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Keratin 8 (K8) is the main intestinal epithelial intermediate filament protein with proposed roles for colonic epithelial cell integrity. Here, we used mice lacking K8 in intestinal epithelial cells (floxed K8 and Villin-Cre1000 and Villin-CreER t2 ) to investigate the cell-specific roles of intestinal epithelial K8 for colonocyte function and pathologies. Intestinal epithelial K8 deletion decreased K8 partner proteins, K18–K20, 75–95%, and the remaining keratin filaments were located at the colonocyte apical regions with type II K7, which decreased 30%. 2-Deoxy-2-[ 18 F]-fluoroglucose positron emission tomography in vivo imaging identified a metabolic phenotype in the lower gut of the conditional K8 knockouts. These mice developed intestinal barrier leakiness, mild diarrhea, and epithelial damage, especially in the proximal colon. Mice exhibited shifted differentiation from enterocytes to goblet cells, displayed longer crypts and an increased number of Ki67 + transit-amplifying cells in the colon. Significant proproliferative and regenerative signaling occurred in the IL-22, STAT3, and pRb pathways, with minor effects on inflammatory parameters, which, however, increased in aging mice. Importantly, colonocyte K8 deletion induced a dramatically increased sensitivity to azoxymethane-induced tumorigenesis. In conclusion, intestinal epithelial K8 plays a significant role in colonocyte epithelial integrity maintenance, proliferation regulation and tumor suppression. Graphical abstract

Purpose Due to potential drug-drug interactions and subsequent bleeding risk, analgesic use should be reviewed when an oral anticoagulant is initiated. The aim of this study was to compare use of non-steroidal anti-inflammatory drugs (NSAIDs) and other analgesics before and after oral anticoagulant initiation. Methods All individuals who initiated warfarin, dabigatran, or rivaroxaban between January 2012 and September 2013 were identified from the Finnish Prescription Register. Prevalence of analgesic use during 3 months after oral anticoagulant initiation was compared to analgesic use during 4 months before initiation. Analgesics included were NSAIDs, paracetamol, paracetamol in doses ≥2 g/day, tramadol, and other opioids. Conditional logistic regression was used to calculate odds ratios (OR) with 95 % confidence intervals (CI). Results In total, 54,025 initiated warfarin, 16,894 rivaroxaban, and 1569 dabigatran. The odds of NSAID use decreased among warfarin initiators (odds ratio (OR) 0.10; 95 % confidence interval (CI) 0.09–0.10); 2.6 % used NSAID after initiation. In contrast, the odds of NSAID use increased among rivaroxaban (OR 3.56; 95 % CI 3.37–3.75) and dabigatran initiators (OR 1.44; 95 % CI 1.16–1.78). The proportions using NSAIDs after the initiation were 69 and 32 %, respectively. However, NSAID use decreased among dabigatran initiators with confirmed atrial fibrillation (OR 0.46; 95 % CI 0.23–0.92) and among rivaroxaban initiators with a daily dose of ≥15 mg (OR 0.28; 95 % CI 0.19–0.40). Conclusions The use of NSAIDs decreases extensively among warfarin initiators which is encouraging. However, the use of NSAIDs increases among rivaroxaban and dabigatran initiators. This is a concern as the bleeding risk may increase due to potential pharmacodynamic interactions.

This article summarizes the results for a total of 189 female and 63 male university students (mean age 23 and 26 years, respectively) from the following vocal capacity tests: measurement of (1) vital capacity, (2) average airflow in phonation (on [o:]), (3) maximum duration of sustained blowing, (4) maximum phonation time (on [o:, z:]), (5) maximum duration of [s:], (6) the ratio of the duration of [s:] to [z:] (s/z ratio), (7) phonation quotient (the ratio between vital capacity and maximum phonation time), (8) the lowest possible tone, (9) mean fundamental frequency (F0) in normal and loud text reading and in shouting, (10) difference between the lowest tone and mean F0 in text reading and in shouting, (11) F0 range in text reading, (12) equivalent sound level of normal and loud reading and of shouting in maximum loudness, (13) phonetogram (voice range profile) and (14) long-term average spectrum of text reading. Voice quality is also evaluated perceptually, and additionally, data on subjects’ self-reported vocal fatigue symptoms in general or after a vocally loading task were collected. The value of these measurements from the point of view of assessment of vocal capacity will be discussed.

This study compared the effects of Voice Massage™ (VM) and a voice hygiene lecture (VHL) on 60 female teachers. VM is a Finnish massage method which treats muscles related to voice production. All subjects attended the VHL (3 h). Half of them were randomly assigned to the VM group, the other half received only VHL. VM was given 5 times in 1-hour sessions at intervals of 1–2 weeks. At the beginning and end of the autumn school term, before and after a working day, (1) a 1-min reading sample was recorded at both the subject’s habitual loudness and loudly, (2) a prolonged phonation on [a:] was recorded at habitual speaking pitch and (3) a questionnaire on voice quality, ease or difficulty of phonation, and tiredness of the throat was completed. The reading samples were analysed for the fundamental frequency (F₀), equivalent sound level (Leq) and α-ratio [Leq (1–5 kHz) – Leq (50–1,000 Hz)]. The vowel samples were analysed for the F₀ and Leq, as well as for jitter and shimmer. The reading samples were also evaluated perceptually by 3 speech trainers. The mean F₀ and difficulty of phonation increased from the beginning to the end of the term in the VHL group (p = 0.026, p = 0.007, respectively). In the VM group, the perceived firmness of loud reading decreased (p = 0.026). The results suggest that VM may help in sustaining vocal well-being during a school term.

This study addressed two self-evaluation questionnaires in investigating the effects of voice hygiene lecture (VHL, 3 h) and additional voice training (VT) or Voice Massage™ (VM; both 5 h) in 90 female teachers. The subjects assessed their voice quality, ease of phonation and tiredness of throat before and after a working day at the beginning and end of the school term using a visual analogue scale (VAS) (Questionnaire 1). At the end of the term, the degree of positive influence of the interventions was reported on VAS, and the type of influence was indicated by choosing one or more of three alternatives (voice quality, audibility and endurance) or by writing a free comment (Questionnaire 2). Questionnaire 1 was pretested and found to be reliable and valid for self-evaluation of voice. At the end of term, the VM and VT groups reported more positive influence of the interventions than did the VHL group. The reported influence did not correlate with working-day-related changes in sensations. Increased difficulty of phonation and tiredness of throat was found in the VHL group at the end of the term. However, the groups did not differ significantly from each other. The challenges of self-evaluations as outcome measures are discussed.