Quinoa, scientifically known as Chenopodium quinoa Willd., is well recognized for its exceptional nutritional composition and potential benefits for human health. This research aims to conduct a ...phytochemical analysis of nutraceutical properties and biologcal activities of seven different quinoa cultivars, namely, red, white, Amarilla marangani, kancolla, Giza 02, Amarilla sacaca, and black. The analysis of ground seeds revealed that Giza 02, white, and A. marangani had the most significant protein, fat, ash, and carbohydrates, respectively. Furthermore, the MeOH extracts of the various quinoa genotypes exhibited high levels of total phenolic, flavonoid, condensed tannin and reducing sugar contents in the seed extracts obtained using consecutive solvents. In addition, HPLC-DAD analysis revealed the presence of seven phenolic compounds, which may be classified into four families: phenolic acid, flavonoids, coumarins, and stilbenes. The IC50 values for the antioxidant activity ranged from 6.4 to 7.7 µg/mL. Furthermore, the variability in the antibacterial activity across different genotypes and gram-positive and gram-negative bacterial species was observed, and the efficacy of the CYHA-red extract against Micrococcus luteus was the highest. The findings of this study indicate that the incorporation of quinoa into the arid and Saharan cultivation system has the potential to enhance the nutritional and nutraceutical characteristics of the seeds.
Occipital headache, the perception of pain in the back of the head, is commonly described by patients diagnosed with migraine, tension-type headache, and occipital neuralgia. The greater and lesser ...occipital nerves play central role in the pathophysiology of occipital headache. In the clinical setup, such headaches are often treated with onabotulinumtoxinA, a neurotoxin capable of disrupting ability of nociceptors to get activated and/or release proinflammatory neuropeptides. Attempting to understand better onabotulinumtoxinA mechanism of action in reducing headache frequency, we sought to determine its effects on expression of inflammatory genes in injected occipital tissues. To achieve this goal, we injected 40 units of onabotulinumtoxinA into 4 muscle groups (occipitalis, splenius capitis, semispinalis capitis, and trapezius muscles - all located on one side of the occiput) of patients with chronic bilateral occipital headache scheduled for occipital nerve decompression surgery 1-month latter. At the time of surgery, we collected discarded muscle, fascia and periosteum tissues from respective locations on both sides of the neck and occiput and performed targeted transcriptome analyses to determine expression level of inflammatory genes in onabotulinumtoxinA-injected and onabotulinumA-uninjected tissues. We found that (a) onabotulinumtoxinA alters expression of inflammatory genes largely in periosteum, minimally in muscle and not at all in fascia; (b) expression of inflammatory genes in uninjected periosteum and muscle is significantly higher in historical onabotulinumA responders than historical non-responders; (c) in historical responders' periosteum, onabotulinumA decreases expression of nearly all significantly altered genes, gene sets that define well-recognized inflammatory pathways (e.g., pathways involved in adaptive/innate immune response, lymphocyte activation, and cytokine, chemokine, NF-kB, TNF and interferon signaling), and abundance of 12 different immune cell classes (e.g., neutrophils, macrophages, cytotoxic T-, NK-, Th1-, B- and dendritic-cells), whereas in historical non-responders it increases gene expression but to a level that is nearly identical to the level observed in the uninjected periosteum and muscle of historical responders, and surprisingly, (d) that the anti-inflammatory effects of onabotulinumA are far less apparent in muscles and absent in fascia. These findings suggest that in historical responders' periosteum - but not muscle or fascia - inflammation contributes to the pathophysiology of occipital headache, and that further consideration should be given to the possibility that onabotulinumA mechanism of action in migraine prevention could also be achieved through its ability to reduce pre-existing inflammation, likely through localized interaction that lead to reduction in abundance of immune cells in the calvarial periosteum.
