ZAK beta is activated by cellular compression and mediates contraction-induced MAP kinase signaling in skeletal muscle

Mechanical inputs give rise to p38 and JNK activation, which mediate adaptive physiological responses in various tissues. In skeletal muscle, contraction-induced p38 and JNK signaling ensure adaptation to exercise, muscle repair, and hypertrophy. However, the mechanisms by which muscle fibers sense mechanical load to activate this signaling have remained elusive. Here, we show that the upstream MAP3K ZAK beta is activated by cellular compression induced by osmotic shock and cyclic compression in vitro, and muscle contraction in vivo. This function relies on ZAKO's ability to recognize stress fibers in cells and Z-discs in muscle fibers when mechanically perturbed. Consequently, ZAK-deficient mice present with skeletal muscle defects characterized by fibers with centralized nuclei and progressive adaptation towards a slower myosin profile. Our results highlight how cells in general respond to mechanical compressive load and how mechanical forces generated during muscle contraction are translated into MAP kinase signaling.Peer reviewe

Bedömning av laborativt arbete i matematik

Det övergripande syftet med det här examensarbetet har varit att undersöka om det laborativa arbetet inom matematiken beaktas vid bedömning av elevernas kunskaper. Vi har också undersökt om lä-rarna dokumenterar detta arbete för att få en tydligare bild av elevers kunskaper och i så fall hur denna dokumentation sker. Undersökningen utfördes på en skola där de arbetar aktivt med labo-rativt arbete i matematiken. På skolan intervjuade vi tre lärare vilka undervisar i år 1-3, samt observerade deras lektioner i matematik-verkstaden. Under intervjuerna svarade lärarna att de tog hänsyn till det laborativa arbetet vid sina bedömningar av eleverna. Resultatet av undersökningen ledde till att vi upptäckte att det är viktigt att man arbetar efter någon typ av dokumentationsmodell för att kunna se, höra och komma ihåg varje elevs inlärningsprocess

A prospective study of angiogenic markers and postmenopausal breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial

Purpose Pro-angiogenic factors are positively associated with breast tumor staging and poorer prognosis, but their role in the etiology of breast cancer has not been assessed. Methods: We measured serum levels of the pro-angiogenic vascular endothelial growth factor A (VEGF), and placental growth factor (PlGF) and anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) in 352 incident breast cancer cases [mean age at diagnosis 67 (range 55–83)] and 352 non-cases in the prostate, lung, colorectal, and ovarian screening trial (women enrolled 1993–2001, followed through 2005) matched on age and date of enrollment. Cases were followed on average 4.2 years from blood draw to diagnosis, range 3.9–12.8 years; 53 % were estrogen receptor positive/progesterone receptor positive (ER+/PR+), and 13 % were ER−/PR−. Quartile-specific hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using weighted Cox proportional hazards regression models adjusted for known breast cancer risk factors. An ordinal variable for the angiogenic markers was used to test for trend in the HR. Results: Comparing the highest to lowest quartile, multivariable HR were 0.90 for VEGF (95 % CI 0.33–2.43, p trend = 0.88), 1.38 for sFlt-1 (95 % CI 0.63–3.04, p trend = 0.63), and 0.62 for PlGF (95 % CI 0.19–2.00, p trend = 0.73). Risk patterns were not altered when all angiogenic markers were included in the model simultaneously, or by restricting analyses to invasive breast cancers, to cases diagnosed two or more years after blood collection or to ER+ tumors. Conclusions: There was no evidence of an increased breast cancer risk associated with circulating levels of pro-angiogenic markers VEGF and PlGF or a reduced risk with circulating levels of anti-angiogenic marker sFlt-1. Electronic supplementary material The online version of this article (doi:10.1007/s10552-016-0779-5) contains supplementary material, which is available to authorized users

Intrapartum pudendal nerve block analgesia and risk of postpartum urinary retention: a cohort study

Introduction and hypothesis: Pudendal nerve block analgesia (PNB) is used as pain relief in the final stage of childbirth. We hypothesized that PNB is associated with higher rates of postpartum urinary retention. Methods: We performed a cohort study among primiparous women with a singleton, cephalic vaginal birth at Oslo University Hospital, Norway. Women receiving PNB were included in the exposed group, while the subsequent woman giving birth without PNB was included in the unexposed group. We compared the likelihood of postpartum urinary retention, defined as catheterization within 3 h after birth. Logistic regression analysis stratified by mode of delivery was performed adjusting for epidural analgesia, episiotomy and birth unit. Results: Of the 1007 included women, 499 were exposed to PNB and 508 were unexposed. In adjusted analyses, women exposed to PNB did not differ in likelihood of postpartum urinary retention compared to women unexposed to PNB in either spontaneous (odds ratio[OR]: 0.82, 95% confidence interval [CI] 0.55–1.22) or instrumental (OR 1.45, 95% CI 0.89–2.39) births. Furthermore, no differences between the groups were observed with excessive residual urine volume or catheterization after > 3 h. Conclusions: PNB was associated with neither risk of postpartum urinary retention nor excessive residual urine volume and is therefore unlikely to hamper future bladder function

