The Exosome-Transmitted lncRNA LOC100132249 Induces Endothelial Dysfunction in Diabetic Retinopathy.
Diabetic retinopathy (DR), one of the most common microangiopathic complications in diabetes, causes severe visual damage among working-age populations. Retinal vascular endothelial cells, the key cell type in DR pathogenesis, are responsible for abnormal retinal angiogenesis in advanced stages of DR. The roles of exosomes in DR have been largely unknown. In this study, we report the first evidence that exosomes derived from the vitreous humor of patients with proliferative DR (PDR-exo) promote proliferation, migration, and tube formation of human retinal vascular endothelial cells (HRVECs). We identified long noncoding RNA (lncRNA) LOC100132249 enrichment in PDR-exo via high-throughput sequencing. This lncRNA, also mainly derived from HRVECs, promoted angiogenesis both in vitro and in vivo. Mechanistically, LOC100132249 acted as a competing endogenous sponge of miRNA-199a-5p (miR-199a-5p), thus regulating the endothelial-mesenchymal transition promoter SNAI1 via activation of the Wnt/β-catenin pathway and ultimately resulting in endothelial dysfunction. In conclusion, our findings underscored the pathogenic role of endothelial-derived exosomes via the LOC100132249/miR-199a-5p/SNAI1 axis in DR angiogenesis and may shed light on new therapeutic strategies for future treatment of DR. This study provides the first evidence that exosomes derived from vitreous humor from patients with proliferative diabetic retinopathy participate in angiogenesis. The findings demonstrate an unreported long noncoding RNA (lncRNA), LOC100132249, by exosomal sequencing of vitreous humor. The newly found lncRNA LOC100132249, mainly derived from endothelial cells, promotes angiogenesis via an miRNA-199a-5p/SNAI1/Wnt/β-catenin axis in a pro-endothelial-mesenchymal transition manner.


A comparison of felodipine and propranolol as additions to hydrochlorothiazide in the treatment of hypertension.
Eighty one patients with uncomplicated hypertension who required additional antihypertensive medication (diastolic Phase V [dBP] greater than or equal to 95 mm Hg) after 4 weeks treatment with hydrochlorothiazide (HCTZ) 25 mg o.m. were randomized to receive felodipine 5 mg b.i.d. (n = 40) or propranolol (n = 41) 80 mg b.i.d. in addition to HCTZ 25 mg o.m. If the dBP measured about 12 h post-dose was not less than or equal to 90 mm Hg after 4 weeks, the dose of felodipine or propranolol was doubled. The double blind trial period was 8 weeks for all patients. Over the 8 week period, felodipine reduced the seated dBP from 100 to 83 mm Hg and propranolol from 101 to 86 mm Hg. The attained seated dBPs were significantly different in the two groups. About one third of patients in each group received the high dose of second-line therapy. After 8 weeks 91% of patients receiving HCTZ+felodipine and 84% receiving HCTZ+propranolol had a dBP less than or equal to 90 mm Hg. Both regimens were well-tolerated with an equal incidence but different pattern of adverse events (felodipine: flushing, headache and peripheral oedema; propranolol: dyspepsia, fatigue and vasospasm). In this 8-week study, felodipine and propranolol were safe and effective second-line antihypertensive drugs when added to hydrochlorothiazide. At the doses selected, felodipine was at least as effective as propranolol.


Component-resolved diagnosis of wasp (yellow jacket) venom allergy.
Wasp venom allergy is a potentially life-threatening condition with serious consequences of diagnostic error. To assess whether component-resolved diagnosis, using non-glycosylated recombinant allergen components from yellow jacket can add to the diagnosis of wasp venom allergy. In total, 148 patients with a wasp (yellow jacket) allergy were included, 91 with unequivocal tests, 26 with double positivity of serum-specific IgE (sIgE) to both venoms, 21 with discrepant sIgE and skin test results and finally 10 having their diagnosis only confirmed by basophil activation test (negative sIgE and skin test results). Specific IgE to recombinant species-specific allergen components Ves v 1 and Ves v 5 from yellow jacket, Api m 1 from honeybee and Ves v 5 complemented wasp venom were tested by ImmunoCAP. Overall, combined use of sIgE to rVes v 1 and rVes v 5 allowed correct diagnosis in 139 of the 148 patients (94%) and rApi m 1 was demonstrable in only one patient. Supplementing the traditional yellow jacket allergosorbent with rVes v 5 allowed to correctly diagnose wasp allergy in patients sensitized to Ves v 5 but demonstrating a negative sIgE to wasp venom. Component-resolved diagnoses with the wasp-specific recombinant allergen components Ves v 1 and Ves v 5 is a reliable method to diagnose yellow jacket allergy and can help to take out the sting of difficult cases. However, as the number of patients with doubt after conventional tests is small, larger collaborative studies are needed to draw more definitive conclusions. Whether the rVes v 5 supplemented yellow jacket allergosorbent constitutes an asset in the diagnostic management of wasp venom allergy remains to be further established.


Mesolimbic and mesocortical dopamine activation induced by phencyclidine: contrasting pattern to striatal response.
The effects of acute administration of phencyclidine, an indirect dopamine agonist, on biochemical indices of dopaminergic activation were examined in mesocortical, mesolimbic and nigrostriatal regions of the rat. High doses (10 mg/kg) of phencyclidine resulted in a marked increase in levels of the dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid in all mesolimbic and mesocortical sites examined, as well as in the ventral tegmental area, source of the dopaminergic innervation of mesolimbic/cortical sites. In contrast, levels of both metabolites decreased in the striatum and tended to decrease in the substantia nigra, source of the striatal dopaminergic innervation. The metabolite response to phencyclidine was dose-related. These data indicate that the mesolimbic and mesocortical dopaminergic neurons are activated by phencyclidine. Since the firing rate of both A10 (ventral tegmental area) and A9 (substantia nigra) dopamine neurons has previously been shown to be increased by phencyclidine, these data suggest that phencyclidine results in a differential regulation of presynaptic release of dopamine in mesolimbic/cortical as opposed to nigrostriatal dopaminergic regions.


Microbiological contamination of digested products from anaerobic co-digestion of bovine manure and agricultural by-products.
This study was performed to investigate the microbiological contamination of digestate product (DP) obtained from the anaerobic co-digestion of bovine manure and agricultural by-products. Microbiological analyses were performed on bovine manure, fresh DP, liquid and solid fractions and stored liquid fraction of DP. A statistically significant reduction of faecal bacterial indicator was found after anaerobic digestion except for enterococci. After liquid/solid DP separation, bacteria tend to be concentrated in the solid fraction. Storage does not seem to influence the indicator parameters, except for enterococci. Escherichia coli O157:H7 and Yersinia were not found in any samples analysed. Salmonella was rarely detected in DP samples and its derivates, while Listeria monocytogenes was encountered in many samples. The results obtained indicate that the hygienic quality of DP is for almost all microbiological parameters better than that of the bovine manure (range of reduction 1.6-3.1 log10) and suggest the need to identify specific pathogen indicators related to the hygienic characteristics of DPs. This study highlights that the anaerobic co-digestion of bovine manure and agricultural by-products in a field-scale biogas plant does not increase human health risk with respect to the use of animal manure for agricultural fertilization.


Catalytic wet oxidation of ammonia: why is N2 formed preferentially against NO3 -?
The role of catalyst and the reason for the preferential formation of N(2) in the catalytic oxidation reaction of ammonia in water over a Ru (3wt.%)/TiO(2) catalyst were elucidated. It was verified that the catalyst in the reaction had no direct relevance to the selective formation of N(2), but was responsible only for the oxidation of aqueous ammonia, NH(3)(aq), finally giving a molecule of nitrous acid. The preferential production of N(2) was experimentally demonstrated due to the homogeneous aqueous phase reaction of the nitrous acid-dissociated NO(2)(-) with NH(4)(+) ions. Even under the highly oxidizing condition, NO(2)(-) was much more likely to react with NH(4)(+) to form N(2) than being oxidized over the catalyst to NO(3)(-) as long as NH(4)(+) was available in solution.


Ultrasensitive detection of butyrylcholinesterase activity based on self-polymerization modulated fluorescence of sulfur quantum dots.
Butyrylcholinesterase (BChE) is an important clinical diagnosing index for liver dysfunction and organophosphate toxicity. However, the current assays for BChE activity are suffering from the relative poor detection sensitivity. In this work, an ultrasensitive fluorescence assay for BChE activity was developed based on the self-polymerization modulated fluorescence of sulfur quantum dots (S-dots). The luminescence of S-dots can be quenched by the self-polymerized dopamine. The hydrolysate of substrates, thiocholine, under the catalysis of BChE can reduce dopamine, which results in the inhibition of self-polymerization and the fluorescence recovery of S-dots. BChE can be quantitatively detected by recording the recovered fluorescence of S-dots, and a linear relationship is observed between the ratio of fluorescence and the concentration of BChE in the range from 0.01 to 10 U/L. A limit of detection as low as 0.0069 U/L calculated, which is the lowest number so far. The assay also shows excellent selectivity towards various interference species and acetylcholinesterase. These features allowed the direct detection of BChE activity in human serum, demonstrating the great practical applications of our assay.


SYBR Green I: fluorescence properties and interaction with DNA.
In this study, we have investigated the fluorescence properties of SYBR Green I (SG) dye and its interaction with double-stranded DNA (dsDNA). SG/dsDNA complexes were studied using various spectroscopic techniques, including fluorescence resonance energy transfer and time-resolved fluorescence techniques. It is shown that SG quenching in the free state has an intrinsic intramolecular origin; thus, the observed >1,000-fold SG fluorescence enhancement in complex with DNA can be explained by a dampening of its intra-molecular motions. Analysis of the obtained SG/DNA binding isotherms in solutions of different ionic strength and of SG/DNA association in the presence of a DNA minor groove binder, Hoechst 33258, revealed multiple modes of interaction of SG inner groups with DNA. In addition to interaction within the DNA minor groove, both intercalation between base pairs and stabilization of the electrostatic SG/DNA complex contributed to increased SG affinity to double-stranded DNA. We show that both fluorescence and the excited state lifetime of SG dramatically increase in viscous solvents, demonstrating an approximate 200-fold enhancement in 100 % glycerol, compared to water, which also makes SG a prospective fluorescent viscosity probe. A proposed structural model of the SG/DNA complex is compared and discussed with results recently reported for the closely related PicoGreen chromophore.


