Seizure-related complication rate in a residential population with epilepsy and intellectual disability (ECOMRAID-trial).

INTRODUCTION: The aim of the ECOMRAID trial (Epileptic seizure related Complication RAte in residential population of persons with epilepsy and Intellectual Disability) was to study seizure-related complications (status epilepticus, respiratory complications, or other severe complications) in people with epilepsy and intellectual disability living in a residential setting. The results of the present study are a prerequisite for performing a prospective study into the effectiveness of nocturnal surveillance patients with high risk for Sudden unexpected death in epilepsy (SUDEP). MATERIAL AND METHODS: A retrospective study was conducted in three general residential care institutions and one residential specialized epilepsy clinic. In this 5-year cohort, we collected the following data: age (at inclusion and in case of death), sex, type of residential care, different types of complications, rescue/emergency medication administration, transfers to another department (internal midcare / monitoring unit or general hospital) and a self-designed SUDEP risk score. Our primary research questions were to assess the number of patients who experienced seizure-related complications and their individual complication rates. The secondary research questions were to document the relationship of these complications with the SUDEP risk score, with the type of residential living, and with the frequency of interventions by caregivers. RESULTS: We included 370 patients (1790 patient-years) and in 135 of them, we found 717 seizure-related complications. The following complication rates were found: all complications: at 36%, status epilepticus: at 13%, respiratory complications: at 5%, and other complications at 26%. In residential care institutions, we found fewer patients with complications compared to the specialized epilepsy clinic (all complications 24% vs 42%, OR 0.44, p < 0.01; status epilepticus 5% vs 17%, OR 0.27, p < 0.01; other: complications 19% vs 30%, OR 0.56, p < 0.05). In residential care institutions, we found more "other complications" than in the specialized epilepsy clinic (89% vs 71%, OR 3.13, p < 0.0001). The annual frequency of all complications together was higher in residential care institutions (range 0 to 21 vs 0 to 10, p < 0.05). Rescue medication was given to 75% of the patients, but more often in the specialized epilepsy clinic (median 2.6 vs 0.5 times/patient/year, p < 0.001). In the specialized epilepsy clinic, more patients were transferred to a midcare / monitoring unit or general hospital (56% vs 9%, OR 13.44, p < 0.0001) with higher yearly frequencies (median 0.2 vs 0.0, p < 0.001). There were no reported cases of SUDEP. The median SUDEP risk score was higher in the specialized epilepsy clinic (5 vs 4, p < 0.05) and was weakly correlated with the status epilepticus (ρ = 0.20, p < 0.001) and (total) complication rate (ρ = 0.18, p < 0.001). CONCLUSION: We found seizure-related complications in more than one-third of the patients with epilepsy and intellectual disability living in a residential setting over a period of 5 years. The data also quantify seizure-related complications in patients with epilepsy and intellectual disability.

Dark Sweet Cherry (Prunus avium) Anthocyanins Suppressed ERK1/2-Akt/mTOR Cell Signaling and Oxidative Stress: Implications for TNBC Growth and Invasion.

This study aimed to assess dark sweet cherry (DSC) total polyphenols (WE) and anthocyanins (ACN) against metastatic breast cancer (BC). The WE and ACN anticancer activity and underlying mechanisms were assessed in vitro using 4T1 BC cells. A pilot study using a BALB/C mouse syngeneic model bearing 4T1 tumors assessed the anti-metastatic potential of ACN in vivo. ACN inhibited cell viability with higher potency than WE and reduced reactive oxygen species (ROS) (IC50 = 58.6 µg cyanidin 3-glucoside equivalent (C3G)/mL or 122 µM). ACN induced p38 stress-related intrinsic apoptosis, leading to caspase-3 cleavage and total PARP decrease. ACN suppressed ERK1/2 and Akt/mTOR signaling pathways, which are abnormally activated in BC and promote motility and invasion. This was consistent with suppression of VCAM-1 mRNA, Scr phosphorylation and 88.6% reduction of cells migrating to wounded area. The pilot in vivo results supported the ACN-mediated suppression of angiogenesis in tumors and lungs. ACN also lowered Cenpf mRNA in lungs, associated with lung metastasis lesions and poor survival. Results demonstrated the dual Akt-ERK inhibitory role of ACN and suppression of their downstream pro-invasive targets. These results encourage a larger scale in vivo study to confirm that ACN may help to fight BC invasion and metastasis.

