Comparing Anthropometric Methods To Quantify Relations Between Adiposity And Headache

Obesity is associated with increased risk for chronic migraine and migraine progression, but associations with episodic migraine (em) and episodic tension-type headache (tth) are unclear. Most studies have relied on bmi as an indicator of adiposity. More accurate anthropometric measures that distinguish adipose tissue from other body tissue are critical to examine adiposity-headache associations, including validated measures of abdominal adiposity and established measurement formulas such as body adiposity index (bai) and body composition equations developed by Peterson et al. (2003) and Garcia et al. (2005). The present study explored adiposity-headache associations by employing established anthropometric measures of adiposity and comparing individuals with migraine, with tth, and without headache. Participants were 109 young adults meeting ichd-3 criteria for tth or migraine, or without headache. Ninety-three percent of migraineurs had em, and 92.5% of tth sufferers had etth. Researchers measured each participant and calculated adiposity as a function of: bmi, waist circumference, bai, waist-to-hip ratio, and the aforementioned body composition equations. Headache severity and frequency were obtained via diagnostic interview (sdih-3), and headache-related disability was assessed by the headache impact test (hit-6). Manova and a subsequent mancova did not reveal significant differences in adiposity between migraine, tth, and non-headache groups. Regression analyses indicated that among migraineurs, adiposity accounted for 11%, 13%, and 10% of the variance in headache severity, frequency, and disability, respectively, though these proportions were not statistically significant. Among participants with tth, adiposity accounted for 8% (p = .82), 21% (p =.23), and 39% (p = .009) of the variance in headache severity, frequency, and disability. The association with disability among those with tth fell short of significance after Bonferroni correction for multiple comparisons. Adiposity did not differ between headache groups, and no significant associations were found between adiposity and headache frequency, severity, and disability. Findings extend upon existing literature that has established a positive association between obesity and chronic headache, suggesting that adiposity may not be a distinguishing characteristic among individuals with em and etth. Longitudinal studies that employ gold standard methods of adiposity measurement among diverse samples are needed to further clarify the role of adiposity in headache

Replication Fork Stability Confers Chemoresistance in BRCA-deficient Cells

Brca1- and Brca2-deficient cells have reduced capacity to repair DNA double-strand breaks (DSBs) by homologous recombination (HR) and consequently are hypersensitive to DNA damaging agents, including cisplatin and poly(ADP-ribose) polymerase (PARP) inhibitors. Here we show that loss of the MLL3/4 complex protein, PTIP, protects Brca1/2-deficient cells from DNA damage and rescues the lethality of Brca2-deficient embryonic stem cells. However, PTIP deficiency does not restore HR activity at DSBs. Instead, its absence inhibits the recruitment of the MRE11 nuclease to stalled replication forks, which in turn protects nascent DNA strands from extensive degradation. More generally, acquisition of PARPi and cisplatin resistance is associated with replication fork (RF) protection in Brca2-deficient tumor cells that do not develop Brca2 reversion mutations. Disruption of multiple proteins, including PARP1 and CHD4, leads to the same end point of RF protection, highlighting the complexities by which tumor cells evade chemotherapeutic interventions and acquire drug resistance