Hydrogen-driven subsurface lithoautotrophic microbial ecosystems (SLiMEs): do they exist and why should we care?
One of the keys to success of many anaerobic ecosystems is the process of syntrophic intercellular hydrogen transfer. This process facilitates the overall reaction by end-product removal, taking advantage of a wide variety of organisms that are able to use hydrogen directly as an energy source by uptake hydrogenases. Thus, the issue is not whether there are hydrogen-driven processes or communities but whether there are hydrogen-driven communities that exist and persist independently of the products of photosynthesis (so-called subsurface lithoautotrophic microbial ecosystems, or SLiMEs). It is the proof of long-term independence from photosynthesis and its products that is the most difficult issue to establish, and perhaps the most important one with regard to searching for SLiMEs both on and off our planet. Although the evidence is not yet unequivocal, a growing body of evidence supports the existence of SLiME-like communities: if they exist, the implications are immense with regard to understanding subsurface environments on Earth, looking for present day analogs of early Earth and the search for life in other worlds.


Changes in oral health conditions among 6- to 15-year-old children in Auvergne (France) 1987-1991.
A representative sample of 1,200 schoolchildren of Auvergne (France) ranging in age from 6 to 15 years was randomly selected. Dental caries experience was determined using the dft, DMFT and DMFS indices. The plaque index and the gingival index were also recorded. Comparison with an identical 1987 study enabled the changes in schoolchildren's dental health to be examined. Significant reductions were observed in all age groups for the DMFT and DMFS indices and in the 6-9-year-old group for the dft index. The mean DMFT score for 12-year-old children was 1.97 in 1991, as compared to the score of 4.62 reported in 1987 (57.3 per cent reduction). While no significant variation was observed in the gingival index, the plaque index decreased significantly for the 7-14-year-old group. The comparison confirmed the trend to a lower caries experience in schoolchildren in Auvergne as in many Western European countries.


Testicular germ cell tumor in patient with Klinefelter syndrome.
Although mediastinal germ cell tumors are known to occur with a greater frequency in patients with Klinefelter syndrome, reports of testicular germ cell tumors occurring in such patients are rare. We report a case of a nonseminomatous germ cell tumor in a patient with Klinefelter syndrome and suggest that such an association may occur more frequently than has been reported previously.


Antibacterial Mode of Action of β-Amyrin Promotes Apoptosis-Like Death in Escherichia coli by Producing Reactive Oxygen Species.
β-Amyrin is a pentacyclic triterpene widely distributed in leaves and stems worldwide. The ability of β-amyrin to induce the production of reactive oxygen species (ROS) in microorganisms suggests its potential as an antimicrobial agent. Thus, this study aimed to elucidate the antibacterial mode of action of β-amyrin. We treated Escherichia coli cells with β-amyrin and found that it triggered ROS accumulation. Excessive stress caused by ROS, particularly hydroxyl radicals, induces glutathione (GSH) dysfunction. GSH protects cells from oxidative and osmotic stresses; thus, its dysfunction leads to membrane depolarization. The resultant change in membrane potential leads to the release of apoptotic proteins, such as caspases. The activated caspases-like protein promotes the cleavage of DNA into single strands, which is a hallmark of apoptosis-like death in bacteria. Apoptotic cells usually undergo events such as DNA fragmentation and phosphatidylserine exposure, differentiating them from necrotic cells, and the cells treated with β-amyrin in this study were positive for annexin V and negative for propidium iodide, indicating apoptosis-like death. In conclusion, our findings suggest that the antibacterial mode of action of β-amyrin involves the induction of ROS, which resulted in apoptosis-like death in E. coli.


Analysis of risk taking in adults with a history of high risk behavior.
Antisocial behavior often involves frequent risk-taking, e.g. excessive substance use and criminality, which may lead to destructive consequences. In the present study, adults with a history of high-risk behavior (primarily drug dependence and conduct disorder) and matched controls worked on a novel laboratory task designed to measure risk-taking. The contingencies of the task were such that choosing a 'risky' response option resulted in a net loss of monetary earnings compared to a safer, more conservative response alternative. The risky option offered a low probability of a large monetary reward or a high probability of a smaller monetary loss. The non-risky option protected current earnings. High-risk history subjects chose the risky option more often, had lower overall earnings, and were more likely to persist in making (losing) risky responses following a single gain on the risky option. The data support theories of maladaptive behavior focused on hypersensitivity to reward and insensitivity to aversive events.


Home chemical and microbial transitions across urbanization.
Urbanization represents a profound shift in human behaviour, and has considerable cultural and health-associated consequences1,2. Here, we investigate chemical and microbial characteristics of houses and their human occupants across an urbanization gradient in the Amazon rainforest, from a remote Peruvian Amerindian village to the Brazilian city of Manaus. Urbanization was found to be associated with reduced microbial outdoor exposure, increased contact with housing materials, antimicrobials and cleaning products, and increased exposure to chemical diversity. The degree of urbanization correlated with changes in the composition of house bacterial and microeukaryotic communities, increased house and skin fungal diversity, and an increase in the relative abundance of human skin-associated fungi and bacteria in houses. Overall, our results indicate that urbanization has large-scale effects on chemical and microbial exposures and on the human microbiota.


Re-Evaluating the Evidence for Faecal Microbiota Transplantation 'Super-Donors' in Inflammatory Bowel Disease.
Faecal microbiota transplantation [FMT] is a recommended treatment for recurrent Clostridioides difficile infection, and there is promise that FMT may be effective for conditions such as inflammatory bowel disease [IBD]. Previous FMT clinical trials have considered the possibility of a 'donor effect', that is, that FMT material from different donors has different clinical efficacies. Here we re-evaluate evidence for donor effects in published FMT clinical trials for IBD. In ten of 12 published studies, no statistically significant donor effect was detected when rigorously re-evaluating the original analyses. One study showed statistically significant separation of microbiota composition of pools of donor stool when stratified by patient outcome. One study reported a significant effect but did not have underlying data available for re-evaluation. When quantifying the uncertainty on the magnitude of the donor effect, confidence intervals were large, including both zero donor effects and very substantial donor effects. Although we found very little evidence for donor effects, the existing data cannot rule out the possibility that donor effects are clinically important. Large clinical trials prospectively designed to detect donor effects are probably needed to determine if donor effects are clinically relevant for IBD.


Do trauma cue exposure and/or PTSD symptom severity intensify selective approach bias toward cannabis cues in regular cannabis users with trauma histories?
Trauma cue-elicited activation of automatic cannabis-related cognitive biases are theorized to contribute to comorbid posttraumatic stress disorder and cannabis use disorder. This phenomenon can be studied experimentally by combining the trauma cue reactivity paradigm (CRP) with cannabis-related cognitive processing tasks. In this study, we used a computerized cannabis approach-avoidance task (AAT) to assess automatic cannabis (vs. neutral) approach bias following personalized trauma (vs. neutral) CRP exposure. We hypothesized that selective cannabis (vs. neutral) approach biases on the AAT would be larger among participants with higher PTSD symptom severity, particularly following trauma (vs. neutral) cue exposure. We used a within-subjects experimental design with a continuous between-subjects moderator (PTSD symptom severity). Participants were exposed to both a trauma and neutral CRP in random order, completing a cannabis AAT (cannabis vs. neutral stimuli) following each cue exposure. Current cannabis users with histories of psychological trauma (n = 50; 34% male; mean age = 37.8 years) described their most traumatic lifetime event, and a similarly-detailed neutral event, according to an established interview protocol that served as the CRP. As hypothesized, an AAT stimulus type x PTSD symptom severity interaction emerged (p = .042) with approach bias greater to cannabis than neutral stimuli for participants with higher (p = .006), but not lower (p = .36), PTSD symptom severity. Contrasting expectations, the stimulus type x PTSD symptoms effect was not intensified by trauma cue exposure (p = .19). Selective cannabis approach bias may be chronically activated in cannabis users with higher PTSD symptom severity and may serve as an automatic cognitive mechanism to help explain PTSD-CUD co-morbidity.


First trimester cystic hygroma: does early detection matter?
To describe the association of abnormal outcomes with fetal cystic hygroma detected when crown-rump length measures less than 45 mm, and to compare them to outcomes among fetuses with cystic hygroma detected when crown-rump length measures 45-84 mm. We performed a retrospective cohort study of fetuses with first trimester nuchal cystic hygroma from 2005 to 2015. A total of 212 fetuses were included. Abnormal karyotype was found in 20 of 46 (43.4%) fetuses with cystic hygroma detected when crown-rump length measured below 45 mm, compared to 108 of 148 (73%) fetuses with cystic hygroma detected at crown-rump lengths of 45-84 mm (p = 0.001). There were no differences in rates of major structural anomaly (27% vs 36%; p = 0.53) or pregnancy loss (23% vs 7%; p = 0.22) among fetuses with normal karyotype. Those with cystic hygroma diagnosed at crown-rump lengths below 45 mm were more likely to have a normal neonatal outcome compared to cases diagnosed with crown-rump lengths of 45-84 mm (25% vs 11%; p = 0.02). Cystic hygroma detected when crown-rump length measures below 45 mm have lower rates of chromosomal abnormalities and a higher proportion of normal birth outcomes when compared to those detected later in the first trimester. © 2016 John Wiley & Sons, Ltd.


Disinfection of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium and Acinetobacter baumannii using Klaran WD array system.
Hospital-associated infections (HAIs) are a major burden in healthcare systems. In this study, UVC LEDs emitting radiation from 260 to 270 nm were evaluated for effectiveness in reducing methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium and Acinetobacter baumannii . The array has four WD LEDs, each with 70 mW placed at 7 cm from test organisms. With 11.76 mJ cm-2, the study obtained 99.99% reduction (log10 reduction factor of 4) against MRSA and VRE. For A. baumannii , 9 mJ cm-2 obtained 99.999% reduction (log10 reduction factor of 5). These results present scientific evidence on how effective UVC LEDs can be used in the fight against HAIs.


Distribution of neurotensin binding sites in the caudal brainstem of the rat: a light microscopic radioautographic study.
Specific high-affinity neurotensin binding sites were labeled in sections of the rat caudal brainstem using a monoiodinated ligand, and their distribution was examined by light microscopic radioautography after fixation with glutaraldehyde. In the medulla, labeled binding sites were mainly concentrated within the dorsal motor nucleus of the vagus, the nucleus of the solitary tract, the external cuneate nucleus, the lateral reticular nucleus, the medial vestibular nucleus, the retrofacial nucleus, the linearis nucleus, the paragigantocellular nucleus and the nucleus raphe pallidus. Within the pons, neurotensin binding sites were detected in the reticulotegmental nucleus, the pontine nuclei, the dorsal tegmental nucleus, the laterodorsal and pedunculopontine tegmental nuclei and the nuclei raphe dorsalis and medianus. Most nuclei found here to contain high densities of neurotensin binding sites have been shown to stain intensely for acetylcholinesterase, suggesting a possible association between this enzyme and neurotensin receptors.


