Sucrose for analgesia in newborn infants undergoing painful procedures.
Administration of oral sucrose with and without non-nutritive sucking is the most frequently studied non-pharmacological intervention for procedural pain relief in neonates. To determine the efficacy, effect of dose and safety of oral sucrose for relieving procedural pain in neonates. We used the standard methods of the Cochrane Neonatal Review Group. Electronic and manual searches were performed in November 2011 for published randomised controlled trials (RCTs) in MEDLINE (1950 to November 2011), EMBASE (1980 to 2011), CINAHL (1982 to November 2011) and the Cochrane Central Register of Controlled Trials (The Cochrane Library). We did not impose language restrictions. RCTs in which term, preterm, or both term and preterm neonates (postnatal age maximum of 28 days after reaching 40 weeks' postmenstrual age) received sucrose for procedural pain. Control conditions included no treatment, water, pacifier, positioning/containing or breastfeeding. Main outcome measures were physiological, behavioural, or both pain indicators with or without composite pain scores. A mean difference (MD) with 95% confidence intervals (CI) using the fixed-effect model was reported for continuous outcome measures. Trial quality was assessed as per The Cochrane Collaboration Fifty-seven studies enrolling 4730 infants were included. Results from only a few studies could be combined in meta-analyses. When Premature Infant Pain Profile (PIPP) scores were pooled, sucrose groups had significantly lower scores at 30 seconds (weighted mean difference (WMD) -1.76; 95% CI -2.54 to - 0.97; 4 trials; 264 neonates] and 60 seconds (WMD -2.05; 95% CI -3.08 to -1.02; 3 trials' 195 neonates) post-heel lance. For retinopathy of prematurity (ROP) examinations, sucrose did not significantly reduce PIPP scores (WMD -0.65; 95% CI -1.88 to 0.59; 3 trials; 82 neonates). There were no differences in adverse effects between sucrose and control groups. Sucrose significantly reduced duration of total crying time (WMD -39 seconds; 95% CI -44 to -34; 2 trials; 88 neonates), but did not reduce duration of first cry during heel lance (WMD -9 seconds; 95% CI -20 to 2; 3 trials; 192 neonates). Oxygen saturation (%) was significantly lower in infants given sucrose during ROP examination compared to controls (WMD -2.6; 95% CI -4.9 to - 0.2; 2 trials; 62 neonates). Results of individual trials that could not be incorporated in meta-analyses supported these findings. The effects of sucrose on long-term neurodevelopmental outcomes are unknown. Sucrose is safe and effective for reducing procedural pain from single events. An optimal dose could not be identified due to inconsistency in effective sucrose dosage among studies. Further investigation on repeated administration of sucrose in neonates and the use of sucrose in combination with other non-pharmacological and pharmacological interventions is needed. Sucrose use in extremely preterm, unstable, ventilated (or a combination of these) neonates needs to be addressed. Additional research is needed to determine the minimally effective dose of sucrose during a single painful procedure and the effect of repeated sucrose administration on immediate (pain intensity) and long-term (neurodevelopmental) outcomes.


Antagonism of chemotherapy-induced cytotoxicity for human breast cancer cells by antiestrogens.
In a prior National Surgical Adjuvant Breast and Bowel Project (NSABP) adjuvant study, the addition of the antiestrogen tamoxifen to chemotherapy with melphalan and fluorouracil adversely affected survival in several patient subsets, suggesting an antagonistic drug interaction. To investigate this possibility, we studied the interaction of tamoxifen and other antiestrogens with several cytotoxic drugs in cultured human breast cancer cell lines. Clinically relevant concentrations of tamoxifen and melphalan reduced colony survival of estrogen receptor (ER)-positive breast cancer cells when used alone in a colony-forming assay. However, pretreatment of cells with tamoxifen followed by exposure to melphalan resulted in antagonism, with more colonies surviving treatment with the combination than with melphalan alone. Identical effects were seen using several other triphenylethelene antiestrogens. An antagonistic interaction was observed even with a brief preincubation with tamoxifen that had no effect on cell proliferation, indicating that antagonism was not due to tamoxifen's known cell kinetic effects. Tamoxifen even antagonized melphalan cytotoxicity in ER-negative breast cancer cells and in cultured liver cells. An additive drug interaction occurred when melphalan was combined with pharmacologic concentrations of estradiol or medroxyprogesterone acetate, but antagonism was also observed with dexamethasone. Tamoxifen also antagonized the cytotoxicity of fluorouracil in these cells. However, an additive interaction occurred when the antiestrogen was combined with doxorubicin or 4-hydroxy-cyclophosphamide, an alkylating agent that is transported into the cell by a different carrier-mediated mechanism than melphalan. To avoid potential antagonism in the clinic, combinations of tamoxifen with melphalan and/or fluorouracil should be avoided.


Effects of pantoprazole as a HIF-1α inhibitor on human gastric adenocarcinoma sgc-7901 cells.
Previously, it has been demonstrated that HIF-1α has close connection with malignant tumor progression, aggressive behavior and prognosis. In addition, proton pump inhibitors (PPIs) have been reported to selectively induce tumor cell apoptosis, thus exerting its anticancer effects. In vitro and in vivo our study revealed that pantoprazole (PPZ) inhibited tumor cells proliferation, induced apoptosis and decreased the expression of HIF-1α protein. In summary, PPZ could suppress tumor growth acting as a HIF-1α protein inhibitor.


Ewing's sarcoma of the sacrum.
Radiological findings in a case of spinal Ewing' s sarcoma are reported. A lytic lesion with soft tissue component in the sacrum was identified. Ewing's sarcoma should be included in the differential diagnosis, especially when a child has a lytic lesion with soft tissue extension in the spine.


Coffee consumption and blood pressure: an Italian study.
The relation between habitual coffee consumption and blood pressure was studied in 500 Italian subjects, males and females, aged 18-62 years. After allowing for sex, age and weight, the pressure levels showed a significant decrease with increasing coffee consumption. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were respectively 130.4 +/- 1.8 (SE) mmHg and 81.5 +/- 1.1 mmHg for non-coffee drinkers, 129.4 +/- 1.4 and 82.2 +/- 0.9 mmHg for 1 cup per day, 128.4 +/- 0.8 and 81.4 +/- 0.5 mmHg for 2-3 cups per day, 124.9 +/- 1.1 and 78.8 +/- 0.7 mmHg for 4-6 cups per day, and 124.1 +/- 2.5 and 78.7 +/- 1.6 mmHg for more than 6 cups of coffee daily (analysis of covariance: SBP F = 3.46, 4 df, P less than 0.01; DBP F = 3.46, 4 df, P less than 0.01). Even after correcting pressure levels for habitual alcohol intake and cigarette smoking, we observed a mean reduction in SBP and DBP of 0.80 mmHg and 0.48 mmHg respectively per cup per day.


Placement of occipital condyle screws for occipitocervical fixation in a pediatric patient with occipitocervical instability after decompression for Chiari malformation.
In cadaveric studies and recently in one adult patient the occipital condyle has been studied as an option to allow bone purchase by fixation devices. In the current case the authors describe the use of occipital condyle screws in a child undergoing occipitocervical fixation. To the best of the authors' knowledge this case is the first reported instance of this technique in a pediatric patient. This girl had a history of posterior fossa decompression for Chiari malformation Type I when she was 22 months of age. When she was 6 years old she presented with neck pain on flexion and extension of her head. Magnetic resonance imaging in flexion and extension revealed occipitocervical instability. She underwent an occiput to C-2 posterior arthrodesis with bilateral screw placement in the occipital condyles, C-2 lamina, and C-1 lateral masses. Postoperatively, she was neurologically intact. Computed tomography demonstrated a stable construct, and her cervical pain had resolved on follow-up.


Rhizobium oryzae sp. nov., isolated from the wild rice Oryza alta.
During a study of endophytic nitrogen-fixing bacteria present in the wild rice species Oryza alta, eight novel isolates were obtained from surface-sterilized roots and classified in the genus Rhizobium on the basis of almost-complete 16S rRNA gene sequence analysis. These strains can nodulate Phaseolus vulgaris and Glycine max. The highly similar protein patterns, DNA fingerprint patterns of insertion sequence-based PCR (IS-PCR) and DNA-DNA hybridizations showed that these novel isolates were members of the same species. The closest phylogenetic relatives of the representative strain Alt 505(T) of the novel group were Rhizobium etli CFN 42(T) and Rhizobium indigoferae CCBAU 71714(T), with 96.2 and 96.0% 16S rRNA gene sequence similarity, respectively. Low DNA-DNA relatedness with the type strains of R. etli, R. indigoferae, Rhizobium hainanense, Rhizobium mongolense and Rhizobium galegae and differences in IS-PCR fingerprinting patterns, SDS-PAGE of proteins, antibiotic resistance, phenotypic tests and comparison of cellular fatty acids with Rhizobium species indicated that the novel group of isolates were distinct from previously described species. Based on these results, we propose to place them in a novel species, as Rhizobium oryzae sp. nov. The type strain is Alt 505(T) (=LMG 24253(T) =CGMCC 1.7048(T)).


Histochemical localization of esterases in Avitellina lahorea Woodland, 1927 (Cestoda: Anoplocephalida).
Specific and non-specific esterases have been localized in sections and whole mounts of Avitellina lahorea, an intestinal parasite of sheep and goats. Non-specific esterases (NSE) were found in the sucker muscles, post-acetabular ganglia, nerve trunks, tegument, excretory canals, cirrus sac, vagina, uterus and the inner membrane of the embryophore. Acetylcholinesterase (AChE) was observed in all the above organs, including vas deferens and sperm ducts, but was absent from excretory canals and eggs. Tests with acetylthiocholine iodide (AThChI) revealed the nervous system, vas deferens, sperm ducts, uterus, cirrus sac and the vagina. The intensity of activity of AChE and AThChI was weak compared to NSE.


The structure and function of frail male veterans' informal networks.
This research focuses on the role of informal networks in providing emotional support, instrumental aid, and assistance with chronic disease management for frail male veterans. Telephone interviews were conducted with nursing home eligible veterans living in the community. Name-generating questions were used to illicit network members. Data on 198 frail male veterans indicate that they have about three people they rely on for emotional support, instrumental aid, health appraisal, and health monitoring. Networks are composed primarily of family, and adult sons are mentioned almost as often as adult daughters. Findings illustrate not only the role women play as providers of the majority of informal care to veterans but also the substantial role adult sons have in providing support to their fathers. Many veterans are at risk of institutionalization by having no one to provide instrumental support and health monitoring.


