Editorial: biomarkers in neurology

Neurological disorders constitute a major health and socioeconomic problem. They represent the second cause of death and the leading cause of disability throughout the world. Despite the implementation of strategies and intervention programs to reduce the burden, over the past 25 years, the incidence, prevalence, mortality, and disability rates of neurological disorders are rising globally, mainly due to population aging and growth (1). This has placed heavy pressure on health-care systems pointing out the urgent need to identify new strategies to improve patient outcomes and reduce health costs by enabling more effective drug development and establishing a more personalized medicine approach. Rapid scientific and technical advances have enabled reliable and affordable measurement of novel biomarkers—biological indicators that objectively measure and evaluate physiological or pathophysiological processes or pharmacological responses to a therapeutic intervention (2)—which have been suggested to help assessment and management of patients with neurological disorders beyond current practice standards (3–5). Evidence suggests a potential variety of clinical applications, including enhancing diagnostic and prognostic accuracy, improving the existing decision criteria for early diagnosis and risk stratification, as well as assisting in disease monitoring, and acting as surrogate endpoints in experimental studies and clinical trials (6–10). In addition, biomarkers may reliably capture the different aspects of disease heterogeneity and pathogenesis, helping characterize patients, and thereby informing targeted tailored treatments and predicting response outcomes to interventions (11–18). However, despite large numbers of candidate biomarkers have been proposed and extensively evaluated, very few are currently integrated into routine clinical practice and the quest for novel brain injury markers in still ongoing (19)

P-Wave Dispersion and Its Relationship with the Severity of the Coronary Artery Disease in Patients with Stable Angina

Background: In Electrocardiography (ECG), the term "P-wave dispersion" (PWD) refers to variation between maximum and minimum P-waves recorded from various Electrocardiography leads. P-wave analysis in ECG may become more widely used marker in many clinical contexts as a result of improved methods for capturing and analyzing this ECG. The link between (PD) and severity of coronary artery disease (CAD) was established among personnel who had stable form of CAD. Objective: We wanted to determine if there was an association between P wave dispersion and CAD severity in patients who had stable CAD.Patients and methods: At Al-Hussein University Hospital Cath Lab, 51 consecutive patients were referred for diagnostic coronary angiography in a cross-sectional trial. They were classified into group A (control group, n=8), who were found to have normal coronary angiography and group B (n = 43), who were found to have coronary artery disease. Results: P wave dispersion was significantly different across cases, with 95.3 percent of patients having abnormal P wave dispersion compared to 100 percent of control cases. P wave dispersion and Gensini score were statistically significantly different between cases and controls where cases had significantly higher scores than controls. Dispersion of P waves was statistically linked to number of vessels affected as well as Gensini scores. The P wave dispersion and the Gensini score showed a strong positive association.Conclusion: Stable coronary artery disease (CAD) patients had aberrant PWD, according to the findings of this study, in patients with stable coronary artery disease, severity of the CAD is correlated with P wave dispersion

Temperature, water activity and gas composition effects on the growth and aflatoxin production by Aspergillus flavus on paddy

The main aim of this study was to evaluate the combined effects of temperature with water activity (aw) and CO2 with aw on the growth and aflatoxin production by Aspergillus flavus Link on paddy. The effects of temperature (20–30 °C) and aw (0.92–0.98) on the relationship between colony diameter and aflatoxin production, and the influence of aw (0.92–0.98) and CO2 (20–80%) on the growth and toxin production were studied using full factorial design. Colony diameters were regularly measured and aflatoxins were periodically analyzed using HPLC with fluorescence detector. The growth and aflatoxin formation increased with aw at the temperatures studied, and toxin production was positively correlated with the incubation time and colony diameter. Except at 0.92 aw, as much as 80% CO2 failed to inhibit the growth of fungi completely. However, at all aw levels studied the growth parameters as estimated by Baranyi function and aflatoxin were affected by the increment in CO2 where growth rates and aflatoxin were negatively correlated with CO2 while the lag phase durations were positively correlated with CO2. Under 0.98 aw, the atmosphere enriched with 20% and 80% CO2 lead to at least 59% and 88% reduction in growth and 47% and 97% in the toxin production, respectively. At 0.95 aw, the lag phases of both isolates in average increased by a factor of 1.7–12 when the CO2 levels in the headspace were between 20 and 80% compared to the control. The growth rate and lag phase durations under the modified atmospheres were successfully described using a polynomial equation (R2 > 0.97). The results of the study could form a basis of indicative guidelines on the possible control of A. flavus and aflatoxin in paddy during temporary storage prior to drying

