Although prenatal genetic testing has been available for more than 3 decades, the number of conditions that can be detected has increased exponentially over the past decade. This commentary describes ...currently available prenatal genetic screening and diagnostic tests and explores practical and social considerations related to prenatal testing.
Supply expenses occupy an ever-increasing portion of the expense budget in today's increasingly technologically complex operating rooms. Yet, little has been studied and published in the anesthesia ...literature. This review attempts to bring the topic of supply management to anesthesiologists, who play a significant role in operating room management.
Little investigative work has been performed on supply management. Anecdotal reports suggest the benefits of a perpetual inventory system over a periodic inventory system. A perpetual inventory system uses utilization data to update inventory on hand continually and this information is linked to purchasing and restocking, whereas a periodic inventory system counts inventory at some regular intervals (such as annually) and uses average utilization to set par levels.
On the basis of application of operational management concepts, ways of taking advantage of a perpetual inventory system to achieve savings in supply expenses are outlined. These include linking the operating room scheduling and supply order system, distributor-driven just-in-time delivery of case carts, continual updating of preference lists based on utilization patterns, increasing inventory turnovers, standardizing surgical practices, and vendor consignment of high unit-cost items such as implants. In addition, Lean principles of visual management and elimination of eight wastes may be applicable to supply management.
Int22h1/Int22h2‐mediated Xq28 duplication syndrome is a relatively new X‐linked intellectual disability syndrome, arising from duplications of the subregion flanked by intron 22 homologous regions 1 ...and 2 on the q arm of chromosome X. Its primary manifestations include variable cognitive deficits, distinct facial dysmorphia, and neurobehavioral abnormalities that mainly include hyperactivity, irritability, and autistic behavior. Affected males are hemizygous for the duplication, which explains their often more severe manifestations compared with heterozygous females. In this report, we describe the cases of nine individuals recently identified having the syndrome, highlighting unique and previously unreported findings of this syndrome. Specifically, we report for the first time in this syndrome, two cases with de novo duplications, three receiving prenatal diagnosis with the syndrome, and three others having atypical versions of the duplication. Among the latter, one proband has a shortened version spanning only the centromeric half of the typical duplication, while the other two cases have a nearly identical length duplication as the classical duplication, with the exception that their duplication's breakpoints are telomerically shifted by about 0.2 Mb. Finally, we shed light on two new manifestations in this syndrome, vertebral anomalies and multiple malignancies, which possibly expand the phenotypic spectrum of the syndrome.
The L1 cell adhesion molecule (L1CAM) is a neuronal gene involved in the development of the nervous system. Mutations in L1CAM are known to cause several clinically overlapping X linked mental ...retardation conditions: X linked hydrocephalus (HSAS), MASA syndrome (mental retardation, aphasia, shuffling gait, adducted thumbs), spastic paraplegia type I (SPG1), and X linked agenesis of the corpus callosum (ACC). In an analysis of a family with HSAS, we identified a C-->T transition (C924T) in exon 8 that was initially thought to have no effect on the protein sequence as the alteration affected the third base of a codon (G308G). Extensive analysis of the other 27 exons showed no other alteration. A review of the sequence surrounding position 924 indicated that the C-->T transition created a potential 5' splice site consensus sequence, which would result in an in frame deletion of 69 bp from exon 8 and 23 amino acids of the L1CAM protein. RT-PCR of the RNA from an affected male fetus and subsequent sequence analysis confirmed the use of the new splice site. This is the first report of a silent nucleotide substitution in L1CAM giving rise to an alteration at the protein level. Furthermore, it shows that as mutation analysis plays an ever more important role in human genetics, the identification of a synonymous base change should not be routinely discounted as a neutral polymorphism.
In this clinical trial, an 18-month behavioral weight-loss intervention resulted in significant weight loss in persons with serious mental illness. This vulnerable population should not be excluded ...from weight-loss intervention.
Persons with serious mental illness, such as schizophrenia, bipolar disorder, and major depression, have mortality rates that are two to more than three times as high as the rate in the overall population, and the primary cause of death in such persons is cardiovascular disease.
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Concomitantly, this vulnerable population has an extremely high prevalence of obesity, nearly twice that of the overall population.
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Therefore, it is not surprising that persons with serious mental illness have an increased burden of weight-related conditions, including heightened risk of diabetes mellitus, hypertension, dyslipidemia, and certain cancers.
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Obesity is multifactorial in persons . . .
