Abstract Purpose Fever occurs commonly in the critically ill patients and may adversely affect outcome. Acetaminophen is one of the most commonly used antipyretic agents in the intensive care unit; ...however, there is little evidence that it is effective in this population. The objective of this study was to analyze the antipyretic activity of acetaminophen in critically ill patients. Materials and Methods We performed a retrospective study of medical intensive care unit and surgical intensive care unit patients with systemic inflammatory response syndrome and compared the resolution of fever in the presence and absence of acetaminophen treatment by comparing the absolute reduction in body temperature and the rate of cooling over comparable time frames in fevers that were untreated and those treated with acetaminophen. Results We analyzed 166 febrile episodes (body temperature, >38°C) in 59 patients with systemic inflammatory response syndrome without cancer, neurologic disease, or liver disease. Acetaminophen was administered for 88 of 166 fevers. Febrile episodes in which other antipyretic drugs or external cooling were administered were excluded. The response to acetaminophen was variable, but the absolute temperature reduction was slightly higher (mean, 0.86 versus 0.56°C; P = .0362), and the cooling rate was slightly more rapid (mean, 0.20 versus 0.13°C per hour; P = .0152) in acetaminophen-treated versus untreated fevers. There were no obvious differences between the most and least responsive patients. Conclusions We conclude that acetaminophen has significant albeit modest antipyretic activity in critically ill patients.
The present study investigated the effects of children without disabilities on maternal physical and mental health in families with adolescents or adults with fragile X syndrome. Mothers with the ...FMR1 premutation (N = 87) reported on behavior problems and functional limitations of their adolescent or adult child with fragile X syndrome and their own physical and mental health. Mothers also provided a blood sample to determine FMR1 CGG repeat length. The proportion of unaffected children in the family significantly buffered the effect of both child behavior problems and functional limitations on maternal self-rated health, such that having a higher proportion of unaffected children in the family had a protective effect on maternal health when the target child had more severe behavior problems and functional limitations. There was a similar buffering process for maternal depressive symptoms but at a trend level. Additionally, maternal CGG repeat length had a significant curvilinear association with self-rated health, indicating that mothers with midrange repeat lengths reported the poorest health, whereas mothers with lower and higher repeat lengths in the premutation range reported better health. The data suggest that unaffected children in the family may be an important resource for premutation carrier mothers. Findings are consistent with previous research indicating that mothers with varying levels of genetic liability have variable risk for health problems.
Cerebral amyloid β-protein angiopathy (CAA) is a key pathological feature of patients with Alzheimer's disease and certain related disorders. In these conditions the CAA is characterized by the ...deposition of Aβ within the cerebral vessel wall and, in severe cases, hemorrhagic stroke. Several mutations have been identified within the Aβ region of the Aβ protein precursor (AβPP) gene that appear to enhance the severity of CAA. We recently described a new mutation within the Aβ region (D23N) of AβPP that is associated with severe CAA in an Iowa kindred (Grabowski, T. J., Cho, H. S., Vonsattel, J. P. G., Rebeck, G. W., and Greenberg, S. M. (2001) Ann. Neurol. 49, 697–705). In the present study, we investigated the effect of this new D23N mutation on the processing of AβPP and the pathogenic properties of Aβ. Neither the D23N Iowa mutation nor the E22Q Dutch mutation affected the amyloidogenic processing of AβPP expressed in H4 cells. The A21G Flemish mutation, in contrast, resulted in a 2.3-fold increase in secreted Aβ peptide. We also tested synthetic wild-type and mutant Aβ40 peptides for fibrillogenesis and toxicity toward cultured human cerebrovascular smooth muscle (HCSM) cells. The E22Q Dutch, D23N Iowa, and E22Q,D23N Dutch/Iowa double mutant Aβ40 peptides rapidly assembled in solution to form fibrils, whereas wild-type and A21G Flemish Aβ40 peptides exhibited little fibril formation. Similarly, the E22Q Dutch and D23N Iowa Aβ40 peptides were found to induce robust pathologic responses in cultured HCSM cells, including elevated levels of cell-associated AβPP, proteolytic breakdown of smooth muscle cell α-actin, and cell death. Double mutant E22Q,D23N Dutch/Iowa Aβ40 was more potent than either single mutant form of Aβ in causing pathologic responses in HCSM cells. These data suggest that the different CAA mutations in AβPP may exert their pathogenic effects through different mechanisms. Whereas the A21G Flemish mutation appears to enhance Aβ production, the E22Q Dutch and D23N Iowa mutations enhance fibrillogenesis and the pathogenicity of Aβ toward HCSM cells.