The Rcs phosphorelay: a complex signal transduction system.
RcsC, RcsB, and RcsA were first identified as a sensor kinase, a response regulator, and an auxiliary regulatory protein, respectively, regulating the genes of capsular polysaccharide synthesis. Recent advances have demonstrated that these proteins are part of a complex phosphorelay, in which phosphate travels from the histidine kinase domain in RcsC to a response regulator domain in the same protein; from there to a phosphotransfer protein, RcsD; and from there to RcsB. In addition to capsule synthesis, which requires the unstable regulatory protein RcsA, RcsB also stimulates transcription of a small RNA, RprA; the cell division gene ftsZ; and genes encoding membrane and periplasmic proteins, including the osmotically inducible genes osmB and osmC. The Rcs system appears to play an important role in the later stages of biofilm development; induction of Rcs signaling by surfaces is consistent with this role.


Duodenal-jejunal bypass surgery up-regulates the expression of the hepatic insulin signaling proteins and the key regulatory enzymes of intestinal gluconeogenesis in diabetic Goto-Kakizaki rats.
Duodenal-jejunal bypass (DJB), which is not routinely applied in metabolic surgery, is an effective surgical procedure in terms of type 2 diabetes mellitus resolution. However, the underlying mechanisms are still undefined. Our aim was to investigate the diabetic improvement by DJB and to explore the changes in hepatic insulin signaling proteins and regulatory enzymes of gluconeogenesis after DJB in a non-obese diabetic rat model. Sixteen adult male Goto-Kakizaki rats were randomly divided into DJB and sham-operated groups. The body weight, food intake, hormone levels, and glucose metabolism were measured. The levels of protein expression and phosphorylation of insulin receptor-beta (IR-β) and insulin receptor substrate 2 (IRS-2) were evaluated in the liver. We also detected the expression of key regulatory enzymes of gluconeogenesis [phosphoenoylpyruvate carboxykinase-1 (PCK1), glucose-6-phosphatase-alpha (G6Pase-α)] in small intestine and liver. DJB induced significant diabetic improvement with higher postprandial glucagons-like peptide 1, peptide YY, and insulin levels, but without weight loss. The DJB group exhibited increased expression and phosphorylation of IR-β and IRS-2 in liver, up-regulated the expression of PCK1 and G6Pase-α in small intestine, and down-regulated the expression of these enzymes in liver. DJB is effective in up-regulating the expression of the key proteins in the hepatic insulin signaling pathway and the key regulatory enzymes of intestinal gluconeogenesis and down-regulating the expression of the key regulatory enzymes of hepatic gluconeogenesis without weight loss. Our study helps to reveal the potential role of hepatic insulin signaling pathway and intestinal gluconeogenesis in ameliorating insulin resistance after metabolic surgery.


[Anatomical division and electromyographic assessment within latissimus dorsi].
To evaluate the anatomical division within latissimus dorsi and its electromyographic change as shoulder articulation movement. Using anatomical observation, projection of trophic vessel and nerve of latissimus dorsi was marked in the surface of skin. Electromyographic assessment of different area of latissimus dorsi was measured. The latissimus dorsi was mainly supplied by thoracodorsal and its interior and external branches. The latissimus dorsi can be divided three area based on these anatomical result. Electromyographic amplitude in the three areas of muscle are different. Lastissimus dorsi can be divided into three areas by thoracodorsal vessel and nerve. The third area fibres were utilized preferentially when subjects performed six kinds of movements of the shoulder joint.


Hydrogen-bonding effects on infrared spectra from anharmonic computations: uracil-water complexes and uracil dimers.
Hydrogen-bonding interactions lead to significant changes in the infrared (IR) spectrum, like frequency shifts of the order of magnitude of hundreds of cm(-1) and increases of IR intensity for bands related to vibrational modes of functional groups directly involved in the hydrogen-bonded bridges. We are actively developing a comprehensive and robust computational protocol aimed at the quantitative reproduction of the spectra of bio-organic and hybrid organic/inorganic molecular systems with a proper account of the variety of intra- and intermolecular interactions. We have resorted to fully anharmonic quantum mechanical computations within the generalized second-order vibrational perturbation theory (GVPT2) approach, combined with the B3LYP-D3 method, in conjunction with basis sets of double-ζ plus polarization quality. Such an approach has been validated in a previous work ( Phys. Chem. Chem. Phys. 2014 , 16 , 10112 - 10128 ) for simulating the IR spectra of the monomers of nucleobases and some of their dimers. In the present contribution we have extended our computational protocol toward hybrid models, with the harmonic part computed at the B2PLYP level, in conjunction with the maug-cc-pVTZ basis set, or by a cost-effective ONIOM B2PLYP:B3LYP focused model, where only part of the molecular system forming the hydrogen bonds is treated at the B2PLYP level of theory. In this work experimental frequencies available for a set of four uracil-water complexes have been considered as references for the computational methodologies applied to the simulation of hydrogen-bonding effects on the infrared spectrum, obtaining average uncertainties of about 22 cm(-1) for B3LYP-D3/N07D and improved description within 10 cm(-1) by hybrid B2PLYP/B3LYP-D3 approaches. The same computational schemes have been next applied to simulate fully anharmonic IR spectra of six different hydrogen-bonded uracil dimers, providing reliable support for future experimental investigations on hydrogen-bonded systems.


Small finger pollicization in the radial club hand.
This article describes pollicization of the small finger. A procedure that should only be used in the rare instance of an inoperable radial club hand. Children with bilateral radial club hands and severe, fixed radial deviation of the hand at the end of the forearm, and stiff elbows that cannot be mobilized either with a tendon transfer, splinting, or triceps release can be considered candidates for this operation. The technique, as described by Dieter Buck-Gramcko for pollicization of the index finger, was modified to be used in this procedure.


Cancer incidence in the agricultural health study.
This large, prospective cohort study of private applicators, commercial applicators, and spouses of farmer applicators was undertaken to ascertain the etiology of cancers elevated in agriculture. The participants were matched to cancer registry files in Iowa and North Carolina. Incident cases were identified from enrollment through 31 December 2002. Standardized incidence ratios (SIR) were used to compare the cancer incidence of the participants with that of the total population in the two states. The overall cancer incidence among farmers [SIR 0.88, 95% confidence interval (95% CI) 0.84-0.91] and their spouses (SIR 0.84, 95% CI 0.80-0.90) were significantly lower than expected, particularly for respiratory and urinary cancers. Commercial pesticide applicators had an overall cancer incidence comparable with the expected (SIR 1.01, 95% CI 0.84-1.20). Smoking prevalence was significantly lower than the national average. Prostate cancer was elevated among private applicators (SIR 1.24, 95% CI 1.18-1.33) and commercial applicators (SIR 1.37, 0.98-1.86). Excess ovarian cancer was observed for female applicators (SIR 2.97, 95% CI 1.28-5.85), but not for female spouses (SIR 0.55, 95% CI 0.38-0.78). Female spouses had a significant excess of melanoma (SIR 1.64, 95% CI 1.24-2.09), which was not observed among pesticide applicators. Low overall cancer incidence rates seem to be a result of low overall smoking prevalence and other lifestyle factors, while excess cancer of the prostate and ovaries among applicators may be occupationally related. The excess risk of melanoma observed among spouses was unexpected.


The chain length of dietary saturated fatty acids affects human postprandial lipemia.
Saturated fats increase total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) and are linked to coronary artery disease risk. The effect of variance in chain length of saturated fatty acids (SFA) on coronary artery disease in human postprandial lipemia is not well elucidated. A total of 20 healthy volunteers were challenged with 3 test meals, similar in fat content (~31% en) but varying in saturated SFA content and polyunsaturated/saturated fatty acid ratios (P/S). The 3 meals were lauric + myristic acid-rich (LM), P/S 0.19; palmitic acid-rich (POL), P/S 0.31; and stearic acid-rich (STE), P/S 0.22. Blood was sampled at fasted baseline and 2, 4, 5, 6, and 8 hours. Plasma lipids (triacylglycerol [TAG]) and lipoproteins (TC, LDL-C, high density lipoprotein-cholesterol [HDL-C]) were evaluated. Varying SFA in the test meal significantly impacted postprandial TAG response (p < 0.05). Plasma TAG peaked at 5 hours for STE, 4 hours for POL, and 2 hours for LM test meals. Area-under-the-curve (AUC) for plasma TAG was increased significantly after STE treatment (STE > LM by 32.2%, p = 0.003; STE > POL by 27.9%, p = 0.023) but was not significantly different between POL and LM (POL > LM by 6.0%, p > 0.05). At 2 hours, plasma HDL-C increased significantly after the LM and POL test meals compared with STE (p < 0.05). In comparison to the STE test meal, HDL-C AUC was elevated 14.0% (p = 0.005) and 7.6% (p = 0.023) by the LM and POL test meals, respectively. The TC response was also increased significantly by LM compared with both POL and STE test meals (p < 0.05). Chain length of saturates clearly mediated postmeal plasma TAG and HDL-C changes.


A new improved accelerated diagnostic protocol safely identifies low-risk patients with chest pain in the emergency department.
To assess whether the accelerated diagnostic protocol (ADP) studied in the Asia Pacific Evaluation of Chest Pain Trial (ASPECT) could be optimized to effectively risk stratify patients with symptoms suggestive of acute coronary syndrome (ACS) and allow early discharge of very-low-risk patients. Patients presenting to the emergency department (ED) with chest pain were prospectively enrolled between November 2007 and April 2010. Blood samples were analyzed at 0 and 2 hours postpresentation with a point-of-care multimarker panel (POC-MMP; troponin I [TnI], creatine kinase myocardial band [CKMB] isoenzyme fraction, and myoglobin) and a high-sensitivity cardiac troponin T assay (hsTnT). Patients received standard care. The original ADP (Thrombolysis in Myocardial Infarction [TIMI] risk score = 0, no ischemic electrocardiogram [ECG] changes, and the multimarker panel negative) was compared with an ADP using the point of care TnI only, hsTnT only, or TIMI risk score = 0 to 1. Primary outcome was ACS within 30 days. Of the 1,000 patients recruited, 362 (36.2%) had ACS. There were 12.3% identified as low risk by the original ADP with a sensitivity for ACS of 99.2% (95% confidence interval [CI] = 97.5% to 99.8%). The ADP with the point of care TnI only or hsTnT had the same sensitivity, but identified more patients for discharge (15.0% vs. 12.3%). Including patients with a TIMI risk score of 1 identified more patients as low risk (19.7%), but with a lower sensitivity (97.0% vs. 99.2%). An ADP consisting of a TIMI risk score of 0, no new ECG changes, and negative troponin at 0 and 2 hours postpresentation safely identifies patients at low risk of ACS, in whom discharge without further evaluation can be considered.


