Canada's National Advisory Committee on immunization: Adaptations and challenges during the COVID-19 pandemic.

The COVID-19 pandemic has challenged traditional vaccine guidance infrastructure and frameworks, and added urgency and complexity to the operation of National Immunization Technical Advisory Groups (NITAGs). Canada's National Advisory Committee on Immunization (NACI) provides immunization guidance to the Public Health Agency of Canada (PHAC) who publicly shares expert and evidence-informed guidance with Canadian provinces and territories. Throughout the pandemic, NACI and PHAC implemented many adaptations to meet urgent needs for pandemic vaccine guidance.

Inhibition of Complement Factor 3 in Geographic Atrophy with NGM621: Phase 1 Dose-Escalation Study Results.

Purpose: To evaluate the safety and tolerability of single and multiple intravitreal injections of NGM621 in patients with geographic atrophy (GA) and to characterize the pharmacokinetics and immunogenic potential.

Design: Multicenter, open-label, single- and multiple-dose phase 1 study.

Methods: Fifteen patients enrolled at 4 sites in the United States.

CRTC1/MAML2 directs a PGC-1α-IGF-1 circuit that confers vulnerability to PPARγ inhibition.

Mucoepidermoid carcinoma (MEC) is a life-threatening salivary gland cancer that is driven primarily by a transcriptional coactivator fusion composed of cyclic AMP-regulated transcriptional coactivator 1 (CRTC1) and mastermind-like 2 (MAML2). The mechanisms by which the chimeric CRTC1/MAML2 (C1/M2) oncoprotein rewires gene expression programs that promote tumorigenesis remain poorly understood. Here, we show that C1/M2 induces transcriptional activation of the non-canonical peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) splice variant PGC-1α4, which regulates peroxisome proliferator-activated receptor gamma (PPARγ)-mediated insulin-like growth factor 1 (IGF-1) expression.

Visual Function Decline Resulting from Geographic Atrophy: Results from the Chroma and Spectri Phase 3 Trials.

Purpose: To assess visual function outcomes to 48 weeks in patients with bilateral geographic atrophy (GA) secondary to age-related macular degeneration included in 2 interventional clinical trials: relationship to baseline lesion size, outcomes by baseline lesion characteristic subgroups, and correlation of visual function outcomes with GA area.

Design: The Chroma and Spectri studies (ClinicalTrials.gov identifiers, NCT02247479 and NCT02247531, respectively) were identically designed phase 3, double-masked, multicenter, randomized, sham injection-controlled clinical trials that evaluated intravitreal lampalizumab in GA.

Natural History of Geographic Atrophy Secondary to Age-Related Macular Degeneration: Results from the Prospective Proxima A and B Clinical Trials.

Purpose: To better characterize visual function decline and geographic atrophy (GA) progression secondary to age-related macular degeneration (AMD).

Design: Proxima A (NCT02479386)/Proxima B (NCT02399072) were global, prospective, noninterventional, observational clinical trials.

Participants: Eligible patients were aged ≥50 years.

Engineered BRET-Based Biologic Light Sources Enable Spatiotemporal Control over Diverse Optogenetic Systems.

Light-inducible optogenetic systems offer precise spatiotemporal control over a myriad of biologic processes. Unfortunately, current systems are inherently limited by their dependence on external light sources for their activation. Further, the utility of laser/LED-based illumination strategies are often constrained by the need for invasive surgical procedures to deliver such devices and local heat production, photobleaching and phototoxicity that compromises cell and tissue viability.

The Progression of Geographic Atrophy Secondary to Age-Related Macular Degeneration.

Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) that leads to progressive and irreversible loss of visual function. Geographic atrophy is defined by the presence of sharply demarcated atrophic lesions of the outer retina, resulting from loss of photoreceptors, retinal pigment epithelium (RPE), and underlying choriocapillaris. These lesions typically appear first in the perifoveal macula, initially sparing the foveal center, and over time often expand and coalesce to include the fovea.

Targeting factor D of the alternative complement pathway reduces geographic atrophy progression secondary to age-related macular degeneration.

Geographic atrophy is an advanced form of age-related macular degeneration (AMD) and a leading cause of vision loss for which there are no approved treatments. Genetic studies in AMD patients have implicated dysregulation of the alternative complement pathway in the pathogenesis of geographic atrophy. Lampalizumab is a potential therapeutic that targets complement factor D, a pivotal activator of the alternative complement pathway.

THE PATHOPHYSIOLOGY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION AND THE COMPLEMENT PATHWAY AS A THERAPEUTIC TARGET.

Purpose: Geographic atrophy (GA) is an advanced, vision-threatening form of age-related macular degeneration (AMD) affecting approximately five million individuals worldwide. To date, there are no approved therapeutics for GA treatment; however, several are in clinical trials. This review focuses on the pathophysiology of GA, particularly the role of complement cascade dysregulation and emerging therapies targeting the complement cascade.

CLINICAL ENDPOINTS FOR THE STUDY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

Purpose: To summarize the recent literature describing the application of modern technologies in the study of patients with geographic atrophy (GA) secondary to age-related macular degeneration.

Methods: Review of the literature describing the terms and definitions used to describe GA, imaging modalities used to capture and measure GA, and the tests of visual function and functional deficits that occur in patients with GA.

Results: In this paper, we describe the evolution of the definitions used to describe GA.

Reconciliation of sequence data and updated annotation of the genome of Agrobacterium tumefaciens C58, and distribution of a linear chromosome in the genus Agrobacterium.