Dietary intake and risk assessment of elements for 1- and 2-year-old children in the Netherlands.

In 2017, a total diet study (TDS) was conducted in the Netherlands to determine the intake of elements by 1- and 2-year-old children. Concentrations of 47 elements were analysed and long-term dietary intake was calculated for 24 elements. The 95th percentile (P95) intake estimates were compared with a tolerable daily or weekly intake (TDI or TWI) or tolerable upper intake level (UL), or a margin of exposure (MOE) was calculated. The P95 intake of cadmium and zinc exceeded the TWI or UL, respectively, and the P95 intake of inorganic arsenic and lead resulted in low MOEs. Food subgroups contributing most to the intake were "potatoes" for cadmium, "milk and milk-based beverages" for zinc, "concentrated fruit juices" and "rice" for inorganic arsenic, and "candies" for lead. For inorganic mercury, it could not be established if the intake was (too) high. P95 intake estimates of the other elements for which a risk characterisation could be performed were below the health-based guidance values. It was noted that the P50 intake estimate of manganese was a factor of 3 higher than the adequate intake level. Due to the absence of a UL, it is not clear if this intake is of concern.

Severe autonomic nervous system imbalance in Lennox-Gastaut syndrome patients demonstrated by heart rate variability recordings.

OBJECTIVE: Patients diagnosed with Lennox Gastaut syndrome (LGS), an epileptic encephalopathy characterized by usually drug resistant generalized and focal seizures, are often considered as candidates for vagus nerve stimulation (VNS). Recent research shows that heart rate variability (HRV) differs in epilepsy patients and is related to VNS treatment response. This study investigated pre-ictal HRV in generalized onset seizures of patients with LGS in correlation with their VNS response. METHODS: In drug resistant epilepsy (DRE) patients diagnosed with LGS video-electroencephalography recording was performed during their pre-surgical evaluation. Six HRV parameters (time and-, frequency domain, non-linear parameters) were evaluated for every seizure in epochs of 10 min at baseline (60 to 50 min before seizure onset) and pre-ictally (10 min prior to seizure onset). The results were correlated to VNS response after one year of VNS therapy. RESULTS: Seven patients and 31 seizures were included, two patients were classified as VNS responders (≥ 50 % seizure reduction). No difference in pre-ictal HRV parameters between VNS responders and VNS non-responders could be found, but high frequency (HF) power, reflecting the parasympathetic tone increased significantly in the pre-ictal epoch in both VNS responders and VNS non-responders (p = 0.017, p = 0.004). SIGNIFICANCE: In this pilot data pre-ictal HRV did not differ in VNS responders compared to VNS non-responders, but showed a significant increase in HF power - a parasympathetic overdrive - in both VNS responders and VNS non-responders. This sudden autonomic imbalance might have an influence on the cardiovascular system in the ictal period. Generalized tonic-clonic seizures are regarded as the main risk factor for SUDEP and severe seizure-induced autonomic imbalance may play a role in the pathophysiological pathway.

Dark Sweet Cherry (Prunus avium) Phenolics Enriched in Anthocyanins Induced Apoptosis in MDA-MB-453 Breast Cancer Cells through MAPK-Dependent Signaling and Reduced Invasion via Akt and PLCγ-1 Downregulation.

