Small noncoding microRNAs (miRNAs) have been shown to be abnormally expressed in every tumor type examined. The importance of miRNAs as potential cancer prognostic indicators is underscored by their ...involvement in the regulation of basic cellular processes such as cell proliferation, differentiation, and apoptosis. In this study, miRNA expression profiles of head and neck squamous cell carcinoma (HNSCC) tumor and adjacent normal tissue were examined by microarray analysis and validated by quantitative TaqMan real-time polymerase chain reaction. Using TaqMan real-time polymerase chain reaction we measured the quantitative associations between a subset of miRNAs identified on microarrays in primary tumors at diagnosis and cancer survival in a cohort of 104 HNSCC patients undergoing treatment with curative intent. The majority of miRNAs exhibiting altered expression in primary human HNSCC tumors (including miR-1 , miR-133a , miR-205 , and let-7d ) show lower expression levels relative to normal adjacent tissue. In contrast, hsa-miR-21 is frequently overexpressed in human HNSCC tumors. Using univariate and multivariable statistical models we show that low levels of hsa-miR205 are significantly associated with loco-regional recurrence independent of disease severity at diagnosis and treatment. In addition, combined low levels of hsa-miR-205 and hsa-let-7d expression in HNSCC tumors are significantly associated with poor head and neck cancer survival Our results show that miRNA expression levels can be used as prognostic markers of head and neck cancer.
To provide a quantitative meta-analysis of the antidepressant effects of sleep deprivation to complement qualitative reviews addressing response rates.
English-language studies from 1974 to 2016 ...using the keywords sleep deprivation and depression searched through PubMed and PsycINFO databases.
A total of 66 independent studies met criteria for inclusion: conducted experimental sleep deprivation, reported the percentage of the sample that responded to sleep deprivation, provided a priori definition of antidepressant response, and did not seamlessly combine sleep deprivation with other therapies (eg, chronotherapeutics, repetitive transcranial magnetic stimulation).
Data extracted included percentage of responders, type of sample (eg, bipolar, unipolar), type of sleep deprivation (eg, total, partial), demographics, medication use, type of outcome measure used, and definition of response (eg, 30% reduction in depression ratings). Data were analyzed with meta-analysis of proportions and a Poisson mixed-effects regression model.
The overall response rate to sleep deprivation was 45% among studies that utilized a randomized control group and 50% among studies that did not. The response to sleep deprivation was not affected significantly by the type of sleep deprivation performed, the nature of the clinical sample, medication status, the definition of response used, or age and gender of the sample.
These findings support a significant effect of sleep deprivation and suggest the need for future studies on the phenotypic nature of the antidepressant response to sleep deprivation, on the neurobiological mechanisms of action, and on moderators of the sleep deprivation treatment response in depression.
To systematically review (1) biomechanical properties of augmented elbow ulnar collateral ligament (UCL) repair compared with reconstruction and (2) clinical efficacy and complication rates of UCL ...repair with and without augmentation.
A systematic review was completed August 15, 2023, identifying articles that (1) biomechanically compared suture augmented UCL repair and reconstruction and (2) clinically evaluated medial elbow UCL repairs. Search terms included: “UCL repair” OR “internal brace” OR “suture augmentation” AND “UCL reconstruction.” For inclusion, biomechanical studies compared augmented repair with reconstruction; clinical studies required clinical outcomes with minimum 6-month follow-up. Biomechanical data included torsional stiffness, gap formation, peak torque, and failure torque. Clinical data included return to previous level of play, time to return, functional outcomes, and complications.
In total, 8 biomechanical and 9 clinical studies were included (5 with and 4 without augmentation). In most biomechanical studies, augmented repairs demonstrated less gap formation, with equivalent torsional stiffness, failure load, and peak torque compared with reconstruction. Clinical outcomes in 104 patients without augmentation demonstrated return to previous level of 50% to 94% for nonprofessional athletes and 29% for professional baseball pitchers. Suture augmented repairs in 554 patients demonstrated return to previous level from 92% to 96%, at 3.8 to 7.4 months, with Kerlan Jobe Orthopaedic Clinic scores of 86 to 95. The overall complication rate for augmented UCL repair was 8.7%; most commonly ulnar neuropraxia (6%).