Intrapartum pudendal nerve block analgesia and risk of postpartum urinary retention: a cohort study

Introduction and hypothesis: Pudendal nerve block analgesia (PNB) is used as pain relief in the final stage of childbirth. We hypothesized that PNB is associated with higher rates of postpartum urinary retention. Methods: We performed a cohort study among primiparous women with a singleton, cephalic vaginal birth at Oslo University Hospital, Norway. Women receiving PNB were included in the exposed group, while the subsequent woman giving birth without PNB was included in the unexposed group. We compared the likelihood of postpartum urinary retention, defined as catheterization within 3 h after birth. Logistic regression analysis stratified by mode of delivery was performed adjusting for epidural analgesia, episiotomy and birth unit. Results: Of the 1007 included women, 499 were exposed to PNB and 508 were unexposed. In adjusted analyses, women exposed to PNB did not differ in likelihood of postpartum urinary retention compared to women unexposed to PNB in either spontaneous (odds ratio[OR]: 0.82, 95% confidence interval [CI] 0.55–1.22) or instrumental (OR 1.45, 95% CI 0.89–2.39) births. Furthermore, no differences between the groups were observed with excessive residual urine volume or catheterization after > 3 h. Conclusions: PNB was associated with neither risk of postpartum urinary retention nor excessive residual urine volume and is therefore unlikely to hamper future bladder function

Intrapartum pudendal nerve block analgesia and risk of postpartum urinary retention: a cohort study

Introduction and hypothesis: Pudendal nerve block analgesia (PNB) is used as pain relief in the final stage of childbirth. We hypothesized that PNB is associated with higher rates of postpartum urinary retention. Methods: We performed a cohort study among primiparous women with a singleton, cephalic vaginal birth at Oslo University Hospital, Norway. Women receiving PNB were included in the exposed group, while the subsequent woman giving birth without PNB was included in the unexposed group. We compared the likelihood of postpartum urinary retention, defined as catheterization within 3 h after birth. Logistic regression analysis stratified by mode of delivery was performed adjusting for epidural analgesia, episiotomy and birth unit. Results: Of the 1007 included women, 499 were exposed to PNB and 508 were unexposed. In adjusted analyses, women exposed to PNB did not differ in likelihood of postpartum urinary retention compared to women unexposed to PNB in either spontaneous (odds ratio[OR]: 0.82, 95% confidence interval [CI] 0.55–1.22) or instrumental (OR 1.45, 95% CI 0.89–2.39) births. Furthermore, no differences between the groups were observed with excessive residual urine volume or catheterization after > 3 h. Conclusions: PNB was associated with neither risk of postpartum urinary retention nor excessive residual urine volume and is therefore unlikely to hamper future bladder function

The provision of epidural analgesia during labor according to maternal birthplace: a Norwegian register study

Background: The provision of epidural analgesia during labor is ideally a shared decision between the woman and her health care provider. However, immigrant characteristics such as maternal birthplace could affect decisionmaking and thus access to pain relief. We aimed to assess disparities in the provision of epidural analgesia in planned vaginal birth according to maternal region of birth. Methods: We performed a nation-wide register study of 842,496 live-born singleton deliveries in Norway between 2000 and 2015. Maternal birthplace was categorized according to the Global Burden of Disease framework. The provision of epidural analgesia was compared in regression models stratified by parity and mode of delivery. Results: Compared to native-born women, primiparous women from Latin America/Caribbean countries with an instrumental vaginal delivery were most likely to be provided epidural analgesia (OR 2.12, 95%CI 1.69–2.66), whilst multiparous women from Sub-Saharan Africa with a spontaneous vaginal delivery were least likely to be provided epidural analgesia (OR 0.42, 95% C 0.39–0.44). Longer residence time was associated with a higher likelihood of being provided analgesia, whereas effects of maternal education varied by Global Burden of Disease group. Conclusions: Disparities in the likelihood of being provided epidural analgesia were observed by maternal birthplace. Further studies are needed to consider whether the identified disparities represent women’s own preferences or if they are the result of heterogeneous access to analgesia during labor