The O-antigen flippase Wzk can substitute for MurJ in peptidoglycan synthesis in Helicobacter pylori and Escherichia coli

The peptidoglycan (PG) cell wall is an essential component of the cell envelope of most bacteria. Biogenesis of PG involves a lipid-linked disaccharide-pentapeptide intermediate called lipid II, which must be translocated across the cytoplasmic membrane after it is synthesized in the inner leaflet of this bilayer. Accordingly, it has been demonstrated that MurJ, the proposed lipid II flippase in Escherichia coli, is required for PG biogenesis, and thereby viability. In contrast, MurJ is not essential in Bacillus subtilis because this bacterium produces AmJ, an unrelated protein that is functionally redundant with MurJ. In this study, we investigated why MurJ is not essential in the prominent gastric pathogen, Helicobacter pylori. We found that in this bacterium, Wzk, the ABC (ATP-binding cassette) transporter that flips the lipid-linked O- or Lewis- antigen precursors across the inner membrane, is redundant with MurJ for cell viability. Heterologous expression of wzk in E. coli also suppresses the lethality caused by the loss of murJ. Furthermore, we show that this cross-species complementation is abolished when Wzk is inactivated by mutations that target a domain predicted to be required for ATPase activity. Our results suggest that Wzk can flip lipid II, implying that Wzk is the flippase with the most relaxed specificity for lipid-linked saccharides ever identified

Antioxidant lipoxygenase inhibitors from the leaf extracts of Simmondsia chinensis

AbstractObjectiveTo isolate and identify chemical constituents with antioxidant and lipoxygenase inhibitory effects of the ethanolic extract of Simmondsia chinensis (Jojoba) leaves.MethodsThe alcoholic extract was subjected to successive solvent fractionation. The antioxidant active fractions (chloroform, ethyl acetate and aqueous fractions) were subjected to a combination of different chromatographic techniques guided by the antioxidant assay with DPPH. The structures of the isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. The antioxidant activity was assessed quantitively using DPPH and β-carotene methods. The inhibitory potential against enzyme lipoxygenase was assessed on soybean lipoxygenase enzyme.ResultsTen flavonoids and four lignans were isolated. Flavonoid aglycones showed stronger antioxidant and lipoxygenase inhibitory effects than their glycosides. Lignoid glycosides showed moderate to weak antioxidant and lipoxygenase inhibitory effects.ConclusionsA total of 14 compounds were isolated and identified from Simmondsia chinensis; 12 of them were isolated for the first time. This is the first report that highlights deeply on the phenolic content of jojoba and their potential biological activities and shows the importance of this plant as a good source of phenolics in particular the flavonoid content

Depression following major life transitions in women: a review and theory

Depression can occur due to common major life transitions, such as giving birth, menopause, retirement, empty-nest transition, and midlife crisis. Although some of these transitions are perceived as positive (e.g., giving birth), they may still lead to depression. We conducted a systematic literature review of the factors underlying the occurrence of depression following major life transition in some individuals. This review shows that major common life transitions can cause depression if they are sudden, major, and lead to loss (or change) of life roles (e.g., no longer doing motherly or fatherly chores after children leave family home). Accordingly, we provide a theoretical framework that explains depression caused by transitions in women. One of the most potential therapeutic methods of ameliorating depression associated with life transitions is either helping individuals accept their new roles (e.g., accepting new role as a mother to ameliorate postpartum depression symptoms) or providing them with novel life roles (e.g., volunteering after retirement or children leave family home) may help them overcome their illness

MicroRNA-208a: a Good Diagnostic Marker and a Predictor of no-Reflow in STEMI Patients Undergoing Primary Percutaneuos Coronary Intervention

