Neuroprotective effects of p62(SQSTM1)-engineered lactic acid bacteria in Alzheimer's disease: a pre-clinical study.

Alzheimer's disease (AD) is a progressive neurodegeneration characterized by neuron death ending in memory and cognitive decline. A major concern in AD research is the identification of new therapeutics that could prevent or delay the onset of the disorder, with current treatments being effective only in reducing symptoms. In this perspective, the use of engineered probiotics as therapeutic tools for the delivery of molecules to eukaryotic cells is finding application in several disorders.

A general evidence-based sequence variant control limit for recombinant therapeutic protein development.

Sequence variants (SVs) resulting from unintended amino acid substitutions in recombinant therapeutic proteins have increasingly gained attention from both regulatory agencies and the biopharmaceutical industry given their potential impact on efficacy and safety. With well-optimized production systems, such sequence variants usually exist at very low levels in the final protein products due to the high fidelity of DNA replication and protein biosynthesis process in mammalian expression systems such as Chinese hamster ovary cell lines. However, their levels can be significantly elevated in cases where the selected production cell line has unexpected DNA mutations or the manufacturing process is not fully optimized, for example, if depletion of certain amino acids occurs in the cell culture media in bioreactors.

Sympathetic function and markers of inflammation in well-controlled HIV.

Purpose: HIV-associated autonomic neuropathy (HIV-AN) is common and may be associated with both sympathetic and parasympathetic dysfunction. Sympathetic nervous system (SNS) dysfunction occurs on a continuum of hyper-to hypo-adrenergic function, and may be a mediator between psychological stress and chronic inflammation. We sought to describe patterns of SNS dysfunction in people living with HIV, and to determine whether SNS dysfunction is associated with markers of systemic inflammation (focusing on IL-6 and TNF-α) and pain and anxiety.

Discontinuation of Immunosuppressive Medications in Children With Inflammatory Bowel Disease on Combination Therapy.

We determined the frequency and factors associated with the first clinical relapse after immunomodulator (IM) withdrawal in a cohort of children with inflammatory bowel disease on combination therapy. A total of 105 patients (89 with Crohn disease [CD]) in clinical remission were included (91 [86.7%] were on infliximab, 53 [50.

Broad Antibody and Cellular Immune Response From a Phase 2 Clinical Trial With a Novel Multivalent Poxvirus-Based Respiratory Syncytial Virus Vaccine.

Background: Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in young children and the elderly. Protective immunity is not generated after repeated infections, but vaccination may hopefully prove effective.

Methods: This phase 2 clinical study investigated a multivalent RSV vaccine (MVA-BN-RSV) designed to induce broad antibody and cellular immune responses by encoding RSV surface proteins F, G (for both A and B subtypes), and internal antigens (M2, N).

Reopening Colleges and Universities During the COVID-19 Pandemic.

In their article, Cheng and colleagues present the plan for reopening colleges and universities in Taiwan. There are important differences between Taiwan and other countries, but residential colleges and universities present similar challenges to pandemic control for all. Considering how well Taiwan has managed COVID-19 overall, the editorialists believe that the plan for safely reopening colleges and universities in Taiwan offers important principles.

Multimodal radiomics and cyst fluid inflammatory markers model to predict preoperative risk in intraductal papillary mucinous neoplasms.

Our paper contributes to the burgeoning field of surgical data science. Specifically, multimodal integration of relevant patient data is used to determine who should undergo a complex pancreatic resection. Intraductal papillary mucinous neoplasms (IPMNs) represent cystic precursor lesions of pancreatic cancer with varying risk for malignancy.

Use of patient-generated health data across healthcare settings: implications for health systems.

Objective: The growing prevalence of chronic conditions requiring changes in lifestyle and at-home self-management has increased interest in and need for supplementing clinic visits with data generated by patients outside the clinic. Patient-generated health data (PGHD) support the ability to diagnose and manage chronic conditions, to improve health outcomes, and have the potential to facilitate more "connected health" between patients and their care teams; however, health systems have been slow to adopt PGHD use in clinical care.

