The Auditory Afferent Pathway as a Clinical Marker of Alzheimer's Disease.

Brain stem neural tracts and nuclei may be disturbed prior to observable neuronal atrophy in AD. In this perspective, we discuss the notion of functional deficits presenting prior to structural abnormalities in Alzheimer's disease (AD). Imaging of inferior colliculi using magnetic resonance spectroscopy (MRS) shows significant decrease in the neuronal markers, N acetyl aspartate/creatine ratio and increase in the glial marker myo-Inositol, in subjects with Mini-Mental State Examination scores greater than 24 and with no signs of atrophy in their MRI of the medial temporal lobe. Abnormalities in components of the auditory event-related potentials (ERPs) are described in cognitive impairment including AD. We observed a significant decrease in amplitude and increase in latency during the first 10 ms of auditory evoked potentials measured on electroencephalography (EEG) indicating slow auditory response of the brainstem. EEG spectral power recorded at the cortex is also associated with neural activity at the level of the inferior colliculi. We postulate that a functional examination of auditory afferent pathways, using non-invasive techniques, such as MRS, brain stem auditory evoked potentials (BAEPs) and ERPs may improve diagnostic accuracy of AD. Functional changes precede structural changes and it is important to further understand the relationship between biochemical and electrophysiological measures such as MRS, BAEPs and EEG.

Mitigating the impact of COVID-19 on tuberculosis and HIV services: a cross-sectional survey of 669 health professionals in 64 low and middle-income countries

ObjectiveThe experiences of frontline healthcare professionals are essential in identifying strategies to mitigate the disruption to healthcare services caused by the COVID-19 pandemic. MethodsWe conducted a cross-sectional study of TB and HIV professionals in low and middle-income countries (LMIC). Between May 12 and August 6 2020, we collected qualitative and quantitative data using an online survey in 11 languages. We used descriptive statistics and thematic analysis to analyse responses. Findings669 respondents from 64 countries completed the survey. Over 40% stated that it was either impossible or much harder for TB and HIV patients to reach healthcare facilities since COVID-19. The most common barriers reported to affect patients were: fear of getting infected with SARS-CoV-2, transport disruptions and movement restrictions. 37% and 28% of responses about TB and HIV stated that healthcare provider access to facilities was also severely impacted. Strategies to address reduced transport needs and costs - including proactive coordination between the health and transport sector and cards that facilitate lower cost or easier travel - were presented in qualitative responses. Access to non-medical support for patients, such as food supplementation or counselling, was severely disrupted according to 36% and 31% of HIV and TB respondents respectively; qualitative data suggested that the need for such services was exacerbated. ConclusionPatients and healthcare providers across numerous LMIC faced substantial challenges in accessing healthcare facilities, and non-medical support for patients was particularly impacted. Synthesising recommendations of frontline professionals should be prioritised for informing policymakers and healthcare service delivery organisations.

Inflammatory Myofibroblastic Tumor: A Rare Presentation and an Effective Treatment with Crizotinib.

Inflammatory myofibroblastic tumor (IMT) is a rare entity of neoplastic origin. It usually occurs in children and adolescents and most commonly involves pulmonary and gastrointestinal sites. Here, the authors present two cases; one is the nine months old boy with a subcutaneous IMT in the left temporal region that was treated successfully with surgical resection. To the best of our knowledge, this is the first reported case of a subcutaneous IMT in this particular region. The second is an eight years old girl with an IMT of the right hemi-pelvis. The mass had complete surgical excision with clear margins and no residual disease. She was kept on regular follow-up with ultrasound abdomen. However, her disease relapsed with the appearance of lesions in right iliac fossa, right ovary, and liver. Biopsy of the relapsed abdominal mass confirmed ALK-positive IMT. She was treated with ALK inhibitor Crizotinib. She was monitored with regular blood complete picture, hepatic and renal function test, and ultrasound abdomen. Her lesions started regressing within one month, and she achieved complete remission after 6 months of treatment.

Isolation and antiproliferative activity of triterpenoids and fatty acids from the leaves and stem of Turraea vogelii Hook. f. ex benth.

