Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS.

Chimeric Antigen Receptor (CAR) T-cells have emerged as a powerful immunotherapy for various forms of cancer and show promise in treating HIV-1 infection. However, significant limitations are persistence and whether peripheral T cell-based products can respond to malignant or infected cells that may reappear months or years after treatment remains unclear. Hematopoietic Stem/Progenitor Cells (HSPCs) are capable of long-term engraftment and have the potential to overcome these limitations.

Patient and Caregiver Assessment of the Benefits From the Clinical Use of Amyloid PET Imaging.

Introduction: Few studies to date have explored patient and caregiver views on the clinical use of amyloid positron emission tomography (PET).

Methods: A 7-item questionnaire assessing patient and caregiver views (510 total respondents) toward amyloid PET imaging was advertised broadly through alz.org/trialmatch.

Effect of maternal high-fat diet on key components of the placental and hepatic endocannabinoid system.

Maternal obesity in pregnancy has been linked to a spectrum of adverse developmental changes. Involvement of eCBs in obesity is well characterized. However, information regarding eCB physiology in obesity associated with pregnancy is sparse.

Neuropsychiatric signs and symptoms of Alzheimer's disease: New treatment paradigms.

Neuropsychiatric symptoms (NPSs) are hallmarks of Alzheimer's disease (AD), causing substantial distress for both people with dementia and their caregivers, and contributing to early institutionalization. They are among the earliest signs and symptoms of neurocognitive disorders and incipient cognitive decline, yet are under-recognized and often challenging to treat. With this in mind, the Alzheimer's Association convened a Research Roundtable in May 2016, bringing together experts from academia, industry, and regulatory agencies to discuss the latest understanding of NPSs and review the development of therapeutics and biomarkers of NPSs in AD.

Multiple comorbid neuropathologies in the setting of Alzheimer's disease neuropathology and implications for drug development.

Dementia is often characterized as being caused by one of several major diseases, such as Alzheimer's disease (AD), cerebrovascular disease, Lewy body disease, or a frontotemporal degeneration. Failure to acknowledge that more than one entity may be present precludes attempts to understand interactive relationships. The clinicopathological studies of dementia demonstrate that multiple pathologic processes often coexist.

EXPANSION of diabetes education in a United States-Mexico border community (Expanding Services for Patients to Acquire New Skills, Set Goals, and Improve Overall Knowledge).

Objectives: To describe the process used by a pharmacy team at a community health center to coordinate and expand diabetes education services (English and Spanish) for a predominantly Hispanic, Spanish-speaking population.

Setting: The project was implemented at 2 clinics in a federally qualified community health center system based in a low-income southwest U.S.

Recognition of an obstacle in a flow using artificial neural networks.

In this work a series of artificial neural networks (ANNs) has been developed with the capacity to estimate the size and location of an obstacle obstructing the flow in a pipe. The ANNs learn the size and location of the obstacle by reading the profiles of the dynamic pressure q or the x component of the velocity v_{x} of the fluid at a certain distance from the obstacle. Data to train the ANN were generated using numerical simulations with a two-dimensional lattice Boltzmann code.

A Single Set of Interneurons Drives Opposite Behaviors in C. elegans.

Many chemosensory stimuli evoke innate behavioral responses that can be either appetitive or aversive, depending on an animal's age, prior experience, nutritional status, and environment [1-9]. However, the circuit mechanisms that enable these valence changes are poorly understood. Here, we show that Caenorhabditis elegans can alternate between attractive or aversive responses to carbon dioxide (CO), depending on its recently experienced CO environment.

New approaches for the enhancement of chimeric antigen receptors for the treatment of HIV.

HIV infection continues to be a life-long chronic disease in spite of the success of antiretroviral therapy (ART) in controlling viral replication and preventing disease progression. However, because of the high cost of treatment, severe side effects, and inefficiency in curing the disease with ART, there is a call for alternative therapies that will provide a functional cure for HIV. Cytotoxic T lymphocytes (CTLs) are vital in the control and clearance of viral infections and therefore immune-based therapies have attempted to engineer HIV-specific CTLs that would be able to clear the infection from the body.

Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers.

The diagnosis of Alzheimer's disease can be improved by the use of biological measures. Biomarkers of functional impairment, neuronal loss, and protein deposition that can be assessed by neuroimaging (ie, MRI and PET) or CSF analysis are increasingly being used to diagnose Alzheimer's disease in research studies and specialist clinical settings. However, the validation of the clinical usefulness of these biomarkers is incomplete, and that is hampering reimbursement for these tests by health insurance providers, their widespread clinical implementation, and improvements in quality of health care.

Identification of two frataxin isoforms in Zea mays: Structural and functional studies.

Frataxin is a ubiquitous protein that plays a role in Fe-S cluster biosynthesis and iron and heme metabolism, although its molecular functions are not entirely clear. In non-photosynthetic eukaryotes, frataxin is encoded by a single gene, and the protein localizes to mitochondria. Here we report the presence of two functional frataxin isoforms in Zea mays, ZmFH-1 and ZmFH-2.