Materials And Methods: We surveyed current and potential users of PGHD to catalog how PGHD is integrated into clinical care at an academic health center.

Alterations in driver genes are predictive of survival in patients with resected pancreatic ductal adenocarcinoma.

Background: KRAS, TP53, CDKN2A, and SMAD4 are established driver genes in pancreatic ductal adenocarcinoma (PDAC). This study was aimed at determining whether the mutational status of driver genes and those involved in DNA repair pathways are associated with clinical outcomes for individuals who undergo resection.

Methods: Eligible individuals were those who underwent resection of PDAC and consented to targeted sequencing of their primary tumor via Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT).

Altered RNA Splicing by Mutant p53 Activates Oncogenic RAS Signaling in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is driven by co-existing mutations in KRAS and TP53. However, how these mutations collaborate to promote this cancer is unknown. Here, we uncover sequence-specific changes in RNA splicing enforced by mutant p53 which enhance KRAS activity.

High body mass index is not associated with increased treatment failure in infliximab treated pediatric patients with inflammatory bowel disease.

Background And Aim: While weight gain during infliximab therapy in inflammatory bowel disease (IBD) is common, there has been limited research evaluating its impact on infliximab efficacy.

Methods: Primary aims of this study were to determine the frequency of excess weight gain (body mass index [BMI] > 25 kg/m) in children with IBD on maintenance infliximab and evaluate the impact on infliximab dosing, serum trough levels, and treatment failure. Secondary aims were to determine differences in weight gain, treatment characteristics, and clinical/biochemical variables between patients with therapeutic and subtherapeutic maintenance therapy trough levels.

Label-Free Quantitative Phosphoproteomics for Algae.

The unicellular alga Chlamydomonas reinhardtii is a model photosynthetic organism for the study of microalgal processes. Along with genomic and transcriptomic studies, proteomic analysis of Chlamydomonas has led to an increased understanding of its metabolic signaling as well as a growing interest in the elucidation of its phosphorylation networks. To this end, mass spectrometry-based proteomics has made great strides in large-scale protein quantitation as well as analysis of posttranslational modifications (PTMs) in a high-throughput manner.

Comparing three approaches for involving patients in research prioritization: a qualitative study of participant experiences.

Background: By participating in priority-setting activities in research, patients and members of the public help ensure that important questions are incorporated into future research agendas. Surveys, focus groups, and online crowdsourcing are increasingly used to obtain input, yet little is known about how they compare for prioritizing research topics. To address this gap, the Study of Methods for Assessing Research Topic Elicitation and pRioritization (SMARTER) evaluated participant satisfaction with the engagement experience across three prioritization activities.

The Nef Protein of the Macrophage Tropic HIV-1 Strain AD8 Counteracts Human BST-2/Tetherin.

Bone Marrow Stromal Cell Antigen 2 (BST-2)/tetherin inhibits the release of numerous enveloped viruses by physically tethering nascent particles to infected cells during the process of viral budding from the cell surface. Tetherin also restricts human immunodeficiency virus (HIV), and pandemic main (M) group HIV type 1s (HIV-1s) are thought to rely exclusively on their Vpu proteins to overcome tetherin-mediated restriction of virus release. However, at least one M group HIV-1 strain, the macrophage-tropic primary AD8 isolate, is unable to express Vpu due to a mutation in its translation initiation codon.

How Neutrophils Meet Their End.

Neutrophil death can transpire via diverse pathways and is regulated by interactions with commensal and pathogenic microorganisms, environmental exposures, and cell age. At steady state, neutrophil turnover and replenishment are continually maintained via a delicate balance between host-mediated responses and microbial forces. Disruptions in this equilibrium directly impact neutrophil numbers in circulation, cell trafficking, antimicrobial defenses, and host well-being.

Improving Quantitative Power in Digital PCR through Digital High-Resolution Melting.

