Prognostic significance of serine-phosphorylated STAT3 expression in pT1-T2 oral tongue carcinoma

Objectives. Phosphorylated (activated) STAT3 (pSTAT3) is a regulator of numerous genes that play an essential part in the onset, development and progression of cancer; it is involved in cell proliferation and preventing apoptosis, and in invasion, angiogenesis, and the evasion of immune surveillance. This study aimed mainly to investigate the potential prognostic role of pSTAT3 expression in oral tongue squamous cell carcinoma (SCC). Methods. Phospho-ser727 STAT3 immunolabeling was correlated with prognostic parameters in 34 consecutive cases of pT1\u2013T2 tongue SCCs undergoing primary surgery. Computer-based image analysis was used for the immunohistochemical reactions analysis. Results. Statistical analysis showed a difference in disease-free survival (DFS) when patients were stratified by pN status (P=0.031). Most tumors had variable degrees (mean\ub1SD, 80.7%\ub123.8%) of intense nuclear immunoreaction to pSTAT3. Our findings rule out any significant association of serine-phosphorylated nuclear STAT3 expression with tumor stage, grade, lymph node metastasis, recurrence rate, or DFS. Conclusion. In spite of these results, it is worth further investigating the role of pSTAT3 (serine-and tyrosine-pSTAT3) in oral tongue SCC in larger series because preclinical models are increasingly showing that several anticancer strategies would benefit from STAT3 phosphorylation inhibition

Numerical simulations of bar formation in the Local Group

This is a pre-copyedited, author-produced PDF of an article accepted for publication in Monthly Notices of the Royal Astronomical Society following peer review. The version of record Monthly Notices of the Royal Astronomical Society 511.2 (2022): 2423-2433 is available online at: https://academic.oup.com/mnras/article-abstract/511/2/2423/6509499#no-access-messageMore than 50 per cent of present-day massive disc galaxies show a rotating stellar bar. Their formation and dynamics have been widely studied both numerically and observationally. Although numerical simulations in the Lambda cold dark matter (ΛCDM) cosmological framework predict the formation of such stellar components, there seems to be a tension between theoretical and observational results. Simulated bars are typically larger in size and have slower pattern speed than observed ones. We study the formation and evolution of barred galaxies, using two ΛCDM zoom-in hydrodynamical simulations of the CLUES project that follow the evolution of a cosmological Local Group-like volume. We found that our simulated bars, at z = 0, are both shorter and faster rotators than previous ones found in other studies on cosmological simulations alleviating the tension mentioned above. These bars match the short tail-end of the observed bar-length distribution. In agreement with previous numerical works, we find that bars form in those systems where the disc self-gravity is dominant over the dark matter halo, making them unstable against bar formation. Our bars developed in the last 3–4 Gyr until they achieve their current length and strength; as bars grow, their lengths increase while their rotation speeds decrease. Despite this slowdown, at redshift z = 0 their rotation speeds and size match well the observational dat

Unilateral inferior turbinate hypoplasia caused by a longstanding (approximately 35 yr) nasal foreign body.

We report the unusual case of a 44-year-old man who presented with a plastic foreign body that had been lodged in his right nasal cavity for approximately 35 years. Initial attempts to remove the object were unsuccessful; only after it was broken into several parts was removal achieved. Rigid nasal endoscopy and computed tomography revealed hypoplasia of the ipsilateral inferior turbinate

Structure and evolutionary history of a large family of NLR proteins in the zebrafish

Multicellular eukaryotes have evolved a range of mechanisms for immune recognition. A widespread family involved in innate immunity are the NACHT-domain and leucine-rich-repeat-containing (NLR) proteins. Mammals have small numbers of NLR proteins, whereas in some species, mostly those without adaptive immune systems, NLRs have expanded into very large families. We describe a family of nearly 400 NLR proteins encoded in the zebrafish genome. The proteins share a defining overall structure, which arose in fishes after a fusion of the core NLR domains with a B30.2 domain, but can be subdivided into four groups based on their NACHT domains. Gene conversion acting differentially on the NACHT and B30.2 domains has shaped the family and created the groups. Evidence of positive selection in the B30.2 domain indicates that this domain rather than the leucine-rich repeats acts as the pathogen recognition module. In an unusual chromosomal organization, the majority of the genes are located on one chromosome arm, interspersed with other large multigene families, including a new family encoding zinc-finger proteins. The NLR-B30.2 proteins represent a new family with diversity in the specific recognition module that is present in fishes in spite of the parallel existence of an adaptive immune system

Cortical gamma-synchrony measured with magnetoencephalography is a marker of clinical status and predicts clinical outcome in stroke survivors.