Dark sweet cherries (DSCs) are rich source of phenolics known to exert anticancer and anti-invasive activities. This study elucidated the molecular mechanisms underlying the activity of DSC phenolics against MDA-MB-453 breast cancer cells In Vitro. Cells were treated with DSC phenolics in whole extract (WE), and fractions enriched in anthocyanins (ACN) and proanthocyanidins (PCN) at concentrations that inhibited cell growth by 50%. Results showed that DSC phenolics suppressed Akt and PLCγ-1 activation, and inhibited cell motility and invasion, but only ACN reached significance. The extrinsic and intrinsic apoptotic pathways were also activated by DSC phenolics via caspase-8 cleavage and increased Bax/Bcl-2 ratio, with ACN exhibiting significant activation and stronger PARP-1 cleavage. Furthermore, sustained activation of mitogen-activated protein kinases (MAPKs) ERK1/2 and p38 was observed wherein ERK1/2 (U0126) and p38 (SB203580) inhibitors confirmed crosstalk ERK1/2-Akt and MAPK intrinsic mitochondrial pathways. In conclusion, DSC phenolics inhibited MDA-MB-453 breast cancer cells by targeting cell signaling pathways that induce apoptosis and suppress cell invasion, with ACN showing enhanced chemopreventive activities.

Performance of concanavalin A-immobilized on polyacrylate beads for the detection of human norovirus and hepatitis A virus in fecal specimens.

Quantitative reverse transcription PCR (qRT-PCR) is a sensitive method for the detection of foodborne viruses in fecal samples. However, the performance of qRT-PCR depends on the efficiency of virus concentration methods. In this study, the effect of Concanavalin A (Con A)-immobilized on polyacrylate beads (Con A-PAB) on the qRT-PCR performance, in terms of sensitivity and specificity to detect foodborne viruses in human fecal specimens was compared with commercial viral RNA extraction kit (VRNA). The detection of foodborne viruses by qRT-PCR was validated by viral genome sequencing. Both Con A-PAB and VRNA methods were equally sensitive and specific for detecting hepatitis A virus in fecal specimens. Even though both methods showed high specificity (100% vs. 100%) for detecting human norovirus (HuNoV), Con A-PAB method exhibited higher sensitivity (100% vs. 42.9%) and accuracy (100% vs. 73.3%) compared to VRNA method. In conclusion, the application of Con A-PAB would improve the performance of qRT-PCR for the detection of HuNoV in fecal samples.

Antitumor potential of dark sweet cherry sweet (Prunus avium) phenolics in suppressing xenograft tumor growth of MDA-MB-453 breast cancer cells.

This study investigated in vivo the antitumor activity of dark sweet cherry (DSC) whole extracted phenolics (WE) and fractions enriched in anthocyanins (ACN) or proanthocyanidins (PCA) in athymic mice xenografted with MDA-MB-453 breast cancer cells. Mice were gavaged with WE, ACN or PCA extracts (150 mg/kg body weight/day) for 36 days. Results showed that tumor growth was suppressed at similar levels by WE, ACN and PCA compared to control group (C) without signs of toxicity or significant changes in mRNA oncogenic biomarkers in tumors or mRNA invasive biomarker in distant organs. Tumor protein analyses showed that WE, ACN and PCA induced at similar levels the stress-regulated ERK1/2 phosphorylation, known to be linked to apoptosis induction. However, ACN showed enhanced antitumor activity through down-regulation of total oncogenic and stress-related Akt, STAT3, p38, JNK and NF-kB proteins. In addition, immunohistochemistry analysis of Ki-67 revealed inhibition of tumor cell proliferation with potency WE ≥ ACN ≥ PCA. Differential quantitative proteomic high-resolution nano-HPLC tandem mass spectrometry analysis of tumors from ACN and C groups revealed the identity of 66 proteins associated with poor breast cancer prognosis that were expressed only in C group (61 proteins) or differentially up-regulated (P<.05) in C group (5 proteins). These findings revealed ACN-targeted proteins associated to tumor growth and invasion and the potential of DSC ACN for breast cancer treatment. Results lead to a follow-up study with highly immunodeficient mice/invasive cell line subtype and advanced tumor development to validate the anti-invasive activity of DSC anthocyanins.

