Corona ions produced by high voltage power lines (HVPL) can alter the local atmospheric electrical environment downwind, potentially increasing electrostatic charge on airborne particulates via ...ion-aerosol attachment. However, previous epidemiological assessments attempting to assess this ‘corona ion hypothesis’ have used proxies e.g. ion concentration or distance from HVPL, rather than aerosol charge state directly, due to difficulties in modeling this quantity. We present a quasi-1D model incorporating both Gaussian plume dynamics and ion-aerosol and ion-ion interaction microphysics which could be applied to future studies of charged aerosol near HVPL. The response of the model to changes in a range of input parameters is characterized, and validation is attempted by means of comparison with previous work where ion- and aerosol concentrations and properties (including electrical mobility and electric charge states) upwind and downwind of HVPL are measured.
mRNA translation decodes nucleotide into amino acid sequences. However, translation has also been shown to affect mRNA stability depending on codon composition in model organisms, although ...universality of this mechanism remains unclear. Here, using three independent approaches to measure exogenous and endogenous mRNA decay, we define which codons are associated with stable or unstable mRNAs in human cells. We demonstrate that the regulatory information affecting mRNA stability is encoded in codons and not in nucleotides. Stabilizing codons tend to be associated with higher tRNA levels and higher charged/total tRNA ratios. While mRNAs enriched in destabilizing codons tend to possess shorter poly(A)-tails, the poly(A)-tail is not required for the codon-mediated mRNA stability. This mechanism depends on translation; however, the number of ribosome loads into a mRNA modulates the codon-mediated effects on gene expression. This work provides definitive evidence that translation strongly affects mRNA stability in a codon-dependent manner in human cells.
Various insults cause ototoxicity in mammals by increasing oxidative stress leading to apoptosis of auditory hair cells (HCs). The thiazolidinediones (TZDs; e.g., pioglitazone) and fibrate (e.g., ...fenofibrate) drugs are used for the treatment of diabetes and dyslipidemia. These agents target the peroxisome proliferator-activated receptors, PPARγ and PPARα, which are transcription factors that influence glucose and lipid metabolism, inflammation, and organ protection. In this study, we explored the effects of pioglitazone and other PPAR agonists to prevent gentamicin-induced oxidative stress and apoptosis in mouse organ of Corti (OC) explants. Western blots showed high levels of PPARγ and PPARα proteins in mouse OC lysates. Immunofluorescence assays indicated that PPARγ and PPARα proteins are present in auditory HCs and other cell types in the mouse cochlea. Gentamicin treatment induced production of reactive oxygen species (ROS), lipid peroxidation, caspase activation, PARP-1 cleavage, and HC apoptosis in cultured OCs. Pioglitazone mediated its anti-apoptotic effects by opposing the increase in ROS induced by gentamicin, which inhibited the subsequent formation of 4-hydroxy-2-nonenal (4-HNE) and activation of pro-apoptotic mediators. Pioglitazone mediated its effects by upregulating genes that control ROS production and detoxification pathways leading to restoration of the reduced:oxidized glutathione ratio. Structurally diverse PPAR agonists were protective of HCs. Pioglitazone (PPARγ-specific), tesaglitazar (PPARγ/α-specific), and fenofibric acid (PPARα-specific) all provided >90% protection from gentamicin toxicity by regulation of overlapping subsets of genes controlling ROS detoxification. This study revealed that PPARs play important roles in the cochlea, and that PPAR-targeting drugs possess therapeutic potential as treatment for hearing loss.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Use of the absorbable deep dermal stapler in wound closure has become more common in plastic surgery because of its possible reduction in operative times and subsequent decrease in operative room ...costs. In this study, we examine the effects of this stapler on operative times and postoperative complications in bilateral reduction mammaplasties.