Continuous monitoring of a monoclonal antibody by size exclusion chromatography reveals a correlation between system suitability parameters and column aging.
Size exclusion chromatography (SEC) is a foundational analytical method to assess product purity of biological molecules. To ensure accurate and reproducible data that meet regulatory agency standards, it is critical to monitor the chromatographic column with efficient and continuous approaches. In this study, 19 SEC columns (Waters Acquity BEH200) were evaluated using an in-house monoclonal antibody made at Regeneron. System suitability parameters (SSPs) were used to monitor the performance of the SEC assay, including USP resolution, USP plate count, USP tailing factor, asymmetry factor, elution time, peak width, and peak height. A general linear model was built and revealed that elution time, peak width, asymmetry factor, and tailing factor increased with injection number, while peak height, resolution, and plate count decreased. After 1000 injections, tailing factor and peak width increased by more than 10%, while resolution and plate count decreased by more than 10% from their respective starting values.


Monitoring ovarian function and detecting pregnancy in felids: A review.
Reliable detection and monitoring of estrus and pregnancy is essential to the effective ex situ conservation of endangered felids. Here, we review the current methods used to detect estrus and pregnancy in felids and describe the advantages and limitations of each. A total of 194 felid-focused publications were reviewed. The methods used included behavioral assessments (61 publications across 24 species), hormone monitoring (124 studies across 28 species), fecal protein monitoring (two studies in cheetah), ultrasonography (31 publications across seven species), vaginal cytology (22 publications across nine species), and laparoscopy (70 publications across 19 species). Behavior-based assessments of reproductive state are often inconsistent and unreliable in felids; thus hormone measurement is the most frequently used method for monitoring estrous cycles (66% of studies). In non-domestic felids, non-invasive fecal- or urine-based hormone metabolite analyses are preferred to blood assessments (66% of endocrine-based publications). While the measurement of fecal estrogen and progestin metabolites are useful for the retrospective assessment of ovarian activity, their use for real-time detection of estrus is limited. Vaginal cytology, laparoscopy and ultrasonography provide an acute and immediate determination of reproductive state but usually require anesthesia or sedation, which can prevent ovulation and cause abortions; thus, their use for pregnancy diagnosis is limited. Fecal progesterone or prostaglandin F2α metabolites can be used to detect pregnancy in most felids (the exception being fecal progestins for Lynx spp.), but only during mid-to-late gestation. Urinary relaxin measurement is a promising method for earlier pregnancy diagnosis (30-40% duration of gestation) but is presently limited by poor assay sensitivity due to the lack of a feline-specific relaxin antibody. Elevated levels of fecal immunoglobulin J chain have been investigated as a tool to detect pregnancy in cheetah (>80% accuracy), but research is lacking on other species. We conclude that there is no single 'best method' for monitoring ovarian activity and detecting pregnancy in felids, and current best practice would involve a combination of existing methods. Non-invasive methods for detecting estrus and pregnancy in felids (e.g., accelerometry and infrared thermography) should also be considered to augment existing methods.


Novel antioxidant peptides in fermented pork sausage: Purification, characterization, and cytoprotective functions on Caco-2 cells.
In this study, crude peptides from fermented sausages inoculated with Lactobacillus plantarum CD101 and Staphylococcus simulans NJ201 were initially separated by ultrafiltration and molecular-sieve chromatography. The obtained fractions with high 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and ferric-reducing antioxidant power values (MWCO-1 and fraction A) were used in Caco-2 cells to evaluate their cytoprotective effect on oxidative damage triggered by H2O2. MWCO-1 and A showed slight cytotoxicity. Increased glutathione peroxidase, catalase, and superoxide dismutase activities and decreased malondialdehyde content were observed in the peptide-treated groups. Fraction A was further purified using reversed high-performance liquid chromatography. Eighty potential antioxidant peptides were identified by liquid chromatography with tandem mass spectrometry, and fourteen antioxidant peptides were synthesized. SDEEVEH and FAGDDAPR showed strong DPPH radical scavenging activity, whereas ALELDSNLYR and QEYDESGPSIVHR presented strong ABTS+· scavenging activity. These peptides might have great potential for food and pharmacological applications.


Retinyl ester hydrolase and vitamin A status in rats treated with 3,3',4, 4'-tetrachlorobiphenyl.
Previous studies have shown that rats exposed to 3,3',4,4'-tetrachlorobiphenyl (TCB) exhibit decreased liver vitamin A stores. The activity of retinyl ester hydrolase (REH), the enzyme responsible for the hydrolysis of the storage form of vitamin A (retinyl esters) into free retinol, may therefore be altered by TCB. This study was carried out to investigate the effect of TCB on vitamin A distribution and on REH activity in the rat. REH activity was measured in liver homogenates and microsomes (650 micrograms protein), in Tris-maleate buffer 0.1 M at pH 7.2 in the presence of 150 mM CHAPS and 1.5 mM retinyl palmitate dispersed in Triton X-100 0.2%. Using these conditions, the kinetic parameters of the enzyme were determined and the inter-animal variation coefficient (10%) allowed statistical comparisons between experimental groups. Male Wistar rats of sufficient or deficient vitamin A status were treated IP with 340 mumol of TCB/kg. Vitamin A levels were significantly depressed in liver. REH activity was decreased about 20%, and serum retinol was decreased about 50%, independent of the initial vitamin A status of the animals. Vitamin A levels in lungs and testes were also decreased, suggesting that TCB could interfere with vitamin A delivery to target organs. The negative effect of TCB on REH activity in vivo was also observed when TCB was added in vitro to the incubation medium at concentrations near to those expected after in vivo treatment. TCB is a non-competitive inhibitor of retinyl palmitate hydrolase.


Cognitive performance correlates with cortical isopeptide immunoreactivity as well as Alzheimer type pathology.
Protein cross-linking and aggregation are important molecular processes in Alzheimer's disease (AD), and tissue transglutaminase (tTG) catalyzes protein cross-linking. To measure tTG, tTG enzyme activity and isopeptide, which is the product of tTG, in brain and to relate them to cognitive scores. tTG and isopeptide levels were measured in frontal gray matter of 10 normal (NCI), 10 mild cognitive impairment (MCI) and 9 AD brains from the Religious Orders Study. tTG enzymatic activity was measured with a fluorescence assay. tTG protein and enzyme activity were highest in AD, but not significantly greater than MCI or NCI. In contrast, isopeptide immunoreactivity in formic acid extracts was significantly greater in AD than NCI and MCI. The level of insoluble formic acid extractable isopeptide correlated with several measures of cognitive function, including word generation and perceptual speed. Multiple linear regression analyses indicated that insoluble isopeptide immunoreactivity could be accounted for by a combination of factors in the formic acid extract, including Abeta, ubiquitin and tau. Accumulation of insoluble proteins with isopeptide bonds correlates with cognitive impairment. The relationship of isopeptide to other proteins that are also enriched in formic acid extracts suggests that several substrates of tTG may play a role in the pathogenesis of AD.


Cardioprotective effects of the YiQiFuMai injection and isolated compounds on attenuating chronic heart failure via NF-κB inactivation and cytokine suppression.
The YiQiFuMai injection (YQFM) is a traditional Chinese medicine for the treatment of chronic heart failure (CHF). The present study not only evaluated the cardioprotective effect and anti-inflammatory mechanism of the YQFM injection in an experimental model of CHF but also investigated its bioactive constituents in vitro. The left anterior descending coronary artery (LAD) in rats was ligated to make an animal model of CHF. From this, electrocardiographic parameters and exterior signs of rat hearts were recorded. Additionally, the histopathology of heart tissues was examined, and parameters of inflammatory stress were measured. Experiments were performed over two months in LAD-ligation rats treated with YQFM or vehicle. Treatment with Captopril was used as a positive control, which has previously been shown to prevent CHF, and rats without LAD-ligation were used as a negative control. Furthermore, we screened and identified potential anti-inflammatory constituents by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) combined with NF-κB activity luciferase reporter assay systems. Further cytokine detection confirmed the anti-inflammatory effects of the potential NF-κB inhibitors from YQFM. The administration of YQFM significantly improved cardiac function and ameliorated the activity level of inflammatory mediators (such as tumor necrosis factor-alpha, interleukin-6, and interleukin-1β) in CHF rats. Eight potential anti-inflammatory ingredients, ginsenosides Rb1, Rg1, Rf, Rh1, Rc, Rb2, Ro, and Rg3, were characterized and confirmed. Among these compounds, ginsenoside Ro was revealed as a new NF-κB inhibitor. The results suggested that NF-κB inactivation and cytokine suppression might be one of the main mechanisms of YQFM that caused ameliorative effects in CHF rats, and the major constituents of ginsenosides were identified playing a key role in the treatment of CHF.


Adaptation to exercise in the cold.
The winter athlete has several potential tactics for sustaining body temperature in the face of severe cold. An increase in the intensity of physical activity may be counter-productive because of increased respiratory heat loss, increased air or water movement over the body surface, and a pumping of air or water beneath the clothing. Shivering can generate heat at a rate of 10 to 15 kJ/min, but it impairs skilled performance, while the resultant glycogen usage hastens the onset of fatigue and mental confusion. Non-shivering thermogenesis could arise in either brown adipose tissue or white fat. Brown adipose tissue generates heat by the action of free fatty acids in uncoupling mitochondrial electron transport, and by noradrenaline-induced membrane depolarisation and sodium pumping. The existence of brown adipose tissue in human adults is controversial, and although there are theoretical mechanisms of heat production in white fat, their contribution to the maintenance of body temperature is small. Acclimatisation to cold develops over the course of about 10 days, and in humans the primary change is an insulative, hypothermic type of response; this reflects the intermittent nature of most occupational and athletic exposures to cold. Nevertheless, with more sustained exposure to cold air or water, humans can apparently develop the humoral type of acclimatisation described in small mammals, with an increased output of noradrenaline and/or thyroxine. The associated mobilisation of free fatty acids suggests the possibility of using winter sport as a pleasant method of treating obesity. In men, a combination of moderate exercise and facial cooling induces a substantial fat loss over a 1- to 2-week period, with an associated ketonuria, proteinuria, and increase of body mass. Possible factors contributing to this fat loss include: (a) a small energy deficit; (b) the energy cost of synthesising new lean tissue; (c) energy loss through the storage and excretion of ketone bodies; (d) catecholamine-induced 'futile' metabolic cycles with increased resting metabolism; and (e) a specific reaction to cold dehydration. Current limitations for the clinical application of such treatment include uncertainty regarding optimal environmental conditions, concern over possible pathological reactions to cold, and suggestions of a less satisfactory fat mobilisation in female patients. Possible interactions between physical fitness and metabolic reactions to cold remain controversial.(ABSTRACT TRUNCATED AT 400 WORDS)