Biomechanically, UCL repair with augmentation provided less gapping with equivalent torsional stiffness and failure compared with reconstruction. Clinically, augmented UCL repair demonstrated excellent return to previous level of play and Kerlan Jobe Orthopaedic Clinic scores with modest complications and time to return. Augmented UCL repair is biomechanically equivalent to reconstruction and may be a viable alternative to reconstruction in indicated athletes.
UCL repair with suture augmentation is biomechanically equivalent to reconstruction and clinically demonstrates excellent outcomes.
Putting a value on injuries to natural assets Bishop, Richard C.; Boyle, Kevin J.; Carson, Richard T. ...
Science (American Association for the Advancement of Science),
04/2017, Letnik:
356, Številka:
6335
Journal Article
Recenzirano
Odprti dostop
When large-scale accidents cause catastrophic damage to natural or cultural resources, government and industry are faced with the challenge of assessing the extent of damages and the magnitude of ...restoration that is warranted. Although market transactions for privately owned assets provide information about how valuable they are to the people involved, the public services of natural assets are not exchanged on markets; thus, efforts to learn about people's values involve either untestable assumptions about how other things people do relate to these services or empirical estimates based on responses to stated-preference surveys. Valuation based on such surveys has been criticized because the respondents are not engaged in real transactions. Our research in the aftermath of the 2010 BP Deepwater Horizon oil spill addresses these criticisms using the first, nationally representative, stated-preference survey that tests whether responses are consistent with rational economic choices that are expected with real transactions. Our results confirm that the survey findings are consistent with economic decisions and would support investing at least $17.2 billion to prevent such injuries in the future to the Gulf of Mexico's natural resources.
To identify deregulated and inhibitory miRNAs and generate novel mimics for replacement nanomedicine for head and neck squamous cell carcinomas (HNSCC).
We integrated miRNA and mRNA expression, copy ...number variation, and DNA methylation results from The Cancer Genome Atlas (TCGA), with a functional genome-wide screen.
We reveal that the miR-30 family is commonly repressed, and all 5 members sharing these seed sequence similarly inhibit HNSCC proliferation
. We uncover a previously unrecognized inverse relationship with overexpression of a network of important predicted target mRNAs deregulated in HNSCC, that includes key molecules involved in proliferation (EGFR, MET, IGF1R, IRS1, E2F7), differentiation (WNT7B, FZD2), adhesion, and invasion (ITGA6, SERPINE1). Reexpression of the most differentially repressed family member, miR-30a-5p, suppressed this mRNA program, selected signaling proteins and pathways, and inhibited cell proliferation, migration, and invasion
. Furthermore, a novel miR-30a-5p mimic formulated into a targeted nanomedicine significantly inhibited HNSCC xenograft tumor growth and target growth receptors EGFR and MET
. Significantly decreased miR-30a/e family expression was related to DNA promoter hypermethylation and/or copy loss in TCGA data, and clinically with decreased disease-specific survival in a validation dataset. Strikingly, decreased miR-30e-5p distinguished oropharyngeal HNSCC with poor prognosis in TCGA (
= 0.002) and validation (
= 0.007) datasets, identifying a novel candidate biomarker and target for this HNSCC subset.
We identify the miR-30 family as an important regulator of signal networks and tumor suppressor in a subset of HNSCC patients, which may benefit from miRNA replacement nanomedicine therapy.
