Modeling of elastic nonlinearities in ferroelectric materials including nonlinear losses: application to nonlinear resonance mode of relaxors single crystals.
(1-x)Pb(Mg1/3Nb2/3)O3-xPbTiO3 (PMN-PT) and (1-x)Pb(Zn1/3Nb2/3)O3-xPbTiO3 (PZN-PT) single crystals are considered to behave like soft Pb(Zr,Ti)O3 (PZT) ceramics because of their small mechanical quality factor Qm and poor stability under external disturbances (Qm > 500-1000 for hard PZT ceramic, and Qm < 100 for soft PZT and PMN-PT and PZN-PT single crystals). At weak signal excitation of the first resonance mode, the displacement at the end of a lateral bar is proportional to the Q31d31 figure of merit that is very close to that found for hard PZT. Indeed the very large piezoelectric coefficient compensates the low Qm. But increasing alternating current (AC) field results in the appearance of strong non-linearities through a shift of the resonance frequency and jumps phenomenon observed on increasing and decreasing frequency sweep. It is shown in this paper that these nonlinearities are due to the nonlinear elastic compliance that can be modeled by a third order development of the constitutive piezoelectric equations. Experiments on PMN-PT and PZN-PT single crystals are used for comparison with the model to show the viability of the approach. Both the frequency shift and jumps phenomenon are simulated with a very good agreement with experimental results. The importance is also shown of losses associated with the third order term responsible for the large decrease of the mechanical quality factor for high strain levels. Thus, the nonlinear losses are related to the hysteresis of domain wall motion when subjected to large displacements.


A novel heteropolysaccharide isolated from custard apple pulp and its immunomodulatory activity in mouse macrophages and dendritic cells.
In this study, a novel heteropolysaccharide (ASPA80-1) with an average molecular weight of 5.48 × 104 Da was isolated and structurally elucidated from custard apple pulp (Annona squamosa) through DEAE-cellulose, Sephadex G-100 and Sephacryl S-300 HR chromatography and spectral analysis. ASPA80-1 is a water-soluble polysaccharide and it is a polymer consisting of predominant amounts of (1 → 3)-linked-L-arabinose (Ara) residues, small amounts of (1 → 6)-linked-D-galactose (Gal), (1 → 3,5)-linked-L-arabinose (Ara) residues and terminal linked-L-arabinose (Ara) residues, trace amount of (1 → 4)-linked-D-glucose (Glc) residues and (1 → 2)-linked-L-rhamnose (Rham) residues. ASPA80-1 showed significant effect on antigen-presenting cells (APCs) activation. On the one hand, ASPA80-1 activated RAW264.7 macrophage cells by inducing morphology change, enhancing phagocytic ability, increasing nitric oxide (NO) secretion and promoting expression of major histocompatibility complex class II (MHC II) and cluster of differentiation 86 (CD 86). On the other hand, ASPA80-1 promoted the maturation of dendritic cells (DCs) by inducing longer dendrites, decreasing phagocytic ability and increasing MHC II and CD86 expression. Furthermore, mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathways were activated after the intervention of ASPA80-1 on RAW264.7 cells or DCs. Thus, the novel heteropolysaccharide ASPA80-1 has the potential to be used as an immunoenhancing component in functional foods.


Determining the feline immunodeficiency virus (FIV) status of FIV-vaccinated cats using point-of-care antibody kits.
This study challenges the commonly held view that the feline immunodeficiency virus (FIV) infection status of FIV-vaccinated cats cannot be determined using point-of-care antibody test kits due to indistinguishable antibody production in FIV-vaccinated and naturally FIV-infected cats. The performance of three commercially available point-of-care antibody test kits was compared in a mixed population of FIV-vaccinated (n=119) and FIV-unvaccinated (n=239) cats in Australia. FIV infection status was assigned by considering the results of all antibody kits in concert with results from a commercially available PCR assay (FIV RealPCR™). Two lateral flow immunochromatography test kits (Witness FeLV/FIV; Anigen Rapid FIV/FeLV) had excellent overall sensitivity (100%; 100%) and specificity (98%; 100%) and could discern the true FIV infection status of cats, irrespective of FIV vaccination history. The lateral flow ELISA test kit (SNAP FIV/FeLV Combo) could not determine if antibodies detected were due to previous FIV vaccination, natural FIV infection, or both. The sensitivity and specificity of FIV RealPCR™ for detection of viral and proviral nucleic acid was 92% and 99%, respectively. These results will potentially change the way veterinary practitioners screen for FIV in jurisdictions where FIV vaccination is practiced, especially in shelter scenarios where the feasibility of mass screening is impacted by the cost of testing.


Comparison of the immunological properties of rat cerebral and aortic endothelium.
The immunological properties of cerebral microvascular endothelium were directly compared with those of an extra-cerebral endothelium in vitro. Lymphocyte adhesion to cerebral endothelium is normally low, but is sensitive to induction by interferon-gamma (IFN gamma) and tumour necrosis factor-alpha (TNF alpha). Conversely adhesion to aortic endothelium is normally much higher but it is only marginally sensitive to induction by cytokines. Adhesion to both cell types is Ca2+ and Mg2+ dependent. Mitogen-activated lymphocytes bind more strongly to both endothelia, but adhesion to aortic endothelium is not enhanced further by activation of the endothelium. The observed low binding of lymphocytes to brain endothelium and its rapid induction by cytokines suggest a mechanism to explain why lymphocyte accumulation in brain is normally very low but rapidly increases during immune responses. Both cell types express similar levels of class I major histocompatibility complex (MHC) molecules, and this is enhanced by IFN gamma with similar responsiveness to different levels of IFN gamma. MHC class II molecules are absent from these cells but may be induced: although both endothelia respond to similar levels of cytokines, the surface density induced on brain endothelium is approximately 2- to 3-fold higher at all levels of IFN gamma.


Charge isomers of urinary bikunin (trypsin inhibitor).
It was observed that the purified urinary bikunin (trypsin inhibitor) consisted of four major isomers with different electric charges which could be separated by HPLC using a Mono Q column. These isomers revealed the same antitrypsin activity and did not show any differences in the apparent molecular weight by SDS-PAGE, amino-acid composition, N-terminal amino-acid sequence (1-40) and C-terminal amino acid (Leu). The contents of sialic acid and uronic acid were also identical among these isomers. However, analysis of chondroitin sulfate revealed all the glycosaminoglycan chains of these isomers were undersulfated, comprising nonsulfated and 4-sulfated disaccharide units, and 4-sulfated disaccharide unit ratio varied among these isomers. After the chondroitin ABC lyase digestion, all the isomers were eluted at the same position on a Mono Q column chromatography. These results indicated that charge isomers of urinary bikunin was attributed to the difference on sulfation ratio in a glycosaminoglycan chain.


Research progress on the lipid-lowering and weight loss effects of tea and the mechanism of its functional components.
Obesity caused by poor eating habits has become a great challenge faced by public health organizations worldwide. Optimizing dietary intake and ingesting special foods containing biologically active substances (such as polyphenols, alkaloids, and terpenes) is a safe and effective dietary intervention to prevent the occurrence and development of obesity. Tea contains several active dietary factors, and daily tea consumption has been shown to have various health benefits, especially in regulating human metabolic diseases. Here, we reviewed recent advances in research on tea and its functional components in improving obesity-related metabolic dysfunction, and gut microbiota homeostasis and related clinical research. Furthermore, the potential mechanisms by which the functional components of tea could promote lipid-lowering and weight-loss effects by regulating fat synthesis/metabolism, glucose metabolism, gut microbial homeostasis, and liver function were summarized. The research results showing a "positive effect" or "no effect" objectively evaluates the lipid-lowering and weight-loss effects of the functional components of tea. This review provides a new scientific basis for further research on the functional ingredients of tea for lipid lowering and weight loss and the development of lipid-lowering and weight-loss functional foods and beverages derived from tea.


Descriptive epidemiology of gastric adenocarcinoma in the state of Texas by ethnicity: Hispanic versus White non-Hispanic.
We aimed to evaluate the clinicopathological and demographic characteristics of gastric adenocarcinoma in Hispanics and compare these trends with those found in non-Hispanic Whites in Texas. Records of patients with gastric adenocarcinoma found in the Texas Cancer Registry from 1995 to 2006 were reviewed. Four ethnic-geographic groups were formed: Hispanics residing in El Paso County (a county on the Texas-Mexico border), White non-Hispanics in El Paso County, Hispanics from the remaining counties of Texas combined, and White non-Hispanics from the remaining counties of Texas combined. Adjusted prevalence ratios (PRs) for the outcome of late stage at diagnosis were calculated. Of 9949 patients, 561 patients were El Paso County residents, of whom 83% were Hispanics. Among the four ethnic-geographic groups, the age-adjusted incidence was the highest in Hispanics in El Paso County (15.5 cases/100000). Tumor pathobiology varied by ethnicity. White non-Hispanics were more likely than Hispanics to have a proximal tumor and less likely to have a poorly differentiated or undifferentiated tumor. In El Paso County, patients in each of the eight age groups under 75 years compared to patients aged ≥85 years were significantly more likely to be at late stage (adjusted PRs 1.44-1.71). The incidence of gastric adenocarcinoma is higher in Hispanics than in Whites in both El Paso County and the remaining portion of Texas. Hispanics have a higher grade of gastric adenocarcinoma. The prevalence of late stage at the time of diagnosis is higher in younger patients than in older patients.


Mycophenolate mofetil therapy for inflammatory eye disease.
To evaluate treatment outcomes with mycophenolate mofetil in patients with inflammatory eye disease. Retrospective case series. Eighty-four consecutive patients with inflammatory eye disease treated with mycophenolate mofetil at an academic referral center. Medical records were reviewed for treatment with mycophenolate mofetil. Dose of mycophenolate mofetil, response to therapy, dose of prednisone, use of other immunosuppressive drugs, and side effects associated with the use of mycophenolate mofetil were recorded. Ability to control ocular inflammation with mycophenolate mofetil and to taper prednisone to < or =10 mg daily, and incidence of treatment-related side effects. Of the 84 patients treated with mycophenolate mofetil, 61% had uveitis, 17% had scleritis, 11% had mucous membrane pemphigoid, and 11% had orbital or other inflammatory disease. Forty-three percent of patients treated with mycophenolate mofetil had been treated with at least one other immunosuppressive drug previously. The median dose of prednisone at the start of mycophenolate mofetil therapy was 40 mg, and 82% of the patients were considered a treatment success, as judged by the ability to control the inflammation and taper prednisone to < or =10 mg daily. Median time to treatment success was 3.5 months. Mycophenolate mofetil therapy was discontinued due to insufficient efficacy at a rate of 0.10 per person-year (PY) and due to side effects at a rate of 0.08/PY. The most frequent side effect was gastrointestinal upset, with a rate of 0.19/PY. These data suggest that mycophenolate mofetil may be an effective corticosteroid-sparing agent in the treatment of inflammatory eye disease with a manageable side effect profile.


