Lactic acid bacteria feeding reversed the malformed eye structures and ameliorated gut microbiota profiles of Drosophila melanogaster Alzheimer's disease model.

AIMS: To utilize transgenic GMR-Aß42 Drosophila melanogaster as a model to evaluate potential Alzheimer's disease (AD)-reversal effects via the administration of lactic acid bacteria (LAB) strains, and associations of LAB with changes in gut microbiota profiles. METHODS AND RESULTS: Wild-type flies (Oregon-R) were crossed with glass multimer reporter-GAL4 (GMR-GAL4) to produce GMR-OreR (Control), while UAS-Aß42 (#33769) were crossed with GMR-GAL4 to produce transgenic Drosophila line that expressed Aß42 (GMR-Aß42). Feed containing seven different LAB strains (Lactobacillus paracasei 0291, Lactobacillus helveticus 1515, Lactobacillus reuteri 30242, L. reuteri 8513d, Lactobacillus fermentum 8312, Lactobacillus casei Y, Lactobacillus sakei Probio65) were given to GMR-Aß42 respectively, while feed without LAB strains were given to control and transgenic GMR-Aß42.nf Drosophila lines. The morphology of the eyes was viewed with scanning electron microscopy (SEM). The changes in gut microbiota profiles associated with LAB were analysed using 16s high throughput sequencing. Malformation of eye structures in transgenic GMR-Aß42 Drosophila were reversed upon the administration of LAB strains, with more prevalent effects from L. sakei Probio65 and L. paracasei 0291. The GMR-Aß42.nf group showed dominance of Wolbachia in the gut, a genus that was almost absent in the normal control group (P < 0·05). The administration of L. sakei Probio65 and L. paracasei 0291 reduced the abundance of Wolbachia accompanied by increased abundance of Stenotrophomonas and Acetobacter (P < 0·05), resembling the microbial profile of the control group. CONCLUSIONS: Lactobacillus sakei Probio65 and Lactobacillus paracasei 0291 have more prominent effects in reversing malformed eye of transgenic GMR-Aß42 Drosophila, and reducing the abundance of Wolbachia accompanied by an increased abundance of Stenotrophomonas and Acetobacter. SIGNIFICANCE AND IMPACT OF THE STUDY: Potentials of LAB to prevent and/or alleviate the onset and pathogenesis of neurodegenerative diseases such as AD, supporting brain health strategies along the gut-brain axis.

The molecular mechanisms of probiotic strains in improving ageing bone and muscle of d-galactose-induced ageing rats.

AIM: The aim of this study was to evaluate the molecular mechanisms of Lactobacillus strains in improving ageing of the musculoskeletal system. METHODS AND RESULTS: The anti-ageing mechanism of three probiotics strains Lactobacillus fermentum DR9, Lactobacillus paracasei OFS 0291 and L. helveticus OFS 1515 were evaluated on gastrocnemius muscle and tibia of d-galactose-induced ageing rats. Upon senescence induction, aged rats demonstrated reduced antioxidative genes CAT and SOD expression in both bone and muscle compared to the young rats (P < 0·05). Strain L. fermentum DR9 demonstrated improved expression of SOD in bone and muscle compared to the aged rats (P < 0·05). In the evaluation of myogenesis-related genes, L. paracasei OFS 0291 and L. fermentum DR9 increased the mRNA expression of IGF-1; L. helveticus OFS 1515 and L. fermentum DR9 reduced the expression of MyoD, in contrast to the aged controls (P < 0·05). Protective effects of L. fermentum DR9 on ageing muscle were believed to be contributed by increased AMPK-α2 expression. Among the osteoclastogenesis genes studied, TNF-α expression was highly elevated in tibia of aged rats, while all three probiotics strains ameliorated the expression. Lactobacillus fermentum DR9 also reduced the expression of IL-6 and TRAP in tibia when compared to the aged rats (P < 0·05). All probiotics treatment resulted in declined proinflammatory cytokines IL-1ß in muscle and bone. CONCLUSIONS: Lactobacillus fermentum DR9 appeared to be the strongest strain in modulation of musculoskeletal health during ageing. SIGNIFICANCE AND IMPACT OF THE STUDY: The study demonstrated the protective effects of the bacteria on muscle and bone through antioxidative and anti-inflammatory actions. Therefore, L. fermentum DR9 may serve as a promising targeted anti-ageing therapy.