Prevalence of depression, risk factors, and quality of life in patients with epilepsy in a remote area of western Rajasthan.
Depression is a common psychiatric disorder in patients with epilepsy. This study aimed to determine the prevalence and related risk factors for depression among people with epilepsy and their quality of life. Hospital-based cross-sectional study was carried out among 352 individuals with epilepsy from April 2020 to September 2020. Purposive sampling was used to recruit participants over a specified period. The Beck's Depression Inventory-II (BDI-II) was used to measure depression severity, the Perceived Stress Scale (PSS) to assess stress level, the Oslo 3 Social Support Scale (OSSS-3) to assess social support, and the WHOQOL-BREF scale to estimate quality of life (QoL). The statistical analysis was carried out using SPSS version 20. Logistic regression analysis was done to determine the risk factors for depression. A total of 352 study participants were considered in the study. The prevalence of depression was found to be 41.19%. In the final multivariate analysis, the independent variables that influenced depression were socioeconomic status (OR 2.75, CI 1.21-5.41), frequency of seizures in the previous year (OR 2.17, CI 1.08-5.26), duration of illness (OR 3.49, CI 1.03-7.52), and poor social support (OR 6.37, CI 1.85-9.48) at p-value < 0.05. When compared to patients without depression, the average mean score (SD) in all four domains was lower in physical 39.01 (4.61), psychological 43.93 (8.13), social 52.89 (10.44), and environmental domains 47.14 (6.99) in patients with depression in BREF quality-of-life scale. There was a statistically significant difference in the physical, psychological, and social domains (p-value < 0.05). In people with epilepsy, depression was quite common. Patients that were depressed had a lower QoL. Clinicians should pay special attention to people with epilepsy who lack social support, have low socioeconomic status, longer duration of illness, and have more seizure frequency. Qualified clinicians should do early depression-focused screenings for people with epilepsy.


Association of automated carotid IMT measurement and HbA1c in Japanese patients with coronary artery disease.
The purpose of this study was to evaluate whether carotid IMT (cIMT) identified using automated software is associated with HbA1c in Japanese patients with coronary artery disease. 370 consecutive patients (males 218; median age 69 years ± 11) who underwent carotid-US and first coronary angiography were prospectively analyzed. After ultrasonographic examinations were performed, the plaque score (PS) was calculated and automated IMT analysis was obtained with a dedicated algorithm. Pearson correlation analysis was performed to calculate the association between automated IMT, PS and HbA1c. The mean value of cIMT was 1.00 ± 0.47 mm for the right carotid and 1.04 ± 0.49 mm for the left carotid; the average bilateral value was 1.02 ± 0.43 mm. No significant difference of cIMT was detected between men and women. We found a direct correlation between cIMT values and HbA1c (p=0.0007) whereas the plaque score did not correlate with the HbA1c values (p>0.05) CONCLUSION: The results of our study confirm that automated cIMT values and levels of HbA1c in Japanese patients with coronary artery disease are correlated whereas the plaque score does not show a statistically significant correlation.


Polylactide inhibition of carcinoma cell growth in vitro.
Normal fibroblasts and epithelial tumor cells were challenged by exposure for 24 hours to extracts of a pure metal, a metal alloy, and a polymer used in facial reconstruction to assess cellular growth effects. While none of these materials significantly altered fibroblast growth rates, poly-L-lactide inhibited carcinoma cell growth at 5.0% extract concentration. No carcinoma cell growth effects were seen from exposure to stainless steel or commercially pure titanium extracts.


Separation of growth-stimulating activity of BSA fraction V from the bulk of albumin using Heparin Sepharose Chromatography.
Bovine serum albumin (BSA) is a potential source of biological contamination in cell culture medium. The aim of this work was to attempt to replace BSA in low serum and serum-free medium (SFM). BSA fraction V was subjected to a variety of processes in order to determine if the growth promoting activity observed for NRK cells could be extracted from the BSA molecule. These included solvent extractions, diafiltration, reverse phase HPLC and affinity chromatography using heparin sepharose. Solvent extraction and diafiltration failed to remove the activity from the BSA. Affinity chromatography using heparin sepharose indicated that all of the activity observed with BSA was retained in the 0.5 M NaCl fraction and was associated with less than 3% of the original protein. The major protein band in the 0.5 M NaCl fraction had the same apparent molecular weight as albumin (as seen by SDS-PAGE and analytical reverse phase HPLC). Unlike the untreated BSA, the 0.5 M NaCl fraction was partially susceptible to proteolytic digestion and to variations in pH.


In vivo human head MRI at 10.5T: A radiofrequency safety study and preliminary imaging results.
The purpose of this study is to safely acquire the first human head images at 10.5T. To ensure safety of subjects, we validated the electromagnetic simulation model of our coil. We obtained quantitative agreement between simulated and experimental B1+ and specific absorption rate (SAR). Using the validated coil model, we calculated radiofrequency power levels to safely image human subjects. We conducted all experiments and imaging sessions in a controlled radiofrequency safety lab and the whole-body 10.5T scanner in the Center for Magnetic Resonance Research. Quantitative agreement between the simulated and experimental results was obtained including S-parameters, B1+ maps, and SAR. We calculated peak 10 g average SAR using 4 different realistic human body models for a quadrature excitation and demonstrated that the peak 10 g SAR variation between subjects was less than 30%. We calculated safe power limits based on this set and used those limits to acquire T2 - and T2∗ -weighted images of human subjects at 10.5T. In this study, we acquired the first in vivo human head images at 10.5T using an 8-channel transmit/receive coil. We implemented and expanded a previously proposed workflow to validate the electromagnetic simulation model of the 8-channel transmit/receive coil. Using the validated coil model, we calculated radiofrequency power levels to safely image human subjects.


Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Primer for Emergency Physicians.
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) impose a significant burden on patients and the emergency health care system. Patients with COPD who present to the emergency department (ED) often have comorbidities that can complicate their management. To discuss strategies for the management of acute exacerbations in the ED, from initial assessment through disposition, to enable effective patient care and minimize the risk of treatment failure and prevent hospital readmissions. Establishing a correct diagnosis early on is critical; therefore, initial evaluations should be aimed at differentiating COPD exacerbations from other life-threatening conditions. Disposition decisions are based on the intensity of symptoms, presence of comorbidities, severity of the disease, and response to therapy. Patients who are appropriate for discharge from the ED should be prescribed evidence-based treatments and smoking cessation to prevent disease progression. A patient-centric discharge care plan should include medication reconciliation; bedside "teach-back," wherein patients demonstrate proper inhaler usage; and prompt follow-up. An effective assessment, accurate diagnosis, and appropriate discharge plan for patients with AECOPD could improve treatment outcomes, reduce hospitalization, and decrease unplanned repeat visits to the ED.


Phosphorylation of the vesicle-tethering protein p115 by a casein kinase II-like enzyme is required for Golgi reassembly from isolated mitotic fragments.
Coat protein I (COPI) transport vesicles can be tethered to Golgi membranes by a complex of fibrous, coiled-coil proteins comprising p115, Giantin and GM130. p115 has been postulated to act as a bridge, linking Giantin on the vesicle to GM130 on the Golgi membrane. Here we show that the acidic COOH terminus of p115 mediates binding to both GM130 and Giantin as well as linking the two together. Phosphorylation of serine 941 within this acidic domain enhances the binding as well as the link between them. Phosphorylation is mediated by casein kinase II (CKII) or a CKII-like kinase. Surprisingly, the highly conserved NH(2)-terminal head domain of p115 is not required for the NSF (N-ethylmaleimide-sensitive fusion protein)-catalyzed reassembly of cisternae from mitotic Golgi fragments in a cell-free system. However, the ability of p115 to link GM130 to Giantin and the phosphorylation of p115 at serine 941 are required for NSF-catalyzed cisternal regrowth. p115 phosphorylation may be required for the transition from COPI vesicle tethering to COPI vesicle docking, an event that involves the formation of trans-SNARE [corrected] (trans-soluble NSF attachment protein [SNAP] receptor) complexes.


An unusual co-occurrence of Langerhans cell histiocytosis and Rosai-Dorfman disease: report of a case and review of the literature.
The co-occurrence of Langerhans cell histiocytosis (LCH; disorder characterized by proliferation of Langerhans cells) and Rosai-Dorfman disease (RDD; histiocytic entity that is one of the non-Langerhans cell diseases) is extremely rare and raises several questions regarding the nature of the diseases. We describe a 10-year-old boy who presented with a 3-month history of right scalp swelling. Clinical, pathological, and imaging evaluation disclosed multiple LCH of bone and cutaneous RDD. After initiating prednisone and vinblastine therapy, the patient developed an asymptomatic diffuse papular eruption. Biopsy revealed cutaneous RDD. Treatment was continued with a good response of bone LCH and significant amelioration of the cutaneous findings. Co-occurrence of LCH and RDD is a rare phenomenon. Various explanations, including the role of chemotherapy, are suggested based on our and several previously reported cases.


Non-hyaluronic acid fillers.
Fillers are numerous, and the products currently available have effects that may last from a few months to many years. These are used to treat facial wrinkles, and some of the new fillers exert a stimulatory effect, restoring volume in focal areas of the face by inducing collagen fibers. The dermasurgeon should thoroughly understand the indications and uses of these fillers to meet fully a patient's expectations. Some fillers are biodegradable (12-18 months), others slowly biodegradable (2-5 years), whereas others are permanent implants. The disadvantage of the traditional biodegradable fillers is their short duration (6-12 months). Over the past decade, semipermanent fillers (polylactic acid and ceramics) have been used: they do have a longer effect, but they might induce granulomas especially on the lips. Also, permanent fillers are traditionally linked to a higher incidence of granulomas and extrusions, although with the new formulations, the adverse events are decreased.


