There is a paucity of data relating to neurodevelopmental outcomes in infants born late and moderately preterm (LMPT; 32(+0)-36(+6) weeks). This paper present the results of a prospective, ...population-based study of 2-year outcomes following LMPT birth.
1130 LMPT and 1255 term-born children were recruited at birth. At 2 years corrected age, parents completed a questionnaire to assess neurosensory (vision, hearing, motor) impairments and the Parent Report of Children's Abilities-Revised to identify cognitive impairment. Relative risks for adverse outcomes were adjusted for sex, socio-economic status and small for gestational age, and weighted to account for over-sampling of term-born multiples. Risk factors for cognitive impairment were explored using multivariable analyses.
Parents of 638 (57%) LMPT infants and 765 (62%) controls completed questionnaires. Among LMPT infants, 1.6% had neurosensory impairment compared with 0.3% of controls (RR 4.89, 95% CI 1.07 to 22.25). Cognitive impairments were the most common adverse outcome: LMPT 6.3%; controls 2.4% (RR 2.09, 95% CI 1.19 to 3.64). LMPT infants were at twice the risk for neurodevelopmental disability (RR 2.19, 95% CI 1.27 to 3.75). Independent risk factors for cognitive impairment in LMPT infants were male sex, socio-economic disadvantage, non-white ethnicity, preeclampsia and not receiving breast milk at discharge.
Compared with term-born peers, LMPT infants are at double the risk for neurodevelopmental disability at 2 years of age, with the majority of impairments observed in the cognitive domain. Male sex, socio-economic disadvantage and preeclampsia are independent predictors of low cognitive scores following LMPT birth.
We describe a method for restoring information lost during statistical thinning in extensive air shower simulations. By converting weighted particles from thinned simulations to swarms of particles ...with similar characteristics, we obtain a result that is essentially identical to the thinned shower, and which is very similar to non-thinned simulations of showers. We call this method dethinning. Using non-thinned showers on a large scale is impossible because of unrealistic CPU time requirements, but with thinned showers that have been dethinned, it is possible to carry out large-scale simulation studies of the detector response for ultra-high energy cosmic ray surface arrays. The dethinning method is described in detail and comparisons are presented with parent thinned showers and with non-thinned showers.
Lichen planus is characterized by the histological features of a cell-mediated attack on the epidermis. To see whether there is any defect in cutaneous immunity in non-lesional skin, we measured the ...response to a contact sensitizer in 17 patients with lichen planus and 27 control subjects. Sensitization was induced with 30 micrograms dinitrochlorobenzene applied to the thigh. The subjects were challenged 4 weeks later with three doses of dinitrochlorobenzene (8.8, 12.5 and 17.7 micrograms), and responses were quantified with calipers as the change in skinfold thickness at 48 h. Patients with lichen planus were significantly less responsive with smaller reactions at all challenge doses. These abnormalities suggest that the skin is abnormal in areas unaffected by the rash, and raise the possibility that there may be a primary defect in the cutaneous immune system in lichen planus.
Diurnal variation in inflammatory and immune function is evident in the physiology and pathology of humans and animals, but molecular mechanisms and mediating cell types that provide this gating ...remain unknown. By screening cytokine responses in mice to endotoxin challenge at different times of day, we reveal that the magnitude of response exhibited pronounced temporal dependence, yet only within a subset of proinflammatory cytokines. Disruption of the circadian clockwork in macrophages (primary effector cells of the innate immune system) by conditional targeting of a key clock gene (bmal1) removed all temporal gating of endotoxin-induced cytokine response in cultured cells and in vivo. Loss of circadian gating was coincident with suppressed rev-erbα expression, implicating this nuclear receptor as a potential link between the clock and inflammatory pathways. This finding was confirmed in vivo and in vitro through genetic and pharmacological modulation of REV-ERBα activity. Circadian gating of endotoxin response was lost in rev-erbα–/– mice and in cultured macrophages from these animals, despite maintenance of circadian rhythmicity within these cells. Using human macrophages, which show circadian clock gene oscillations and rhythmic endotoxin responses, we demonstrate that administration of a synthetic REV-ERB ligand, or genetic knockdown of rev-erbα expression, is effective at modulating the production and release of the proinflammatory cytokine IL-6. This work demonstrates that the macrophage clockwork provides temporal gating of systemic responses to endotoxin, and identifies REV-ERBα as the key link between the clock and immune function. REV-ERBα may therefore represent a unique therapeutic target in human inflammatory disease.
