Analysis of the components of Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) and its regulation of γδ T-cell function.

BACKGROUND: Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) is a peptide antigen released from the mycobacterial cytoplasm into the supernatant of Mycobacterium tuberculosis (Mtb) attenuated H37Ra strain after autoclaving at 121 °C for 20 min. Mtb-HAg can specifically induce γδ T-cell proliferation in vitro. However, the exact composition of Mtb-HAg and the protein antigens that are responsible for its function are currently unknown. METHODS: Mtb-HAg extracted from the Mtb H37Ra strain was subjected to LC‒MS mass spectrometry. Twelve of the identified protein fractions were recombinantly expressed in Escherichia coli by genetic engineering technology using pET-28a as a plasmid and purified by Ni-NTA agarose resin to stimulate peripheral blood mononuclear cells (PBMCs) from different healthy individuals. The proliferation of γδ T cells and major γδ T-cell subset types as well as the production of TNF-α and IFN-γ were determined by flow cytometry. Their proliferating γδ T cells were isolated and purified using MACS separation columns, and Mtb H37Ra-infected THP-1 was co-cultured with isolated and purified γδ T cells to quantify Mycobacterium viability by counting CFUs. RESULTS: In this study, Mtb-HAg from the attenuated Mtb H37Ra strain was analysed by LC‒MS mass spectrometry, and a total of 564 proteins were identified. Analysis of the identified protein fractions revealed that the major protein components included heat shock proteins and Mtb-specific antigenic proteins. Recombinant expression of 10 of these proteins in by Escherichia coli genetic engineering technology was used to successfully stimulate PBMCs from different healthy individuals, but 2 of the proteins, EsxJ and EsxA, were not expressed. Flow cytometry results showed that, compared with the IL-2 control, HspX, GroEL1, and GroES specifically induced γδ T-cell expansion, with Vγ2δ2 T cells as the main subset, and the secretion of the antimicrobial cytokines TNF-α and IFN-γ. In contrast, HtpG, DnaK, GroEL2, HbhA, Mpt63, EsxB, and EsxN were unable to promote γδ T-cell proliferation and the secretion of TNF-α and IFN-γ. None of the above recombinant proteins were able to induce the secretion of TNF-α and IFN-γ by αß T cells. In addition, TNF-α, IFN-γ-producing γδ T cells inhibit the growth of intracellular Mtb. CONCLUSION: Activated γδ T cells induced by Mtb-HAg components HspX, GroES, GroEL1 to produce TNF-α, IFN-γ modulate macrophages to inhibit intracellular Mtb growth. These data lay the foundation for subsequent studies on the mechanism by which Mtb-HAg induces γδ T-cell proliferation in vitro, as well as the development of preventive and therapeutic vaccines and rapid diagnostic reagents.

Correlation between vessel density and thickness in the retina and choroid of severe non-proliferative diabetic retinopathy patients.

Objectives: To explore the correlation between the vessel density (VD) of the retina and choroid vascular plexuses and the thicknesses of their respective retinal layers and choroid membranes in participants with severe non-proliferative diabetic retinopathy (NPDR). Methods: We retrospectively analyzed the data of 42 eyes of 42 participants with diabetes mellitus (DM) and severe NPDR. In addition, 41 eyes of 41 healthy controls were evaluated. Measurements were taken for both groups using optical coherence tomography angiography (OCTA), including the area and perimeter of the foveal vascular zone (FAZ) and the vascular density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choroid capillary (CC). These measurements were compared with the retinal thickness (RT) of the inner/intermediate retinal layers and choroidal thickness (CT). The study evaluated the correlation between RT or CT and VD in the respective vascular networks, namely superficial capillary plexus (SCP), deep capillary plexus (DCP), or CC. Results: The inner RT and VD in all plexuses were significantly lower in the severe NPDR group than in the healthy controls. Furthermore, the FAZ area and perimeter were larger in the severe NPDR group. Inner RT was correlated with VD in the SCP group (r=0.67 and r=0.71 in the healthy control and severe NPDR groups, respectively; p<0.05). CT negatively correlated with VD in the CC (r=-0.697 and r=-0.759 in the healthy control and severe NPDR groups, respectively; p<0.05). Intermediate RT significantly correlated with VD in the DCP of the severe NPDR group (r=-0.55, p<0.05), but not in the healthy control group. Conclusions: Retinal or choroidal thickness strongly correlated with VD. Therefore, patients with severe NPDR must consider the distinct anatomical and functional entities of the various retinal layers and the choroid.