Investigation of scrambled ions in tandem mass spectra. Part 1. Statistical characterization.
Scrambled ions have become the focus of recent investigations of peptide fragmentation. Here, an investigation of more than 390,000 high quality CID mass spectra is presented to explore the extent of scrambled ions in mass spectra and the possible fragmentation rules during scramble reactions. For the former, scrambled ions generally make up more than 10 % of mass spectra in number, although the abundances are less than 0.1 of the base peak. For the latter, relatively preferential re-opening sites were found for aliphatic residues Ala, Ile, Leu, and other residues such as Met, Gln, Ser, Phe, and Thr, whereas disfavored sites were found for basic residues Arg, Lys, and His, and Trp for both scrambled b and a ions. Similar preferential order in re-opening reaction was found in the reaction of losing internal residues when cleavage occurs at C-terminal side of 20 residues. However, when cleavage occurs at N-terminal side, Glu, Phe, and Trp become the most preferential sites. These results provide a deep insight into cleavage rules during scramble reactions for prediction of peptide mass spectra. Also, an additional investigation of whether scrambled ions could help discriminate false identifications from correct identifications was performed. Probing the number fraction of scrambled ions in falsely and correctly interpreted spectra and analyzing the correlation between scrambled ions and SEQUEST scores XCorr and Sp showed scrambled ions could at some extent help improve the discrimination in singly charged identifications, whereas no improvement was found for multiply charged results.


Modulation of mesenchymal stem cell chondrogenesis in a tunable hyaluronic acid hydrogel microenvironment.
An injectable and biodegradable hydrogel system comprising hyaluronic acid-tyramine (HA-Tyr) conjugates can safely undergo covalent cross-linking in vivo by the addition of small amounts of peroxidase and hydrogen peroxide (H(2)O(2)), with the independent tuning of the gelation rate and degree of cross-linking. Such hydrogel networks with tunable mechanical and degradation properties may provide the additional level of control needed to enhance chondrogenesis and overall cartilage tissue formation in vitro and in vivo. In this study, HA-Tyr hydrogels were explored as biomimetic matrices for caprine mesenchymal stem cells (MSCs) in cartilage tissue engineering. The compressive modulus, equilibrium swelling and degradation rate could be controlled by varying the concentration of H(2)O(2) as the oxidant in the oxidative coupling reaction. Cellular condensation reflected by the increase in effective number density of rounded cells in lacunae was greater in softer hydrogel matrices with lower cross-linking that displayed enhanced scaffold contracture. Conversely, within higher cross-linked matrices, cells adopted a more elongated morphology, with a reduced degree of cellular condensation. Furthermore, the degree of hydrogel cross-linking also modulated matrix biosynthesis and cartilage tissue histogenesis. Lower cross-linked matrix enhanced chondrogenesis with increases in the percentage of cells with chondrocytic morphology; biosynthetic rates of glycosaminoglycan and type II collagen; and hyaline cartilage tissue formation. With increasing cross-linking degree and matrix stiffness, a shift in MSC differentiation toward fibrous phenotypes with the formation of fibrocartilage and fibrous tissues was observed. These findings suggest that the tunable three-dimensional microenvironment of the HA-Tyr hydrogels modulates cellular condensation during chondrogenesis and has a dramatic impact on spatial organization of cells, matrix biosynthesis, and overall cartilage tissue histogenesis.


A robust-digital QRS-detection algorithm for arrhythmia monitoring.
The success of automated patient monitoring is primarily dependent on the ability to detect normal as well as bizarre QRS-complexes. In this paper a new robust single lead QRS-detection algorithm is presented. The QRS detector can be separated into five different blocks, namely, a noise filter, a differentiator, an energy collector, a minimal distance classifier, and a minimax trimmer. Each block accounts for some characteristic features of QRS complexes (steepness, duration, etc.). The time delay introduced by this algorithm for making a decision is less then one second, allowing real-time applications. The performance of the QRS detector is analyzed and results are presented.


Lipid classes and fatty acid composition of the tropical nudibranch mollusks Chromodoris sp. and Phyllidia coelestis.
Two nudibranch mollusks, Chromodoris sp. and Phyllidia coelestis, collected from tropical waters of the Northwestern Pacific, were analyzed for lipids. The aim of this study was to fill the gap in knowledge of lipid biochemistry of mollusks. Phospholipids (PL) were the dominating lipid class followed by sterols (13%). Neutral lipids were not detected in Chromodoris sp. By contrast, P. coelestis contained TAG, diacylglyceryl ether, long chain alcohol and esters of sterols. Among PL, PC was predominant (about 50%); PE, PS and CAEP were almost in equal proportions. Sixty five FA were identified as methyl esters and N-acyl pyrrolidides by GC-MS. The sea slugs exhibited a wide diversity of FA. The common marine n-3 PUFA, 20:5n-6 and 22:6n-3, constituted 0.6-1.3% of the total FA, whereas n-6 PUFA, 22:4n-6, 20:4n-6, and 18:2n-6, were the main (25%). Among monounsaturated FA, 7-21:1 was the main (up to 6.2%). The non-methylene-interrupted (NMI) FA were found (9.4 and 12.4%), including the known 5,11-20:2, 5,13-20:2, 7,13-22:2, 7,15-22:2 and a novel isomer 7,13-21:2 (up to 3.9%). The pathway of its biosynthesis was suggested. A series of very long chain FA (VLC FA), with the main 5,9-25:2 and 5,9-26:2, were identified. High level of VLC FA (8.7 and 11.7%) in sea slugs is apparently the result of predation on sponges. Another unique feature concerned a high abundance of various odd and branched FA (16.7 and 34%), which could have originated from the dietary origin or symbiotic bacteria. This is the first report on lipid and FA composition of nudibranchs.


Mesenteric and portal vein thrombosis, a rare complication in a patient with polycystic ovary syndrome: A case report and review of literature.
One of the rare complications of polycystic ovarian syndrome (PCOS) treated with combination contraceptives is venous thrombosis. However, there is currently no information on intestinal necrosis and portal venous thrombosis in polycystic ovary syndrome patients, and diagnosis is frequently delayed in these situations. We report a case of a 30-year old female patient who experienced a sudden onset of rectal bleeding and severe abdominal pain. Superior mesenteric vein thrombosis was detected with Doppler ultrasonography. Right portal vein thrombosis was discovered on contrast-enhanced tomography of the abdomen; it was treated with enoxaparin sodium without improvement. A colonoscopy was then conducted; it revealed a distal descending colon with proximal sigmoid colon ischemia alterations. During a laparoscopic, ischemic portion were removed. On follow-up after two weeks, the patient was still on enoxaparin sodium (80 mg twice daily) in good general condition. Portal vein thrombosis (PVT) and Superior mesenteric venous thrombosis (MVT) are rare forms of venous thrombosis and unusual conditions. Superior MVT related to hormonal contraception and PCOS is uncommon. To best of our knowledge, here we report the first case of PCOS presented with acute intestinal ischemia related to MVT. Except for the correlation between PCOS and the use of combination contraceptives, no predisposing factor for portal vein thrombosis was found. Our case report indicates the need for clinicians to consider acute intestinal ischemia in patients with polycystic ovarian disease who have acute abdominal pain and atypical site of thrombosis.


Inter-hemispheric lateralization of event related potentials; motoric versus non-motoric cortical activity.
To study hemispheric lateralization of cortical potentials associated with motoric and non-motoric function, cortical activity was recorded accompanying either finger extension or saccadic eye movements in a contingent negative variation (CNV) paradigm. Subjects viewed computer-generated pacing stimuli, presented in the left visual hemi-field, and were instructed to either initiate or inhibit a motor response following an imperative signal. Motoric lateralization was assessed by means of the lateralized readiness potential (LRP). In addition, a measure complementary to the LRP was introduced to investigate non-motoric lateralization (NML). Contralateral inter-hemispheric lateralization was evident in the LRP preceding finger movement, but was absent prior to eye movements. However, pre-saccadic cortical response profiles did exhibit a right hemispheric, non-motoric lateralization (NML) during stimulus presentation. Comparable non-motoric lateralization was found for finger extension. Results of the present study suggest that non-motoric lateralization may be a contributing factor to the frequently reported inter-hemispheric asymmetry preceding self-initiated saccadic eye movements. Results of the present study also suggest that the latter may be related to a covert shift of visuospatial attention toward the saccadic target. Associated shifts of attention are suppressed in a CNV paradigm, where attentional focus is primarily on the CNV stimulus during the pre-saccade period.


Which drug-induced side effects would be tolerated in the prospect of seizure control?
There is ample evidence that side effects of antiepileptic pharmacotherapy negatively affect quality of life, adherence, and long-term retention. The study was set up to evaluate the anticipated tolerance of common side effects provided that a 50% or 100% reduction of seizure frequency would be achieved. An anonymous inquiry in 79 consecutive patients with epilepsy comprised questions regarding the severity of epilepsy/seizures and the perceived impact of seizures and drug treatment on daily functioning and a 10-tiered rating which assesses 11 common behavioral/psychiatric, cognitive, physiological, or physical side effects according to the degree to which they would be tolerated. Least acceptance was evident for psychiatric side effects followed by cognitive, physiological, and physical side effects. Weight gain and tiredness were the most tolerated side effects. The overall low acceptance of negative side effects was slightly higher in the case of a 100% vs. 50% seizure frequency reduction (28% vs. 21% of the maximum toleration score regarding all side effects). Surely, there is a trade-off between the severity of epilepsy, seizure control, and the acceptance of adverse treatment effects. However, the data disclose that psychiatric and cognitive side effects are least accepted. Thus, consideration of individual tolerance and monitoring of side effects in addition to seizures may increase adherence and therapy success.


Financial Preparedness for Birth Among Rural Zambian Women: Do Antenatal Care Contacts Make a Difference?
Financial constraints are one of the biggest barriers for women of low-income countries to receive necessary reproductive health services. Educating women about the importance of saving money has been incorporated as a component of antenatal care (ANC) contacts, but little is known whether ANC contacts influence women's saving. A secondary analysis was conducted on data from a cross-sectional household survey study of 1109 women who recently gave birth in two rural districts of Zambia. Receiving ANC contacts early and often and discussing saving money during ANC were associated with saving money for the mother's birth, but not with saving enough money for the most recent birth. Continued effort is needed to encourage women to attend ANC contacts earlier and more frequently. Additionally, the importance of saving money for birth should be discussed during ANC contacts. Future studies need to explore why women's action in saving does not necessarily lead to saving enough for childbirth.