Lactobacillus plantarum DR7 improved brain health in aging rats via the serotonin, inflammatory and apoptosis pathways.

Aging processes affect the brain in many ways, ranging from cellular to functional levels which lead to cognitive decline and increased oxidative stress. The aim of this study was to investigate the potentials of Lactobacillus plantarum DR7 on brain health including cognitive and memory functions during aging and the impacts of high fat diet during a 12-week period. Male Sprague-Dawley rats were separated into six groups: (1) young animals on normal diet (ND, (2) young animals on a high fat diet (HFD), (3) aged animals on ND, (4) aged animals on HFD, (5) aged animals on HFD and L. plantarum DR7 (109 cfu/day) and (6) aged animals receiving HFD and lovastatin. To induce ageing, all rats in group 3 to 6 were injected sub-cutaneously at 600 mg/kg/day of D-galactose daily. The administration of DR7 has reduced anxiety accompanied by enhanced memory during behavioural assessments in aged-HFD rats (P<0.05). Hippocampal concentration of all three pro-inflammatory cytokines were increased during aging but reduced upon administration of both statin and DR7. Expressions of hippocampal neurotransmitters and apoptosis genes showed reduced expressions of indoleamine dioxygenase and P53 accompanied by increased expression of TPH1 in aged- HFD rats administered with DR7, indicating potential effects of DR7 along the pathways of serotonin and oxidative senescence. This study provided an insight into potentials of L. plantarum DR7 as a prospective dietary strategy to improve cognitive functions during aging. This study provided an insight into potentials of L. plantarum DR7 as a prospective dietary strategy to improve cognitive functions during aging.

Optimum resource allocation in optical wireless systems with energy-efficient fog and cloud architectures.

Optical wireless communication (OWC) is a promising technology that can provide high data rates while supporting multiple users. The optical wireless (OW) physical layer has been researched extensively, however, less work was devoted to multiple access and how the OW front end is connected to the network. In this paper, an OWC system which employs a wavelength division multiple access (WDMA) scheme is studied, for the purpose of supporting multiple users. In addition, a cloud/fog architecture is proposed for the first time for OWC to provide processing capabilities. The cloud/fog-integrated architecture uses visible indoor light to create high data rate connections with potential mobile nodes. These OW nodes are further clustered and used as fog mini servers to provide processing services through the OW channel for other users. Additional fog-processing units are located in the room, the building, the campus and at the metro level. Further processing capabilities are provided by remote cloud sites. Two mixed-integer linear programming (MILP) models were proposed to numerically study networking and processing in OW systems. The first MILP model was developed and used to optimize resource allocation in the indoor OWC systems, in particular, the allocation of access points (APs) and wavelengths to users, while the second MILP model was developed to optimize the placement of processing tasks in the different fog and cloud nodes available. The optimization of tasks placement in the cloud/fog-integrated architecture was analysed using the MILP models. Multiple scenarios were considered where the mobile node locations were varied in the room and the amount of processing and data rate requested by each OW node was varied. The results help to identify the optimum colour and AP to use for communication for a given mobile node location and OWC system configuration, the optimum location to place processing and the impact of the network architecture. This article is part of the theme issue 'Optical wireless communication'.

Lactobacillus probiotics improved the gut microbiota profile of a Drosophila melanogaster Alzheimer's disease model and alleviated neurodegeneration in the eye.

Alzheimer's disease (AD) is a progressive disease and one of the most common forms of neurodegenerative disorders. Emerging evidence is supporting the use of various strategies that modulate gut microbiota to exert neurological and psychological changes. This includes the utilisation of probiotics as a natural and dietary intervention for brain health. Here, we showed the potential AD-reversal effects of Lactobacillus probiotics through feeding to our Drosophila melanogaster AD model. The administration of Lactobacillus strains was able to rescue the rough eye phenotype (REP) seen in AD-induced Drosophila, with a more prominent effect observed upon the administration of Lactobacillus plantarum DR7 (DR7). Furthermore, we analysed the gut microbiota of the AD-induced Drosophila and found elevated levels of Wolbachia. The administration of DR7 restored the gut microbiota diversity of AD-induced Drosophila with a significant reduction in Wolbachia's relative abundance, accompanied by an increase of Stenotrophomonas and Acetobacter. Through functional predictive analyses, Wolbachia was predicted to be positively correlated with neurodegenerative disorders, such as Parkinson's, Huntington's and Alzheimer's diseases, while Stenotrophomonas was negatively correlated with these neurodegenerative disorders. Altogether, our data exhibited DR7's ability to ameliorate the AD effects in our AD-induced Drosophila. Thus, we propose that Wolbachia be used as a potential biomarker for AD.