Influence of nifedipine on arterial baroreflex modulation of heart rate control during dynamic increases in arterial pressure: studies in normal man.
Studies in animals have demonstrated that calcium channel blocking agents exert important influences on autonomic mechanisms in addition to their direct vascular effects. Previous studies in our laboratory showed that clinical doses of nifedipine sensitized baroreceptor-mediated control of peripheral vascular resistance in normal human subjects. However, baroreflex control of vascular tone does not necessarily imply parallel control of heart rate. A series of experiments was therefore performed to test the hypothesis that therapeutic doses of nifedipine would potentiate arterial baroreflex modulation of heart rate during ramp increases of arterial pressure in normal volunteers. Arterial baroreflex control was assessed by measuring heart interval (HI) responses to dynamic ramp elevation of systolic arterial pressure (SAP) with bolus administration of phenylephrine (PE) before and after nifedipine or placebo in 19 normal subjects. Arterial baroreflex control was calculated from the slope of the regression of SAP on succeeding HI during the first 18 cardiac cycles following onset of rise of SAP after PE bolus. In 13 subjects, bolus PE produced an increase in SAP from 125 +/- 3 mm Hg to 152 +/- 5 mm Hg (p less than 0.01), with a resultant increase in HI from 1110 +/- 57 msec to 1541 +/- 87 msec (p less than 0.01). The baroreflex response was linear (r greater than 0.80, p less than 0.025) and = 17.8 +/- 3.3 msec/mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)


Measurement of the adhesive strength of a gingival cell line to agar.
A new technique is described for measuring the adhesive strength of a gingival cell line to an agar substratum by the modification of the original "blister" test for adhesives. A cell monolayer was developed on a Petri dish with a hole in the center of the growing surface, overlayed with agar, and the system pressurized to debond the cells from the agar surface. Pressure changes were measured by a capacitance pressure transducer the output of which was measured by a strip-chart recorder. The modulus (E) of the agar overlay was determined and used in the calculation of the adhesive-bond strength (gammaalpha). The gammaalpha yield for the gingival cell line (cell-agar debond) was 48.8 ergs per cm2, and for the control (no cells) (agar-polystyrene debond) was 30.0 ergs per cm2.


Relationship between a stress membrane protein of Oenococcus oeni and glyceraldehyde-3-phosphate dehydrogenases.
The goal of this study was to analyze how the profiles of membrane proteins of Oenococcus oeni change under particular stress conditions of wine. Sodium dodecyl sulfate polyacrylamide gel electrophoresis protein profiles of membrane fraction showed that a 40-kDa protein was overexpressed in the presence of SO2. The sequence of its N-terminal fragment showed a significant identity with glyceraldehyde-3-phosphate dehydrogenases (GAPDHs), but the protein showed no GAPDH activity. This sequence was compared with those of other GAPDHs with ClustalW alignment, and it was found to be somewhat similar to that of the cell-wall and membrane proteins of other lactic acid bacteria.


Does accelerometry reflect hand function in infants at risk of unilateral cerebral palsy? A secondary analysis of BB-Bim results.
Infants at high-risk of unilateral Cerebral Palsy (UCP) may have asymmetry in upper extremity movement and function, which should be identified as soon as possible for management. To explore the feasibility of using two AX3 Axivity monitors in wrist-worn bracelets to quantify movements, and to identify whether accelerometry parameters are consistent with hand function. 6 infants at high risk of UCP (aged 3 to -12 months) were included in a Single-Case Experimental Design to explore the impact of an 8-week bimanual stimulation home program. Each week of the baseline (randomized duration 4-7 weeks) and 8-week program, the Hand Assessment for Infants (HAI) was performed and accelerometry parameters were collected during HAI and also during spontaneous activity, several times a week. Actimetry was analyzed during HAI and 238 spontaneous activity sessions (mean 42 ± 21 min). Actimetry ratios distribution and evolution show a high variability, especially for spontaneous activity. No strong correlation was found between HAI scores and accelerometry parameters, either collected during HAI, or during spontaneous activity times. Despite its feasibility, using accelerometry bracelets looks unreliable for detecting and monitoring hand function in infants under one year.


Human beta-globin messenger RNA. I. Nucleotide sequences derived from complementary RNA.
Sequence analysis studies were carried out on human beta-globin mRNA (beta-mRNA) prepared from alpha-thalassemic, sickle cell, and Hb A reticulocytes. Highly purified beta-mRNA served as substrate for the preparation of cDNA by RNA-dependent DNA polymerase. The cDNA was transcribed by Escherichia coli RNA polymerase and the resulting cRNA was analyzed. Over 300 nucleotides were assigned to the beta-mRNA coding region and 37 nucleotides were assigned to the 3'-terminal noncoding region. The normal termination codon is UAA which is separated by 28 nucleotides from an out of phase UAA triplet. The origin of each of the abnormally long beta-globin variants Tak and Cranston is consistent with reduplication of dinucleotides prior to the normal termination codon, and both globin variants can terminate at the out of phase UAA.


Isolation and characterization of two novel halotolerant Catechol 2, 3-dioxygenases from a halophilic bacterial consortium.
Study of enzymes in halophiles will help to understand the mechanism of aromatic hydrocarbons degradation in saline environment. In this study, two novel catechol 2,3-dioxygenases (C23O1 and C23O2) were cloned and overexpressed from a halophilic bacterial consortium enriched from an oil-contaminated saline soil. Phylogenetic analysis indicated that the novel C23Os and their relatives formed a new branch in subfamily I.2.A of extradiol dioxygenases and the sequence differences were further analyzed by amino acid sequence alignment. Two enzymes with the halotolerant feature were active over a range of 0-30% salinity and they performed more stable at high salinity than in the absence of salt. Surface electrostatic potential and amino acids composition calculation suggested high acidic residues content, accounting for their tolerance to high salinity. Moreover, two enzymes were further characterized. The enzymes activity both increased in the presence of Fe(3+), Fe(2+), Cu(2+) and Al(3+) and showed no significant inhibition by other tested metal ions. The optimal temperatures for the C23Os were 40 °C and 60 °C and their best substrates were catechol and 4-methylcatechol respectively. As the firstly isolated and characterized catechol dioxygenases from halophiles, the two halotolerant C23Os presented novel characteristics suggesting their potential application in aromatic hydrocarbons biodegradation.


A genome wide quantitative trait linkage analysis for serum lipids in type 2 diabetes in an African population.
Lipid abnormalities are strongly linked with coronary heart disease and are common in type 2 diabetes. However, little is known about the genetic determinants of serum lipids in African populations. An autosomal genome scan was performed for linkage to five plasma lipid phenotypes (total cholesterol, triglycerides (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and VLDL-cholesterol (VLDL-C)) in the Africa-America Diabetes Mellitus (AADM) study. Two hundred and ninety-five affected sibling pairs with type 2 diabetes mellitus enrolled from Ghana and Nigeria were genotyped for 390 microsatellite markers with an average inter-marker distance of 9cM. Multipoint variance components linkage analysis showed that HDL-C had a LOD score of 4.34 near marker D7S3061 and 3.00 near marker D7S513. Some clustering of linkage evidence to several lipid phenotypes was observed on chromosomes 5 (LDL-C, total cholesterol, VLDL-C), chromosome 7 (HDL-C, TG) and chromosome 19 (total cholesterol, LDL-C, TG). Principal component analysis of the five phenotypes yielded two factors, one (TG, HDL-C and VLDL) of which was linked to QTLs on chromosomes 2, 5 and 7, while the other (total cholesterol and LDL-C) was linked to a different set of QTLs on chromosomes 2, 5 and 18. Several of these regions have been reported to be linked to lipids in other studies. Follow up investigations are warranted in view of the central role serum lipids play in the aetiopathogenesis of cardiovascular disease.


Pulmonary artery occlusion post immunotherapy for hilar node-positive lung cancer.
We present the case of a patient who developed pulmonary artery occlusion following immune-checkpoint inhibitor (ICI) therapy for non-small cell lung cancer. A 69-year-old man with squamous cell carcinoma (yc-T1cN0M0), initially diagnosed at c-stage IVA (T3N1M1b), in the upper lobe of the left lung, was scheduled to undergo salvage lung resection after ICI therapy. However, he exhibited an occlusion of the lingular pulmonary artery near the clinically metastatic hilar lymph node. To avoid severe adhesions, the patient underwent successful wedge resection without dividing pulmonary vessels and was discharged without complications. Surgeons should be prepared for pulmonary artery changes following ICI therapy.


Refining the Apgar score cut-off point for newborns at risk.
To evaluate the Apgar score predictive power for mortality during different periods in the first year of life in a population with a very low mortality rate. The records of all singleton live births without severe congenital malformations and length of gestation >25 wk (n = 976635) were collected from the Swedish Medical Birth Registry, 1990 to 1998. Receiver operating characteristic (ROC) analysis was utilized. Both the 1-min and the 5-min Apgar scores were shown to be good discriminators for early mortality, with the area under the ROC curve >0.85. For babies at risk of early death, the selected cut-off values for the 1-min Apgar score was <8 for preterm (true-positive (TP) rate: 83.9%; false-positive (FP) rate: 17.7%) and term babies (TP rate: 69.4%; FP rate: 6.7%). At 5 min, the analysis revealed that newborns with an Apgar score <9 were at risk for early death (preterm babies: TP rate: 79.8%; FP rate: 13.3%; term babies: TP rate: 73.8%; FP rate: 3.4%). Our analysis did not support the common practice in the clinic or in research of grouping infants at risk in Apgar score groups, i.e. a score below 4 or a score below 7. However, the data presented here allow the clinicians and researchers to identify and define a suitable cut-off point in relation to the quality of neonatal care and resources available, rather than adhering to a historical cut-off value that has not been studied in depth.


High-sensitivity C-reactive protein and white blood cell count equally predict development of the metabolic syndrome in a Japanese health screening population.
To compare high-sensitivity C-reactive protein (hs-CRP) and white blood cell count (WBC) as a predictor of metabolic syndrome (MetS). Hazard ratios (HRs) adjusted for age, smoking, and other confounding covariates and areas under receiver operating characteristic curve (AUCs) of hs-CRP and WBC for developing MetS were calculated in 1,463 men and 920 women from a Japanese health screening population who were free from MetS, diabetes, histories of coronary heart disease, and stroke at baseline and followed through 3 years. The adjusted HRs (95% confidence interval-CI; p value) of MetS for each 1 SD increases in log hs-CRP, and log WBC were 1.345 (1.166-1.553; <0.001) and 1.406 (1.188-1.664; <0.001), respectively, in men and 1.388 (1.110-1.736; 0.004) and 1.358 (1.072-1.721; 0.011), respectively, in women. However, the HRs became nonsignificant after further adjusted for the components of MetS. The AUCs (95% CI; p value) of hs-CRP and WBC for predicting MetS were 0.616 (0.573-0.660; <0.001) and 0.613 (0.566-0.659; <0.001), respectively, in men and 0.636 (0.573-0.698; <0.001) and 0.606 (0.538-0.673; 0.003), respectively, in women. Hs-CRP and WBC equally predict development of MetS, but both are poor predictors of MetS in a Japanese health screening population where obesity is not prevailing.