Hypertension is the strongest modifiable risk factor for subcortical ischemic changes and is also a risk factor for Alzheimer's dementia. We used neuroimaging to investigate the pathological basis of ...early cognitive symptoms in patients with hypertension.
In this cross-sectional cohort study 67 patients age >60 years with hypertension and Clinical Dementia Rating scale score of 0.5 without dementia, and without history of symptomatic stroke, underwent MRI for measurement of subcortical vascular changes and positron emission tomography (PET) scan with Pittsburgh Compound B (PiB-PET) to detect beta-amyloid deposition. These imaging measures were related to neuropsychological tests of memory, executive function and processing speed.
Mean age was 75.0 (standard deviation, SD, 7.3). Mean neuropsychological Z scores were: episodic memory -0.63 (SD 1.23), executive function -0.40 (SD 1.10), processing speed -0.24 (SD 0.88); 22 of the 67 subjects met criteria for mild cognitive impairment (MCI) and the remaining 45 subjects had subjective cognitive concerns only. In multivariable models adjusting for age and years of education, each 0.1 unit increase in mean cortical PiB-PET binding was associated with 0.14 lower mean Z score for episodic memory (95% CI -0.28 to -0.01). This means that for every 0.1 unit increase in mean cortical PiB-PET, episodic memory was 0.14 standard deviations lower. White matter hyperintensity volume, silent brain infarcts and microbleeds were not associated with neuropsychological test scores.
Episodic memory was prominently affected in hypertensive participants with MCI or subjective cognitive concerns, and was associated with PiB-PET binding. This suggests a prominent role for Alzheimer pathology in cognitive impairment even in hypertensive participants at elevated risk for vascular cognitive impairment.
Childbearing is one of the most emotional and transformative events in a woman's life. This study aims to explore the impact COVID-19 had on childbirth, postpartum, and the first year since giving ...birth.
This was a qualitative study using data previously collected for a larger study of women who had given birth during the COVID-19 pandemic in the United States. The findings presented here are from an analysis of a subset of open-ended questions. Sixty-six participants completed questions about how COVID-19 affected childbearing and postpartum experiences. Data was analyzed using inductive thematic analysis.
Thematic analysis of the data identified five major themes and several subthemes, including: (1) amplification of new mother typical emotions (positive emotions and negative emotions), (2) financial impact on mothers and their families, (3) persistent impact of COVID-19, (4) new mom paradigm crash (first time mothers and experienced mothers faced different issues such as lack of education and support, adding a layer to the day-to-day, and negotiating time with others) and (5) validating the importance of maternal health. On the whole, participants were overwhelmed, isolated, and did not have enough physical and emotional support. There was a lack of supportive maternal healthcare both in the short-term and long-term, with an emphasis on poor postpartum support.
This study supports previous findings that women who gave birth and entered motherhood during the COVID-19 pandemic were impacted in many ways. These findings contribute to the understanding of women's experiences not just in the immediate postpartum period, but in their daily lives one year after childbirth. The results highlight that our nation's traditional maternal healthcare model may be insufficient, especially when facing a national crisis. Strain placed on the healthcare system by COVID-19 impacted both the physical and mental health of mothers who were often left with inadequate care, education, and support. Our findings point to the need for more supportive maternal health both during childbirth and postpartum.
The assessment of macrophage response to nanoparticles is a central component in the evaluation of new nanoparticle designs for future in vivo application. This work investigates which feature, ...nanoparticle size or charge, is more predictive of non-specific uptake of nanoparticles by macrophages. This was investigated by synthesizing a library of polymer-coated iron oxide micelles, spanning a range of 30-100 nm in diameter and -23 mV to +9 mV, and measuring internalization into macrophages in vitro. Nanoparticle size and charge both contributed towards non-specific uptake, but within the ranges investigated, size appears to be a more dominant predictor of uptake. Based on these results, a protease-responsive nanoparticle was synthesized, displaying a matrix metalloproteinase-9 (MMP-9)-cleavable polymeric corona. These nanoparticles are able to respond to MMP-9 activity through the shedding of 10-20 nm of hydrodynamic diameter. This MMP-9-triggered decrease in nanoparticle size also led to up to a six-fold decrease in nanoparticle internalization by macrophages and is observable by T(2)-weighted magnetic resonance imaging. These findings guide the design of imaging or therapeutic nanoparticles for in vivo targeting of macrophage activity in pathologic states.
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