A retrospective, observational cohort study was conducted via electronic chart review on patients who underwent bilateral reduction mammaplasties. Patients were stratified by wound closure method. One group was closed with sutures only, and in the other group, deep dermal staples were used during closure of the inframammary fold incision. Incidences of patient comorbidities and postoperative complications were compared. In addition, a financial cost analysis was performed.
The final patient cohort included 62 patients. Operative time was reduced by an average of 21.8 minutes when using deep dermal staples during closure, compared with when closing solely with sutures (P = 0.032). When controlling for mass of breast tissue removed and type of pedicle, deep dermal staple closure still predicted a reduction of 26.5 (SE, 9.9) minutes in operative time (P = 0.010). Postoperative complications were not affected by wound closure method (odds ratio, 4.36; 95% confidence interval, 0.91-31.7, P = 0.087). Though not statistically significant, financial charge was decreased with usage of deep dermal staples (P = 0.34).
Use of absorbable deep dermal staples produces a significant decrease in operative time for reduction mammaplasties with no increase in postoperative complication rates.
Abstract
Objectives
Our study compares two types of later life marital dissolution that occur after age 50—divorce and widowhood—and their associations with repartnership status (i.e., remarried, ...cohabiting, or unpartnered).
Method
We used data from the Health and Retirement Study to provide a portrait of later life divorce and widowhood for women and men. Next, we tested whether marital dissolution type is related to women’s and men’s repartnered status, distinguishing among remarrieds, cohabitors, and unpartnereds, net of key sociodemographic indicators.
Results
Divorcees are more often repartnered through either remarriage or cohabitation than are widoweds. This gap persists among women net of an array of sociodemographic factors. For men, the differential is reduced to nonsignificance with the inclusion of these factors.
Discussion
Later life marital dissolution increasingly occurs through divorce rather than widowhood, and divorce is more often followed by repartnership. The results from this study suggest that gerontological research should not solely focus on widowhood but also should pay attention to divorce and repartnering during later life.
Amphotericin B (AMB) is used most commonly in severe systemic life-threatening fungal infections. There is currently an unmet need for an efficacious (AMB) formulation amenable to oral administration ...with better bioavailability and lower nephrotoxicity. Novel PEGylated polylactic-polyglycolic acid copolymer (PLGA-PEG) nanoparticles (NPs) formulations of AMB were therefore studied for their ability to kill Candida albicans (C. albicans). The antifungal activity of AMB formulations was assessed in C. albicans. Its bioavalability was investigated in nine groups of rats (n = 6). Toxicity was examined by an in vitro blood hemolysis assay, and in vivo nephrotoxicity after single and multiple dosing for a week by blood urea nitrogen (BUN) and plasma creatinine (PCr) measurements. The MIC of AMB loaded to PLGA-PEG NPs against C. albicans was reduced two to threefold compared with free AMB. Novel oral AMB delivery loaded to PLGA-PEG NPs was markedly systemically available compared to Fungizone® in rats. The addition of 2% of GA to the AMB formulation significantly (p < 0.05) improved the bioavailability from 1.5 to 10.5% and the relative bioavailability was > 790% that of Fungizone®. The novel AMB formulations showed minimal toxicity and better efficacy compared to Fungizone®. No nephrotoxicity in rats was detected after a week of multiple dosing of AMB NPs based on BUN and PCr, which remained at normal levels. An oral delivery system of AMB-loaded to PLGA-PEG NPs with better efficacy and minimal toxicity was formulated. The addition of glycyrrhizic acid (GA) to AMB NPs formulation resulted in a significant oral absorption and improved bioavailability in rats.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
Older adults are at the forefront of family change as a declining share experiences lifelong marriage and rates of cohabitation and divorce in later life continue to rise. The goal of this ...article is to review recent scholarship on marriage, cohabitation, and divorce among older adults and identify directions for future research. The varied family experiences characterizing the later life course demonstrate the importance of moving beyond marital status to capture additional dimensions of the marital biography, including transitions, timing, duration, and sequencing. Cohabitation operates as an alternative to marriage for older adults and is increasingly replacing remarriage following divorce or widowhood. The gray divorce rate has doubled in recent decades as older adults abandon marriage in favor of unmarried partnerships or singlehood. The retreat from marriage among older adults raises important questions about the ramifications of family change for health and well-being as well as access to caregivers given that spouses historically have been the primary source of care.