Pneumonia among under-five children in Alexandria, Egypt: a case-control study.
Pneumonia among under-five children constitutes a major public health concern. Studies examining risk factors for pneumonia in Egypt are limited. To identify risk factors of pneumonia among under-five children in Alexandria, Egypt. An observational case-control study was conducted over a 5-month period (September 2017-January 2018) in three main pediatric hospitals in Alexandria. A predesigned questionnaire was used to interview 660 mothers of under-five children (330 pneumonia cases and 330 control). The questionnaire included potential risk factors for pneumonia which were categorized into child-related factors, socio-demographic factors, and environmental factors. The mean age of the children was 23.14 ± 18.61 months with a range of 1-59 months. Nearly two-thirds (58.5%) were boys. Nine factors were found to be independently associated with pneumonia: age ≤ 12 months (OR = 1.925; 95% CI, 1.356-2.733; P < 0.001), male gender (OR = 1.646; 95% CI, 1.162-2.332; P = 0.005), birth order ≥ 4 (OR = 2.154; 95% CI, 1.282-3.617; P = 0.004), low birth weight (OR = 2.562; 95% CI, 1.718-3.821; P < 0.001), prematurity (OR = 2.019; 95% CI, 1.154-3.531; P = 0.014), place of delivery either at home (OR = 5.669; 95% CI, 1.063-30.237; P = 0.042) or at a public hospital (OR = 1.616; 95% CI, 1.131-2.310; P = 0.008), presence of concomitant illness (OR = 1.902; 95% CI, 1.043-3.469; P = 0.036), poor home aeration (OR = 3.586; 95% CI, 1.971-6.522; P < 0.001), and exposure to outdoor air pollution (OR = 2.403; 95% CI, 1.417-4.076; P = 0.001). Several risk factors were significantly related to pneumonia among under-five children. Identifying such factors is important for developing interventions to reduce pneumonia burden among under-five in Egypt.


A comprehensive model of allergic rhinitis in guinea pigs.
The economic and social impact of allergic rhinitis is substantial. The effectiveness of currently available medications is limited and therefore investigations for more effective drugs is essential. This study was intended to establish a model of allergic rhinitis in guinea pigs that can be utilized for further investigation of new drugs. Male Dunkin Hartley guinea pigs were sensitized intranasally to, and challenged with, ovalbumin. Sneezing (SN) and nose rubbing (NR) response to allergen challenge were observed on day 21 post-initiation of sensitization in conscious guinea pigs. Nasal blockade (NB), leukocyte infiltration, and lung inflation pressure (LIP) were assessed in the same guinea pigs 23-28 days post-initiation of sensitization. A ventilator/flow method was used to measure NB and LIP. Leukocyte infiltration into nasal lavage fluid 60 min after challenge in the same animals was recorded as total and differential cell counts. Sensitized guinea pigs produced acute allergic responses after allergen challenge. This was characterized by increases in SN, NR, NB, and eosinophil infiltration. In addition, intranasal allergen challenge did not change lung inflation pressure. Allergen-induced rhinitis in guinea pigs resembles that in humans. The model reported in this study can be used to reflect the effectiveness of drugs currently used to treat allergic rhinitis and to investigate new potential drugs for the treatment of allergic rhinitis.


Immunosuppressive treatment of idiopathic thrombocytopenic purpura in children.
Eleven children with symptomatic idiopathic thrombocytopenia were treated with immunosuppressive agents. Ten children received cyclophosphamide; 1 was given azathioprine. Only 1 child produced a full response, and 6 subsequently needed splenectomy which was curative. It is concluded that immunosuppressive treatment is ineffective in childhood thrombocytopenia and that splenectomy remains the treatment of choice for the rare case which fails to settle spontaneously or respond to corticosteroids.


[Osteotomy as access: iliac spine and iliac crest].
Autologous bone transplants are still the gold standard for defect filling materials and no other material has such a high biological potential. Proven surgical techniques for harvesting cancellous and cortical autografts in the pelvis, the problems and complications are described. The second part of the paper explains the safe handling of osteotomy of the superior anterior iliac spine for pelvic osteotomy and tumor surgery.


Brain angiotensin II binding and central [Sar1,Ala8]angiotensin responses in normal rats and the New Zealand strain of genetically hypertensive rats.
1. Specific angiotensin II (ANGII) receptor binding was measured in regions of the brains of the New Zealand gentically hypertensive and normal rats. 2. ANGII receptor binding was consistently lower in the septum, midbrain, thalamus and posterior medulla of the genetically hypertensive rats than in normal rats. 3. Blood pressure responses to intraventricular injections of ANGII and an ANGII antagonist [Sar1,Ala8]angiotensin were studied in conscious and pentobarbitone-anaesthetized genetically hypertensive and normal rats. In conscious rats no significant difference between the two strains of rat was detected. 4. In pentobarbitone-anaesthetized rats intraventricular injection of 40 microgram of [Sar1,Ala8]angiotensin had a hypotensive effect which was three times greater in the genetically hypertensive rats than that observed in normal rats. The latency of this hypotensive effect was longer than the latency of the hypertensive effect of ANGII. 5. The drinking responses to intraventricular injections of ANGII were similar in genetically hypertensive and normal rats. 6. The physiological role of the ANGII system is discussed and it is concluded that an abnormality of this system in the brain may well be responsible for the hypertension found in the genetically hypertensive rat.


High-resolution manometry in patients with idiopathic inflammatory myopathy: Elevated prevalence of esophageal involvement and differences according to autoantibody status and clinical subset.
In this study we assessed high-resolution manometry (HRM) findings in patients with dermatomyositis and polymyositis. From 2008 to 2015, we performed a cross-sectional study of myositis patients. A survey of esophageal symptoms and HRM data were analyzed and compared among different clinical and serologic groups. Twenty-four (45%) of the 53 patients included in the study had manometric involvement that was not correlated with any esophageal symptom (P = 0.8). Failed waves (34% vs. 0%, P = 0.004) and decreased upper esophageal sphincter pressure (50 vs. 70 mm Hg, P = 0.03) were more common in polymyositis than in dermatomyositis patients. Jackhammer esophagus was more common in anti-TIF1-γ patients (30% vs. 9%, P = 0.04), and lower esophageal sphincter involvement (47% vs. 25%, P = 0.03) was more prevalent in patients with the antisynthetase syndrome. Esophageal involvement is common in myositis patients, but it correlates poorly with esophageal symptoms. Specific clinical and serologic groups have different manometric features. Muscle Nerve 56: 386-392, 2017.


Organic dyes based on selenophene for efficient dye-sensitized solar cell.
The investigation of dye-sensitized solar cells (DSSCs) based on different donor groups linked with cyanoacrylic acid electron acceptor by Selenophene as π-bridged (D-π-A) was performed based on density functional theory (DFT) time-dependent DFT (TDDFT). Different functional were tested W97XD, PBEPBE, CAM-B3LYP, and B3PW91, and compared with experimental results of the reference D1. The theoretical results with CAM-B3LYP functional at 6-311G (d,p) basis sets were capable of predicting the absorption maximum that has been reported experimentally. Calculations were made to establish the conformational orientation of the cyanoacrylic acid group and evaluate the effect of changing donor units' on the electronic properties of the ground state. Structural and electronic properties, along with the photovoltaic properties, were investigated. The LUMO and HOMO energy levels of these dyes can positively affect the process of electron injection and dye regeneration. Light-harvesting efficiency (LHE), injection driving force (ΔGinject), and total reorganization energy (total) were also discussed. To further support the previous proprieties, electronic excited state energies were obtained by TDDFT// CAM-B3LYP/6-311G(d,p) calculations. The calculated results of these dyes reveal that D8 dye possessing triphenylamine donor unit has the best electronic, optical properties, and photovoltaic parameters.


A very significant correlation between carcinogenic activity of polycyclic hydrocarbons and certain properties of their transition states in the range of the lowest triplet states of the DNA.
A very significant correlation between carcinogenic power of polycyclic aromatic hydrocarbons and their probability of photoinduced double resonance transitions in the UV-range of about 3 to 3.5 eV is shown. The resonance can be interpreted in terms of the lowest triplet state energy of thymine at 3.25 eV and the energy difference between the triplet states of A--T and G--C base pairs. The correlation has been predicted from a hypothesis which describes cell communication by photon interaction within a cell population.


Effects of weight loss during a very low carbohydrate diet on specific adipose tissue depots and insulin sensitivity in older adults with obesity: a randomized clinical trial.
Insulin resistance and accumulation of visceral adipose tissue (VAT) and intermuscular adipose tissue (IMAT) place aging adults with obesity at high risk of cardio-metabolic disease. A very low carbohydrate diet (VLCD) may be a means of promoting fat loss from the visceral cavity and skeletal muscle, without compromising lean mass, and improve insulin sensitivity in aging adults with obesity. To determine if a VLCD promotes a greater loss of fat (total, visceral and intermuscular), preserves lean mass, and improves insulin sensitivity compared to a standard CHO-based/low-fat diet (LFD) in older adults with obesity. Thirty-four men and women aged 60-75 years with obesity (body mass index [BMI] 30-40 kg/m2) were randomized to a diet prescription of either a VLCD (< 10:25:> 65% energy from CHO:protein:fat) or LFD diet (55:25:20) for 8 weeks. Body composition by dual-energy X-ray absorptiometry (DXA), fat distribution by magnetic resonance imaging (MRI), insulin sensitivity by euglycemic hyperinsulinemic clamp, and lipids by a fasting blood draw were assessed at baseline and after the intervention. Participants lost an average of 9.7 and 2.0% in total fat following the VLCD and LFD, respectively (p < 0.01). The VLCD group experienced ~ 3-fold greater loss in VAT compared to the LFD group (- 22.8% vs - 1.0%, p < 0.001) and a greater decrease in thigh-IMAT (- 24.4% vs - 1.0%, p < 0.01). The VLCD group also had significantly greater thigh skeletal muscle (SM) at 8 weeks following adjustment for change in total fat mass. Finally, the VLCD had greater increases in insulin sensitivity and HDL-C and decreases in fasting insulin and triglycerides compared to the LFD group. Weight loss resulting from consumption of a diet lower in CHO and higher in fat may be beneficial for older adults with obesity by depleting adipose tissue depots most strongly implicated in poor metabolic and functional outcomes and by improving insulin sensitivity and the lipid profile. NCT02760641. Registered 03 May 2016 - Retrospectively registered.


