Biofilms and Helicobacter pylori: Dissemination and persistence within the environment and host

The presence of viable Helicobacter pylori(H. pylori) in the environment is considered to contribute to the levels of H. pylori found in the human population, which also aids to increase its genetic variability and its environment adaptability and persistence. H. pylori form biofilms both within the in vitro and in vivo envi-ronment. This represents an important attribute that assists the survival of this bacterium within environ-ments that are both hostile and adverse to prolifera-tion. It is the aim of this paper to review the ability of H. pylori to form biofilms in vivo and in vitro and to address the inherent mechanisms considered to sig-nificantly enhance its persistence within the host and in external environments. Furthermore, the dissemi-nation of H. pylori in the external environment and within in the human body and its impact upon infec-tion control shall be discussed.

Standardization of choroidal thickness measurements using enhanced depth imaging optical coherence tomography

AIM: To describe and evaluate a standardized protocol for measuring the choroidal thickness(Ch T) using enhanced depth imaging optical coherence tomography(EDI OCT).METHODS: Single 9 mm EDI OCT line scans across the fovea were used for this study. The protocol used in this study classified the EDI OCT images into four groups based on the appearance of the choroidal-scleral interface and suprachoroidal space. Two evaluation iterations of experiments were performed: first, the protocol was validated in a pilot study of 12 healthy eyes. Afterwards, the applicability of the protocol was tested in 82 eyes of patients with diabetes. Inter-observer and intra-observer agreements on image classifications were performed using Cohen’s kappa coefficient(κ). Intraclass correlation coefficient(ICC) and Bland-Altman’s methodology were used for the measurement of the Ch T.RESULTS: There was a moderate(κ=0.42) and perfect(κ =1) inter- and intra-observer agreements on image classifications from healthy eyes images and substantial(κ =0.66) and almost perfect(κ =0.86) agreements from diabetic eyes images. The proposed protocol showed excellent inter- and intra-observer agreements for the Ch T measurements on both, healthy eyes and diabetic eyes(ICC 】0.90 in all image categories). The Bland-Altman plot showed a relatively large Ch T measurement agreement in the scans that contained less visible choroidal outer boundary. CONCLUSION: A protocol to standardize Ch T measurements in EDI OCT images has been developed;the results obtained using this protocol show that the technique is accurate and reliable for routine clinical practice and research.

Stability of freeze-dried pH-responsive dextrin nanogels containing doxorubicin

Induction of non-specific toxicities by doxorubicin(DOX) has restricted conventional DOXbased chemotherapy. p H-responsive dextrin nanogels(DNGs) have been fabricated in order to incorporate and deliver DOX to specific(targeted) sites. However, adequate stability studies of DOX-loaded DNGs are required for selection of storage conditions. The aim of this study was therefore to evaluate the accelerated(25 °C/60% RH) and long-term(5 °C) stability of DNGs prepared with formaldehyde(FDNGs) and glyoxal(GDNGs) as cross-linker by determining the change in their physicochemical properties. The mean diameter decreased with time during long-term storage. The drug content between freshly prepared(initial day) and after storage at 5 °C for 180 days of DOX-loaded FDNGs and DOX-loaded GDNGs was not significantly different(p > 0.05), but decreased after storage under the accelerated condition. The release of DOX from all DNGs was pH-dependent. However, DNGs kept under the accelerated condition showed higher amount of DOX release than those stored at 5 °C and the freshly prepared ones. The results indicate that the stability of DNGs could be improved by their storage at 5 °C.

降脂药理学有什么新进展?整合基础研究和临床研究以改善患者治疗结果

自20世纪90年代以来,使用他汀类药物(以下简称他汀)一直是降脂治疗的主要方法。大量大规模随机对照试验表明,使用他汀疗法一年后,低密度脂蛋白(LDL)每年降低约1 mmol·L^(-1),主要心血管事件的风险降低约25%[1]。最近降脂领域的讨论集中在新的降脂药上,尤其是pro-protein convertase subtilisin/kexin type 9(PCSK9)抑制剂。

Altered white matter microarchitecture in Parkinson’s disease:a voxel-based meta-analysis of diffusion tensor imaging studies

This study aimed to define the most consistent white matter microarchitecture pattern in Parkinson’s disease(PD)reflected by fractional anisotropy(FA),addressing clinical profiles and methodology-related heterogeneity.Web-based publication databases were searched to conduct a meta-analysis of whole-brain diffusion tensor imaging studies comparing PD with healthy controls(HC)using the anisotropic effect size–signed differential mapping.A total of 808 patients with PD and 760 HC coming from 27 databases were finally included.Subgroup analyses were conducted considering heterogeneity with respect to medication status,disease stage,analysis methods,and the number of diffusion directions in acquisition.Compared with HC,patients with PD had decreased FA in the left middle cerebellar peduncle,corpus callosum(CC),left inferior fronto-occipital fasciculus,and right inferior longitudinal fasciculus.Most of the main results remained unchanged in subgroup metaanalyses of medicated patients,early stage patients,voxel-based analysis,and acquisition with˂30 diffusion directions.The subgroup meta-analysis of medication-free patients showed FA decrease in the right olfactory cortex.The cerebellum and CC,associated with typical motor impairment,showed the most consistent FA decreases in PD.Medication status,analysis approaches,and the number of diffusion directions have an important impact on the findings,needing careful evaluation in future meta-analyses.