Multiple QTLs influencing triglyceride and HDL and total cholesterol levels identified in families with atherogenic dyslipidemia.
We conducted a genome-wide scan using variance components linkage analysis to localize quantitative-trait loci (QTLs) influencing triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol, and total cholesterol (TC) levels in 3,071 subjects from 459 families with atherogenic dyslipidemia. The most significant evidence for linkage to TG levels was found in a subset of Turkish families at 11q22 [logarithm of the odds ratio (LOD)=3.34] and at 17q12 (LOD=3.44). We performed sequential oligogenic linkage analysis to examine whether multiple QTLs jointly influence TG levels in the Turkish families. These analyses revealed loci at 20q13 that showed strong epistatic effects with 11q22 (conditional LOD=3.15) and at 7q36 that showed strong epistatic effects with 17q12 (conditional LOD=3.21). We also found linkage on the 8p21 region for TG in the entire group of families (LOD=3.08). For HDL-C levels, evidence of linkage was identified on chromosome 15 in the Turkish families (LOD=3.05) and on chromosome 5 in the entire group of families (LOD=2.83). Linkage to QTLs for TC was found at 8p23 in the entire group of families (LOD=4.05) and at 5q13 in a subset of Turkish and Mediterranean families (LOD=3.72). These QTLs provide important clues for the further investigation of genes responsible for these complex lipid phenotypes. These data also indicate that a large proportion of the variance of TG levels in the Turkish population is explained by the interaction of multiple genetic loci.


Impact of the Ki-67 proliferation index on response to peptide receptor radionuclide therapy.
The role of the Ki-67 tumour proliferation index (PI) in predicting the efficacy of peptide receptor radionuclide therapy (PRRT) in gastroenteropancreatic tumours (GEP-NET) remains undetermined. This single-centre analysis focused on the potential therapeutic impact of this immunohistochemical parameter. A total of 81 consecutive GEP-NET patients treated with (177)Lu-DOTA-octreotate (mean activity of 7.9 GBq per cycle, usually four treatment cycles at standard intervals of 3 months) were retrospectively analysed. Both an evaluable PI and tumour response (modified SWOG criteria) were required for patient inclusion. Response of tumours with a PI of ≤20% (partial response 40%, minor response 15%, stable disease 34%, progressive disease 11%) was comparable in all PI subsets, including those with a PI of 20%. However, G3 tumours (PI > 20%) showed progression in 71% of patients. Response to PRRT is consistent over the PI range of ≤20% (G1 + G2). Contrary to preliminary previous suggestions, a PI of 15% or 20% should not preclude candidates from somatostatin receptor-targeted radiotherapy.


In-silico decongested trial effects on the impaired breathing function of a bulldog suffering from severe brachycephalic obstructive airway syndrome.
Brachycephalic obstructive airway syndrome (BOAS) susceptible dogs (e.g., French bulldog), suffer health complications related to deficient breathing primarily due to anatomical airway geometry. Surgical interventions are known to provide acceptable functional and cosmetic results; however, the long-term post-surgery outcome is not well known. In silico analysis provides an objective measure to quantify the respiratory function in postoperative dogs which is critical for successful long-term outcomes. A virtual surgery to open the airway can explore the ability for improved breathing in an obstructed airway of a patient dog, thus supporting surgeons in pre-surgery planning using computational fluid dynamics. In this study five surgical interventions were generated with a gradual increment of decongested levels in a bulldog based on computed tomography images. The effects of the decongested airways on the breathing function of a patient bulldog, i.e., airflow characteristics, pressure drop, wall shear stress, and air-conditioning capacity, were quantified by benchmarking against a clinically healthy bulldog using computational fluid dynamics (CFD) method. Our findings demonstrated a promising decrease in excessive airstream velocity, pressure drop, and wall shear stress in virtual surgical scenarios, while constantly preserving adequate air-conditioning efficiency. A linear fit curve was proposed to correlate the reduction in the pressure drop and decongested level. The in silico analysis is a viable tool providing visual and quantitative insight into new unexplored surgical techniques.


Meta-Analysis Comparing Dual Versus Single Antiplatelet Therapy in Combination With Antithrombotic Therapy in Patients With Atrial Fibrillation Who Underwent Percutaneous Coronary Intervention With Stent Implantation.
The coexistence of atrial fibrillation and coronary artery disease is commonly found in clinical practice. The aim of this meta-analysis is to compare the clinical efficacy and safety of dual versus single antiplatelet therapy in combination with antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention. PubMed, EMBASE and Web of Science databases were systematically evaluated for articles published up to October 31, 2017. The risk ratios (RR) were extracted from each study. Pooled estimates with corresponding 95% confidence intervals (CI) were estimated by a fixed or random-effects model. Eight studies involving a total of 10,861 patients with atrial fibrillation were included in this meta-analysis. Five thousand sixty-six participants received dual antiplatelet therapy together with warfarin or new oral anticoagulation (triple antithrombotic therapy, TT) and 5,795 participants received single antiplatelet therapy together with warfarin or new oral anticoagulation (dual antithrombotic therapy). TT was associated with a significantly higher incidence of all (RR 1.45, p <0.001) and major (RR 1.77, p <0.001) bleeding events, but no difference with regard to stroke, in-stent thrombosis, major adverse cardiovascular events, and all-cause mortality rate. In conclusion, as compared to TT, dual antithrombotic therapy is equally effective in reducing stroke, in-stent thrombosis, major adverse cardiovascular events, and all-cause mortality rate, but shows beneficial effect in reducing overall bleeding incidence in atrial fibrillation patients who underwent percutaneous coronary intervention.


[Personality, accentuated traits and personality disorders. A contribution to dimensional diagnosis of personality disorders].
A dimensional diagnostic system for personality disorders (PD) postulates continuous transition from normal to disordered personalities (continuity hypothesis) and universal validity of basic personality dimensions (universal hypothesis). The present study investigates the validity of Leonhard's concept of attenuated personalities that define a conceptual link between normal personality dimensions and PD. Nine possible continuous transitions between three conceptual levels (Big Five personality factors, nine attenuated personality traits, nine PD) were tested by questionnaire data obtained from a mentally healthy (n = 166) and a clinical sample (n = 78). Both samples differed significantly in nearly all variables. However, they showed substantial similarity concerning the (in)validity of single continua and the complex structure of all variables as analyzed by multidimensional scaling. The concept of attenuated personalities could be validated for six out of nine tested continua and can be recommended for application in dimensional models of personality and personality disorders.


Clinical tolerance and metabolism of a fat emulsion containing carnitine and gamma-linolenic acid.
The purpose of the present study was to study the metabolism and evaluate the tolerance of a new fat emulsion, which is rich in gamma-linolenic acid and has been supplemented with carnitine. 24 adult male volunteers participated in an open, randomised, crossover study where half of the subjects were given Intralipid 20% (IL) on day one followed by administration of the supplemented fat emulsion (FE) on day two, the other half being treated in the reverse order. Both fat emulsions were first administered as a bolus dose of 0.10 g triglycerides per kg BW (an intravenous fat tolerance test) followed 40 min later by a continuous intravenous infusion during 4 h at a rate of 0.21 g triglycerides per min. The plasma fractional elimination rate, k(2)-value, was lower for FE than for IL (4.6 +/- 1.8 vs 5.3 +/- 1.6% per min, P < 0.05, mean +/- SD). Infusion of FE, as distinct from IL administration, was accompanied by a marked increase in serum gamma-linolenic acid concentration (239 +/- 133 vs 0 +/- 11 mumol/l, P < 0.05). No differences between FE and IL were discernible regarding the serum concentrations of dihomo-gamma linolenic acid (C 20: 3omega6), arachidonic acid (C 20: 4omega6), adrenic acid (C 22: 4omega6) or docosapentanaenoic acid (C 22: 5omega6). Leucocyte chemotaxis and random migration increased, 0.5 +/- 0.3 arb. units (P < 0.01) and 0.2 +/- 0.2 arb. units (P < 0.05), during infusion of FE but no such effect was noted during IL administration. No effect of the fat emulsion composition and carnitine was detected on phagocytosis and oxidative metabolism of neutrophil leucocytes. In conclusion, the new fat emulsion containing a relatively high proportion of gammalinolenic acid and supplemented with carnitine was found to be well tolerated although it was eliminated from plasma at a 13% slower rate. The supplemented fat emulsion had a moderate stimulatory effect on leukocyte chemotaxis.


Composition of cuticular waxes coating flag leaf blades and peduncles of Triticum aestivum cv. Bethlehem.
The work herein presents comprehensive analyses of the cuticular wax mixtures covering the flag leaf blade and peduncle of bread wheat (Triticum aestivum) cv. Bethlehem. Overall, Gas Chromatography-Mass Spectrometry and Flame Ionization Detection revealed a wax coverage of flag leaf blades (16 μg/cm(2)) a third that of peduncles (49 μg/cm(2)). Flag leaf blade wax was dominated by 1-alkanols, while peduncle wax contained primarily β-diketone and hydroxy-β-diketones, thus suggesting differential regulation of the acyl reduction and β-diketone biosynthetic pathways in the two analyzed organs. The characteristic chain length distributions of the various wax compound classes are discussed in light of their individual biosynthetic pathways and biosynthetic relationships between classes. Along with previously reported wheat wax compound classes (fatty acids, 1-alkanols, 1-alkanol esters, aldehydes, alkanes, β-diketone, hydroxy-β-diketones, alkylresorcinols and methyl alkylresorcinols), esters of 2-alkanols and three types of aromatic esters (benzyl, phenethyl and p-hydroxyphenethyl) are also reported. In particular, 2-heptanol esters were identified. Detailed analyses of the isomer distributions within 1-alkanol and 2-alkanol ester homologs revealed distinct patterns of esterified acids and alcohols, suggesting several wax ester synthases with very different substrate preferences in both wheat organs. Terpenoids, including two terpenoid esters, were present only in peduncle wax.


Association of serum C-reactive protein and indices of body fat distribution and overweight in Mexican American children.
Few data have been published on the association of indices of body fat distribution and components of the insulin resistance syndrome and serum C-reactive protein (CRP), an acute phase protein and putative risk factor for cardiovascular morbidity, in representative samples of total populations of children or in Hispanic Americans, who have a high prevalence of obesity and diabetes as adults. To evaluate the association of waist-to-hip ratio (WHR) and body mass index (BMI) and components of the insulin resistance syndrome with CRP in Mexican American children and to assess the independence of the association. Cross-sectional survey of a large national sample, the Third National Health and Nutrition Examination Survey. Mexican American children aged 6-11 years. Body circumferences, skinfold thickness, BMI, blood pressure, and serum CRP and lipid concentrations. Overall, 11% of children had detectable CRP (> 0.21 mg/dL). CRP was not associated with age, gender, or birth weight. WHR showed significant positive associations with serum CRP concentration independent of BMI. BMI was also significantly associated with CRP independent of WHR. CRP was significantly associated with HDL cholesterol but not triglyceride, or systolic blood pressure, concentration after controlling for BMI. Further research is needed on the associations of serum CRP concentration with WHR and other indices of body fat distribution and obesity to elucidate the mechanisms and significance of these associations.