Chloroform extract from the leaves of Turraea vogelii Hook f. ex Benth demonstrated cytotoxic activity against a chronic myelogenous leukemia cell, K-562 with IC50 of 14.27 µg/mL, while chloroform, ethyl acetate and methanol extracts from the stem of the plant inhibited K-562 cells growth with IC50 of 19.50, 24.10 and 85.40 µg/mL respectively. Bioactive chloroform extract of Turraea vogelii leaves affords two triterpenoids: oleana-12,15,20-trien-3ß-ol (1), and oleana-11,13-dien-3ß,16α,28-triol (2), with six fatty esters, ethyl hexaeicos-5-enoate (3), 3-hydroxy-1,2,3-propanetriyltris(tetadecanoate) (4), 1,2,3-propanetriyl(7Z,7'Z,7''Z)tris(-7-hexadecenoate) (5), 1,2,3-propanetriyl(5Z,5'Z,5''Z)tris(-5-hexadecenoate) (6), 1,2,3-propanetriyltris(octadecanoate) (7), and 2ß-hydroxymethyl tetraeicosanoate (8). Tetradecane (9), four fatty acids: hexadecanoic acid (10), tetradecanoic acid (11), (Z)-9-eicosenoic acid (12), and ethyl tetradec-7-enoate (13) were isolated from chloroform extract of Turraea vogelii stem. 1,2,3-propanetriyltris(heptadecanoate) (14), (Z)-9-octadecenoic acid (15) and (Z)-7-tetradecenoic acid (16) were isolated from ethyl acetate extract while (Z)-5-pentadecenoic acid (17) was obtained from methanol extract of the plant stem. Compounds 1, 2, 5, 6, 11, 12, 15, 16 and 17 exhibited pronounced antiproliferative activity against K-562 cell lines.

Peripheral Biomarker for Vascular Disorders.

Atherosclerosis is the underlying cause of most myocardial infarction (MI) and ischaemic stroke episodes. An early sign of atherosclerosis is hypertrophy of the arterial wall. It is known that increased intima media thickness (IMT) is a non-invasive marker of arterial wall alteration, which can easily be assessed in the carotid arteries by high-resolution B-mode ultrasound. Similarly, the other key element of MI and ischaemic strokes is the N-methyl-D-aspartate (NMDA) receptor which is an ionotropic glutamate receptor that mediates the vast majority of excitatory neurotransmission in the brain. NMDA activation requires the binding of both glutamate and a coagonist like D-serine to its glycine site. A special enzyme, serine racemase (SR), is required for the conversion of L-serine into D-serine, and alterations in SR activities lead to a variety of physiological and pathological conditions ranging from synaptic plasticity to ischemia, MI, and stroke. The amount of D-serine available for the activation of glutamatergic signalling is largely determined by SR and we have developed ways to estimate its levels in human blood samples and correlate it with the IMT. This research based short communication describes our pilot study, which clearly suggests that there is a direct relationship between the SR, D-serine, and IMT. In this article, we will discuss whether the activity of SR can determine the future consequences resulting from vascular pathologies such as MI and stroke.

Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases.

Cardiovascular disease (CVD) is the leading cause of death in the world and our approach to the control and management of CVD mortality is limited. Nattokinase (NK), the most active ingredient of natto, possesses a variety of favourable cardiovascular effects and the consumption of Natto has been linked to a reduction in CVD mortality. Recent research has demonstrated that NK has potent fibrinolytic activity, antihypertensive, anti-atherosclerotic, and lipid-lowering, antiplatelet, and neuroprotective effects. This review covers the major pharmacologic effects of NK with a focus on its clinical relevance to CVD. It outlines the advantages of NK and the outstanding issues pertaining to NK pharmacokinetics. Available evidence suggests that NK is a unique natural compound that possesses several key cardiovascular beneficial effects for patients with CVD and is therefore an ideal drug candidate for the prevention and treatment of CVD. Nattokinase is a promising alternative in the management of CVD.