Tension pneumopericardium after removal of pericardiocentesis drainage catheter.
This image showed tension pneumopericardium caused by removing the pericardiocentesis catheter, which was inserted to drain malignant pericardial effusion. Tension pneumopericardium is a rare and potentially fatal event. Mortality from tension pneumopericardium can be as high as 50%. Therefore, it is important to suspect and detect early, if the patient complained of dyspnea after removing the pericardiocentesis drainage catheter.


Assessment of the transcription levels for the complement activation control system in eutopic endometrium in women with two or more consecutive miscarriages of unknown etiology.
Human endometrium, deciuda and placenta have been shown to express factors that inhibit the complement activation cascade - decay-accelerating factor (DAF), membrane cofactor protein (MCP) and the C3 complement component. In the following study we have analyzed the transcripts levels for DAF, MCP and heparin-binding epidermal growth factor-like growth factor (HB-EGF), the C3 complement component and receptor for vascular endothelial growth factor (VEGFR1) as markers of endometrial unbalance between factors activating the complement system in women with consecutive miscarriages. Study enrolled 30 women with at least two consecutive miscarriages, and 19 healthly women, that comprised the control group. RNA was isolated from endometrial samples. Transcripts levels of DAF and MCP was higher in women with consecutive miscarriages compared to controls, 0.78 vs 5.08 (p<0.001) and 0.25 vs 0.17 (p=0.001) respectively. In consecutive miscarriages group, DAF and MCP expression was correlated with the C3 expression, with r=0.60; p<0.001 and r= 0.40; p=0.03 respectively. Correlation between DAF and C3 was also noted in controls, 0.70; p=0.001. In women with two or more consecutive miscarriages the analysis proved higher expression of genes that encode proteins that inhibit the complement cascade. Further studies are needed to confirm that this might be a reaction to increased presence of the complement factors, which like C3 that are synthesized in the endometrium.


Sequestration of host-plant-derived flavonoids by lycaenid butterflyPolyommatus icarus.
Larvae of the lycaenid butterflyPolyommatus icarus were reared on inflorescences ofCoronilla varia andMedicago sativa, which are rich in flavonoids. Twelve different flavonoids (five compounds from the former and nine from the latter), including aglycones andO-glycosides of kaempferol, quercetin, and myricetin were isolated and identified by spectroscopic means. NMR and MS data for the new acylated glycoside kaempferol 3-O-6″-(3-hydroxy-3-methylglutaroyl)-β-D-glucopyranoside are reported. Comparative HPLC analysis of the respective host plants and of larvae, pupae, and imagines ofP. icarus indicated selective uptake and accumulation of kaempferol vs. quercetin and myricetin derivatives. The latter were excreted largely unchanged through the feces. Irrespective of the larval host plant kaempferol 3-O-glucoside was found as the major flavonoid in larvae, pupae, and imagines ofP. icarus, accounting for approximately 83-92% of all soluble flavonoids in adult butterflies. Within the imagines, approximately 80% of all flavonoids are stored in the wings (especially in the orange submarginal lunules), whereas the remaining 20% reside in the bodies. Feeding experiments with artificial diet demonstrated that the insects are able to form kaempferol 3-O-glucoside by glucosylation of dietary kaempferol. Possible functions of the sequestered flavonoids, especially for mate recognition ofP. icarus, are discussed.


No association between HPV infection and the neoplastic progression of esophageal squamous cell carcinoma: result from a cross-sectional study in a high-risk region of China.
Esophageal cancer is a leading cause of cancer death, especially in developing countries. In high-risk regions, squamous cell carcinoma is the most common type of esophageal cancer, and its etiology remains poorly understood. The purpose of this study was to evaluate the association between human papillomavirus (HPV) infection and esophageal squamous cell carcinoma (ESCC) and related precursor lesions in a high-risk area of China. We conducted a cross-sectional study among adult inhabitants of Linxian, China. All subjects were interviewed about potential risk factors, had the length of their esophagus sampled by a balloon cytology examination and underwent endoscopy with mucosal iodine staining and biopsy of all unstained lesions. A multivalent HPV hybridization probe, Digene Hybrid Capture II (Gaithersburg, MD), which recognizes high-risk types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68, was used to determine the HPV infection status of the cytologic specimens, and the endoscopic biopsies were used to classify each subject's esophageal disease. 740 subjects completed the cytologic and endoscopic exams, and 702 had adequate cytologic and biopsy specimens. Using a cutpoint of > or =3.0 pg/ml of HPV DNA to define a positive test, HPV positivity was identified in 13% (61/475) of subjects without squamous dysplasia, 8% (8/102) with mild dysplasia, 7% (6/83) with moderate dysplasia, 16% (6/38) with severe dysplasia and zero (0/4) with invasive ESCC. Changing the cutpoint defining a positive test did not change the association of HPV infection and dysplasia grade. In this high-risk population, infection of esophageal cells with high-risk HPV types occurs in 13% of asymptomatic adults with no evidence of squamous dysplasia and a similar proportion of individuals with mild, moderate or severe dysplasia. This suggests that HPV infection is not a major risk factor for ESCC in this high-risk Chinese population. Further studies are warranted to determine if infection with this agent is associated with neoplastic progression in a subset of cases.


Levetiracetam vs. brivaracetam for adults with refractory focal seizures: A meta-analysis and indirect comparison.
The study aimed to compare the efficacy and tolerability of levetiracetam (LEV) and brivaracetam (BRV) in adults with refractory focal seizures. We systematically queried Medline, Embase, and the Cochrane Library. We looked for additional studies in the references of all identified publications and ClinicalTrials.gov. The cutoff day was November 6, 2015. Randomized, double-blind, placebo-controlled trials were included. The indirect comparison for 50% responder rate, seizure-free rate, and adverse effects were conducted. Thirteen trials enrolling 1765 patients in the LEV group and 1919 patients in the BRV group were included. No statistically significant differences were found in efficacy between LEV and BRV at various dose levels. However, most risk ratios (RRs) at three dose levels and the overall RR were >1 for 50% response proportions. The majority of statistically significant differences for adverse events and withdrawal of LEV and BRV were found at high- and middle-dose levels. The indirect comparison of adverse effects (AEs) showed statistically statistical differences in dizziness. Our results suggested that LEV might have a slightly higher efficacy with a lower probability of dizziness compared with BRV for patients with refractory focal seizures.


Prenatal ultrasound findings of linear nevus sebaceous and its association with cystic adenomatoid malformation of the lung.
Nevus sebaceous is a congenital hamartomatous skin lesion that is commonly associated with other abnormalities and is most frequently located on the face and head. To our knowledge, there are no previous reports of the ultrasonographic appearance of nevus sebaceous or of an association with cystic adenomatoid malformation of the lung. A patient was referred at 25 weeks' gestation with multiple fetal anomalies, including echogenic soft-tissue structures external to the cranium and face, a large right-side intrathoracic mass, and abdominal ascites. After a preterm delivery, nevus sebaceous and a congenital cystic adenomatoid malformation of the lung were diagnosed. Neonatal death occurred secondary to pulmonary hypoplasia. Nevus sebaceous should be considered in the differential diagnosis when echogenic soft-tissue structures are seen on prenatal ultrasound. A detailed ultrasound examination is warranted to rule out other associated abnormalities.


Effects of 2-deoxy-D-glucose, glucose and insulin on efferent activity in gastric vagus nerve.
Intracarotid injection of 2-deoxy-D-glucose and insulin increased the efferent activity in the gastric vagus nerve of anesthetized rats, while glucose injection transiently decreased vagus activity.


Effects of physical exercise in the perception of life satisfaction and immunological function in HIV-infected patients: Non-randomized clinical trial.
there is a lack of research about the relationship between exercise and the psychological well-being of HIV-infected (Human Immunodeficiency Virus) patients. the objective of this study was to investigate the influence of a physical training program on life satisfaction and on the immunological function in HIV-patients. a total of 29 HIV-seropositive patients [age: 45 ± 2 yrs; Body Mass Index (BMI): 22.8 ± 1.0 kg/m² ; TCD4: 20.5 ± 2.0%] were allocated to the control (CG, n=10) and to the experimental groups (EG, n=19). The EG participated in an exercise program combining aerobic, strength, and flexibility exercises for a period of 12 weeks [3 times/week of 30 min of aerobic exercise (workload corresponding to 150 bpm-PWC150); 50 min of strength exercises (3 sets of 12 repetitions in 5 exercises at 60-80% 12 RM); and 10 min of flexibility exercises (2 sets of 30 seconds at maximal range of motion of 8 exercises)]. The immunological function was assessed by flow citometry [absolute and relative TCD4 cells counting] and the life satisfaction was assessed by the Life Satisfaction Index (LSI). the analysis of variance (ANOVA) showed no significant differences for relative and absolute CD4 T counts for both groups, however, a slight enhancement trend in the EG [16%, p=0.19] was observed. There was a significant improvement of LSI [approximately 15%; P<0.05] in EG, but not for CG. a physical activity program of moderate intensity improved life satisfaction perception in HIV-infected patients with no immunological function impairment.


Metabolic substrates alter attachment and differentiated functions of proximal tubule cell culture.
Proximal tubules cultured in vitro gradually lose their differentiated functions. Because standard culture media lacks several substrates important for renal proximal tubule oxidative metabolism, whether a mixture of substrates including butyrate, alanine, and lactate (BAL) would modify growth and/or differentiated function of proximal tubular cells in culture was examined. Tubules cultured in media supplemented with 2 mM butyrate, alanine, and lactate exhibited enhanced attachment but did not exhibit an altered growth rate. Higher levels of phosphoenolpyruvate carboxykinase and leucine-amino peptidase were sustained, although these activities were still diminished in comparison with that in fresh tubules. Sodium-dependent glucose uptake and dome formation--other reflections of epithelial cell differentiated function--also were enhanced. These studies demonstrate that the substrates used to culture proximal tubules can modify both their attachment and their manifestation of differentiated function in culture.


