An evaluation of behavioral treatments for insomnia in the older adult.

Behavioral treatments were evaluated for their effect on the subjective and objective sleep of older adult insomniacs (N = 53) aged 47 to 76 years. Conditions were support and sleep hygiene, support and sleep hygiene plus progressive relaxation, support and sleep hygiene plus stimulus control, or a measurement control group. The results indicated that all groups, including the measurement control group, were effective in improving the sleep diary assessed awakenings, nap time, and feeling refreshed upon awakening. Subjects at 3 weeks felt less depressed and felt that they had more control over their sleep. Stimulus control was most effective in improving sleep at the posttherapy period. A 2-year follow-up showed that the stimulus control subjects most frequently used the treatment instructions and had shorter sleep latencies and highest sleep quality. Behavioral treatments were found to be effective in improving the perception of sleep among older adult insomniacs.     

The effects of continuous exposure to epidermal growth factor on the spontaneous transformation of cultured rat liver epithelial cells.

A long-term continuous exposure to epidermal growth factor (EGF) enhanced the tumorigenicity of spontaneously transformed cells arising in a clonal population of normal cultured rat liver epithelial cells propagated in a selective growth condition. Lengthy EGF exposure also induced the expression of several phenotypes that differed from the phenotypes of rat liver epithelial cells transformed spontaneously in the absence of EGF. Epidermal growth factor treatment caused consistently an enhancement of the constitutive mRNA expression of transforming growth factor-alpha (TGF-alpha), but not of the EGF receptor and transforming growth factor-beta. The overexpression of TGF-alpha persisted in cell lines derived from tumors formed by the EGF-treated transformed cells. These tumors also exhibited high metastatic incidence and ductal cell differentiation. In contrast, untreated spontaneously transformed cells formed non-metastatic tumors with hepatocellular differentiation. These results suggest that long-term, continuous exposure to EGF/TGF-alpha may modulate the phenotypic expressions of neoplastic transformation.     

Molecular cytogenetic analysis of non-small cell lung carcinoma by spectral karyotyping and comparative genomic hybridization

The overall pattern of chromosomal changes detected by spectral karyotype (SKY) analysis of two cell lines of each major histological subtype of NSCLC, namely squamous cell carcinoma (SQCC) and adenocarcinoma (ADC), indicated a greater degree of chromosomal rearrangement, than was present or predicted by either comparative genomic hybridization (CGH) or G-banding analysis alone. To investigate these observations, CGH was used to screen DNA derived from 8 primary tumors and 15 cell lines. The results indicated that the most frequently gained chromosome arms were 5p (70%), 8q (65%), 15q (52%), 20q (48%), 1q (43%), 19q (39%), 3q (35%), and 11q (35%). Chromosomal losses were less frequently observed, and included 18q (39%), 9 (35%), 6q (30%), 13q (21%), 5q12-q32 (17%), and 19p (17%). Amplifications were found on 2p23-p24, 3q24-q27, 5p, 6cen-p21.1, 6q26, 7p21, 7q31, 8q, 11q13-qter, 20q12-q13.2. Comparison between CGH findings of the two major histological subtypes showed that gains at 1q22-q32.2, 15q, 20q, and losses at 6q, 13q, and 18q was common in ADCs, whereas SQCCs exhibited gains/amplifications at 3q. Distal 8q was gained by CGH in 65% of tumors of both subtypes. Low level MYCC amplification was confirmed by direct fluorescence in situ hybridization (FISH) analysis. The pattern of overall chromosomal changes detected using combinations of molecular cytogenetic analytical methods suggests that it will be easier to detect recurrent subtype-dependent aberrations in NSCLC.     

