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ABSTRACTObjective: Nonrestorative sleep and sleep disorders are commonly reported in patients suffering from craniomandibular (CMD) and craniocervical dysfunctions (CCD). This study aimed to investigate polysomnographic characteristics and the reduction of pain before and after treatment in these patients.Methods: Seventy-four patients with sleep disorders and evident CMD and CCD were included. Manual therapy and an Aqualizer® were used in the therapeutic group. Polysomnographic measurements were conducted pre- and post-therapy.Results: The number of sleep stage alterations and the sleep stage index differed significantly between pre- and post-therapeutic measurements. Between both groups, these parameters were significantly different, as well (p = .001 and p= .012). The subjective perception of sleep quality improved in 81.6% post-therapy (p < .001).Discussion: Manual therapy and the application of an Aqualizer® may improve sleep quality in patients suffering from CMD and CCD. Pain may not be the main cause for the sleep disorders in CMD and CCD.

Sex disparity in cancer is so far inadequately considered, and components of its basis are rather unknown. We reveal that male versus female pancreatic cancer (PC) patients and mice show shortened survival, more frequent liver metastasis, and elevated hepatic metastasis-promoting gene expression. Tissue inhibitor of metalloproteinases 1 (TIMP1) was the secreted factor with the strongest male-biased expression in patient-derived pancreatic tumors. Male-specific up-regulation of systemic TIMP1 was demonstrated in PC mouse models and patients. Using TIMP1-competent and TIMP1-deficient PC mouse models, we established a causal role of TIMP1 in determining shortened survival and increased liver metastasis in males. Observing TIMP1 expression as a risk parameter in males led to identification of a subpopulation exhibiting increased TIMP1 levels (T1HI males) in both primary tumors and blood. T1HI males showed increased risk for liver metastasis development not only in PC but also in colorectal cancer and melanoma. This study reveals a lifestyle-independent sex disparity in liver metastasis and may open new avenues toward precision medicine.