Dysphagia, dysarthria and aphasia following a first acute ischaemic stroke: incidence and associated factors.

BACKGROUND AND PURPOSE: Dysphagia, dysarthria and aphasia are common symptoms following acute stroke; however, limited data are available from recent prospective clinical trials. The aim of this study was to determine the incidence and associated factors of dysphagia, dysarthria and aphasia following a first acute ischaemic stroke in patients admitted to a comprehensive stroke center. METHODS: All first ischaemic stroke patients admitted to the Stroke Unit of Ghent University Hospital within 48 h after symptom onset were enrolled in this prospective study between March 2018 and October 2019. Dysphagia and communication screenings were performed within 3 days after admission. When dysphagia, dysarthria and/or aphasia were assumed, standardized assessments were performed. Incidence rates were calculated as point estimates (%) with 95% confidence intervals (CI). Associated factors were calculated via multivariate binary logistic regression analyses. RESULTS: Dysphagia, dysarthria and aphasia were present in 23% (95% CI, 17-31), 44% (95% CI, 37-52) and 23% (95% CI, 17-30), respectively of 151 first ischaemic stroke patients [67 female, mean age 67 (SD 14) years]. Separate multivariate binary logistic regression analyses showed that dysphagia, dysarthria and aphasia were significantly associated with age-adjusted stroke severity at baseline [odds ratio (OR), 1.16; 95% CI, 1.09-1.23; OR, 1.13; 95% CI, 1.07-1.20 and OR, 1.11; 95% CI, 1.05-1.17 respectively]. Corrected for stroke severity, the risk for aphasia increased by 4% per year of age (OR, 1.04; 95% CI, 1.00-1.07). Adjusted for age and stroke severity, aphasia was significantly associated with large artery atherosclerosis as stroke etiology (OR, 3.91; 95% CI, 1.18-12.98). CONCLUSIONS: This trial showed a high incidence of dysphagia, dysarthria and aphasia following acute ischaemic stroke. Stroke severity was an associated factor for all three symptoms.

Neurological manifestations and neuro-invasive mechanisms of the severe acute respiratory syndrome coronavirus type 2.

BACKGROUND AND PURPOSE: Infections with coronaviruses are not always confined to the respiratory tract and various neurological manifestations have been reported. The aim of this study was to perform a review to describe neurological manifestations in patients with COVID-19 and possible neuro-invasive mechanisms of Sars-CoV-2. METHODS: PubMed, Web of Science and COVID-dedicated databases were searched for the combination of COVID-19 terminology and neurology terminology up to 10 May 2020. Social media channels were followed up between 15 March and 10 May 2020 for postings with the same scope. Neurological manifestations were extracted from the identified papers and combined to provide a useful summary for the neurologist in clinical practice. RESULTS: Neurological manifestations potentially related to COVID-19 have been reported in large studies, case series and case reports and include acute cerebrovascular diseases, impaired consciousness, cranial nerve manifestations and autoimmune disorders such as the Guillain-Barré syndrome often present in patients with more severe COVID-19. Cranial nerve symptoms such as olfactory and gustatory dysfunctions are highly prevalent in patients with mild to moderate COVID-19 even without associated nasal symptoms and often present in an early stage of the disease. CONCLUSION: Physicians should be aware of the neurological manifestations in patients with COVID-19, especially when rapid clinical deterioration occurs. The neurological symptoms in COVID-19 patients may be due to direct viral neurological injury or indirect neuroinflammatory and autoimmune mechanisms. No antiviral treatments against the virus or vaccines for its prevention are available and the long-term consequences of the infection on human health remain uncertain especially with regard to the neurological system.

