Molecular and functional characterization of the adiponectin (AdipoQ) gene in goat skeletal muscle satellite cells.
It is commonly accepted that adiponectin binds to its two receptors to regulate fatty acid metabolism in adipocytes. To better understand their functions in the regulation of intramuscular adipogenesis in goats, we cloned the three genes (adiponectin [AdipoQ], adiponectin receptor 1 [AdipoR1], and AdipoR2) encoding these proteins and detected their mRNA distribution in different tissues. We also determined the role of AdipoQ in the adipogenic differentiation of goat skeletal muscle satellite cells (SMSCs). SMSCs were isolated using 1 mg/mL Pronase E from the longissimus dorsi muscles of 3-day-old female Nanjiang brown goats. Adipogenic differentiation was induced in satellite cells by transferring the cells to Dulbecco's modified Eagle's medium supplemented with an isobutylmethylxanthine, dexamethasone and insulin cocktail. The pEGFP-N1-AD plasmid was transfected into SMSCs using Lipofectamine 2000. Expression of adiponectin in tissues and SMSCs was detected by quantitative polymerase chain reaction and immunocytochemical staining. The three genes were predominantly expressed in adipose and skeletal muscle tissues. According to fluorescence and immunocytochemical analyses, adiponectin protein expression was only observed in the cytoplasm, suggesting that adiponectin is localized to the cytoplasm of goat SMSCs. In SMSCs overexpressing the AdipoQ gene, adiponectin promoted SMSC differentiation into adipocytes and significantly (p<0.05) up-regulated expression of AdipoR2, acetyl-CoA carboxylase, fatty-acid synthase, and sterol regulatory element-binding protein-1, though expression of CCAAT/enhancer-binding protein-α, peroxisome proliferator-activated receptor γ, and AdipoR1 did not change significantly. Adiponectin induced SMSC differentiation into adipocytes, indicating that adiponectin may promote intramuscular adipogenesis in goat SMSC.


Successful stenting of a brachial artery occlusion following surgical retrieval of a twisted diagnostic catheter during transradial coronary angiography.
Coronary angiography and percutaneous coronary intervention via radial access has been progressively performed over the last three decades and has become standard of care. Even though the radial approach, compared with femoral access, is safe and is also associated with less bleeding in patients with myocardial infarction, it may be problematic in some cases. Here, we describe an 80-year-old woman with brachial artery dissection due to a twisted diagnostic catheter during transradial coronary angiography, who subsequently underwent surgical retrieval of the catheter.


Metabolic profiling and flux analysis of MEL-2 human embryonic stem cells during exponential growth at physiological and atmospheric oxygen concentrations.
As human embryonic stem cells (hESCs) steadily progress towards regenerative medicine applications there is an increasing emphasis on the development of bioreactor platforms that enable expansion of these cells to clinically relevant numbers. Surprisingly little is known about the metabolic requirements of hESCs, precluding the rational design and optimisation of such platforms. In this study, we undertook an in-depth characterisation of MEL-2 hESC metabolic behaviour during the exponential growth phase, combining metabolic profiling and flux analysis tools at physiological (hypoxic) and atmospheric (normoxic) oxygen concentrations. To overcome variability in growth profiles and the problem of closing mass balances in a complex environment, we developed protocols to accurately measure uptake and production rates of metabolites, cell density, growth rate and biomass composition, and designed a metabolic flux analysis model for estimating internal rates. hESCs are commonly considered to be highly glycolytic with inactive or immature mitochondria, however, whilst the results of this study confirmed that glycolysis is indeed highly active, we show that at least in MEL-2 hESC, it is supported by the use of oxidative phosphorylation within the mitochondria utilising carbon sources, such as glutamine to maximise ATP production. Under both conditions, glycolysis was disconnected from the mitochondria with all of the glucose being converted to lactate. No difference in the growth rates of cells cultured under physiological or atmospheric oxygen concentrations was observed nor did this cause differences in fluxes through the majority of the internal metabolic pathways associated with biogenesis. These results suggest that hESCs display the conventional Warburg effect, with high aerobic activity despite high lactate production, challenging the idea of an anaerobic metabolism with low mitochondrial activity. The results of this study provide new insight that can be used in rational bioreactor design and in the development of novel culture media for hESC maintenance and expansion.


Neuroendocrine and metabolic determinants of the adaptation of GH/IGF-I axis to obesity.
Obese patients show marked impairment in spontaneous secretion as well as in the somatotroph responsiveness to all provocative stimuli. GH insufficiency in obese patients has been reported reversible after long-term diet and marked weight loss but somatotroph secretion is not restored by fasting. Among potential neuroendocrine causes, GHRH hypoactivity has been shown but it is likely that alterations in the influence of ghrelin, the gastric-derived natural ligand of the GHS-R, and or of the NPY/leptin interplay could have a role. Among metabolic alterations, the chronic elevation of FFA levels and hyperinsulinism probably have a key role in causing GH insufficiency in obesity. Despite marked GH insufficiency, total IGF-I levels are basically preserved while free IGF-I levels are even increased thus questioning real hypoactivity of GH/IGF-I axis in obesity. Peripheral GH hypersensitivity due to increased GH receptor status, hyperinsulinism and reduced IGFBP-I levels likely explain almost normal total IGF-I and increased free IGF-I levels which, in turn, probably exert an increased negative feedback action on somatotroph cells.


Genome, integration, and transduction of a novel temperate phage of Helicobacter pylori.
Helicobacter pylori is a common human pathogen that has been identified to be carcinogenic. This study isolated the temperate bacteriophage 1961P from the lysate of a clinical strain of H. pylori isolated in Taiwan. The bacteriophage has an icosahedral head and a short tail, typical of the Podoviridae family. Its double-stranded DNA genome is 26,836 bp long and has 33 open reading frames. Only 9 of the predicted proteins have homologs of known functions, while the remaining 24 are only similar to unknown proteins encoded by Helicobacter prophages and remnants. Analysis of sequences proximal to the phage-host junctions suggests that 1961P may integrate into the host chromosome via a mechanism similar to that of bacteriophage lambda. In addition, 1961P is capable of generalized transduction. To the best of our knowledge, this is the first report of the isolation, characterization, genome analysis, integration, and transduction of a Helicobacter pylori phage.


Thiol oxidation by nitrosative stress: Cellular localization in human spermatozoa.
Peroxynitrite is a highly reactive nitrogen species and when it is generated at high levels it causes nitrosative stress, an important cause of impaired sperm function. High levels of peroxynitrite have been shown to correlate with decreased semen quality in infertile men. Thiol groups in sperm are mainly found in enzymes, antioxidant molecules, and structural proteins in the axoneme. Peroxynitrite primarily reacts with thiol groups of cysteine-containing proteins. Although it is well known that peroxynitrite oxidizes sulfhydryl groups in sperm, the subcellular localization of this oxidation remains unknown. The main objective of this study was to establish the subcellular localization of peroxynitrite-induced nitrosative stress in thiol groups and its relation to sperm motility in human spermatozoa. For this purpose, spermatozoa from healthy donors were exposed in vitro to 3-morpholinosydnonimine (SIN-1), a compound which generates peroxynitrite. In order to detect peroxynitrite and reduced thiol groups, the fluorescent probes, dihydrorhodamine 123 and monobromobimane (mBBr), were used respectively. Sperm viability was analyzed by propidium iodide staining. Peroxynitrite generation and thiol redox state were monitored by confocal microscopy whereas sperm viability was evaluated by flow cytometry. Sperm motility was analyzed by CASA using the ISAS(®) system. The results showed that exposure of human spermatozoa to peroxynitrite results in increased thiol oxidation which is mainly localized in the sperm head and principal piece regions. Thiol oxidation was associated with motility loss. The high susceptibility of thiol groups to peroxynitrite-induced oxidation could explain, at least in part, the negative effect of reactive nitrogen species on sperm motility. DHR: dihydrorhodamine 123; mBBr: monobromobimane ONOO(-): peroxynitrite RNS: reactive nitrogen species RFI: relative fluorescence intensity SIN-1: 3-morpholinosydnonimine CASA: Computer-Aided Sperm Analysis PARP: poli ADP ribose polimerasa VCL: curvilinear velocity VSL: straight-line velocity VAP: average path velocity PRDXs: peroxiredoxins ODF: outer dense fiber ODF1: outer dense fiber 1 PI: propidium iodide DMSO: dimethyl sulfoxide SD: standard deviation analysis of variance.


A light sheet fluorescence microscopy protocol for Caenorhabditis elegans larvae and adults.
Light sheet fluorescence microscopy (LSFM) has become a method of choice for live imaging because of its fast acquisition and reduced photobleaching and phototoxicity. Despite the strengths and growing availability of LSFM systems, no generalized LSFM mounting protocol has been adapted for live imaging of post-embryonic stages of C. elegans. A major challenge has been to develop methods to limit animal movement using a mounting media that matches the refractive index of the optical system. Here, we describe a simple mounting and immobilization protocol using a refractive-index matched UV-curable hydrogel within fluorinated ethylene propylene (FEP) tubes for efficient and reliable imaging of larval and adult C. elegans stages.


Involvement of propionate side chains of the heme in circular dichroism of myoglobin: experimental and theoretical analyses.
Incorporation of the heme into globin induces a prominent circular dichroism (CD) band in the Soret region. The appearance of heme optical activity is widely believed to arise from the interaction between the heme and aromatic residues of the globin. However, hemoglobin (Hb) containing the reversed heme exhibits a CD spectrum obviously different from that of native Hb, indicating that the interactions of heme side chains with globin contribute to the appearance of heme optical activity. We examined this possibility by comparing CD spectra of native myoglobin (Mb) and those of Mb reconstituted with synthetic hemes lacking vinyl and/or propionate. Replacement of 2,4-vinyl groups with methyl induced moderate changes. In contrast, replacement of 6,7-propionate groups with carboxylate resulted in complete disappearance of the positive Soret CD band. To get theoretical basis for the contributions of 6,7-side chains on the band, we investigated the CD spectra at a time-dependent density functional theory level. In the antiparallel conformation of the 6,7-side chains, the rotational strengths were calculated to be positive, on the other hand in the parallel conformation to be negative. We also found that the weak Soret CD band in 2,4-dimethyl-6,7-dicarboxyheme can be explained by canceling between different carboxyl conformers.


