Transcriptomic and Immunophenotypic Characterization of Tumor Immune Microenvironment in Squamous Cell Carcinoma of the Oral Tongue

The tumor immune microenvironment of oral tongue squamous cell carcinoma may be accountable for differences in clinical behavior, particularly between different age groups. We performed RNA expression profiling and evaluated tumor infiltrating lymphocytes (TILs) and their T-cell subsets in order to assess the functional status of oral tongue squamous cell carcinoma tumor microenvironment and detect potentially clinically useful associations. Archival surgical pathology material from sixteen oral tongue squamous cell carcinoma patients was microscopically evaluated for TIL densities. RNA was extracted from macrodissected whole tumor sections and normal controls and RNA expression profiling was performed by the NanoString PanCancer IO 360 Gene Expression Panel. Immunostains for CD4, CD8 and FOXP3 were evaluated manually and by digital image analysis. Oral tongue squamous cell carcinomas had increased TIL densities, numerically dominated by CD4 + T cells, followed by CD8 + and FOXP3 + T cells. RNA expression profiling of tumors versus normal controls showed tumor signature upregulation in inhibitory immune signaling (CTLA4, TIGIT and PD-L2), followed by inhibitory tumor mechanisms (IDO1, TGF-β, B7-H3 and PD-L1). Patients older than 44 years showed a tumor microenvironment with increased Tregs and CTLA4 expression. Immunohistochemically assessed CD8% correlated well with molecular signatures related to CD8 + cytotoxic T-cell functions. FOXP3% correlated significantly with CTLA4 upregulation. CTLA4 molecular signature could be predicted by FOXP3% assessed by immunohistochemistry (R² = 0.619, p = 0.026). Oral tongue squamous cell carcinoma hosts a complex inhibitory immune microenvironment, partially reflected in immunohistochemically quantified CD8 + and FOXP3 + T-cell subsets. Immunohistochemistry can be a useful screening tool for detecting tumors with upregulated expression of the targetable molecule CTLA4.Electronic supplementary materialThe online version of this article (10.1007/s12105-020-01229-w) contains supplementary material, which is available to authorized users.     

Newlywed Couples’ Own and Partner Sexual Disgust Sensitivities Interact to Predict Their Marital Satisfaction Through Their Sexual Satisfaction

Archives of Sexual Behavior - Sex is integral to maintaining a satisfying long-term romantic relationship such as marriage. It is thus important to identify the factors that promote sexual...     

Understanding the financial impact of a diagnosis of young onset dementia on individuals and families in the United Kingdom: Results of an online survey

Although literature on postdiagnostic support for people affected by young onset dementia acknowledges financial concerns, this topic has remained underresearched. The aim of this study was to explore the financial impact of a diagnosis of young onset dementia on individuals and families. An online survey, comprising binary yes/no, multiple-response and open-ended questions, was codesigned with people living with young onset dementia. The survey was promoted via networks and online platforms. Data were collected from August to October 2019. Survey respondents across the United Kingdom (n = 55) who had received a diagnosis of young onset dementia were aged between 45 and 64, were at different stages of dementia and had been diagnosed with thirteen different types of dementia. Of the 55 respondents, 71% (n = 39) had received assistance from family members when completing the survey. The main financial impact of a diagnosis of young onset dementia resulted from premature loss of income and reduced and often deferred pension entitlements. In some cases, care-costs became unaffordable. Lack of clarity of processes and procedures around needs assessments, carers' assessments and financial assessments by different organisations resulted in some families having to ask for legal advice and, in some cases, involved lengthy appeal processes. Future research needs to involve Adult Social Care and Third Sector organisations to help codesign and test financial management interventions to support people affected by this progressive health condition.     

A new species of Stephanostomum Looss, 1899 (Digenea, Acanthocolpidae) with a bizarre oral sucker: S. adlardi sp. nov. from the common coral trout Plectropomus leopardus (Lacepède, 1802) (Perciformes, Serranidae) from Lizard Island, Great Barrier Reef

A new species of Acanthocolpidae, Stephanostomum adlardi is described from the serranid Plectropomus leopardus from Lizard Island in the northern Great Barrier Reef. It differs from all previously described acanthocolpids in the structure of the oral sucker which is extended into dorsal and ventral lobes each bearing a row of spines. A phylogenetic tree estimated from combined nuclear small and partial large ribosomal RNA gene sequences shows that, despite the unusual oral sucker structure, the species is a true member of the genus Stephanostomum. The molecular results also suggest that Monostephanostomum nolani is derived from within Stephanostomum.     

An image-based modeling framework for patient-specific computational hemodynamics

We present a modeling framework designed for patient-specific computational hemodynamics to be performed in the context of large-scale studies. The framework takes advantage of the integration of image processing, geometric analysis and mesh generation techniques, with an accent on full automation and high-level interaction. Image segmentation is performed using implicit deformable models taking advantage of a novel approach for selective initialization of vascular branches, as well as of a strategy for the segmentation of small vessels. A robust definition of centerlines provides objective geometric criteria for the automation of surface editing and mesh generation. The framework is available as part of an open-source effort, the Vascular Modeling Toolkit, a first step towards the sharing of tools and data which will be necessary for computational hemodynamics to play a role in evidence-based medicine.     