Rapid detection of beta-globin gene (HBB) mutations coupling heteroduplex and primer-extension analysis by DHPLC

Beta-thalassemia is a common inherited disease, resulting from one or more of a total of more than 200 different mutations in the beta-globin gene (HBB). Efficient and reliable mutation-screening methods are essential in order to establish appropriate prevention programs for at-risk populations based upon a molecular diagnosis. We have developed a rapid and highly-specific mutation screening test for the diagnosis of beta-thalassemia by coupling heteroduplex and primer-extension analysis based on the denaturing high performance liquid chromatography (DHPLC) system. A total of 161 healthy heterozygous Taiwanese carriers featuring 10 different HBB mutations and 30 patients exhibiting 12 different compound heterozygous or homozygous HBB mutations were subjected to DHPLC. The elution profile for the heteroduplex analysis of DHPLC could be successfully used to identify the common disease-causing mutations of HBB. To further confirm the sequence variants, we developed a technique combining multiplex primer-extension analysis coupled with DHPLC for the genotyping of eight common disease-causing mutations in the HBB gene. Overall, by coupling heteroduplex and primer-extension analysis based upon DHPLC, we were able to unambiguously identify the most-common beta-thalassemia mutations corresponding to more than 99% of HBB alleles among the Taiwanese population. In conclusion, compared to classic approaches to mutation screening for this malady, we suggest that DHPLC is an excellent technique to be applied to the genetic screening of prenatal and postnatal individuals as a part of a diagnosis program for beta-thalassemia and provides a more-efficient, economic, and sensitive means to undertake such a screening program.     

Comparison of serum specific IgE antibodies to staphylococcal enterotoxins between atopic children with and without atopic dermatitis

BACKGROUND: The skin of patients with atopic dermatitis (AD) exhibits a striking susceptibility to colonization and infection by Staphylococcus aureus. The exotoxins secreted by S. aureus can act as superantigens and classic allergens, inducing the production of functionally relevant specific IgE antibodies. The aim of this study was to compare the levels and positive rates of serum staphylococcal enterotoxin A (SEA)- and staphylococcal enterotoxin B (SEB)-specific IgE between atopic children with and without AD. METHODS: Sixty children with AD, 55 children with respiratory allergy without AD, and 24 nonatopic healthy children were studied. The levels and positive rates of serum SEA- and SEB-specific IgE were compared among three groups. The correlation between the levels or positive rates of serum SEA/SEB-specific IgE and the severity of AD or the presence of previous skin infections was studied. RESULTS: The children with AD had significantly higher levels and positive rates of serum SEA- and SEB-specific IgE than the atopic children without AD (P < 0.001) and the nonatopic children (P < 0.001). There was no significant difference in the levels and positive rates of serum SEA- and SEB-specific IgE between the atopic children without AD and the nonatopic children. With or without adjustment for the potential confounding effect of total serum IgE levels, the levels and positive rates of serum SEA- and SEB-specific IgE were significantly correlated with severity of AD (P <0.005), but they were not significantly different between AD children with and without previous skin infections. CONCLUSIONS: SEA and SEB may contribute to chronic inflammation and exacerbation of AD through the IgE-mediated immune response.     

Inconsistent effects of all-trans retinoic acid on different clones of chemically transformed rat liver epithelial cells

The effects of all-trans retinoic acid (RA) on the growth andbiochemical properties of five clonal strains of neoplasticallytransformed rat liver epithelial cells were studied. These cellstrains were derived clonally from a single line of normal diploidrat liver epithelial cells that had been transformed by treatmentwith N-methyl-N'-nitro-N-nitrosoguanidine. The results showthat RA induces inconsistent alterations in selected phenotypicproperties of these five different cell strains. Retinoic acideither depressed, enhanced or produced no effect on the colony-formingability in soft agar, on the activity of -glutamyl transpeptidase,on the amount of cell-associated fibronectin, and on the bindingcapacity of ¹²⁵I-epidermal growth factor (EGF). The only consistentcorrelation observed among cell strains was between the cellularability to grow in soft agar and the amount of cell-associatedfibronectin. Enhancement of anchorage-independent growth byretinoic acid was not mediated through changes in the numberof EGF receptors. Our data demonstrate that the responses toretinoic acid of clonal subpopulations of chemically transformedrat liver epithelial cells are inconsistent, even when the clonalsubpopulations are derived from a common precursor.     

Veridical causal inference using propensity score methods for comparative effectiveness research with medical claims

Health Services and Outcomes Research Methodology - Medical insurance claims are becoming increasingly common data sources to answer a variety of questions in biomedical research. Although...     