Lactobacillus plantarum DR7 alleviates stress and anxiety in adults: a randomised, double-blind, placebo-controlled study.

Probiotics have been reported to exert beneficial effects along the gut-brain axis. This randomised, double-blind and placebo-controlled human study aimed to evaluate such properties of Lactobacillus plantarum DR7 and its accompanying mechanisms in stressed adults. One hundred and eleven (n=111; DR7 n=56, placebo n=55) stressed adults were recruited based on moderate stress levels using the PSS-10 questionnaire. The consumption of DR7 (1×109 cfu/day) for 12 weeks reduced symptoms of stress (P=0.024), anxiety (P=0.001), and total psychological scores (P=0.022) as early as 8 weeks among stressed adults compared to the placebo group as assessed by the DASS-42 questionnaire. Plasma cortisol level was reduced among DR7 subjects as compared to the placebo, accompanied by reduced plasma pro-inflammatory cytokines, such as interferon-γ and transforming growth factor-α and increased plasma anti-inflammatory cytokines, such as interleukin 10 (P<0.05). DR7 better improved cognitive and memory functions in normal adults (>30 years old), such as basic attention, emotional cognition, and associate learning (P<0.05), as compared to the placebo and young adults (<30 years old). The administration of DR7 enhanced the serotonin pathway, as observed by lowered expressions of plasma dopamine ß-hydroxylase (DBH), tyrosine hydroxylase (TH), indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase accompanied by increased expressions of tryptophan hydroxylase-2 and 5-hydroxytryptamine receptor-6, while stabilising the dopamine pathway as observed via stabilised expressions of TH and DBH over 12 weeks as compared to the placebo (P<0.05). Our results indicated that DR7 fulfil the requirement of a probiotic strain as per recommendation of FAO/WHO and could be applicable as a natural strategy to improve psychological functions, cognitive health and memory in stressed adults.

Lactobacilli modulated AMPK activity and prevented telomere shortening in ageing rats.

This study aimed to evaluate the anti-ageing effects of different strains of lactobacilli putative probiotics on an ageing rat model as induced by D-galactose and a high fat diet. Male Sprague-Dawley rats were fed with high fat diet (54% kcal fat) and injected with D-galactose daily for 12 weeks to induce ageing. The effects of putative probiotic strains on age-related impairment such as telomere length, plasma lipid peroxidation, hepatic 5'adenosine monophosphate-activated protein kinase (AMPK) expression, as well as endurance performance were evaluated. Administration of statin, Lactobacillus plantarum DR7 (LP-DR7), Lactobacillus fermentum DR9 (LF-DR9), and Lactobacillus reuteri 8513d (LR-8513d) significantly reduced the shortening of telomere and increased the expression of AMPK subunit-α1 (P<0.05). Plasma lipid peroxidation was lower (P<0.05) in groups administered with statin and LF-DR9 as compared to the control. AMPK subunit-α2 was elevated in rats administered with LP-DR7 as compared to the control (P<0.05). Using an in vivo ageing rat model, the current study has illustrated the potentials of lactobacilli putative probiotics in alleviation of age-related impairment in a strain-dependent manner.

Perceptions of Healthcare Professionals on the Usage of Percutaneous Endoscopic Gastrostomy in a Teaching Hospital from a Middle-Income South East Asian Country.

OBJECTIVE: To explore the perceptions of healthcare professionals' (HCPs) in a South East Asian nation towards percutaneous endoscopic gastrostomy (PEG) feeding. DESIGN: Semi-structured, qualitative interviews. SETTINGS: A teaching hospital in Kuala Lumpur, Malaysia. PARTICIPANTS: A total of 17 healthcare professionals aged 23-43 years, 82% women. RESULTS: Thematic analysis revealed five themes that represent HCPs' perceptions in relation to the usage of PEG feeding: 1) knowledge of HCPs, 2) communication, 3) understanding among patients, and 4) financial and affordability. CONCLUSION: The rationale for reluctance towards PEG feeding observed in this regions was explained by lack of education, knowledge, communication, team work, and financial support. Future studies should assess the effects of educational programmes among HCPs and changes in policies to promote affordability on the utilization of PEG feeding in this region.

