Notes

Ligand-Specific Allosteric Coupling Controls G-Protein-Coupled Receptor Signaling.
nd benign mirror electrical changes not caused by collateral circulation diverting blood to ischemic area from non-diseased artery. BACKGROUND Orientation to bodily signals reflects the ways in which individuals interpret their bodily sensations. Such orientation is formed within early interpersonal context. Findings reveal that trauma may result in catastrophic and fearful orientation towards bodily signals. However, not much is known regarding the link between trauma and orientation towards the body as manifested within a family intergenerational context. OBJECTIVE This study examines the link between child maltreatment, complex posttraumatic stress symptoms (CPTS symptoms), and a posttraumatic orientation to bodily signals among dyads of mothers and their young adult daughters. PARTICIPANTS AND SETTING 194 mother-daughter dyads (mothers' mean age = 56, SD = 6.3; daughters' mean age = 26, SD = 3.03) completed self-reported questionnaires, assessing child maltreatment (CTQ), CPTS symptoms (ITQ), and orientation to bodily signals (pain catastrophizing, anxiety sensitivity-physical, body vigilance). RESULTS Orientation to bodily signals was associated with child maltreatment, through the mediation of CPTS symptoms among mothers (indirect effects between 0.13-0.28; p > 0.021) and daughters (indirect effects between 0.21-0.11; p > 0.032). Mothers' child maltreatment was associated with daughters' child maltreatment (effect = 0.35; p less then 0.001), and mothers' orientation to bodily signals was associated with daughters' orientation (effects between 0.19-0.27; p less then 0.016). Daughters' orientation to bodily signals was partially associated with mothers' child maltreatment through mothers' CPTS symptoms and orientation to body (indirect effect = 0.064; p = 0.023). CONCLUSIONS Child maltreatment is implicated in posttraumatic orientation towards bodily signals. Such secondary processes may be intergenerationally transmitted. BACKGROUND Despite the number of studies showing the link between maternal adverse childhood experiences (ACEs) and offspring's neural development and mental health, little is known about the impacts of maternal ACEs on offspring's academic performance in the adolescent period. OBJECTIVE To examine the associations between maternal ACEs and self-rated academic performance in adolescent offspring. PARTICIPANTS AND SETTING Data from the population-based Kochi Child Health Impact of Living Difficulty (K-CHILD) study, conducted in 2016, was analyzed. Participants included 10,810 children in fifth grade, eighth grade, and eleventh grade living in Kochi prefecture, Japan, and data from maternal respondents were used (n = 7964). METHODS Maternal ACEs, childhood social economic status, current mental health, current socioeconomic status and maternal maltreatment of child were assessed by mothers. Self-rated academic performance was reported by children using a 5-point Likert scale. Ordinal logistic regression analyses were performed, which excluded children with lower self-esteem to avoid measurement bias on self-rated academic performance due to low self-esteem. RESULTS A higher number of maternal ACEs had a dose-response relationship with lower self-rated academic performance in adolescent offspring after adjusting for confounder (p trend less then 0.001). Specifically, adolescents of mothers who experienced parent loss were more likely to report lower self-rated academic performance (OR = 1.31; 95 %CI = 1.16-1.47), whereas adolescents of mothers who experienced maltreatment in childhood showed no association (OR = 1.10, 95 %CI = 0.99-1.22). CONCLUSIONS Maternal ACEs, and especially maternal parent loss, were associated with lower self-rated academic performance in adolescent offspring. Further study is needed to elucidate the possible mechanism underlying this association. BACKGROUND Child maltreatment reports (CMR) are both common and strongly associated with various negative outcomes. OBJECTIVE To examine CMR risks by child age, early childhood context, current/cumulative economic status (welfare receipt), race, and other risk factors with a longitudinal dataset. PARTICIPANTS AND SETTING The CAN sample included 2,111 children having a CMR ≤ age 3, suggestive of a harmful early childhood context. The AFDC sample included 1,923 children having AFDC but no CMR ≤ age 3, suggestive of early childhood protective factors despite poverty. METHODS We estimated the CMR likelihood at each age from 1-17 years based on various risk factors while following up children from 1995-2009. RESULTS During follow-up, CMR likelihoods were substantially higher for the CAN sample than for the AFDC sample. The age-CMR relationship was strongly negative for the CAN sample (OR = 0.87, 95% CI = 0.86-0.88). This relationship was weaker for the AFDC sample (OR = 0.92, 0.89-0.95) and became non-significant for children who exited welfare. Current welfare receipt remained a strong predictor of CMR likelihoods for both CAN (OR = 2.32, 1.98-2.71) and AFDC (OR = 2.08, 1.61-2.68) samples. Prior welfare receipt moderately increased CMR likelihoods among those not currently on welfare. Controlling for other risk factors, White children had the highest likelihood of CMR. Other child and parent level vulnerabilities also increased CMR risk over time. CONCLUSIONS This study highlights the importance of longitudinal analytic approaches and the utility of cross-sector administrative data in improving our ability to understand and predict CMRs over time. Congenital radioulnar synostosis (RUS) is a rare skeletal disorder that is characterized by fusion of the radius and ulna. As the etiology of RUS is largely unknown, its treatment options are currently