[Heptavalent-pneumococcal conjugate vaccine (Prevenar). Differences in effectiveness between populations].
This article reviews the publications on the effectiveness of heptavalent-pneumococcal conjugate vaccine (PCV7) in the prevention of invasive pneumococcal disease (IPD) in children under five years of age. It also analyses the characteristics of the vaccine and its impact on the epidemiology of IPD in different places. Before the introduction of PCV7, the percentage of cases of IPD due to vaccine serogroups oscillated between 89% in the United States and 43% in Asia. In Spain it was 68%. Active laboratory-based surveillance shows that the introduction of PCV7 has had a highly variable impact on the incidence of IPD, with falls oscillating between 91% in the United States and 12% in Navarre, Spain. The global effectiveness of VNC7v in published studies varies between 31% and 89%, chiefly depending on the patterns of pneumococcal serotypes in each place. Numerous studies show a variable replacement capacity of the pneumococci, which means the effect of the vaccine can be reduced, as non-vaccine serotypes occupy the space left by the vaccine ones. A study in Navarre has found a risk of IPD due to non-vaccine serotypes that is 6 times higher in vaccinated children than in unvaccinated ones. In places where less than 70% of the serotypes that cause IPD are represented in the VNC7v, the effectiveness of its introduction in the vaccination will probably be slight and the routine vaccination schedule serotypes fast. In these cases, VNC7v could be reserved for children with IPD risk factors.


The life course, care pathways and elements of vulnerability. A picture of health needs in a vulnerable population.
This paper presents a contextual approach to the assessment of dental health needs based on a life course approach with vulnerability integrated within the assessment of need. Life course approaches to needs assessment,health care planning and commissioning of services are gaining popularity as there is a move away from simpler assessments of need based purely on population demographics such as age. The use of an assessment of vulnerability will be essential in the development of care pathways that are based on patient and population need rather than demand. As an example of the health needs of a vulnerable population data are presented on an oral health needs assessment within nursing and residential homes in the North West of England. These data serve to demonstrate the challenges of the disease burden within such a population but also the complexities of commissioning and delivering services to this group of patients. Care pathways designed to assist such patients should consider not only prevention and treatment modalities but also the means of implementing such therapies in varying settings and utilising the whole dental team.


False-positive buprenorphine by CEDIA in patients prescribed amisulpride or sulpiride.
Buprenorphine is a potent partial opioid agonist that is analyzed in urine to (i) monitor adherence to maintenance or detoxification therapy and (ii) detect illicit use. Buprenorphine analysis is commonly conducted on urine by immunoassay, but is subject to cross-reactivity from other drugs/drug metabolites, including morphine, codeine and dihydrocodeine. This study reports false-positive buprenorphine analysis [Thermo Fisher Scientific cloned enzyme donor immunoassay (CEDIA)] in patients who denied unauthorized buprenorphine use prior to sampling, but who had been prescribed amisulpride. In two cases, confirmatory analysis by liquid chromatography-tandem mass spectrometry was negative (<0.5 µg/L) for buprenorphine and metabolites and positive for amisulpride. Although the cross-reactivity of amisulpride and sulpiride in the CEDIA buprenorphine assay is low (estimated at 0.003 and 0.002%, respectively), it remains a significant consideration given the likely high concentrations of these compounds in urine relative to the low cutoff of the buprenorphine assay. Neither amisulpride nor sulpiride was listed as potential sources of interference on the CEDIA data sheet when this work was performed. These findings highlight the importance of confirming immunoassay-positive buprenorphine results using a more selective analytical technique.


Tailoring copper oxide semiconductor nanorod arrays for photoelectrochemical reduction of carbon dioxide to methanol.
Solar photoelectrochemical reduction of carbon dioxide to methanol in aqueous media was driven on hybrid CuO/Cu2O semiconductor nanorod arrays for the first time. A two-step synthesis was designed and demonstrated for the preparation of these hybrid copper oxide one-dimensional nanostructures on copper substrates. The first step consisted in the growth of CuO nanorods by thermal oxidation of a copper foil at 400 °C. In the second step, controlled electrodeposition of p-type Cu2O crystallites on the CuO walls was performed. The resulting nanorod morphology with controllable wall thickness by adjusting the Cu2O electrodeposition time as well as their surface/bulk chemical composition were probed by scanning electron microscopy, X-ray diffraction and Raman spectroscopy. Photoelectrosynthesis of methanol from carbon dioxide was demonstrated at -0.2 V vs SHE under simulated AM1.5 solar irradiation on optimized hybrid CuO/Cu2O nanorod electrodes and without assistance of any homogeneous catalyst (such as pyridine or imidazole) in the electrolyte. The hybrid composition, ensuring double pathway for photoelectron injection to CO2, along with high surface area were found to be crucial for efficient performance in methanol generation under solar illumination. Methanol formation, tracked by gas chromatography/mass spectrometry, indicated Faradaic efficiencies of ~95%.


Structure of reversible computation determines the self-duality of quantum theory.
Predictions for measurement outcomes in physical theories are usually computed by combining two distinct notions: a state, describing the physical system, and an observable, describing the measurement which is performed. In quantum theory, however, both notions are in some sense identical: outcome probabilities are given by the overlap between two state vectors--quantum theory is self-dual. In this Letter, we show that this notion of self-duality can be understood from a dynamical point of view. We prove that self-duality follows from a computational primitive called bit symmetry: every logical bit can be mapped to any other logical bit by a reversible transformation. Specifically, we consider probabilistic theories more general than quantum theory, and prove that every bit-symmetric theory must necessarily be self-dual. We also show that bit symmetry yields stronger restrictions on the set of allowed bipartite states than the no-signalling principle alone, suggesting reversible time evolution as a possible reason for limitations of nonlocality.


Vanadate-resistant mutants of Candida albicans show alterations in phosphate uptake.
Phosphate uptake studies in different strains of the dimorphic pathogenic yeast Candida albicans were undertaken to show that this yeast actively transported phosphate with an apparent Km in the range of 90-170 microM. The uptake was pH dependent and derepressible under phosphate starvation. Vanadate-resistant (van) mutants of C. albicans showed a 20-70% reduction in the rate of phosphate uptake in high phosphate medium and was associated with an increased Km and reduced Vmax. The magnitude of derepression under phosphate starvation was different between van mutants. These results demonstrate that van mutants may have developed resistance by modifying the rate of entry of vanadate.


[Postnatal development of the spine in sheep and goats].
From the first day to the age of eight years and a half, post-natal development of spinal column was studied in 84 sheep of the Merino breed and 40 crossbred goats. At birth time the axial skeleton was observed to have a high degree of development. Coalescence of the components of spinal column segments starts soon after birth and generally terminates by the third year of life. In animals above three years of age ossification or calcification centres occur in the cartilaginous margin of the spinal process of the second cervical vertebra and in lig. supraspinale . The heads of all ribs and processes ( extremitates ) of the last caudal vertebrae also ossify after birth. The time of the coalescence of the components of vertebrae is about the same in sheep and goats; in some sections it may be even earlier or later in the goat than in sheep. No sexual dimorphism was observed in the coalescence of the components of vertebrae in small ruminants.


Periodicity-induced effects in the scattering and absorption of light by infinite and finite gratings of circular silver nanowires.
We study numerically the effect of periodicity on the plasmon-assisted scattering and absorption of visible light by infinite and finite gratings of circular silver nanowires. The infinite grating is a convenient object of analysis because of the possibility to reduce the scattering problem to one period. We use the well-established method of partial separation of variables however make an important improvement by casting the resulting matrix equation to the Fredholm second-kind type, which guarantees convergence. If the silver wires have sub-wavelength radii, then two types of resonances co-exist and may lead to enhanced reflection and absorption: the plasmon-type and the grating-type. Each type is caused by different complex poles of the field function. The low-Q plasmon poles cluster near the wavelength where dielectric function equals -1. The grating-type poles make multiplets located in close proximity of Rayleigh wavelengths, tending to them if the wires get thinner. They have high Q-factors and, if excited, display intensive near-field patterns. A similar interplay between the two types of resonances takes place for finite gratings of silver wires, the sharpness of the grating-type peak getting greater for longer gratings. By tuning carefully the grating period, one can bring together two resonances and enhance the resonant scattering of light per wire by several times.


3B, a novel photosensitizer, inhibits glycolysis and inflammation via miR-155-5p and breaks the JAK/STAT3/SOCS1 feedback loop in human breast cancer cells.
Compared to normal cells, most cancer cells produce ATP by glycolysis under aerobic conditions rather than via the tricarboxylic acid cycle (TCA). This study is intended to determine whether 3B, a novel photosensitizer, can inhibit glycolysis and inflammation in breast cancer cells. We showed that 3B had the ability to repress glucose consumption as well as the generation of ATP, lactate and lactate dehydrogenase. 3B-PDT not only inhibited the expression of IL-1β and IL-6 but also affected the JAK-STAT3 inflammatory pathway in vitro. The present study showed that 3B featured a significant inhibitory effect on the expression of microRNA-155-5p and SOCS1 might serve as a target gene. In vivo studies revealed that 3B inhibited tumor growth and exhibited almost no side effects. Therefore, through the anti-glycolytic effect and breakage of the JAK/STAT3/SOCS1 feedback loop via miR-155-5p, 3B may potentially serve as a potential therapeutic agent against breast cancer.


Interferon beta but not glatiramer acetate therapy aggravates headaches in MS.
Type and frequency of headaches during immunomodulatory therapy in MS were determined in 167 consecutive patients. In a prospective group of 65 patients beginning interferon beta therapy, headache frequency and duration increased in 18% of all and in 35% of patients with pre-existing headache by more than 50% during the first 6 months. In two retrospective groups, increased headache frequency was reported by 34% of 53 patients on interferon beta, but by only 6% of 49 patients during at least 6 months of glatiramer acetate therapy.


Identification of tumorigenic retinal stem-like cells in human solid retinoblastomas.
Retinoblastoma (RB) is the most common malignant tumor of the retina in human children. Although it has been hypothesized for a long time that RB derives from multipotent retinal stem cells (RSCs) or retinoblasts, the direct evidence that the presence of tumorigenic RSCs in RB tumors is still lacking. Some studies indicate that malignant tumors contain tumor stem cells similar to their normal tissue stem cell counterparts. With in vitro culture and differentiation method we demonstrate that tumorigenic retinal stem-like cells (RSLCs) indeed exist in RB lesions and that RB tumor-derived cultures encompass undifferentiated cells capable of extensive proliferation as clonal nonadherent neurospheres and can differentiate into different retinal cells in vitro. Interestingly, cultured cells expressed retinal development related genes including nestin, CD133, pax6, chx10 and Rx, and overexpressed Bmi-1, a gene required for self-renewal and proliferation of stem cells. Significantly, when these cultured cells were intraocularly transplanted into SCID mice, they gave rise to new tumors with histomorphological features and immunophenotypes similar to their parental primary RBs. The results show that RBs contain tumorigenic RSLCs that contribute to tumorigenesis. This study provides a new insight to investigate the histogenesis of RBs and establishes a model for other RB research.