Heart Rate Variability as a Biomarker for Predicting Stroke, Post-stroke Complications and Functionality.

BACKGROUND: Heart rate variability (HRV) is a non-invasive measure of the function of the autonomic nervous system, and its dynamic nature may provide a means through which stroke and its associated complications may be predicted, monitored, and managed. OBJECTIVE: The objective of this review is to identify and provide a critique on the most recent uses of HRV in stroke diagnosis/management and highlight areas that warrant further research. METHODS: The MEDLINE, CINAHL, and OVID MEDLINE databases were canvassed using a systematic search strategy, for articles investigating the use of HRV in stroke diagnosis and management. Initial paper selections were based on title alone, and final paper inclusion was informed by a full-text critical appraisal. RESULTS: The systematic search returned 98 records, of which 51 were unique. Following screening, 22 records were included in the final systematic review. The included papers provided some information regarding predicting incident stroke, which largely seems to be best predicted by time- and frequency-domain HRV parameters. Furthermore, post-stroke complications and functionality are similarly predicted by time- and frequency-domain parameters, as well as non-linear parameters in some instances. CONCLUSIONS: Current research provides good evidence that HRV parameters may have utility as a biomarker for stroke and for post-stroke complications and/or functionality. Future research would benefit from the integration of non-linear, and novel parameters, the hybridisation of HRV parameters, and the expansion of the utilisation of predictive regression and hazard modelling.

Isolation and antiproliferative activity of chemical constituents from Asystasia buettneri Lindau.

N-hexane and methanol extracts of Asystasia buettneri Lindau aerial parts exhibited antiproliferative activity on leukaemia blood carcinoma, K-562. Hexadecane (1), 1,3-propan-2-ol (9Z,12'Z,15″Z)-bis(doeicos-9,12,15-trienoate) (2), hydrocarbon, 2,3,3,10,23-pentamethyl tetraeicos-10,13,16-trien-1-ol (3), hexadecanoic acid (4) and taraxerol (5) were isolated from n-hexane extract; stigmasterol (6) and (Z)-9-octadecenoic acid (7) were isolated from ethyl acetate extract; while unsaturated hydrocarbons, octadecene (8), 8-methyl tetradec-6-ene (9) and 19-methyl eicos-1-ene (10), fatty acids, (Z)-5-hexadecenoic acid (11), 11,22-dimethyl ethyltrieicos-11-enoate (12) and taraxasterol (13) were isolated from methanol extract of the plant. Compounds 4, 5, 7, 11, 12 and 13 exhibited antiproliferative activity against K-562, while compounds 5, 6, 7 and 9 revealed antiproliferative activity by inhibiting hepatic liver (WRL68) cell lines.

Recent advances in molecular biomarkers for diabetes mellitus: a systematic review.

CONTEXT: Diabetes is a growing global metabolic epidemic. Current research is focussing on exploring how the biological processes and clinical outcomes of diabetes are related and developing novel biomarkers to measure these relationships, as this can subsequently improve diagnostic, therapeutic and management capacity. OBJECTIVE: The objective of this study is to identify the most recent advances in molecular biomarkers of diabetes and directions that warrant further research. METHODS: Using a systematic search strategy, the MEDLINE, CINAHL and OVID MEDLINE databases were canvassed for articles that investigated molecular biomarkers for diabetes. Initial selections were made based on article title, whilst final inclusion was informed by a critical appraisal of the full text of each article. RESULTS: The systematic search returned 246 records, of which 113 were unique. Following screening, 29 records were included in the final review. Three main research strategies (the development of novel technologies, broad biomarker panels, and targeted approaches) identified a number of potential biomarkers for diabetes including miR-126, C-reactive protein, 2-aminoadipic acid and betatrophin. CONCLUSION: The most promising research avenue identified is the detection and quantification of micro RNA. Further, the utilisation of functionalised electrodes as a means to detect biomarker compounds also warrants attention.

Impact of statins on risk and survival of ovarian cancer / 부인종양

No abstract available.

