Understanding the different modifiable and non‐modifiable factors and their positive or negative influence on parental and child satisfaction is essential to providing high‐quality perioperative ...care. The purpose of this review is to focus on the perioperative environment and to report the various modifiable and non‐modifiable factors that are associated with satisfaction. We found that factors such as quality of clinician‐patient communication, clinician attitudes, teamwork, shared decision‐making, and improved perioperative information were associated with increased parent and child satisfaction. Interventions such as preparation programs integrating role‐play, teaching of coping skills, and family‐centered programs were highly rated by parents and children. Healthcare providers and institutions should consider the above variables when treating children and their parents in the perioperative setting.
Microglial activation is an early and common feature of almost all neuropathologies, including multiple sclerosis, Alzheimer's disease and mechanical injury. To better understand the relative ...contributions microglia make toward neurodegeneration and neuroprotection, we used TOGA® to identify molecules expressed by microglia and regulated by inflammatory signals. Triggering receptor expressed on myeloid cells‐2 (TREM‐2) was among the mRNAs identified as being expressed by unactivated microglia, but down‐regulated by lipopolysaccharide/interferon γ. In the healthy CNS, not all microglia expressed TREM‐2. Microglial expression of TREM‐2 varied not only between brain regions but also within each brain region. Brain regions with an incomplete blood–brain barrier had the lowest percentages of TREM‐2‐ expressing microglia, whereas the lateral entorhinal and cingulate cortex had the highest percentages. A novel form of TREM‐2b that lacked a transmembrane domain was detected, perhaps indicating a soluble form of the protein. Taken together, these data suggest that (1) subsets of microglia are specialized to respond to defined extracellular signals; and (2) regional variations in TREM‐2 expression may contribute to the varying sensitivities of different brain regions to similar pathological signals.
The purpose of this investigation was to summarize current research on diagnosis, outcomes, and management of frail patients undergoing orthopedic surgery. Because frail patients are at increased ...risk of negative post-operative outcomes including increased 30-day mortality and post-operative complications including infections and delirium, such a review is timely. Strategies including supervised exercise training programs before surgery, early identification of frailty, prophylactic antibiotics, regular drug chart review, regular monitoring of electrolytes, and other strategies to prevent post-operative delirium are helpful in the management of frail orthopedic patients. It is important for surgeons and anesthesiologists to take action in attempt to alleviate adverse post-operative outcomes in frail patients. Ultimately, more research is needed to identify new strategies and to evaluate whether pre-operative optimization can effectively mitigate post-operative outcomes in large-scale randomized controlled trials.
Damaging
variants cause cardiac outflow tract defects, sometimes with pancreatic and diaphragmic malformations. To define molecular mechanisms for these diverse developmental defects, we studied ...transcriptional and epigenetic responses to
loss of function (LoF) and missense variants during cardiomyocyte differentiation of isogenic human induced pluripotent stem cells. We show that GATA6 is a pioneer factor in cardiac development, regulating
that activates
and
that with
orchestrates outflow tract formation. LoF variants perturbed cardiac genes and also endoderm lineage genes that direct
expression and pancreatic development. Remarkably, an exon 4
missense variant, highly associated with extra-cardiac malformations, caused ectopic pioneer activities, profoundly diminishing
,
and
expression and increasing normal retinoic acid signaling that promotes diaphragm development. These aberrant epigenetic and transcriptional signatures illuminate the molecular mechanisms for cardiovascular malformations, pancreas and diaphragm dysgenesis that arise in patients with distinct
variants.
Germline mutations of BRCA1 and BRCA2 predispose individuals to a high risk of breast and ovarian cancer, and elevated risk of other cancers, including those of the pancreas and prostate. BRCA2 ...mutation carriers may have increased risk of uveal melanoma (UM) and cutaneous melanoma (CM), but associations with these cancers in BRCA1 mutation carriers have been mixed. Here, we further assessed whether UM and CM are associated with BRCA1 or BRCA2 by assessing the presence, segregation and reported/predicted pathogenicity of rare germline mutations (variant allele frequency < 0.01) in families with multiple members affected by these cancers. Whole-genome or exome sequencing was performed on 160 CM and/or UM families from Australia, the Netherlands, Denmark and Sweden. Between one and five cases were sequenced from each family, totalling 307 individuals. Sanger sequencing was performed to validate BRCA1 and BRCA2 germline variants and to assess carrier status in other available family members. A nonsense and a frameshift mutation were identified in BRCA1, both resulting in premature truncation of the protein (the first at p.Q516 and the second at codon 91, after the introduction of seven amino acids due to a frameshift deletion). These variants co-segregated with CM in individuals who consented for testing and were present in individuals with pancreatic, prostate and breast cancer in the respective families. In addition, 33 rare missense mutations (variant allele frequency ranging from 0.00782 to 0.000001 in the aggregated ExAC data) were identified in 34 families. Examining the previously reported evidence of functional consequence of these variants revealed all had been classified as either benign or of unknown consequence. Seeking further evidence of an association between BRCA1 variants and melanoma, we examined two whole-genome/exome sequenced collections of sporadic CM patients (total N = 763). We identified one individual with a deleterious BRCA1 variant, however, this allele was lost (with the wild-type allele remaining) in the corresponding CM, indicating that defective BRCA1 was not a driver of tumorigenesis in this instance. Although this is the first time that deleterious BRCA1 mutations have been described in high-density CM families, we conclude that there is an insufficient burden of evidence to state that the increased familial CM or UM susceptibility is because of these variants. In addition, in conjunction with other studies, we conclude that the previously described association between BRCA2 mutations and UM susceptibility represents a rare source of increased risk.
The ALS (agglutinin-like sequence) gene family encodes proteins that play a role in adherence of the yeast Candida albicans to endothelial and epithelial cells. The proteins are proposed as virulence ...factors for this important fungal pathogen of humans. We analyzed 66 C. albicans strains, representing a worldwide collection of 266 infection-causing isolates, and discovered 60 alleles of the ALS7 open reading frame (ORF). Differences between alleles were largely caused by rearrangements of repeat elements in the so-called tandem repeat domain (21 different types occurred) and the VASES region (19 different types). C. albicans is diploid, and combinations of ALS7 alleles generated 49 different genotypes. ALS7 expression was detected in samples isolated directly from five oral candidosis patients. ORFs in the opposite direction contained within the ALS7 ORF were also transcribed in all strains tested. Isolates representing a more pathogenic general-purpose genotype (GPG) cluster of strains tended to have more tandem repeats than other strains. Two types of VASES regions were largely exclusive to GPG strains; the remaining types were largely exclusive to noncluster strains. Our results provide evidence that ALS7 is a hypermutable contingency locus and important for the success of C. albicans as an opportunistic pathogen of humans.
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