Longitudinal course of mild parkinsonian signs in elderly people: A population-based study in Japan.
We aimed to clarify the longitudinal course of mild parkinsonian signs (MPS) and their association with dementia and functional disability by conducting a comprehensive epidemiological study, including brain MRI, and assessments of cognition, depression, and sleep, in people aged ≥65years living in Ama-cho. We diagnosed MPS and parkinsonism (PS) using a modified Unified Parkinson's Disease Rating Scale. The phase I study was conducted between 2008 and 2010 (n=729) and the phase II between 2011 and 2013 (n=436). By phase II, 8.5% of the phase I participants without PS had developed PS. In addition to older age, a lower Mini-Mental State Examination (MMSE) score, and lower body mass index, the MPS rigidity subtype was a significant independent predictor of PS onset. By phase II, 10.1% of the participants without dementia or PS at phase I had developed dementia. Older age, lower MMSE score, and the axial dysfunction and tremor MPS subtypes were significant independent predictors of dementia development. By phase II, 38.8% of participants with MPS at phase I showed no motor symptoms. Younger age and adequate sleep were significant predictors for this reversion. Periventricular and deep white matter hyperintensity Fazekas scores increased with the evolution of parkinsonian signs. MPS is therefore critically, although sometimes reversibly, associated with PS and dementia development in elderly people.


Pelvic floor ultrasound imaging: are physiotherapists interchangeable in the assessment of levator hiatal biometry?
To evaluate inter-examiner reliability in the ultrasound (US) assessment of levator hiatal dimensions when different physiotherapists perform independent data acquisition and analysis. In this cross-sectional observational study, 14 asymptomatic nulliparous women were imaged at rest, during pelvic floor muscle contraction, and during Valsalva manoeuvre by two physiotherapists using three-dimensional (3D) and four-dimensional (4D) transperineal US. Examiners each measured the dimensions of the levator hiatus (area and antero-posterior and transverse diameters) from the US volumes they respectively acquired. Inter-examiner reliability was determined using intra-class correlation coefficients (ICCs), and inter-examiner agreement was determined using Bland-Altman analyses. The ICC results demonstrated very good inter-examiner reliability (ICC=0.84-0.98); Bland-Altman results showed high inter-examiner agreement across all measurements. Trained examiners may be considered interchangeable in the US assessment of levator hiatal biometry. Overall, trained physiotherapists using transperineal US imaging to assess levator hiatal biometry can be confident when comparing their own clinical findings to those of their colleagues and to findings published in the literature.


δ-Catenin promotes E-cadherin processing and activates β-catenin-mediated signaling: implications on human prostate cancer progression.
δ-Catenin binds the juxtamembrane domain of E-cadherin and is known to be overexpressed in some human tumors. However, the functions of δ-catenin in epithelial cells and carcinomas remain elusive. We found that prostate cancer cells overexpressing δ-catenin show an increase in multi-layer growth in culture. In these cells, δ-catenin colocalizes with E-cadherin at the plasma membrane, and the E-cadherin processing is noticeably elevated. E-Cadherin processing induced by δ-catenin is serum-dependent and requires MMP- and PS-1/γ-secretase-mediated activities. A deletion mutant of δ-catenin that deprives the ability of δ-catenin to bind E-cadherin or to recruit PS-1 to E-cadherin totally abolishes the δ-catenin-induced E-cadherin processing and the multi-layer growth of the cells. In addition, prostate cancer cells overexpressing δ-catenin display an elevated total β-catenin level and increase its nuclear distribution, resulting in the activation of β-catenin/LEF-1-mediated transcription and their downstream target genes as well as androgen receptor-mediated transcription. Indeed, human prostate tumor xenograft in nude mice, which is derived from cells overexpressing δ-catenin, shows increased β-catenin nuclear localization and more rapid growth rates. Moreover, the metastatic xenograft tumor weights positively correlate with the level of 29kD E-cadherin fragment, and primary human prostate tumor tissues also show elevated levels of δ-catenin expression and the E-cadherin processing. Taken together, these results suggest that δ-catenin plays an important role in prostate cancer progression through inducing E-cadherin processing and thereby activating β-catenin-mediated oncogenic signals.


Lessons learned from 20 years of newborn screening for cystic fibrosis.
To compare three cystic fibrosis (CF) newborn screening strategies used in Victoria since 1989. Retrospective review of newborn screening and clinical records for people with CF born in Victoria between 1989 and 2008 to compare screening strategies: repeat immunoreactive trypsinogen (IRT) testing (IRT/IRT, 1989-1990), IRT and p.F508del mutation analysis (IRT/p.F508del, 1991-2006) and IRT with analysis of 12 CFTR mutations (IRT/12 mutations, 2007-2008). Total number of infants screened, people identified with CF (by screening or clinical diagnosis), number of CF-affected terminations of pregnancy, and number of carriers detected. There were 420 people born with CF (live-birth prevalence, 1/3139; 95% CI, 1/2853-1/3462) and 78 CF-affected pregnancy terminations (overall prevalence, 1/2647; 95% CI, 1/2425-1/2896). Of the babies born with CF, 283 (67.4%) were detected by newborn screening alone, 61 (14.5%) had meconium ileus, 33 (7.9%) had a family history of CF, nine (2.1%) were diagnosed antenatally, and 34 (8.1%) were missed by screening (17 missed because IRT level was < 99th percentile, two with repeat IRT level not elevated, 14 without a screened CFTR mutation, and one with missing data). The sensitivities of the protocols were 86.6% for IRT/IRT, 89.9% for IRT/p.F508del, and 95.8% for IRT/12 mutations. Including 12 mutations in the analysis detected one patient who would otherwise have been missed and, had this protocol been implemented from 1989, it would have detected four others. Most babies with CF without meconium ileus, a family history or antenatal diagnosis are detected by newborn screening. Despite improved sensitivity with the 12-mutation analysis, most infants detected would have been diagnosed using the IRT/p.F508del protocol.


Fluoronaphthyridines as antibacterial agents. 6. Synthesis and structure-activity relationships of new chiral 7-(1-, 3-, 4-, and 6-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)naphthyridine analogues of 7-[(1R,4R)-2,5- diazabicyclo[2.2.1]heptan-2-yl]-1-(1,1-dimethylethyl)-6-fluoro-1,4-dihy dro-4-oxo-1,8-naphthyridine-3-carboxylic acid. Influence of the configuration on blood pressure in dogs. A quinolone-class effect.
A series of novel chiral 7-(1-, 3-, 4-, and 6-methyl-[(1R,4R)-2,5- diazabicyclo[2.2.1]heptan-2-yl]-substituted naphthyridines has been prepared with the aim of obtaining good in vitro and in vivo antibacterial agents with a decrease of the pseudoallergic type reaction when compared to that observed with 7[(1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1-(1,1-dimethylethyl )1,4- dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid (1a) (BMY 40062). The derivatives 7-[(1R,4R,6S)-6-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]- 1-(1,1-dimethylethyl)-6-fluro-1,4-dihydro-4-oxo-1,8-naphthyridine- 3-carboxylic acid (41) and 7-[(1R,4R,6S)-6-methyl-2,5-diazabicyclo[2.2.1]heptan-2- yl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxy lic acid (49) showed potent in vitro and in vivo antibacterial activity against Gram-positive and Gram-negative bacteria. The derivative 49 displayed a less marked decrease in blood pressure (MAP), compared to that of 1a, after intravenous infusion in dogs and was selected as a potential candidate for preclinical trials.


Antiepileptic drug treatment: outcomes and adherence.
The goal in treating patients with epilepsy is a cost-effective approach to the elimination of seizures or a reduction in their number and frequency while avoiding drug interactions and side effects, so as to achieve the best possible quality of life. Among the desirable outcomes are an enhanced understanding of epilepsy by patients, caregivers, and society, and a lessening of the psychosocial risks of this disease. Patients fail to achieve their goals and outcomes when they fail to adhere to the drug regimen or when a less-than-adequate drug regimen is prescribed. To help improve adherence, once- or twice-daily formulations should be used. New antiepileptic drugs (AEDs) increase the possibility of effective treatment for a patient who initially fails therapy. Working together, patients and clinicians can maximize the effectiveness of AED therapy and the potential for achieving desired goals and outcomes.


Colloid milium. A clincopathologic study of four cases.
Four cases of colloid medium are presented. The light and electron microscopic pathological changes are described and the important role of the sunlight exposure in producing these lesions in out-door workers in Iran is emphasized.


Effects of disuse and nerve stump length on the development of fibrillation in denervated soleus muscle.
Both in normal (control) and in cordotomized (disused) rats, the soleus muscle was denervated either by cutting the sciatic nerve near the trochanter (proximal denervation) or by cutting the soleus nerve near the insertion into the muscle (distal denervation). In the control muscles, the development of fibrillation was not dependent on the level of nerve section. In disused muscles, the development of fibrillation was greater following distal denervation that following the proximal one.


Heterologous expression and characterization of ToxA1 haplotype from India and its interaction with Tsn1 for spot blotch susceptibility in spring wheat.
ToxA, a necrotrophic effector protein, is present in the genome of fungal species like Parastagnospora nodorum, Pyrenophora tritici-repentis and Bipolaris sorokiniana. Tsn1 is the sensitivity gene in the host whose presence indicates more susceptibility to ToxA carrying pathogen, and ToxA-Tsn1 interaction follows an inverse gene-for-gene relationship. The present study involved cloning and expressing the ToxA1 haplotype from B. sorokiniana. It was found that the amplicon exhibited an expected product size of 471 bp. Sequence analysis of the ToxA1 nucleotide sequence revealed the highest identity, 99.79%, with P. tritici-repentis. The protein expression analysis showed peak expression at 16.5 kDa. Phylogenetic analysis of the ToxA1 sequence from all the Bipolaris isolates formed an independent clade along with P. tritici-repentis and diverged from P. nodorum. ToxA-Tsn1 interaction was studied in 18 wheat genotypes (11 Tsn1 and 7 tsn1) at both seedling and adult stages, validating the inverse gene-for-gene relationship, as the toxin activity was highest in the K68 genotype (Tsn1) and lowest in WAMI280 (tsn1). The study indicates that the haplotype ToxA1 is prevailing in the Indian population of B. sorokiniana. It would be desirable for wheat breeders to select genotypes with tsn1 locus for making wheat resistant to spot blotch.


Colloid chemistry of nanocatalysts: a molecular view.
Recent advances of a colloidal chemistry can offer great opportunities to fabricate and design nanocatalysts. Comprehensive understanding of a basic concept and theory of the colloidal synthetic chemistry facilitates to engineer elaborate nano-architectures such as bi- or multi-metallic, heterodimers, and core/shell. This colloidal solution technique not only enables to synthesize high surface mesoporous materials, but also provides a versatile tool to incorporate nanoparticles into mesoporous materials or onto substrates. For green chemistry, catalysis research has been pursued to design and fabricate a catalyst system that produces only one desired product (100% selectivity) at high turnover rates to reduce the production of undesirable wastes. Recent studies have shown that several molecular factors such as the surface structures, composition, and oxidation states affect the turnover frequency and reaction selectivity depending on the size, morphology, and composition of metal nanoparticles. Multipath reactions have been utilized to study the reaction selectivity as a function of size and shape of platinum nanoparticles. In the past, catalysts were evaluated and compared with characterizations before and after catalytic reaction. Much progress on in situ surface characterization techniques has permitted real-time monitoring of working catalysts under various conditions and provides molecular information during the reaction.


