bmj;369/may07_6/m1803/FAF1faPhoto credit: Abbas GhazanfarOn 25 March Adil El-Tayar, a renowned organ transplantation specialist, became the first working NHS surgeon to die from covid-19 in hospital...

OBJECTIVE

Neonatal diabetes has been shown to be associated with high neuropsychiatric morbidity in a genotype-phenotype–dependent manner. However, the specific impact of different mutations on intellectual functioning is still insufficiently characterized. Specifically, only a small number of subjects with developmental delay have been comprehensively assessed, creating a knowledge gap about patients carrying the heaviest burden.

Northrop Grumman Corp. and Raytheon Missiles and Defense will partner to develop the Defense Department's next missile interceptor, they announced on Monday.

Raytheon was awarded a $325 million contract for repair of the Advanced Targeting Forward Looking Infrared System in the F/A-18 Super Hornet aircraft Tuesday, according to the Pentagon.

Raytheon Missile Systems was awarded a $19 million contract modification to exercise options for Navy Rolling Airframe Missile and Guided Missile Launching Systems, according to the Department of Defense.

Jennifer M. Yamamoto
Jul 1, 2018; 41:1346-1361
Reconsidering Pregnancy With Diabetes

There is an art to conveying just who you are at every stage of your dental practice. One minute you could be a single-dentist practice with a hygienist and a receptionist, and then, the next thing you know, you could have a group practice and maybe even several locations.

OBJECTIVE

Transient neonatal diabetes mellitus (TNDM) occurs during the 1st year of life and remits during childhood. We investigated glucose metabolism and socioeducational outcomes in adults.

Let's say there are 10 houses on your street and a giant pothole develops right in the middle of the block. Everyone benefits if the pothole gets fixed, but that might require multiple calls to municipal authorities and a lot of hassle. Since every resident benefits even if he or she does nothing...

By Emily Reynolds. Findings have implications for judges, police officers, and others involved with gathering evidence and interviewing eyewitnesses.

Cricket -- Australia -- Anecdotes.

Wildlife conservation -- Australia.

Paris : Delahaye, 1863.

Edinburgh : Hodges and Smith, 1834-1840.

Berlin : Heuser, 1889.

Berlin : C. Nohring, 1868.

London : Hurst, Chance, 1831.

Paris : Steinheil, 1899.

Paris : G. Steinheil, 1895.

Dublin : printed for Hodges and Smith, 1831.

London : Printed by Mary Clark, and are to be sold by John Clark, at Mercers Chappel at the Lower End of Cheapside, MDCLXXVIII. [1678]

Rockville, Maryland : National Institute on Drug Abuse, 1984.

Rockville, Maryland : National Institute on Drug Abuse, 1979.

Hydrocephalus is a pathologic condition associated with various brain diseases, including Alzheimer's disease (AD). Dysfunctional ependymal cells (EpCs) are believed to contribute to the development of hydrocephalus. It is thus of interest to investigate EpCs' development and function. Here, we report that vacuolar protein sorting-associated protein 35 (VPS35) is critical for EpC differentiation, ciliogenesis, and survival, and thus preventing neonatal hydrocephalus. VPS35 is abundantly expressed in EpCs. Mice with conditional knock-out (cKO) of Vps35 in embryonic (Vps35^GFAP-Cre and Vps35^Emx1-Cre) or postnatal (Vps35^Foxj1-CreER) EpC progenitors exhibit enlarged lateral ventricles (LVs) and hydrocephalus-like pathology. Further studies reveal marked reductions in EpCs and their cilia in both Vps35^GFAP-Cre and Vps35^Foxj1-CreER mutant mice. The reduced EpCs appear to be due to impairments in EpC differentiation and survival. Additionally, both Vps35^GFAP-Cre and Vps35^Foxj1-CreER neonatal pups exhibit increased cell proliferation and death largely in a region close to LV-EpCs. Many microglia close to the mutant LV-EpC region become activated. Depletion of the microglia by PLX3397, an antagonist of colony-stimulating factor 1 receptor (CSF1R), restores LV-EpCs and diminishes the pathology of neonatal hydrocephalus in Vps35^Foxj1-CreER mice. Taken together, these observations suggest unrecognized functions of Vps35 in EpC differentiation, ciliogenesis, and survival in neonatal LV, and reveal pathologic roles of locally activated microglia in EpC homeostasis and hydrocephalus development.