Two groups independently sequenced the Agrobacterium tumefaciens C58 genome in 2001. We report here consolidation of these sequences, updated annotation, and additional analysis of the evolutionary history of the linear chromosome, which is apparently limited to the biovar I group of Agrobacterium.

Experiences of older adult women diagnosed with attention deficit hyperactivity disorder.

Attention Deficit Hyperactivity Disorder (ADHD), usually diagnosed in children, is known to persist into adulthood. However, the research has not examined the disorder in older adults. This article describes a preliminary qualitative study of the experiences of women over age 62 who were diagnosed with ADHD after the age of 60.

An observational retrospective subgroup analysis of verteporfin photodynamic therapy-naive and previously treated patients in the focus trial.

Purpose: To perform a retrospective post hoc subgroup analysis of the FOCUS trial to assess the visual acuity outcomes and treatment benefits for patients receiving combination therapy who, at the time of enrollment, were naive to verteporfin photodynamic therapy (PDT) or had previously received PDT.

Methods: In this retrospective post hoc analysis of 24-month data from the FOCUS trial, PDT-naive and previously PDT-treated patients (n = 162) were included. Patients were randomized in a 2:1 ratio to receive 0.

Central projections of trigeminal afferents innervating the face in naked mole-rats (Heterocephalus glaber).

In this study, we examined the topography of projections from facial afferents to the trigeminal brainstem nuclear complex (TBNC) in naked mole-rats using the neuronal tracer CTB-HRP. Tracer injections were made in a ventral to dorsal sequence that included the tooth pulp and dental ligament, ventral buccal pad, vibrissae, and the forehead. Labeled terminals were identified throughout the rostrocaudal extent of the TBNC, including the principal nucleus (Pr5), pars oralis (Sp5O), pars interpolaris (Sp5I), and pars caudalis (Sp5C) of the spinal trigeminal nucleus.

Growing out of a caste--reproduction and the making of the queen mole-rat.

Naked mole-rats have a eusocial colony structure consisting of non-reproductive workers and a reproductively active caste where a single, dominant queen and 1-3 males produce all of the offspring. Well-established queens have elongated bodies that characterize their caste. Worker females retain the ability to transform into queens, however the trigger and time course for this physical transformation remain a mystery.

Touching on somatosensory specializations in mammals.

Specialized species often reveal general principles of brain organization and provide systems for analysis of sensory function. Subterranean species dependent on touch have particularly large somatosensory areas with modular cortical representations of sensory surfaces. Some species have added cortical areas to processing networks, have developed tactile foveas and have superior colliculi primarily devoted to somatosensation rather than vision.

Cortical, callosal, and thalamic connections from primary somatosensory cortex in the naked mole-rat (Heterocephalus glaber), with special emphasis on the connectivity of the incisor representation.

We investigated the distribution of cortical, callosal, and thalamic connections from the primary somatosensory area (S1) in naked mole-rats, concentrating on lower incisor and forelimb representations. A neuronal tracer (WGA-HRP) was injected into the center of each respective representation under guidance from microelectrode recordings of neuronal activity. The locations of cells and terminals were determined by aligning plots of labeled cells with flattened cortical sections reacted for cytochrome oxidase.

Organization of somatosensory cortical areas in the naked mole-rat (Heterocephalus glaber).

Multiunit electrophysiology was combined with histological analysis of cortical sections to investigate the organization of somatosensory areas in the naked mole-rat. We provide new details for the organization of primary somatosensory cortex (S1) and identify cortical modules and barrels that correspond to the representations of different body parts. In addition, details of the location and organization of secondary somatosensory cortex (S2) are reported, and evidence for a third somatosensory representation, likely the parietal ventral area (PV), is provided and discussed.

Plasticity of the cortical dentition representation after tooth extraction in naked mole-rats.

Naked mole-rats (Heterocephalus glaber) have a large cortical representation of their behaviorally important front teeth, accounting for 30% of primary somatosensory cortex (SI). Here we investigated the plasticity of this dental representation after the extraction of a single lower tooth. The representation of the contralateral lower incisor normally accounts for approximately 15% of somatosensory cortex in mole-rats.

BAF57 governs androgen receptor action and androgen-dependent proliferation through SWI/SNF.

Androgen receptor (AR) activity is required for prostate cancer development and progression. Thus, there is a major impetus to understand the regulation of AR action. We and others have previously shown that AR transactivation potential is dependent on the presence of an active SWI/SNF chromatin remodeling complex.

Organization of somatosensory cortex in the laboratory rat (Rattus norvegicus): Evidence for two lateral areas joined at the representation of the teeth.

Lateral somatosensory areas have not been explored in detail in rats, and theories on the organization of this region are based largely on anatomical tracing experiments. We investigated the topography of this region by using microelectrode recordings, which were related to flattened cortical sections processed for cytochrome oxidase (CO). Two lateral somatosensory areas were identified, each containing a complete representation of the body.

Expression of Smad4 in the FaDu cell line partially restores TGF-beta growth inhibition but is not sufficient to regulate fibronectin expression or suppress tumorigenicity.

Mutations of the Smad4 gene, a member of a group of TGF-beta signal transduction components, occur in several types of cancer suggesting that its inactivation significantly affects TGF-beta responsiveness in these tumors. To further investigate the role of Smad4 with respect to TGF-beta signaling and carcinogenesis, we re-expressed the Smad4 gene in the Smad4-deficient cancer cell line FaDu by microcell-mediated chromosome transfer (MMCT) and retroviral infection to closely approximate physiological protein levels. The Smad4-expressing FaDu clones were then evaluated for TGF-beta responsiveness to assess the role of Smad4 in TGF-beta-induced growth inhibition and target gene regulation.