CTAB-mediated, single-step preparation of competent Escherichia coli, Bifidobacterium sp. and Kluyveromyces lactis cells.

An efficient and reproducible method for transformation depends on the competency of the organism. We have developed a simple method for the preparation of competent Escherichia coli, Kluyveromyces lactis, and Bifidobacterium sp. by using a buffer containing cetyl trimethyl ammonium bromide (CTAB) and permits efficient uptake of plasmid DNA and ligation-reaction products. Cells are harvested, washed, mixed with 1-10 µg/ml CTAB, incubated, and followed by a buffer wash. For long-term storage of competent cells, bacteria may be frozen in 10% glycerol without the addition of other components. The transformation process is very simple; plasmid DNA and the cells are mixed and incubated for 5-60 min at 4 °C; no heat pulse is required, and the duration of incubation at 4 °C is not crucial.

Peripheral markers of Alzheimer's disease: surveillance of white blood cells.

Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. This is a mechanism of innate immunity, which may cause an increase in the number of monocytes and neutrophils circulating in the blood. Literature indicated that chronic inflammation might be a factor in developing neurological problems, including Alzheimer's, Parkinson's and other similar illnesses. Our main objective is to identify peripheral markers of Alzheimer's disease and for that purpose; we are looking at the profile of white blood cells focusing on monocytes, neutrophils, lymphocytes and basophils. Twenty-seven patients of Alzheimer's disease (AD), diagnosed by magnetic resonance imaging and neuropsychological tests were observed for their blood profile. Key observations during this study were that the levels of monocytes in the blood of the diagnosed AD patients were high irrespective of their age and sex. For those patients whose monocytes were in normal range their neutrophil levels were significantly high. Whereas blood levels of lymphocytes and basophils were found to be constantly low. Escalated levels of monocytes and neutrophils are hallmarks of chronic inflammation and may be precursor to Alzheimer's disease. A low lymphocyte count specifies that the body's resistance to fight infection is substantially reduced, whereas low basophil levels indicates their over utilization due to chronic allergic inflammatory condition. Future studies involved closer look at the cytokines produced by these white blood cells especially TNF IL-1, and IL-12, which are products of monocytes. Likewise, blood glucose and creatinine levels were high whereas calcium ions were low. Our studies indicated that white blood cells along with other inflammatory byproducts may act as peripheral markers for early diagnosis of Alzheimer's disease.

Effects of season (summer & winter) on electrical characteristics of skeletal muscle membranes of the spiny-tailed lizard, Uromastix hardwickii.

This study deals with the observation of changes with temperature variations of the seasons in the muscular electrical excitability in the reptile Uromastix hardwickii. Freshly captured adult animals of both the sexes were used in all the experiments, and the gastrocnemius (skeletal) muscles were dissected out. The muscle samples were digested with digestive fluid (pepsin & Hcl), stirred, settled and supernatant was removed, till whitish fluid having clear cells obtained for patch clamp recording of ionic currents and potentials. Resting membrane potentials and action potentials of reptilian cell membranes were measured in whole cell current mode. The glass microelectrodes, with a tip diameter 2-3 microm and tip resistance 5-6 MW (when filled with intracellular solution) were used in these experiments. The present study was carried out to investigate the electrical characteristics of the skeletal muscles of this species of Uromastix, which are not studied earlier. The average mean values of resting membrane potential, action potential and its durations showed no significant changes with the change in the season, but other components of action potential including threshold potential, after-potential and its duration were found to be increased significantly (P < 0.05) in summer as compared to winter. Temperature dependency of these parameters with seasonal variation, are studied for the first time in the gastrocnemius (skeletal) muscles of Uromastix hardwickii. Hence seasonal changes in the components of action potential are invariably associated with changes in environmental temperature, and may be responsible for changes in the activities and homeostasis of these animals; and possibly indicating underlying mechanism of hibernation.

Understanding the biology of 16 kDa antigen of Mycobacterium tuberculosis: scope in diagnosis, vaccine design and therapy.