The core feature of an economic exchange is a decision to trade one good for another, based on a comparison of relative value. Economists have long recognized, however, that the value an individual ...ascribes to a good during decision making (i.e., their relative willingness to trade for that good) does not always map onto the reward they actually experience. Here, we show that experienced value and decision value are represented in distinct regions of ventromedial prefrontal cortex (VMPFC) during the passive consumption of rewards. Participants viewed two categories of rewards-images of faces that varied in their attractiveness and monetary gains and losses-while being scanned using functional magnetic resonance imaging. An independent market task, in which participants exchanged some of the money that they had earned for brief views of attractive faces, determined the relative decision value associated with each category. We found that activation of anterior VMPFC increased with increasing experienced value, but not decision value, for both reward categories. In contrast, activation of posterior VMPFC predicted each individual's relative decision value for face and monetary stimuli. These results indicate not only that experienced value and decision value are represented in distinct regions of VMPFC, but also that decision value signals are evident even in the absence of an overt choice task. We conclude that decisions are made by comparing neural representations of the value of different goods encoded in posterior VMPFC in a common, relative currency.
While its prognostic significance remains unclear, p16INK4a protein expression is increasingly being used as a surrogate marker for oncogenic human papillomavirus (HPV) infection in head and neck ...squamous cell carcinomas (HNSCC). To evaluate the prognostic utility of p16 expression in HNSCC, we prospectively collected 163 primary tumor specimens from histologically confirmed HNSCC patients who were followed for up to 9.4 years. Formalin fixed tumor specimens were tested for p16 protein expression by immunohistochemistry (IHC). HPV type‐16 DNA and RNA was detected by MY09/11‐PCR and E6/E7 RT‐PCR on matched frozen tissue, respectively. P16 protein expression was detected more often in oropharyngeal tumors (53%) as compared with laryngeal (24%), hypopharyngeal (8%) or oral cavity tumors (4%; p < 0.0001). With respect to prognosis, p16‐positive oropharyngeal tumors exhibited significantly better overall survival than p16‐negative tumors (log‐rank test p = 0.04), whereas no survival benefit was observed for nonoropharyngeal tumors. However, when both p16 and HPV DNA test results were considered, concordantly positive nonoropharyngeal tumors had significantly better disease‐specific survival than concordantly negative nonoropharyngeal tumors after controlling for sex, nodal stage, tumor size, tumor subsite, primary tumor site number, smoking and drinking adjusted hazard ratio (HR) = 0.04, 0.01–0.54. Compared with concordantly negative nonoropharyngeal HNSCC, p16(+)/HPV16(−) nonoropharyngeal HNSCC (n = 13, 7%) demonstrated no significant improvement in disease‐specific survival when HPV16 was detected by RNA (adjusted HR = 0.83, 0.22–3.17). Our findings show that p16 IHC alone has potential as a prognostic test for oropharyngeal cancer survival, but combined p16/HPV testing is necessary to identify HPV‐associated nonoropharyngeal HNSCC with better prognosis.
What's new?
How useful is p16 detection in predicting the outcome of head and neck cancer? Cancers containing HPV have better outcomes than those without, and detecting expression of p16 sometimes stands in for HPV testing. These authors looked for p16 and HPV DNA in primary head and neck tumor specimens. They found that patients with oropharyngeal cancers did survive better when their tumors expressed p16. For non‐oropharyngeal cancers, however, survival improved only when both p16 and HPV turned up. Having p16 but not HPV didn't improve outcomes. Thus, p16 expression alone is not enough to make a prognosis in non‐oropharyngeal cancers.
Whether arthroscopic partial meniscectomy for symptomatic patients with a meniscal tear and knee osteoarthritis results in better functional outcomes than nonoperative therapy is uncertain.
We ...conducted a multicenter, randomized, controlled trial involving symptomatic patients 45 years of age or older with a meniscal tear and evidence of mild-to-moderate osteoarthritis on imaging. We randomly assigned 351 patients to surgery and postoperative physical therapy or to a standardized physical-therapy regimen (with the option to cross over to surgery at the discretion of the patient and surgeon). The patients were evaluated at 6 and 12 months. The primary outcome was the difference between the groups with respect to the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical-function score (ranging from 0 to 100, with higher scores indicating more severe symptoms) 6 months after randomization.