Analysis of KRAS and NRAS Gene Mutations in Arab Asian Children With Acute Leukemia: High Frequency of RAS Mutations in Acute Lymphoblastic Leukemia.

BACKGROUND: KRAS and NRAS gene mutations are frequently observed in childhood leukemia. The objective of this study was to determine the frequency of RAS mutations and the association between RAS mutations and other genetic aberrations in Arab Asian children with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). METHODS: Diagnostic samples of 485 patients (<18 years) with acute leukemia from Iraq and Jordan were obtained, using Flinders Technology Associates filter papers. Polymerase chain reaction and direct sequencing were performed in Japan. RESULTS: RAS mutations were detected in 86/318 (27%) of ALL cases and 35/167 (21%) of AML cases. The frequency of NRAS mutation was similar to that of KRAS mutation in ALL. Two RAS mutations were detected in nine patients. Among 264 Iraqi patients with ALL, RAS mutation was significantly associated with lower initial white blood cell count. Of 57 patients with chimeric transcripts, only two patients with either TEL-AML1 or E2A-PBX1 had KRAS mutation. The frequency of NRAS mutation was four times higher than that of KRAS mutation in AML. FAB-M4 and M5 subsets were associated with RAS mutation. Among 134 Iraqi patients with AML, 18 patients had RAS mutations and other genetic aberrations. In particular, 9 of 25 (36%) with MLL-rearrangement had RAS mutations. CONCLUSION: The prevalence of oncogenic RAS mutations was higher among Arab Asian children than in other countries. RAS mutations in AML were found to coexist with other genetic aberrations, particularly MLL rearrangement.

Percutaneous endoscopic gastrostomy versus nasogastric feeding in older individuals with non-stroke dysphagia: a systematic review.

OBJECTIVE: The objective of this systematic review was to evaluate existing studies on the effectiveness of percutaneous endoscopic gastrostomy (PEG) feeding compared to nasogastric (NG) feeding for patients with non-stroke related dysphagia. METHODS: We searched Ovid MEDLINE, EMBASE, the Cochrane Library, Web of Science and PubMed databases through to December 2013 using the terms "percutaneous endoscopic gastrostomy", "gastrostomy", "PEG", "nasogastric", "nasogastric tube", "nasogastric feeding" and "intubation". We included randomized controlled trials (RCTs) and non-RCTs which compared PEG with NG feeding in individuals with non-stroke dysphagia. RESULTS: 9 studies involving 847 participants were included in the final analysis, including two randomized trials. Pooled analysis indicated no significant difference in the risk of pneumonia [relative risk (RR) = 1.18, 95% confidence interval (CI) = 0.87-1.60] and overall complications [relative risk (RR) = 0.80, 95% confidence interval (CI) = 0.63-1.02] between PEG and NG feeding. A meta-analysis was not possible for mortality and nutritional outcomes, but three studies suggested improved mortality outcomes with PEG feeding while two out of three studies reported PEG feeding to be better from a nutritional perspective. CONCLUSIONS: Firm conclusions could not be derived on whether PEG feeding is beneficial over NG feeding in older persons with non-stroke dysphagia, as previously published literature were unclear or had a high risk of bias. A well-designed and adequately powered RCT, which includes carer strain and quality of life as outcome measures is therefore urgently needed.

Frequent coexistence of RAS mutations in RUNX1-mutated acute myeloid leukemia in Arab Asian children.

