Ultrafast adaptive optics for imaging the living human eye.

Adaptive optics (AO) is a powerful method for correcting dynamic aberrations in numerous applications. When applied to the eye, it enables cellular-resolution retinal imaging and enhanced visual performance and stimulation. Most ophthalmic AO systems correct dynamic aberrations up to 1-2 Hz, the commonly-known cutoff frequency for correcting ocular aberrations.

Propagation of distinct CWD prion strains during peripheral and intracerebral challenges of gene-targeted mice.

Since prion diseases result from infection and neurodegeneration of the central nervous system (CNS), experimental characterizations of prion strain properties customarily rely on the outcomes of intracerebral challenges. However, natural transmission of certain prions, including those causing chronic wasting disease (CWD) in elk and deer, depends on propagation in peripheral host compartments prior to CNS infection. Using gene-targeted GtE and GtQ mice, which accurately control cellular elk or deer PrP expression, we assessed the impact that peripheral or intracerebral exposures play on CWD prion strain propagation and resulting CNS abnormalities.

Adaptive foraging behaviours in the Horn of Africa during Toba supereruption.

Although modern humans left Africa multiple times over 100,000 years ago, those broadly ancestral to non-Africans dispersed less than 100,000 years ago. Most models hold that these events occurred through green corridors created during humid periods because arid intervals constrained population movements. Here we report an archaeological site-Shinfa-Metema 1, in the lowlands of northwest Ethiopia, with Youngest Toba Tuff cryptotephra dated to around 74,000 years ago-that provides early and rare evidence of intensive riverine-based foraging aided by the likely adoption of the bow and arrow.

Basicranial evidence suggests picrodontid mammals are not stem primates.

The Picrodontidae from the middle Palaeocene of North America are enigmatic placental mammals that were allied with various mammalian groups but are generally now considered to have close affinities to paromomyid and palaechthonid plesiadapiforms based on proposed dental synapomorphies. The picrodontid fossil record consists entirely of dental and gnathic remains except for one partial cranium of (AMNH 17180). Here, we use µCT technology to unveil previously undocumented morphology in AMNH 17180, describe and compare the basicranial morphology of a picrodontid for the first time, and incorporate these new data into cladistic analyses.

Xylazine in the drug supply: Emerging threats and lessons learned in areas with high levels of adulteration.

Background: Xylazine, a sedative analgesic drug approved as an animal tranquilizer but not for human use, has become an adulterant in the illicit opioid marketplace in North America. Recently declared an emerging health threat in the U.S.

Sweat Production During Continuous and Interval Aerobic Exercise.

Aerobic exercise within the habitable volume of small spacecraft needed for space exploration beyond low Earth orbit is expected to challenge the capacity of environmental control systems. Moisture control is a primary concern. Crewmembers will contribute moisture to the cabin environment in the form of sweat while exercising.

"I Am a Human": A Process Evaluation of a Nurse-Led Community-Based, Palliative Care Program in Liberia, West Africa.

Liberia is a postwar, post-Ebola, and low-income nation in West Africa with minimal to no palliative care access. In 2017, Partners In Health in collaboration with the Liberian Ministry of Health invested in the development of a nurse-led, community-based palliative care team in southeastern Maryland County at JJ Dossen Memorial Hospital. Between 2017 and 2022, the 9-member team (8 nurses, 1 physician assistant) has enrolled 142 patients under their care.

Novel Prion Strain as Cause of Chronic Wasting Disease in a Moose, Finland.

Our previous studies using gene-targeted mouse models of chronic wasting disease (CWD) demonstrated that Norway and North America cervids are infected with distinct prion strains that respond differently to naturally occurring amino acid variation at residue 226 of the prion protein. Here we performed transmissions in gene-targeted mice to investigate the properties of prions causing newly emergent CWD in moose in Finland. Although CWD prions from Finland and Norway moose had comparable responses to primary structural differences at residue 226, other distinctive criteria, including transmission kinetics, patterns of neuronal degeneration, and conformational features of prions generated in the brains of diseased mice, demonstrated that the strain properties of Finland moose CWD prions are different from those previously characterized in Norway CWD.

