The Democracy Fund + UCLA Nationscape Project found some misinformation about the coronavirus is more widespread that you might think.

Zhengui Xia
Sep 1, 1996; 16:5425-5436
Articles

Synaptic dysfunction provoking dysregulated cortical neural circuits is currently hypothesized as a key pathophysiological process underlying clinical manifestations in Alzheimer's disease and related neurodegenerative tauopathies. Here, we conducted PET along with postmortem assays to investigate time course changes of excitatory and inhibitory synaptic constituents in an rTg4510 mouse model of tauopathy, which develops tau pathologies leading to noticeable brain atrophy at 5-6 months of age. Both male and female mice were analyzed in this study. We observed that radiosignals derived from [¹¹C]flumazenil, a tracer for benzodiazepine receptor, in rTg4510 mice were significantly lower than the levels in nontransgenic littermates at 2-3 months of age. In contrast, retentions of (E)-[¹¹C]ABP688, a tracer for mGluR5, were unaltered relative to controls at 2 months of age but then gradually declined with aging in parallel with progressive brain atrophy. Biochemical and immunohistochemical assessment of postmortem brain tissues demonstrated that inhibitory, but not excitatory, synaptic constituents selectively diminished without overt loss of somas of GABAergic interneurons in the neocortex and hippocampus of rTg4510 mice at 2 months of age, which was concurrent with enhanced immunoreactivity of cFos, a well-characterized immediate early gene, suggesting that impaired inhibitory neurotransmission may cause hyperexcitability of cortical circuits. Our findings indicate that tau-induced disruption of the inhibitory synapse may be a critical trigger of progressive neurodegeneration, resulting in massive neuronal loss, and PET assessments of inhibitory versus excitatory synapses potentially offer in vivo indices for hyperexcitability and excitotoxicity early in the etiologic pathway of neurodegenerative tauopathies.

SIGNIFICANCE STATEMENT In this study, we examined the in vivo status of excitatory and inhibitory synapses in the brain of the rTg4510 tauopathy mouse model by PET imaging with (E)-[¹¹C]ABP688 and [¹¹C]flumazenil, respectively. We identified inhibitory synapse as being significantly dysregulated before brain atrophy at 2 months of age, while excitatory synapse stayed relatively intact at this stage. In line with this observation, postmortem assessment of brain tissues demonstrated selective attenuation of inhibitory synaptic constituents accompanied by the upregulation of cFos before the formation of tau pathology in the forebrain at young ages. Our findings indicate that selective degeneration of inhibitory synapse with hyperexcitability in the cortical circuit constitutes the critical early pathophysiology of tauopathy.

N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that play critical roles in neuronal development and nervous system function. Here, we developed a model to study NMDARs in early development in zebrafish, by generating CRISPR-mediated lesions in the NMDAR genes, grin1a and grin1b, which encode the obligatory GluN1 subunits. While receptors containing grin1a or grin1b show high Ca²⁺ permeability, like their mammalian counterpart, grin1a is expressed earlier and more broadly in development than grin1b. Both grin1a^–/– and grin1b^–/– zebrafish are viable. Unlike in rodents, where the grin1 knockout is embryonic lethal, grin1 double-mutant fish (grin1a^–/–; grin1b^–/–), which lack all NMDAR-mediated synaptic transmission, survive until ~10 d dpf (days post fertilization), providing a unique opportunity to explore NMDAR function during development and in generating behaviors. Many behavioral defects in the grin1 double-mutant larvae, including abnormal evoked responses to light and acoustic stimuli, prey-capture deficits, and a failure to habituate to acoustic stimuli, are replicated by short-term treatment with the NMDAR antagonist MK-801, suggesting that they arise from acute effects of compromised NMDAR-mediated transmission. Other defects, however, such as periods of hyperactivity and alterations in place preference, are not phenocopied by MK-801, suggesting a developmental origin. Together, we have developed a unique model to study NMDARs in the developing vertebrate nervous system.

SIGNIFICANCE STATEMENT Rapid communication between cells in the nervous system depends on ion channels that are directly activated by chemical neurotransmitters. One such ligand-gated ion channel, the NMDAR, impacts nearly all forms of nervous system function. It has been challenging, however, to study the prolonged absence of NMDARs in vertebrates, and hence their role in nervous system development, due to experimental limitations. Here, we demonstrate that zebrafish lacking all NMDAR transmission are viable through early development and are capable of a wide range of stereotypic behaviors. As such, this zebrafish model provides a unique opportunity to study the role of NMDAR in the development of the early vertebrate nervous system.

