Evaluation of risk prediction scores for adults hospitalized with COVID-19 in a highly-vaccinated population, Aotearoa New Zealand 2022.

Objectives: COVID-19 severity prediction scores need further validation due to evolving COVID-19 illness. We evaluated existing COVID-19 risk prediction scores in Aotearoa New Zealand, including for Māori and Pacific peoples who have been inequitably affected by COVID-19.

Methods: We conducted a multicenter retrospective cohort study in adults hospitalized with COVID-19 from January to May 2022, including all Māori and Pacific patients, and every second non-Māori, non-Pacific (NMNP) patient to achieve equal analytic power by ethnic grouping.

Calnexin, an ER stress-induced protein, is a prognostic marker and potential therapeutic target in colorectal cancer.

Background: Colorectal cancer (CRC) is a leading cause of cancer mortality in the Western world and commonly treated with genotoxic chemotherapy. Stress in the endoplasmic reticulum (ER) was implicated to contribute to chemotherapeutic resistance. Hence, ER stress related protein may be of prognostic or therapeutic significance.

Sex, age, and hunger regulate behavioral prioritization through dynamic modulation of chemoreceptor expression.

Background: Adaptive behavioral prioritization requires flexible outputs from fixed neural circuits. In C. elegans, the prioritization of feeding versus mate searching depends on biological sex (males will abandon food to search for mates, whereas hermaphrodites will not) as well as developmental stage and feeding status.

Systems analysis of BCL2 protein family interactions establishes a model to predict responses to chemotherapy.

Apoptotic desensitization is a hallmark of cancer cells, but present knowledge of molecular systems controlling apoptosis has yet to provide significant prognostic insights. Here, we report findings from a systems study of the intrinsic pathway of apoptosis by BCL2 family proteins and clinical translation of its findings into a model with applications in colorectal cancer (CRC). By determining absolute protein quantifications in CRC cells and patient tumor samples, we found that BAK and BAX were expressed more highly than their antiapoptotic inhibitors.

Early oligodendrocyte/myelin pathology in Alzheimer's disease mice constitutes a novel therapeutic target.

The detection of myelin disruptions in Alzheimer's disease (AD)-affected brain raises the possibility that oligodendrocytes undergo pathophysiological assault over the protracted course of this neurodegenerative disease. Oligodendrocyte compromise arising from direct toxic effects imparted by pathological amyloid-beta peptides and/or through signals derived from degenerating neurons could play an important role in the disease process. We previously demonstrated that 3xTg-AD mice, which harbor the human amyloid precursor protein Swedish mutant transgene, presenilin knock-in mutation, and tau P301L mutant transgene, exhibit significant alterations in overall myelination patterns and oligodendrocyte status at time points preceding the appearance of amyloid and tau pathology.

Abeta-directed single-chain antibody delivery via a serotype-1 AAV vector improves learning behavior and pathology in Alzheimer's disease mice.

Alzheimer's disease (AD) is a progressive dementing disorder characterized by age-related amyloid-beta (Abeta) deposition, neurofibrillary tangles, and synapse and neuronal loss. It is widely recognized that Abeta is a principal pathogenic mediator of AD. Our goal was to develop an immunotherapeutic approach, which would specifically lead to the clearance and/or neutralization of Abeta in the triple transgenic mouse model (3xTg-AD).

An improved method for generating consistent soluble amyloid-beta oligomer preparations for in vitro neurotoxicity studies.

Soluble Abeta oligomers are recognized as playing a key role in Alzheimer's disease (AD) pathophysiology. Despite their significance, many investigators encounter difficulty generating reliable preparations for in vitro and in vivo experiments. Solutions of Abeta are often unstable and soluble conformer profiles inconsistent.

Effects of herpes simplex virus amplicon transduction on murine dendritic cells.

The herpes simplex virus (HSV)-based amplicon is a versatile vaccine platform that has been preclinically vetted as a gene-based immunotherapeutic for cancer, HIV, and neurodegenerative disorders. Although it is well known that injection of dendritic cells (DCs) transduced ex vivo with helper virus-free HSV amplicon vectors expressing disease-relevant antigens induces antigen-specific immune responses, the cellular receptor(s) by which the amplicon virion gains entry into DCs, as well as the effects that viral vector transduction impinges on the physiological status of these cells, is less understood. Herein, we examine the effects of amplicon transduction on mouse bone marrow-derived DCs.

Potential of chemo-immunotherapy and radioimmunotherapy in relapsed primary central nervous system (CNS) lymphoma.

Five patients with relapsed PCNSL were given chemo-immunotherapy (rituximab followed by carboplatin and methotrexate) with osmotic blood-brain barrier (BBB) opening. Four patients achieved CR and one patient had stable disease. Two patients (2/5) had durable responses (survival: 230+, 122+, 82, 42, 38 weeks).

Alterations in striatal dopamine catabolism precede loss of substantia nigra neurons in a mouse model of juvenile neuronal ceroid lipofuscinosis.

Batten disease, or juvenile neuronal ceroid lipofuscinosis (JNCL), results from mutations in the CLN3 gene. This disorder presents clinically around the age of 5 years with visual deficits progressing to include seizures, cognitive impairment, motor deterioration, hallucinations, and premature death by the third to fourth decade of life. The motor deficits include coordination and gait abnormalities, myoclonic jerks, inability to initiate movements, and spasticity.

Translational considerations for CNS gene therapy.

Gene transfer is being rigorously evaluated in the laboratory in the preparation for the development of clinical therapies. Many CNS diseases, which have proved more challenging to treat than peripheral disorders, are prime candidates for gene therapy. However, there are numerous considerations in the development of gene therapy, including delivery, maintenance of expression, transgene level regulation, toxicity of the viral vector system and safety of the gene product.

Kangaroo care: national survey of practice, knowledge, barriers, and perceptions.

Purpose: A national survey was conducted to assess practice, knowledge, barriers, and perceptions regarding Kangaroo Care (KC)--the holding of diaper-clad preterm infants skin-to-skin, chest-to-chest by parents.

Design: A descriptive survey was conducted.

Methods: Kangaroo Care Questionnaires (KCQs), developed for the study, were sent to nurse managers in all hospitals in the United States that were identified as providing neonatal intensive care services (N = 1,133), and were to be completed by the nurse most familiar with the practice of KC in that unit.