Lenalidomide is a second generation immunomodulatory agent (IMiD), which currently represents the standard of care for treatment of transfusion dependent lower risk myelodysplastic syndrome (MDS) ...patients with deletion (5q). Lenalidomide has unique activity with a high transfusion independence rate observed in this subset of patients. In this article we summarize the clinical experience using lenalidomide for treatment of del (5q) MDS. We highlight the mechanism of action and the recent advances in understanding the biology of del (5q) MDS. We also explore its potential use and the efforts to further improve its activity in non-del (5q) MDS.
A combination of online and offline mass spectrometric techniques was used to characterize the chemical composition of secondary organic aerosol (SOA) generated from the photooxidation of α-pinene in ...an atmospheric simulation chamber. The filter inlet for gases and
aerosols (FIGAERO) coupled with a high-resolution time-of-flight iodide
chemical ionization mass spectrometer (I−-ToF-CIMS) was employed to
track the evolution of gaseous and particulate components. Extracts of
aerosol particles sampled onto a filter at the end of each experiment were
analysed using ultra-performance liquid chromatography ultra-high-resolution tandem mass spectrometry (LC-Orbitrap MS). Each technique was used to investigate the major SOA elemental group contributions in each system. The online CIMS particle-phase measurements show that organic species containing
exclusively carbon, hydrogen, and oxygen (CHO group) dominate the
contribution to the ion signals from the SOA products, broadly consistent
with the LC-Orbitrap MS negative mode analysis, which was better able to
identify the sulfur-containing fraction. An increased abundance of high-carbon-number (nC≥16) compounds additionally containing nitrogen (CHON group) was detected in the LC-Orbitrap MS positive ionization mode,
indicating a fraction missed by the negative-mode and CIMS measurements.
Time series of gas-phase and particle-phase oxidation products provided by
online measurements allowed investigation of the gas-phase chemistry of
those products by hierarchical clustering analysis to assess the phase
partitioning of individual molecular compositions. The particle-phase
clustering was used to inform the selection of components for targeted
structural analysis of the offline samples. Saturation concentrations
derived from nearly simultaneous gaseous and particulate measurements of the
same ions by FIGAERO-CIMS were compared with those estimated from the
molecular structure based on the LC-Orbitrap MS measurements to interpret
the component partitioning behaviour. This paper explores the insight
brought to the interpretation of SOA chemical composition by the combined
application of online FIGAERO-CIMS and offline LC-Orbitrap MS analytical
techniques.
Monosodium glutamate (MSG), a commonly used flavor enhancer, has been reported to induce hepatic and renal dysfunctions. In this study, the palliative role of protocatechuic acid (PCA) in ...MSG-administered rats was elucidated. Adult male rats were assigned to four groups, namely control, MSG (4 g/kg), PCA (100 mg/kg), and the last group was co-administered MSG and PCA at aforementioned doses for 7 days. Results showed that MSG augmented the hepatic and renal functions markers as well as glucose, triglycerides, total cholesterol, and low-density lipoprotein levels. Moreover, marked increases in malondialdehyde levels accompanied by declines in glutathione levels and notable decreases in the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were observed in MSG-treated group. The MSG-mediated oxidative stress was further confirmed by downregulation of nuclear factor erythroid 2–related factor 2 (Nrf2) gene expression levels in both tissues. In addition, MSG enhanced the hepatorenal inflammation as witnessed by increased inflammatory cytokines (interleukin-1b and tumor necrosis factor-α) and elevated nuclear factor-κB (NF-κB) levels. Further, significant increases in Bcl-2-associated X protein (Bax) levels together with decreases in B-cell lymphoma 2 (Bcl-2) levels were observed in MSG administration. Histopathological screening supported the biochemical and molecular findings. In contrast, co-treatment of rats with PCA resulted in remarkable enhancement of the antioxidant cellular capacity, suppression of inflammatory mediators, and apoptosis. These effects are possibly endorsed for activation of Nrf-2 and suppression of NF-kB signaling pathways. Collectively, addition of PCA counteracted MSG-induced hepatorenal injuries through modulation of oxidative, inflammatory and apoptotic alterations.