The tuberal hypothalamus is comprised of the dorsomedial, ventromedial, and arcuate nuclei, as well as parts of the lateral hypothalamic area, and it governs a wide range of physiologies. During neurogenesis, tuberal hypothalamic neurons are thought to be born in a dorsal-to-ventral and outside-in pattern, although the accuracy of this description has been questioned over the years. Moreover, the intrinsic factors that control the timing of neurogenesis in this region are poorly characterized. Proneural genes, including Achate-scute-like 1 (Ascl1) and Neurogenin 3 (Neurog3) are widely expressed in hypothalamic progenitors and contribute to lineage commitment and subtype-specific neuronal identifies, but the potential role of Neurogenin 2 (Neurog2) remains unexplored. Birthdating in male and female mice showed that tuberal hypothalamic neurogenesis begins as early as E9.5 in the lateral hypothalamic and arcuate and rapidly expands to dorsomedial and ventromedial neurons by E10.5, peaking throughout the region by E11.5. We confirmed an outside-in trend, except for neurons born at E9.5, and uncovered a rostrocaudal progression but did not confirm a dorsal-ventral patterning to tuberal hypothalamic neuronal birth. In the absence of Neurog2, neurogenesis stalls, with a significant reduction in early-born BrdU⁺ cells but no change at later time points. Further, the loss of Ascl1 yielded a similar delay in neuronal birth, suggesting that Ascl1 cannot rescue the loss of Neurog2 and that these proneural genes act independently in the tuberal hypothalamus. Together, our findings show that Neurog2 functions as a classical proneural gene to regulate the temporal progression of tuberal hypothalamic neurogenesis.

SIGNIFICANCE STATEMENT Here, we investigated the general timing and pattern of neurogenesis within the tuberal hypothalamus. Our results confirmed an outside-in trend of neurogenesis and uncovered a rostrocaudal progression. We also showed that Neurog2 acts as a classical proneural gene and is responsible for regulating the birth of early-born neurons within the ventromedial hypothalamus, acting independently of Ascl1. In addition, we revealed a role for Neurog2 in cell fate specification and differentiation of ventromedial -specific neurons. Last, Neurog2 does not have cross-inhibitory effects on Neurog1, Neurog3, and Ascl1. These findings are the first to reveal a role for Neurog2 in hypothalamic development.

The Nunavut government says there is no set limit on how much money it is prepared to spend on hotels for residents required to isolate before they return home.

BIS Bulletin No 7, April 2020. Past epidemics had long-lasting effects on economies through illness and the loss of lives, while Covid-19 is marked by widespread containment measures and relatively lower fatalities among young people. The short-term costs of Covid-19 will probably dwarf those of past epidemics, due to the unprecedented and synchronised global sudden stop in economic activity induced by containment measures. The current estimated impact on global GDP growth for 2020 is around -4%, with substantial downside risks if containment policies are prolonged. Output losses are larger for major economies.

The number of people evaluated for signs of stroke at U.S. hospitals has dropped by nearly 40% during the COVID-19 pandemic, according to a study led by researchers from Washington University School of Medicine in St. Louis who analyzed stroke evaluations at more than 800 hospitals across 49 states and the District of Columbia.

Information technology, health care, and consumer discretionary stocks that outperformed in the last decade have done well in the first four months of 2020.

The NHL is hoping to convince teams the league should move the 2020 draft to early June and hold it virtually, according to a report.

Information technology, health care, and consumer discretionary stocks that outperformed in the last decade have done well in the first four months of 2020.

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BACKGROUND AND OBJECTIVES:

Systems of care emphasize parent-delivered intervention for children with autism spectrum disorder (ASD). Meanwhile, multiple studies document psychological distress within these parents. This pilot longitudinal randomized controlled trial compared the parent-implemented Early Start Denver Model (P-ESDM) to P-ESDM plus mindfulness-based stress reduction (MBSR) for parents. We evaluated changes in parent functioning during active treatment and at follow-up.