Neurophysiological investigations of drug resistant epilepsy patients treated with vagus nerve stimulation to differentiate responders from non-responders.

BACKGROUND AND PURPOSE: In patients treated with vagus nerve stimulation (VNS) for drug resistant epilepsy (DRE), up to a third of patients will eventually not respond to the therapy. As VNS therapy requires surgery for device implantation, prediction of response prior to surgery is desirable. It is hypothesized that neurophysiological investigations related to the mechanisms of action of VNS may help to differentiate VNS responders from non-responders prior to the initiation of therapy. METHODS: In a prospective series of DRE patients, polysomnography, heart rate variability (HRV) and cognitive event related potentials were recorded. Polysomnography and HRV were repeated after 1 year of treatment with VNS. Polysomnography, HRV and cognitive event related potentials were compared between VNS responders (≥50% reduction in seizure frequency) and non-responders. RESULTS: Fifteen out of 30 patients became VNS responders after 1 year of VNS treatment. Prior to treatment with VNS, the amount of deep sleep (NREM 3), the HRV high frequency (HF) power and the P3b amplitude were significantly different in responders compared to non-responders (P = 0.007; P = 0.001; P = 0.03). CONCLUSION: Three neurophysiological parameters, NREM 3, HRV HF and P3b amplitude, were found to be significantly different in DRE patients who became responders to VNS treatment prior to initiation of their treatment with VNS. These non-invasive recordings may be used as characteristics for response in future studies and help avoid unsuccessful implantations. Mechanistically these findings may be related to changes in brain regions involved in the so-called vagal afferent network.

Structural Characterization of Cranberry Arabinoxyloglucan Oligosaccharides.

Cranberry ( Vaccinium macrocarpon) products are widely available in North American food, juice, and dietary supplement markets. The use of cranberry is popular for the prevention of urinary tract infections (UTIs) and other reported health benefits. Preliminary findings by our research group indicate that arabinoxyloglucan oligosaccharides are present in cranberry products and may contribute to the antiadhesion properties of urine produced after cranberry consumption, but relatively little is known regarding the oligosaccharide components of cranberry. This report describes the isolation from two cranberry sources and the complete structure elucidation of two arabinoxyloglucan oligosaccharides through the use of carbohydrate-specific NMR spectroscopic and chemical derivatization methods. These compounds were identified as the heptasaccharide ß-d-glucopyranosyl-(1→4)-[α-d-xylopyranosyl-(1→6)]-ß-d-glucopyranosyl-(1→4)-ß-d-glucopyranosyl-(1→4)-[α-l-arabinofuranosyl-(1→2)-α-d-xylopyranosyl-(1→6)]-ß-d-glucopyranose (1) and the octasaccharide ß-d-glucopyranosyl-(1→4)-[α-l-arabinofuranosyl-(1→2)-α-d-xylopyranosyl-(1→6)]-ß-d-glucopyranosyl-(1→4)-ß-d-glucopyranosyl-(1→4)-[α-l-arabinofuranosyl-(1→2)-α-d-xylopyranosyl-(1→6)]-ß-d-glucopyranose (2). Selected fractions and the isolated compounds were subjected to antimicrobial, cell viability, and E. coli antiadhesion assays. Results indicated that enriched fractions and purified compounds lacked antimicrobial and cytotoxic effects, supporting the potential use of such compounds for disease prevention without the risk for resistance development. Preliminary antiadhesion results indicated that mixtures of oligosaccharides exhibited greater antiadhesion properties than purified fractions or pure compounds. The potential use of cranberry oligosaccharides for the prevention of UTIs warrants continued investigations of this complex compound series.

Quinoa intake reduces plasma and liver cholesterol, lessens obesity-associated inflammation, and helps to prevent hepatic steatosis in obese db/db mouse.