Ulnar Neuropathy due to Volar/Ulnar Displacement of the Flexor Tendons after Open Carpal Tunnel Release: Case Report.
Ulnar nerve neuropathy is a rare complication following the carpal tunnel release. Above all, compression neuropathy is much rare. We report an acute ulnar nerve neuropathy following open carpal tunnel release due to the volar and ulnar displacement of the flexor tendons from the carpal tunnel and review the literature.


Effects of a stable prostacyclin analogue beraprost sodium on VEGF and PAI-1 gene expression in vascular smooth muscle cells.
Beraprost sodium, an orally active prostacyclin analogue, has proved to be beneficial for the patients with primary pulmonary hypertension and obstructive peripheral arterial disease. In this study, we examined the effects of BPS on the expression of the VEGF and PAI-1 genes in vascular smooth muscle cells. The mRNA levels for VEGF were increased by BPS in C2/2 cells and cultured rat aortic smooth muscle cells. In contrast, PAI-1 mRNA levels were significantly decreased by BPS. Luciferase assays and mRNA decay assays showed that BPS increases VEGF promoter activity and has no effects on its mRNA stability. Likewise, BPS decreases PAI-1 promoter activity without affecting its mRNA stability. Experiments using various pharmacological inhibitors for protein kinases showed that activation of cAMP-dependent protein kinase (PKA) was involved in BPS-mediated regulation of VEGF and PAI-1 mRNA expression. Overexpression of CREB (cAMP-responsive element binding protein) induces VEGF promoter and reduces PAI-1 promoter activities. CREMepsilon, a dominant negative form of CREB, inhibits BPS-mediated changes in VEGF and PAI-1 promoter activities. While BPS augmented hypoxia-induced VEGF mRNA expression, it blunted hypoxia-induced PAI-1 mRNA expression. These results suggest that BPS increases VEGF and decreases PAI-1 gene expression through PKA/CREB-dependent mechanisms in vascular smooth muscle cells. Because these effects are observed more prominently under the hypoxic condition compared to normoxic condition, BPS may have a potential to relieve hypoxia by inducing neovasculization and by reducing thrombosis.


Hypoperfusion is a potential inducer of immunosuppressive network in Alzheimer's disease.
Alzheimer's disease (AD) is a progressive neurodegenerative disease which causes a non-reversible cognitive impairment and dementia. The primary cause of late-onset AD remains unknown although its pathology was discovered over a century ago. Recently, the vascular hypothesis of AD has received backing from evidence emerging from neuroimaging studies which have revealed the presence of a significant hypoperfusion in the brain regions vulnerable to AD pathology. In fact, hypoxia can explain many of the pathological changes evident in AD pathology, e.g. the deposition of β-amyloid plaques and chronic low-grade inflammation. Hypoxia-inducible factor-1α (HIF-1α) stimulates inflammatory responses and modulates both innate and adaptive immunity. It is known that hypoxia-induced inflammation evokes compensatory anti-inflammatory response involving tissue-resident microglia/macrophages and infiltrated immune cells. Hypoxia/HIF-1α induce immunosuppression by (i) increasing the expression of immunosuppressive genes, (ii) stimulating adenosinergic signaling, (iii) enhancing aerobic glycolysis, i.e. lactate production, and (iv) augmenting the secretion of immunosuppressive exosomes. Interestingly, it seems that these common mechanisms are also involved in the pathogenesis of AD. In AD pathology, an enhanced immunosuppression appears, e.g. as a shift in microglia/macrophage phenotypes towards the anti-inflammatory M2 phenotype and an increase in the numbers of regulatory T cells (Treg). The augmented anti-inflammatory capacity promotes the resolution of acute inflammation but persistent inflammation has crucial effects not only on immune cells but also harmful responses to the homeostasis of AD brain. I will examine in detail the mechanisms of the hypoperfusion/hypoxia-induced immunosuppressive state in general and especially, in its association with AD pathogenesis. These immunological observations support the vascular hypothesis of AD pathology.


Coronary risk factors and plasma sex hormones.
Recent studies have reported higher plasma estradiol levels in male survivors of acute myocardial infarction. This finding has raised the possibility that hyperestrogenemia may consitiute a separate coronary risk factor. In 443 men, aged 30, 40, 50, and 60, we assessed the relationship between plasma levels of estradiol, testosterone, and testosterone-binding globulin and coronary risk factors: fasting plasma concentrations of triglyceride, cholesterol, and high-density lipoprotein, blood pressure, and smoking and leisure-time physical activity patterns. Plasma estradiol concentrations were found to correlate significantly with body weight. After adjustment for this association, we found that the mean plasma estradiol concentration still was significantly higher in smokers than in nonsmokers. No other correlation could be estabilished between plasma hormone levels and coronary risk factors. The relative hyperestrogenemia reported in men with previous myocardial infarction may be due to an effect of smoking but may also reflect the relationship between body weight and plasma estradiol levels. Future studies should consider the demonstrated association between plasma estrogen levels and smoking.


Genetic architecture of subspecies divergence in trace mineral accumulation and elemental correlations in the rice grain.
Genome differentiation has shaped the divergence in element concentration between rice subspecies and contributed to the correlation among trace minerals in the rice grain. The balance between trace minerals in rice, a staple food for more than half of the world's population, is crucial for human health. However, the genetic basis underlying the correlation between trace minerals has not been fully elucidated. To address this issue, we first quantified the concentrations of 11 trace minerals in the grains of a diversity panel of 575 rice cultivars. We found that eight elements were accumulated at significantly different levels between the indica and japonica subspecies, and we also observed significant correlation patterns among a number of elements. Further, using a genome-wide association study, we identified a total of 96 significant association loci (SALs). The differentiation of the major-effect SALs along with the different number of high-concentration alleles present in the two subspecies shaped the different element performance in indica and japonica varieties. Only a few SALs located in clusters and the majority of SALs showed subspecies/subgroup differentiation, indicating that the correlations between elements in the diversity panel were mainly caused by genome differentiation instead of shared genetic basis. The genetic architecture unveiled in this study will facilitate improvement in breeding for trace mineral content.


The Promise of Wisconsin's 1999 Comprehensive Planning Law: Land-Use Policy Reforms to Support Active Living.
Weaving together the disciplines of planning and policy change with the emerging research of active living, this article explores the competing interests and underlying political forces behind the design and passage of Wisconsin's Comprehensive Planning Law of 1999. While Wisconsin's law remains a work in progress, it illustrates the contemporary policy battles over land use and smart growth and the resurgence of the property-rights movement. It further highlights the influence of smart-growth coalitions and policy networks on planning reform. The authors suggest that planning practitioners and active-living proponents can adapt and transfer these policy lessons from Wisconsin to address the complex relationships of the built environment, physical activity, and the nation's current obesity problem through state and local planning reforms.


When the bleeding won't stop: a case report on a patient with hemophilia.
A 39-year-old male developed severely prolonged bleeding after periodontal surgery because of a previously undetected clotting Factor XI deficiency (Hemophilia C). Diagnosis and treatment of this bleeding disorder are discussed.


Hematological toxicity of carboplatin for gynecological cancer according to body mass index.
The aim of the present study was to analyze how patient weight affects the hematological toxicity of carboplatin and whether this toxicity is more prevalent in overweight patients. We performed a retrospective 2-year study of patients diagnosed with a gynecological cancer and whose treatment regimen contained carboplatin (AUC dose = 5 or 6) and paclitaxel (dose = 175 mg/m(2)) every 3 weeks (CP scheme). We recorded all severe hematological events (thrombocytopenia, neutropenia, and/or anemia grade III/IV) according to the CTCAE v4.03, as well as treatment modifications and the need for granulocyte colony-stimulating factors (G-CSF) and/or erythropoietin (EPO) or packed red blood cells (PRBC). Patients with a body mass index (BMI) ≥27 kg/m(2) were considered as overweight (OW) and those with a BMI <27 kg/m(2) were considered as normal weight (NW). Fifty-two patients met the inclusion criteria (21 patients in the OW group, 31 patients in the NW group). The OW group showed a higher incidence of thrombocytopenia (95% confidence intervals (CI) 1.51-27.72; p < 0.02) and anemia (95% CI 1.06-33.63; p < 0.05). Moreover, this was reflected in a greater number of changes in the usual CP regimen (95% CI 2.19-44.32; p < 0.01). The need for G-CSF and/or EPO/PRBC was also significantly higher in the OW group (95% CI 1.08-12.16; p < 0.04). Carboplatin dosing based on real weight in obese patients resulted in increased hematologic toxicity, mainly thrombocytopenia. Dose adjustment based on other descriptors of weight, such as adjusted weight, may be better tolerated by patients. However, future studies are needed to demonstrate not only better safety of carboplatin but also improved survival rates.


Variable phenotype including Leigh syndrome with a 9185T>C mutation in the MTATP6 gene.
We describe 15 members of a Caucasian family with an apparently homoplasmic T-->C mutation at nucleotide position 9185 (9185T>C) in the mtDNA encoded MTATP6 (ATPase 6) gene. The clinical phenotype is extremely variable and includes late-onset Leigh syndrome (LS), isolated demyelinating peripheral neuropathy and neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP). Following recent reports of this same mutation in a single case and in a family with late-onset LS and NARP-like features, our paper emphasises the role of MTATP6 in LS and expands the associated clinical phenotype further.


Influence of calcitonin treatment on the bone structure and mineral content in osteoarthritis.
8 femoral heads removed in 4 patients operated on by bilateral total hip replacement for osteoarthritis were evaluated. 3 patients were treated with Calcitonin between the first and the second operation. X-ray powder diffractometry analysis showed an improvement of bone crystallinity in the Calcitonin treated patients.


Corrigendum to "Experience and lessons learned from blunt cerebrovascular injuries: A case report" [Heliyon 9 (3) (March 2023) Article e13968].
[This corrects the article DOI: 10.1016/j.heliyon.2023.e13968.].