Relationship between visual acuity and OCT angiography parameters in diabetic retinopathy eyes after treatment.

PURPOSE: To assess the relationship between visual acuity and OCT angiography parameters in diabetic retinopathy eyes after treatment, and to analyze the relative factors in PDR eyes. METHODS: A total of 89 eyes, including 42 eyes with non-PDR (NPDR), and 47 eyes after vitrectomy with PDR were included and underwent OCTA. All images were processed by Python or FIJI. Multivariable linear regression models were used to analyze the associations between postoperative BCVA and OCTA parameters in PDR patients. RESULTS: Postoperative OCTA parameters including deep capillary plexus (DCP) parafoveal and perifoveal vessel density (VD), DCP parafoveal and perifoveal vessel length density (VLD), DCP fractal dimension (FD), choriocapillaris plexus (CCP) VD, CCP VLD, were significantly lower in the PDR group than in the NPDR group. In the superficial capillary plexus (SCP), we found a negative correlation between the postoperative BCVA and VD (parafovea: ß coefficient = -0.351, p = 0.023; perifovea: ß coefficient = -0.338, p = 0.036). Perifoveal VLD (ß coefficient = -0.343, p = 0.031) and FD (ß coefficient = -0.375, p = 0.016) of the SCP were also negatively correlated with postoperative BCVA. Regarding the DCP, perifoveal VD (ß coefficient = -0.396, p = 0.008), perifoveal VLD (ß coefficient = -0.334, p = 0.025), vessel tortuosity (VT) (ß coefficient = -0.369, p = 0.015) were negatively correlated with postoperative BCVA. In CCP, VLD (ß coefficient = -0.373, p = 0.023) and number of flow voids (ß coefficient = -0.334, p = 0.036) exhibited a negative association with postoperative BCVA. CONCLUSIONS: Postoperative BCVA of PDR patients was related to OCTA parameters of the SCP (parafoveal and perifoveal VD, perifoveal VLD and FD), DCP (perifoveal VD, VLD, and VT) and CCP (VLD and number of flow voids).

Systems modelling as an approach for eliciting the mechanisms for hip fracture recovery among older adults in a participatory stakeholder engagement setting.

Introduction: Due to an aging population, the rising prevalence and incidence of hip fractures and the associated health and economic burden present a challenge to healthcare systems worldwide. Studies have shown that a complex interplay of physiological, psychological, and social factors often affects the recovery trajectories of older adults with hip fractures, often complicating the recovery process. Methods: This research aims to actively engage stakeholders (including doctors, physiotherapists, hip fracture patients, and caregivers) using the systems modeling methodology of Group Model Building (GMB) to elicit the factors that promote or inhibit hip fracture recovery, incorporating a feedback perspective to inform system-wide interventions. Hip fracture stakeholder engagement was facilitated through the Group Model Building approach in a two-half-day workshop of 25 stakeholders. This approach combined different techniques to develop a comprehensive qualitative whole-system view model of the factors that promote or inhibit hip fracture recovery. Results: A conceptual, qualitative model of the dynamics of hip fracture recovery was developed that draws on stakeholders' personal experiences through a moderated interaction. Stakeholders identified four domains (i.e., expectation formation, rehabilitation, affordability/availability, and resilience building) that play a significant role in the hip fracture recovery journey.. Discussion: The insight that recovery of loss of function due to hip fracture is attributed to (a) the recognition of a gap between pre-fracture physical function and current physical function; and (b) the marshaling of psychological resilience to respond promptly to a physical functional loss via uptake of rehabilitation services is supported by findings and has several policy implications.