Efflux of taurine from renal brush border membrane vesicles: Is it adaptively regulated?

The uptake of the -amino acid taurine by rat renal brush border membrane vesicles (BBMV) adapts to changes in dietary sulfur amino acid intake. Initial rateV _max upregulates after ingestion of a low methionine and taurine diet (LTD) and downregulates after a high taurine diet (HTD). This is reflected in vivo by hypotaurinuria after a LTD (90% reduction in excretion) and an 18-fold increase in urine taurine after a HTD. This study was performed to determine whether taurine efflux from BBMV is adaptively regulated by external taurine concentration or by diet. Vesicles were preloaded with varying concentrations of radiolabelled and unlabelled taurine and a 150 mM concentration of various salts. Efflux conditions were: taurine and 150 mM salt inside and 150 mM salt outside. The efflux of five concentrations of taurine (10–500 M) was linear over 6 min, reached equilibrium by 21 min, and was dependent upon intravesicular taurine content. The kinetic characteristics of efflux (E) were significantly different from influx (I):K _m=109.8±5.8 (E) versus 23.6±4.2 (I),P<0.001 [time of linearity=360 s (E) vs. 20 s (I)]. Efflux of taurine was dependent on the presence of both sodium and chloride in the system, but neither external taurine content (0,100 M, 1,000 M) nor external -alanine altered initial efflux. Feeding rats a normal diet, LTD, or fasting altered taurine uptake but not efflux. Efflux does not appear to play a role in the adaptive regulation of taurine transport found in all mammalian species.     

Twenty-year review of the surgical management of perianal Crohn's disease

PURPOSE: A retrospective analysis of 48 patients treated over a 20-year period (March 1973–April 1993) was undertaken to assess the results of our practice of early surgical intervention in suppurative complications of perianal Crohn's disease. METHODS: All patients were either seen in the office within the last six months or contacted by phone. RESULTS: The average age of our patients was 30 years at initial diagnosis. Thirty-four patients (71 percent) initially presented with intestinal disease and four (8 percent) with only perianal disease. Thirteen patients (27 percent) initially presented with simultaneous intestinal and perianal disease. The various fistulas at initial presentation included 8 intersphincteric (17 percent), 14 transphincteric (29 percent), 11 complex or multiple (23 percent), 5 rectovaginal (10 percent), and 2 unclassified, for a total of 40 patients. Eight patients (17 percent) presented with only an abscess. Eighty five percent of our patients healed after their first procedure, with an average time to heal of 2.8 months. Thirteen (27 percent) patients had recurrences after initial healing of their wounds. The mean time to recurrence after healing was 5.25 years. Fifty-four percent of our recurrences (7 patients) were treated by incision and drainage of an abscess only. Seven of 13 recurrences healed after the second procedure (54 percent), and 5 of 6 healed after a third procedure (83 percent). Only seven (14 percent) of our patients underwent a proctocolectomy during the study period, through September, 1993. Our overall probability of avoiding proctectomy and healing perineal wounds of 86 percent is consistent with published literature. CONCLUSIONS: Early aggressive surgical management of suppurative complications of perianal Crohn's disease before complex management problems ensue results in a high incidence of healing and a low risk of subsequent proctectomy.     

Self-Directed Treatment of Intermittent Heartburn: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Evaluation of Antacid and Low Doses of an H(2)-Receptor Antagonist (Famotidine)

BACKGROUND: Heartburn, a common symptom, is self-treated with oral antacids. Efficacy of antacids has not been demonstrated for individual, spontaneous heartburn episodes. METHODS: We conducted a double-blind, randomized, placebo-controlled, parallel-group study of self-directed treatment for episodic heartburn comparing famotidine (FAM) 5, 10, or 20 mg and antacid (11 mEq ANC) to placebo (PBO) during a 4-week period. Twenty-nine US investigators enrolled a total of 565 outpatients, ages 18--81 years (mean 44.1 years) with heartburn but not seeking care for heartburn. Treatment of spontaneous heartburn episodes was permitted as needed, up to twice daily, with self-administered test drug. An open-label, backup antacid was provided to use if test drug did not provide adequate relief. Patients assessed heartburn relief hourly and recorded use of backup antacid. Relief was defined as complete relief of symptoms without the use of backup antacid. RESULTS: The media proportion of episodes relieved was: PBO, 41%; FAM 5 mg, 59%, 0.05 less-than-or-equal p < 0.10; FAM 10 mg, 70%, p < 0.001; FAM 20 mg, 69%, p < 0.001; antacid, 62%, p < 0.05 (p-values versus PBO). Supplemental analyses incorporating time to relief confirmed that famotidine and antacid provided more rapid and more frequent relief than placebo (odds ratio for relief relative to PBO: FAM 5 mg, 1.55, p = 0.003; FAM 10 mg, 1.94, p < 0.001; FAM 20 mg, 2.13, p < 0.001; antacid 1.57, p = 0.003). The tolerability profile was similar with famotidine, antacid, and placebo. CONCLUSIONS: The positive results with antacid demonstrated for the first time the efficacy of antacid in self-treatment of individual heartburn episodes and provided internal validation of this study paradigm. Patients in this study self-medicated effectively using low doses of famotidine on an as needed basis for spontaneous episodes of heartburn.