C-terminal incorporation of fluorogenic and affinity labels using wild-type and mutagenized carboxypeptidase Y.
The ability to carry out specific C-terminal modification or labeling of peptides and proteins has a broad range of applications. It is well established that this may be achieved by protease-catalyzed transacylation reactions and that carboxypeptidase Y (CPD-Y) is suitable for this due to its broad specificity and stability in the presence of denaturants. Furthermore, CPD-Y is characterized by a S'1 binding site that is open to solvent and, thus, capable of catalyzing a transpeptidation reaction with nucleophiles that extend beyond the perimeter of the active site. However, one major drawback with CPD-Y is that the yield of the reaction is highly dependent on the nature of the leaving group; e.g., with large apolar leaving groups the yield of the reaction does not exceed 15%. In the present publication it is demonstrated that mutants of CPD-Y, designed for low leaving group dependence, efficiently incorporate biocytin amide as well as a new fluorescent nucleophile, N'-Abz-Lysine amide (ablysin amide), into peptides and proteins.


The origin of charge localization observed in organic photovoltaic materials.
Two of the primary hurdles facing organic electronics and photovoltaics are their low charge mobility and the inability to disentangle morphological and molecular effects on charge transport. Specific chemical groups such as alkyl side chains are often added to enable spin-casting and to improve overall power efficiency and morphologies, but their exact influence on mobility is poorly understood. Here, we use two-photon photoemission spectroscopy to study the charge transport properties of two organic semiconductors, one with and one without alkyl substituents (sexithiophene and dihexyl-sexithiophene). We show that the hydrocarbon side chains are responsible for charge localization within 230 fs. This implies that other chemical groups should be used instead of alkyl ligands to achieve the highest performance in organic photovoltaics and electronics.


In-line quantification of drug and excipients in cohesive powder blends by near infrared spectroscopy.
This work was aimed at investigating the utility of near infrared (NIR) spectroscopy for simultaneous in-line quantification of drug and excipients in cohesive powder blends in a bin blender. A model formulation containing micronized chlorpheniramine maleate (microCPM), lactose, microcrystalline cellulose (MCC) and magnesium stearate (MgSt) was selected for the blending study. An optical head comprising a sapphire window mounted on the lid of the bin was used to collect in-line NIR spectral data of the powder blends. Validated partial least square (PLS) calibration models were used to quantify each component from the NIR spectra of the blends. Additionally, effects of premixing by sieving and high shear mixing and use of an internal prism fixed within the bin on the mixing performance of each component were studied. The statistical results obtained for PLS calibration models and their validation showed the sensitivity of NIR for accurate quantification of blend components. The blend prepared with high shear premixing and with prism achieved uniformity more rapidly than that with high shear premixing but without prism during blending in a bin blender. Premixing using sieving proved to be inadequate for uniform mixing of the blend components as none of the components except MgSt achieved uniform distribution after the preset blending time when blended in the bin blender. This study demonstrated that by high speed sampling and rapid spectral acquisition, distribution of individual blend components can be assessed with high accuracy during blending. Furthermore, high shear premixing facilitated rapid distribution and uniformity achievement of blend components. This technique may be used to monitor the relative distribution of individual blend components in real time and thus, to assess the performance of a bin blender for mixing of cohesive multi-component powder blends during development and production.


Characteristics and application of S1-P1 nucleases in biotechnology and medicine.
3'-nucleases/nucleotidases of the S1-P1 family (EC 3.1.30.1) are single-strand-specific or non-specific zinc-dependent phosphoesterases present in plants, fungi, protozoan parasites, and in some bacteria. They participate in a wide variety of biological processes and their current biotechnological applications rely on their single-strand preference, nucleotide non-specificity, a broad range of catalytic conditions and high stability. We summarize the present and potential utilization of these enzymes in biotechnology and medicine in the context of their biochemical and structure-function properties. Explanation of unanswered questions for bacterial and trypanosomatid representatives could facilitate development of emerging applications in medicine.


Update in pituitary 2010.
This manuscript is based on an invited lecture entitled "The Year in Pituitary," presented at the 91st Annual Meeting of The Endocrine Society in San Diego, California, on June 21, 2010. The purpose of the lecture was to highlight new or evolving issues in the management of pituitary disease. Papers selected were published in major journals between January 2009 and June 2010. Issues addressed include the safety of cabergoline in pregnancy, recurrence of hyperprolactinemia after dopamine agonist withdrawal, pegvisomant and hepatic dysfunction, and high-dose hydrocortisone as a predictor of mortality in patients with acromegaly.


[Farmacological effect of retabolil on aldosterone level and arterial pressure in rats under the action of vibrations].
The experiments were performed on male rats, which were subjected to single and multiply repeated vibrations (low-frequency, horizontal, high-amplitude) analogous to the action of motor transport vibrations. It is established that the administration of retabolil produces a hypotensive effect and blocks the vibration-induced increase in the level of hypertensive hormone aldosterone. Under conditions of the multiply repeated action of vibrations, both effects were realized via micro-opioid receptors. In the case of a single action, these receptors were only involved in a hypotensive effect but not mediated in aldosterone suppression. Both these effects were absent in the control group of animals (not subjected to vibrations). Therefore, retabolil can be used as a hypotensive and aldosterone-blocking drug for vibration-induced hypertension in animals and, probably, in humans.


Heart rate turbulence and clinical prognosis in hypertrophic cardiomyopathy and myocardial infarction.
Short-term fluctuations in sinus cycle length after a single ventricular premature complex (VPC) have attracted considerable interest and has been termed heart rate turbulence (HRT). The onset and slope of HRT have each been reported to be independent and powerful predictors of clinical prognosis in patients with myocardial infarction (MI), but there are no data available for patients with hypertrophic cardiomyopathy (HCM). Thus the present study analyzed the 2 HRT variables to determine their prognostic value in HCM patients. Holter monitoring data were obtained from 104 HCM patients, 44 MI patients and 56 normal controls, from which singular VPCs followed by >or=20 normal sinus beats were isolated and the HRT onset and slope were automatically calculated. HRT onset and slope were abnormal in MI patients, but not in HCM patients, as compared with normal control subjects (onset -1.1+/-2.9, -2.1+/-3.4, -1.4+/-5.1%; slope 10.6 +/-8.6, 18.0+/-13.9, 16.6+/-9.7 ms/beat, respectively). During the follow-up period of 27+/-10 months, 7 HCM patients and 10 MI patients either died from cardiac death or were hospitalized for congestive heart failure. In MI patients, HRT onset was higher and the HRT slope was lower in patients with cardiac events than in patients without (onset 1.1+/-2.7 vs -1.7+/-2.7%, p=0.011; slope 5.7+/-4.3 vs 12.0+/-9.0 ms/beat, p=0.028). In HCM patients, however, the HRT onset and slope were similar between patients with and without cardiac events (onset -2.0+/-2.0 vs -2.1 +/-3.5%, p=0.98; slope 18.1+/-10.9 vs 18.0+/-14.0 ms/beat, p=0.68). In conclusion, unlike MI patients, the HRT variables in selected HCM patients were not abnormal and failed to predict the clinical prognosis.


Binocular vision enhances a rapidly evolving affordance priming effect: behavioural and TMS evidence.
Extensive research has suggested that simply viewing an object can automatically prime compatible actions for object manipulation, known as affordances. Here we explored the generation of covert motor plans afforded by real objects with precision ('pinchable') or whole-hand/power ('graspable') grip significance under different types of vision. In Experiment 1, participants viewed real object primes either monocularly or binocularly and responded to orthogonal auditory stimuli by making precision or power grips. Pinchable primes facilitated congruent precision grip responses relative to incongruent power grips, and vice versa for graspable primes, but only in the binocular vision condition. To examine the temporal evolution of the binocular affordance effect, participants in Experiment 2 always viewed the objects binocularly but made no responses, instead receiving a transcranial magnetic stimulation pulse over their primary motor cortex at three different times (150, 300, 450ms) after prime onset. Motor evoked potentials (MEPs) recorded from a pinching muscle were selectively increased when subjects were primed with a pinchable object, whereas MEPs from a muscle associated with power grips were increased when viewing graspable stimuli. This interaction was obtained both 300 and 450ms (but not 150ms) after the visual onset of the prime, characterising for the first time the rapid development of binocular grip-specific affordances predicted by functional accounts of the affordance effect.


Neurohormonal Factors Involved in the Control of the Nocturnal Prolactin Surge that Precedes Parturition in the Rat.
A nocturnal surge of prolactin (PRL) occurs in the dark period preceding parturition in the rat. The roles of oxytocin, vasoactive intestinal peptide (VIP), serotonin and the opioids in controlling the antepartum PRL surge were investigated by examining PRL secretion over the last 2 days of pregnancy in the presence of antagonists to these neurohormonal factors. Serial blood samples were collected from unanesthetized, freely moving rats via indwelling jugular cannulae, and plasma PRL was measured by radioimmunoassay. In control rats PRL levels rose in a nocturnal surge peaking at 223 ± 34 ng/ml (n = 6) at 0500 h on day 21 of pregnancy, the day of parturition. Intra-arterial infusion of the oxytocin antagonist desGly-NH(2) d(CH(2) )(5) [Tyr(Me)(2) , Thr(4) ]-OVT at a dose sufficient to completely block milk ejection (10 μg/h) had no effect on this PRL surge. Infusion of the VIP antagonist [4Cl-D-Phe(6) ,Leu(17) ]-VIP at 2 μg/h from 2200 h on day 20 until 0500 h on day 21 significantly attenuated the antepartum PRL surge, reducing the peak to 76 ± 28 ng/ml at 0500 h on day 21 (n = 6; P<0.001). Naloxone, the opiate receptor antagonist, inhibited the antepartum PRL surge in a dose-dependent manner. Infused at 2 mg/h naloxone partially reduced the magnitude of the PRL surge, which peaked at 128 ± 24 ng/ml at 0300 h on day 21 (n = 4; P<0.05), while at 10 mg/h naloxone totally abolished the PRL surge (n = 6; P<0.001). Injection of the serotonin synthesis inhibitor ρ-chlorophenylalanine (250 mg/kg, sc at 1700 h on days 19 and 20 of pregnancy) increased the magnitude of the antepartum PRL surge to a peak of 327 ± 48 ng/ml at 0500 h on day 21 (n = 5), compared with 244 ± 24 ng/ml at the same time in vehicle-injected controls (P<0.05; n = 5). The results demonstrate that the antepartum PRL surge is stimulated by an opioid mechanism, and also by VIP. Oxytocin and serotonin have no role in stimulating PRL secretion during late pregnancy.