Background: The outcome of stroke survivors is difficult to anticipate. While the extent of the anatomical brain lesion is only poorly correlated with the prognosis, functional measures of cortical synchrony, brain networks and cortical plasticity seem to be good predictors of clinical recovery. In this field, gamma (>30 Hz) cortical synchrony is an ideal marker of brain function, as it plays a crucial role for the integration of information, it is an indirect marker of Glutamate/GABA balance and it directly estimates the reserve of parvalbulin-positive neurons, key players in synaptic plasticity. In this study we measured gamma synchronization driven by external auditory stimulation with magnetoencephalography and tested whether it was predictive of the clinical outcome in stroke survivors undergoing intensive rehabilitation in a tertiary rehabilitation center. Material and methods: Eleven stroke survivors undergoing intensive rehabilitation were prospectively recruited. Gamma synchrony was measured non-invasively within one month from stroke onset with magnetoencephalography, both at rest and during entrainment with external 40 Hz amplitude modulated binaural sounds. Lesion location and volume were quantitatively assessed through a high-resolution anatomical MRI. Barthel index (BI) and Functional Independence Measure (FIM) scales were measured at the beginning and at the end of the admission to the rehabilitation unit. Results: The spatial distribution of cortical gamma synchrony was altered, and the physiological right hemispheric dominance observed in healthy controls was attenuated or lost. Entrained gamma synchronization (but not resting state gamma synchrony) showed a very high correlation with the clinical status at both admission and discharge (both BI and FIM). Neither clinical status nor gamma synchrony showed a correlation with lesion volume. Conclusions: Cortical gamma synchrony related to auditory entrainment can be reliably measured in stroke patients. Gamma synchrony is strongly associated with the clinical outcome of stroke survivors undergoing rehabilitation

The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936

Background: The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, but it is currently unclear what drives individual differences. We examine cross-sectional and longitudinal associations between the epigenetic clock and four mortality-linked markers of physical and mental fitness: lung function, walking speed, grip strength and cognitive ability. Methods: DNA methylation-based age acceleration (residuals of the epigenetic clock estimate regressed on chronological age) were estimated in the Lothian Birth Cohort 1936 at ages 70 (n=920), 73 (n=299) and 76 (n=273) years. General cognitive ability, walking speed, lung function and grip strength were measured concurrently. Cross-sectional correlations between age acceleration and the fitness variables were calculated. Longitudinal change in the epigenetic clock estimates and the fitness variables were assessed via linear mixed models and latent growth curves. Epigenetic age acceleration at age 70 was used as a predictor of longitudinal change in fitness. Epigenome-wide association studies (EWASs) were conducted on the four fitness measures. Results: Cross-sectional correlations were significant between greater age acceleration and poorer performance on the lung function, cognition and grip strength measures (r range: -0.07 to -0.05, P range: 9.7 x 10 to 0.024). All of the fitness variables declined over time but age acceleration did not correlate with subsequent change over 6 years. There were no EWAS hits for the fitness traits. Conclusions: Markers of physical and mental fitness are associated with the epigenetic clock (lower abilities associated with age acceleration). However, age acceleration does not associate with decline in these measures, at least over a relatively short follow-up

Association Between Raised Inflammatory Markers and Cognitive Decline in Elderly People With Type 2 Diabetes: The Edinburgh Type 2 Diabetes Study

OBJECTIVE-To determine whether circulating levels of the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha are associated with cognitive ability and estimated lifetime cognitive decline in an elderly population with type 2 diabetes. RESEARCH DESIGN AND METHODS-A cross-sectional study of 1,066 men and women aged 60-75 years with type 2 diabetes and living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study), was performed. Seven cognitive tests were used to measure abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility. The results were used to derive a general intelligence factor (g). A vocabulary-based test was administered as an estimate of peak prior cognitive ability. Results on the cognitive tests were assessed for statistical association with inflammatory markers measured in a venous blood sample at the time of cognitive testing. RESULTS-Higher IL-6 and TNF-alpha levels were associated with poorer age- and sex-adjusted scores on the majority of the individual cognitive tests. They were also associated with g using standardized regression coefficients -0.074 to -0.173 (P < 0.05). After adjusting for vocabulary, education level, cardiovascular dysfunction, duration of diabetes, and glycemic control, R,6 remained associated with three of the cognitive tests and with g. CONCLUSIONS-In this representative population of people with type 2 diabetes, elevated circulating levels of inflammatory markers were associated with poorer cognitive ability. IL-6 levels were also associated with estimated lifetime cognitive decline. Diabetes 59:710-713, 201