BACKGROUND:

Long delays between parents’ initial concerns about their children’s development and a subsequent autism spectrum disorder (ASD) diagnosis are common. Although discussions between parents and providers about early ASD concerns can be difficult, they are critical for initiating early, specialized services. The principles of shared decision-making can facilitate these discussions. This qualitative study was designed to gain insights from parents of young children with ASD about their experiences communicating with primary care providers with the goal of identifying strategies for improving conversations and decision-making regarding the early detection of ASD.

A Fin24 user who was forced into early retirement is struggling to pay credit card debt amounting to over R109 000. An expert responds.

"Indeed, the Christ-like patience which the church fathers extolled is much deeper than waiting quietly for a bus," says Arley. "Rather, it is a sacrificial and enduring compassion for others, which our Lord embodied in His life and ultimately on the cross."

PRISON governors have been handed the power to veto prisoners they have concerns over being released early - as plans are pushed forward for up to 450 prisoners to be freed to allow inmates to socially distance in cells.

WHETHER through shrewd planning, good fortune or a bit of both, Edinburgh managed to complete the bulk of their business for next season before rugby came grinding to a halt. When precisely play resumes is, of course, unknown and out of their control, but they are at least confident that they will be in good shape to hit the ground running.

The free literacy app Khan Academy Kids boosted early literacy skills in children and parents said it improved their home-teaching skills.

Having a bachelor's degree, a top-notch grade point average, and a relatively high level of work experience actually reduce the chance that a job applicant will be called in for an interview with a child-care provider, concludes new research by Kent State and Arizona State universities.

New data show that a growing percentage of children, especially those from well-off households, attend center-based care in the year before they attend kindergarten.

There's a new focus on getting more training to early-childhood educators, but there's a dearth of information about what constitutes a high-quality, teacher-preparation program.

Expert says labels, books, and writing centers all help with skill development

The Center for American Progress has released a set of recommendations for governors in 2019 that includes things such as full-day universal preschool and the study of pre-term births, which can cause learning difficulties.

Half of Americans in 22 states live in "child-care deserts"—places where there are more than three children for every child-care slot—according to a new geographic analysis by the Center on American Progress, a liberal think tank.

Without rigorous research that accurately reflects the current population, early education won't deliver for all students, write two education researchers.

Democrat Gavin Newsom, who takes office Jan. 7, plans to expand full-day kindergarten and child-care offerings in the state, according to media reports.

Federal funding for state-administered child-care-assistance programs has declined since 2001, leaving many low-income families struggling to find child care, finds a study by the National Women's Law Center.

Families may be less likely to take advantage of early-childhood education programs if they work nonstandard hours, finds a new report from the National Research Center on Hispanic Children and Families.

Education needs to stop going around in circles, writes Stanford’s Thomas S. Dee.

Investing in early learning makes the biggest impact on a student's achievement, says Marion County, S.C., Superintendent Kandace Bethea. When a teacher is not available, we have to find other ways to get the job done, such as community partnerships.

Waterford UPSTART, an online program that offers literacy and math enrichment lessons aimed at preschoolers, received support from a philanthropy dedicated to funding "bold ideas for social change."

The World Health Organization issued guidelines for children under 5, including its first recommendations on how much time children should be spending in front of a digital screen.

A new report by the Government Accountability Office provides the first comprehensive nationwide look at state early education programs and how they are funded.

Babies as young as 12 months are exposed to nearly an hour a day of screen time, despite warnings from pediatricians to avoid digital media exposure for children under a year and a half, according to a new analysis.

The largest experiment to date comparing commercial math curricula gives a slight edge to two popular programs.

With their spring season canceled due to the global coronavirus pandemic, three senior student-athletes reflect on their time as Penn State Schuylkill Nittany Lions.

The National Children's Study, a large-scale, longitudinal, birth cohort study of US children that endeavors to identify preventable and environmental origins of chronic diseases, has begun recruitment.

In a highly diverse, urban setting, pregnant women can be recruited to participate in the National Children's Study at rates similar to those obtained in clinic settings. Refinements to the pregnancy screener and other components are needed to optimize implementation. (Read the full article)

Prematurely born children have an increased prevalence of behavioral problems in the long term. Knowledge regarding the effects of early intervention programs is sparse, and more randomized controlled trials are warranted.

A modified version of the Mother-Infant Transaction Program showed beneficial effects on behavioral outcomes reported by both parents of preterm infants with birth weights of <2000 g at a corrected age of 5 years. (Read the full article)

Overweight has been associated with an increased risk of asthma in children, although the published literature is contradictory. How change in overweight status during childhood affects asthma risk has not been well studied.