Progressive atrioventricular conduction block in a mouse myotonic dystrophy model.
Myotonic dystrophy is caused by expansion of a CTG trinucleotide repeat on human chromosome 19, and leads to progressive skeletal myopathy and atrioventricular conduction disturbances. A murine model of myotonic dystrophy has been designed by targeted disruption of the myotonic dystrophy protein kinase (DMPK) gene. The DMPK-deficient mice display abnormalities in A-V conduction characteristics, similar to the human cardiac phenotype. The purpose of this study was to determine whether age-related progression of A-V block occurs in a mouse model of DMPK-deficiency. Surface ECGs and intracardiac electrophysiology (EP) studies were performed in 60 immature and 90 adult homozygous (DMPK-/-), heterozygous (DMPK+/-), and wild-type (WT) DMPK+/+ control mice. Complete studies were obtained on 141 of 150 mice. The RR, PR, QRS, and QT intervals were measured on ECG. Sinus node recovery time, AV refractory periods, paced AV Wenckebach and 2:1 block cycle lengths, atrial and ventricular effective refractory periods were compared between genotypes and age groups. There were no differences in ECG intervals or EP findings in the young mutant mice, but progressive PR prolongation in older mice. The A-V conduction defects are also sensitive to DMPK gene dosage. Adult DMPK-/- mice develop 1 degrees, 2 degrees and 3 degrees A-V block, whereas DMPK+/- mice develop only 1 degrees heart block. These data demonstrate that both age and DMPK dose are important factors regulating cardiac conduction in myotonic dystrophy. This mouse model of DM is remarkably similar to the human phenotype, with age-related progression in atrioventricular conduction defects.


Measurement of the diffusion of liquids into dental restorative resins by stray-field nuclear magnetic resonance imaging (STRAFI).
The purpose of this investigation was to determine the diffusion mechanism for water/ethanol mixtures in a diacrylate dental resin by direct observation of the absorbed liquid profiles using NMR microimaging. Frequency-swept stray-field magnetic resonance imaging (STRAFI) was used. Solutions containing 25-65% by volume ethanol remained in contact with visible light cured 54% TEGDMA: 46% modified TUDMA sheets while measurements were made. The diffusion profiles were recorded periodically for diffusion times up to 10 h, to a depth of 360 microm and with readings taken at 24 microm intervals. For all liquid mixtures, diffusion was found to be Fickian with coefficients that increased progressively and smoothly with alcohol content in the diffusing mixture, from 2.4 x 10(-13) to 150 x 10(-13) m2 s(-1). A rule of mixtures approach, as suggested by Kwei and Zupko, gave a satisfactory description of the ethanol fraction dependence of the diffusivity. Frequency-swept STRAFI offers a new and unique opportunity to produce spatially resolved measurements of the liquids in dental resins to high resolution. In this study, absorption was investigated since an understanding of its mechanism is fundamental to limiting consequent environmental degradation. STRAFI has great potential for other applications, for example drying, liquid exchange, etc. Since STRAFI can discriminate 1H in the liquid from those in softened polymer additional applications are envisaged.


The temperature of bupivacaine 0.5% affects the sensory level of spinal anesthesia.
Three milliliters of plain bupivacaine 0.5% was injected intrathecally in two groups of 20 patients. Group 1 received a solution that had been equilibrated to 37 degrees C, group 2 received a solution that had been equilibrated to 4 degrees C. Patients were kept sitting for 3 minutes after injection. All observations were observer-blind. The differences between segmental levels of sensory loss between groups 1 and 2 (T4 and T9, respectively) and of temperature loss (T3 and T8, respectively) 10 and 20 minutes after injection of bupivacaine were statistically significant. It is concluded that the time needed for thermal equilibration in the cerebrospinal fluid and hence temperature of the injected solution plays an important role in the sensory spread of plain bupivacaine 0.5%.


Dorsal Cheilectomy Using Great Toe Metatarsophalangeal Joint Arthroscopy for the Treatment of Hallux Rigidus.
Great toe metatarsophalangeal joint (MTPJ) arthroscopy has been described in the literature for more than 50 years for treatment of a multitude of first MTPJ pathologies, including hallux rigidus, hallux valgus, and osteochondritis dissecans, among others. Despite this, the use of great toe MTPJ arthroscopy has not become widely used for treatment of these conditions as the result of reported difficulties with adequate visualization of the joint surface and manipulation of surrounding soft-tissue structures with the instruments available. We propose a simple technique with illustrations of the operating room setup and procedural steps to perform a dorsal cheilectomy in those with early-stage hallux rigidus using great toe MTPJ arthroscopy and a minimally invasive surgical burr in a way that is reproducible by foot and ankle surgeons.


Plasma aluminum levels (unstimulated and stimulated): clinical and biochemical findings in 185 patients undergoing chronic hemodialysis for 4 to 95 months.
Plasma aluminum levels (unstimulated and stimulated by deferoxamine infusion), along with signs and symptoms associated with aluminum overload, were evaluated in 185 patients (97 men, 88 women; mean age, 58 +/- 8 years) who had been undergoing dialysis for 4 to 95 months and who were still receiving treatment in 1985 at a free-standing dialysis facility which has always used water purified by reverse osmosis. Monthly water aluminum levels never exceeded 15 micrograms/L; therefore, the major source of aluminum in these patients was oral phosphate binders. Unstimulated plasma aluminum levels ranged from 7 to 392 micrograms/L, averaged 81.5 +/- 56.4, and did not correlate with the duration of dialysis (r = 0.07; P greater than 0.31) or frequency of symptoms. Stimulated plasma aluminum levels increased in a linear fashion (r = 0.57; P less than 0.0001) with time on dialysis; however, there was no statistical association between the stimulated aluminum levels and a variety of nonspecific musculoskeletal or CNS symptoms, evidence of hyperparathyroidism, hematocrit, or calcium or phosphorus levels. These findings suggest that total body aluminum, as reflected in deferoxamine-stimulated serum aluminum levels, increases as a function of time undergoing dialysis.


Treatment of infantile hemangioma by intralesional injection of propranolol combined with compound betamethasone.
To explore the effective and convenient methods of infantile hemangioma treatment. From October 2010 to June 2014, 31 infantile hemangioma patients admitted to our hospital, were administered propranolol combined with betamethasone injection treatment of lesions. All patients were followed for 6 months-2 years. In treated patients, 24 patients with tumor had complete or nearly complete remission while 6 patients showed partial regression. In 1 patient the tumor had no evident change. Adverse reactions of the therapy included local tissue atrophy, ulcer and anorexia, mild diarrhea in the early treatment. Ulcer wound healed after dressing change. Treatment of infantile hemangioma lesions with an injection of propranolol combined with betamethasone showed good efficacy. The method is safe and reliable with clear curative effect, convenient, less complicated, and especially suitable for patients with a small area infantile hemangioma.


Pyrosequencing with di-base addition for single nucleotide polymorphism genotyping.
We develop color code-based pyrosequencing with di-base addition for analysis of single nucleotide polymorphisms (SNPs). When a di-base is added into the polymerization, one or several two-color code(s) containing the type and the number of incorporated nucleotides will be produced. The code information obtained in a single run is useful to genotype SNPs as each allelic variant will give a specific pattern compared to the two other variants. Special care has to be taken while designing the di-base dispensation order. Here, we present a detailed protocol for establishing sequence-specific di-base addition to avoid nonsynchronous extension at the SNP sites. By using this technology, as few as 50 copies of DNA templates were accurately sequenced. Higher signals were produced and thus a relatively lower sample amount was required. Furthermore, the read length of per flow was increased, making simultaneous identification of multiple SNPs in a single sequencing run possible. Validation of the method was performed by using templates with two SNPs covering 37 bp and with three SNPs covering 58 bp as well as 82 bp. These SNPs were successfully genotyped by using only a sequencing primer in a single PCR/sequencing run. Our results demonstrated that this technology could be potentially developed into a powerful methodology to accurately determine SNPs so as to diagnose clinical settings.


Osseous suprascapular canal: rare variant that would hinder suprascapular nerve block and posterior surgical approach.
To report atypical anatomical variation of an osseous suprascapular canal, and to elaborate on its clinical significance as a potential anatomical factor that could obscure a direct posterior surgical approach and suprascapular nerve block. Osteological observational study of the scapula with emphasis on the suprascapular space. The pool of investigated sample size was collectively 768 specimens composed of 529 adult dry scapulae (240 paired, 289 un-paired), 54 children dry scapulae, 135 wet scapulae observed during cadaveric dissections, 47 retrospective 3D CT reconstructions, and 3 retrospective full sequence shoulder MRI. The two reported cases came from the 240 (120 skeleton) observed paired scapulae. Furthermore, the osseous suprascapular canal was examined by X-rays and its internal path was exposed by CT sections. A narrative review was conducted to investigate any relevant reports on the subject matter. Two left dry bone scapulae with unilateral osseous suprascapular canal were found. The incidence of this atypical morphology of an osseous canal is probably five cases reported in three studies including this cases study. The reported cases aid in explaining additional possible anatomical factors that could lead to below threshold anesthetic effect in posterior suprascapular nerve block procedures. Therefore, it is more practical to visualize the suprascapular canal by some imaging method before attempting to blindly access the suprascapular nerve in nerve block or posterior surgical approach due to the rare potential existence of an ossified barrier hindering the procedure. V Basic Science Research.


Anticonvulsant activity of antagonists and partial agonists for the NMDA receptor-associated glycine site in the kindling model of epilepsy.
Several previous studies have shown that competitive and uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists are ineffective as anticonvulsants in fully amygdala kindled rats, i.e. a widely-used model of complex-partial seizures (limbic epilepsy). In the present experiments, different categories of ligands for the NMDA receptor-associated glycine modulatory site were evaluated in the kindling model in rats. For this purpose, the 'silent' glycine antagonist 7-chlorokynurenic acid (7-CKA), the low efficacy glycine partial agonist (+)-HA-966 (R(+)-3-amino-1-hydroxypyrrolid- 2-one), and the high efficacy glycine partial agonist D-cycloserine (D-CS) were used. In view of the poor brain penetration of some of these compounds after systemic administration, all drugs were injected bilaterally into the lateral ventricles of fully kindled rat. Anticonvulsant activity was evaluated by determination of the threshold for induction of focal afterdischarges in the amygdala (ADT) and by monitoring seizure parameters (seizure severity, seizure duration, afterdischarge duration) at ADT current. In addition to anticonvulsant activity, the behavioural adverse effects of test drugs were determined. All three drugs increased the focal seizure threshold, although at different potencies. In terms of injected dosages and percentage ADT increase, the most potent compound was 7-CKA, followed by (+)-HA-966 and D-CS. None of the drugs induced behavioural adverse effects or motor impairment (measured in the rotarod test) at anticonvulsant doses. However, D-CS produced proconvulsant effects at higher doses. The data demonstrate that pharmacological manipulation of the glycine modulatory site of the NMDA receptor is an effective means of increasing seizure threshold in amygdala-kindled rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Somatostatin 1-28 circulates in human plasma.
The gel filtration profile of immunoreactive somatostatin in human plasma in the fasting state is not well established as a consequence of insufficient sensitivity of the combined chromatography and radioimmunoassay procedures usually employed. We here report the gel filtration profiles of plasma samples after somatostatin concentration by batchwise immunoaffinity chromatography. The results clearly and reliably document the presence of a circulating peptide in human plasma with a gel permeation chromatography profile identical to the one of synthetic somatostatin 1-28. Approximately 46% of the total somatostatin-like immunoreactivity in plasma is due to this component.