Features characterising cardiac autonomic neuropathy in diabetes using ensembled classification.
Using supervised machine learning to classify the severity of cardiovascular autonomic neuropathy (CAN). The aims were 1) to investigate which features contribute to characterising CAN 2) to generate an ensembled set of features that best describes the variation in CAN classification. Eighty-two features from demographic, beat-to-beat, biochemical, and inflammation were obtained from 204 people with diabetes and used in three machine-learning-classifiers, these are: support vector machine, decision tree, and random forest. All data were ensembled using a weighted mean of the features from each classifier. The 10 most important features derived from the domains: Beat-to-beat, inflammation markers, disease-duration, and age. Beat-to-beat measures associate with CAN as diagnosis is mainly based on cardiac reflex responses, disease-duration and age are also related to CAN development throughout disease progression. The inflammation markers may reflect the underlying disease process, and therefore, new treatment modalities targeting systemic low-grade inflammation should potentially be tested to prevent the development of CAN. Cardiac reflex responses should be monitored closely to diagnose and classify severity levels of CAN accurately. Standard clinical biochemical analytes, such as glycaemic level, lipidic level, or kidney function were not included in the ten most important features. Beat-to-beat measures accounted for approximately 60% of the features in the ensembled data.


[Topography of age-related size changes in corneal endothelial cells].
Age-related changes in corneal endothelial cell size were investigated in 116 eyes, from newborn to 96 years of age, by light microscopy. The preliminary findings show a regional distribution of cell changes on the endothelial surface. The endothelium of a newborn was homogeneous in cell size and shape. From the third decade of life onward, polymorphism and cell size variations occurred in the central endothelium. In corneas of patients over 50 years old, one-third of the cases often had a geographic arrangement of cells of increased size in the mid-periphery (3.5-4.0 mm paracentrally). Small cells were always predominant at the periphery.


Herbicide-resistant alfalfa cells: an example of gene amplification in plants.
We have selected alfalfa suspension cell lines that are 20- to 100-fold more resistant than wild-type cells to the nonselective herbicide L-phosphinothricin, a mixed competitive inhibitor of glutamine synthetase (GS). GS enzyme levels are three- to sevenfold elevated in the variant cell line. Partial amino acid sequences of two cyanogen bromide cleavage peptides have been determined on GS purified from the variant cell line and used to confirm the identity of a 276-base pair GS cDNA clone. Southern blot analysis of wild-type and variant cell DNAs using this cDNA as a probe indicate that resistance to L-phosphinothricin is a consequence of a four- to 11-fold amplification of one GS gene resulting in about an eightfold increase in mRNA levels, and an increased enzyme synthesis sufficient to overcome the toxic effects of the inhibitor.


Elementary steps of iron catalysis: exploring the links between iron alkyl and iron olefin complexes for their relevance in C-H activation and C-C bond formation.
The alkylation of complexes 2 and 7 with Grignard reagents containing β-hydrogen atoms is a process of considerable relevance for the understanding of C-H activation as well as C-C bond formation mediated by low-valent iron species. Specifically, reaction of 2 with EtMgBr under an ethylene atmosphere affords the bis-ethylene complex 1 which is an active precatalyst for prototype [2+2+2] cycloaddition reactions and a valuable probe for mechanistic studies. This aspect is illustrated by its conversion into the bis-alkyne complex 6 as an unprecedented representation of a cycloaddition catalyst loaded with two substrates molecules. On the other hand, alkylation of 2 with 1 equivalent of cyclohexylmagnesium bromide furnished the unique iron alkyl species 11 with a 14-electron count, which has no less than four β-H atoms but is nevertheless stable at low temperature against β-hydride elimination. In contrast, the exhaustive alkylation of 1 with cyclohexylmagnesium bromide triggers two consecutive C-H activation reactions mediated by a single iron center. The resulting complex has a diene dihydride character in solution (15), whereas its structure in the solid state is more consistent with an η(3) -allyl iron hydride rendition featuring an additional agostic interaction (14). Finally, the preparation of the cyclopentadienyl iron complex 25 illustrates how an iron-mediated C-H activation cascade can be coaxed to induce a stereoselective CC bond formation. The structures of all relevant new iron complexes in the solid state are presented.


COX-2 inhibitors can down-regulate in vivo antibody response against T-dependent antigens.
There are many studies demonstrating by different experimental models that non-steroidal antiinflammatory drugs (NSAIDs), also known as cyclooxygenase-2 (COX-2) inhibitors, can modulate immune response such as lymphoid cells differentiation and proliferation. There are experimental data which show that activated B cells can express mRNA COX-2, release prostaglandins (PGs) and produce immunoglobulins in PGs dependent manner. In this study, using different COX-2 inhibitors and applying personalized immunization scheme, we confirmed that it is possible to modulate in vivo antibody response against T cell dependent antigens, substantiating the importance of PGE2 and E prostanoid receptor (EP-R) in antibody generation. Our results point out the fact that we must be more careful when we apply vaccines containing T-cell dependent antigens, such as tetanus or diphteric anatoxin, to the patients under an intense antiinflammatory treatment.


Effect of lifestyle on periodontal disease status in diabetic patients.
Lifestyle and socioeconomic status have been associated with the disease status of diabetic patients. However, there have been few reports on the relationship between these factors and the periodontal condition of diabetics. We assessed the association between disease status and lifestyle of diabetic patients and clinical features of advanced periodontitis such as deep probing depths and severe alveolar bone loss. Fifty-seven diabetic patients were examined in this study. Clinical assessment of probing pocket depth and radiographic alveolar bone loss was performed. Data regarding diabetic status and lifestyle of the diabetic patients were also recorded and statistically analysed by logistic regression. Drinking habits and high values of hemoglobin A1c (HbA1c) (>9.0%) were significantly associated with deep probing depth. The odds ratios (OR) of these factors were 7.72 (95% confidence interval (CI), 1.80 to 33.19), and 6.10 (95% CI = 1.23 to 30.25), respectively. Presence of complications such as retinopathy (OR = 8.86, 95% CI, 1.99 to 39.40), irascible behaviour (OR = 8.40, 95% CI = 1.33 to 53.17) and high value of HbA1c (OR = 4.94, 95% CI = 1.14 to 21.46) were significantly related to mean advanced alveolar bone loss. Only the high value of HbA1c (OR = 3.53, 95% CI = 1.06 to 11.73) was detected as a significant factor related to advanced periodontitis, characterised by more than 50% mean alveolar bone loss, or two or more teeth with probing depth greater than 6 mm. In conclusion, drinking habit and irascible behaviour are correlated with the periodontal disease condition of diabetic patients, in addition to a high value of HbA1c (>9.0%). Lifestyle and psychosocial stress may affect the periodontal disease status of diabetic patients.


Arsenic contamination of rural community wells in Nicaragua: A review of two decades of experience.
Several surveys have been conducted in Nicaragua between 1996 and 2015 confirming the presence of high levels of arsenic (>10 μg/L). In this paper, these peer-reviewed (n = 2) and non-peer reviewed sources (n = 14) have been combined to provide an extensive overview of the arsenic contamination of drinking water sources in Nicaragua. So far, arsenic contamination has been detected in over 80 rural communities located in 34 municipalities of the country and arsenic poisoning has been identified in at least six of those communities. The source of arsenic contamination in Nicaragua is probably volcanic in origin, both from volcanic rocks and geothermal fluids which are distributed across the country. Arsenic may have directly entered into the groundwater by geothermally-influenced water bodies, or indirectly by reductive dissolution or alkali desorption, depending on the local geochemical conditions.


Phosphatidylinositol 4,5-bisphosphate anchors cytosolic group IVA phospholipase A2 to perinuclear membranes and decreases its calcium requirement for translocation in live cells.
The eicosanoids are centrally involved in the onset and resolution of inflammatory processes. A key enzyme in eicosanoid biosynthesis during inflammation is group IVA phospholipase A2 (also known as cytosolic phospholipase A2alpha, cPLA2alpha). This enzyme is responsible for generating free arachidonic acid from membrane phospholipids. cPLA2alpha translocates to perinuclear membranes shortly after cell activation, in a process that is governed by the increased availability of intracellular Ca2+. However, cPLA2alpha also catalyzes membrane phospholipid hydrolysis in response to agonists that do not mobilize intracellular Ca2+. How cPLA2alpha interacts with membranes under these conditions is a major, still unresolved issue. Here, we report that phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] promotes translocation of cPLA2alpha to perinuclear membranes of intact cells in a manner that is independent of rises in the intracellular Ca2+ concentration. PtdIns(4,5)P2 anchors the enzyme to perinuclear membranes and allows for a proper interaction with its phospholipid substrate to release arachidonic acid.


The Cancer Genetics Network: recruitment results and pilot studies.
The National Cancer Institute established the Cancer Genetics Network (CGN) to support collaborative investigations into the genetic basis of cancer susceptibility, explore mechanisms to integrate this new knowledge into medical practice, and identify ways of addressing the associated psychosocial, ethical, legal, and public health issues. The CGN has developed the complex infrastructure required to support the projects, including the establishment of guidelines and policies, uniform methods, standard questionnaires to be used by all of the centers, and a standard format for submission of data to the Informatics Center. Cancer patients and their family members have been invited to enroll and be included in a pool of potential study participants. The Information Technology Group is responsible for support of the design, implementation, and maintenance of the multicenter Network-wide research protocols. As of January 2004, the CGN contained data on 23,995 probands (participants) and 425,798 family members. As a resource for cancer genetic studies, the CGN has a large number of probands and first-degree relatives with and without cancer and with multiple ethnicities. Different study designs can be used including case-control, case-case, and family studies. The unique resources of the CGN are available for studies on cancer genetic susceptibility, translational research, and behavioral research. The CGN is now at a point where approved collaborators may have access to enrolled patients and their families for special studies, as well as to the clinical, environmental and family cancer history data banked in the Informatics Center.


The paradoxical effects of analgesics and the development of chronic migraine.
In a subgroup of individuals episodic migraine evolves into a stage where individuals have headaches on more days than not. Among the risk factors for chronification, excessive use of analgesic medications figure prominently and reviewing this topic is the scope of this article. The issue of causality is discussed and evidence suggesting that specific medications, at critical doses, are risk factors for chronic migraine (CM) is reviewed. The concept of critical dose of exposure for different classes is presented and biological plausibility and putative mechanisms are reviewed.