Heat shock proteins (HSPs) are conserved and ubiquitous house keeping entities that act as molecular chaperones, which protect the cell from damage during stress. One such HSP, the 16 kDa antigen, from Mycobacterium tuberculosis (Mtb) has received considerable attention due to its importance in tuberculosis latency and immunodominant property. In this article, we discuss about the potential role of 16 kDa antigen of Mtb in latency, its expression, regulation, and implication in host immune response. We also highlight the scope of employing 16 kDa in early diagnosis, development of vaccine and as a potential drug target.

Nigella sativa extract as a potent antioxidant for petrochemical-induced oxidative stress.

Various beneficial properties has been attributed to Nigella sativa, including its antioxidant potential. Previously, it was reported that supercritical fluid extraction (SFE) could be used to obtain N. sativa extract rich in antioxidants. In the present study, N. sativa extracts prepared using the previously optimized SFE as well as the traditional Soxhlet extraction approaches were analyzed for various known antioxidants. N. sativa extracts were found to prevent protein carbonyl formation as well as depletion of intracellular glutathione (GSH) in fibroblasts exposed to toluene. Furthermore, partially purified SFE and Soxhlet fractions could prevent loss of hepatic GSH in toluene-induced oxidative stressed Wistar rats as well as in L929 fibroblasts. The results showed that SFE-produced N. sativa extract is richer in antioxidants than the Soxhlet approach. It was also shown using preparative silica gel and reverse phase chromatography that different fractions of SFE-extracted or Soxhlet-extracted N. sativa had different levels of protective effects with regards to GSH depletion in vivo as well as in cell culture. Although fractions rich in thymoquinone were found to be most potent in terms of antioxidant capacity, the data indicates that the protective effects of N. sativa may not only be due to thymoquinone, but perhaps other antioxidants.

Investigating GABA and its function in platelets as compared to neurons.

We have recently suggested that platelets could be used as a model for neuronal receptors. In this paper we have investigated gamma-aminobutyric acid (GABA) metabolism and GABA receptors in platelets and in cultured neurons to see whether platelets' GABA mimics neuronal GABA receptor activities. We used the ELISA technique for detecting the GABA concentration in platelet rich plasma and cultured neurons. The functional effects of GABA and its receptor ligands on platelets were determined using an aggregometer. We found that the GABA concentration is 30% lower in platelets than in neurons and in both preparations GABA was metabolized by GABA transaminase (GABA-T). GABA potentiated calcium dependent platelet aggregation with a higher value in washed platelets suspension (WPS) then in platelet rich plasma (PRP). This effect was inhibited by benzodiazepines, calcium channel blockers and the selective phosphoinositide 3-kinase antagonist Wortmannin. GABA neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. We concluded that platelets could be further developed to be used as a peripheral model to study neuronal GABAergic function and its abnormality in diseases such as epilepsy and schizophrenia. Furthermore our results indicated that PI3-kinase is involved in calcium dependent GABA induced platelet aggregation as this synergistic effect is inhibited by Wortmannin in dose dependent manner.

Behavior in children with Down syndrome.

OBJECTIVE: To highlight the differences in behaviors in children with diagnosis of Down syndrome. METHOD: Eight children with Down syndrome who displayed autistic features were compared with eight Down syndrome children without autistic features. These children were randomly selected and were matched for age and level of retardation. Standardized Psychological tests were administered to tap the behavioral differences. Mann-Whitney U test was used for significance of difference between both the groups. RESULTS: Down syndrome children without Autism Spectrum Disorder had better communication and socialization skills than children with Down syndrome with Autism Spectrum Disorder. Down syndrome children with Autism Spectrum Disorder displayed more restricted repetitive and stereotyped patterns of behaviors, interests and activities. CONCLUSION: Our findings indicate that Autism Spectrum Disorder manifests as a distinct behavioral phenomenon in Down syndrome. Hence it is important for professionals to consider the possibility of a dual diagnosis which will entitle the child to a more specialized and effective educational and intervention services.

The metabolism of serotonin in neuronal cells in culture and platelets.