A Cloned Recombinant Vesicular Stomatitis Virus-Vectored Marburg Vaccine, PHV01, Protects Guinea Pigs from Lethal Marburg Virus Disease.

Marburg virus (MARV) is a negative-sense, single-stranded RNA virus that belongs to the family. Despite having caused numerous outbreaks of severe hemorrhagic fever with high case fatality rates, there are still no clinically approved therapeutics or vaccines to treat or prevent MARV disease. Recombinant vesicular stomatitis viruses (rVSVs) expressing heterologous viral glycoproteins have shown remarkable promise as live-attenuated vaccine vectors, with an rVSV-based Ebola virus vaccine having received regulatory approval in the United States and numerous other countries.

Editorial: Maternal Bonding: How and Why Does It Matter?

In 1970, Klaus and Kennell endorsed the idea of a sensitive period immediately after birth, associated with skin-to-skin contact, that was key to a human mother developing an affectional bond with her infant. Since that time, studies have investigated how the mother's affectional bond to her infant supports infant development as well as a variety of factors that impact the development of such a bond, including maternal engagement in fetal movements, experiences during the birth process, social support including that from the partner, and maternal mental health. This editorial aims to set the large, longitudinal study by Le Bas et al.

Vocal brain development in infants of mothers with serious mental illness (CAPRI-Voc): study protocol.

Introduction: Improving the lives of children and adolescents with parental mental illness (CAPRI) remains an urgent political and public health concern for the UK and European Union. Recurrent parental mental illness is believed to lead to fractures in the family, academic and social lives of these children, yet interventions are poorly targeted and non-specific. Part of an interdisciplinary programme of work (the CAPRI Programme; grant number: 682741), CAPRI-Voc aims to achieve two goals: first, to test the feasibility of our longitudinal imaging paradigm in mother-infant pairs where the mother has a diagnosis of severe mental illness.

Cone photoreceptor dysfunction in retinitis pigmentosa revealed by optoretinography.

Retinitis pigmentosa (RP) is the most common group of inherited retinal degenerative diseases, whose most debilitating phase is cone photoreceptor death. Perimetric and electroretinographic methods are the gold standards for diagnosing and monitoring RP and assessing cone function. However, these methods lack the spatial resolution and sensitivity to assess disease progression at the level of individual photoreceptor cells, where the disease originates and whose degradation causes vision loss.

Adaptive selection of a prion strain conformer corresponding to established North American CWD during propagation of novel emergent Norwegian strains in mice expressing elk or deer prion protein.

Prions are infectious proteins causing fatal, transmissible neurodegenerative diseases of animals and humans. Replication involves template-directed refolding of host encoded prion protein, PrPC, by its infectious conformation, PrPSc. Following its discovery in captive Colorado deer in 1967, uncontrollable contagious transmission of chronic wasting disease (CWD) led to an expanded geographic range in increasing numbers of free-ranging and captive North American (NA) cervids.

Development of Emotion Regulation in Typically Developing Children.

Emotion regulation (ER) is a complex process that combines inherent as well as environmental and learned components of reactivity and regulation. Elements of ER are present from birth and are elaborated across development. An understanding of emotion dysregulation requires careful examination of all the elements that constitute typical ER so that relevant domains can be therapeutically targeted.

Analysis of Caenorhabditis elegans acetylcholine synthesis mutants reveals a temperature-sensitive requirement for cholinergic neuromuscular function.

In Caenorhabditis elegans, the cha-1 gene encodes choline acetyltransferase (ChAT), the enzyme that synthesizes the neurotransmitter acetylcholine. We have analyzed a large number of cha-1 hypomorphic mutants, most of which are missense alleles. Some homozygous cha-1 mutants have approximately normal ChAT immunoreactivity; many other alleles lead to consistent reductions in synaptic immunostaining, although the residual protein appears to be stable.