Comparison of bandwidths in the inferior colliculus and the auditory nerve. I. Measurement using a spectrally manipulated stimulus.
A defining feature of auditory systems across animal divisions is the ability to sort different frequency components of a sound into separate neural frequency channels. Narrowband filtering in the auditory periphery is of obvious advantage for the representation of sound spectrum and manifests itself pervasively in human psychophysical studies as the critical band. Peripheral filtering also alters coding of the temporal waveform, so that temporal responses in the auditory periphery reflect both the stimulus waveform and peripheral filtering. Temporal coding is essential for the measurement of the time delay between waveforms at the two ears-a critical component of sound localization. A number of human psychophysical studies have shown a wider effective critical bandwidth with binaural stimuli than with monaural stimuli, although other studies found no difference. Here we directly compare binaural and monaural bandwidths (BWs) in the anesthetized cat. We measure monaural BW in the auditory nerve (AN) and binaural BW in the inferior colliculus (IC) using spectrally manipulated broadband noise and response metrics that reflect spike timing. The stimulus was a pair of noise tokens that were interaurally in phase for all frequencies below a certain flip frequency (f(flip)) and that had an interaural phase difference of pi above f(flip). The response was measured as a function of f(flip) and, using a separate stimulus protocol, as a function of interaural correlation. We find that both AN and IC filter BW depend on characteristic frequency, but that there is no difference in mean BW between the AN and IC.


Spectrophotometric study of acidity constants of Alizarine Red S in various water-organic solvent.
The acidity constants of Alizarine Red S were determined spectrophotometrically at 25 degrees C and at constant ionic strength 0.1 M (KNO3) in pure water as well as in aqueous media containing variable mole percentages (5-70%) of organic solvents. The organic solvents used were methanol, ethanol, N,N-dimethyl formamide (DMF), dimethyl sulfoxide (DMSO), acetonitrile and dioxan. The acidity constants of all related equilibria are estimated using the whole spectral fitting of the collected data to an established factor analysis model. DATAN program was applied for determining of acidity constants and pure spectra of different form of Alizarine Red S. The obtained results indicated that acidity constants decrease as the content of an organic solvent in the medium increases. There are linear relationship between acidity constants and the mole fraction of various organic solvents in the solvent mixtures. Effect of various solvents on acidity constants and pure spectrum of each component are also discussed.


MicroRNA-150 promote apoptosis of ovine ovarian granulosa cells by targeting STAR gene.
To better understand the function of oar-miR-150 in the ovine granulosa cells (GCs) during the estrus cycle, the five turpan sheep were selected for detection of the expression of oar-miR-150 in follicular and luteal ovaries, respectively. Then the granulosa cells treated with oar-miR-150 mimics or negative control (NC) were analyzed by qPCR to assess the expression of genes involved in steroidogenic and apoptosis. Expression of oar-miR-150 was increased in follicular phase compared with that in luteal ovaries. STAR was a target gene of miR-150 with oar-miR-150 mimic or inhibitor and luciferase reporter assay. Overexpression of oar-miR-150 promoted expression of bax, bcl2 and Casp3 expression and declined the expression of STAR, Cyp11a1 and HSD3B1 in vitro. Taken together, these results demonstrate that the oar-miR-150 promote GCs apoptosis through modifying the expression of genes involved in progesterone synthesis.


Control of wilt disease of lentil through bio control agents and organic amendments in Tarai region of Uttarakhand, India.
The present work aimed at evaluating the efficacy of bioagents and organic amendments against lentil wilt pathogen. Field trials were carried out consecutively during Rabi 2010-11 and 2011-12 crop seasons in Randomized Block Design (RBD) with three replications, using 'Pant L-639' a popular cultivar. The plot size was 3.0 x 1.5 m2 with row spacing of 30 cm. Effect of selected bioagents and organic amendments on disease incidence, 1000 grain weight and yield kg ha' of lentil was recorded. It was observed that seed treatment with Trichoderma harizanum + Pseudomonas fluorescens significant by reduced 1.73% (2010-11) and 1.93% (2011-12) in Fusarium wilt disease incidence and increase in grain yield 507.6 kg ha(-1) and 496.0 kg ha(-1) respectively during both crop seasons. Among organic amendments, minimum wilt disease incidence of 1.69% (2010-11) and 1.81% (2011-12) and maximum grain yield 496.3 kg ha(-1) (2010-11) and 484.0 kg ha(-1) (2011-12) were observed in farm yard manure + spent compost treated plots. This indicates that these treatments have important roles in biologically based management strategies for controling Fusarium wilt disease under organic mode of lentil cultivation in Uttarakhand State.


Subependymal mass lesions and peripheral polyneuropathy in adult-onset glutaric aciduria type I.
Glutaric aciduria type I (GA-I) is an autosomal recessive disease caused by a deficiency of the mitochondrial enzyme glutaryl CoA dehydrogenase (GCDH). This metabolic block causes increased urinary concentrations of glutaric and 3-hydroxyglutaric acids. The accumulation and excretion of glutarylcarnitine esters leads to secondary carnitine deficiency. GA-I has an incidence of 1:30,000. The clinical hallmark of GA-I is an acute encephalopathic crisis, with bilateral striatal necrosis presented by severe dystonic dyskinetic disorder. Most patients have their first symptoms during infancy, but some have a less severe form of the disease and some may even remain asymptomatic.


Unusual enantioselective cytoplasm-to-nucleus translocation and photosensitization of the chiral Ru(II) cationic complex via simple ion-pairing with lipophilic weak acid counter-anions.
Targeted and enantioselective delivery of chiral diagnostic-probes and therapeutics into specific compartments inside cells is of utmost importance in the improvement of disease detection and treatment. The classical DNA 'light-switch' ruthenium(II)-polypyridyl complex, [Ru(DIP)2(dppz)]Cl2 (DIP = 4,7-diphenyl-1,10-phenanthroline, dppz = dipyridophenazine) has been shown to be accumulated only in the cytoplasm and membrane, but excluded from its intended nuclear DNA target. In this study, the cationic [Ru(DIP)2(dppz)]2+ is found to be redirected into live-cell nucleus in the presence of lipophilic 3,5-dichlorophenolate or flufenamate counter-anions via ion-pairing mechanism, while maintaining its original DNA recognition characteristics. Interestingly and unexpectedly, further studies show that only the Δ-enantiomer is selectively translocated into nucleus while the Λ-enantiomer remains trapped in cytoplasm, which is found to be mainly due to their differential enantioselective binding affinities with cytoplasmic proteins and nuclear DNA. More importantly, only the nucleus-relocalized Δ-enantiomer can induce obvious DNA damage and cell apoptosis upon prolonged visible-light irradiation. Thus, the use of Δ-enantiomer can significantly reduce the dosage needed for maximal treatment effect. This represents the first report of enantioselective targeting and photosensitization of classical Ru(II) complex via simple ion-pairing with suitable weak acid counter-anions, which opens new opportunities for more effective enantioselective cancer treatment.


Placental vascular pathology as a mechanism of disease in pregnancy complications.
Inadequate placental development results in pregnancy complications. The extent and the degree of defective deep placentation may explain why a similar insult would result in different clinical presentations. The relative new categorization of the placental lesions, separating the non-infectious lesions into lesions that are consistent with maternal and fetal circulation abnormalities, and the infectious lesions into maternal and fetal inflammatory responses, provides us an additional tool to determine the placental maternal and fetal role in the various pregnancy complications. Placental vascular lesions are different in pregnancies complicated by preeclampsia (predominant maternal vascular supply lesions), by fetal growth restriction (FGR) (predominant fetal vascular supply lesions), and by preeclampsia with FGR (both maternal and fetal compartments are involved). Moreover, placental vascular lesions are also different in relation to gestational age at disease onset, as in early- and late-onset preeclampsia, FGR, Fetal death and preterm labor.


Study of Interactions of an Anticancer Drug Neratinib With Bovine Serum Albumin: Spectroscopic and Molecular Docking Approach.
Binding of therapeutic agents to plasma proteins, particularly to serum albumin, provides valuable information in the drug development. This study was designed to evaluate the binding interaction of neratinib with bovine serum albumin (BSA). Neratinib blocks HER2 signaling and is effective in trastuzumab-resistant breast cancer treatment. Spectrofluorometric, UV spectrophotometric, and fourier transform infrared (FT-IR) and molecular docking experiments were performed to study this interaction. The fluorescence of BSA is attributed to the presence of tryptophan (Trp) residues. The fluorescence of BSA in presence of neratinib was studied using the excitation wavelength of 280 nm and the emission was measured at 300-500 nm at three different temperatures. Neratinib quenched the BSA intrinsic fluorescence by static mechanism. A complex formation occurred due to the interaction leading to BSA absorption shift. The fluorescence, UV- absorption, three dimensional fluorescence and FT-IR data showed conformational changes occurred in BSA after interaction with neratinib. The binding constant values decreased as the temperature increased suggesting an instable complex formation at high temperature. Site I (sub-domain IIA) was observed as the principal binding site for neratinib. Hydrogen bonding and Van der Waals forces were suggested to be involved in the BSA-neratinib interaction due to the negative values of entropy and enthalpy changes.


Application of Appropriate Use Criteria for Initial Transthoracic Echocardiography in an Academic Outpatient Pediatric Cardiology Program.
Transthoracic echocardiography (TTE) is a non-invasive diagnostic modality for children with suspected heart disease. The American College of Cardiology published Appropriate Use Criteria (AUC) for an initial outpatient pediatric TTE in 2014 to promote effective care and improve resource utilization. The objective was to determine the appropriateness of TTE per the published AUC in a single academic pediatric cardiology clinic as a baseline performance quality measure. The echocardiography database was used to identify initial outpatient TTE in children during January-March 2014. TTE indications (appropriate [A], may be appropriate [M], or rarely appropriate [R]) and findings (normal, incidental, or abnormal) were recorded. The effect of AUC and age groups on yield of abnormal TTE findings was analyzed. Of the 2166 screened studies, our study cohort consisted of 247 TTEs. Indications rated A, M, and R were found in 129, 27, and 90, respectively, and 1 was unclassifiable. Majority of TTE (n = 183) were normal, although incidental findings were noted in 32 and abnormal findings in 32 cases. Abnormal findings were noted in 26/129 of A, 2/27 of M, and 4/90 of R. Indications rated A were significantly associated with yield of abnormal TTE findings, adjusted by age group. Infants and adolescents were more likely to have abnormal TTE findings compared to young children. Recently published AUC were validated for initial TTE in the outpatient pediatric cardiology clinic. Appropriateness rated by AUC was highly associated with yield of abnormal TTE findings and worked best in infants and adolescent.


