Consequences of redefining Alzheimer's disease in terms of amyloid burden without regard to cognitive decline

正Alzheimer’s disease(AD)redefined:For the past century,AD has been defined as a disease of progressive cognitive decline paired with a burden of amyloid-β(Aβ)plaques and pathologic tau tangles in the hippocampus and forebrain.However,a recent Framework paper jointly sponsored by the National Institute on Aging and the Alzheimer’s Association(Jack et al.,2018)proposes new classification guidelines for AD,which,if adopted,will have profound     

COVID-19 Among US Dialysis Patients: Risk Factors and Outcomes From a National Dialysis Provider

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Improving Breastfeeding Environments and Feeding Practices in Family Child Care Homes with the Go NAP SACC Program

Maternal and Child Health Journal - Breastfeeding and responsive feeding are important practices that support the health of infants and women. In the United States, breastfeeding continuation rates...     

Validating a diagnostic GCA ultrasonography service against temporal artery biopsy and long-term clinical outcomes

Clinical Rheumatology - Currently, there is no mechanism for service validation of diagnostic ultrasonography (US) for giant cell arteritis (GCA). Temporal artery biopsy (TAB) and classification...     

Bispecific antibody based therapeutics: Strengths and challenges

Monoclonal antibody-based targeted therapy has greatly improved treatment options for patients. However, long-term efficacy of such antibodies is limited by resistance mechanisms. New insights into the mechanisms by which tumors evade immune control have driven innovative therapeutic strategies to eliminate cancer by re-directing immune cells to tumors. Advances in protein engineering technology have generated multiple bispecific antibody (BsAb) formats capable of targeting multiple antigens as a single agent. Approval of two BsAb and three check point blocking mAbs represent a paradigm shift in the use of antibody constructs. Since BsAbs can directly target immune cells to tumors, drug resistance and severe adverse effects are much reduced. The wave of next generation “bispecific or multispecific antibodies” has advanced multiple candidates into ongoing clinical trials. In this review, we focus on preclinical and clinical studies in hematological malignancies as well as discuss reasons for the limited success of BsAbs against solid tumors.     

Depression Change Profiles in Adolescents Treated for Comorbid Depression/Substance Abuse and Profile Membership Predictors

Using data from a randomized trial in which adolescents with depressive and substance use disorders (SUD) received treatments for both disorders in either a sequenced or coordinated manner, we (a) determine the number and nature of depression response profiles through 1-year posttreatment and (b) examine whether 8 previously identified factors predict profile membership. There were 170 adolescents (M age = 16.4 years; 22% female; 28% Hispanic, 61% Non-Hispanic White) with comorbid depressive disorder/SUD randomized to one of three sequences of receiving the Adolescent Coping With Depression Course and Functional Family Therapy for SUD (depression treatment followed by SUD treatment; SUD treatment followed by depression treatment; coordinated treatment). Depression was assessed at 7 points from baseline to 1-year follow-up. A 4-class solution fit the data best, with groups labeled Mildly Depressed Responders (57.1%), Depressed Responders (18.8%), Depressed Non-Responders (12.9%), and Depressed with Recurrence (11.2%). The 4 change profiles differed on indices of all but 1 predictor (age); most differences were driven by lower scores among Mildly Depressed Responders. Profile membership was most strongly predicted by depression severity, cognitive distortions, hopelessness, and global functioning. The strongest predictor of Nonresponse was low family cohesion, whereas Recurrence was associated with hopelessness, suicide attempts, and starting treatment near the end of the school year. Most depressed adolescents experienced a positive response that was maintained. Understanding the most common profiles of depression change during and following treatment and the variables that predict change can help improve treatment outcomes and advance tailoring efforts.