SIGNIFICANCE STATEMENT This study reports critical functions of vacuolar protein sorting-associated protein 35 (VPS35) not only in promoting ependymal cell (EpC) differentiation, ciliogenesis, and survival, but also in preventing local microglial activation. The dysfunctional EpCs and activated microglia are likely to induce hydrocephalus.

Neonatal stroke is as frequent as stroke in the elderly, but many pathophysiological injury aspects are distinct in neonates, including immune signaling. While myeloid cells can traffic into the brain via multiple routes, the choroid plexus (CP) has been identified as a uniquely educated gate for immune cell traffic during health and disease. To understand the mechanisms of myeloid cell trafficking via the CP and their influence on neonatal stroke, we characterized the phenotypes of CP-infiltrating myeloid cells after transient middle cerebral artery occlusion (tMCAO) in neonatal mice of both sexes in relation to blood-brain barrier permeability, injury, microglial activation, and CX3CR1-CCR2 signaling, focusing on the dynamics early after reperfusion. We demonstrate rapid recruitment of multiple myeloid phenotypes in the CP ipsilateral to the injury, including inflammatory CD45⁺CD11b⁺Ly6c^highCD86⁺, beneficial CD45⁺CD11b⁺Ly6c^lowCD206⁺, and CD45⁺CD11b⁺Ly6c^lowLy6g^high cells, but only minor leukocyte infiltration into acutely ischemic-reperfused cortex and negligible vascular albumin leakage. We report that CX3CR1-CCR2-mediated myeloid cell recruitment contributes to stroke injury. Considering the complexity of inflammatory cascades triggered by stroke and a role for TLR2 in injury, we also used direct TLR2 stimulation as an independent injury model. TLR2 agonist rapidly recruited myeloid cells to the CP, increased leukocytosis in the CSF and blood, but infiltration into the cortex remained low over time. While the magnitude and the phenotypes of myeloid cells diverged between tMCAO and TLR2 stimulation, in both models, disruption of CX3CR1-CCR2 signaling attenuated both monocyte and neutrophil trafficking to the CP and cortex.

SIGNIFICANCE STATEMENT Stroke during the neonatal period leads to long-term disabilities. The mechanisms of ischemic injury and inflammatory response differ greatly between the immature and adult brain. We examined leukocyte trafficking via the choroid plexus (CP) following neonatal stroke in relation to blood-brain barrier integrity, injury, microglial activation, and signaling via CX3CR1 and CCR2 receptors, or following direct TLR2 stimulation. Ischemia-reperfusion triggered marked unilateral CX3CR1-CCR2 dependent accumulation of diverse leukocyte subpopulations in the CP without inducing extravascular albumin leakage or major leukocyte infiltration into the brain. Disrupted CX3CR1-CCR2 signaling was neuroprotective in part by attenuating monocyte and neutrophil trafficking. Understanding the migratory patterns of CP-infiltrating myeloid cells with intact and disrupted CX3CR1-CCR2 signaling could identify novel therapeutic targets to protect the neonatal brain.

The find could help pin down when the South Pole turned icy

As the planet deals with the pandemic and the crisis involving the spread of COVID-19, the world of sport watches and waits alongside the global population. This Saturday, March 21, will be the first of five weeks of programming at CBC Sports which will showcase some of the memorable moments from the most recent editions of the Olympics.

Watch Olympic Games Replay, a look back at some of the most exciting moments in past Games. On this week's edition of the program, watch action from the Pyeongchang 2018 figure skating competitions.

For all the sporting moments Mark Blinch has captured through his lens for nearly two decades, there is only one he has taken the trouble to hang in his home.

Words: Abbie Lyall

A PUBLIC health professor has warned that the Scottish Government’s strategy to escape the lockdown will encounter “a big problem” unless test results can be provided quicker.

IT’S strange the different things people took away from Theresa May’s teary goodbye in Downing Street yesterday.

The American politician John Nance Garner is better remembered for something he said rather than anything he did as Franklin Roosevelt’s vice-president.