Effect of Reproductive Stage-Waterlogging on the Growth and Yield of Upland Cotton (Gossypium hirsutum).

The reproductive stage of cotton (Gossypium sp.) is highly sensitive to waterlogging. The identification of potential elite upland cotton (Gossypium hirsutum) cultivar(s) having higher waterlogging tolerance is crucial to expanding cotton cultivation in the low-lying areas. The present study was designed to investigate the effect of waterlogging on the reproductive development of four elite upland cotton cultivars, namely, Rupali-1, CB-12, CB-13, and DM-3, against four waterlogging durations (e.g., 0, 3, 6, and 9-day). Waterlogging stress significantly impacted morpho-physiological, biochemical, and yield attributes of cotton. Two cotton cultivars, e.g., CB-12 and Rupali-1, showed the lowest reduction in plant height (6 and 9%, respectively) and boll weight (8 and 5%, respectively) at the highest waterlogging duration of 9 days. Physiological and biochemical data revealed that higher leaf chlorophyll, proline, and relative water contents, and lower malondialdehyde contents, particularly in CB-12 and Rupali-1, were positively correlated with yield. Notably, CB-12 and Rupali-1 had higher seed cotton weight (90.34 and 83.10 g, respectively), lint weight (40.12 and 39.32 g, respectively), and seed weight (49.47 and 43.78 g, respectively) per plant than CB-13 and DM-3 in response to the highest duration of waterlogging of 9 days. Moreover, extensive multivariate analyses like Spearman correlation and the principle component analysis revealed that CB-12 and Rupali-1 had greater coefficients in yield and physiological attributes at 9-day waterlogging, whereas CB-13 and DM-3 were sensitive cultivars in response to the same levels of waterlogging. Thus, CB-12 and Rupali-1 might be well adapted to the low-lying waterlogging-prone areas for high and sustained yield.

Exploring relationship among nitrogen fertilizer, yield and nitrogen use efficiency in modern wheat varieties under subtropical condition.

Due to variations in the length of crop growth and the dynamics of soil nitrogen, the nitrogen (N) requirements of different wheat varieties may change. In this relation, during two successive wheat-growing seasons in 2018 and 2019, pot experiments were conducted to assess relationship among N fertilizer, yield and efficiency of N use in contemporary wheat varieties. Ten varieties of wheat viz. BARI Gom -24, BARI Gom -25, BARI Gom -26, BARI Gom -27, BARI Gom -28, BARI Gom -29, BARI Gom-30, BARI Gom-31, BARI Gom-32, and BARI Gom-33 and four N levels e.g. N 0, N 45 kg ha-1, N 90 kg ha-1 and N 135 kg ha-1 were used in the study. Completely randomized design (CRD) was followed with three replications. Wheat yield and yield-contributing elements like spike length, 1000- grain weight, and grain yield enhanced at N levels up to N 90 kg ha-1. The principal component analysis illustrated that the range BARI -32 had the most grain manufacturing and N use efficiency with N 90 kg ha-1 application. Correlation depicted that there is a robust relation amongst N use, yield and N use efficiency. Dendrogram organized primarily based totally at the resemblance via way of means of Euclidean distance among wheat varieties and it was confirmed that varieties allocated in clusters II had been greater diverse. The end consequence found out big hereditary difference in wheat which could doubtlessly be used for the wide range cultivation and breeding plan.

Effects of reducing, stabilizing, and antibiotic agents on "Candidatus Kuenenia stuttgartiensis".