Randomized controlled trials in mild cognitive impairment: Sources of variability.

Objective: To examine the variability in performance among placebo groups in randomized controlled trials for mild cognitive impairment (MCI).

Methods: Placebo group data were obtained from 2 National Institute on Aging (NIA) MCI randomized controlled trials, the Alzheimer's Disease Cooperative Study (ADCS) MCI trial and the Alzheimer's Disease Neuroimaging Initiative (ADNI), which is a simulated clinical trial, in addition to industry-sponsored clinical trials involving rivastigmine, galantamine, rofecoxib, and donepezil. The data were collated for common measurement instruments.

Chimeric antigen receptor engineered stem cells: a novel HIV therapy.

Despite the success of combination antiretroviral therapy (cART) for suppressing HIV and improving patients' quality of life, HIV persists in cART-treated patients and remains an incurable disease. Financial burdens and health consequences of lifelong cART treatment call for novel HIV therapies that result in a permanent cure. Cellular immunity is central in controlling HIV replication.

The biomarker-based diagnosis of Alzheimer's disease. 1-ethical and societal issues.

There is great interest in the use of biomarkers to assist in the timely identification of Alzheimer's disease (AD) in individuals with mild symptoms. However, the inclusion of AD biomarkers in clinical criteria poses socioethical challenges. The Geneva Task Force for the Roadmap of Alzheimer's Biomarkers was established to deliver a systematic strategic research agenda (aka roadmap) to promote efficient and effective validation of AD biomarkers and to foster their uptake in clinical practice.

Alzheimer's disease: The next frontier-Special Report 2017.

In the history of medicine, one means to progress is when we make the decision that our assumptions and definitions of disease are no longer consistent with the scientific evidence, and no longer serve our health care needs. The arc of scientific progress is now requiring a change in how we diagnose Alzheimer's disease. Both the National Institute on Aging-Alzheimer's Association (NIA-AA) 2011 workgroup and the International Work Group (IWG) have proposed guidelines that use detectable measures of biological changes in the brain, commonly known as biological markers, or biomarkers, as part of the diagnosis.

Comparison of Two Intensive Bowel Cleansing Regimens in Patients With Previous Poor Bowel Preparation: A Randomized Controlled Study.

Objectives: Inadequate bowel cleansing is a major burden for endoscopy units. The aim of this study was to compare two intensive bowel cleansing regimens in patients with previous colonoscopy with inadequate bowel preparation.

Methods: Patients with inadequate cleansing at index colonoscopy were randomized to 4-L split-dose polyethylene-glycol (PEG) regimen vs.

True's beaked whale () in Macaronesia.

The True's beaked whale (, True 1913) is a poorly known member of the Ziphiidae family. Its distribution in the northern hemisphere is thought to be restricted to the temperate or warm temperate waters of the North Atlantic, while a few stranding records from the southern hemisphere suggest a wider and antitropical distribution, extending to waters from the Atlantic coast of Brazil to South Africa, Mozambique, Australia and the Tasman Sea coast of New Zealand. This paper (i) reports the first molecular confirmation of the occurrence of the True's beaked whale at the southern limit of its distribution recorded in the northeast Atlantic: the Azores and Canary Islands (macaronesian ecoregion); (ii) describes a new colouration for this species using evidence from a whale with molecular species confirmation; and (iii) contributes to the sparse worldwide database of live sightings, including the first underwater video recording of this species and close images of a calf.

Risk factors for inadequate bowel preparation: a validated predictive score.

 Inadequate bowel cleansing negatively affects the efficiency of colonoscopy in routine clinical practice. The aim of this study was to design and validate a predictive model for inadequate bowel cleanliness.  The model was built from 667 consecutive outpatients (development cohort) who were prospectively scheduled for colonoscopy between June and September 2014.

In silico discovery and in vitro activity of inhibitors against 7,8-diaminopelargonic acid synthase ( BioA).

Computer-aided drug discovery and development approaches such as virtual screening, molecular docking, and in silico drug property calculations have been utilized in this effort to discover new lead compounds against tuberculosis. The enzyme 7,8-diaminopelargonic acid aminotransferase (BioA) in (), primarily involved in the lipid biosynthesis pathway, was chosen as the drug target due to the fact that humans are not capable of synthesizing biotin endogenously. The computational screening of 4.

A Family of Single Copy repABC-Type Shuttle Vectors Stably Maintained in the Alpha-Proteobacterium Sinorhizobium meliloti.

A considerable share of bacterial species maintains segmented genomes. Plant symbiotic α-proteobacterial rhizobia contain up to six repABC-type replicons in addition to the primary chromosome. These low or unit-copy replicons, classified as secondary chromosomes, chromids, or megaplasmids, are exclusively found in α-proteobacteria.

Consensus classification of posterior cortical atrophy.

Introduction: A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings.

Methods: Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA.

Results: A three-level classification framework for PCA is described comprising both syndrome- and disease-level descriptions.