AMP-activated protein kinase (AMPK) is activated in adipocytes during exercise and other states in which lipolysis is stimulated. However, the mechanism(s) responsible for this effect and its ...physiological relevance are unclear. To examine these questions, 3T3-L1 adipocytes were treated with cAMP-inducing agents (isoproterenol, forskolin, and isobutylmethylxanthine), which stimulate lipolysis and activate AMPK. When lipolysis was partially inhibited with the general lipase inhibitor orlistat, AMPK activation by these agents was also partially reduced, but the increases in cAMP levels and cAMP-dependent protein kinase (PKA) activity were unaffected. Likewise, small hairpin RNA-mediated silencing of adipose tissue triglyceride lipase inhibited both forskolin-stimulated lipolysis and AMPK activation but not that of PKA. Forskolin treatment increased the AMP:ATP ratio, and this too was reduced by orlistat. When acyl-CoA synthetase, which catalyzes the conversion of fatty acids to fatty acyl-CoA, was inhibited with triacsin C, the increases in both AMPK activity and AMP:ATP ratio were blunted. Isoproterenol-stimulated lipolysis was accompanied by an increase in oxidative stress, an effect that was quintupled in cells incubated with the AMPK inhibitor compound C. The isoproterenol-induced increase in the AMP:ATP ratio was also much greater in these cells. In conclusion, the results indicate that activation of AMPK in adipocytes by cAMP-inducing agents is a consequence of lipolysis and not of PKA activation. They suggest that AMPK activation in this setting is caused by an increase in the AMP:ATP ratio that appears to be due, at least in part, to the acylation of fatty acids. Finally, this AMPK activation appears to restrain the energy depletion and oxidative stress caused by lipolysis.
Every aspect of the medical field has been heavily affected by the coronavirus disease 2019 (COVID-19) pandemic, and neurosurgical services are no exception. Several departments have reported their ...experiences and protocols to provide insights for others impacted. The goals of this study are to report the load and variety of neurosurgical cases and clinic visits after discontinuing the COVID-19 Battle Plan at an academic tertiary care referral center to provide insights for other departments going through the same transition.
The clinical data of all patients who underwent a neurosurgical intervention between May 4, 2020, and June 4, 2020 were obtained from a prospectively maintained database. Data of the control group were retrospectively collected from the medical records to compare the types of surgeries/interventions and clinic visits performed by the same neurosurgical service before the COVID-19 pandemic started.
One hundred sixty-one patients underwent neurosurgical interventions, and seven-hundred one patients were seen in clinic appointments, in the 4-week period following easing back from our COVID-19 “Battle Plan.” Discontinuing the “Battle Plan” resulted in increases in case load to above-average practice after a week but a continued decrease in clinic appointments throughout the 4 weeks compared with average practice.
As policy-shaping crises like pandemics abate, easing back to “typical” practice can be completed effectively by appropriately allocating resources. This can be accomplished by anticipating increases in neurosurgical volume, specifically in the functional/epilepsy and brain tumor subspecialties, as well as continued decreases in neurosurgical clinic volume, specifically in elective spine.