Anaerobic ammon ium oxidizing (anammox) bacteria oxidize ammonium and reduce nitrite, producing N2, and could play a major role in energy-optimized wastewater treatment. However, sensitivity to various environmental conditions and slow growth currently hinder their wide application. Here, we attempted to determine online the effect of environmental stresses on anammox bacteria by using an overnight batch activity test with whole cells, in which anammox activity was calculated by quantifying N2 production via headspace-pressure monitoring. A planktonic mixed culture dominated by "Candidatus Kuenenia stuttgartiensis" strain CSTR1 was cultivated in a 30-L semi-continuous stirring tank reactor. In overnight resting-cell anammox activity tests, oxygen caused strong inhibition of anammox activity, which was reversed by sodium sulfite (30 µM). The tested antibiotics sulfamethoxazole, kanamycin, and ciprofloxacin elicited their effect on a dose-dependent manner; however, strain CSTR1 was highly resistant to sulfamethoxazole. Anammox activity was improved by activated carbon and Fe2O3. Protein expression analysis from resting cells after anammox activity stimulation revealed that NapC/NirT family cytochrome c (KsCSTR_12840), hydrazine synthase, hydrazine dehydrogenase, hydroxylamine oxidase, and nitrate:nitrite oxidoreductase were upregulated, while a putative hydroxylamine oxidoreductase HAO (KsCSTR_49490) was downregulated. These findings contribute to the growing knowledge on anammox bacteria physiology, eventually leading to the control of anammox bacteria growth and activity in real-world application. KEY POINTS: • Sulfite additions can reverse oxygen inhibition of the anammox process • Anammox activity was improved by activated carbon and ferric oxide • Sulfamethoxazole marginally affected anammox activity.

Optimum Nitrogen Application Acclimatizes Root Morpho-Physiological Traits and Yield Potential in Rice under Subtropical Conditions.

Nitrogen (N) is a highly essential macronutrient for plant root growth and grain yield (GY). To assess the relationship among N, root traits, and the yield of boro (dry season irrigated) rice, a pot experiment was performed in the Department of Agronomy, Bangladesh Agricultural University, Mymensingh, Bangladesh, during the boro rice season of 2020-2021. Three boro rice varieties, namely BRRI dhan29, Hira-2, and Binadhan-10, were planted at four N doses: 0 kg ha-1 (N0), 70 kg ha-1 (N70), 140 kg ha-1 (N140), and 210 kg ha-1 (N210). The experiment was conducted following a completely randomized design with three replicates. The varieties were evaluated for root number (RN), root length (RL), root volume (RV), root porosity (RP), leaf area index (LAI), total dry matter (TDM), and yield. The results indicated that the Binadhan-10, Hira-2, and BRRI dhan29 varieties produced better root characteristics under at the N140 and N210 levels. A substantial positive association was noticed between the grain yield and the root traits, except for root porosity. Based on the root traits and growth dynamics, Binadhan-10 performed the best at the N140 level and produced the highest grain yield (26.96 g pot-1), followed by Hira-2 (26.35 g pot-1) and BRRI dhan29 (25.90 g pot-1).

Challenges in osteoporosis treatment initiation in geriatric patients admitted under the hip-fracture pathway.

Osteoporosis is often untreated especially in older people. This study found a low prescribing rate of osteoporosis treatment medication of 22.4% in older people admitted under the hip-fracture pathway. Factors associated with greater odds of being prescribed osteoporosis medications are categorized into patient-related, physician-related and system-related factors. INTRODUCTION: Osteoporosis represents a growing healthcare problem which is often overlooked by healthcare providers and untreated especially in older people. This study aims to assess the rate of osteoporosis treatment initiation and to investigate underlying physician and system-related barriers in geriatric patients admitted for hip fracture. METHODS: A retrospective study was conducted on patients aged 60 years and older, admitted under the hip-fracture pathway from January 2019 to December 2019. Data collected included demographics, co-morbid conditions and laboratory data. Clinical charts were reviewed for whether bone mineral density (BMD) scan has been ordered, plans for bone health were made and reflected in the discharge summary, and if appropriate memos were written. The primary outcome was the prescription of osteoporosis treatment medications. Prescription lists were also reviewed for prescribing patterns of calcium and vitamin D. RESULTS: A total of 375 patients older than 60 years old were identified. 281 patients who fit the inclusion and exclusion criteria with complete data were further analysed. Within 1 year of hip fracture admission, 63 (22.4%) of them were prescribed with osteoporosis treatment. Multivariate logistic regression identified milder stage of CKD (p = 0.038, OR = 0.617, 95% CI 0.392-0.973) and BMD scan performed (p < 0.001, OR = 6.515, 95% CI 3.180-13.348) as independent factors associated with the prescription of osteoporosis treatment within 1 year of hip fracture admission. CONCLUSION: The rate of osteoporosis treatment initiation post-hip fracture is low. Systematic solutions will need to be established to ensure that osteoporosis treatment is addressed prior to discharge.