The purpose of this study was to investigate if quinoa (Chenopodium quinoa Willd.), a good source of nutrients, fibre, and phytochemicals, can modulate risk disease biomarkers on obese-diabetic (db/db) mice. The db/db mice fed quinoa-supplemented (quinoa) or AIN-93G diet (obese) were compared to lean control fed AIN-93G diet. Quinoa intake reduced at significant level plasma total-cholesterol (total-c), LDL-c, and oxidized-LDL to levels similar to lean; lessened protein carbonyls and interleukin (IL)-6. The hepatic steatosis and total-c accumulation in liver were also similar between lean and quinoa and lower than obese. Quinoa fibre and phytochemicals may have contributed to these health benefits. However, quinoa intake increased plasma insulin and did not protect from other pathophysiological manifestations of the db/db research model. More studies are needed with other research models and quinoa doses achievable by human diet to validate the clinical relevance of this study.

Non-anthocyanin phenolics in cherry (Prunus avium L.) modulate IL-6, liver lipids and expression of PPARδ and LXRs in obese diabetic (db/db) mice.

Anthocyanin-rich cherries are known for preventing/decreasing risk factors associated with obesity; however, the specific benefits exerted by cherry non-anthocyanin phenolics are not clear. Obese diabetic (db/db) mice fed a diet supplemented with anthocyanin-depleted cherry powder (cherry) were compared to db/db (obese) or lean counterparts (lean) fed a control isocaloric diet for 12 weeks. The reduced plasma interleukin (IL)-6 and improved liver health may be mediated by cherry fibre and non-anthocyanin phenolics. Benefits for liver health included reduction of lipids and protein carbonyls, and modulation of peroxisome proliferator-activated receptor (PPAR)δ mRNA to resemble levels in lean. Lack of plasma antilipidemic, improvement of antioxidant defenses, and PPARα/γ mRNA modulation in liver suggest cherry anthocyanins specific benefits. This is the first study to elucidate in vivo the potential benefits of cherry non-anthocyanin phenolics for diabetes-induced liver disorders and the importance of choosing processing technologies that preserve anthocyanins and health benefits of whole cherries.

MEG-guided analysis of 7T-MRI in patients with epilepsy.

PURPOSE: To study possible detection of structural abnormalities on 7T MRI that were not detected on 3T MRI and estimate the added value of MEG-guidance. For abnormalities found, analysis of convergence between clinical, MEG and 7T MRI localization of suspected epileptogenic foci. METHODS: In adult patients with well-documented localization-related epilepsy in whom a previous 3T MRI did not demonstrate an epileptogenic lesion but MEG indicated a plausible epileptogenic focus, 7T MRI was performed. Based on semiologic data, visual analysis of the 7T images was performed as well as based on prior MEG results. Correlation with other data from the patient charts, for as far as these were available, was analysed. To establish the level of concordance between the three observers the generalized or Fleiss kappa was calculated. RESULTS: In 3/19 patients abnormalities that, based on semiology, could plausibly represent an epileptogenic lesion were detected using 7T MRI. In an additional 3/19 an abnormality was detected after MEG-guidance. However, in these later cases there was no concordance among the three observers with regard to the presence of a structural abnormality. In one of these three cases intracranial recording was performed, proving the possible abnormality on 7T MRI to be the epileptogenic focus. CONCLUSIONS: In 32% of patients 7T MRI showed abnormalities that could indicate an epileptogenic lesion whereas previous 3T MRI did not, especially when visual inspection was guided by the presence of focal interictal MEG abnormalities.

Evaluating the evidence for non-monotonic dose-response relationships: A systematic literature review and (re-)analysis of in vivo toxicity data in the area of food safety.