MicroRNA-208a is a cardiac specific oligo-nucleotide. We aimed at investigating the ability of microRNA-208a to diagnose myocardial infarction and predict the outcome of primary percutaneuos coronary angiography (PCI). Patients (n = 75) presented by chest pain were recruited into two groups. Group 1 (n = 40) had ST elevation myocardial infarction (STEMI) and underwent primary PCI: 21 patients had sufficient reperfusion and 19 had no-reflow. Group 2 (n = 35) had negative cardiac troponins (cTns). Plasma microRNA-208a expression was assessed using quantitative polymerase chain reaction and patients were followed for occurrence of in-hospital major adverse cardiac events (MACE). MicroRNA-208a could diagnose of MI (AUC of 0.926). After primary PCI, it was superior to cTnT in prediction of no-reflow (AUC difference of 0.231, P = 0.0233) and MACE (AUC difference of 0.367, P = 0.0053). Accordingly, circulating levels of miR-208a can be used as a diagnostic marker of MI and a predictor of no-reflow and in-hospital MACE

siRNA blocking of mammalian target of rapamycin (mTOR) attenuates pathology in annonacin-induced tauopathy in mice

Tauopathy is a pathological hallmark of many neurodegenerative diseases. It is characterized by abnormal aggregates of pathological phosphotau and somatodendritic redistribution. One suggested strategy for treating tauopathy is to stimulate autophagy, hence, getting rid of these pathological protein aggregates. One key controller of autophagy is mTOR. Since stimulation of mTOR leads to inhibition of autophagy, inhibitors of mTOR will cause stimulation of autophagy process. In this report, tauopathy was induced in mice using annonacin. Blocking of mTOR was achieved through stereotaxic injection of siRNA against mTOR. The behavioral and immunohistochemical evaluation revealed the development of tauopathy model as proven by deterioration of behavioral performance in open field test and significant tau aggregates in annonacin-treated mice. Blocking of mTOR revealed significant clearance of tau aggregates in the injected side; however, tau expression was not affected by mTOR blockage

FOXRED1 silencing in mice: a possible animal model for leigh syndrome.

Leigh syndrome (LS) is one of the most puzzling mitochondrial disorders, which is also known as subacute necrotizing encephalopathy. It has an incidence of 1 in 77,000 live births worldwide with poor prognosis. Currently, there is a poor understanding of the underlying pathophysiological mechanisms of the disease without any available effective treatment. Hence, the inevitability for developing suitable animal and cellular models needed for the development of successful new therapeutic modalities. In this short report, we blocked FOXRED1 gene with small interfering RNA (siRNA) using C57bl/6 mice. Results showed neurobehavioral changes in the injected mice along with parallel degeneration in corpus striatum and sparing of the substantia nigra similar to what happen in Leigh syndrome cases. FOXRED1 blockage could serve as a new animal model for Leigh syndrome due to defective CI, which echoes damage to corpus striatum and affection of the central dopaminergic system in this disease. Further preclinical studies are required to validate this model

Effect of intranasal stem cell administration on the nigrostriatal system in a mouse model of Parkinson's disease

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. It affects the locomotor system, leading to a final severe disability through degeneration of dopaminergic neurons. Despite several therapeutic approaches used, no treatment has been proven to be effective; however, cell therapy may be a promising therapeutic method. In addition, the use of the intranasal (IN) route has been advocated for delivering various therapies to the brain. In the present study, the IN route was used for administration of mesenchymal stem cells (MSCs) in a mouse model of PD, with the aim to evaluate IN delivery as an alternative route for cell based therapy administration in PD. The PD model was developed in C57BL/6 mice using intraperitoneal rotenone administration for 60 consecutive days. MSCs were isolated from the mononuclear cell fraction of pooled bone marrow from C57BL/6 mice and incubated with micrometer‑sized iron oxide (MPIO) particles. For IN administration, we used a 20 µl of 5x105 cell suspension. Neurobehavioral assessment of the mice was performed, and after sacrifice, brain sections were stained with Prussian blue to detect the MPIO‑labeled MSCs. In addition, immunohistochemical evaluation was conducted to detect tyrosine hydroxylase (TH) antibodies in the corpus striatum and dopaminergic neurons in the substantia nigra pars compacta (SNpc). The neurobehavioral assessment revealed progressive deterioration in the locomotor functions of the rotenone group, which was improved following MSC administration. Histopathological evaluation of brain sections in the rotenone+MSC group revealed successful delivery of MSCs, evidenced by positive Prussian blue staining. Furthermore, rotenone treatment led to significant decrease in dopaminergic neuron number in SNpc, as well as similar decrease in the corpus striatum fiber density. By contrast, in animals receiving IN administration of MSCs, the degeneration caused by rotenone treatment was significantly counteracted. In conclusion, the present study validated that IN delivery of MSCs may be a potential safe, easy and cheap alternative route for stem cell treatment in neurodegenerative disorder