Dissecting the Relationship between Root Morphological Traits and Yield Attributes in Diverse Rice Cultivars under Subtropical Condition.

Understanding the link between root morphological traits and yields is crucial for improving crop management. To evaluate this link, a pot experiment was conducted in the net house of the Department of Agronomy, Bangladesh Agricultural University, Mymensingh, Bangladesh during the boro(dry season irrigated) rice growing season of 2019-20. Thirteen cultivars, named BRRI dhan29, BRRI dhan58, BRRI dhan67, BRRI dhan74, BRRI dhan81, Binadhan-8, Binadhan-10, Hira-2, Tej gold, SL8H, Jagliboro, Rata boro, and Lakhai, were used following a completely randomized design (CRD) with three replications. The cultivars were screened for root number (RN), root length (RL), root volume (RV), root porosity (RP), leaf area index (LAI), total dry matter (TDM), and grain yield (GY). A considerable variation in root traits, LAI, and TDM were found among the studied cultivars, and the highest GY (26.26 g pot-1)was found for Binahan-10. Thirteen cultivars were grouped into three clusters using hierarchical cluster analysis, where clusters 1, 2, and 3 assembled with 3, 5, and 5 cultivars, respectively. Considering all of the studied traits, Cluster 3 (Binadhan-10, Hira-2, BRRI dhan29, BRRI dhan58, and Tejgold) showed promise, followed by Cluster 2 (BRRI dhan81, BRRI dhan67, SL8H, BRRI dhan74, and Binadhan-8). Principal component analysis (PCA) revealed that the RV, RDW, RFW, TDM, and GY are effective traits for rice cultivation.

Changes in viable bacterial counts and physicochemical parameters of water used during live transportation of Pangasius catfish (Pangasianodon hypophthalmus) in Bangladesh.

Objective: The study was undertaken to assess the changes in viable bacterial counts and physicochemical parameters of water used during the live transportation of Pangasius catfish (Pangasianodon hypophthalmus). The correlations between the changing patterns of these parameters were also established. Materials and Methods: Water samples were collected every 2 h interval, plated onto agar plates for assesing viable bacterial counts. Physicochemical parameters, namely, water temperature, dissolved oxygen (DO), pH, and ammonia (NH3) concentration in the water were measured with a glass thermometer, DO test kit, pH test kit, and total NH3 measurement kit, respectively. Results: The viable bacterial counts increased significantly from 0 to 2 h in all the studied channels and remained almost similar up to the end of the supply channels. The water temperature was almost stable regardless of the supply channels and transportation period at around 30°C. The DO concentration and pH level decreased, and NH3 concentrations increased gradually in all the supply channels. The viable bacterial counts were inversely correlated to the DO levels and directly associated with the NH3 concentrations of the water used during the live transportation of Pangasius catfish. Conclusions: Gradual increase in viable bacterial counts and fluctuation in some vital physicochemical parameters with the duration of transportation indicated an unfavorable environment for the survival of Pangasius catfish.

Analysis of the active components and mechanism of Shufeng Jiedu capsule against COVID-19 based on network pharmacology and molecular docking.

