Background: Early-onset Alzheimer's disease (EOAD) presents a different clinical profile than late-onset Alzheimer's disease (LOAD). Neuroimaging studies have demonstrated that patients with EOAD present more atrophy and functional disconnection than LOAD patients. However, it remains unknown whether the interhemispheric functional disconnection or its underlying structural impairment contributes to the different clinical profiles of EOAD and LOAD. Methods: According to the arbitrary cut-off age of 65, we included 22 EOAD patients, 27 LOAD patients and 38 healthy controls (further divided into 21 relatively young and 17 old controls). Participants underwent resting-state functional MRI, diffusion tensor imaging (DTI) and comprehensive neuropsychological assessments. We used voxel-mirrored homotopic connectivity (VMHC) to examine interhemispheric functional connectivity. Then, we calculated the diffusion index based on tract-based spatial statistics (TBSS). Two-sample t-tests were used to assess the interhemispheric connectivity differences between each patient group and its corresponding control group. Results: We found that the EOAD patients had lower VMHC in the hippocampus, parahippocampal gyrus (PHG), superior temporal gyrus (STG) and inferior parietal cortex (IPC) than did controls. Consistently, the EOAD patients exhibited white matter (WM) tract impairment in the posterior regions. On the other hand, the LOAD patients displayed increased VMHC and impaired WM tracts in the frontal region. Correlation analyses showed that VMHC in the IPC was related to executive function in the EOAD patients (r = -0.67, P < 0.05). Conclusion: In contrast to the LOAD patients, patients with EOAD exhibited more widely disrupted interhemispheric functional and structural connectivity, which overlapped well across brain regions. In addition, for the EOAD patients, decreased interhemispheric connectivity related to executive deficits. Our study suggested that different interhemispheric connectivity damage patterns may contribute to the distinct clinical profiles in EOAD and LOAD.

Delivery of gene therapy as well as of biologic therapeutics is often hampered by the immune response of the subject receiving the therapy. We have reported that effective gene therapy for hemophilia utilizing platelets as a delivery vehicle engenders profound tolerance to the therapeutic product. In this study, we investigated whether this strategy can be applied to induce immune tolerance to a non-coagulant protein and explored the fundamental mechanism of immune tolerance induced by platelet-targeted gene delivery. We used ovalbumin (OVA) as a surrogate non-coagulant protein and constructed a lentiviral vector in which OVA is driven by the platelet-specific αIIb promoter. Platelet-specific OVA expression was introduced by bone marrow transduction and transplantation. Greater than 95% of OVA was stored in platelet α-granules. Control mice immunized with OVA generated OVA-specific IgG antibodies; however, mice expressing OVA in platelets did not. Furthermore, OVA expression in platelets was sufficient to prevent the rejection of skin grafts from CAG-OVA mice, demonstrating that immune tolerance developed in platelet-specific OVA-transduced recipients. To assess the mechanism(s) involved in this tolerance we used OTII mice that express CD4+ effector T cells specific for an OVA-derived peptide. After platelet-specific OVA gene transfer, these mice showed normal thymic maturation of the T cells ruling against central tolerance. In the periphery, tolerance involved elimination of OVA-specific CD4+ effector T cells by apoptosis and expansion of an OVA-specific regulatory T cell population. These experiments reveal the existence of natural peripheral tolerance processes to platelet granule contents which can be co-opted to deliver therapeutically important products.

CD169+ macrophages are part of the innate immune system and capture pathogens that enter secondary lymphoid organs such as the spleen and the lymph nodes. Their strategic location in the marginal zone of the spleen and the subcapsular sinus in the lymph node enables them to capture antigens from the blood and the lymph respectively. Interestingly, these specific CD169+ macrophages do not destroy the antigens they obtain, but instead, transfer it to B cells and dendritic cells (DCs) which facilitates the induction of strong adaptive immune responses. This latter characteristic of the CD169+ macrophages can be exploited by specifically targeting tumor antigens to CD169+ macrophages for the induction of specific T cell immunity. In the current study we target protein and peptide antigen as antibody-antigen conjugates to CD169+ macrophages. We monitored the primary, memory, and recall T cell responses and evaluated the anti-tumor immune responses after immunization. In conclusion, both protein and peptide targeting to CD169 resulted in strong primary, memory, and recall T cell responses and protective immunity against melanoma, which indicates that both forms of antigen can be further explored as anti-cancer vaccination strategy.