Near-infrared analysis of soluble and insoluble dietary fiber fractions of cereal food products.
The use of near-infrared (NIR) reflectance spectroscopy for the rapid and accurate measurement of soluble and insoluble dietary fiber was explored in a diverse group of cereal products. Ground samples were analyzed for soluble and insoluble dietary fiber (AOAC Method 991.43) and scanned (NIRSystems 6500 monochromator) to obtain NIR spectra. Modified PLS models were developed to predict insoluble and soluble dietary fiber using data sets expanded to include products with high fat and high sugar contents. The models predicted insoluble dietary fiber accurately with an SECV of 1.54% and an R(2) of 0.98 (AOAC determined range of 0-48.77%) and soluble dietary fiber less accurately with an SECV of 1.15% and an R(2) of 0.82 (AOAC determined range of 0-13.84%). Prediction of independent validation samples by the soluble fiber model resulted in a bias that may be related to the way the reference method treats samples with different soluble fiber constituents. The insoluble fiber model can be used to rapidly monitor insoluble dietary fiber in cereal products for nutrition labeling.


Fancy a gene? A surprisingly complex evolutionary history of peroxiredoxins.
While the phylum Apicomplexa includes "only" several thousand described species of obligatory parasites of animals, it may in fact be the most specious group of parasitic protists with over a million species 1. The best known representatives are Plasmodium spp., Toxoplasma gondii and Cryptosporidium spp., which belong to the most important and widespread human parasites exacting an enormous disease burden. On the other hand, dinoflagellates and colpodellids, which are monophyletic with the apicomplexans, are ecologically highly significant, as they belong to the most abundant marine protists 2. As the common ancestor of these groups was most likely a free-living photosynthesizing protist, one wonders, which evolutionary forces contributed to the dramatic transition of some of its descendants into the arguably most successful intracellular parasites? Although a range of various processes and mechanisms contributed to this transition, most likely it also involved an acquisition of genes via horizontal gene transfer (HGT), which might have provided typical characteristics of a parasitic cell, such as immune escape, nutritional dependence and the capacity to invade other cells.


Modalities of in vitro IgM and IgG production by peripheral blood lymphocytes of chronic lymphocytic leukemia patients and healthy volunteers.
In vitro spontaneous and mitogen (LPS, rIFN alpha and PWM) or cytokine (rIL-2) induced IgM and IgG production by peripheral blood lymphocytes of 15 CLL patients and 16 healthy volunteers has been determined. This study has shown: (1) that there is no difference between healthy donors and CLL patients in respect to level and variability of spontaneous immunoglobulin production by their lymphocyte cultures; (2) that there is no correlation between the percentage of B cells in individual cell cultures obtained from CLL patients and the amount of spontaneously produced IgM or IgG; (3) that there is a correlation between spontaneous in vitro IgM production and IgM content in the serum of the patient; (4) that in CLL patients selective augmentation of IgM production could be obtained after stimulation with PWM or rIL-2, but only in those cultures which spontaneously produce more than 35 ng/ml of IgM and (5) that the number of lymphocyte cultures able to be stimulated to IgM production is about 10 times smaller when they originate from CLL patients than from healthy volunteers. These findings are in line with the view that B cells in CLL patients often do not differentiate due to the insufficiency of factor(s) secreted by their own activated T-cells, but that in essence they follow the same differentiation pathway as normal B-cells.


Neurologic abnormalities in two patients with facial hemiatrophy and sclerosis coexisting with morphea.
Progressive facial hemiatrophy or Parry-Romberg syndrome is a rare entity characterized by unilateral atrophy of the skin, subcutaneous tissue, and the underlying bony structures. This syndrome has many features of linear scleroderma en coup de sabre but is distinguished by more extensive involvement of the lower face and by only slight cutaneous sclerosis. We describe two unusual children with both atrophic and sclerotic changes of half of the face coexisting with multiple plaques of typical morphea. Both children developed neurologic disturbances with cranial magnetic resonance imaging (MRI) abnormalities 2 years and 15 years, respectively, after the onset of cutaneous lesions. Thus considering that it may not be possible to correlate impairment in neurologic function and cutaneous disease, as illustrated by our patients, we emphasize the importance of an accurate follow-up.


The impact of lifestyle and socioeconomic parameters on body fat level in early childhood.
The aim of this study was to examine the differences between selected lifestyle and socioeconomic parameters among preschool (3-7 years of age) children of differing adiposity status. The study was conducted from February to June 2018 in 20 randomly selected kindergartens in Kraków, Poland. Triceps, biceps, subscapular, suprailiac, abdominal and calf skinfold thicknesses were measured. The sum of all six skinfolds was calculated and the children were subsequently characterized by low (≤-1 SD [standard deviation]), normal (-1 to 1 SD) or high body fat (≥1 SD). Socioeconomic and lifestyle characteristics were obtained using a questionnaire filled out by the children's parents or legal guardians. Preschool children in the high adiposity category had, on average, fewer siblings and longer screen time; additionally, their parents had lower education and more often worked in manual jobs, in comparison to the children in the low and average adiposity categories. In conclusion, it was observed that children in different adiposity categories varied in terms of some socioeconomic as well as lifestyle characteristics. Knowledge regarding the influence that those factors can have on the metabolic health of children is essential for children's present as well as future well-being. Moreover, it can help health care professionals and parents decide what intervention and/ or preventive measures should be undertaken to ensure the best possible outcomes, as the development of successful obesity prevention strategies should rely on evidence-based information. Nonetheless, future research examining the issue of factors influencing the metabolic health of children, as well as these outcomes later in life, is crucial. Well-planned studies including a large number of individuals, as well as longitudinal research, will be particularly beneficial in this regard.


Cholinergic manipulations affect sensory responses but not attentional enhancement in macaque MT.
Attentional modulation in the visual cortex of primates is characterized by multiplicative changes of sensory responses with changes in the attentional state of the animal. The cholinergic system has been linked to such gain changes in V1. Here, we aim to determine if a similar link exists in macaque area MT. While rhesus monkeys performed a top-down spatial attention task, we locally injected a cholinergic agonist or antagonist and recorded single-cell activity. Although we confirmed cholinergic influences on sensory responses, there was no additional cholinergic effect on the attentional gain changes. Neither a muscarinic blockage nor a local increase in acetylcholine led to a significant change in the magnitude of spatial attention effects on firing rates. This suggests that the cellular mechanisms of attentional modulation in the extrastriate cortex cannot be directly inferred from those in the primary visual cortex.


Cross effects of resveratrol and mesenchymal stem cells on liver regeneration and homing in partially hepatectomized rats.
In this study, we examined the effect of preoperatively administered resveratrol (RV) and mesenchymal stem cells (MSCs) on regeneration of partially hepatectomized rat liver. We also evaluated the effect of RV on homing of MSCs. MSCs were isolated from bone marrow and cultured in vitro. Wistar albino rats were randomly divided into four groups. In groups, rats received (1) no treatment, (2) single dose RV, (3) MSCs and (4) RV plus MSCs before partial hepatectomy (PH). Injected MSCs were traced by labeling them with green fluorescent protein, and liver regeneration was determined by comparison of liver weight gain, histological examination and immunohistochemical staining with proliferating cell nuclear antigen (PCNA) for mitotic cells. The expression levels of tumor necrosis factor -alpha (TNF-α), interleukin-6 (IL-6) and hepatocyte growth factor (HGF) were also determined in the parafin sections of liver specimens with immunohistochemical staining. Administration of RV and MSCs separately or together enhanced liver regeneration despite decreasing the TNF-α and IL-6 expression. This positive contribution was probably due to direct raising effect on HGF for RV and HGF expression for MSCs that we demonstrated with immunohistochemical staining. Additionally, RV increased the homing of MSCs in liver probably related to life prolonging effect on MSCs. These results indicate that preoperative RV as well as MSCs application enhances liver regeneration after partial hepatectomy in rats. Paying attention to RV about the effect on liver regeneration and homing of MSCs might be the goal of further investigations.


Probing electrostatic interactions in cytochrome c using site-directed chemical modification.
This communication reports the generation of an electrostatic probe using chemical modification of methionine side chains. The alkylation of methionine by iodoacetamide was achieved in a set of Saccharomyces cerevisiae iso-1-cytochrome c mutants, introducing the nontitratable, nondelocalized positive charge of a carboxyamidomethylmethionine sulfonium (CAMMS) ion at five surface and one buried site in the protein. Changes in redox potential and its variation with temperature were used to calculate microscopic effective dielectric constants operating between the probe and the heme iron. Dielectric constants (epsilon) derived from deltadeltaG values were not useful due to entropic effects, but epsilon(deltadeltaH) gave results that supported the theory. The effect on biological activity of surface derivatization was interpreted in terms of protein-protein interactions. The introduction of an electrostatic probe in cytochrome c often resulted in marked effects on activity with one of two physiological partners: cytochrome c reductase, especially if introduced at position 65, and cytochrome c oxidase, if at position 28.


Preoperative Predictive Model of Narrow Pelvis in Laparoscopic Radical Prostatectomy Through Computed Tomography.
Objective: At present, prostate cancer radical surgery still lacks an objective standard for predicting the anatomic difficulty of surgery through preoperative examination. Due to the poor prognosis and surgical complications caused by "Narrow Pelvis," a pelvic model for prediction is urgently needed. The purpose of this study is to present objective preoperative assessing indicators to predict the surgical difficulty caused by pelvic anatomic abnormalities during laparoscopic radical prostatectomy (LRP). Methods: Patients undergoing LRP were retrospectively analyzed and separated into "Common Pelvis" or "Difficult Pelvis" groups according to the preset criteria. The clinical data and pelvic imaging data of the two groups were compared to obtain statistically significant differences. The results were compared and validated in 500 ordinary males. Logistic regression analysis was performed to optimize these indicators into a scoring model, "Laparoscopic Radical Prostatectomy Narrow Pelvic Predictive Index (LRP-NPPI)" for predicting "Difficult Pelvis." Results: Of the 145 patients undergoing LRP, 22 (15.2%) were included in the "Difficult Pelvis" group. Patients in the "Difficult Pelvis" group were more likely to have a narrower, shorter, deeper, more flattened pelvis, greater body mass index, more history of previous pelvic surgery, and greater prostate volume. Moreover, the larger amount of intraoperative blood loss and longer operation time were related. Compared with the "Common Pelvis" group, patients in the "Difficult Pelvis" have higher score of LRP-NPPI (p < 0.05). Conclusion: With the model we proposed, it is possible to predict patients with pelvic anatomical difficulties during LRP.