This study aims to evaluate the evidence for the existence of non-monotonic dose-responses (NMDRs) of substances in the area of food safety. This review was performed following the systematic review methodology with the aim to identify in vivo studies published between January 2002 and February 2015 containing evidence for potential NMDRs. Inclusion and reliability criteria were defined and used to select relevant and reliable studies. A set of six checkpoints was developed to establish the likelihood that the data retrieved contained evidence for NMDR. In this review, 49 in vivo studies were identified as relevant and reliable, of which 42 were used for dose-response analysis. These studies contained 179 in vivo dose-response datasets with at least five dose groups (and a control group) as fewer doses cannot provide evidence for NMDR. These datasets were extracted and analyzed using the PROAST software package. The resulting dose-response relationships were evaluated for possible evidence of NMDRs by applying the six checkpoints. In total, 10 out of the 179 in vivo datasets fulfilled all six checkpoints. While these datasets could be considered as providing evidence for NMDR, replicated studies would still be needed to check if the results can be reproduced to rule out that the non-monotonicity was caused by incidental anomalies in that specific study. This approach, combining a systematic review with a set of checkpoints, is new and appears useful for future evaluations of the dose response datasets regarding evidence of non-monotonicity.

Challenges in the management of community pharmacies in Malaysia.

BACKGROUND: The provision of professional pharmacy services by community pharmacists continues to be limited, particularly in low and middle income countries. It was postulated that multiple management challenges faced by community pharmacists contribute to this situation. OBJECTIVE: The primary aim of the research was to determine the challenges faced in the management of community pharmacies in Sarawak (the largest state in Malaysia), and practical strategies to cope and overcome the challenges. METHODS: Semi-structured interviews were carried out with community pharmacists practising in Sarawak. Purposive and snowball sampling were employed to ensure a diverse group of informants. The interviews were audio-recorded and transcribed verbatim, with the resultant data analysed using thematic analysis. Data collection, coding, interpretation were carried out iteratively until theoretical saturation. RESULTS: Twenty respondents from different demographic characteristics were recruited. Six major themes were identified. Management challenges faced by community pharmacists traverse five major domains: market competition, legislative issues, customers' knowledge and expectations, macroeconomic impacts and operational challenges. Most of these challenges require government intervention to be resolved. In the meantime, improving customer service and expanding the range of professional services were seen as the most viable strategies to cope with existing challenges. The main concern is that current legislative and economic landscape may hinder these strategies. Enactment of dispensing separation and more protective measures against market competition were suggested to alleviate the challenges faced. CONCLUSION: Numerous management challenges faced by community pharmacists that distract them from delivering professional pharmacy services have been highlighted. Urgent affirmative actions by the government are warranted in supporting community pharmacists to realise and maximise their potentials.

Challenges in the management of community pharmacies in Malaysia

Background: The provision of professional pharmacy services by community pharmacists continues to be limited, particularly in low and middle income countries. It was postulated that multiple management challenges faced by community pharmacists contribute to this situation. Objective: The primary aim of the research was to determine the challenges faced in the management of community pharmacies in Sarawak (the largest state in Malaysia), and practical strategies to cope and overcome the challenges. Methods: Semi-structured interviews were carried out with community pharmacists practising in Sarawak. Purposive and snowball sampling were employed to ensure a diverse group of informants. The interviews were audio-recorded and transcribed verbatim, with the resultant data analysed using thematic analysis. Data collection, coding, interpretation were carried out iteratively until theoretical saturation. Results: Twenty respondents from different demographic characteristics were recruited. Six major themes were identified. Management challenges faced by community pharmacists traverse five major domains: market competition, legislative issues, customers’ knowledge and expectations, macroeconomic impacts and operational challenges. Most of these challenges require government intervention to be resolved. In the meantime, improving customer service and expanding the range of professional services were seen as the most viable strategies to cope with existing challenges. The main concern is that current legislative and economic landscape may hinder these strategies. Enactment of dispensing separation and more protective measures against market competition were suggested to alleviate the challenges faced. Conclusion: Numerous management challenges faced by community pharmacists that distract them from delivering professional pharmacy services have been highlighted. Urgent affirmative actions by the government are warranted in supporting community pharmacists to realise and maximise their potentials (AU)

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Red raspberry (Rubus idaeus L.) intake decreases oxidative stress in obese diabetic (db/db) mice.