Entropy and irreversibility in dynamical systems.
A method of defining non-equilibrium entropy for a chaotic dynamical system is proposed which, unlike the usual method based on Boltzmann's principle S = klog W, does not involve the concept of a macroscopic state. The idea is illustrated using an example based on Arnold's 'cat' map. The example also demonstrates that it is possible to have irreversible behaviour, involving a large increase of entropy, in a chaotic system with only two degrees of freedom.


Blood pressure lability: triggers, implications, and options.
Blood pressure lability is a phenomenon in which there is a wide range of extreme highs and lows in blood pressure measurements. These highs and lows occur at irregular intervals, and it is difficult for health care providers to isolate when this phenomenon occurs. Hypertension and hypotension occurring within minutes of the other can cause a showering of embolized blood clots to travel to the brain, heart, or lungs. The labile nature of the blood pressure can lead to the evolution of an ischemic stroke, heart failure, angina, and myocardial infarction. The aim of this article is to describe the relationship between blood pressure lability and ischemic stroke, including triggers, implications, and treatment options. A case study is included to illustrate treatment options available to health care providers.


Infrared spectra, Raman spectra, microwave dielectric properties and simulation for effective permittivity of temperature stable ceramics AMoO4-TiO2 (A = Ca, Sr).
In this work, temperature stable microwave dielectric materials (1 - x)AMoO(4)-xTiO(2) (A = Ca, Sr) were prepared by a solid state reaction method. The phase composition, sintering behaviors, microstructures, microwave dielectric properties, effective permittivity and vibrational phonon modes were investigated. The X-ray diffraction pattern and scanning electron microscope analysis indicated that the AMoO(4) (A = Ca, Sr) phase could coexist with the TiO(2) phase. The effective dielectric constants of the AMoO(4)-TiO(2) composites were calculated by the finite element method (FEM), compared with the measured values and the numerical results obtained by the classical mixing rules. The correlation between the dielectric properties and the crystal structures were studied using IR and Raman spectroscopy. The infrared spectra were analyzed using the classical harmonic oscillator model, and revealed that the external vibration modes of AMoO(4) (A = Ca, Sr) had the most significant influence on the dielectric constant. The Raman spectra showed that there were strong interactions in the [MoO(4)] tetrahedron due to the sharp and intense Raman modes. Finally, the low-firing (900 °C) microwave dielectric ceramics were obtained with 3 wt% H(3)BO(3)-CuO addition (BCu), and they possess good microwave dielectric properties with ε(r) = 10.6-13, high Q×f values (40 700-72 050 GHz), and near-zero temperature coefficients of resonant frequency (TCF or τ(f) values). These results also show that (1 - x)AMoO(4)-xTiO(2)-BCu (A = Ca, Sr) ceramics are good candidates for microwave electronic device applications.


5-(2-Cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB): correlation of hypnotic and convulsant properties with alterations of synaptosomal 45Ca2+ influx.
Male ICR mice (20-35 g) were given either 5-(2-cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB) alone (10-15 mg/kg i.p.) or CHEB (25-75 mg/kg i.p.) after a 1 h pretreatment with phenobarbital (75 mg/kg i.p.). CHEB alone (10 mg/kg) produced excitatory behavior but not convulsive seizures. Higher doses (11-15 mg/kg) produced convulsive seizures resulting in death. Pretreatment with phenobarbital prevented seizure activity. Following phenobarbital pretreatment, CHEB in doses of 50 and 75, but not 25 mg/kg, resulted in hypnosis of 53 +/- 16 and 64 +/- 9 min duration, respectively. In vitro, CHEB (10-200 microM) significantly inhibited 'fast-phase' (3 s) K+-stimulated 45Ca2+ uptake into cerebrocortical synaptosomes. CHEB (10 and 100 microM) also significantly increased basal 45Ca2+ uptake. The addition of CHEB (50 and 100 microM) or pentobarbital (100 microM) to striatal synaptosomes inhibited 'fast-phase' K+-stimulated 45Ca2+ uptake and endogenous dopamine release. CHEB (10-200 microM), but not pentobarbital (100 microM), produced a time- and dose-dependent increase in the resting release of endogenous dopamine from striatal synaptosomes. The results of this study show that CHEB possesses hypnotic activity if its lethal convulsant actions are blocked. The hypnotic actions of CHEB appear to correlate with inhibition of voltage-dependent calcium channels in brain synaptosomes.


A PET study on cortical and subcortical control of pelvic floor musculature in women.
The pelvic floor musculature plays an important role in behaviors such as defecation, micturition, mating behavior, and vomiting. A recent positron emission tomography (PET) study revealed that structures belonging to the emotional motor system are involved in the control of the pelvic floor during micturition. However, there also exist brain structures involved in the voluntary motor control of the pelvic floor, and the present PET study was designed to identify these structures. Six adult female volunteers were scanned with the bolus injection of H2(15)O during the following four conditions: (1) rest, (2) repetitive pelvic floor straining, (3) sustained pelvic floor straining, and (4) sustained abdominal straining. The results revealed that the superomedial precentral gyrus, the most medial portion of the motor cortex, is activated during pelvic floor contraction and the superolateral precentral gyrus during contraction of the abdominal musculature. In these conditions, significant activations were also found in the cerebellum, supplementary motor cortex, and thalamus. The right anterior cingulate gyrus was activated during sustained pelvic floor straining. No activations were found in subcortical structures belonging to the emotional motor system. The results are discussed in light of the existing literature on human control of the pelvic floor and micturition.


Changes in distribution of the phases of mitosis in human tumor xenografts following drug treatment.
Distribution of individual mitotic phases in different human xenografts on nude mice showed significant changes after treatment with a range of drugs when compared with untreated controls. The total amount of mitoses in prophase significantly decreased in all responsive tumors while those in all other phases increased but in a very variable degree. There was some correlation in between the range of the mitotic phase distribution changes and the degree of tumor response to treatment.


[An investigation of glottic movement and vocal cord evoked electromyography following unilateral cricoarytenoid joint injuries in rabbits].
The unilateral cricoarytenoid joints of rabbits were bluntly injured. Observations on glottic movement and vocal cord evoked electromyography were performed. The results confirm that injury of the cricoarytenoid joint always causes disturbances in ipsilateral vocal cord movement. But the evoked electrical activities of the ipsilateral vocal cord muscles were normal not only in acute stage but also in chronic stage. The above results may provide the experimental basis for clinical differentiation of disturbances in glottic movement.


Comparison of the in situ and in vivo intestinal disappearance of ruminally protected methionine.
We designed a switchback expriment to compare the intestinal disappearance of ruminally protected Met determined in situ or in vivo over three consecutive periods. Four nonlactating Holstein heifers (477+/-36 kg) with cannulae in the rumen, duodenum, and ileum were fed a diet based on timothy silage to meet requirements for maintenance (dry matter intake = 8.72+/-0.15 kg). A total of 16 bags, containing 1.5 g of ruminally protected Met, were incubated in the rumen (4.5 h) of each cow and transferred to an acid-pepsin solution to simulate the abomasum (2.5 h). Following each incubation, bags were recovered and three bags were dried at 55 degrees C and analyzed for Met. Remaining bags were introduced directly into the duodenal or ileal cannula for the in situ method, while for the in vivo method, the content of remaining bags was transferred into gelatin capsules before their introduction in the duodenal or ileal cannula. Spot samples of digesta were collected during a 96-h period, with Co-EDTA and Cr-mordanted fiber used as indigestible markers to estimate in vivo digestibility. The disappearance of Met in the small intestine determined in vivo tended to be higher than in situ (74.45 vs. 43.65+/-1.79%). Our results indicate that when used to assess intestinal availability of ruminally protected Met, the mobile nylon bag technique can underestimate the true bioavailability of Met.


Genome-wide sequencing of Phytophthora lateralis reveals genetic variation among isolates from Lawson cypress (Chamaecyparis lawsoniana) in Northern Ireland.
Phytophthora lateralis is a fungus-like (oomycete) pathogen of trees in the family Cupressaceae, including Chamaecyparis lawsoniana (Lawson cypress or Port Orford cedar). Known in North America since the 1920s, presumably having been accidentally introduced from its assumed East Asian centre of origin, until recently, this pathogen has not been identified causing disease in Europe except for a few isolated outbreaks. However, since 2010, there have been several reports of infection of C. lawsoniana by P. lateralis in the United Kingdom, including Northern Ireland. We sequenced the genomes of four isolates of P. lateralis from two sites in Northern Ireland in 2011. Comparison with the closely related tree and shrub pathogen P. ramorum (cause of ramorum disease of larch and other species in the UK) shows that P. lateralis shares 91.47% nucleotide sequence identity over the core conserved compartments of the genome. The genomes of the four Northern Ireland isolates are almost identical, but we identified several single-nucleotide polymorphisms (SNPs) that distinguish between isolates, thereby presenting potential molecular markers of use for tracking routes of spread and in epidemiological studies. Our data reveal very low rates of heterozygosity (compared with P. ramorum), consistent with inbreeding within this P. lateralis population.


Rapid and reversible generation of a microscale pH gradient using surface electric fields.
We report a method for the rapid and reversible generation of microscale pH gradients using a spatially varied electric field. A linear gradient in electrochemical potential is produced on an electrode surface consisting of a platinum catalyst layer on indium-tin oxide-coated glass by the application of two different potential values at spatially distinct surface locations. The resulting potential gradient drives the oxidation and reduction of water at different rates along the surface, as dictated by the local applied potential. A nonuniform distribution of pH in the neighboring solution results due to the variation in surface reaction rates. The extent and magnitude of the pH gradient can be controlled by the appropriate selection of applied potential values. In addition, the gradient can be rapidly turned on or off and reversibly switched between various profiles. The size of the pH gradient can be readily modified by changing the dimensions of the electrode and contact pads to allow integration into chip-scale devices. Characteristics of the pH gradient are described, including experimental and theoretical evidence of significant improvement in time response over competing methods for the generation of microscale pH gradients.


Improved immuno double labelling for cell and structural biology.
Colloidal gold is the most widely used electron dense marker in biological electron microscopy. The development of procedures for making gold particles of very defined sizes has made double or even multiple labelling possible using gold of two or more different sizes. Lately a new type of electron dense marker has been developed consisting of ligand-stabilized metal atom clusters rather than colloidal particles. The differences between these two types of markers are highlighted and the advantages of using metal atom clusters for immuno labelling of certain biological specimens are discussed. Possible methods of distinguishing two such cluster labels in double labelling experiments are reviewed.


