was administered (-19.74 U/L; 95% CI, -25.36 to -14.12; I2 = 0.0%). The present meta-analysis does not suggest the efficacy of vitamin D supplementation on NAFLD treatment.


Camelobaetidius guaycara, a new species of Baetidae (Ephemeroptera) from Costa Rica, Central America.
The nymphs of a new species of Camelobaetidius (Ephemeroptera: Baetidae) possibly related to the South American species of this genus were found on the Atlantic and Pacific slopes of Costa Rica. Among other characteristics it is distinguished by having the anterodorsal arc of labrum with 1 + 6 setae, the first two frayed, ventrally 4 small setae near the lateral margin, and a minute seta near the anterior margin, on both sides of the cleft; the left mandible incisors with 6 denticles similar in size and the tip of the slender process extended at about the same level as the incisors; the paraglossa and glossa equal in length and a little shorter than segment II of labial palp, and a short triangular distomedial projection on segment II of labial palp; small nipple-like thoracic gills at base of forecoxa; claws with 27-32 denticles; posterior margin of abdominal terga with rounded spines; paraproct with 1-3 sclerotized spines, and cerci approximately 12% longer than the median filament. Both sexes present several different colorations. Some data on microhabitat preferences of nymphs are also given.


Wavelength-Tunable Electroluminescent Light Sources from Individual Ga-Doped ZnO Microwires.
Electrically driven wavelength-tunable light emission from biased individual Ga-doped ZnO microwires (ZnO:Ga MWs) is demonstrated. Single crystalline ZnO:Ga MWs with different Ga-doping concentrations have been synthesized using a one-step chemical vapor deposition method. Strong electrically driven light emission from individual ZnO:Ga MW based devices is realized with tunable colors, and the emission region is localized toward the center of the wires. Increasing Ga-doping concentration in the MWs can lead to the redshift of electroluminescent emissions in the visible range. Interestingly, owing to the lack of rectification characteristics, relevant electrical measurement results show that the alternating current-driven light emission functions excellently on the ZnO:Ga MWs. Consequently, individual ZnO:Ga MWs, which can be analogous to incandescent sources, offer unique possibilities for future electroluminescence light sources. This typical multicolor emitter can be used to rival and complement other conventional semiconductor devices in displays and lighting.


Obstetric analgesia utilization in labor pain management and associated factors among obstetric care providers in the West Shewa Zone, Central Ethiopia.
Labor pain is the worst pain that almost every woman experiences during childbirth. Labor pain management plays a crucial role in promoting maternal-wellbeing, contributing enormously to maternal satisfaction with the childbirth experience and the high quality of services. Although there have been previous studies, they have primarily been conducted at referral or general hospitals located in urban settings. Thus, this study aimed to assess the utilization of labor pain analgesia and associated factors among obstetric care providers at all levels of health facilities in central Ethiopia. A multicenter institution-based cross-sectional study design was employed from 1 July to 30 September 2020. Simple random sampling using the lottery method was employed to select 399 obstetric care providers. The data were entered into Epi-data version 4.2 and analyzed using SPSS version 26. Bivariate and multivariable logistic regression analysis were used to identify the associated factors. The adjusted odds ratio with its 95% confidence interval and p value ⩽ 0.05 were used to identify associated factors. The overall utilization of obstetric analgesia was 46% (95% confidence interval: 41.2%-50.8%). Being a Midwife (adjusted odds ratio: 2.10, 95% confidence interval: 1.27-3.47), having heard of the World Health Organization pain ladder (adjusted odds ratio: 2.95, 95% confidence interval: 1.73-5.01), having favorable attitude (adjusted odds ratio: 1.89, 95% confidence interval: 1.17-3.05), the expectation of obstetric care providers about labor pain (adjusted odds ratio: 3.26, 95% confidence interval: 1.27-8.36), having training on labor pain management (adjusted odds ratio: 2.51, 95% confidence interval: 1.03-6.07), and presence of chance for preference of obstetric analgesia for mothers in the facility (adjusted odds ratio = 2.30, 95% confidence interval: 1.33-3.98) were identified as factors significantly associated with the practice of obstetric analgesia among obstetric care providers. The overall use of labor pain management methods among obstetric care providers is low. Professional category, provider attitude, labor pain severity expectations, and having training were found to be factors associated with the use of obstetric analgesia. Therefore, working on adapting and disseminating the harmonized guideline and protocols on labor pain management and provision of training for obstetric care providers on labor pain management techniques were recommended.


Associations between human milk oligosaccharides (HMOs) and eating behaviour in Hispanic infants at 1 and 6 months of age.
Human milk oligosaccharides (HMOs) are naturally occurring glycans in human breast milk that act as prebiotics in the infant gut. Prebiotics have been demonstrated to suppress appetite in both adults and children. Therefore, HMOs may affect infant eating behaviour. To determine if HMOs in breast milk are associated with eating behaviour in Hispanic infants. Cross-sectional analysis of a prospective cohort of Hispanic mother-infant dyads (1-month, n = 157; 6-months, n = 69). Breast milk samples were screened for 19 HMOs using high pressure liquid chromatography, and eating behaviour was assessed using the Baby Eating Behaviour Questionnaire (BEBQ). We conducted multiple linear regressions to examine associations between HMOs and BEBQ scores, adjusted for maternal pre-pregnancy BMI, infant sex, birthweight, delivery mode and number of breastfeedings per day. We stratified by HMO secretor status-a genetic determinant of the types of HMOs produced. At 1 month, LNnT (lacto-N-neotetraose; P = .04) was negatively associated with food responsiveness in the total sample, while DFLNT (difucosyllacto-N-tetrose; P = .03) and DSLNT (disialyl-LNT; P = .04) were negatively associated with food responsiveness in secretors only. At 6 months, LSTc (sialyllacto-N-tetraose c; P = .01), FLNH (fucosyllacto-N-hexaose; P = .03), LNH (lacto-N-hexaose; P = .006) and DSLNH (disialyllacto-N-hexaose; P = .05) were positively associated with food responsiveness in both the total sample and secretors only. We found several HMOs that were both positively and negatively associated with infant food responsiveness, which is a measure of drive to eat.