The sight of Scottish ministers boarding flights to far-flung destinations in order to “sell Scotland to the world” has been a familiar one for more than half a century.

Readers have been quick to voice their opinion after it was reported that Nicola Sturgeon missed six emergency coronavirus Cobra meetings.

NICOLA Sturgeon could issue a change to the Scottish Government's policy on allowing outdoor exercise over the weekend - after Wales indicated the guidance will be relaxed from Monday.

WE should be wary of comparing the crisis of war with the crisis of coronavirus, but the 75th anniversary of VE Day is a reminder of what a national emergency can do to a leader. It can reveal their weaknesses and end their career, or it can highlight the qualities and skills that are needed in a time of trouble.

Little is known about the pharmacokinetics and required dosage of metronidazole in preterm neonates.

In this study the pharmacokinetics of metronidazole in preterm neonates was investigated by measurement of the drug in dried blood-spot samples. A dosage regimen is proposed that should result in more appropriate, less frequent dosing in the most preterm neonates. (Read the full article)

Two UK models predict the risk of mortality in very preterm Western infants (1) alive at onset of labor and (2) admitted for neonatal intensive care. Prognostic models need temporal and geographic validation to evaluate their performance.

The 2 models showed very good performance in a recent large cohort of very preterm infants born in another Western country. The accurate performance of both models suggests application in clinical practice (Read the full article)

Several studies have focused on birth weight heritability, reporting results that range between 40% and 80%. Few studies have focused on the process of weight gain and were mainly based on heterogeneous samples of infants.

The present work looks at a uniform set of healthy preterm newborn twins. The resulting high heritability estimate could suggest using the inclusion criteria to identify genes that regulate postnatal weight gain or failure. (Read the full article)

Recent studies have called into question the benefit of perioperative corticosteroids in children undergoing heart surgery, but have been limited by small sample size, the lack of placebo control, and the grouping of various steroid regimens together in analysis.

We evaluated outcomes across methylprednisolone regimens versus no steroids in a large cohort of neonates and found no mortality or length-of-stay benefit associated with any regimen, and a higher risk of infection in certain subgroups. (Read the full article)

Although China has the largest birth population in the world and a number of multicenter studies of neonatal respiratory failure are reported, there is a paucity of data regarding outcome measurement of very premature neonates requiring respiratory care and surfactant therapy.

This study is the largest survey, to date, in a Chinese network of 55 NICUs that presents the incidence, morbidity, and mortality rates, with risk factors of neonatal respiratory failure, with special emphasis on surfactant-treated very immature infants. (Read the full article)

The very preterm neonate is more susceptible to bacterial infection; this is thought to be due to immaturity of the innate immune response.

Monocytes have an anti-inflammatory profile at birth and are hyporesponsive to inflammatory stimuli in fetuses born very prematurely. This reflects the response to the pro-inflammatory events leading to preterm birth as well as gestational immaturity. (Read the full article)

Staphylococcus aureus is a leading cause of infections in infants. Staphylococcal colonization is a known risk factor for infection, but whether maternal colonization plays a role in subsequent colonization in the infant is unclear.

This prospective study found that infants born to women colonized with S aureus either during their third trimester of pregnancy or at the time of delivery are more likely to harbor S aureus than are those born to noncolonized women. (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)

High or low lymphocyte counts at birth have been reported as a marker for subsequent intraventricular hemorrhage, retinopathy of prematurity, and periventricular leukomalacia. However, this conclusion is questionable because reference ranges for lymphocyte counts have not been constructed by using large numbers of neonates.

This study provides reference ranges for lymphocytes of neonates. A high count at birth is associated with early onset sepsis and IVH and a low count with early onset sepsis, IVH, and retinopathy of prematurity. Among neonates with birth asphyxia, a low count identifies a high risk for death. (Read the full article)

Late-onset hypocalcemia is common in neonates, often presents with seizures or tetany, and is often attributed to transient hypoparathyroidism.

Late-onset hypocalcemia in neonates is often a sign of coexisting vitamin D deficiency and hypomagnesemia and is readily managed with therapy of limited duration, and neonates presenting with tetany or seizures due to hypocalcemia are unlikely to benefit from neuroimaging studies. (Read the full article)