Machine learning for detecting mesial temporal lobe epilepsy by structural and functional neuroimaging

Mesial temporal lobe epilepsy(mTLE),the most common type of focal epilepsy,is associated with functional and structural brain alterations.Machine learning(ML)techniques have been successfully used in discriminating mTLE from healthy controls.However,either functional or structural neuroimaging data are mostly used separately as input,and the opportunity to combine both has not been exploited yet.We conducted a multimodal ML study based on functional and structural neuroimaging measures.We enrolled 37 patients with left mTLE,37 patients with right mTLE,and 74 healthy controls and trained a support vector ML model to distinguish them by using each measure and the combinations of the measures.For each single measure,we obtained a mean accuracy of 74%and 69%for discriminating left mTLE and right mTLE from controls,respectively,and 64%when all patients were combined.We achieved an accuracy of 78%by integrating functional data and 79%by integrating structural data for left mTLE,and the highest accuracy of 84%was obtained when all functional and structural measures were combined.These findings suggest that combining multimodal measures within a single model is a promising direction for improving the classification of individual patients with mTLE.

Targeting IL-22 and IL-22R protects against experimental osteoarthritis

Osteoarthritis(OA)is characterized by cartilage degradation,pain,and synovitis.1 Joint inflammation driven by cytokines has been demonstrated to cause cartilage degradation and pain.2 However,approaches to neutralize cytokines,such as IL-1 and TNF-α,known to be involved in OA have shown poor clinical efficacy.3 There is an unmet clinical need to find better anti-inflammatory and pain targets for OA therapy and to elucidate the role of other cytokines in OA pathogenesis.Previous studies have shown that IL-22 and its receptor IL-22R play central roles in inflammation and diseases such as psoriasis,ulcerative colitis,graft-versus-host disease,certain infections and tumors,as well as in liver and pancreas damage.4,5 The role of IL-22/IL-22R and the potential for therapeutic targeting of both proteins in OA remain largely unknown,which we sought to investigate.

A feeder-free,human plasma-derived hydrogel for maintenance of a human embryonic stem cell phenotype in vitro

Background:Human embryonic stem cells(hESCs)represent a tremendous resource for cell therapies and the study of human development;however to maintain their undifferentiated state in vitro they routinely require the use of mouse embryonic fibroblast(MEF)feeder-layers and exogenous protein media supplementation.Results:These well established requirements can be overcome and in this study,it will be demonstrated that phenotypic stability of hESCs can be maintained using a novel,human plasma protein-based hydrogel as an extracellular culture matrix without the use of feeder cell co-culture.hESCs were resuspended in human platelet poor plasma(PPP),which was gelled by the addition of calcium containing DMEM-based hESC culture medium.Phenotypic and genomic expression of the pluripotency markers OCT4,NANOG and SOX2 were measured using immunohistochemistry and qRT-PCR respectively.Typical hESC morphology was demonstrated throughout in vitro culture and both viability and phenotypic stability were maintained throughout extended culture,up to 25 passages.Conclusions:PPP-derived hydrogel has demonstrated to be an efficacious alternative to MEF co-culture with its hydrophilicity allowing for this substrate to be delivered via minimally invasive procedures in a liquid phase with polymerization ensuing in situ.Together this provides a novel technique for the study of this unique group of stem cells in either 2D or 3D both in vitro and in vivo.

Protecting against different subtypes of influenza viruses:a nanoparticle approach

A recent article by Wang et al.elegantly synthesized new nanoparticles consisting of cyclic guanosine monophosphate–adenosine monophosphate(cGAMP),which were administered alongside vaccines,to successfully deliver into the lungs of animals leading to protection against different subtypes of influenza infection without inflammatory side effects.

Adiponectin exacerbates influenza infection in elderly individuals via IL-18

Dear Editor,Influenza affects humans of all ages;however,elderly people have increased susceptibility to infections and are especially predisposed to complications.1 A number of global efforts have increased influenza vaccination administration in elderly people to reduce complications,particularly when seasonal influenza infections peak.2 To date,much is known about how influenza infection and host immunity interact during pathogenesis,which has led to a number of vaccines.3,4 However,the impact of influenza vaccines in older people is modest.2 Hence,the underlying pathophysiological mechanisms responsible for the worsening of influenza infection in old age are still elusive.

Mapping the T cell response to COVID-19

A recent article by Grifoni et al.elegantly demonstrated the ability to measure and understand the human CD4+and CD8+T cell responses to SARS-CoV-2 infection.1 These findings highlighted below gave new insights into the immunopathogenesis of COVID-19,the crossreactivity of the SARS-CoV-2 infections,the potential targets of T cells,and for vaccine design.

T_(H)17 cells...Sorting the good out from the bad

A recent article by Wu et al.1 demonstrated how targeting inflammatory TH17 cells can be achieved by blocking glycolysis pathway genes.These findings could lead to potential drugs to selective target“bad”inflammatory TH17 cells,while not disturbing“good”homeostatic TH17 cells in patients with autoimmune diseases.