Bruton's tyrosine kinase (Btk) has a key role in the signaling pathways of receptors essential for the B lymphocyte response. Given its implication in B cell-related immunodeficiencies, leukemias/lymphomas and autoimmunity, Btk is studied intensely and is a target for therapy. Here, using primary B cells from distinct mouse models and the pharmacological inhibitors ibrutinib and acalabrutinib, we report distinct roles for Btk in antigen-triggered immune synapse (IS) formation. Btk recruitment to the plasma membrane regulates the B cell ability to trigger IS formation as well as its appropriate molecular assembly; Btk shuttling/scaffold activities seem more relevant than the kinase function on that. Btk-kinase activity controls antigen accumulation at the IS through the PLCγ2/Ca2+ axis. Impaired Btk membrane-recruitment or kinase function likewise alters antigen-triggered microtubule-organizing center (MTOC) polarization to the IS, B cell activation and proliferation. Data also show that, for B cell function, IS architecture is as important as the quantity of antigen that accumulates at the synapse.

There are no biomarkers to facilitate the identification of patients with ulcerative colitis (UC) who are at high risk for developing colorectal cancer (CRC). In our current study, we used rectal tissues from UC patients to identify aberrant DNA methylations and evaluated whether they could be used to identify UC patients with coexisting colorectal neoplasia.

Recurrence of non-muscle invasive bladder cancer (NMIBC) after initial management occurs in 60-70% of patients. Predictive criteria for recurrence remain only clinical and pathological. The aim of this study was to investigate the prognostic significance of the proportion of checkpoint HLA-G's receptor ILT2-expressing peripheral CD8+ T cells.

Previous systematic reviews have concluded that lumbar traction is not effective for patients with low back pain (LBP), yet many clinicians continue to assert its clinical effectiveness.

Anemia in pregnancy may not only be associated with maternal morbidity and mortality but can also be detrimental to the fetus. A definitive diagnosis of anemia is a pre-requisite to unravelling possible cause(s), to allow appropriate treatment intervention. It is hypothesised that measured hemoglobin (HGB), complemented by biochemical and other hematological parameters would enhance anemia diagnosis.

Preeclampsia (PE) is a serious maternal complication during pregnancy. Associated arterial stiffness in PE patients leads to increased risks of cardiovascular diseases later in life. Cholesterol efflux capacity, especially ATP binding cassette transporter A1 (ABCA1) dependent capacity, has been proposed to be a likely mediator of arterial stiffness. In the present study, we aimed to evaluate the effect of an apolipoprotein A1 mimetic peptide ATI-5261 on arterial stiffness in a mouse model of PE.

Given the high morbidity and the trend of younger individuals being affected observed in cervical cancer, it is important to identify sensitive and effective biomarkers for predicting the survival outcome of patients. Based on data from 307 cervical cancer cases acquired from The Cancer Genome Atlas portal, 1920 differentially expressed mRNAs, 70 microRNAs(miRNAs), and 493 long non-coding(lncRNAs) were screened by comparing cervical cancer tissues with paracancerous tissues. A competing endogenous (ceRNA) network containing 50 lncRNAs, 16 miRNAs, and 81 mRNAs was constructed. Eighteen RNAs, comprising 13 mRNAs, 2 miRNAs, and 3 lncRNAs, were identified as significant prognostic factors by univariate Cox proportional hazards regression. ETS-related gene and fatty acid synthase signatures were discovered using a multivariate Cox regression model built to identify independent prognostic factors in cervical cancer patients. Receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off value for distinguishing the risk level of cervical cancer patients. High-risk patients exhibited a poorer prognosis than low-risk patients did. This study focused on ceRNA networks to provide a novel perspective and insight into cervical cancer and suggested that the identified signature can serve as an independent prognostic biomarker in cervical cancer.