Falsely elevated plasma creatinine due to monoclonal gammopathy Analytical interference may give rise to falsely elevated as well as reduced clinical biochemical results. Hemolysis, icterus and lipemia in patient samples are well-known causes of analytical interference. Laboratories usually automatically check for these interferences and take them into account. However, other causes of interference are more difficult to detect, such as those caused by heterophilic antibodies and in this case a falsely elevated plasma creatinine level caused by a monoclonal IgM gammopathy. Analytical interference should be considered in cases with unexpected laboratory results and inconsistent pattern of results, in which contact and discussion with the laboratory is advised.


Inhibition of axon reflex vasodilatation by topically applied capsaicin.
Topical application of capsaicin to human skin produced an initial burning erythematous reaction which diminished over 24 hr leaving the skin unresponsive to histamine-induced axon reflex vasodilatation without altering sensitivity to pain, touch and temperature. Depletion of substance P from local sensory nerve terminals is suggested as a possible explanation for this capsaicin effect.


[Late complications in patients with aplastic anemia].
Of 145 patients with severe aplastic anemia (SAA) treated in Basel from 1976 to 1987, 34 underwent bone marrow transplantation (BMT) and 111 received ALG therapy. We have analyzed the incidence of late complications in both groups of patients. 34 patients treated with ALG developed a hematological complication, 10 a myelodysplastic syndrome (MDS) and 18 paroxysmal nocturnal hemoglobinuria (PNH) associated with clinical symptoms in 12. Two patients had both MDS and PNH. Eight suffered relapse of SAA. After BMT neither of these complications occurred. Most of the non-hematological problems were associated with therapy. In the ALG group androgens were responsible for impotence and gynecomastia in men, deep voice in women and liver tumors in 4 patients. Four other patients developed aseptic necrosis of the hip and one carcinoma of the breast. The most severe late complication after BMT was chronic graft-versus-host disease (GvHD), occurring in patients still receiving methotrexate for prophylaxis of GvHD.


[Lichen sclerosus et atrophicus as a cause of genital lesions in a girl].
In a 10-year old girl with irritated vulva lichen sclerosus et atrophicus (LSA) was diagnosed. She was successfully treated with local application of equal amounts of a cortisol ointment and zinc oil. LSA is a disease of the skin infrequently seen in children, and then mostly in girls. Diagnosis is based on typical lesions in the anogenital region (sharply delineated ivory discoloration, moderate sclerosis and atrophy, haemorrhagic erosions). Knowledge of this disease is important in order to distinguish it from sexual abuse.


Depression and the social developmental context of adolescence.
This article examines the interrelations of personal and social factors in fostering longitudinal patterns of depressive symptoms, using 3 waves of data from high school students in the Boston area. Previously depressed and nondepressed youths differed markedly in their emotional responsiveness to family and friend relations. Chronically depressed youths were unresponsive to family problems, but were highly reactive to peer relations. Among previously asymptomatic youths, family relations exerted greater effects on depressed mood than relations with peers. Further analyses suggest a process through which chronic family turmoil shapes long-term mental health while also intensifying the distancing from family and investment in peer relationships that typically occurs in adolescence. Findings illustrate the importance of modeling transactions between personal and environmental factors in research on adolescent mental health and development.


Avoiding Heparinization of Arterial Line and Maintaining Acceptable Arterial Waveform After Cardiac Surgery: A Randomized Clinical Trial.
Invasive and continuous blood pressure (BP) monitoring is crucial after cardiac surgery. Accuracy of BP measurement mostly depends on patency of arterial catheter and acceptable waveform. Heparinized saline flush usually used for this purpose may be accompanied by potential heparin adverse effects. The aim of this study was to compare heparinized and non-heparinized saline flush to maintain acceptable arterial waveform after cardiac surgery. In a double blind randomized trial study, 100 patients undergoing elective cardiac surgery were randomized to using heparinized (n = 50) or non-heparinized (normal) saline flush (n = 50) to maintain patency of arterial catheter after operation. Indwelling arterial catheters were checked daily for acceptable arterial waveform for three days as primary outcome measures. Frequency of acceptable arterial waveform ranged from 66% to 80%, in first, second and third postoperative days. There were no statistically significant differences between heparinized and non-heparinized saline groups regarding acceptable arterial waveforms in all the three postoperative days (all P values > 0.05). Using non-heparinized normal saline is suitable to maintain acceptable arterial waveform for short-term (three days) after adult cardiac surgery considering potential adverse effects of heparin.


Two novel outlier detection approaches based on unsupervised possibilistic and fuzzy clustering.
Outliers are data points that significantly deviate from other data points in a data set because of different mechanisms or unusual processes. Outlier detection is one of the intensively studied research topics for identification of novelties, frauds, anomalies, deviations or exceptions in addition to its use for data cleansing in data science. In this study, we propose two novel outlier detection approaches using the typicality degrees which are the partitioning result of unsupervised possibilistic clustering algorithms. The proposed approaches are based on finding the atypical data points below a predefined threshold value, a possibilistic level for evaluating a point as an outlier. The experiments on the synthetic and real data sets showed that the proposed approaches can be successfully used to detect outliers without considering the structure and distribution of the features in multidimensional data sets.


Improving influenza vaccination coverage in the pediatric asthma population: the case for combined methodologies.
The Advisory Committee on Immunization Practices recommends annual influenza vaccine for pediatric asthma patients. Despite considerable risk for influenza complications in pediatric asthma patients, including hospitalization and death, influenza vaccination among children with asthma remains low, especially among low-income pediatric asthma patients. Multiple interventions have been attempted to increase immunization in the pediatric asthma population, including recall and reminders, parent/patient education, and physician education. More recently, information technology methods have been employed, including electronic alerts and computerized physician order entry/clinical decision support interventions. Each of these interventions, as well as a recent legislative intervention, has evidence of effectiveness, but none achieved the Healthy People 2020 vaccination goals of 80 percent for this population. This goal may be achievable with a combination of these methodologies and strategies that increase access to care for underserved patients.


Asbestos in water sources of the Bazhenovskoye chrysotile asbestos deposit.
The paper provides measurements of asbestos fiber levels in water sources from the area of the Bazhenovskoye chrysotile asbestos deposit. All study water samples contained asbestos fibers at concentrations one to three orders below the values standardized in the USA (7 x 10(6) fibers/liter). All the identified fibers belonged to chrysotile asbestos and no amphibole asbestos, such as tremolite asbestos, has been identified. The anthropogenic load of asbestos fibers in Asbest City's environment is increasing in the volume of 5.770 x 10(14) fibers/liter or 10.2 kg of chrysotile asbestos. The authors consider it advisable to continue studies to measure asbestos levels in the water sources in the areas located in the vicinity of other Russian asbestos deposits.


Risk factors associated with the salmonella status of dairy farms in England and Wales.
Between October 1999 and February 2001 the salmonella status of 449 dairy farms in England and Wales was determined by environmental sampling on up to four occasions. Data were collected through interview-based questionnaires, and multivariable analyses were used to identify risk factors associated with the farms either being Salmonella positive (prevalence data) or becoming Salmonella positive (incidence data). Region, herd size, month of visit and the lack of a clean visitor parking area were significantly associated with the prevalence of Salmonella species, and there was a significant trend towards an increased risk in late summer and autumn. The introduction of six- to 24-month-old cattle into a herd was associated with a reduced prevalence, but the introduction of adult cattle only, or calves with other cattle, was associated with an increased (but not significant) risk of farms being Salmonella positive. Month of visit, the lack of a clean visitor parking area, the use of part-time workers and not feeding calves whole milk, but not region or herd size, were associated with an increased incidence of salmonella.


Characteristics of carotid atherosclerosis in elderly patients with type 2 diabetes at different disease course, and the intervention by statins in very elderly patients.
Chronic complications of diabetes have become the leading cause of death in elderly patients with diabetes. Carotid atherosclerosis, one of the major complications, was evaluated and the effects of atorvastatin on carotid atherosclerosis in very elderly patients with type 2 diabetes were observed. Patients were divided into three groups: (i) disease course <5 years; (ii) disease course 5-10 years; (iii) disease course >10 years, and carotid atherosclerosis was evaluated. The very elderly patients were treated with statins, and the effect was observed. Carotid intima-media thickness values, plaque instability and levels of homocysteine, cystatin, and C-reactive protein in diabetes patients were significantly higher than those in the healthy control group, whereas levels of C-peptide and estimated glomerular filtration rate in the patients were significantly lower. In patients with type 2 diabetes for >10 years, intima-media thickness values and plaque instability were obviously higher than those in patients with type 2 diabetes for <5 years, while levels of fasting C-peptide and estimated glomerular filtration rate were lower than those in patients with type 2 diabetes for <5 years. In the very elderly patients, after statins treatment, intima-media thickness values, levels of homocysteine and C-reactive protein were significantly reduced, as well as the number of unstable plaques. In the elderly patients with type 2 diabetes, carotid atherosclerosis-related factors increased obviously, and renal function declined obviously, which were closely related to the disease course. Atorvastatin significantly reduced homocysteine and C-reactive protein, and delayed and reversed the progress of carotid atherosclerosis in very elderly patients with type 2 diabetes.


[Retracted] The Fanconi anemia pathway sensitizes to DNA alkylating agents by inducing JNK‑p53‑dependent mitochondrial apoptosis in breast cancer cells.
Following the publication of the above paper, a concerned reader drew to the Editor's attention that one of the fluorescence microscopic images featured in Fig. 4A had previously appeared in a different form (a portion of data in a different orientation) in another article published by the same authors [Yu J, Zhao L, Li Y, Li N, He M, Bai H, Yu Z, Zheng Z, Mi X, Wang E and We M: Silencing of Fanconi anemia complementation group F exhibits potent chemosensitization of mitomycin C activity in breast cancer cells. J Breast Cancer 16: 291‑299, 2013]. Furthermore, the data panel shown for the 'MDA‑MB‑231/untreated' experiment in Fig. 4A in the above paper appeared to be duplicated as the 'MDA‑MB‑231/MMC + control shRNA' experiment, albeit stained differently. After having received a request from the authors to publish a corrigendum in view of the errors identified in Fig. 4 of the above paper, the Editor of International Journal of Oncology has conducted an independent investigation of the matter and determined that this article should be retracted from the Journal on account of a lack of confidence in the presented data. Upon receiving this decision, the authors were not in agreement that the paper should be retracted. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [the original article was published in International Journal of Oncology 45: 129‑138, 2014; DOI: 10.3892/ijo.2014.2400].