Many medical centers are faced with a major challenge in making an accurate diagnosis of heparin-induced thrombocytopenia (HIT) and ensuring appropriate changes in management strategy in line with ...guideline recommendations. We report the initial and long-term impact and challenges of institution-wide changes in the diagnosis and management of HIT in the inpatient setting at an academic medical center. We established a HIT Task Force, consisting of a multidisciplinary team of non-malignant hematologists, nursing, pharmacist, pathology, blood bank and clinical lab informatics. Changes were implemented from 2011 to 2012. In 2013, testing for PF4 and SRA decreased by 37.5 and 85%, respectively. 100% of positive PF4 received an automatic hematology consult to guide management, leading to a 78% reduction in the use of direct thrombin inhibitors. Annual audits in the subsequent years demonstrated increasing testing for HIT due to changes in the electronic ordering system. Through continuous monitoring, these shortfalls were detected and intervene early on with continued success. The implementation of a centralized hospital-wide protocol via a multidisciplinary task force that coordinates testing and treatment of patients suspected of having HIT led to a substantial reduction in PF4 and SRA testing, as well as use of DTIs, resulting in a safe and cost-effective approach for the diagnosis and treatment of HIT. Our study highlights the important of continuous monitoring to maintain the improvements made. Despite our initial success, annual re-auditing allowed for early detection of challenges, which then allowed appropriate early intervention.
Cognitive Aging in Parents of Children with Disabilities Song, Jieun; Mailick, Marsha R; Greenberg, Jan S ...
The journals of gerontology. Series B, Psychological sciences and social sciences,
09/2016, Letnik:
71, Številka:
5
Journal Article
Recenzirano
Odprti dostop
This study examines the cognitive functioning of parents of children with disabilities, specifically, whether there is an evidence of accelerated cognitive aging among these parents. In addition, the ...study investigates the moderating influences of two variables: parents' gender and stress from negative parenting experience.
The analyses utilize data from the National Survey of Midlife in the United States (2005). The analytic sample consisted of two groups of parents, who completed the cognitive battery, the interview, and the mail-back survey: 128 parents who had children with childhood-onset disabilities and 512 matched comparison parents who had only nondisabled children.
Age differences in episodic memory were more pronounced among mothers of children with disabilities than among mothers with nondisabled children, especially among mothers with higher levels of negative parenting experience. In contrast, there were no interaction effects of parenting status, age, and negative parenting experience among fathers.
The results show that parenting children with disabilities over a prolonged period of time jeopardizes cognitive function (especially memory) among older mothers, possibly via the mechanism of heightened parenting stress due to higher levels of negative parenting experience.
Objective: Perilipin is a class of protein‐coating lipid droplets in adipocytes and steroidogenic cells. Our purpose was to examine the association between common single‐nucleotide polymorphisms ...(SNPs) at the perilipin (PLIN) locus and obesity, as well as related phenotypes, in unrelated American adults.
Research Methods and Procedures: Four PLIN SNPs (PLIN 6209T>C, 11482G>A, 13041A>G, and 14995A>T) were typed in 734 white subjects (373 men and 361 women) attending a residential lifestyle intervention program. The baseline anthropometric and biochemical measures were used. Obesity was defined as BMI ≥ 30 kg/m2.
Results: Multivariate analysis demonstrated that, in women, two of the SNPs (13041A>G, and 14995A>T) were significantly associated with percentage body fat (p = 0.016 for 13041A>G and p = 0.010 for 14995A>T) and waist circumference (p = 0.020 for 13041A>G and p = 0.045 for 14995A>T). Moreover, haplotype analysis using these two SNPs indicated that haplotypes A/T and G/T were both associated with significantly increased obesity risk (odds ratio = 1.76, 95% confidence interval 1.07 to 2.90 for haplotype A/T, and odds ratio = 1.73, 95% confidence interval 1.06 to 2.82 for haplotype G/T) when compared with haplotype A/A. No significant associations between PLIN variations and obesity were found in men.
Discussion: Our data support the hypothesis that the PLIN locus may be a significant genetic determinant for obesity risk in whites and that women are more sensitive to the genetic effects of perilipin than men.
Although an increasing number of individuals with autism spectrum disorders are entering adulthood, currently there are few evidence-based programs for individuals later in the life course. In this ...paper we present an overview of recent research on outcomes for adolescents and adults with ASD and highlight the role of the family for individuals with ASD during the transition to adulthood. We also discuss multi-family group psychoeducation as a promising model for use with individuals with ASD who are transitioning to adulthood.
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