BACKGROUND: RUNX1 mutation plays an important role in adult leukemic transformation. However, its contribution to the development of childhood leukemia remains unclear. In the present study, we analyzed point mutations of RUNX1 gene in children and adolescents with acute myeloid leukemia (AML) from Iraq and Jordan. PROCEDURE: Bone marrow and/or peripheral blood samples were collected from 178 patients of Arab Asian ethnicity (aged ≤17 years) newly diagnosed with AML: 145 samples from Iraq and 33 samples from Jordan. Direct DNA sequencing was performed on six genes including RUNX1 gene (exons 3-8). RESULTS: RUNX1 point mutations were identified in 10 (5.6%) of 178 patients. One patient possessed biallelic mutations of RUNX1 gene. C-terminal area was the predominant site of RUNX1 mutations (eight in C-terminal and two in N-terminal). Patients with RUNX1 mutations were significantly older than those with wild-type of the gene. Additionally, AML M0 subtype was more frequently found in patients with RUNX1 mutations. Both RUNX1 mutations and RAS mutations were identified in 4 of 10 children. Three patients with RUNX1 mutation had FLT3-ITD. On the other hand, 36 (21.4%) and 25 (14.9%) of 168 patients with wild-type of the gene had a RAS mutation and FLT3-ITD, respectively. Eight of 10 patients with RUNX1 mutations died of hematological relapse. CONCLUSION: The incidence of RUNX1 mutations in Arab Asian children and adolescents with AML was 5.6%. Further studies are required to clarify whether RAS mutations contribute to the development of pediatric AML associated with RUNX1 mutations.

Analysis of class I and II aberrations in Iraqi childhood acute myeloid leukemia using filter paper cards.

The lack of molecular diagnosis in the field of cancer in Iraq has motivated us to perform a genetic analysis of pediatric acute myelogenous leukemia (AML), including class I and II aberrations. Peripheral blood or bone marrow cells were collected from 134 AML children aged ≤15 years. Flinders Technology Associates (FTA) filter paper cards were used to transfer dried blood samples from five Iraqi hospitals to Japan. DNA sequencing was performed to identify class I mutations. Nested RT-PCR was used to detect class II aberrations, except that MLL rearrangement was detected according to long distance inverse-PCR. NPM1 and FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations were analyzed by GeneScan using DNA template. Among 134 Iraqi pediatric AML samples, the most prevalent FAB subtype was M2 (33.6 %) followed by M3 (17.9 %). Class I mutations: 20 (14.9 %), 8 (6.0 %), and 8 (6.0 %) patients had FLT3-ITD, FLT3-TKD, and KIT mutations, respectively. Class II mutations: 24 (17.9 %), 19 (14.2 %), and 9 (6.7 %) children had PML-RARA, RUNX1-RUNX1T1, and CBFB-MYH11 transcripts, respectively. MLL rearrangements were detected in 25 (18.7 %) patients. NPM1 mutation was detected in seven (5.2 %) cases. Collectively, approximately 30 % of AML children were proved to carry favorable prognostic genetic abnormalities, whereas approximately 10 % had high FLT3-ITD allelic burden and needed a special treatment plan including allogeneic hematopoietic stem cell transplantation. Acute promyelocytic leukemia (APL) was frequent among Iraqi pediatric AML. It is likely that molecular diagnosis using FTA cards in underdeveloped countries could guide doctors towards an appropriate treatment strategy.

Genetic evaluation of childhood acute lymphoblastic leukemia in Iraq using FTA cards.

BACKGROUND: Genetic examination of childhood leukemia has not been available in Iraq. We here report the frequency of TEL-AML1, E2A-PBX1, MLL-AF4, and BCR-ABL chimeric transcripts in 264 Iraqi children newly diagnosed with acute lymphoblastic leukemia (ALL), using FTA cards impregnated with bone marrow aspirate or whole blood. PATIENTS AND METHODS: The diagnosis of ALL was made according to standard French-American-British morphologic criteria. Based on the results of storage temperature and duration, most of the FTA samples were preserved at 4°C for up to 6 weeks in five Iraqi hospitals and then transferred to Japan for molecular analysis. Nested reverse transcription-polymerase chain reaction was adopted for the analysis. RESULTS: TEL-AML1 chimeric transcript product was found in 32 (12.1%) of 264 ALL patients. Eleven (4.2%) patients, 4 (1.5%) patients, and 11 (4.2%) patients had E2A-PBX1 mRNA, MLL-AF4 mRNA, and BCR-ABL mRNA, respectively. One patient had both TEL-AML1 and E2A-PBX1 fusion genes. The incidence of TEL-AML1 in Iraqi ALL children appears to be similar to or slightly higher than those of Jordan (12%) and Kuwait (7%). The prevalence and clinical findings of ALL patients with either E2A-PBX1 or BCR-ABL were comparable to the data reported elsewhere. CONCLUSION: International collaboration via FTA cards may be helpful to improve diagnosis and management of patients with hematological malignancies in low-income and underdeveloped countries.