Allelopathic potential of Leucaena leucocephala (Lam.) de Wit leaf extracts on native species.
Allelopathy is seen as one of the possible factors that favor the invasion of exotic plants in the environment, as these species, by releasing allelochemicals, can negatively interfere with the establishment of native plants, facilitating the growth and dissemination of invasive exotic plants. This study aimed to verify the possible allelopathic effects of Leucaena leucocephala (Lam.) de Wit (leucaena) on native tree species Pterogyne nitens Tul. and Peltophorum dubium (Spreng.) Taub., via laboratory bioassays. We used Petri dishes containing seeds of native species and aqueous extract of leucaena leaves with 2, 4, 8, 10 and 20% concentrations (m/v) for germination tests and estimated the percentage, mean time, and germination speed index at the end of the germination period. For initial growth, we kept the Petri dishes containing aqueous leucaena extract and germinated seeds of native species in a germination chamber at 25 °C, and after 48 hours we obtained the length of the primary root, hypocotyl, and fresh and dry biomass of the seedlings. We obtained the a, b, and total chlorophyll and carotenoid content of seedling leaves kept in the aqueous extract at different concentrations. We verified the content of total phenolic compounds in mg/L from the aqueous leucaena extracts. Both native species showed a reduction in the percentage and germination speed index when in contact with the aqueous leucaena extracts at the highest concentrations. The initial growth of native species was also negatively affected, and P. nitens showed a reduction of all growth parameters analyzed in all concentrations of the aqueous extract. P. dubium showed a reduction in growth, especially at the highest concentrations. The effects can be associated with phenolic compounds present in leucaena extracts, and we found the highest total phenolic content in the extract with the highest concentration. The results show the allelopathic potential of leucaena, which may contribute to this plant ability to settle in natural areas.


Comparisons of Submental and Groin Vascularized Lymph Node Flaps Transfer for Breast Cancer-Related Lymphedema.
The vascularized groin and submental lymph node (VGLN and VSLN) flaps are valuable options in the treatment of lymphedema. This study was to compare outcomes between VGLN and VSLN transfers for breast cancer-related lymphedema. Between January 2008 and December 2016, VGLN and VSLN transfers for upper limb lymphedema were compared including flap characteristics, flap elevation time, complications, and limb circumference changes. All flaps survived. Similar vein (2.6 versus 3.2 mm; P = 0.3) and artery diameter (2.1 versus 2.8 mm; P = 0.3) and number of lymph nodes (3 versus 4; P = 0.4) were found between VGLN and VSLN groups, respectively. Circumferential reduction rate was higher in VSLN than VGLN (P = 0.04) group. Vascular complication rate with salvage rate was not statistically different between the 2 groups. Donor-site complication and total complication rates were statistically higher in VGLN than VSLN flaps (7.7% versus 0%, P = 0.004; 46.2% versus 23.3%, P = 0.002). At a mean 39.8 ± 22.4 months, the circumferential reduction rate was statistically higher in VSLN than in the VGLN group (55.5 ± 14.3% versus 48.4 ± 23.9%, P = 0.04). Both flaps were effectively decreased in the episodes of cellulitis. Both VGLN and VSLN flaps are valuable surgical options in treating breast cancer-related lymphedema. However, the VSLN flap for breast cancer-related lymphedema is better in providing more significant improvements in limb circumference, a faster flap harvest time, decreased complication rates, and minimal donor-site iatrogenic lymphedema.


Cardiovascular diseases in kidney transplant recipients: the role of anemia.
Cardiovascular diseases are among the leading causes of mortality and death associated graft loss in kidney transplant recipients. Recently, there has been an increased awareness of the potential role of nontraditional risk factors such as anemia in contributing to the increased burden of cardiovascular diseases in kidney transplant recipients. Studies that are primarily based on retrospective data analyses have shown an association between anemia and cardiovascular outcomes. These findings underscore the need for prospective studies to better understand these risks and to implement management strategies that would have a positive impact on patient and graft outcomes. On the basis of the available data, this article reviews the magnitude of cardiovascular diseases and anemia in kidney transplant recipients with a focus on the role of anemia on cardiovascular outcomes in these patients.


[The island of Mauritius: insularity, tropicality, modernity, a dialogue in the form of a lesson].
Mauritius, a lost volcanic island in the indian ocean situated at the 20th degree of latitude, is a tiny state which got its independence in 1968. The isolation, the tropicality, the demographic boom, the ethnic diversity and the absence of raw materials could funnel this peaceful beauty to become a hot-bed of desperation and violence. This place which is one of the most densely populated areas, is an example of modern democracy and cultural coexistence. Owing to a skillful and pragmatic politic, its leaders have transformed handicaps into trump cards. The allocation of a part of the GNP for social and hygienic investments had been the locomotive pulling the train of improvements and raising the standard of living for the inhabitants. The ageing population, the rapidity of evolution the demographic and health transitions are expression of this skillful politic. In less than twenty years, this island conquered underdevelopment and proved that there is no tropical fatality when a programme of health accompanies development.


[The morphology of a main bronchial stump area after diaphragmopexy or omentopexy].
The present paper presents 5 microscopic investigations of the morphology of a major bronchial stump area or tracheobronchial anastomosis after tightly fixing a vascularized diaphragmatic or omental flap. The cadaveric material of female patients who had died in different periods after diaphragmopexy or omentopexy was investigated. The authors' observations support the fact that diaphragmatic or omental flaps tightly sutured to the tracheobronchial wall can provide its revascularization and regeneration of the bronchial stump or tracheobronchial anastomosis.


Association between abdominal aortic plaque and coronary artery disease.
Currently, the association between abdominal aortic plaques and coronary artery disease (CAD) has not yet been clarified clearly. The purpose of this study was to determine the prevalence of abdominal aortic plaques by ultrasound imaging and to explore its association with CAD in patients undergoing coronary angiography. Between October 2014 and June 2015, a prospective study was conducted in the Department of Cardiology at Guangdong General Hospital, Guangzhou, People's Republic of China. Ultrasound scanning of the abdominal aortas was performed in 1,667 consecutive patients undergoing coronary angiography. Clinical characteristics and coronary profile were collected from the patients. Of the 1,667 study patients (male, 68.9%; mean age, 63±11 years) undergoing coronary angiography, 1,268 had CAD. Compared with 399 patients without CAD, 1,268 patients with CAD had higher prevalence of abdominal aortic plaques (37.3% vs 17%, P<0.001). In multivariate analysis, abdominal aortic plaques served as independent factors associated with the presence of CAD (odds ratio =2.08; 95% confidence interval =1.50-2.90; P<0.001). Of the 1,268 patients with CAD, the prevalence of abdominal aortic plaques was 27.0% (98/363) in patients with one-vessel disease, 35.0% (107/306) in patients with two-vessel disease, and 44.7% (268/599) in patients with three-vessel disease. Stepwise increases in the prevalence of abdominal aortic plaque was found depending on the number of stenotic coronary vessels (P<0.001; P-value for trend <0.001). In an ordinal logistic regression model, abdominal aortic plaques served as independent factors associated with the severity of CAD according to the number of stenotic coronary vessels (P<0.001). The prevalence of abdominal aortic plaques was higher in patients with CAD than in those without CAD. Abdominal aortic plaque was an independent factor associated with the presence and severity of CAD.


Startle reflex potentiation during aversive picture viewing as an indicator of trait fear.
Measures of fearfulness and measures of psychopathy show positive and negative associations, respectively, with startle reflex potentiation during unpleasant picture viewing. We tested the hypothesis that a common bipolar trait dimension underlies these differing associations. Blink responses to noise probes were recorded during pleasant, neutral, and unpleasant pictures in 88 undergraduates assessed with a battery of self-report scales indexing fear and psychopathy/fearlessness. A significant positive association was found between an omnibus index of fear, consisting of scores on the first component from a principal components analysis of these various scales, and startle potentiation during aversive picture viewing. This association was most robust, across participants overall and within gender subgroups, for scenes that were most directly threatening. Implications for psychophysiological research on individual differences and psychopathology are discussed.


Aerobic capacity in black adolescent girls.
Our purpose was to determine the aerobic capacities (VO2max) of a group of black female adolescents (age = 11.4-15.8 years) randomly chosen from a single urban school. Of 91 girls selected, 64 performed an incremental treadmill running test to volitional exhaustion and achieved VO2max as determined from expired gas measures. Other measures included height (m), weight (kg), and calf and triceps skinfolds (for % fat estimates). Girls were also asked whether they had achieved menarche. VO2max averaged 37.3 +/- 6.2 ml.kg-1 x min-1 and was significantly correlated (r[62]) with height (-.32, p < .01), body mass index (-.63, p < .001), and % fat (-.65, p < .001) but not with age (-.16, p > .10). Postmenarchal girls were significantly taller and older than premenarchal girls. Contrary to previous studies, the girls' VO2max values were not related to biological age. Our subjects' aerobic capacity values averaged 14% less than those of nonblack U.S. female adolescents previously reported in the literature. This difference in VO2max was primarily a function of body weight. Study implications support the possibility that overweight in adult black women may originate prior to or during early adolescence. Future longitudinal studies should be designed to investigate the effects of aerobic fitness on cardiovascular risk factor reduction in black adolescent girls.


Effect of latitude on flavonoid biosynthesis in plants.
The growth conditions in different latitudes vary markedly with season, day length, light quality and temperature. Many plant species have adapted well to the distinct environments through different strategies, one of which is the production of additional secondary metabolites. Flavonoids are a widely spread group of plant secondary metabolites that are involved in many crucial functions of plants. Our understanding of the biosynthesis, occurrence and function of flavonoids has increased rapidly in recent decades. Numerous studies have been published on the influence of environmental factors on the biosynthesis of flavonoids. However, extensive long-term studies that examine the effect of the characteristics of northern climates on flavonoid biosynthesis are still scarce. This review focuses on the current knowledge about the effect of light intensity, photoperiod and temperature on the gene-environment interaction related to flavonoid biosynthesis in plants.