Object
The relentless natural progression of petroclival meningiomas mandates their treatment. The management of these tumors, however, is challenging. Among the issues debated are goals of ...treatment, outcomes, and quality of life, appropriate extent of surgical removal, the role of skull base approaches, and the efficacy of combined decompressive surgery and radiosurgery. The authors report on the outcome in a series of patients treated with the goal of total removal.
Methods
The authors conducted a retrospective analysis of 64 cases of petroclival meningiomas operated on by the senior author (O.A.) from 1988 to 2012, strictly defined as those originating medial to the fifth cranial nerve on the upper two-thirds of the clivus. The patients' average age was 49 years; the average tumor size (maximum diameter) was 35.48 ± 10.09 mm (with 59 tumors > 20 mm), and cavernous sinus extension was present in 39 patients. The mean duration of follow-up was 71.57 months (range 4–276 months).
Results
In 42 patients, the operative reports allowed the grading of resection. Grade I resection (tumor, dura, and bone) was achieved in 17 patients (40.4%); there was no recurrence in this group (p = 0.0045). Grade II (tumor, dura) was achieved in 15 patients (36%). There was a statistically significant difference in the rate of recurrence with respect to resection grade (Grades I and II vs other grades, p = 0.0052). In all patients, tumor removal was classified based on postoperative contrast-enhanced MRI, and gross-total resection (GTR) was considered to be achieved if there was no enhancement present; on this basis, GTR was achieved in 41 (64%) of 64 patients, with a significantly lower recurrence rate in these patients than in the group with residual enhancement (p = 0.00348). One patient died from pulmonary embolism after discharge.
The mean Karnofsky Performance Status (KPS) score was 85.31 preoperatively (median 90) and improved on follow-up to 88, with 30 patients (47%) having an improved KPS score on follow-up. Three patients suffered a permanent deficit that significantly affected their KPS. Cerebrospinal fluid leak occurred in 8 patients (12.5%), with 2 of them requiring exploration. Eighty-nine percent of the patients had cranial nerve deficits on presentation; of the 54 patients with more than 2 months of follow-up, 21 (32.8%) had persisting cranial nerve deficits. The overall odds of permanent cranial nerve deficit of treated petroclival meningioma was 6.2%. There was no difference with respect to immediate postoperative cranial nerve deficit in patients who had GTR compared with those who had subtotal resection.
Conclusions
Total removal (Grade I or II resection) of petroclival meningiomas is achievable in 76.4% of cases and is facilitated by the use of skull base approaches, with good outcome and functional status. In cases in which circumstances prevent total removal, residual tumors can be followed until progression is evident, at which point further intervention can be planned.
Aims
Recent studies have demonstrated that stimulating pyruvate dehydrogenase (PDH, gene Pdha1), the rate‐limiting enzyme of glucose oxidation, can reverse obesity‐induced non‐alcoholic fatty liver ...disease (NAFLD), which can be achieved via treatment with the antianginal ranolazine. Accordingly, our aim was to determine whether ranolazine's ability to mitigate obesity‐induced NAFLD and hyperglycaemia requires increases in hepatic PDH activity.
Methods
We generated liver‐specific PDH‐deficient (Pdha1Liver−/−) mice, which were provided a high‐fat diet for 12 weeks to induce obesity. Pdha1Liver−/− mice and their albumin‐Cre (AlbCre) littermates were randomized to treatment with either vehicle control or ranolazine (50 mg/kg) once daily via oral gavage during the final 5 weeks, following which we assessed glucose and pyruvate tolerance.
Results
Pdha1Liver−/− mice exhibited no overt phenotypic differences (e.g. adiposity, glucose tolerance) when compared to their AlbCre littermates. Of interest, ranolazine treatment improved glucose tolerance and mildly reduced hepatic triacylglycerol content in obese AlbCre mice but not in obese Pdha1Liver−/− mice. The latter was independent of changes in hepatic mRNA expression of genes involved in regulating lipogenesis.
Conclusions
Liver‐specific PDH deficiency is insufficient to promote an NAFLD phenotype. Nonetheless, hepatic PDH activity partially contributes to how the antianginal ranolazine improves glucose tolerance and alleviates hepatic steatosis in obesity.
