Sleep disturbances are a common complaint of anxiety patients and constitute a hallmark feature of post-traumatic stress disorder (PTSD). Emerging evidence suggests that poor sleep is not only a secondary symptom of anxiety- and trauma-related disorders but represents a risk factor in their development, for example by interfering with emotional memory processing. Fear extinction is a critical mechanism for the attenuation of fearful and traumatic memories and multiple studies suggest that healthy sleep is crucial for the formation of extinction memories. However, fear extinction is often impaired in anxiety- and trauma-related disorders-an endophenotype that is perfectly modelled in the 129S1/SvImJ inbred mouse strain. To investigate whether these mice exhibit altered sleep at baseline that could predispose them towards maladaptive fear processing, we compared their circadian sleep/wake patterns to those of typically extinction-competent C57BL/6 mice. We found significant differences regarding diurnal distribution of sleep and wakefulness, but also sleep architecture, spectral features and sleep spindle events. With regard to sleep disturbances reported by anxiety- and PTSD patients, our findings strengthen the 129S1/SvImJ mouse models' face validity and highlight it as a platform to investigate novel, sleep-focused diagnostic and therapeutic strategies. Whether the identified alterations causally contribute to its pathological anxiety/PTSD-like phenotype will, however, have to be addressed in future studies.Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia (PPE), is a major side effect of capecitabine. Although the pathogenesis of HFS remains unknown, some studies suggested a potential involvement of inflammation in its pathogenesis. Proton pump inhibitors (PPIs) have been reported to have anti-inflammatory effects. In this study, we investigated the ameliorative effects of omeprazole, a PPI on capecitabine-related HFS in mice model, and a real-world database. Repeated administration of capecitabine (200 mg/kg, p.o., five times a week for 3 weeks) increased fluid content, redness, and tumor necrosis factor (TNF)-α substance of the mice hind paw. Co-administration of omeprazole (20 mg/kg, p.o., at the same schedule) significantly inhibited these changes induced by capecitabine. Moreover, based on the clinical database analysis of the Food and Drug Administration Adverse Event Reporting System, the group that has used any PPIs had a lower reporting rate of capecitabine-related PPE than the group that has not used any PPIs. (6.25% vs. 8.31%, p  less then  0.0001, reporting odds ratio (ROR) 0.74, 95% confidence interval (CI) 0.65-0.83). Our results suggest that omeprazole may be a potential prophylactic agent for capecitabine-induced HFS.The Chauvet cave (UNESCO World Heritage site, France) is located in the Ardèche Gorge, a unique physical and cultural landscape. Its setting within the gorge-overlooking a meander cutoff containing a natural arch called the Pont d'Arc-is also remarkable. Investigating possible associations between sites' physical and cultural settings, chronologies of human occupation, and access conditions has become a major theme in archeological research. The present study aims to reconstruct the landscape of the Pont d'Arc meander cutoff during the Upper Paleolithic, when humans were present in the Chauvet Cave. We used uranium-series and electron spin resonance analyses to date the formation of the Pont d'Arc natural arch in the Combe d'Arc meander cutoff, near the Chauvet Cave. Results show that the meander became totally cutoff between 108 and 138 ka (95%). Hence, the natural arch formed before the Upper Paleolithic and the first known human presence in the Chauvet Cave, dated to 37 ka cal BP. These results allowed us to reconstruct a key part of the landscape surrounding the Chauvet Cave when it was being used by Upper-Paleolithic societies.In some breast cancer (BC) patients, an examination of lymph nodes dissected during sentinel lymph node biopsy (SLNB) demonstrates a presence of metastatic lesions and extracapsular extension (ECE) in a SLN. This study aimed to evaluate clinical relevance of ECE in BC patients. This is a retrospective analysis of 891 patients with cancer metastases to SLN, referred to supplementary axillary lymph node dissection (ALND), hospitalized between Jan 2007 and Dec 2017. Clinical and epidemiological data was evaluated. Long-term treatment outcomes were analysed. In 433 (48.6%) patients, cancer metastases were limited to the SLN (group I), in 61 (6.8%) patients the SLN capsule was exceeded focally (≤ 1 mm-group II). SB203580 price In 397 (44.6%) patients, a more extensive ECE was found (> 1 mm-group III). Metastases to non-sentinel lymph nodes (nSLNs) were diagnosed in 27.0% patients from group I, 44.3% patients from group II and in 49.6% patients from group III. No statistically significant differences were observed in long-term treatment outcomes for compared groups. The presence of ECE is accompanied by a higher stage of metastatic lesions in the lymphatic system. The differences in this respect were statistically significant, when compared to the group of ECE(-) patients. ECE, regardless of its extent, did not impact the long-term treatment results. ECE remains an indication for supplementary ALND and for other equivalent cancer treatment procedures, regardless of ECE size.Patients with Lynch syndrome have a high risk of colorectal cancer (CRC). In this study, we estimated the age- and sex-specific cumulative risks of CRC in Han Chinese patients with Lynch syndrome caused by the pathogenic germline mutations in MLH1 or MSH2 in Taiwan. Based on 321 mutation carriers and 419 non-mutation carriers from 75 pedigrees collected in an Amsterdam criteria family registry in Taiwan, the age- and sex-specific cumulative risks of CRC in male carriers of mutation in MLH1 and MSH2 at the age of 70 years were 60.3% (95% confidence interval (CI) = 31.1%-89.9%) and 76.7% (95% CI = 37.2%-99.0%), respectively. For females, the cumulative risks of CRC at the age of 70 were estimated to be 30.6% (95% CI = 14.3%-57.7%) and 49.3% (95% CI = 21.9%-84.5%) in the carriers of MLH1 and MSH2 germline mutations, respectively. In conclusion, the cumulative risks of CRC at the age of 70 in the Han Chinese patients is higher in mutation carriers than non-mutation carriers and male mutation carriers have a higher cumulative risk of developing CRC than the female mutation carriers.