Accelerating Sulfur Redox Chemistry by Atomically Dispersed Zn-N4 Sites Coupled with Pyridine-N Defects on Porous Carbon Sheets.
Single-atom catalysts (SACs) with specific N-coordinated configurations immobilized on the carbon substrates have recently been verified to effectively alleviate the shuttle effect of lithium polysulfides (LiPSs) in lithium-sulfur (Li─S) batteries. Herein, a versatile molten salt (KCl/ZnCl2 )-mediated pyrolysis strategy is demonstrated to fabricate Zn SACs composed of well-defined Zn-N4 sites embedded into porous carbon sheets with rich pyridine-N defects (Zn─N/CS). The electrochemical kinetic analysis and theoretical calculations reveal the critical roles of Zn-N4 active sites and surrounding pyridine-N defects in enhancing adsorption toward LiPS intermediates and catalyzing their liquid-solid conversion. It is confirmed by reducing the overpotential of the rate-determining step of Li2 S2 to Li2 S and the energy barrier for Li2 S decomposition, thus the Zn─N/CS guarantees fast redox kinetics between LiPSs and Li2 S products. As a proof of concept demonstration, the assembled Li─S batteries with the Zn─N/CS-based sulfur cathode deliver a high specific capacity of 1132 mAh g-1 at 0.1 C and remarkable capacity retention of 72.2% over 800 cycles at 2 C. Furthermore, a considerable areal capacity of 6.14 mAh cm-2 at 0.2 C can still be released with a high sulfur loading of 7.0 mg cm-2 , highlighting the practical applications of the as-obtained Zn─N/CS cathode in Li─S batteries.


Black chokeberry (Aronia melanocarpa L.) polyphenols attenuate obesity-induced colonic inflammation by regulating gut microbiota and the TLR4/NF-κB signaling pathway in high fat diet-fed rats.
This study investigated the potential benefits of black chokeberry polyphenol (BCP) supplementation on lipopolysaccharide (LPS)-stimulated inflammatory response in RAW264.7 cells and obesity-induced colonic inflammation in a high fat diet (HFD)-fed rat model. Our findings demonstrated that BCP treatment effectively reduced the production of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and MCP-1) in LPS-induced RAW264.7 cells and concurrently mitigated oxidative stress by modulating the levels of malondialdehyde (MDA), catalase (CAT), and glutathione peroxidase (GSH-Px) in a dose-dependent manner. Furthermore, BCP supplementation significantly ameliorated HFD-induced obesity, improved glucose tolerance, and reduced systemic inflammation in HFD-fed rats. Notably, BCP treatment suppressed the mRNA expression of pro-inflammatory cytokines and alleviated intestinal barrier dysfunction by regulating the mRNA and protein expression of key tight junction proteins (ZO-1, occludin, and claudin-1), thereby inhibiting colonic inflammation caused by the TLR4/NF-κB signaling pathway. Additionally, BCP treatment altered the composition and function of the gut microbiota, leading to an increase in the total content of short-chain fatty acids (SCFAs), particularly acetic acid, propionic acid, isobutyric acid, and butyric acid. Collectively, our results highlighted the potential of BCP supplementation as a promising prebiotic strategy for treating obesity-induced colonic inflammation.


Swelling of the intratemporal facial nerve in Ramsay Hunt syndrome.
Although Ramsay Hunt syndrome is one of the most important diseases causing peripheral facial palsy, the detailed pathology of the disease in the intratemporal facial nerve remains unclear. The purpose of this study was to increase knowledge of the pathogenesis of the syndrome by means of surgical findings. Between April 1976 and March 1997 we performed subtotal decompression of the facial nerve in 74 patients with severe Ramsay Hunt syndrome. The grade of nerve swelling was assessed using a microscope and recorded in a standardized form. The relationships between nerve swelling, the timing of surgery and the swelling of each segment were analyzed. Pronounced neural swelling, involving the geniculate ganglion and the horizontal segment, was consistent finding in the acute phase. Although the incidence of pronounced swelling of the horizontal segment gradually declined with time after onset, in most cases nerve swelling persisted even beyond the 16th week after onset. These data suggest that diffuse viral neuritis occurs throughout the intratemporal facial nerve. We assume that the viral inflammatory swelling involving the geniculate ganglion and horizontal segment is mostly responsible for the acute facial palsy in the acute phase.


Photonic crystal biosensors towards on-chip integration.
Photonic crystal technology has attracted large interest in the last years. The possibility to generate highly sensitive sensor elements with photonic crystal structures is very promising for medical or environmental applications. The low-cost fabrication on the mass scale is as advantageous as the compactness and reliability of photonic crystal biosensors. The possibility to integrate microfluidic channels together with photonic crystal structures allows for highly compact devices. This article reviews different types of photonic crystal sensors including 1D photonic crystal biosensors, biosensors with photonic crystal slabs, photonic crystal waveguide biosensors and biosensors with photonic crystal microcavities. Their applications in biomolecular and pathogen detection are highlighted. The sensitivities and the detection limits of the different biosensors are compared. The focus is on the possibilities to integrate photonic crystal biosensors on-chip.


The spread of alcohol consumption behavior in a large social network.
Alcohol consumption has important health-related consequences and numerous biological and social determinants. To explore quantitatively whether alcohol consumption behavior spreads from person to person in a large social network of friends, coworkers, siblings, spouses, and neighbors, followed for 32 years. Longitudinal network cohort study. The Framingham Heart Study. 12 067 persons assessed at several time points between 1971 and 2003. Self-reported alcohol consumption (number of drinks per week on average over the past year and number of days drinking within the past week) and social network ties, measured at each time point. Clusters of drinkers and abstainers were present in the network at all time points, and the clusters extended to 3 degrees of separation. These clusters were not only due to selective formation of social ties among drinkers but also seem to reflect interpersonal influence. Changes in the alcohol consumption behavior of a person's social network had a statistically significant effect on that person's subsequent alcohol consumption behavior. The behaviors of immediate neighbors and coworkers were not significantly associated with a person's drinking behavior, but the behavior of relatives and friends was. A nonclinical measure of alcohol consumption was used. Also, it is unclear whether the effects on long-term health are positive or negative, because alcohol has been shown to be both harmful and protective. Finally, not all network ties were observed. Network phenomena seem to influence alcohol consumption behavior. This has implications for clinical and public health interventions and further supports group-level interventions to reduce problematic drinking.


Mapping and morphometric analysis of synapses and spines on fusiform cells in the dorsal cochlear nucleus.
Fusiform cells are the main integrative units of the mammalian dorsal cochlear nucleus (DCN), collecting and processing inputs from auditory and other sources before transmitting information to higher levels of the auditory system. Despite much previous work describing these cells and the sources and pharmacological identity of their synaptic inputs, information on the three-dimensional organization and utltrastructure of synapses on these cells is currently very limited. This information is essential since an understanding of synaptic plasticity and remodeling and pathologies underlying disease states and hearing disorders must begin with knowledge of the normal characteristics of synapses on these cells, particularly those features that determine the strength of their influence on the various compartments of the cell. Here, we employed serial block face scanning electron microscopy (SBFSEM) followed by 3D reconstructions to map and quantitatively characterize synaptic features on DCN fusiform cells. Our results reveal a relative sparseness of synapses on the somata of fusiform cells but a dense distribution of synapses on apical and basal dendrites. Synapses on apical dendrites were smaller and more numerous than on basal dendrites. The vast majority of axosomatic terminals were found to be linked to other terminals connected by the same axon or different branches of the same axon, suggesting a high degree of divergent input to fusiform cells. The size of terminals was correlated with the number of mitochondria and with the number of active zones, which was highly correlated with the number of postsynaptic densities, suggesting that larger terminals exert more powerful influence on the cell than smaller terminals. These size differences suggest that the input to basal dendrites, most likely those from the auditory nerve, provide the most powerful sources of input to fusiform cells, while those to apical dendrites (e.g., parallel fiber) are weaker but more numerous.


Dynamic contrast-enhanced MRI of nasopharyngeal carcinoma: correlation of quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters with hypoxia-inducible factor 1α expression and tumor grade/stage.
Abnormal microangiogenesis and microenvironmental disturbances within the Nasopharyngeal carcinoma (NPC) can exacerbate tumor hypoxia, which may increase radiotherapy resistance and thus lead to poor prognosis in NPC patients. A non-invasive imaging technique, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which can reflect the tumor blood perfusion and angiogenesis status, was used to investigate the relationships of DCE-MRI parameters with hypoxia-inducible factor 1 alpha (HIF-1α) expression and tumor grades in NPC patients. 42 treatment-naive patients with pathologically confirmed NPC were enrolled in this analysis. Plain magnetic resonance scans and DCE-MRI scans were performed before treatment, and post-processing was performed to calculate the relative enhancement (RE), maximum relative enhancement (MRE), maximum enhancement (ME), wash-in rate (WIR), wash-out rate (WOR), time to peak (TTP), and area under the curve (AUC). Immunohistochemistry was used to detect HIF-1α expression in electronasopharyngeal fiberoscopic specimens. The clinical grade/stage of NPC was jointly assessed by an experienced radiologist and a radiotherapist. The potential correlations of the DCE-MRI parameters with HIF-1α expression and clinical grades were analyzed. The statistical analysis was performed using SPSS 17.0 software package. Among DCE-MRI parameters, RE, ME, and MRE were associated with the positive expression of HIF-lα in NPC and could reflect the hypoxic status in the local microenvironment of the cancer foci in vivo. RE, ME, and MRE were significantly higher in the positive HIF-1α expression group than in the negative HIF-1α expression group (F=5.281, P=0.027; F=11.923, P=0.001; F=6.228, P=0.017). RE, ME, and MRE were significantly correlated with clinical grade (F=3.646, P=0.021; F=3.204, P=0.034, F=3.050, P=0.040) and T stage (F=6.578, P=0.001; F=3.540, P=0.023; F=4.384, P=0.010). The values of RE, MRE, and ME gradually increased as the clinical grade and T stage increased. DCE-MRI is a valuable imaging technique for the noninvasive evaluation of hypoxia in NPC, the development of individualized treatment protocols, and the prediction of efficacy.


Missed nursing care: a qualitative study.
The purpose of this study was to determine nursing care regularly missed on medical-surgical units and reasons for missed care. Nine elements of regularly missed nursing care (ambulation, turning, delayed or missed feedings, patient teaching, discharge planning, emotional support, hygiene, intake and output documentation, and surveillance) and 7 themes relative to the reasons for missing this care were reported by nursing staff.