Semaphorin7A and its receptors: pleiotropic regulators of immune cell function, bone homeostasis, and neural development.
Semaphorins form a large, evolutionary conserved family of cellular guidance signals. The semaphorin family contains several secreted and transmembrane proteins, but only one GPI-anchored member, Semaphorin7A (Sema7A). Although originally identified in immune cells, as CDw108, Sema7A displays widespread expression outside the immune system. It is therefore not surprising that accumulating evidence supports roles for this protein in a wide variety of biological processes in different organ systems and in disease. Well-characterized biological effects of Sema7A include those during bone and immune cell regulation, neuron migration and neurite growth. These effects are mediated by two receptors, plexinC1 and integrins. However, most of what is known today about Sema7A signaling concerns Sema7A-integrin interactions. Here, we review our current knowledge of Sema7A function and signaling in different organ systems, highlighting commonalities between the cellular effects and signaling pathways activated by Sema7A in different cell types. Furthermore, we discuss a potential role for Sema7A in disease and provide directions for further research.


The electronic video endoscope: clinical experience with 1200 diagnostic and therapeutic cases in the community hospital.
Gastrointestinal endoscopic examinations with the Welch-Allyn and Fujinon electronic video endoscopes were evaluated in four phases in our community hospital endoscopy unit. Resolution and clinical comparisons to fiberoptic instruments offered advantages for the electronic systems. A review of 1200 consecutive procedures for efficacy, safety, and maintenance considerations was conducted. The use of the video endoscopes as first choice for nearly all diagnostic and therapeutic procedures was more favorable than for the ongoing experience with fiberoptic instruments.


Cell damage by oxygen free radicals.
The exposure of isolated and cultured cells to oxygen free radicals generated extracellularly or intracellularly during the metabolism of foreing compounds results in the development of damage that eventually lead to cell death. Multiple mechanisms are involved in these cytopathological processes, including direct attack of free radicals to macromolecules essential for cell life, as well as indirect activation of catabolic processes such as proteases, endonucleases and phospholipases. A key role in triggering these indirect events is played by Ca(2+) whose cytosolic concentration during oxidative stress raises well above the physiological limits.


Dietary nucleotides do not alter erythrocyte long-chain polyunsaturated fatty acids in formula-fed term infants.
There have been conflicting reports regarding the effectiveness of dietary nucleotides (NT) to regulate tissue desaturases and hence stimulate accumulation of both n-6 and n-3 long-chain polyunsaturated fatty acids (LCPUFA). The aim of this study was to examine the effect of NT-supplemented cow's milk-based formula on erythrocyte phospholipid FA status in a large randomized controlled trial involving a well-nourished infant population born at term. Formula-fed infants were allocated to control formula with an innate level of NT at 10 mg/L (n = 102), or formula fortified with NT at 34 mg/L (n = 98). A parallel group of breastfed infants was included as a reference. Peripheral blood samples were collected by venipuncture at 7 mon of age and erythrocyte phospholipid FA determined by capillary GC. Erythrocyte LCPUFA levels did not differ between the NT-supplemented and control formula groups and were reduced in both groups compared with breastfed infants. We conclude that there is no induction of LCPUFA accumulation in erythrocyte phospholipids of term, formula-fed infants following 7 mon of NT supplementation.


Automated derivation and refinement of sequence length patterns for protein sequences using evolutionary computation.
Several stratagems are used in protein bioinformatics for the classification of proteins based on sequence, structure or function. We explore the concept of a minimal signature embedded in a sequence that defines the likely position of a protein in a classification. Specifically, we address the derivation of sparse profiles for the G-protein coupled receptor (GPCR) clan of integral membrane proteins. We present an evolutionary algorithm (EA) for the derivation of sparse profiles (signatures) without the need to supply a multiple alignment. We also apply an evolution strategy (ES) to the problem of pattern and profile refinement. Patterns were derived for the GPCR 'superfamily' and GPCR families 1-3 individually from starting populations of randomly generated signatures, using a database of integral membrane protein sequences and an objective function using a modified receiver operator characteristic (ROC) statistic. The signature derived for the family 1 GPCR sequences was shown to perform very well in a stringent cross-validation test, detecting 76% of unseen GPCR sequences at 5% error. Application of the ES refinement method to a signature developed by a previously described method [Sadowski, M.I., Parish, J.H., 2003. Automated generation and refinement of protein signatures: case study with G-protein coupled receptors. Bioinformatics 19, 727-734] resulted in a 6% increase of coverage for 5% error as measured in the validation test. We note that there might be a limit to this or any classification of proteins based on patterns or schemata.


Aesthetics and lateral thoracotomy in the neonate.
Lateral thoracotomy is a relatively common procedure in the neonate. Early reports on the incidence of shoulder deformity, scoliosis, and winged scapula rapidly led to a muscle-sparing approach. Scar cosmesis, however, received less attention. Better education and increasing sophistication have led to a higher aesthetic expectation by the public. Since 1988 the authors have combined both principles in the high axillary skin crease approach to lateral thoracotomy in 27 children with esophageal atresia and tracheoesophageal fistula and two children with a patent ductus arteriosus. Access was not restricted, and early healing was uncomplicated by wound breakdown or infection. Scar aesthetics is excellent and is enhanced by the natural tendency of the scar to migrate into the axilla. Long-term morbidity has been singularly absent. Parent appreciation and operator satisfaction have been noteworthy.


Effects of the international economic sanctions on access to medicine of the Iranian people: A systematic review.
We hypothesized that the international economic sanctions have affected various groups of Iranian people and have compromised their right to access medicines. Scopus and MEDLINE from their inception to 15 May 2022 were systematically searched for related published original manuscripts. The following keywords were used (title/abstract): "sanction(s)" AND "Iran". The inclusion criteria were all human studies and articles written in English. We could identify 24 articles. Sanctions have severely restricted patients with thalassemia, haemophilia, epilepsy, and multiple sclerosis from receiving their medical needs. Surveys and interviews of patients, healthcare professionals, and policy-makers have repeatedly shown that sanctions have greatly affected the health system in Iran. International economic sanctions have limited access of the Iranian people to medicines and are associated with the suffering of Iranians. This situation should provide a lesson for policymakers in other similar instances worldwide.


Gingival Toll-like receptor and cytokine messenger RNA levels in equine periodontitis and oral health.
Equine periodontitis is a common and painful condition. However, the disease often goes unnoticed by owners and is thus a major welfare concern. The aetiopathogenesis of the condition remains poorly understood and has been investigated in few studies. The innate immune system is known to play an important role in human periodontitis, but its role in equine periodontitis has not been examined. To quantify the messenger (m)RNA levels of Toll-like receptors (TLRs) and cytokines in gingival tissue from orally healthy horses and those affected by periodontitis. Observational study. Gingival tissue samples were taken post-mortem from 13 horses with no clinical signs of oral disease and 20 horses with periodontitis. mRNA levels of TLR2, TLR4 and TLR9 and cytokines interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), IL-4, IL-6, IL-10, IL-12, IL-17 and interferon-γ (IFN-γ) were determined using quantitative real-time PCR. The statistical significance of results was assessed using appropriate t tests. mRNA levels of all TLRs and cytokines were upregulated in equine periodontitis. Significant increases in mRNA levels of TLR2, TLR9, IL-4, IL-10, IL-12 (P≤0.05) and IFN-γ (P≤0.01) were observed for both unweighted and age-weighted analyses of diseased gingival tissue samples compared with healthy gingival samples. In comparisons of samples of periodontitis lesions with healthy gingival control samples from the same horse, significant increases in mRNA levels of TLR4, TLR9, IL-10, IFN-γ (P≤0.05), TLR2, IL-1β and IL-12p35 (P≤0.01) were observed. This study has provided an initial insight into the involvement of the immune system in equine periodontitis. Increased mRNA levels of TLR2, TLR4 and TLR9 indicate substantial microbial challenge in diseased gingival tissue. A mixed Th1/Th2/Th17 cytokine response is produced in equine periodontitis. Further studies are required to more fully characterise the role of the innate immune system in this disease.


Point-of-care hand hygiene: preventing infection behind the curtain.
Best practices for hand hygiene provide indications for performance of hand hygiene at specific points in time during patient care. For hand hygiene to prevent infections, hand hygiene resources must be readily available to health care workers whenever required. This article reviews practices and recommendations intended to facilitate hand hygiene behavior at the point of care (POC) within the health care setting. Key aspects of POC hand hygiene include the provision of alcohol-based hand rub products, integration of dispensing solutions within the patient zone, consideration of patient care workflow, and dispenser designs that optimize acceptance and usage.


Lactulose ingestion increases faecal bifidobacterial counts: a randomised double-blind study in healthy humans.
Faecal bifidobacteria and lactobacilli, perceived as exerting health-promoting properties, may be increased by ingestion of high-dose lactulose in humans. The effects of low and well-tolerated doses of lactulose are not well known. The aim of the study was to assess the effects of prolonged low-dose lactulose administration on faecal bifidobacteria and selected metabolic indexes potentially involved in colonic carcinogenesis. In all, 16 healthy volunteers were included in this controlled, randomised, double-blind, parallel group trial. Participants ingested lactulose or placebo (sucrose) at a dose of 5 g b.i.d. for 6 weeks. Stools were regularly collected at baseline (d0), and after 3 (d21) and 6 (d42) weeks of sugar ingestion. Tolerance was evaluated using a daily chart. Faecal bifidobacterial counts were higher in lactulose than in sucrose group (P=0.03). Lactulose ingestion led to a significant increase in faecal bifidobacteria counts from d0 to d21 and d42 ((m+/-s.e.m.) 8.25+/-0.53, 8.96+/-0.40 and 9.54+/-0.28 log colony-forming units/g wet wt (CFU/g), respectively (P=0.048)). Placebo ingestion did not lead to any faecal bifidobacterial count change. Total anaerobes, Lactobacillus and pH were not significantly changed throughout the study in the two groups. Neither faecal bile acids nor neutral sterols were modified by lactulose. Excess flatus was more common in the lactulose group (P=0.03), but was very mild. Bloating and borborygmi did not differ between both the groups. A measure of 10 g lactulose/day increases faecal bifidobacterial counts, and lactulose fulfils the criteria requested to be considered as a prebiotic.