Variation in opioid utilization among neonates with gastroschisis

PurposeRepetitive painful stimuli and early exposure to opioids places neonates at risk for neurocognitive delays. We aimed to understand opioid utilization for neonates with gastroschisis.MethodsWe performed a retrospective review of infants with gastroschisis at a tertiary children's hospital (2017–2019). Multivariate linear regression was performed to analyze variations in opioid use.ResultsAmong 30 patients with gastroschisis, 33% were managed by primary suture-less closure, 7% by primary sutured closure, 40% by spring silo, and 20% by handsewn silo. The proportion of pain medication used was: morphine (89%), acetaminophen (8%), and fentanyl (3%). Opioids were used for a median of 6.5 days (range 0–20) per patient. Median total opioid administered across all patients was 2.2 morphine milligram equivalents (MME)/kg (IQR 0.7–3.3). Following definitive closure, median opioid use was 0.2 MME/kg (IQR 0.1–0.8). With multivariate regression, 45% of the variation in MME use was associated with the type of surgery after adjusting for weight, gestational age, and gender, p = 0.02. After definitive fascial closure, there was no significant variations in opioid use.ConclusionThere is a significant variation in the utilization of opioid, primarily prior to fascial closure. Understanding pain needs and standardization may improve opioid stewardship in infants with gastroschisis. 197/200Level of EvidenceLevel III     

Cryoanalgesia enhances recovery from minimally invasive repair of pectus excavatum resulting in reduced length of stay: A case-matched analysis of NSQIP-Pediatric patients

PurposePain control is challenging after minimally invasive repair of pectus excavatum (MIRPE). Cryoanalgesia, which temporarily ablates peripheral nerves, improves pain control and may accelerate post-operative recovery. We hypothesized that cryoanalgesia would be associated with shorter length of stay (LOS) in children undergoing MIRPE.MethodsA matched cohort study was conducted of children (<18 years) who underwent MIRPE 2016–2018, using the National Surgical Quality Improvement Program-Pediatric database. Each patient who received cryoanalgesia during MIRPE was matched to four controls (no cryoanalgesia). Univariate and multilevel regression analyses were performed.ResultsThirty-five patients who received cryoanalgesia during MIRPE were matched to 140 controls. Patients who received cryoanalgesia had a LOS reduction with similar secondary outcomes (operative time, rates of complication, reoperation, and readmission). On multilevel regression adjusted for matched groups, cryoanalgesia was associated with a 1.3-day reduction in LOS (95% CI ?1.8 to ?0.8, p < 0.001). On sensitivity analysis excluding patients with complications, cryoanalgesia remained associated with a LOS reduction.ConclusionsCryoanalgesia is a promising adjunct in the care of pediatric patients undergoing MIRPE. Utilization is associated with a shorter LOS without an increase in operative time or complications. Cryoanalgesia should be considered for inclusion in enhanced recovery strategies for patients undergoing MIRPE.     

Rapid induction of cytokine gene expression in the lung after single and fractionated doses of radiation

PURPOSE: To investigate cytokine gene expression in the lung after single and fractionated doses of radiation, and to investigate the effect of steroids and the genetic background. MATERIALS AND METHODS: Expression of cytokine genes (mTNF-alpha, mIL-1alpha, mIL-1beta, mIL-2, mIL-3, mIL-4, mIL-5, mIL-6, mIFN-gamma) in the lungs of C3H/HeJ and C57BL/6J mice was measured by RNase protection assay at different times after various doses of radiation. The effects of dexamethasone and fractionated radiation treatment on gene expression were also studied. RESULTS: IL-1beta was the major cytokine induced in the lungs of C3H/HeJ mice within the first day after thoracic irradiation. Radiation doses as low as 1 Gy were effective. Responses to 20 Gy irradiation peaked within 4-8h and subsided by 24 h. With the exception of IL-1alpha and TNF-alpha, the other cytokines that were investigated had undetectable pre-treatment mRNA levels and were not radiation inducible. Similar responses were seen in C57BL/6J mice, although TNF-alpha was induced and there were some quantitative differences. Pre-treatment of C3H/HeJ mice with dexamethasone reduced basal and induced IL-1 levels, but complete inhibition was not achieved. Dexamethasone was also effective if given immediately after irradiation. Fractionated daily doses of radiation (4 Gy/day) helped to maintain cytokine gene expression for a longer period. CONCLUSIONS: Inflammatory genes are rapidly induced in the lung by irradiation. This response cannot be readily abolished by steroid pre-treatment. Fractionated treatment schedules help to perpetuate the response.