Recurrence of pulmonary intravascular bronchoalveolar tumor with mediastinal metastasis 20 years later

SummaryPulmonary intravascular bronchoalveolar tumor (IVBAT) also recognized as pulmonary epithelioid hemangioendothelioma, is a rare malignant vascular tumor of unknown etiology. IVBAT is a tumor of multicentric origin and the lungs are rarely involved, with only about 60 cases of pulmonary IVBAT described in the literature. The prognosis is unpredictable, with life expectancy ranging from 1 to 15 years. We report an unusual case of pulmonary IVBAT that recurred in the lung with metastasis to the mediastinum

CD4(+) T follicular helper and IgA(+) B cell numbers in gut biopsies from HIV-infected subjects on antiretroviral therapy are similar to HIV-uninfected individuals

BACKGROUND: Disruption of gastrointestinal tract epithelial and immune barriers contribute to microbial translocation, systemic inflammation, and progression of HIV-1 infection. Antiretroviral therapy (ART) may lead to reconstitution of CD4(+) T cells in gut-associated lymphoid tissue (GALT), but its impact on humoral immunity within GALT is unclear. Therefore, we studied CD4(+) subsets, including T follicular helper cells (Tfh), as well as resident B cells that have switched to IgA production, in gut biopsies, from HIV(+) subjects on suppressive ART compared to HIV-negative controls (HNC). METHODS: Twenty-three HIV(+) subjects on ART and 22 HNC undergoing colonoscopy were recruited to the study. Single-cell suspensions were prepared from biopsies from left colon (LC), right colon (RC), and terminal ileum (TI). T and B lymphocyte subsets, as well as EpCAM(+) epithelial cells, were accurately enumerated by flow cytometry, using counting beads. RESULTS: No significant differences in the number of recovered epithelial cells were observed between the two subject groups. However, the median TI CD4(+) T cell count/10(6) epithelial cells was 2.4-fold lower in HIV(+) subjects versus HNC (19,679 versus 47,504 cells; p = 0.02). Similarly, median LC CD4(+) T cell counts were reduced in HIV(+) subjects (8,358 versus 18,577; p = 0.03) but were not reduced in RC. Importantly, we found no significant differences in Tfh or IgA(+) B cell counts at either site between HIV(+) subjects and HNC. Further analysis showed no difference in CD4(+), Tfh, or IgA(+) B cell counts between subjects who commenced ART in primary compared to chronic HIV-1 infection. Despite the decrease in total CD4 T cells, we could not identify a selective decrease of other key subsets of CD4(+) T cells, including CCR5(+) cells, CD127(+) long-term memory cells, CD103(+) tissue-resident cells, or CD161(+) cells (surrogate marker for Th17), but there was a slight increase in the proportion of T regulatory cells. CONCLUSION: While there were lower absolute CD4(+) counts in the TI and LC in HIV(+) subjects on ART, they were not associated with significantly reduced Tfh cell counts or IgA(+) B cells, suggesting that this important vanguard of adaptive immune defense against luminal microbial products is normalized following ART.John Zaunders, Mark Danta, Michelle Bailey, Gerald Mak, Katherine Marks, Nabila Seddiki, Yin Xu, David J. Templeton, David A. Cooper, Mark A. Boyd, Anthony D. Kelleher and Kersten K. Koelsc

The Transcription Factor NF-ATc1 Regulates Lymphocyte Proliferation and Th2 Cytokine Production

AbstractNF-ATc1 is a member of a family of genes that encodes the cytoplasmic component of the nuclear factor of activated T cells (NF-AT). In activated T cells, nuclear NF-AT binds to the promoter regions of multiple cytokine genes and induces their transcription. The role of NF-ATc1 was investigated in recombination activating gene-1 (RAG-1)–deficient blastocyst complementation assays using homozygous NF-ATc1−/− mutant ES cell lines. NF-ATc1−/−/RAG-1−/− chimeric mice showed reduced numbers of thymocytes and impaired proliferation of peripheral lymphocytes, but normal production of IL-2. Induction in vitro of Th2 responses, as demonstrated by a decrease in IL-4 and IL-6 production, was impaired in mutant T cells. These data indicate that NF-ATc1 plays roles in the development of T lymphocytes and in the differentiation of the Th2 response

Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

BackgroundHistologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.MethodsThis was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0–4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0–2 vs F3 vs F4; LSM: 2·67; NFS: 0·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.FindingsOf 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44–63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33–91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001 for all comparisons). The tAUC at 5 years were 0·72 (95% CI 0·62–0·81) for histology, 0·76 (0·70–0·83) for LSM-VCTE, 0·74 (0·64–0·82) for FIB-4, and 0·70 (0·63–0·80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression.InterpretationSimple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases

Lexicality and phonological similarity: a challenge for the retrieval-based account of serial recall?

[Abstract]: The retrieval-based account of serial recall (Saint-Aubin & Poirier, 2000) attributes lexicality, phonological similarity, and articulatory suppression effects to a process where long-term representations are used to reconstruct degraded phonological traces. Two experiments tested this assumption by manipulating these factors in the recall of four- and five-item lists. Lexicality enhanced item recall (IR), but only affected position accuracy (PA) for five-item lists under suppression. Phonological similarity influenced both words and non-words, and produced impaired PA in silent and suppressed conditions. Consistent with the retrieval-based account, words and non-words of high-word likeness appear subject to redintegration. However, some findings, like suppression not reducing the phonological similarity impairment in suppressed conditions, present challenges for the retrieval-based account and other models of serial recall

The molecular epidemiology of ocular \u3cem\u3eChlamydia trachomatis\u3c/em\u3e infections in Western Australia: Implications for Trachoma control

We studied the serovar distribution of Chlamydia trachomatis in patients with clinical eye disease in Western Australia. Most disease occurred in indigenous communities and was caused by trachoma serovars Ba and C. Serovar Ba was genetically homogeneous throughout Western Australia and identical to strains previously described in indigenous communities in Northern Territory. This finding probably results from movement of these populations, and suggests that a widely coordinated, rather than local or regional, approach is needed to control trachoma in mobile populations. Serovar C strains within Western Australia were homogeneous but distinct from those in Northern Territory, possibly because of inherent differences in transmissibility or differences in population movements among communities carrying the different serovars. Genital serovars were occasional causes of eye diseases in infants, adolescents, and adults in trachoma-endemic areas. These serovars should be considered in the differential diagnosis of acute follicular conjunctivitis in these groups

The Geographic Distribution of Liver Cancer in Canada Does Not Associate with Cyanobacterial Toxin Exposure

Background: The incidence of liver cancer has been increasing in Canada over the past decade, as has cyanobacterial contamination of Canadian freshwater lakes and drinking water sources. Cyanotoxins released by cyanobacteria have been implicated in the pathogenesis of liver cancer. Objective: To determine whether a geographic association exists between liver cancer and surrogate markers of cyanobacterial contamination of freshwater lakes in Canada. Methods: A negative binomial regression model was employed based on previously identified risk factors for liver cancer. Results: No association existed between the geographic distribution of liver cancer and surrogate markers of cyanobacterial contamination. As predicted, significant associations existed in areas with a high prevalence of hepatitis B virus infection, large immigrant populations and urban residences. Discussion and Conclusions: The results of this study suggest that cyanobacterial contamination of freshwater lakes does not play an important role in the increasing incidence of liver cancer in Canada

Management of Replicated Volume Location Data in the Ficus Replicated File System

Existing techniques to provide name transparency in distributed file systems have been designed for modest scale systems, and do not readily extend to very large configurations. This paper details the approach which is now operational in the Ficus replicated Unix filing environment, and shows how it differs from other methods currently in use. The Ficus mechanism permits optimistic management of the volume location data by exploiting the existing directory reconciliation algorithms which merge directory updates made during network partition. 1 Introduction Most Unix file system implementations separate the maintenance of name binding data into two levels: within a volume (or filesystem), directory entries bind names to low-level identifiers (such as inodes); a second mechanism is used to form a super-tree by &quot;gluing&quot; the set of volumes to each other. The traditional Unix volume super-tree connection mechanism has been widely altered or replaced to support both small and large scale d..