A prospective analysis of risk factors for white matter disease in the brain stem: the Cardiovascular Health Study.
White matter disease (WMD) in the brain stem may be a predictor of poor clinical outcome, independent of WMD in the periventricular and subcortical areas of the brain. Many cardiovascular risk factors such as older age, hypertension, and smoking have been suggested as risk factors for WMD in the periventricular and subcortical areas of the brain. However, no epidemiologic study has examined the associations between cardiovascular risk factors and WMD in the brain stem. A total of 789 participants, aged 65 years or older, from the Cardiovascular Health Study constituted the present study population. WMD, defined as hyperintensive lesions on magnetic resonance imaging (MRI), in the brain stem was measured in 1992/1993 and 1997/1998. Of the 789 participants, 212 (26.9%) had WMD in the brain stem in 1997/1998. In multivariate logistic regression analysis, the presence of WMD in the brain stem in 1997/1998 was significantly associated with several variables measured in 1992/1993: an increase by 5 years of age (OR = 1.51, 95% CI: 1.25-1.83), a 10-pack-years increase in smoking (OR = 1.12, 95% CI: 1.04-1.21), a 0.1-liter increase in first-second forced expiratory volume (OR = 0.95, 95% CI: 0.92-0.99), a 1 micromol/l increase in fibrinogen level (OR = 1.13, 95% CI: 1.03-1.23), and MRI infarction (OR = 2.58, 95% CI: 1.78-3.74). Excluding those (n = 167) with WMD in the brain stem in 1992/1993, the pattern remained. Hypertension was not associated with WMD in the brain stem. Increased age, smoking, lower forced expiratory volume, increased fibrinogen level, and MRI infarction, but not hypertension, may be independent risk factors for WMD in the brain stem in older adults.


Amino acids are necessary for the insulin-induced activation of mTOR/S6K1 signaling and protein synthesis in healthy and insulin resistant human skeletal muscle.
Amino acids (AA) activate the mammalian target of rapamycin (mTOR) signaling pathway but overactivation has a negative feedback effect on insulin signaling which may lead to insulin resistance and type 2 diabetes (T2DM). To determine the effect of reduced AA concentrations on mTOR and insulin signaling during increased nutrient and insulin availability. Six control and six T2DM subjects were studied at baseline and following a 5h AA lowering high energy and insulin clamp. Stable isotopic techniques in combination with femoral catheterizations were used to measure AA kinetics across the leg while muscle biopsies were used to measure mTOR and insulin signaling proteins using immunoblotting techniques. AA concentrations decreased by approximately 30-60% in both groups (p<0.05). Phospho-mTOR, S6K1, eEF2, and eIF2alpha were unchanged in both groups following the clamp (p>0.05). In T2DM subjects, IRS-1 serine phosphorylation was unchanged while phospho-AMPKalpha decreased and phospho-Akt, phospho-AS160 and glucose uptake increased following the clamp (p<0.05). In comparison, AA concentrations were maintained in a separate group during an insulin infusion. In this group, phospho-Akt, mTOR and S6K1 (n=4) increased. Amino acids are necessary for insulin-induced activation of mTOR signaling and protein synthesis in both healthy and insulin resistant skeletal muscle.


Comparison of octenol- and BG Lure-baited biogents sentinel traps and an encephalitis virus surveillance trap in Portland, OR.
Two types of mosquito trap were tested near Smith Lake in Portland, Multnomah County, OR: 2 Biogents Sentinel (BGS) traps baited with carbon dioxide (CO2) and an octenol sachet or a BG Lure, and an encephalitis virus surveillance (EVS) trap with CO2 but without an odor sachet. After 6 trap-nights, the 2 BGS traps caught significantly more mosquitoes than the EVS trap. More Culex tarsalis and an overall greater number of species were caught in the BGS traps. A BGS trap and an EVS trap, both baited with CO2 alone, were compared to investigate whether the difference was due to the attractants or the difference in trap type. The BGS trap caught more mosquitoes but the difference was not significant. The BGS trap, when baited with CO2 and other lures, can be an effective mosquito sampling tool, but further research is needed to understand the importance of the attractants.


Familial Hemophagocytic Lymphohistiocytosis.
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare heritable disorder of immune regulation that is typically characterized by sudden onset of severe systemic illness. Functional impairment or absence of 1 or more of several proteins that participate in lymphocyte cytotoxicity underlies the disease. Although FHL usually presents in infancy, age of onset is variable and dependent on genetic and environmental factors. Initial treatment consists of immune suppression, whereas definitive treatment requires hematopoietic cell transplantation.


Lobectomy versus proton therapy for stage I non-small cell lung cancer.
Lobectomy is the standard treatment for patients with early-stage non-small cell lung cancer (NSCLC). In recent years, an increasing number of patients with lung cancer have been treated using proton therapy (PT). We conducted a propensity score-matched analysis to compare the treatment outcomes of these 2 modalities. We retrospectively reviewed data from 275 patients with histologically confirmed clinical stage I NSCLC who underwent lobectomy (n = 206) or PT (n = 69) at our institution from July 2013 to December 2020. The end points were overall survival (OS), cause-specific survival, recurrence-free survival (RFS), local control, regional lymph node control, and distant control. Propensity score matching was performed to reduce selection bias in the 2 groups. The matched cohort consisted of 59 patients who underwent lobectomy and 59 patients who underwent PT with a median follow-up period of 50 months. There were no significant differences in OS (P = .26), cause-specific survival (P = .33), RFS (P = .53), local control (P = .41), regional lymph node control (P = .98), and distant control (P = .31). In the lobectomy and PT groups, the 5-year OS rate was 85.8% and 79.1%, respectively, the RFS rate was 82.3% and 77.8%, and the local control rate was 92.1% and 96.6%. We found no difference in survival or disease control between lobectomy and PT in patients with histologically confirmed clinical stage I NSCLC. Despite these findings, the potential for unmeasured confounding factors remains, and randomized control trials are needed to better compare these treatment modalities.


The miR-17-92 cluster: Yin and Yang in human cancers.
MicroRNAs (miRNAs) are non-coding RNAs which modulate gene expression via multiple post-transcriptional mechanisms. They are involved in a variety of biological processes, including cell proliferation, metastasis, metabolism, tumorigenesis, and apoptosis. Dysregulation of miRNA expression has been implicated in human cancers, and they may also serve as biomarkers of disease progression and prognosis. The miR-17-92 cluster is one of the most widely studied miRNA clusters, which was initially reported as an oncogene, but was later reported to exhibit tumour suppressive effects in some human cancers. This review summarizes the recent progress and context-dependant role of this cluster in various cancers. We summarize the known mechanisms which regulate miR-17-92 expression and molecular pathways that are in turn controlled by it. We discuss examples where it acts as an oncogene or a tumour suppressor along with key targets affecting hallmarks of cancer. We discuss how cellular contexts regulate the biological effects of miR-17-92. The plausible mechanisms of its paradoxical roles are explained, and mechanisms are described that may contribute to cell fate regulation by miR-17-92. Further, we discuss recently developed strategies to target miR-17-92 cluster in human cancers. MiR-17-92 may serve as a potential biomarker for prognosis and response to therapy as well as a target for cancer prevention and therapeutics.


Regeneration of axons from the adult rat optic nerve: influence of fetal brain grafts, laminin, and artificial basement membrane.
After transection of the optic nerve of adult rats, most of the axons in the proximal stump die and the surviving ones are unable to regenerate into the distal optic nerve. Since the fetal brain has an inherent capacity to regenerate axons, we investigated whether fetal (E16) target regions of optic axons (thalamus and tectum) transplanted to the completely transected optic nerve of adult rats would promote axon regeneration. In control operated rats, axon growth beyond the site of transection was restricted to a few fibers that grew irregularly within the connective tissue scar. By contrast, in grafted animals directed outgrowth of optic axons toward the transplant started at 6 days postoperation (p.o.) and reached its maximum 15 days p.o. and later, when numerous single optic fibers and small axon fascicles had grown toward and into the graft, where they formed arborizations and terminal varicosities. Regenerating optic axons were further advanced than GFAP-positive strands of astroglia that emanated from the proximal optic nerve stump. Laminin immunoreactivity appeared at 6 days p.o. in the zone of reactive astroglia in the terminal part of the optic nerve stump. Later it showed a distribution complementary to the pattern of GFAP immunoreactivity, which it seemd to circumscribe. There was no unequivocal codistribution of laminin immunoreactivity with regenerating axons. In further experiments, target regions from different ontogenetic stages (E14 to neonate and adult) and nontarget regions (E16, cerebral cortex or spinal cord) were grafted to the optic nerve stump. With the exception of the adult grafts, all transplants had effects on axon regeneration comparable to those of E16 target regions. In order to test the effects of extracellular matrix molecules on axon regeneration, a basement membrane gel reconstituted from individual components of the Engelbreth-Holm-Sarcoma (EHS) sarcoma was implanted between proximal and distal optic nerve stumps. No axons were induced to regenerate by this matrix. Likewise, laminin adsorbed to nitrocellulose paper and implanted at the lesion site did not stimulate axon growth from the proximal optic nerve stump. These results indicate that fetal brain is able to induce and direct regrowth of axons from the optic nerve toward the graft across a substrate that is not composed of astroglia or basement membrane components like laminin. The directed growth of axons in the absence of a preformed substrate implies a chemotactic growth response along a concentration gradient mediated by neurotropic molecules released from the graft.


Utility of C-reactive protein and serum amyloid A in the diagnosis of equine protozoal myeloencephalitis.
Accurate antemortem EPM diagnosis requires evidence of intrathecal antibody production. Some advocate the use of acute phase proteins in addition to serology, which alone results in substantial false positives. The purpose of this study was to determine if serum C-reactive protein (CRP) or serum amyloid A (SAA) concentrations were elevated in cases of equine protozoal myeloencephalitis (EPM) compared to other neurological diseases. 25 clinical cases of equine neurological disease: EPM (10), cervical vertebral stenotic myelopathy (CVSM) (10), neuroborreliosis (2), equine motor neuron disease (1), degenerative myelopathy (1), and leukoencephalomalacia (1). Serum and CSF CRP and SAA were measured. Selection criteria included neurologic disease, antemortem diagnosis of EPM or CVSM, or postmortem diagnosis of EPM, CVSM, or other neurologic disease, and availability of serological results and archived samples for testing. Serum SAA and serum CRP levels were generally undetectable or low in horses with EPM (median CRP ≤0.1 mg/L, ≤0.1-14.4 mg/L; median SAA ≤0.1 mg/L, ≤0.1-6.11 mg/L) and CVSM (median CRP ≤0.1, ≤0.1-2.41 mg/L; median SAA ≤0.1mg/L, ≤0.1-13.88 mg/L). CSF CRP and SAA for horses with EPM (median CRP 3.35 mg/l, 0.19-13.43 mg/l; median SAA ≤0.1 mg/L, ≤0.1-2.4 mg/L) and CVSM (median CRP 4.015 mg/L, 0.16-9.62 mg/L; median SAA 0.62 mg/L, ≤0.1-2.91 mg/L) were also undetectable or low. Kruskal-Wallis test showed no statistically significant differences between serum CRP (P = .14), serum SAA (P = .79), spinal fluid CRP (P = .65), or spinal fluid SAA between horses with EPM and CVSM (P = .52). Neither SAA nor CRP in serum or CSF aid diagnosis of EPM.