ABSTRACT: This study investigates the active components and mechanism of Shufeng Jiedu Capsules (SFJDC) against novel coronavirus through network pharmacology and molecular docking.The TCMSP, TCMID, and BATMAN-TCM databases were used to retrieve the components of SFJDC. The active components were screened by ADME (absorption, distribution, metabolism, and excretion) parameters, and identified by Pubchem, Chemical Book, and ChemDraw softwares. The molecular docking ligands were constructed. SARS Coronavirus-2 Major Protease (SARS-CoV-2-Mpro) and angiotension converting enzyme 2 (ACE2) were used as molecular docking receptors. AutoDock software was used for molecular docking. Cytoscape 3.7.1 software was used to generate an herbs-active components-targets network. Gene Ontology gene function and Kyoto Encyclopedia of Genes and Genomes signal pathway analysis were performed by DAVID data.A total of 1244 components were identified from SFJDC, and 210 active components were obtained. Among them, 97 active components were used as docking ligands to dock with SARS-CoV-2-Mpro and ACE2. There were 48 components with good binding activity to SARS-CoV-2-Mpro. Ten active components (including 7-Acetoxy-2-methylisoflavone, Kaempferol, Quercetin, Baicalein, Glabrene, Glucobrassicin, Isoglycyrol, Wogonin, Petunidin, and Luteolin) combined with SARS-CoV-2-Mpro and ACE2 simultaneously. Among them, Kaempferol, Wogonin, and Baicalein showed higher binding activity. The herbs-active components-targets network contained 7 herbs, 10 active components, and 225 targets. The 225 target targets were involved in 653 biological processes of Gene Ontology analysis and 130 signal pathways (false discovery rate ≤ 0.01) of Kyoto Encyclopedia of Genes and Genomes analysis.The active components of SFJDC (such as Kaempferol, Wogonin, and Baicalein) may combine with ACE2 and act on multiple signaling pathways and targets to exert therapeutic effect on novel coronavirus.

Mechanism of Dried Fruiting Bodies of Fomes officinalis Against Alzheimer's Disease： Based on Network Pharmacology and In Vitro Experimental Verification / 中国实验方剂学杂志

ObjectiveTo explore the possible mechanism of dried fruiting bodies of Fomes officinalis （FOA） against Alzheimer's disease （AD） based on network pharmacology and experimental verification. MethodThe effective components of FOA were retrieved from a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM） and previous reports. The targets of the components were searched from PharmMapper and TargetNet， and the targets related to AD from Gene Expression Omnibus （GEO）， DrugBank， among other databases. Thereby， the common targets of FOA and AD were obtained， and the protein-protein interaction （PPI） network and component-target network were established based on STRING and Cytoscape 3.7.1， followed by the topology analysis of the networks， and Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis of the common targets. The results were verified by the molecular docking and the in vitro cell experiment. ResultA total of 24 candidate components and 242 predicted targets of FOA， and 96 common targets of FOA and AD were screened out. The key components included ［2-（1-carboxyhexadecylamino）-2-aminosuccinic acid］， 3-keto-dehydrosulfurenic acid， and eburicoic acid， and the active targets were albumin （ALB）， acetylcholinesterase （AChE）， estrogen receptor 1 （ESR1）， cysteine aspartate-specific protease-3 （Caspase-3）， and beta-secretase1 （BACE1）. The common targets were involved in 392 GO terms， and the key terms were the β-amyloid metabolic process and cholinesterase activity. A total of 77 KEGG pathways were obtained， which mainly included estrogen signaling pathway， cholinergic synapse， and AD. The results of molecular docking showed that 7 components of FOA had high binding affinity to amyloid precursor protein （APP）， BACE1， AChE， and Caspase-3. The cell survival rate rose （P<0.01） and the mRNA and protein expression of APP， BACE1， AChE， and Caspase-3 reduced in FOA groups in a dose-dependent manner compared with those in the model group （P<0.05）. ConclusionThis study reveals for the first time that FOA has multi-component， multi-target， and multi-pathway characteristics in the treatment of AD， which serves as a reference for further explaining the mechanism of FOA against AD.