Ablation of Persistent AF Wright, Matthew, MRCP, PhD
Journal of the American College of Cardiology,
12/2015, Letnik:
66, Številka:
24
Journal Article
Recenzirano
Odprti dostop
Nothing is impossible to a willing heartThe Proverbs and Epigrams of John Heywood (A.D. 1562) (1) The long-term maintenance of sinus rhythm in patients in persistent atrial fibrillation (AF) remains ...a demanding task whatever therapeutic option is taken, but it is a challenge electrophysiologists and surgeons have enthusiastically pursued for several decades. With single procedure success rates (defined by no recurrence of documented arrhythmia) of approximately 70% at 1 year (3) and long-term outcomes (3 to 5 years) of 80% for PV isolation (PVI) with multiple procedures (4,5), this assumption appears correct for paroxysmal AF.
Antecedents of Gray Divorce: A Life Course Perspective Lin, I-Fen; Brown, Susan L; Wright, Matthew R ...
The journals of gerontology. Series B, Psychological sciences and social sciences,
08/2018, Letnik:
73, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Abstract
Objectives
Increasingly, older adults are experiencing divorce, yet little is known about the risk factors associated with divorce after age 50 (termed “gray divorce”). Guided by a life ...course perspective, our study examined whether key later life turning points are related to gray divorce.
Method
We used data from the 1998–2012 Health and Retirement Study to conduct a prospective, couple-level discrete-time event history analysis of the antecedents of gray divorce. Our models incorporated key turning points (empty nest, retirement, and poor health) as well as demographic characteristics and economic resources.
Results
Contrary to our expectations, the onset of an empty nest, the wife’s or husband’s retirement, and the wife’s or husband’s chronic conditions were unrelated to the likelihood of gray divorce. Rather, factors traditionally associated with divorce among younger adults were also salient for older adults. Marital duration, marital quality, home ownership, and wealth were negatively related to the risk of gray divorce.
Discussion
Gray divorce is especially likely to occur among couples who are socially and economically disadvantaged, raising new questions about the consequences of gray divorce for individual health and well-being.
OBJECTIVETo understand how, biologically, the acute event of traumatic brain injury gives rise to a long-term disease, we address the relationship between evolving cortical and subcortical brain ...damage and measures of functional outcome and cognitive functioning at 6 months after injury.
METHODSFor this longitudinal analysis, clinical and MRI data were collected in a tertiary neurointensive care setting in a continuous sample of 157 patients surviving moderate to severe traumatic brain injury between 2000 and 2018. For each patient, we collected T1- and T2-weighted MRI data acutely and at the 6-month follow-up, as well as acute measures of injury severity (Glasgow Coma Scale), follow-up measures of functional impairment (Glasgow Outcome Scale–extended), and, in a subset of patients, neuropsychological measures of attention, executive functions, and episodic memory.
RESULTSIn the final cohort of 113 subcortical and 92 cortical datasets that survived (blind) quality control, extensive atrophy was observed over the first 6 months after injury across the brain. However, only atrophy within subcortical regions, particularly in the left thalamus, was associated with functional outcome and neuropsychological measures of attention, executive functions, and episodic memory. Furthermore, when brought together in an analytical model, longitudinal brain measurements could distinguish good from bad outcome with 90% accuracy, whereas acute brain and clinical measurements alone could achieve only 20% accuracy.
CONCLUSIONDespite great injury heterogeneity, secondary thalamic pathology is a measurable minimum common denominator mechanism directly relating biology to clinical measures of outcome and cognitive functioning, potentially linking the acute event and the longer-term disease of traumatic brain injury.
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