Don't freeze! A native chemical ligation–desulfurization strategy has been employed for the convergent synthesis of a library of defined antifreeze glycopeptides and glycoproteins (AFGPs) ranging in ...size from 1.2 to 19.5 kDa (see picture). These AFGPs possessed the secondary structure of a polyproline type II helix and exhibited significant ice recrystallization inhibition and thermal hysteresis activity.
A blind panic Ayuk, John; Matthews, Tim; Tayebjee, M ...
The Lancet (British edition),
04/2001, Letnik:
357, Številka:
9264
Journal Article
Recenzirano
His serum calcium was repeatedly measured at 1.33 (normal 2.10-2-60) mmol/L, phosphate 1.51 (0.80-1.40) mmol/L, albumin 48 (34-51) g/IL, alkaline phosphatase 159 (73-330) U/L, magnesium 0.70 ...(0.75-1.05) mmol/L, and parathyroid (PTH) 2 (12.0-72.0) ng/L. Urinary calcium excretion showed hypocalcuria (1-4 2.5-7.5 mmol/24 hours). Other investigations were normal and an autoantibody screen was negative. Chvostek's and Trousseau's signs were both absent and an electrocardiogram showed a normal QT interval. A diagnosis of hypoparathyroidism was made and the patient was treated with calcium carbonate 1.25 g three times daily and alfa-calcidol 500 ng daily. Over the following 7 days his serum calcium rose to 1.70 mmol/L and the patient reported a striking improvement in his symptoms of blurred vision and paraesthesiae. His family noticed an improvement in his personality. Fundoscopy at this early stage showed complete resolution of optic disc swelling. Review after 4 weeks showed a serum calcium of 1.91 mmol/L. His visual fields had enlarged substantially (figure B), although both discs were pale. The sertraline had been stopped and his pre-morbid personality had returned. When last seen in January, 2001, he was well with a serum calcium of 2.13 mmol/L.
There is concern regarding the impact of selective serotonin reuptake inhibitors (SSRIs) on suicidal behaviour. Using the target trial framework, we investigated the effect on suicidal behaviour of ...SSRI treatment following a depression diagnosis. We identified 162,267 individuals receiving a depression diagnosis aged 6-59 years during 2006-2018 in Stockholm County, Sweden, after at least 1 year without antidepressant dispensation. Individuals who initiated an SSRI within 28 days of the diagnosis were assigned as SSRI initiators, others as non-initiators. Intention-to-treat and per-protocol effects were estimated; for the latter, individuals were censored when they ceased adhering to their assigned treatment strategy. We applied inverse probability weighting (IPW) to account for baseline confounding in the intention-to-treat analysis, and additionally for treatment non-adherence and time-varying confounding in the per-protocol analysis. The suicidal behaviour risk difference (RD), and risk ratio (RR) between SSRI initiators and non-initiators were estimated at 12 weeks. In the overall cohort, we found an increased risk of suicidal behaviour among SSRI initiators (intention-to-treat RR = 1.50, 95% CI = 1.25, 1.80; per-protocol RR = 1.69, 95% CI = 1.20, 2.36). In age strata, we only found evidence of an increased risk among individuals under age 25, with the greatest risk among 6-17-year-olds (intention-to-treat RR = 2.90, 95% CI = 1.72, 4.91; per-protocol RR = 3.34, 95% CI = 1.59, 7.00). Our finding of an increased suicidal behaviour risk among individuals under age 25 reflects evidence from RCTs. We found no evidence of an effect in the high-risk group of individuals with past suicidal behaviour. Further studies with information on a wider array of confounders are called for.
As the global burden of SARS-CoV-2 infections escalates, so does the evolution of viral variants with increased transmissibility and pathology. In addition to this entrenched diversity, RNA viruses ...can also display genetic diversity within single infected hosts with co-existing viral variants evolving differently in distinct cell types. The BriSΔ variant, originally identified as a viral subpopulation from SARS-CoV-2 isolate hCoV-19/England/02/2020, comprises in the spike an eight amino-acid deletion encompassing a furin recognition motif and S1/S2 cleavage site. We elucidate the structure, function and molecular dynamics of this spike providing mechanistic insight into how the deletion correlates to viral cell tropism, ACE2 receptor binding and infectivity of this SARS-CoV-2 variant. Our results reveal long-range allosteric communication between functional domains that differ in the wild-type and the deletion variant and support a view of SARS-CoV-2 probing multiple evolutionary trajectories in distinct cell types within the same infected host.
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