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.

Background: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.

Patients And Methods: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included.

Understanding, Assessing, and Intervening with Emotion Dysregulation in Autism Spectrum Disorder: A Developmental Perspective.

This article provides a comprehensive review of emotion dysregulation (ED) in individuals with autism spectrum disorder (ASD). The authors describe ED from a developmental perspective, and highlight how aberrations in social development and a restricted-repetitive repertoire of behaviors, render individuals with ASD more vulnerable to ED. The article also summarizes how ED in children and adolescents with ASD has been measured and conceptualized in research and clinic settings.

Revealing How Color Vision Phenotype and Genotype Manifest in Individual Cone Cells.

Purpose: Psychophysical and genetic testing provide substantial information about color vision phenotype and genotype. However, neither reveals how color vision phenotypes and genotypes manifest themselves in individual cones, where color vision and its anomalies are thought to originate. Here, we use adaptive-optics phase-sensitive optical coherence tomography (AO-PSOCT) to investigate these relationships.

Multi-reference global registration of individual A-lines in adaptive optics optical coherence tomography retinal images (Publisher's Note).

The note corrects an error that appeared in Equation 14 of the originally published article.

Multi-reference global registration of individual A-lines in adaptive optics optical coherence tomography retinal images.

Significance: Adaptive optics optical coherence tomography (AO-OCT) technology enables non-invasive, high-resolution three-dimensional (3D) imaging of the retina and promises earlier detection of ocular disease. However, AO-OCT data are corrupted by eye-movement artifacts that must be removed in post-processing, a process rendered time-consuming by the immense quantity of data.

Aim: To efficiently remove eye-movement artifacts at the level of individual A-lines, including those present in any individual reference volume.

Rising Drug Costs for Neurologic Diseases.

The cost of prescription drugs in the United States is rising like never before and has led to an inflection point where clinicians must consider the potential financial damage to the patient and to society related to the more expensive drugs available. Many of the highest-priced drugs are approved as orphan drugs, a legally defined status providing additional benefits to pharmaceutical companies that is intended to incentivize therapeutic development for rare diseases. The Orphan Drug Act has been a great success since it was enacted in 1983, resulting in the development of many innovative, life-changing, and even lifesaving drugs; however, high drug prices place patients at risk for personal bankruptcy, prescription abandonment, and higher rates of hospitalization.

A crisis in US drug pricing: Consequences for patients with neuromuscular diseases, physicians, and society, part 2.

Escalating drug costs place patients at risk for financial toxicity and demand that physicians understand and act on the ethical and economic principles related to drug pricing. This manuscript reviews these principles and provides clinicians with a framework to think about the value of the drugs prescribed for patients with neuromuscular diseases. A key component of addressing the drug pricing crisis will be establishing a value based (benefit/cost) drug pricing framework.

A crisis in US drug pricing: Consequences for patients with neuromuscular diseases, physicians and society, part 1.

Drug prices in the United States have reached astounding heights, negatively impacting patients and society. The vast majority of prescription drug spending is on brand name drugs, which are protected from typical market pressures by FDA exclusivity and intellectual property patents. Drugs to treat "orphan" diseases, of particular relevance to neuromuscular clinicians, are some of the most expensive in all of medicine.

Incomplete glycosylation during prion infection unmasks a prion protein epitope that facilitates prion detection and strain discrimination.

The causative factors underlying conformational conversion of cellular prion protein (PrP) into its infectious counterpart (PrP) during prion infection remain undetermined, in part because of a lack of monoclonal antibodies (mAbs) that can distinguish these conformational isoforms. Here we show that the anti-PrP mAb PRC7 recognizes an epitope that is shielded from detection when glycans are attached to Asn-196. We observed that whereas PrP is predisposed to full glycosylation and is therefore refractory to PRC7 detection, prion infection leads to diminished PrP glycosylation at Asn-196, resulting in an unshielded PRC7 epitope that is amenable to mAb recognition upon renaturation.