Ivory: a recessive white-eyed tryptophan metabolism mutant with intermediate F2 - and R 1 - progenies in the flesh fly Sarcophaga barbata.
The recessive autosomal gene ivory (i) causes white eyes in the flesh fly Sarcophaga barbata. The mutation completely blocks the synthesis of formylkynurenine. Ivory larvae and ivory imagoes are able to synthesize xanthommatin if formylkynurenine and kynurenine respectively are provided with the food. The eye colour of the F2- and the R1-mutants respectively is intermediate because these animals have taken up xanthommatin precursors that were excreted by the wild-type larvae. The white eye colour is not influenced by temperature. The viability of the ivory stock is somewhat lower than that of the wild-type stock. The mutation ivory is homologous to the mutation vermilion of Drosophila melanogaster and to the mutation green of Musca domestica respectively.


Differences in Muscle Activation and Kinematics Between Cable-Based and Selectorized Weight Training.
Signorile, JF, Rendos, NK, Heredia Vargas, HH, Alipio, TC, Regis, RC, Eltoukhy, MM, Nargund, RS, and Romero, MA. Differences in muscle activation and kinematics between cable-based and selectorized weight training. J Strength Cond Res 31(2): 313-322, 2017-Cable resistance training machines are showing resurgent popularity and allow greater number of degrees of freedom than typical selectorized equipment. Given that specific kinetic chains are used during distinct activities of daily living (ADL), cable machines may provide more effective interventions for some ADL, whereas others may be best addressed using selectorized equipment. This study examined differences in activity levels (root mean square of the EMG [rmsEMG]) of 6 major muscles (pectoralis major, PM; anterior deltoid, AD; biceps brachii, BB; rectus abdominis, RA; external obliques, EO; and triceps brachii, TB) and kinematics of multiple joints between a cable and standard selectorized machines during the biceps curl, the chest press, and the overhead press performed at 1.5 seconds per contractile stage. Fifteen individuals (9 men, 6 women; mean age ± SD, 24.33 ± 4.88 years) participated. Machine order was randomized. Significant differences favoring cable training were seen for PM and AD during biceps curl; BB, AD, and EO for chest press; and BB and EO during overhead press (p ≤ 0.05). Greater starting and ending angles were seen for the elbow and shoulder joints during selectorized biceps curl, whereas hip and knee starting and ending angles were greater for cable machine during chest and overhead presses (p < 0.0001). Greater range of motion (ROM) favoring the cable machine was also evident (p < 0.0001). These results indicate that utilization patterns of selected muscles, joint angles, and ROMs can be varied because of machine application even when similar exercises are used, and therefore, these machines can be used selectively in training programs requiring specific motor or biomechanical patterns.


Urinary polyamine levels in the diagnosis of carcinoma of the prostate.
Urinary excretion of the basic polyamine, spermidine, was significantly elevated in patients with prostatic carcinoma as compared to a control group of patients, Of 44 urine specimens from patients with prostatic malignancy 31 had spermidine levels more than 2 mg. per 24 hours, while only 3 of 13 urine specimens from the control groups had levels in excess of this value. The increase in spermidine appeared to be correlated with the histologic grading of the tumor, that is 30 of 34 specimens from patients with grade II, III or IV carcinoma had excessive spermidine excretion and only 1 of 10 urine specimens from patients with grade I tumors had similiar spermidine elevations. High spermidine levles were found in tumors localized to the prostate and in 7 of 8 patients with negative pelvic and para-aortic lymph node biopsies. This study raises the possibility that urinary spermidine determinations may aid in the development of a biochemical screening test for prostatic neoplasms.


Claudin gene expression patterns do not associate with interspecific differences in paracellular nutrient absorption.
Bats exhibit higher paracellular absorption of glucose-sized molecules than non-flying mammals, a phenomenon that may be driven by higher permeability of the intestinal tight junctions. The various claudins, occludin, and other proteins making up the tight junctions are thought to determine their permeability properties. Here we show that absorption of the paracellular probe l-arabinose is higher in a bat (Eptesicus fuscus) than in a vole (Microtus pennsylvanicus) or a hedgehog (Atelerix albiventris). Furthermore, histological measurements demonstrated that hedgehogs have many more enterocytes in their intestines, suggesting that bats cannot have higher absorption of arabinose simply by having more tight junctions. We therefore investigated the mRNA levels of several claudins and occludin, because these proteins may affect permeability of tight junctions to macronutrients. To assess the expression levels of claudins per tight junction, we normalized the mRNA levels of the claudins to the constitutively expressed tight junction protein ZO-1, and combined these with measurements previously made in a bat and a rodent to determine if there were among-species differences. Although expression ratios of several genes varied among species, there was not a consistent difference between bats and non-flyers in the expression ratio of any particular gene. Protein expression patterns may differ from mRNA expression patterns, and might better explain differences among species in arabinose absorption.


Health impacts of large releases of radionuclides. Physical transport and chemical and biological processes in agricultural systems.
The purpose of radioecological models is to make realistic estimates of doses to the public after accidental releases of radionuclides into the environment. Important physical, chemical and biological processes involved in the dispersion and transport of radioactive substances in the atmosphere and along the food-chains are presented. The results of the EURAD (EURopean Acid Deposition) model, predicting the deposition patterns of 131I and 137Cs in Belarus and Ukraine after the Chernobyl accident, are discussed. An overview of the most important ecological processes--such as deposition, interception and translocation, weathering, transfers from soil to plants and from plants to animal/animal products, and seasonality in agricultural environments--is given. Examples corresponding to these individual processes, mainly experimental results after the Chernobyl accident and related to radiocaesium and radioiodine, are shown and discussed.


Acute heart failure in myocardial infarction: principles of treatment.
Congestive heart failure after acute myocardial infarction can extend the area of infarction by worsening the oxygen supply-demand balance. Appropriate treatment requires insight into this pathophysiologic condition and knowledge of the effects of the various therapies available. Understanding of the role of vasodilating and inotropic agents and of mechanical interventions such as ventilation with PEEP is an important aspect of treatment.


Bone mass changes in vivo during the entire reproductive cycle in rats feeding different dietary calcium and calcium/phosphorus ratio content.
The purpose of this study was to quantify in vivo the impact of different dietary Ca contents on the maternal total skeleton and skeletal sub-areas in adult rats during pregnancy and lactation, using DXA. Twenty-four female Wistar rats (approximately 5 months old) were mated and divided into three groups (n = 8) and fed one of the following diets, varying only in Ca content (LCD: 0.14%, NCD: 0.6% or HCD: 1.2%). Pups were adjusted to 8-9 per dam. Maternal ionic calcium and in vivo bone mineral density (BMD) were measured at the beginning, after delivery and after weaning. Regardless of the diet, ionized calcium decreased from onset to weaning ( P < 0.05). At weaning, bone mass decreased 7.3% in NCD, 15% in LCD and 10.5% in HCD from initial values. Total skeleton, whole and proximal tibia and spine BMDs only decreased at delivery in the LCD group ( P < 0.05) but, irrespective of the diet, at weaning, they were lower compared to delivery and initial values ( P < 0.05). LCD group presented the lowest BMD in the proximal tibia and spine regions ( P < 0.05). At birth, pups did not present differences, however, at weaning, LCD pups reached the lowest body weight ( P < 0.05), NCD presented the highest body Ca content ( P < 0.05) and there were no differences between LCD and HCD. This in vivo study showed that regardless of the dietary calcium content, the maternal skeleton is slightly affected by pregnancy but severely affected by lactation. However, the degree of such response appears to depend not only on dietary Ca content but also on dietary Ca/P molar ratio.


L-arginine causes amelioration of cerebrovascular dysfunction and brain inflammation during experimental heatstroke.
Cerebrovascular dysfunction ensuing from severe heatstroke includes intracranial hypertension, cerebral hypoperfusion, and brain inflammation. We attempted to assess whether L-arginine improves survival during experimental heatstroke by attenuating these reactions. Anesthetized rats, 70 min after the start of heat stress (43 degrees C), were divided into two major groups and given the following: vehicle solution (1 mL/kg body weight) or L-arginine (50-250 mg/kg body weight) intravenously. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. Their physiological and biochemical parameters were continuously monitored. When the vehicle-treated rats underwent heat stress, their survival time values were found to be 20 to 26 min. Treatment with i.v. doses of L-arginine significantly improved the survival rate during heatstroke (54-245 min). As compared with those of normothermic controls, all vehicle-treated heatstroke animals displayed higher levels of core temperature, intracranial pressure, and NO metabolite, glutamate, glycerol, lactate-pyruvate ratio, and dihydroxybenzoic acid in hypothalamus. In addition, hypothalamic levels of IL-1beta and TNF-alpha were elevated after heatstroke onset. In contrast, all vehicle-treated heatstroke animals had lower levels of MAP, cerebral perfusion pressure, cerebral blood flow, and brain partial pressure of oxygen. Administration of L-arginine immediately after the onset of heatstroke significantly reduced the intracranial hypertension and the increased levels of NO metabolite, glutamate, glycerol, lactate-pyruvate ratio, and dihydroxybenzoic acid in the hypothalamus that occurred during heatstroke. The heatstroke-induced increased levels of IL-1beta and TNF-alpha in the hypothalamus were suppressed by L-arginine treatment. In contrast, the hypothalamic levels of IL-10 were significantly elevated by L-arginine during heatstroke. The results suggest that L-arginine may cause attenuation of heatstroke by reducing cerebrovascular dysfunction and brain inflammation.


Randomised, controlled study of preoperative electroacupuncture for postoperative pain control after cardiac surgery.
This study aims to evaluate the effects of preoperative electroacupuncture (EA) on the need for opioids in the postoperative stage of conventional cardiac surgery. A prospective, randomised and controlled study was conducted at Unimed Hospital Centre in Joinville, SC, Brazil. The day before the surgery, 32 patients undergoing cardiac surgery were randomised into two groups: patients from the treatment group received preoperative EA at bilateral points (LI4-LI11, LR3-ST36, PC6-TE5) for 30 min with alternating frequencies of 3 and 15 Hz. Patients from the control group received sham transcutaneous electrical nerve stimulation (TENS). Use of fentanyl during the postoperative period was measured. 10 patients were excluded because of hemodynamic and ventilatory instability leaving 13 (10 male) in the treatment group and 9 (4 male) in the control group. The average total doses of fentanyl given were 13.1±2.2 and 16.3±1.6 μg/kg in the treatment and control groups respectively (p<0.002). The doses of patient controlled analgesia were 4.1±2.0 and 6.9±1.7 μg/kg in the treatment and control groups respectively (p<0.003). The number of boluses issued also differed (treatment 13.9±7.0 vs control 24.8±7.0, p<0.002). Pain intensity scores differed between the groups (treatment 2.5±1.1 vs control 4.0±2.0, p<0.04). One patient from the control group experienced drowsiness that justified a change in fentanyl infusion, as decided by the anaesthetist. Preoperative electro-acupuncture in conventional cardiac surgery may reduce the postoperative consumption of fentanyl.