Efficacy and safety of recombinant Bifidobacterium breve carrying HPV16 E7 shRNA and IL-12 gene against mouse cervical cancer xenografts / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：评价口服携带HPV16 E7 shRNA和IL-12基因的重组短双歧杆菌在小鼠体内抗宫颈癌移植瘤的效果。方法：将pMG36e-E7 shRNA、pMG36e-mIL-12D质粒分别转化短双歧杆菌，经筛选鉴定并扩增获得携带HPV16 E7 shRNA和IL-12 基因的重组短双歧杆菌。通过小鼠皮下宫颈癌细胞移植建立荷瘤小鼠模型。口服重组短双歧杆菌1、7 d后，检测小鼠主要器官（心、肝、脾、肺、肾）和肿瘤组织匀浆液或血清在PYG培养基中形成的菌落数量，评价短双歧杆菌的肿瘤靶向性，以小鼠体内肿瘤生长曲线评估重组短双歧杆菌的抗肿瘤效果，通过主要器官切片H-E染色和检测荷瘤小鼠血清相关细胞因子水平评价口服重组短双歧杆菌的安全性。结果：成功制备重组短双歧杆菌和宫颈癌TC-1细胞移植瘤小鼠。7 d后，移植瘤组织匀浆液和血清的菌落数量证实短双歧杆菌具有靶向体内瘤组织的定殖能力，口服重组短双歧杆菌明显抑制荷瘤小鼠的肿瘤生长（P<0.05或P<0.01），但联合使用携带HPV16 E7 shRNA和IL-12基因的重组双歧杆菌的肿瘤抑制率与单独使用的并无显著差异，治疗后未见对荷瘤小鼠主要器官的损伤和血清中IL-12及IFN-γ的水平明显变化。结论：短双歧杆菌可用作靶向肿瘤的治疗性基因分子递送载体，其对宫颈癌移植瘤的疗效明显且安全可控。

Assessment of small intestinal bacterial overgrowth in Alzheimer's disease.

There is great interest in crosstalk between the gastrointestinal and immune systems. Small intestinal bacterial overgrowth (SIBO) is a bowel disorder prevalent among patients with Parkinson's disease; SIBO treatment has been shown to modulate neurological inflammation, motor and cognitive outcomes there. However, to date, no link between Alzheimer's dementia and SIBO has been established. This pilot study sought to estimate the prevalence of SIBO in Alzheimer's dementia in the outpatient setting in Singapore General Hospital. It entailed performing a hydrogen breath test and objectively scoring gastrointestinal symptoms and their severity in 48 patients, comparing symptom scores and mean breath test values in those with mild to moderate Alzheimer's against age- and sex-matched controls that did not fulfill DSM-V criteria for probable Alzheimer's. Here, the prevalence of positive breath tests and symptoms of SIBO were no greater among Alzheimer's patients than in controls. This suggests that the gut microbiome changes and increased bowel inflammation seen in previous studies on Alzheimer's patients are likely effected through pathways other than SIBO, and are likely more complex than a mere increase in small bowel bacterial volume. Rather, future research could be directed along the lines of qualitative changes in small bowel microbiota, or pathologies in other parts of the gastrointestinal tract such as the colon or stomach, aspects which are not adequately captured by the hydrogen breath test. Keywords: Alzheimer's disease; dementia; gut-brain axis; small intestinal bacterial overgrowth; microbiome.

Treatment of dementia and mild cognitive impairment with or without cerebrovascular disease: Expert consensus on the use of Ginkgo biloba extract, EGb 761®.

BACKGROUND: The Ginkgo biloba special extract, EGb 761® has been widely used in the treatment of neuropsychiatric disorders, including Alzheimer's disease (AD). METHODS: To guide clinical practice in the Asian region, the Asian Clinical Expert Group on Neurocognitive Disorders compiled evidence-based consensus recommendations regarding the use of EGb 761® in neurocognitive disorders with/without cerebrovascular disease. RESULTS: Key randomized trials and robust meta-analyses have demonstrated significant improvement in cognitive function, neuropsychiatric symptoms, activities of daily living (ADL) and quality of life with EGb 761® versus placebo in patients with mild-to-moderate dementia. In those with mild cognitive impairment (MCI), EGb 761® has also demonstrated significant symptomatic improvement versus placebo. World Federation of Societies of Biological Psychiatry guidelines list EGb 761® with the same strength of evidence as acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) antagonists e.g. memantine (Grade 3 recommendation; Level B evidence). Only EGb 761® had Level B evidence in improving cognition, behaviour, and ADL in both AD and vascular dementia patients. Safety analyses show EGb 761® to have a positive risk-benefit profile. While concerns have been raised regarding a possible increased bleeding risk, several randomized trials and two meta-analyses have not supported this association. CONCLUSIONS: The Expert Group foresee an important role for EGb 761® , used alone or as an add-on therapy, in the treatment of MCI and dementias, particularly when patients do not derive benefit from acetylcholinesterase inhibitors or NMDA antagonists. EGb 761® should be used in alignment with local clinical practice guidelines.

