Since the US Food and Drug Administration (FDA) approvals of parenteral decitabine and azacitidine, DNA methyltransferase inhibitors, otherwise referred to as DNA hypomethylating agents (HMAs), have been a mainstay in the treatment of higher-risk myelodysplastic syndromes. The development of oral HMAs has been an area of active interest; however, oral bioavailability has been quite poor due to rapid metabolism by cytidine deaminase (CDA). This led to the development of the novel CDA inhibitor cedazuridine, which was combined with an oral formulation of decitabine. Preclinical work demonstrated a pharmacokinetic and pharmacodynamic profile approximate to parenteral decitabine, leading to early-phase clinical trials of oral cedazuridine-decitabine (C-DEC) in myelodysplastic syndromes and chronic myelomonocytic leukemia (CMML). A combination of oral decitabine 35 mg with oral cedazuridine 100 mg was established as the recommended phase 2 dose. Phase 2 data confirmed bioequivalence of C-DEC when compared with parenteral decitabine, and a larger phase 3 trial has demonstrated similar results, leading to the FDA approval of C-DEC for use in intermediate/high-risk myelodysplastic syndrome (MDS) and CMML. This review will focus upon the current role of HMA therapy in MDS/CMML, preclinical and clinical development of C-DEC, and potential roles of oral HMA therapy in myeloid malignancies moving forward.Multisystem inflammatory syndrome in children (MIS-C) emerged in April 2020 in communities with high COVID-19 rates. This new condition is heterogenous but resembles Kawasaki disease (KD), a well-known but poorly understood and clinically heterogenous pediatric inflammatory condition for which weak associations have been found with a myriad of viral illnesses. Epidemiological data clearly indicate that SARS-CoV-2 is the trigger for MIS-C, which typically occurs about 1 mo after infection. These findings support the hypothesis of viral triggers for the various forms of classic KD. We further suggest that rare inborn errors of immunity (IEIs) altering the immune response to SARS-CoV-2 may underlie the pathogenesis of MIS-C in some children. The discovery of monogenic IEIs underlying MIS-C would shed light on its pathogenesis, paving the way for a new genetic approach to classic KD, revisited as a heterogeneous collection of IEIs to viruses.HIV-associated neurocognitive disorders (HAND) criteria are frequently used to describe cognitive impairment in people with HIV (PWH) across diverse populations globally. These criteria typically find 20-60% of PWH meet criteria for HAND, which does not tally with clinical observations in the modern era that cognitive disorders present relatively infrequently. Most with HAND have asymptomatic neurocognitive impairment (ANI), however the significance of low cognitive test performance without symptoms is uncertain.  https://www.selleckchem.com/products/rxdx-106-cep-40783.html  Methods underlying HAND criteria carry a false positive rate that can exceed 20%. Comorbidities, education and complex socioeconomic factors can influence cognitive test performance, further increasing the potential for misclassification. We propose a new framework to characterise cognitive impairment in PWH which requires a clinical history and acknowledges the multifactorial nature of low cognitive test performance. This framework is intended to be applicable across diverse populations globally, be more aligned with clinical observations and more closely represent HIV brain pathology.
  Safe reduction of the cesarean delivery rate is a national priority.
 
  To evaluate the rates of cesarean delivery for nulliparous, term, singleton, vertex (NTSV) births in California in the context of a statewide multifaceted intervention designed to reduce the rates of cesarean delivery.
 
  Observational study of cesarean delivery rates from 2014 to 2019 among 7 574 889 NTSV births in the US and at 238 nonmilitary hospitals providing maternity services in California. From 2016 to 2019, California Maternal Quality Care Collaborative partnered with Smart Care California to implement multiple approaches to decrease the rates of cesarean delivery. Hospitals with rates of cesarean delivery greater than 23.9% for NTSV births were invited to join 1 of 3 cohorts for an 18-month quality improvement collaborative between July 2016 and June 2019.
 
  Within the collaborative, multidisciplinary teams implemented multiple strategies supported by mentorship, shared learning, and rapid-cycle data feedback. Partnerships amontivities was associated with a lower odds of cesarean delivery for NTSV births (24.4% vs 24.6%; adjusted odds ratio, 0.87 [95% CI, 0.85-0.89]).
 
  In this observational study of NTSV births in California from 2014 to 2019, the rates of cesarean delivery decreased over time in the setting of the implementation of a coordinated hospital-level collaborative and statewide initiatives designed to support vaginal birth.
 In this observational study of NTSV births in California from 2014 to 2019, the rates of cesarean delivery decreased over time in the setting of the implementation of a coordinated hospital-level collaborative and statewide initiatives designed to support vaginal birth.
  Trends in type 2 diabetes show an increase in prevalence along with younger age of onset. While vascular complications of early-onset type 2 diabetes are known, the associations with dementia remains unclear.
 
  To determine whether younger age at diabetes onset is more strongly associated with incidence of dementia.
 
  Population-based study in the UK, the Whitehall II prospective cohort study, established in 1985-1988, with clinical examinations in 1991-1993, 1997-1999, 2002-2004, 2007-2009, 2012-2013, and 2015-2016, and linkage to electronic health records until March 2019. The date of final follow-up was March 31, 2019.
 
  Type 2 diabetes, defined as a fasting blood glucose level greater than or equal to 126 mg/dL at clinical examination, physician-diagnosed type 2 diabetes, use of diabetes medication, or hospital record of diabetes between 1985 and 2019.
 
  Incident dementia ascertained through linkage to electronic health records.
 
  Among 10 095 participants (67.3% men; aged 35-55 years in 1985-1988), a total of 1710 cases of diabetes and 639 cases of dementia were recorded over a median follow-up of 31.