The aim of this study is to find a relationship between serotonin (5-HT) and its metabolite 5-hydroxy indol acetic acid (5-HIAA) in hippocampus, frontal neocortex and platelets. Serotonin and 5-HIAA were measured in cultured neurons and compared with those produced by human platelets. The cortical neuronal 5-HIAA/serotonin ratio was 4.7 and for hippocampal neurons it was 3.2. In human platelets, this ratio was 1.35 suggesting that the highest serotonin metabolism occurs in the frontal neocortex followed by the hippocampus and platelets. In the presence of 0.3 microM of p-chlorophenylalanine both cultured neurons and platelets exhibited an approximately 50% decrease in serotonin and 5-HIAA concentration suggesting similarities in the metabolic profile in both preparations. In addition, we found that serotonin by itself does not play any role in platelet aggregation but potentiates this phenomenon in the presence of calcium ionophore A23187. This synergistic interaction between serotonin (2-5 microM) and A23187 (0.5-2 microM) was inhibited by serotonin receptor blockers [methysergide (IC50 = 18 microM) and cyproheptadine (IC50, 20 microM)] and calcium channel blockers (verapamil and diltiazem, IC50 = 20 and 40 microM, respectively) that indicate both mechanisms are receptor mediated. Similarly, U73122, an inhibitor of phospholipase C (PLC), blocked the synergistic effect of serotonin and ionophore at an IC50 value of 9.2 microM. Wortmannin, a phosphoinositide 3-kinase (PI 3-K) inhibitor, also blocked the response (IC50 = 2.6 microM) by inhibiting respiratory burst. However, neither genistein, a tyrosine-specific protein kinase inhibitor, nor chelerythrine, a protein kinase C (PKC) inhibitor, affected aggregation. Our results are strongly suggestive of a synergistic interaction between serotonin type-2 and Ca-ionophore via a PLC/Ca signalling pathway.

Some new prospects in the understanding of the molecular basis of the pathogenesis of stroke.

Stroke is one of the leading causes of mortality and morbidity in advanced countries of the world. Despite the fact that reactive oxygen and nitrogen species (ROS and RNS) are the by-products of normal metabolic processes and mediate important physiological processes, they can inflict damage to the cell if produced in excess due to oxidative stress. In the present review, we focus on the cellular and molecular aspects of ROS and RNS generation and its role in the pathogenesis of stroke produced by hypoxia-reperfusion (H-R) phenomena that elicit oxidative stress. We outline the reasons for the vulnerability of the brain to ischaemic insult, chronic infection and inflammation as well as the natural defence mechanisms against radical mediated injury. We deal with the effect of ROS and RNS on intracellular signaling pathways together with the phenomena of apoptosis, mitochondrial injury and survival associated with these pathways. The intracellular signaling mechanisms influenced by reactive species can have significant effects on the outcome of the condition. Future studies should focus on understanding the molecular mechanisms involved in the action of anti-radicals agents, and their mode of action.

Dual inhibition of cyclooxygenase and lipoxygenase enzymes by human cerebrospinal fluid.

Thromboxane A2 (TXA2) formed in damaged brain tissue and after thromboembolism and subarachnoid haemorrhage is responsible for cerebral vasospasm. In the present study, we examined the effect of human cerebrospinal fluid (CSF) on the production of thromboxane-A2 (TXA2) and 12-hydroxy-eicosatetraenoic acid (12-HETE) by human blood platelets. CSF was drawn by lumbar puncture from normal healthy volunteers (n = 17) and samples judged to be normal after routine examination in the clinical laboratories and were used fresh. We found that CSF inhibited the production of TXA2 and 12-HETE by blood platelets incubated with C14 labelled arachidonic acid (AA) in a concentration-related manner. Further biochemical analysis using proteolytic enzymes, gel filtration and membrane partition chromatography showed that the inhibitory activity was peptidic in nature and associated with a peptide of low molecular weight (1,400 Da). This study is the first to demonstrate that human CSF contains a dual inhibitor of cyclooxygenase (COX) and lipoxygenase enzymes in CSF.