In the intention-to-treat analysis, the mean improvement in the WOMAC score after 6 months was 20.9 points (95% confidence interval CI, 17.9 to 23.9) in the surgical group and 18.5 (95% CI, 15.6 to 21.5) in the physical-therapy group (mean difference, 2.4 points; 95% CI, -1.8 to 6.5). At 6 months, 51 active participants in the study who were assigned to physical therapy alone (30%) had undergone surgery, and 9 patients assigned to surgery (6%) had not undergone surgery. The results at 12 months were similar to those at 6 months. The frequency of adverse events did not differ significantly between the groups.
In the intention-to-treat analysis, we did not find significant differences between the study groups in functional improvement 6 months after randomization; however, 30% of the patients who were assigned to physical therapy alone underwent surgery within 6 months. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; METEOR ClinicalTrials.gov number, NCT00597012.).
A New Strategy for Benefits Transfer Smith, V Kerry; Shaw, W. Douglass; Welsh, Michael P. ...
Environmental & resource economics,
2022/1, Letnik:
81, Številka:
1
Journal Article
Recenzirano
This paper calls for re-focusing the analysis of existing results to evaluate whether there are stable ratios of use value to total willingness to pay for improvements in different types of ...environmental resources. The objective is to develop a screening tool to determine if decisions about the assumed number of users versus nonusers of a resource are likely to be important to aggregate benefit measures for changes in the amount or quality of different environmental resources. Four sets of applications involving different aspects of water resources are considered: nutrients in the Neuse River affecting the Albemarle-Pamlico Estuary; nutrients in the Chesapeake Bay; whitewater rafting on the Colorado River; and the Deepwater Oil Spill in the Gulf of Mexico. The findings suggest a need to add the evaluation of these ratios to the research agenda in benefits transfer.
Detection of human papillomavirus (HPV) in head and neck cancer has therapeutic implications. In situ hybridization and immunohistochemistry for p16 are used by surgical pathologists. We compared the ...sensitivity and specificity of three popular commercial tests for HPV detection in head and neck squamous cell carcinomas with a 'gold standard' HPV PCR assay. A total of 110 prospectively collected, formalin-fixed tumor specimens were compiled onto tissue microarrays and tested for HPV DNA by in situ hybridization with two probe sets, a biotinylated probe for high-risk (HR) HPV types 16/18 (Dako, CA, USA) and a probe cocktail for 16/18, plus 10 additional HR types (Ventana, AZ, USA). The p16(INK4) expression was also assessed using a Pharmingen immunohistochemistry antibody (BD Biosciences, CA, USA). Tissue microarrays were stained and scored at expert laboratories. HPV DNA was detected by MY09/11-PCR, using Gold AmpliTaq and dot-blot hybridization on matched-fresh frozen specimens in a research laboratory. HPV 16 E6 and E7-RNA expression was also measured using RT-PCR. Test performance was assessed by a receiver operating characteristic analysis. HR-HPV DNA types 16, 18 and 35 were detected by MY-PCR in 28% of tumors, with the majority (97%) testing positive for type 16. Compared with MY-PCR, the sensitivity and specificity for HR-HPV DNA detection with Dako in situ hybridization was 21% (95% confidence interval (CI): 7-42) and 100% (95% CI: 93-100), respectively. Corresponding test results by Ventana in situ hybridization were 59% (95% CI: 39-78) and 58% (95% CI: 45-71), respectively. The p16 immunohistochemistry performed better overall than Dako (P=0.042) and Ventana (P=0.055), with a sensitivity of 52% (95% CI: 32-71) and specificity of 93% (95% CI: 84-98). Compared with a gold standard HPV-PCR assay, HPV detection by in situ hybridization was less accurate for head and neck squamous cell carcinoma on tissue microarrays than p16 immunohistochemistry. Further testing is warranted before these assays should be recommended for clinical HPV detection.
PDF
