In-vivo sensitivity to olaparib/irinotecan was seen in ATRX mutant but not wild-type xenografts. Finally, sustained responses to olaparib/irinotecan therapy were seen in an ATRX deleted neuroblastoma patient derived xenograft.

ATRX LoF results in specific DNA damage repair defects that can be therapeutically exploited. In ATRX LoF models, preclinical sensitivity is demonstrated to olaparib and irinotecan, a combination that can be rapidly translated into the clinic.

This work was supported by Christopher’s Smile, Neuroblastoma UK, Cancer Research UK, and the Royal Marsden Hospital NIHR BRC.

This work was supported by Christopher’s Smile, Neuroblastoma UK, Cancer Research UK, and the Royal Marsden Hospital NIHR BRC.

The contribution of substance use disorders to the burden of severe maternal morbidity in the United States is poorly understood. The objective was to estimate the independent association between substance use disorders during pregnancy and risk of severe maternal morbidity.

Retrospective analysis of a weighted 53.4 million delivery hospitalizations from 2003 to 2016 among females aged>18 in the National Inpatient Sample. We constructed measures of substance use disorders using diagnostic codes for cannabis, opioids, and stimulants (amphetamines or cocaine) abuse or dependence during pregnancy. The outcome was the presence of any of the 21 CDC indicators of severe maternal morbidity. Using weighted multivariable logistic regression, we estimated the association between substance use disorders and adjusted risk of severe maternal morbidity. Because older age at delivery is predictive of severe maternal morbidity, we tested for effect modification between substance use and maternal age by age group (18-34 y vs >34 y).

Pregnant women with an opioid use disorder had an increased risk of severe maternal morbidity compared with women without an opioid use disorder (18-34 years aOR 1.51; 95 % CI 1.41,1.61, >34 years aOR 1.17; 95 % CI 1.00,1.38). Compared with their counterparts without stimulant use disorders, pregnant women with a simulant use disorder (amphetamines, cocaine) had an increased risk of severe maternal morbidity (18-34 years aOR 1.92; 95 % CI 1.80,2.0, >34 years aOR 1.85; 95 % CI 1.66,2.06). Cannabis use disorders were not associated with an increased risk of severe maternal morbidity.

Substance use disorders during pregnancy, particularly opioids, amphetamines, and cocaine use disorders, may contribute to severe maternal morbidity in the United States.

Substance use disorders during pregnancy, particularly opioids, amphetamines, and cocaine use disorders, may contribute to severe maternal morbidity in the United States.

There is little data on the prevalence and effects of eating disorders in patients with T2DM.

To evaluate the presence of eating disorders (ED) and their association with glycemic control and metabolic parameters in adult patients with type 2 diabetes mellitus (T2DM).

A cross-sectional study was conducted in the endocrinology outpatient unit of our tertiary care centre between January 2017 to December 2018. Eating Attitudes Test (EAT-26) and Binge Eating Scale (BES) questionnaires were used to screen for ED in adults with T2DM (group 1) and controls without T2DM (group 2). Cut off scores ≥18 on BES was considered as a positive screen for Binge eating disorder in participants with and without T2DM. A score of ≥30 on EAT-26 was defined as abnormal for participants with T2DM and ≥20 for those without T2DM. Formal psychiatric assessment was done to diagnose ED in those who screened positive on the basis of scores on BES or EAT-26 or both. Demographic, anthropometric and relevant medical details like duratiof eating disorders are lower (in both controls and patients with T2DM) than those reported from developed western countries.

The coronavirus disease-2019 (COVID-19) pandemic impacted healthcare services for kidney disease patients. Lockdown and social distancing were mandated in Kurdistan, Iraq to combat the transmission of the infection. The report analyzed the impact of the COVID-19 pandemic on kidney disease patient care in Duhok City, Kurdistan Region of Iraq.

This study took place in the Duhok Kidney Disease and Transplant Center and compared data from February-April 2019 and 2020.

The average number of patients visiting the consultation unit per week was reduced from 68.67±13.6, to 33.42±29.36 (P=0.001) during the pandemic. In the dialysis unit, weekly hemodialysis sessions were reduced from 341.5 to 306.42 sessions (P=0.002). The number of patients visiting the kidney transplant consultation unit was significantly reduced (135.7±37.7 versus 102.5±26.3; P=0.005). The number of kidney transplant operations per week was reduced from 1.167 to 0.5 (P=0.025).

The COVID-19 pandemic interrupted healthcare services and may continue to impart long-term negative consequences for kidney disease patients.

The COVID-19 pandemic interrupted healthcare services and may continue to impart long-term negative consequences for kidney disease patients.

Long-term treatment of Parkinson’s disease (PD) with l-DOPA typically leads to development of l-DOPA induced dyskinesia (LID). Amantadine, an NMDA antagonist, attenuates LID, but with limited efficacy and considerable side-effects. NLX-112 (also known as befiradol or F13640), a highly selective and efficacious 5-HT

receptor agonist, reduced LID when tested in rodent and marmoset models of PD.

The effects of NLX-112 (0.03, 0.1 and 0.3mg/kg PO) on established LID evoked by acute challenge with l-DOPA (27.5±3.8mg/kg PO) were assessed in MPTP-treated cynomolgus macaques. Amantadine (10mg/kg PO) was tested as a positive control. Plasma exposure of NLX-112 (0.1mg/kg PO) was determined.

NLX-112 significantly and dose-dependently reduced median LID levels by up to 96% during the first hour post-administration (0.3mg/kg). this website Moreover, NLX-112 reduced the duration of ‘bad on-time’ associated with disabling LID by up to 48% (0.3mg/kg). In contrast, NLX-112 had negligible impact on the anti-parkinsonian benefit of ling an alternative for patients in whom amantadine is poorly tolerated or without useful effect.