Effects of fresh frozen plasma, Ringer's acetate and albumin on plasma volume and on circulating glycocalyx components following haemorrhagic shock in rats.
Early use of fresh frozen plasma (FFP) in haemorrhagic shock is associated with improved outcome. This effect may partly be due to protection of the endothelial glycocalyx and/or secondary to a superior efficacy of FFP as a plasma volume expander compared to crystalloids. The objective of the present study was to investigate if protection of the glycocalyx by FFP can be demonstrated when potential differences in plasma volume (PV) following resuscitation are accounted for. Rats were subjected to a volume-controlled haemorrhage (30 ml/kg). At 2.5 h after haemorrhage, animals were randomized to resuscitation with FFP (37.5 ml/kg), albumin (30 ml/kg) or Ringer's acetate (RA) (135 ml/kg, 4.5 times the bleed volume). PV was measured 2 h after completion of resuscitation using (125)I-albumin and effects on endothelial glycocalyx were evaluated by measuring circulating heparan sulphate and syndecan-1. Hemodynamic effects of resuscitation were evaluated by measuring lactate and mean arterial pressure (MAP). Resuscitation with FFP or albumin resulted in plasma volume expansion equalling the blood loss (to 55 ± 5 ml/kg and 54 ± 4 ml/kg (mean ± S.D.), respectively), whereas plasma volume expansion in RA group was lower (to 42 ± 7 ml/kg). Plasma concentration of heparan sulphate was lower in the FFP and albumin groups than in the RA group at 2 h after resuscitation. After correcting for differences in plasma volume, no significant difference in circulating amount of heparan sulphate was detected between the FFP and albumin groups (2879 ± 1075 μg/kg and 3318 ± 1814 μg/kg, respectively, P = 0.4) and the RA group (3731 ± 777 μg/kg). No differences between the groups in plasma concentration or amount of circulating syndecan-1 were detected after resuscitation. After resuscitation, MAP was higher in the FFP and albumin groups than in the RA group. Lactate did not differ between the FFP and RA groups after resuscitation. Improved outcome in trauma by FFP could in part be explained by better plasma volume expansion compared to crystalloids. The decrease in plasma concentration of markers of glycocalyx degradation after resuscitation with FFP are largely secondary to differences in plasma volume and may not accurately reflect effects of FFP on the glycocalyx.


Reconstructing Foveola by Foveolar Internal Limiting Membrane Non-Peeling and Tissue Repositioning for Lamellar Hole-Related Epiretinal Proliferation.
Differences in the pathogenesis and clinical characteristics between lamellar macular hole (LMH) with and without LMH-associated epiretinal proliferation (LHEP) can have surgical implications. This study investigated the effects of treating LHEP by foveolar internal limiting membrane (ILM) non-peeling and epiretinal proliferative (EP) tissue repositioning on visual acuity and foveolar architecture. Consecutive patients with LHEP treated at our institution were enrolled. The eyes were divided into a conventional total ILM peeling group (group 1, n = 11) and a foveolar ILM non-peeling group (group 2, n = 22). In group 2, a doughnut-shaped ILM was peeled, leaving a 400-μm-diameter ILM without elevated margin over the foveola after EP tissue repositioning. The EP tissue was elevated, trimmed, and inverted into the LMH. Postoperatively, the LMH was sealed in all eyes in group 2, with significantly better best-corrected visual acuity (-0.26 vs -0.10 logMAR; p = 0.002). A smaller retinal defect (p = 0.003), a more restored ellipsoid zone (p = 0.002), and a more smooth foveal depression (p < 0.001) were achieved in group 2. Foveolar ILM non-peeling and EP tissue repositioning sealed the LMH, released the tangential traction, and achieved better visual acuity. The presumed foveolar architecture may be reconstructed surgically. LMH with LHEP could have a combined degenerative and tractional mechanism.


Profile of morbidity among elderly at home health care service in Southern Saudi Arabia.
This study aimed to determine the profile of morbidity among elderly registered at home health care service in the Armed Forces Hospital of Southern Region, Kingdom of Saudi Arabia. A retrospective study was conducted (over a period of 6 months during year 2011) and data was collected by reviewing of medical records of all elderly patients of elderly. The total number of elderly ≥ 60 years were 880. The most prevalent morbidity is hypertension (59.1%) followed by diabetes mellitus (57.3%), stroke (34.9%), dementia (28.5%), osteoarthritis (24.2%) and Alzheimer (21.4%). Females are at higher risks of having many types elderly diseases compared to males. The highest risk was for obesity (OR = 9.1; 95% CI = 3.51- 12.8), followed by osteoporosis (OR = 8.7; 95% CI = 15.10 - 9.13) and fracture neck femur (OR = 3.9; 95 CI = 2.11 - 6.91). In addition, females were also at higher risks of having Osteoarthritis and thyroid disorder. On the other hand, males are more susceptible to hypertension (OR = 1.4; 95 % CI = 1.07 - 1.85), stroke (OR = 1.3; 95 % CI = 1.08 - 1.89) and renal diseases (OR = 2.4; 95% CI = 1.25 - 4.54). It is concluded that there is a great need for preventive, curative and rehabilitative program in order to introduce high quality of health care services to elderly.


The Impact of Stigma and Social Support on Development of Post-traumatic Growth Among Persons Living with HIV.
Given high rates of trauma in people living with HIV (PLH) and the health benefits of posttraumatic growth (PTG), understanding how to foster PTG in PLH exposed to trauma could be of interest to clinical psychologists working with this population. The current study examined factors theoretically related to development of PTG in PLH, namely HIV-related stigma, disclosure of HIV status, and emotional support. A sample of 334 HIV-positive adults answered a battery of self-report questionnaires. HIV-related stigma, disclosure to sexual partners, and emotional support were significant predictors of PTG: stigma was associated with lower PTG, whereas disclosure and emotional support were associated with higher PTG. Disclosure and emotional support remained significantly associated with PTG in the model including demographic factors and stigma. These findings highlight the need for development of interventions that can aid PLH in disclosing their HIV status to sexual partners and increasing available social support.


Interactive effects of serotonin and acetylcholine on neurite elongation.
Serotonin (5-HT) inhibits elongation of neurites of specific identified neurons. Here we report a novel, growth-enabling action of another neurotransmitter, acetylcholine (ACh). When applied simultaneously with serotonin, ACh prevents the inhibition of Helisoma neuron B19 neurite elongation that would occur in response to application of 5-HT alone. We also report that ACh prevents the rise in growth cone Ca2+ that would occur in response to application of 5-HT alone and that ACh blocks the electrical excitatory effect of 5-HT on neuron B19. These results support the hypothesis that growth cone motility and neurite elongation can be regulated by voltage-gated Ca2+ fluxes and suggest that the dynamics of neurite morphology may be complexly regulated by an array of neurotransmitters, as is functional electrical activity.


An innovative S-scheme AgCl/MIL-100(Fe) heterojunction for visible-light-driven degradation of sulfamethazine and mechanism insight.
The development of high efficient photocatalysts for antibiotics contamination in water remains a severe challenge. In this study, a novel step-scheme (S-scheme) photocatalytic heterojunction nanocomposites were fabricated from integrating AgCl nanoparticles on the MIL-100(Fe) octahedron surface through facile multi-stage stirring strategy. The S-scheme heterojunction structure in AgCl/MIL-100(Fe) (AM) nanocomposite provided a more rational utilization of electrons (e-) and holes (h+), accelerated the carrier transport at the junction interface, and enhanced the overall photocatalytic performance of nanomaterials. The visible-light-driven photocatalysts were used to degrade sulfamethazine (SMZ) which attained a high removal efficiency (99.9%). The reaction mechanisms of SMZ degradation in the AM photocatalytic system were explored by electron spin resonance (ESR) and active species capture experiments, which superoxide radical (•O2-), hydroxyl radical (•OH), and h+ performed as major roles. More importantly, the SMZ degradation pathway and toxicity assessment were proposed. There were four main pathways of SMZ degradation, including the processes of oxidation, hydroxylation, denitrification, and desulfonation. The toxicity of the final products in each pathway was lower than that of the parent according to the toxicity evaluation results. Therefore, this work might provide new insights into the environmentally-friendly photocatalytic processes of S-scheme AM nanocomposites for the efficient degradation of antibiotics pollutants.


The receptor for human sex steroid binding protein (SBP) is expressed on membranes of neoplastic endometrium.
Sex steroid binding protein (SBP) receptor was detected on cell membranes obtained from human endometrium adenocarcinoma. The binding of SBP was proved to be highly specific, saturable, and at high affinity. It was, additionally, shown to occur at two sites at different affinities, as previously described for other human tissues. SBP was, therefore, demonstrated to recognized a specific receptor on endometrium adenocarcinoma membranes. The effect of steroid hormones on SBP-receptor interaction was also evaluated. Both dihydrotestosterone and estradiol were shown to inhibit the binding of SBP to its specific receptor on neoplastic membranes. Testosterone at a dose of 10(-9) M was shown not to interfere to a significant extent with SBP-receptor binding. The sensitivity for estradiol we had previously observed in normal premenopausal endometrium was completely lost in postmenopausal neoplastic tissue. These observations suggest that the SBP-membrane recognition system is still present in neoplastic postmenopausal endometrium, but it has been modified either by the postmenopausal endogenous milieu or by the neoplastic transformation.


Thyroarytenoid muscle activity associated with hypophonia in Parkinson disease and aging.
To compare electromyographic (EMG) amplitudes of the thyroarytenoid (TA) muscle in young and older individuals and individuals with idiopathic PD (IPD) under conditions of known vocal loudness (sound pressure level). Voice disorders frequently accompany aging and IPD, but it is unclear how laryngeal muscle physiology is affected by these processes and how changes in laryngeal muscle activity result in characteristic changes of the voice. Absolute and relative (to maximum) EMG amplitudes of the TA muscle were compared during speech and nonspeech tasks. Corresponding sound pressure level (SPL) measures were obtained for the speech tasks. Absolute TA amplitudes were consistently the highest in the young individuals, lowest in the individuals with IPD, and intermediate in the older individuals. Relative TA amplitudes were generally the highest for the young individuals, lowest for the older individuals, and intermediate for the individuals with IPD. SPL findings showed the older individuals and individuals with IPD produced most of the speech tasks with comparable SPLs, and these levels were consistently lower than those of the young individuals. Reduced levels of TA muscle activity may contribute to the characteristic hypophonic voice disorders that frequently accompany IPD and aging.


