Transactions of The Faraday Society最新文献

The liver fulfills many vital functions for the body, among them bile formation and detoxification. Bile salts are organic anions, are the major constituents of bile and are at high concentrations cytotoxic. Detoxification exposes the liver to many harmful compounds. This function is therefore potentially damaging to the liver. Impaired bile formation may lead to hepatic accumulation of bile salts and subsequently to liver disease. Diagnosis of liver diseases involves the measurement of so-called liver function parameters. This overview aims to characterize and summarize the role of organic anion transporters in bile formation at the protein level under normal physiologic conditions and in liver function tests used for diagnosing liver diseases in pathophysiologic situations.

Bacterial flora has clinical significance for the host. The metabolic environment created by this flora influences immunotherapy in urothelial carcinoma. However, there are no reports on the clinical significance of bacterial flora in the host bloodstream. We aimed to clarify the correlation between extracellular vesicle (EV)-derived blood microflora information and tumor immunological status in urothelial carcinoma (UC) patients. Serum samples were collected from 20 healthy donors, 50 patients with localized UC, and 31 patients with metastatic UC (mUC) who had undergone pembrolizumab treatment. Bacterial DNA in EVs was extracted from each sample. Metagenomic sequencing was performed after amplification of the V1-V2 region of the bacterial 16S rRNA gene. Using the matched tumor tissue and serum samples, we revealed that the smaller amount of peripheral EVs carrying Firmicutes DNA was significantly correlated with the higher number of infiltrating T cells within tumor tissues (CD3; p = 0.015, CD4; p = 0.039, CD8; p = 0.0084) and the higher expression of activation markers on their surface (ICOS on both CD4; p = 0.0013 and CD8 T cells; p = 0.016 and 4-1BB on CD4 T cells; p = 0.016). In terms of circulating metabolic information, L-Ser and L-Pro levels, which play important roles in T cell expansion and proliferation, were significantly higher in the Firmicutes-low group (p = 0.010). All of the patients with higher Firmicutes abundance had disease progression without any clinical response (p = 0.026) and significantly inferior prognosis for pembrolizumab therapy (p = 0.035). This is the first study on the importance of peripheral bacterial EVs in cancer patients treated with cancer immunotherapy.

Dementia is a major health concern globally and cross-culturally with progressive decline in cognition, mobility and communication. There are few interventions for end-stage dementia (ESD) although music interventions have been observed to be accessible for people with mid to late-stage dementia. The lack of protocols and measures suited to ESD has limited research into the effects of music therapy. Measure sensitivity to minimal responsiveness is one limitation to the use of existing music intervention measures with ESD. This exploratory study examined the clinical utility of the Music Therapy Assessment Tool for Awareness in Disorders of Consciousness (MATADOC) for use with people with end-stage dementia, including preliminary reliability and validity. The MATADOC is a standardized assessment for minimally responsive patients with disorders of consciousness and may be useful for ESD. Using repeated measures with blinded MATADOC-trained raters, MATADOC data were collected with a small convenience sample of people with ESD in a residential care setting. Clinical utility data were collected from the raters and evaluated using a multidimensional model. To explore its functionality, MATADOC outcomes were compared to another measure for music interventions in dementia. The MATADOC may be useful for assessing functioning and responsiveness to music interventions for people with ESD without the risk of floor effects. Modifying the MATADOC protocol and assessment documentation prior to testing with a larger sample will enhance its sensitivity specific to ESD and age-related needs, providing a new music-based ESD assessment.

Objective: Anaphylaxis is an acute, life-threatening, systemic hypersensitivity reaction. It is usually triggered by drugs, foods, and insect stings. The primary objective of our study is to determine the factors affecting drug-induced anaphylaxis to contribute to early diagnosis and treatment in these patients.

Methods: Patients over 18 years old who were diagnosed drug-induced anaphylaxis in the Goztepe Hospital within a period of 1 year were evaluated prospectively. Patients demographical data, etiological factors, clinical findings, and treatment information were recorded.

Results: Forty-four patients were enrolled in the study of which 25 (56.8%) were female. The median age of women and men was 54 (min: 22, max 82) and 44 (min 18, max 82), respectively. Twenty-three (52%) of them had a history of anaphylaxis. The most common causes of drug-induced anaphylaxis were antibiotics (36%) and nonsteroidal anti-inflammatory drugs (18%), respectively. Adrenaline was applied to 17 (38%) of the patients in the treatment.

Conclusion: Antibiotics were the most common drugs causing drug-induced anaphylaxis and adrenaline was underused which is the first-line treatment in the anaphylaxis. Some clinicians refrain from administering adrenaline. The reasons underlying this approach should be investigated.