A new type of defect in the gene for bilirubin uridine 5'-diphosphate-glucuronosyltransferase in a patient with Crigler-Najjar syndrome type I.
Crigler-Najjar syndrome (CN) type I, which is characterized by the complete absence of bilirubin uridine 5'-diphosphate-glucuronosyltransferase (UGT) activity, is inherited as an autosomal recessive trait associated with unconjugated hyperbilirubinemia. Phenobarbital has no effect on the bilirubin concentration in the serum of patients with CN type I. Recently, cDNA for two human liver bilirubin UGT (UGT1A and UGT1D) were isolated, and their genetic organization was determined. The UGT1A (UGT1*1) and UGT1D (UGT1*4) genes each have a unique exon 1, whereas exons 2-5 are common to both genes. It has been predicted that some defect in the exons common to both genes is responsible for the absence of UGT1A and UGT1D activities in CN type I, and five cases with such a mutation have been reported. We describe here a new type of defect in the gene for bilirubin UGT in a patient with CN type I, namely, an abnormality in the exon 1 that is characteristic of the UGT1A gene. This mutation is a single nucleotide substitution, that is, C is changed to A at base position 840 in UGT1A cDNA, and this change results in a stop codon. Our patient is homozygous for the defect, and his nonconsanguineous parents and elder brother, who are clinically normal, are heterozygous for the defective allele. No mutation was detected in any exons of the UGT1D gene. Our results suggest that a homozygous nonsense or deletion mutation is detected not only in the exons common to UGT1A and UGT1D genes but also in unique exon 1 of UGT1A in CN type I.


Formation of redispersible polyelectrolyte complex nanoparticles from gallic acid-chitosan conjugate and gum arabic.
Polyelectrolyte complex (PEC) nanoparticles between chitosan (CS) and biomacromolecules offer better physicochemical properties as delivery vehicles for nutrients than other CS-based nanoparticles. Our major objective was to fabricate PEC nanoparticles between water soluble gallic acid-chitosan conjugate (GA-CS) and gum arabic. The optimal fabrication method, physicochemical characteristics and stability were investigated. Furthermore, we also evaluated the effects of nano spray drying technology on the morphology and redispersibility of nanoparticle powders using Buchi B-90 Nano Spray Dryer. Results showed that the mass ratio between GA-CS and gum arabic and the preparation pH had significant contributions in determining the particle size and count rate of the nanoparticles, with the ratio of 3:1 and pH 5.0 being the optimal conditions that resulted in 112.2nm and 122.9kcps. The polyethylene glycol (PEG) played a vital role in forming the well-separated spray dried nanoparticles. The most homogeneous nanoparticles with the smoothest surface were obtained when the mass ratio of GA-CS and PEG was 1:0.5. In addition, the GA-CS/gum arabic spray dried nanoparticles exhibited excellent water-redispersibiliy compared to native CS/gum arabic nanoparticles. Our results demonstrated GA-CS/gum arabic nanoparticles were successfully fabricated with promising physicochemical properties and great potential for their applications in food and pharmaceutical industries.


Reaction of the potent bacterial mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) with 2'-deoxyadenosine and calf thymus DNA: identification of fluorescent propenoformyl derivatives.
The potent bacterial mutagen and drinking water disinfection byproduct 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) was reacted with 2'-deoxyadenosine and calf thymus DNA in aqueous solutions at neutral conditions. HPLC analyses of the 2'-deoxyadenosine reaction mixtures showed that two previously unidentified products were formed. The products were isolated by preparative C18 chromatography, and their structures were characterized by UV absorbance, fluorescence emission, 1H and 13C NMR spectroscopy, and mass spectrometry. It was concluded that in both products a propeno bridge had been incorporated between N-1 and N6 of the adenine unit. In one of the products, the propeno bridge carried a formyl group [3-(2'-deoxy-beta-D-ribofuranosyl)-7H-8-formyl[2,1-i]pyrimidopurine++ + (pfA-dR)], and in the other the substituents consisted of a formyl group and a chlorine atom [3-(2'-deoxy-beta-D-ribofuranosyl)-7H-8-formyl-9-chloro[2,1-i]pyrimid opurine (Cl-pfA-dR)]. These novel adducts exhibited fluorescence in the visible region with emission maxima around 460 nm. The yields of the products in reactions performed at pH 7.4 and 37 degrees C were about 0.03 mol %. In reaction of MX with calf thymus DNA, the adduct pfA-dR was formed and its yield was about 0.6 adduct/10(5) nucleotides.