Among children whose weight has normalized, high BMI during the first 4 years of life does not increase the risk of asthma at school age. Current high BMI is associated with increased risk of asthma and sensitization to inhalant allergens. (Read the full article)

The quality of the relationship between mother and child affects the child’s neurodevelopment, emotion regulation, and stress response. Extreme or sustained stress responses are associated with dysregulation of physiologic systems involved in energy balance, which could lead to obesity.

The prevalence of obesity in adolescence was more than twice as high among those youth who in early childhood had poor-quality relationships with their mothers compared with those with better relationships. (Read the full article)

Traumatic brain injury in school-aged children is associated with intellectual, behavioral, and social deficits. Research into outcomes of children injured before 3 years of age is limited despite data suggesting a high incidence of injury in this age group.

Results show that a moderate to severe traumatic brain injury before 3 years of age is associated with lowered cognitive function. Furthermore, this study highlights the link between social disadvantage and poor outcomes after traumatic brain injury in early childhood. (Read the full article)

The evidence base for obesity prevention is extremely limited. Although minority youth are at higher risk of obesity, and early childhood is a critical period for prevention, only 1 program has demonstrated sustained effects on obesity in young minority children.

Among youth at high risk for obesity based on income, minority status, and child behavior problems, early intervention that promotes effective parenting led to meaningful differences in obesity in preadolescence. Early family intervention is an innovative and promising approach. (Read the full article)

Preterm, growth-restricted infants are at high risk of necrotizing enterocolitis (NEC). NEC occurs most frequently in infants who have received enteral feeds. It is common practice to delay introduction of enteral feeds in these infants.

Early introduction of enteral feeds results in earlier achievement of full enteral feeding. Early feeding is not associated with a higher risk of NEC. Delayed feeding is associated with a higher risk of cholestasis. (Read the full article)

The presumed causes of neonatal deaths globally have remained unchanged over the past decade and include infections (~30%), prematurity (~30%), and asphyxia (~25%). Great uncertainty surrounds these estimates and, in addition, cases are likely misclassified as stillbirths.

These observational findings indicate that asphyxia accounts for a much higher percentage (60% of early deaths). Prematurity (18%), low birth weight (8%), and overt infection are much less common. The 5-minute Apgar score is an unreliable indicator of birth asphyxia. (Read the full article)

Cumulative social factors in childhood have been associated with obesity in adulthood. Little is known regarding the role of accumulation of social stressors and obesity in early life.

Cumulative social adversities were associated with increased odds of early-onset obesity among girls. In addition, those with a higher number of stressors at a single time period had elevated odds for obesity by 5 years of age. (Read the full article)

Neonatal follow-up programs are designed in part to identify developmental delays among high-risk infants after NICU hospitalization and make referrals to state-funded early intervention. Early intervention has been shown to benefit children with developmental delays.

Many high-risk infants demonstrating developmental delays at neonatal follow-up programs are not referred to early intervention. Subspecialty clinics share responsibility with the medical home in referring children from birth through three years with developmental problems to early intervention services. (Read the full article)

Early speech and language delays are risk factors for later developmental and social difficulties. It is easier to identify them retrospectively than prospectively. Population characteristics and prevalence rates make screening problematic.

Using data from a birth cohort, this study identifies predictors of language performance at 5 years and 4 patterns of change between 3 and 5 years, comparing those who change with those whose profile remains low across time points. (Read the full article)

Celiac disease is an immunologic disorder with autoimmune features. Sweden experienced an epidemic of celiac disease in infants (1984–1996). Early vaccinations might influence the risk for autoimmune diseases, and could potentially have contributed to celiac disease risk and the epidemic.

Early vaccinations within the national Swedish program are not risk factors for celiac disease, nor do changes over time contribute to explaining the Swedish epidemic. A protective effect by vaccination against tuberculosis (bacillus Calmette-Guérin) is suggested. (Read the full article)

Infantile hemangiomas have a period of rapid growth in early infancy. Most hemangioma growth is completed by 5 months of age, but the majority of patients are not seen by a specialist until after the growth phase is complete.

The most rapid hemangioma growth is between 1 and 2 months of life, much earlier than previously believed. Patients with high-risk hemangiomas should be followed closely, and treatment initiation should be considered before or during the most rapid growth phase. (Read the full article)