[Acquired immunodeficiency syndrome (AIDS) in Lubumbashi. Clinical and epidemiological observations].
26 AIDS cases (13 males and 13 females) have been noticed in the internal medicine service of the Lubumbashi University Clinics, town at the boundary of the south-east of Zaïre. The clinical data are conventional: only heterosexual transmission seems prevalent. The shortage of HIV diagnosis means restrain larger survey, but 5 to 7% of blood givers are AIDS carriers. The risk of AIDS dissemination is real, even in rural areas of some regions with permanent connections of larger urban centres.


Histological evaluation of a replanted tooth retained for 49 years.
A maxillary incisor that had been replanted immediately after avulsion 49 years previously was evaluated histologically after extraction. The histological evaluation revealed resorption of the apical root surface, depositions in cement with different phases and mineral density, and histological changes in the periodontal ligament.


An NAD(P)H:Quinone Oxidoreductase 1 Responsive and Self-Immolative Prodrug of 5-Fluorouracil for Safe and Effective Cancer Therapy.
Tripartite prodrug 1, composed of an NAD(P)H:quinone oxidoreductase 1 (NQO1)-responsive trigger group, a self-immolative linker, and the active drug 5-fluorouracil (5-FU), was designed and synthesized for site-specific cancer therapy. Upon bioreductive activation by NQO1, 1 can release the parent drug 5-FU specifically in NQO1-overexpressing cancer cells. This prodrug exerts comparable antitumor activity and a more favorable safety profile compared with 5-FU both in vitro and in vivo.


Renal scarring on DMSA scan is associated with hypertension and decreased estimated glomerular filtration rate in spina bifida patients in the age of transition to adulthood.
Improved management for spina bifida (SB) has increased the number of patients transitioning to adult care. This trend increases the importance of maintaining renal function concurrently with bladder function in patients with SB. Dimercaptosuccinic acid (DMSA) renal scanning is an optimal tool for investigating renal insufficiency in children with SB; however, the benefits of DMSA scans in adulthood are unclear. The role of DMSA renal scans for patients with SB during the transition to adulthood (15-25 years of age) to reveal their association with current renal function was investigated. DMSA renal scanning was routinely performed patients with SB aged 15-25 years concurrently with examination of serum creatinine, serum cystatin C, urinalysis, and blood pressure between January 2006 and August 2016. Hypertension was defined as systolic or diastolic pressure above the age-specific normal range. The estimated glomerular filtration rate (eGFR) using serum creatinine or cystatin C was calculated; decreased eGFR was defined as eGFR below 90 mL/min/1.73 m2. Patients were divided into two groups according to the absence or presence of renal scarring on DMSA scan. Factors associated with renal function, including hypertension, decreased eGFR, and proteinuria, were compared between groups. Eighty-seven patients (36 males and 51 females) were analyzed. Median age was 19 years (range 15-24 years); 28 patients (32%) had renal scarring. Patients with renal scarring had significantly higher rates of hypertension (n = 13, 46%) and decreased eGFR (n = 5, 18%). However, there was no difference in proteinuria between the groups (Table). The group with renal scarring had significantly lower eGFR. This study showed that DMSA scans in patients with SB aged between 15 and 25 years were useful for assessing renal scarring despite a history of febrile urinary tract infection. DMSA scans could be performed in all patients with SB in the transition to adulthood to detect renal scarring. This study also showed that renal scarring was associated with hypertension and decreased eGFR in this age group. Treatment with antihypertensive drugs should be considered for patients with SB with renal scarring in this age range to protect renal function. Spina bifida patients in the age of transition to adulthood with renal scarring already showed signs of chronic kidney disease, suggesting that DMSA renal scans could be useful to identify patients who require close monitoring of renal function.


Infradian awake and asleep systolic and diastolic blood pressure rhythms in humans.
Blood pressure shows 24-h rhythms with a significant seasonal fluctuation. To characterize 2-month to 12-month infradian rhythms in the mean awake and asleep systolic blood pressure (SBP) and diastolic blood pressure (DBP) in humans. A total of 1689 participants underwent 24-h ambulatory blood pressure monitoring during different periods of the year. The mean daily temperature, humidity, barometric pressure and wind velocity values for the same time span and geographical location were obtained. Fourier analysis was used to fit 12-month, 6-month, 4-month, 3-month and 2-month rhythms to the mean awake and asleep SBP and DBP and to metereological variables. The awake mean SBP and DBP values showed significant 12-month and 3-month rhythms (respectively, R2 = 55%, P < 0.001 and R2 = 45% P < 0.001), with a peak in July (winter) and a trough-peak difference of 6.2 +/- 1.6 mmHg (P < 0.001, SBP) and 4.2 +/- 1.5 mmHg (P < 0.001, DBP). In contrast, asleep blood pressure means showed mainly 3-month rhythms (SBP, R2 = 19%, P < 0.02; DBP, R2 = 43% P < 0.02). Mean daily temperature and humidity showed at 12-month, 6-month, 4-month, 3-month and 2-month rhythms, barometric pressure showed 12-month and 6-month rhythms, and wind velocity showed 12-month and 3-month rhythms. Minimal temperature values and maximal humidity values coincided with elevated blood pressure values. Awake blood pressure means exhibited mainly circannual fluctuations while asleep blood pressure means showed principally 3-month rhythms. Infradian blood pressure variations correlated with some meteorological variables.


Kinetics of energy consumption in human platelets with blocked ATP regeneration.
Abrupt arrest of ATP resynthesis in blood platelets induces a rapid decline in metabolic ATP-ADP. This decline is biexponential with a 7-fold difference in the rate-constants of the two components. Stimulation with thrombin increases both rate-constants, and raises the relative contribution of the rapid component from 60 to 90% of total. The initial decline can be approximated by a single exponential term, yielding the rate-constant for initial ATP hydrolysis. Since this initial decline reflects energy consumption of undisturbed platelets, this approach offers a sensitive means to determine energy consumption and ATP turnover within short time intervals.


Decrease of cyclin D1 in the human lung adenocarcinoma cell line A-427 by 7-hydroxycoumarin.
Coumarin in vivo has antitumor activity in various types of cancer. In vitro, coumarin and 7-hydroxycoumarin, its major biotransformation product in humans, inhibit the proliferation of several human tumor cell lines. The molecular mechanisms of these effects are unknown. To gain information about these mechanisms, we studied the effects of coumarin and 7-hydroxycoumarin in the human lung adenocarcinoma cell line A-427 on the inhibition of: (i) cell proliferation; (ii) cell cycle progression; and (iii) expression of cyclins D1, E and A. The inhibitory concentrations 50 (IC(50)) of both compounds were estimated by cytostatic assays of tetrazolium (MTT) reduction. The effects on cell cycle progression were assayed with propidium iodide and BrdU using DNA histograms and multiparametric flow cytometry. The percentages of cells expressing cyclins D1, E, and A were estimated by means of bivariate flow cytometry using propidium iodide, and FITC-conjugated monoclonal antibodies for each cyclin. The IC(50) (+/-S.E.M. n=3) of 7-hydroxycoumarin and coumarin at 72 h exposure, were 100+/-4.8 and 257+/-8.8 microg/ml, respectively. 7-Hydroxycoumarin at the concentration of 160 microg/ml (1 mM), inhibited the G(1)/S transition of the cell cycle, an action consistent with the cytostatic effect. No significant decreases of cyclins E and A were observed. In contrast, cyclin D1 significantly decreased, which appears to indicate an action of 7-hydroxycoumarin in early events of phase G(1). However, messenger RNA of cyclin D1, assayed by RT-PCR, did not change. This suggests a posttranscriptional effect. The effects of coumarin were not significant. Cyclin D1 is overexpressed in many types of cancer, and its inhibition has been proposed as a pharmacological and therapeutic target for novel antitumor agents. Knowledge of the decrease of cyclin D1 by 7-hydroxycoumarin may lead to its use in cancer therapy, as well as to the development of more active compounds.


Lignans from the bark of Zanthoxylum simulans.
Investigation on the EtOAc extract of the bark of Zanthoxylum simulans led to the isolation of four new lignans including zanthoxylumin A (1), zanthoxylumin B (2), ( - )-magnolin (3), and ( - )-pinoresinol-di-3,3-dimethylallyl ether (4). Their structures were established by comprehensive analysis of the spectral data, especially 1D and 2D NMR spectra.


Mediastinal tracheostomy: unilateral resection of the anterior chest wall.
Since the first reliable mediastinal tracheostomy described by Grillo et al. in 1966, many new techniques have been described in order to reduce the number of complications. We here report the case of a 55-year-old man who was referred for surgery with post-radiochemotherapy recurrence of a double neoplasm of the pharyngolarynx extending to the proximal trachea and the medial part of the oesophagus. Through a median sternotomy, a pharyngolaryngoesophagectomy was performed with an extended tracheal resection. The reconstruction of the upper digestive tract was performed with a gastric pull-up. The mediastinal tracheostomy was performed with a pectoralis major muscular flap through a right unilateral resection of the manubrium, the right clavicular head and the right first and second costal cartilages. Historically, the mediastinal tracheostomy was performed through a large bilateral resection of the anterior chest wall, in order to prevent the tension on the tracheocutaneous sutures. Nowadays, with the possibility of various pedicled flaps, bilateral resection no longer seems to be necessary. This unilateral resection leads to a reduction in post-operative sequelae.


Analgesic effects of melatonin: a review of current evidence from experimental and clinical studies.
Melatonin is an endogenous indoleamine, produced mainly by the pineal gland. Melatonin has been proven to have chronobiotic, antioxidant, antihypertensive, anxiolytic and sedative properties. There are also experimental and clinical data supporting an analgesic role of melatonin. In experimental studies, melatonin shows potent analgesic effects in a dose-dependent manner. In clinical studies, melatonin has been shown to have analgesic benefits in patients with chronic pain (fibromyalgia, irritable bowel syndrome, migraine). The physiologic mechanism underlying the analgesic actions of melatonin has not been clarified. The effects may be linked to G(i) -coupled melatonin receptors, to G(i) -coupled opioid μ-receptors or GABA-B receptors with unknown downstream changes with a consequential reduction in anxiety and pain. Also, the repeated administration of melatonin improves sleep and thereby may reduce anxiety, which leads to lower levels of pain. In this paper, we review the current evidence regarding the analgesic properties of melatonin in animals and humans with chronic pain.