Facial grimacing is used to quantify spontaneous pain in mice and other mammals, but scoring relies on humans with different levels of proficiency. Here, we developed a cloud-based software platform ...called PainFace (http://painface.net) that uses machine learning to detect 4 facial action units of the mouse grimace scale (orbitals, nose, ears, whiskers) and score facial grimaces of black-coated C57BL/6 male and female mice on a 0 to 8 scale. Platform accuracy was validated in 2 different laboratories, with 3 conditions that evoke grimacing-laparotomy surgery, bilateral hindpaw injection of carrageenan, and intraplantar injection of formalin. PainFace can generate up to 1 grimace score per second from a standard 30 frames/s video, making it possible to quantify facial grimacing over time, and operates at a speed that scales with computing power. By analyzing the frequency distribution of grimace scores, we found that mice spent 7x more time in a "high grimace" state following laparotomy surgery relative to sham surgery controls. Our study shows that PainFace reproducibly quantifies facial grimaces indicative of nonevoked spontaneous pain and enables laboratories to standardize and scale-up facial grimace analyses.
Background/Aim: To investigate in variants of primary progressive aphasia (PPA) the association between current clinical and neuroimaging criteria and biochemical/genetic markers at the individual ...level. Methods: Thirty-two PPA patients were classified as non-fluent/agrammatic (nfvPPA), semantic (svPPA), or logopenic variant (lvPPA) or as unclassifiable (uPPA). In all patients, we evaluated the neuroimaging criteria (magnetic resonance imaging and/or single photon emission computed tomography/positron emission tomography) of each variant and studied serum progranulin levels, APOE genotype and Alzheimer’s disease (AD)-cerebrospinal fluid (CSF) biomarkers. Cases with a first-degree family history of early-onset dementia were genetically tested. Results: Ten of 15 (66%) nfvPPA, 5/5 (100%) svPPA and 7/7 (100%) lvPPA patients showed at least one positive neuroimaging-supported diagnostic criterion. All lvPPA and 3/5 (60%) uPPA patients presented AD-CSF biomarkers, which were absent in nfvPPA and svPPA cases. Four (27%) nfvPPA patients had dementia-causing mutations: 2 carried a GRN mutation and 2 the C9ORF72 hexanucleotide expansion. Conclusions: There was an excellent association between clinical criteria and neuroimaging-supported biomarkers in svPPA and lvPPA, as well as with AD-CSF biochemical markers in the lvPPA. Neuroimaging, biochemical and genetic findings in nfvPPA were heterogeneous. Incorporating biochemical/genetic markers into the PPA clinical diagnosis would allow clinicians to improve their predictions of PPA neuropathology, especially in nfvPPA and uPPA cases.
Separate tumor nodules with the same histologic appearance occur in the lungs in a small proportion of patients with primary lung cancer. This article addresses how such tumors can be classified to ...inform the eighth edition of the anatomic classification of lung cancer. Separate tumor nodules should be distinguished from second primary lung cancer, multifocal ground glass/lepidic tumors, and pneumonic-type lung cancer, which are addressed in separate analyses.
Survival of patients with separate tumor nodules in the International Association for the Study of Lung Cancer database were analyzed. This was compared with a systematic literature review.
Survival of clinically staged patients decreased according to the location of the separate tumor nodule relative to the index tumor (same lobe > same side > other side) in N0 and N-any cohorts (all M0 except possible other-side nodules). However, there was also a decrease in the proportion of patients resected; among only surgically resected or among nonresected patients no survival differences were noted. There were no survival differences between patients with same-lobe nodules and those with other T3 tumors, between patients with same-side nodules and those with T4 tumors, and patients with other-side nodules and those with other M1a tumors. The data correlated with those identified in a literature review.
Tumors with same-lobe separate tumor nodules (with the same histologic appearance) are recommended to be classified as T3, same-side nodules as T4, and other-side nodules as M1a. Thus, there is no recommended change between the seventh and eighth edition of the TNM classification of lung cancer.
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