Using point-source atom interferometry (PSI), we characterize the sensitivity of a multiaxis gyroscope based on free-space Raman interrogation of a single source of cold atoms in a glass vacuum cell. The instrument simultaneously measures the acceleration in the direction of the Raman-laser beams and the projection of the rotation vector onto the plane perpendicular to that direction. The sensitivities for the magnitude and direction of the rotation-vector measurement are 0.033°/s and 0.27° with an averaging time of 1 s, respectively. The fractional acceleration sensitivity $\delta g/g$ is $1.6\times {10}^{-5}/\surd \text{Hz}$ . The sensitivity can be increased by increasing the Raman interrogation time, allowing the cold-atom cloud to expand further, correcting the fluctuations in the initial cloud shape, and reducing sources of technical noise. PSI resolves a rotation vector in a plane by measuring a phase gradient. This two-dimensional rotation sensitivity may be specifically important for applications such as tracking the precession of a rotation vector and gyrocompassing.

Background: Although high-risk mutations in identified major susceptibility genes (DNA mismatch repair genes and MUTYH) account for some familial aggregation of colorectal cancer, their population prevalence and the causes of the remaining familial aggregation are not known.Methods: We studied the families of 5,744 colorectal cancer cases (probands) recruited from population cancer registries in the United States, Canada, and Australia and screened probands for mutations in mismatch repair genes and MUTYH We conducted modified segregation analyses using the cancer history of first-degree relatives, conditional on the proband's age at diagnosis. We estimated the prevalence of mutations in the identified genes, the prevalence of HR for unidentified major gene mutations, and the variance of the residual polygenic component.Results: We estimated that 1 in 279 of the population carry mutations in mismatch repair genes (MLH1 = 1 in 1,946, MSH2 = 1 in 2,841, MSH6 = 1 in 758, PMS2 = 1 in 714), 1 in 45 carry mutations in MUTYH, and 1 in 504 carry mutations associated with an average 31-fold increased risk of colorectal cancer in unidentified major genes. The estimated polygenic variance was reduced by 30% to 50% after allowing for unidentified major genes and decreased from 3.3 for age <40 years to 0.5 for age ≥70 years (equivalent to sibling relative risks of 5.1 to 1.3, respectively).Conclusions: Unidentified major genes might explain one third to one half of the missing heritability of colorectal cancer.Impact: Our findings could aid gene discovery and development of better colorectal cancer risk prediction models. Cancer Epidemiol Biomarkers Prev; 26(3); 404-12. ©2016 AACR.

During chronic lentiviral infection, poor clinical outcomes correlate both with systemic inflammation and poor proliferative ability of HIV-specific T cells; however, the connection between the two is not clear. Myeloid-derived suppressor cells (MDSC), which expand during states of elevated circulating inflammatory cytokines, may link the systemic inflammation and poor T cell function characteristic of lentiviral infections. Although MDSC are partially characterized in HIV and SIV infection, questions remain regarding their persistence, activity, and clinical significance. We monitored MDSC frequency and function in SIV-infected rhesus macaques. Low MDSC frequency was observed prior to SIV infection. Post-SIV infection, MDSC were elevated in acute infection and persisted during 7 mo of combination antiretroviral drug therapy (cART). After cART interruption, we observed MDSC expansion of surprising magnitude, the majority being granulocytic MDSC. At all stages of infection, granulocytic MDSC suppressed CD4+ and CD8+ T cell proliferation in response to polyclonal or SIV-specific stimulation. In addition, MDSC frequency correlated significantly with circulating inflammatory cytokines. Acute and post-cART levels of viremia were similar, however, the levels of inflammatory cytokines and MDSC were more pronounced post-cART. Expanded MDSC during SIV infection, especially during the post-cART inflammatory cytokine surge, likely limit cellular responses to infection. As many HIV curative strategies require cART interruption to determine efficacy, our work suggests treatment interruption-induced MDSC may especially undermine the effectiveness of such strategies. MDSC depletion may enhance T cell responses to lentiviral infection and the effectiveness of curative approaches.

The transversely-dividing flabellids consist of five genera (Truncatoflabellum, Placotrochides, Blastotrochus, Placotrochus, and Falcatoflabellum) and 45 species. A dichotomous key is provided for these five genera as well as the species of the genus Truncatoflabellum and Placotrochides, the other three genera being monotypic. A tabular key is also provided for the 38 species of Truncatoflabellum. Two new combinations are suggested (Truncatoflabellum gambierense and Truncatoflabellum sphenodeum) and two new species are described (Truncatoflabellum duncani and Truncatoflabellum mozambiquensis). All but one species are illustrated and accompanied by their known distribution and a guide to the pertinent literature for the species. New records of 19 of the 45 species are listed. The transversely-dividing flabellids range from the Middle Eocene to the Recent at depths of 2-3010 m, and constitute 60% of the 65 known extant species of transversely-dividing Scleractinia.