Applying digital PCR (dPCR) technology to challenging clinical and industrial detection tasks has become more prevalent because of its capability for absolute quantification and rare target detection. However, practices learned from quantitative PCR (qPCR) that promote assay robustness and wide-ranging utility are not readily applied in dPCR. These include internal amplification controls to account for false-negative reactions and amplicon high-resolution melt (HRM) analysis to distinguish true positives from false positives.

mHealth and patient generated health data: stakeholder perspectives on opportunities and barriers for transforming healthcare.

Background: Wearable devices, mobile health apps, and geolocation technologies place the ability to track, monitor and report data in the individuals' hands - or on their bodies. These innovations create an opportunity for "connected health," where individuals collect data outside of the healthcare encounter and report it to care providers. Collection of such patient-generated health data (PGHD) has the potential to impact the delivery of healthcare through remote monitoring, and by allowing patients and healthcare teams to provide targeted and efficient care that aligns with the health status of individual patients.

The sound of tablets during coating erosion, disintegration, deaggregation and dissolution.

This research aims to address a gap in our understanding of the mechanisms by which pharmaceutical tablets achieve highly reproducible and predictable drug release. The present industrial and regulatory practice is centred around tablet dissolution, i.e.

Design and implementation of a molecular imaging elective for third-year pharmacy students.

Objective: To design, implement, and evaluate a molecular imaging elective course that would expose Doctor of Pharmacy (PharmD) students to fundamentals of various imaging modalities and their pre-clinical and clinical applications.

Methods: The "Surveys of Multi-Modality Imaging" course is a two-credit hour elective course offered to third-year PharmD and doctoral students. Experiential learning methods including active learning application-based exercises were used to supplement didactic lectures in the form of field trips (with follow-up debriefings), small group team-based tasks, hands-on demonstrations, visual modelling, gamification with problem sets, concept maps regarding given modalities, and concluding with written summary reports and formal in-class group presentations.

S-Nitroso-Proteome Revealed in Stomatal Guard Cell Response to Flg22.

Nitric oxide (NO) plays an important role in stomata closure induced by environmental stimuli including pathogens. During pathogen challenge, nitric oxide (NO) acts as a second messenger in guard cell signaling networks to activate downstream responses leading to stomata closure. One means by which NO's action is achieved is through the posttranslational modification of cysteine residue(s) of target proteins.

Neonatal necrotizing enterocolitis: a case series examining clinical diagnosis with discrepant versus concordant autopsy results.

Objective: The objective of this study is to determine whether rapidity of death in necrotizing enterocolitis (NEC) increased odds of discordance between clinical and pathological diagnosis.

Study Design: Retrospective case-series study including preterm infants admitted to the NICU.

Results: Twenty-two infants met the selection criteria.

A randomized phase II trial to compare safety and immunogenicity of the MVA-BN smallpox vaccine at various doses in adults with a history of AIDS.

Traditional replicating smallpox vaccines are associated with serious safety concerns in the general population and are contraindicated in immunocompromised individuals. However, this very population remains at greatest risk for severe complications following viral infections, making vaccine prevention particularly relevant. MVA-BN was developed as a non-replicating smallpox vaccine that is potentially safer for people who are immunocompromised.

Hydrocarbon-soluble, hexaanionic fulleride complexes of magnesium.

The reaction of the magnesium(i) complexes [{(nacnac)Mg}], (nacnac = HC(MeCNAr), Ar = Dip (2,6-iPrCH), Dep (2,6-EtCH), Mes (2,4,6-MeCH), Xyl (2,6-MeCH)) with fullerene C afforded a series of hydrocarbon-soluble fulleride complexes [{(nacnac)Mg} C], predominantly with = 6, 4 and 2. C{H} NMR spectroscopic studies show both similarities ( = 6) and differences ( = 4, 2) to previously characterised examples of fulleride complexes and materials with electropositive metal ions. The molecular structures of [{(nacnac)Mg} C] with = 6, 4 and 2 can be described as inverse coordination complexes of [(nacnac)Mg] ions with C anions showing predominantly ionic metal-ligand interactions, and include the first well-defined and soluble complexes of the C ion.