limited. A de novo missense mutation in the zinc finger matrin-type 2 (ZMAT2) gene was newly identified in a 5-year-old boy with RUS using whole-exome sequencing. Herein, we sought to further explore the function of zmat2 in zebrafish. Whole-mount in situ hybridization revealed site-specific expression of zzmat2 in the pectoral fins (equivalent to human upper limbs) and craniofacial regions, while immunohistochemistry showed the expression of zZmat2 in the pectoral fins and heart region. Gene knockdown produced defects in the pectoral fins and dorso-ventral patterning. zzmat2 knockdown also caused embryo dorsalization, a phenotype consistent with reduced/insufficient bone morphogenetic protein (BMP) signaling. These abnormalities were partially rescued by zbmp2b RNA overexpression and fully rescued by simultaneous overexpression of wild-type zzmat2. Importantly, the overexpression of mutant zzmat2 corresponding to the newly-identified mutation did not fully rescue the dorso-ventral patterning defects. The above findings indicate that ZMAT2 regulates skeletal development via the BMP signaling pathway, and its mutation may lead to a loss or reduction in biological activity. Thus, the newly identified ZMAT2 mutation potentially plays a causal role in RUS through deregulation of BMP signaling. Perchloroethene (PCE) is a hazardous and persistent groundwater pollutant. Both treatment with nanoscaled zero-valent iron (nZVI) and biological degradation by bacteria have downsides. Distribution of nZVI underground is difficult and a high percentage of injected nZVI is consumed by anaerobic corrosion, forming H2 rather than being available for PCE dechlorination. On the other hand, microbial PCE degradation can suffer from the absence of H2. This can cause the accumulation of the hazardous metabolites cis-1,2-dichloroethene (DCE) or vinylchloride (VC). The combination of chemical and biological PCE degradation is a promising approach to overcome the disadvantages of each method alone. In this lysimeter study, artificial aquifers were created to test the influence of nZVI on anaerobic microbial PCE dechlorination by a commercially available culture containing Dehalococcoides spp. under field-like conditions. The effect of the combined treatment was investigated with molasses as an additional electron source and after cessation of molasses addition. The combination of nZVI and the Dehalococcoides spp. containing culture led to a PCE discharge in the lysimeter outflow that was 4.7 times smaller than that with nZVI and 1.6 times smaller than with bacterial treatment. Moreover, fully dechlorinated end-products showed an 11-fold increase compared to nZVI and a 4.2-fold increase compared to the microbial culture. The addition of nZVI to the microbial culture also decreased the accumulation of hazardous metabolites by 1.7 (cis-DCE) and 1.2 fold (VC). The stimulatory effect of nZVI on microbial degradation was most obvious after the addition of molasses was stopped. INTRODUCTION In the context of the COVID-19 pandemic, specific recommendations are required for the management of patients with gynecologic cancer. MATERIALS AND METHOD The FRANCOGYN group of the National College of French Gynecologists and Obstetricians (CNGOF) convened to develop recommendations based on the consensus conference model. RESULTS If a patient with a gynecologic cancer presents with COVID-19, surgical management should be postponed for at least 15 days. For cervical cancer, radiotherapy and concomitant radiochemotherapy could replace surgery as first-line treatment and the value of lymph node staging should be reviewed on a case-by-case basis. For advanced ovarian cancers, neoadjuvant chemotherapy should be preferred over primary cytoreduction surgery. It is legitimate not to perform hyperthermic intraperitoneal chemotherapy during the COVID-19 pandemic. For patients who are scheduled to undergo interval surgery, chemotherapy can be continued and surgery performed after 6 cycles. For patients with early stage endometrial cancer of low and intermediate preoperative ESMO risk, hysterectomy with bilateral adnexectomy combined with a sentinel lymph node procedure is recommended. Surgery can be postponed for 1-2 months in low-risk endometrial cancers (FIGO Ia stage on MRI and grade 1-2 endometrioid cancer on endometrial biopsy). For patients of high ESMO risk, the MSKCC algorithm (combining PET-CT and sentinel lymph node biopsy) should be applied to avoid pelvic and lumbar-aortic lymphadenectomy. CONCLUSION During the COVID-19 pandemic, management of a patient with cancer should be adapted to limit the risks associated with the virus without incurring loss of chance. OBJECTIVE 3',5'-Cyclic adenosine monophosphate (cAMP) is a central second messenger governing brown adipocyte differentiation and function. β-adrenergic receptors (β-ARs) stimulate adenylate cyclases which produce cAMP. Moreover, cyclic nucleotide levels are tightly controlled by phosphodiesterases (PDEs), which can generate subcellular microdomains of cAMP. Since the spatio-temporal organization of the cAMP signalling pathway in adipocytes is still unclear, we sought to monitor real-time cAMP dynamics by live cell imaging in pre-mature and mature brown adipocytes from transgenic mice expressing Epac1-camps using a FRET biosensor. METHODS We measured the real-time dynamics of cAMP in murine pre-mature and mature brown adipocytes during stimulation of individual β-AR subtypes, as well as its regulation by PDEs using a Förster Resonance Energy Transfer based biosensor and pharmacological tools. We also correlated these data with β-AR stimulated lipolysis and analysed the expression of β-ARs and PDEs in brown adipocytes using qPCR and immunoblotting.
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