Project Octo-Pills-Engaging community pharmacists in the care of patients from a tertiary hospital: A pilot study.

OBJECTIVE: To evaluate the effectiveness of a pilot model engaging community pharmacists in the collaborative care of patients from a tertiary hospital, in terms of identification and resolution of drug-related problems (DRPs), and patients' acceptance and satisfaction with the program. METHODS: A prospective case series was conducted. Eligible patients were recruited from the tertiary hospital and referred to their preferred community pharmacy for medication reconciliation, review, and counseling. The number and types of DRP identified and resolved during or after the medication review were collated. A patient survey was conducted upon completion of the study. RESULTS: A total of 32 participants completed the study. A total of 63 DRPs were identified from 379 medications reviewed, and 60 (95.2%) were resolved by the community pharmacists. Failure to receive drug (n = 21, 33.3%) and drug interactions (n = 11, 17.5%) were the most common DRPs. Survey feedback indicated that the service was well received. CONCLUSION: In this model, community pharmacists can play an important role in identifying and resolving DRPs by providing patients with medication reconciliation and review services from a more convenient location within their neighborhood.

Project Octo-Pills - A practice model engaging community pharmacists in the care of patients from a tertiary hospital.

Even while pharmacy practice evolves to a more patient-centric mode of practice, local hospitals, due to high patient load as well as space and resource constraints, find it challenging to conduct thorough medication review and physical medication reconciliation for all patients. In light of this, optimizing the local current healthcare system to involve community pharmacists in the care of patients from public hospitals could potentially better cater to the healthcare needs of the older population. Due to easy accessibility, community pharmacies are often the first point of contact in the healthcare system. Project Octo-Pills aims to engage community pharmacists in the collaborative care of patients from a tertiary hospital, providing patients with quality medication reconciliation and review services from a more convenient location within their neighborhood. This paper describes the model for this pilot initiative.

Function projective synchronization of memristor-based Cohen-Grossberg neural networks with time-varying delays.

This paper deals with the problem of function projective synchronization for a class of memristor-based Cohen-Grossberg neural networks with time-varying delays. Based on the theory of differential equations with discontinuous right-hand side, some novel criteria are obtained to realize the function projective synchronization of addressed networks by combining open loop control and linear feedback control. As some special cases, several control strategies are given to ensure the realization of complete synchronization, anti-synchronization and the stabilization of the considered memristor-based Cohen-Grossberg neural network. Finally, a numerical example and its simulations are provided to demonstrate the effectiveness of the obtained results.

Comparison between elderly inpatient fallers with and without dementia.

INTRODUCTION: This study aimed to examine the various factors associated with inpatient falls among patients with and without dementia in a hospital setting. METHODS: This was a retrospective one-year study using data collected from Singapore General Hospital's electronic reporting system for inpatient falls. RESULTS: In the study period, 298 patients aged ≥ 65 years fell during their hospital stay. The majority of the patients (n = 248) did not have dementia. In our study, fallers with dementia were more likely to use ambulatory aids, be visually impaired and have urinary incontinence. More patients with dementia than those without had a history of previous falls, and were placed on fall precaution with restricted freedom of movement, which at times, included restraints. However, the difference between patients who were put on restraints and those who were allowed to move freely was not statistically significant. The majority of falls in both groups occurred at the bedside. We found that fallers without dementia were more likely to fall during the morning shift, whereas fallers with dementia were more likely to fall during the night shift. Fallers with dementia were more likely to be confused at the time of the fall. CONCLUSION: In our study, we found that fallers with dementia were more likely to have visual impairment, have urinary incontinence, use walking aids, and to be confused and physically restrained at the time of the fall. The fallers without dementia in our study may have undiagnosed dementia.