We provide reflectance spectra for 22 South African palmiet wetland species collected in spring 2015 from three wetlands throughout the Cape Floristic Region. In addition, we provide summarized plant functional trait data, as well as supporting and meta-data. Reflectance spectra were collected with a portable ASD Fieldspec Pro using standard methods. The 14 plant functional traits were measured on 10 replicates of each species, following standard protocols. We provide tables detailing these standard methods, as well a table with hypotheses on how these 14 continuous traits, as well as an additional 9 categorical traits, may affect ecosystem service provision. In addition, tables are attached which detail which functional and spectral groups these species belong to, according to the data. Finally, we include a photographic plate of the species data are provide for. We make these data available in an effort to assist in research on the understanding of how traits affect ecosystem service provision in wetlands, and particularly of whether remote sensing can be used to map these traits in wetlands.

Recent studies indicate a stage-specific, differential role for the oncogene Akt on various cancers. In prostate cancer (PCa), suppression of Akt activity in the advanced stages promoted transforming growth factor-β (TGFβ) pathway-mediated epithelial-to-mesenchymal transition (EMT) and metastasis to the lungs. In the current study, we performed Affymetrix analysis to compare the expression profile of microRNAs in the mouse prostate tissues collected at the prostatic inter-epithelial neoplasia (PIN) stage from Transgenic adenocarcinoma of the mouse (TRAMP)/Akt1+/+ versus TRAMP/Akt1-/- mice, and at the advanced stage from TRAMP/Akt1+/+ mice treated with triciribine (Akt inhibitor) versus DMSO-treated control. Our analysis demonstrates that in the early stage, Akt1 in the TRAMP prostate tumors express a set of miRNAs responsible for regulating cancer cell survival, proliferation, and tumor growth, whereas, in the advanced stages, a different set of miRNAs that promote EMT and cancer metastasis is expressed. Our study has identified novel Akt-regulated signature microRNAs in the early and advanced PCa and demonstrates their differential effects on PCa growth and metastasis.

The purpose of this literature review was to examine the existing patient-reported outcome measurement literature to understand the empirical evidence supporting response scale selection in pain measurement for the adult population.

Identification of fungal species based on morphological characteristics is tedious, complex, prone to errors, and thus cannot be completely relied upon. In this study, internal transcribed spacers (ITS 1 and 4)-polymerase chain reaction was employed to amplify DNA of 19 mushroom isolates collected at Environmental Pollution Science and Technology farm, Ilesa, Southwest Nigeria. The PCR amplification of ITS1 and 4 of the mushrooms isolates yielded approximately 850 bp. Amplicons obtained were sequenced and identified using BLASTn in the NCBI. The BLASTn results revealed that Termitomyces aurantiacus (3), Tricholoma matsutake (8), Tricholoma robustum (2), P. ostreatus (4), Schizophyllum commune (1) and Pleurotus pulmonarius (1) were fully represented. Only Tricholoma matsutake (KT273371), Pleurotus pulmonarius (KY962469) and Tricholoma matsutake (AF438605) had 100% similarity with reference strain. However, the phylogenetic analysis of the isolates showed low genetic relatedness with reference strains. This study revealed the novelty of the mushroom strains and thus advocating the need for strict conservation measures and further investigations on their potential benefits to mankind.

Swimming-induced pulmonary oedema (SIPE) can affect people with no underlying health problems, but may be life threatening and is poorly understood. The aim of this systematic review was to synthesise the evidence on SIPE incidence, prevalence, risk factors, short- and long-term outcomes, recurrence and effectiveness of interventions to prevent recurrences.