HDACi-dependent Microenvironmental Normalization Overcomes Tumor Burden-induced T-cell Exhaustion.
T-cell exhaustion limits immunotherapy for the treatment of solid tumors. Although immune checkpoint blockade and adoptive T-cell therapy (ACT) can mediate tumor regression, their potency is often determined by tumor burden. Here, we identified tumor burden-related pathway changes that are conducive to T-cell exhaustion. We then determined whether microenvironmental reprogramming via epigenetic modulation could reverse T-cell exhaustion and improve immunotherapeutic responsiveness. We developed a murine syngeneic tumor model wherein an increased burden ablated therapeutic responsiveness to ACT, which corresponded with systemic induction of T-cell exhaustion. Transcriptome analysis of these large tumors allowed us to characterize changes to immunosuppressive pathway expression during class I histone deacetylase inhibitor MS-275 treatment. We then measured the therapeutic impact of MS-275 during ACT and assessed T-cell exhaustion by transcriptome/phenotypic analysis. ACT durably regressed small tumors but failed to control large tumors, which were associated with systemic T-cell exhaustion and ablation of T-cell responses. Large tumors were defined by an immunosuppressive pathway signature. MS-275 reversed this pathway signature and promoted durable regression of large tumors during ACT. Prototypical exhaustion marker Tim-3 was selectively upregulated in transferred T cells despite displaying a reduced exhaustion signature. Instead, we observed enhanced activation-dependent signaling correlating with enrichment of the IL2-STAT5 signaling axis. Activated CD8+ T-cell responses were predominantly skewed toward terminal effector cell-like CD44+ Tim-3hi TCF1- CD127- KLRG1+ differentiation. Tumor burden-induced pathway changes can be reversed through epigenetic reprogramming, enabling the conversion from T-cell exhaustion to effector lineage differentiation.


SZAP exerts analgesic effects on rheumatalgia in CIA rats by suppressing pain hyperalgesia and inhibiting TRPV1 and P2X3.
ShexiangZhuifeng Analgesic Plaster (SZAP) is a traditional Chinese medicine and transdermal formulation composed of many Chinese herbs and active compounds. SZAP was recently approved by the China Food and Drug Administration for the treatment of pain associated with osteoarticular diseases and is preferred by most rheumatoid arthritis patients in China. However, its mechanism has not been elucidated in detail. We sought to determine the analgesic effect of SZAP in collagen-induced arthritis (CIA) rats and explore the underlying mechanisms of pain transmission, such as via the TRPV1 and P2X3 receptors. After CIA was established, rats were treated with SZAP for 7 days. Paw thickness, arthritis score, and haematoxylin and eosin staining were used to evaluate the effectiveness of SZAP. Paw withdrawal threshold (PWT) and tail-flick latency (TFL) were used to estimate the analgesic effect of SZAP. The levels of PGE2, BK, 5-HT, SP, and CGRP in the serum and synovium were determined using ELISA kits, and ATP in the synovium was measured using HPLC. The expression of TRPV1 and P2X3 in the DRG was detected using western blotting and immunofluorescence. TRPV1 and P2X3 agonists were further used to determine the analgesic effects of SZAP on CIA rats based on PWT and TFL. SZAP not only significantly ameliorated arthritis scores and paw thickness by improving the pathological damage of synovial joints, but also remarkably alleviated pain in CIA rats. Further, treatment with SZAP significantly reduced peripheral 5-HT, PGE2 BK, SP, CGRP, and ATP. Additionally, the expression of TRPV1 and P2X3 in the DRG was markedly downregulated by SZAP. Interestingly, the analgesic effect of SZAP was weakened (reduction of PWT and TFL) when TRPV1 and P2X3 were activated by capsaicin or α,β-meATP, respectively. SZAP ameliorates rheumatalgia by suppressing hyperalgesia and pain transmission through the inhibition of TRPV1 and P2X3 in the DRG of CIA rats.


Sierolomorpha sogdiana spec. nov. from Central Asia, and a World catalogue of Sierolomorphidae (Hymenoptera).
Sierolomorpha sogdiana Lelej & Mokrousov, spec. nov. is described and illustrated from Central Asia (Uzbekistan). A key to the Palaearctic species of Sierolomorpha and a World catalogue of the family Sierolomorphidae (13 species in three genera) are given.


MTT assay with reference to the clinical effect of chemotherapy.
Tumor cells from 40 patients were tested by MTT assay. Five thousand to sixteen thousand tumor cells were plated into 96-well microplates with various concentrations of anticancer agents. After incubation for 48 h, the absorbance of each well was detected with an EIA reader and the effects of the agents were evaluated as positive when the inhibition rate was equal to or more than 50%. Normal cells were also processed under the same conditions, and the absorbance for normal cells was lower than that of tumor cells with statistical significance (P less than 0.05). The efficacy rates of MMC, 5-FU, ADM, and CDDP were 16.7, 8.3, 13.9, and 5.6%, respectively. The overall accuracy of this assay for clinical effects was 83.3%, with one false-positive and five true-negative cases. This MTT assay was also assumed to be useful for in vitro chemosensitivity testing of fresh surgical specimens.


Additive Intralesional Interleukin-2 Improves Progression-Free Survival in a Distinct Subgroup of Melanoma Patients with Prior Progression under Immunotherapy.
A considerable amount of melanoma patients show primary resistance to PD-1 and CTLA-4 inhibitors. We have previously reported a beneficial role of intralesional Interleukin-2 (IL-2) in 9 melanoma patients developing new locoregional metastases under immunotherapy. We have now expanded this retrospective cohort to 27 patients. Patients were evaluated for their tumor characteristics, treatment response and progression-free and overall survival (PFS/OS). In 16 patients, tumor biopsies before and under IL-2 treatment were evaluated for immune markers. The median follow-up time was 16 (1-59) months from start of IL-2 treatment. Treatment response of locoregional metastases was seen in 74% of all patients and response of distant organ metastases in 37% of stage IV patients, respectively. A prolonged PFS and OS was significantly associated with absence of active distant metastases (p = 0.008), response of locoregional metastases (p = 0.002), increase of absolute eosinophil count (AEC) (p < 0.001) and an influx of CD8+ tumor infiltrating lymphocytes (TILs) (p = 0.003). Additional intralesional treatment with IL-2 in patients with locoregional progression under immunotherapy is a well-tolerated, easily feasible therapeutic option especially in patients lacking active distant metastases. A careful patient selection can lead to an improved PFS and OS.


Pronociceptive actions of dynorphin via bradykinin receptors.
The endogenous opioid peptide dynorphin A is distinct from other endogenous opioid peptides in having significant neuronal excitatory and neurotoxic effects that are not mediated by opioid receptors. Some of these non-opioid actions of dynorphin contribute to the development of abnormal pain resulting from a number of pathological conditions. Identifying the mechanisms and the sites of action of dynorphin is essential for understanding the pathophysiology of dynorphin and for exploring novel therapeutic targets for pain. This review will discuss the mechanisms that have been proposed and the recent finding that spinal dynorphin may be an endogenous ligand of bradykinin receptors under pathological conditions to promote pain.


Muscarinic receptor binding characteristics of a human neuroblastoma SK-N-SH and its clones SH-SY5Y and SH-EP1.
The present study examines the muscarinic receptor binding characteristics of parent human neuroblastoma (SK-N-SH) and its neuroblast (SH-SY5Y) and epithelial-like (SH-EP1) clones using [3H]methylscopolamine [( 3H]NMS). Specific [3H]NMS binding to intact SK-N-SH and SH-SY5Y cells was saturable with a Kd of 0.2 nM and Bmax of 100-150 fmol/mg protein. Specific [3H]NMS binding to whole cell preparations of SH-EP 1 could not be detected. Pharmacological analysis of the binding site both in whole cells and membranes of SK-N-SH are indicative of an homogeneous receptor population possessing low affinity for the M1-selective antagonist pirenzepine. The muscarinic receptors expressed by the neuroblast clone, SH-SY5Y were further characterized and shown to have the properties of an homogeneous M3 subtype with low affinity for the M1-selective antagonist pirenzepine and the M2-cardioselective AFDX-116 but high affinity for 4-diphenylacetoxy-N-methyl piperidine methiodide (4-DAMP). In conclusion the SH-SY5Y neuroblastoma should provide an important human neuronal cell model with which to define the regulation of post-receptor events driven by a single receptor population.


Modification of Proteins by Metabolites in Immunity.
Immunometabolism has emerged as a key focus for immunologists, with metabolic change in immune cells becoming as important a determinant for specific immune effector responses as discrete signaling pathways. A key output for these changes involves post-translational modification (PTM) of proteins by metabolites. Products of glycolysis and Krebs cycle pathways can mediate these events, as can lipids, amino acids, and polyamines. A rich and diverse set of PTMs in macrophages and T cells has been uncovered, altering phenotype and modulating immunity and inflammation in different contexts. We review the recent findings in this area and speculate whether they could be of use in the effort to develop therapeutics for immune-related diseases.


Monoamine metabolism in senile dementia of Alzheimer type.
Monoamine metabolism in senile dementia of the Alzheimer-type (SDAT) was assessed by measuring the concentrations of the dopamine metabolite HVA, the noradrenaline metabolite MHPG and serotonin metabolite 5-hydroxy-3-indoleacetic acid (5-HIAA) in post-mortem brains of SDAT patients, a group of control subjects and a group of chronically depressed patients. Concentrations of MHPG and 5-HIAA were significantly reduced in hippocampus and cortical regions of the SDAT group. These changes did not correlate with clinical assessments of the degree of dementia or neuropathological assessment of the degree of Alzheimer-type changes in the SDAT group. It is suggested that changes in monoamine metabolite concentrations are not primarily involved in the pathogenesis of SDAT, and may be secondary to the well established cholinergic deficits.


Effects of the blue-green alga Microcystis aeruginosa on zooplankton competitive relations.
Field distribution patterns and laboratory feeding experiments have suggested that blooms of colonial blue-green algae strongly inhibit relatively large-bodied daphnid cladocerans. We conducted laboratory experiments to test the hypothesis that blooms of the colonial blue-green alga Microcystis aeruginosa would shift competitive dominance away from large-bodied daphnid cladocerans toward smaller-bodied cladocerans, copepods, and rotifers. In laboratory competition experiments, increasing the proportion of M. aeruginosa in the algal food supply resulted in a shift from dominance by the relatively largebodied cladoceran Daphnia ambigua to dominace by the copepod Diaptomus reighardi. The small-bodied cladoceran Bosmina longirostris was always numerically heavily dominant over D. ambigua, but its estimated population biomasses were only slightly higher than those of D. ambigua. Daphnia ambigua consistently outcompeted the rotifer Brachionus calyciflorus. Our results demonstrate that blooms of M. aeruginosa can alter zooplankton competitive relations in laboratory experiments, favoring small-bodied cladocerans and copepods at the expense of large-bodied cladocerans. However, contrary to predictions, blooms of M. aeruginosa did not improve the competitive ability of rotifers.