Cardiomyopathy and angiopathy in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes.
In four patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) in which mutated mitochondrial deoxyribonucleic acid was seen, hypertrophic cardiomyopathy and angiopathy was demonstrated by echocardiography, dipyridamole stress scintigraphy, and cardiac catheterization. On stress scintigraphy with dipyridamole, three patients showed hypoperfusion in the early image and a "filling-in" pattern in the late image. However, coronary angiography did not demonstrate narrowing of the large vessels in these patients. Light and electron microscopy of endomyocardial biopsy specimens indicated abnormal mitochondria, with marked increase in the number and size of mitochondria in endothelium. Modified Gomori's trichrome staining in biopsied endomyocardial specimens revealed a red-purple deposit similar in appearance of the ragged-red fibers in skeletal muscle, a characteristic finding of mitochondrial disease. Deterioration of complex I in the mitochondrial electron transfer system, which is widely observed in various mitochondrial diseases, appeared in biopsied skeletal muscle of our patients, indicating deficiency of some subunits of complex I. These results indicate that mitochondrial diseases such as MELAS show not only cardiomyopathy but also angiopathy. We speculate that proliferation of mitochondria leads to narrowing of the lumen of arterioles, which might be responsible for the ischemic findings observed scintigraphically.


Low carbohydrate ketogenic diet enhances cardiac tolerance to global ischaemia.
The cardio-protective effects of a low carbohydrate ketogenic diet following global ischaemic injury as compared to rats fed a normal and high carbohydrate diet for a period of 19 weeks, were investigated. The reperfusion recovery of coronary flow was highly significant in the low carbohydrate ketogenic diet group. Although the initial reperfusion recovery of the pressure developed in the left ventricle, Pmax was similar in all groups, after 15 minutes, the momentum for faster recovery was maintained in the low carbohydrate ketogenic diet group. Ultrastructural observations of the cardiac muscles have shown that there was a decrease in the number of mitochondria in rats fed a high carbohydrate diet and an increase in the number of mitochondria in those fed a low carbohydrate ketogenic diet as compared to the normal diet group. This study demonstrates that a low carbohydrate ketogenic diet is cardio-protective functionally. Ischaemia and reperfusion lead to cell death. These pathways are regulated and hence are subjected to therapeutic intervention. Previously, we have shown that a low carbohydrate ketogenic diet (LCKD) reduces the risk factors for heart disease in obese patients. This study is aimed at understanding the cardio-protective effects of LCKD following global ischaemic injury in rats. Rats weighing 190-250 g were divided into normal diet (ND), LCKD and high carbohydrate diet (HCD) groups consisting of six animals in each group. Specific diets were given to each group for a period of 19 weeks. Changes in body weight, ultrastructure of the cardiac muscles and the cardio-protective effects of the LCKD group as compared to the ND and HCD groups were investigated in rats following global ischaemic injury. Electron microscopic studies have shown that there was a decrease in the number of mitochondria in rats fed a high carbohydrate diet and an increase in the number of mitochondria in those fed a low carbohydrate ketogenic diet as compared to the normal diet group. Rats on LCKD had a remarkable tolerance to ischaemia and a faster recovery of cardiac function following reperfusion. The initial reperfusion recovery of the pressure developed in the left ventricle, Pmax was similar in all groups. However, after 15 minutes, the momentum for faster recovery was significantly maintained in the LCKD group (P < 0.05). The reperfusion recovery of coronary flow was highly significant (P < 0.05) in the LCKD regime. The increase in left ventricle end diastolic pressure, coronary vascular resistance and the changes in body weight were not significant between the experimental groups. This is a unique study showing ultrastructural variation in cardiac muscle in relation to cardio-protective function in rats fed a low carbohydrate ketogenic diet. This study suggests that the LCKD is cardio-protective functionally. The underlying mechanism of the cardio-protective effect of an LCKD needs to be elucidated.


Curcumin attenuates diabetic encephalopathy in rats: behavioral and biochemical evidences.
Emerging epidemiological data indicates that diabetes is a potential predisposing factor for neuropsychiatric deficits as stroke, cerebrovascular diseases, diabetic encephalopathy, depression and anxiety. Diabetic encephalopathy, characterized by impaired cognitive functions and neurochemical and structural abnormalities, involves direct neuronal damage caused by intracellular glucose. Curcumin, a well-established phenolic antioxidant and anti-inflammatory molecule, is capable of playing an important role against amyloid and dendritic pathology and thus has neuroprotective properties. The aim of the present study was to explore the effect of curcumin (60 mg/kg; p.o.) on cognitive functions, oxidative stress and inflammation in diabetic rats. Learning and memory behaviors were investigated using a spatial version of the Morris water maze test. Acetylcholinesterase activity, a marker of cholinergic dysfunction, was increased by 80% in the cerebral cortex of diabetic rats. There was 107% and 121% rise in thiobarbituric acid reactive substance levels in cerebral cortex and hippocampus of diabetic rats, respectively. Reduced glutathione level and enzymatic activities of superoxide dismutase and catalase were decreased in both cerebral cortex and hippocampal regions of diabetic rat brain. Nitrite levels in cerebral cortex and hippocampus were increased by 112% and 94% respectively. Serum TNF-alpha, a marker for inflammation, was found to increase by 1100% in diabetic rats. Chronic treatment with curcumin (60 mg/kg; p.o.) significantly attenuated cognitive deficit, cholinergic dysfunction, oxidative stress and inflammation in diabetic rats. The results emphasize the involvement of cholinergic dysfunction, oxidative stress and inflammation in the development of cognitive impairment in diabetic animals and point towards the potential of curcumin as an adjuvant therapy to conventional anti-hyperglycemic regimens for the prevention and treatment of diabetic encephalopathy.


A comparison of matched interim analysis publications and final analysis publications in oncology clinical trials.
Progression-free survival is an increasingly popular surrogate end point for overall survival. The strength of correlation between the two end points varies, raising questions about the correlation between results of interim analyses that report mature progression-free survival data with the subsequent final publication that report overall survival. We searched PubMed from 2005 to 2015 for randomized controlled trials that measured both progression-free survival and overall survival. We matched interim publications that reported mature progression-free survival data with their final analyses that reported overall survival. We included 25 matched pairs and 8 unmatched interim analyses whose final analyses are not published. Our primary objectives are to compare interim publications with matched final publications in terms of journal prominence and Altmetric score and to compare progression-free survival and overall survival effect sizes. All interim analyses (n = 33) were prespecified and there was a statistically significant progression-free survival benefit in 31 (93.9%). Only eight matched final analyses had statistically significant overall survival data. Interim analyses were more often published in top-5 general medicine journals (P < 0.01) but not in top-5 oncology journals (P = 0.26). Altmetric scores were higher in interim analyses (P < 0.01). Progression-free survival effect sizes from interim analyses were a median of 31% larger than overall survival effect sizes from final analyses. Interim analyses with progression-free survival data may generate hype in oncology, as evidenced by journal impact factors and Altmetric scores. The cause of this hype may be due, in part, to large progression-free survival effect sizes. Regardless, in trials that investigate progression-free and overall survival, publishing interim analyses with mature progression-free survival data apart from the final analyses with mature overall survival should be cautioned.


Access to specialist palliative care services by people with severe and persistent mental illness: A retrospective cohort study.
Compared to the general population, people with pre-existing serious and persistent mental illness (SPMI) have higher rates of physical illness and die at an earlier age, raising questions about their palliative and end-of-life care needs when they are diagnosed with an incurable physical illness. In the present study, we explored access to specialist palliative care services within one New Zealand health district. Routinely-collected, de-identified patient information on a cohort of people diagnosed with SPMI, and receiving specialist palliative care services from the Capital and Coast District Health Board (CCDHB), was compared to the general population from the same health district. People with SPMI are 3.5 times less likely to receive specialist palliative services compared to the general population from the Capital and Coast District Health Board. The proportion of people identifying as Māori is 1.2 times higher in the SPMI cohort than the general CCDHB population. The SPMI cohort experiences a higher level of deprivation compared to the general population in the CCDHB. The present study confirms that those diagnosed with an SPMI are less likely to use specialist palliative care services at the end of life. Research using a national dataset is needed to determine whether the study findings are applicable to the national population.


Oligoclonal bands measured in unconcentrated cerebrospinal fluid and other biochemical parameters in multiple sclerosis.
Various biochemical parameters of cerebrospinal fluid (CSF) obtained from sixty-nine patients with RRMS (relapse-remitting MS) were compared in this study. Total protein level, white blood cells (WBC) count and presence of oligoclonal bands (OB) in CSF were examined. The presence of OB in unconcentrated CSF using an isoelectrofocusing assay on agarose gels and silver staining were measured in 72 percent of patients. The average CSF total protein level measured by Lowry assay was 269 mg/l (range from 61 to 712 mg/l). The mean level of white blood cells (WBC) was higher than in general population and it was 12 cells/microl. We found an increased level of WBC count among patients with the presence of oligoclonal bands in CSF.


Dynamic programming algorithms for comparing multineuronal spike trains via cost-based metrics and alignments.
Cost-based metrics formalize notions of distance, or dissimilarity, between two spike trains, and are applicable to single- and multineuronal responses. As such, these metrics have been used to characterize neural variability and neural coding. By examining the structure of an efficient algorithm [Aronov D, 2003. Fast algorithm for the metric-space analysis of simultaneous responses of multiple single neurons. J Neurosci Methods 124(2), 175-79] implementing a metric for multineuronal responses, we determine criteria for its generalization, and identify additional efficiencies that are applicable when related dissimilarity measures are computed in parallel. The generalized algorithm provides the means to test a wide range of coding hypotheses.


Pulse-height measurements with a cooled avalanche-photodiode detector.
A cooled avalanche-photodiode (APD) detector has been developed for X-ray diffraction experiments. Although an APD is normally used at room temperature and a high internal gain, the energy resolution can be improved by decreasing temperature and gain. The APD device was cooled to 253 K by a thermoelectric cooler. When the gain was M = 13, the energy resolution was 5% (FWHM) at 16.53 keV with a charge-sensitive preamplifier. By scanning the discriminator threshold level of a fast-counting system, energy spectra were obtained at M approximately 50 and count rates of up to 4.7 x 10(7) s(-1).