Red raspberry fruit intake was investigated on obese diabetic (db/db) mice for 8weeks. Animals fed isocaloric diets (5.3% freeze-dried raspberry, or control) were assessed for obesity-diabetes-disease risk biomarkers. Results showed that raspberry intake improved antioxidant status and lessened plasma interleukin (IL)-6 (0.3-fold of control, p<0.1); most likely through enhancing glutathione peroxidase (GPx) activity in liver (4.3-fold of control), and in blood (2.1-fold of control). Other disease-risk biomarkers were similar between groups (p>0.05). Plasma levels of total cholesterol (T-CHL), low density lipoprotein-cholesterol (LDL-CHL), and resistin were higher in the raspberry group. Overall, the enhanced detoxifying cell defenses exerted by raspberry intake might be due to its polyphenolics and fibre. This study demonstrates in vivo that raspberry intake, at a dose that can be achieved by human consumption, might protect against diabetes-induced oxidative stress.

Evaluation of MEG vs EEG after sleep deprivation in epilepsy.

OBJECTIVE: MEG and EEG after sleep deprivation (EEG-SD) are applied as diagnostic tools in the evaluation of patients with possible epilepsy. There is no gold standard to check whether the diagnosis based on these two modalities is correct. The best standard available is the long-term follow-up of patients. As follow-up of an earlier study in which the additional value of MEG vs EEG-SD diagnosis was evaluated, we investigated the long-term validity of MEG-based and EEG-SD-based diagnosis. MATERIALS AND METHODS: Data collected from 46 patients were used in a comparative study of the last known diagnosis against the original one of 8 years ago. RESULTS: Long-term (3-8 years) sensitivity of sharp phenomena (combining spikes and sharp waves) in routine MEG and in EEG-SD for the diagnosis epilepsy is 71% and 62%, respectively. When compared to the original study, this hardly changed. Over time, uncertainty on diagnosis diminishes. CONCLUSION: MEG as well as EEG-SD are robust long-term predictors for epilepsy.

Cognitive deterioration in adult epilepsy: clinical characteristics of "Accelerated Cognitive Ageing".

OBJECTIVES: "Epileptic dementia" is reported in adults with childhood-onset refractory epilepsy. Cognitive deterioration can also occur in a "second-hit model". MATERIALS AND METHODS: We studied the clinical and neuropsychological characteristics of patients with cognitive deterioration (≥1 SD discrepancy between current IQ and premorbid IQ). Memory function, reaction time and processing speed were also evaluated. Analyses were performed to investigate which clinical characteristics correlated with cognitive deterioration. RESULTS: Twenty-seven patients were included with a mean age of 55.7 years old, an average age at epilepsy onset of 33.9 years and a mean duration of 21.8 years. Over 40% had experienced at least one status epilepticus. About 77.8% had at least one comorbid disease (most of (cardio)vascular origin). Cognitive deterioration scores were significant for both Performance IQ and Full Scale IQ, but not for Verbal IQ. Impairments in fluid functions primarily affected the IQ-scores. Memory was not impaired. Epilepsy factors explained 7% of the variance in deterioration, whereas 38% was explained by relatively low premorbid IQ and educational level, high age at seizure onset and older age. CONCLUSIONS: A subgroup of patients with localization-related epilepsy exhibits cognitive decline characterized by deterioration in PIQ and FSIQ, but with preserved higher order functions (VIQ and memory). Patients typically have epilepsia tarda, comorbid pathology, relatively low educational level and older age. These are factors known to increase the vulnerability of the brain by diminishing cognitive reserve. Cognitive deterioration may develop according to a stepwise "second-hit model", affecting and accelerating the cognitive ageing process.