Resistance of bacteria and fungi to antibiotics is one of the biggest problems that faces public health. The present work was designated to evaluate the antimicrobial activities of saponins from Melanthera elliptica and their synergistic effects with standard antibiotics against pathogenic phenotypes. The plant extract was prepared by maceration in methanol. The methanol extract was partitioned into ethyl acetate and n-butanol extracts. Column chromatography of the n-butanol extract followed by purification of different fractions led to the isolation of four saponins. Their structures were elucidated on the basis of spectra analysis, and by comparison with those from the literature. The antimicrobial activities of the extracts/compounds alone and their combinations with tetracycline and fluconazole were evaluated using the broth microdilution method through the determination of minimum inhibitory concentration (MIC) and minimum microbicidal concentration.

Alzheimer's disease (AD), probably caused by abnormal accumulation of β-amyloid (Aβ) and aberrant phosphorylation of tau, is the most common cause of dementia among older people. Generation of patient-specific neurons by induced pluripotent stem cell (iPSC) technology facilitates exploration of the disease features in live human neurons from AD patients. In this study, we generated iPSCs from two familial AD patients carrying a heterozygous D678H mutation in the APP gene (AD-iPSCs). The neurons derived from our AD-iPSCs demonstrated aberrant accumulation of intracellular and secreted Aβ42 and Aβ40, reduction of serine 9 phosphorylation in glycogen synthase kinase 3β (GSK3β) hyperphosphorylation of threonine 181 and serine 396 in tau protein, impaired neurite outgrowth, downregulation of synaptophysin, and increased caspase 1 activity. The comparison between neurons derived from a sibling pair of wild-type and mutated iPSCs successfully recapitulated these AD phenotypes. Treatment with indole compound NC009-1 (3-((1H-Indole-3-yl)methyl)-4-(2-nitrophenyl)but-3-en-2-one), a potential Aβ aggregation reducer, normalized the Aβ levels and GSK3β and tau phosphorylation, attenuated caspase 1 activity, and improved neurite outgrowth in AD-iPSC-derived neurons. Thus, APP D678H iPSCs-derived neurons recapitulate the cellular characteristics relevant to AD and enable exploration of the underlying pathogenesis and therapeutic strategies for AD.

In Alzheimer's disease, the phosphorylation of tau is a critical event preceding the formation of neurofibrillary tangles. Previous work exploring the impact of a dopamine blocking antipsychotic on tau phosphorylation in a tau transgenic model suggested that extracellular dopamine may play a regulatory role in the phosphorylation state of tau. In order to test this hypothesis, and in order to develop a mouse model of impaired dopamine metabolism and tauopathy, an extant P301L transgenic tau model of Alzheimer's disease and a novel P301L/catechol-O-methyltransferase deleted model (DM mouse) were treated with the norepinephrine reuptake inhibitor reboxetine, and prefrontal dopamine concentrations and the phosphorylated state of tau was quantified. In two experiments, male and female P301L+/+//COMT+/+ and P301L+/+//COMT-/- (DM) mice were treated with reboxetine 20 mg/kg IP. In one experiment, acutely following reboxetine injection, the prefrontal cortex of mice were microdialyzed for dopamine, and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, utilizing the MetaQuant technique. In another experiment, acutely following reboxetine injections, tau phosphorylation was quantified in the frontal cortex, striatum, and hippocampus of the mice. Reboxetine injections were followed by significant increases from baseline in extracellular dopamine concentrations in P301L and DM mice, with significantly higher peak levels in the DM mice. Treatment was also followed by increases in tau phosphorylation spread throughout brain regions, with a larger impact on female mice. Extracellular dopamine concentrations exert an influence on the phosphorylation state of tau, with surges in dopamine associating with acute increases in tau phosphorylation.

Hyperinsulinaemic hypoglycaemia (HH) can occur in isolation or more rarely feature as part of a syndrome. Screening for mutations in the "syndromic" HH genes is guided by phenotype with genetic testing used to confirm the clinical diagnosis. As HH can be the presenting feature of a syndrome, it is possible that mutations will be missed as these genes are not routinely screened in all newly diagnosed individuals. We investigated the frequency of pathogenic variants in syndromic genes in infants with HH who had not been clinically diagnosed with a syndromic disorder at referral for genetic testing.

This study aims to evaluate the genetic and population structure of Vibrio parahaemolyticus in the major coastal regions of China.