Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality.
To systematically review benefits and harms of low-dose aspirin for preventing morbidity and mortality from ...preeclampsia.
MEDLINE, Database of Abstracts of Reviews of Effects, PubMed, and Cochrane Central Register of Controlled Trials (January 2006 to June 2013); previous systematic reviews, clinical trial registries, and surveillance searches for large studies (June 2013 to February 2014).
Randomized, controlled trials (RCTs) to assess benefits among women at high preeclampsia risk and RCTs or large cohort studies of harms among women at any risk level. English-language studies of fair or good quality were included.
Dual quality assessment and abstraction of studies.
Two large, multisite RCTs and 13 smaller RCTs of high-risk women (8 good-quality) were included, in addition to 6 RCTs and 2 observational studies of average-risk women to assess harms (7 good-quality). Depending on baseline risk, aspirin use was associated with absolute risk reductions of 2% to 5% for preeclampsia (relative risk RR, 0.76 95% CI, 0.62 to 0.95), 1% to 5% for intrauterine growth restriction (RR, 0.80 CI, 0.65 to 0.99), and 2% to 4% for preterm birth (RR, 0.86 CI, 0.76 to 0.98). No significant perinatal or maternal harms were identified, but rare harms could not be ruled out. Evidence on long-term outcomes was sparse, but 18-month follow-up from the largest trial found no developmental harms.
Benefits may have been overestimated due to small-study effects. Predictive intervals were not statistically significant. Future studies could shift findings toward the null.
Daily low-dose aspirin beginning as early as the second trimester prevented clinically important health outcomes. No harms were identified, but long-term evidence was limited.
Vitamin and mineral supplements are commonly used to prevent chronic diseases.
To systematically review evidence for the benefit and harms of vitamin and mineral supplements in community-dwelling, ...nutrient-sufficient adults for the primary prevention of cardiovascular disease (CVD) and cancer.
MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects were searched from January 2005 to 29 January 2013, with manual searches of reference lists and gray literature.
Two investigators independently selected and reviewed fair- and good-quality trials for benefit and fair- and good-quality trials and observational studies for harms.
Dual quality assessments and data abstraction.
Two large trials (n = 27 658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.93 95% CI, 0.87 to 0.99). The study that included women showed no effect in that group. High-quality studies (k = 24; n = 324 653) of single and paired nutrients (such as vitamins A, C, or D; folic acid; selenium; or calcium) were scant and heterogeneous and showed no clear evidence of benefit or harm. Neither vitamin E nor β-carotene prevented CVD or cancer, and β-carotene increased lung cancer risk in smokers.
The analysis included only primary prevention studies in adults without known nutritional deficiencies. Studies were conducted in older individuals and included various supplements and doses under the set upper tolerable limits. Duration of most studies was less than 10 years.
Limited evidence supports any benefit from vitamin and mineral supplementation for the prevention of cancer or CVD. Two trials found a small, borderline-significant benefit from multivitamin supplements on cancer in men only and no effect on CVD.
Agency for Healthcare Research and Quality.
Long-term follow-up of population-based randomized, controlled trials (RCTs) has demonstrated that screening for abdominal aortic aneurysms (AAAs) measuring 3 cm or greater decreases AAA-related ...mortality rates in men aged 65 years or older.
To systematically review evidence about the benefits and harms of ultrasonography screening for AAAs in asymptomatic primary care patients.
MEDLINE, the Database of Abstracts of Reviews of Effects, the Cochrane Central Register of Controlled Trials (January 2004 through January 2013), clinical trial registries, reference lists, experts, and a targeted bridge search for population-based screening RCTs through September 2013.
English-language, population-based, fair- to good-quality RCTs and large cohort studies for AAA screening benefits as well as RCTs and cohort and registry studies for harms in adults with AAA.
Dual quality assessment and abstraction of study details and results.
Reviews of 4 RCTs involving 137,214 participants demonstrated that 1-time invitation for AAA screening in men aged 65 years or older reduced AAA rupture and AAA-related mortality rates for up to 10 and 15 years, respectively, but had no statistically significant effect on all-cause mortality rates up to 15 years. Screening was associated with more overall and elective surgeries but fewer emergency operations and lower 30-day operative mortality rates at up to 10- to 15-year follow-up. One RCT involving 9342 women showed that screening had no benefit on AAA-related or all-cause mortality rates.
Trials included mostly white men outside of the United States. Information for subgroups and about rescreening was limited.
One-time invitation for AAA screening in men aged 65 years or older was associated with decreased AAA rupture and AAA-related mortality rates but had little or no effect on all-cause mortality rates.
Agency for Healthcare Research and Quality.
We present the compact Gravimetric Atom Interferometer (GAIN), based on laser-cooled
87
Rb atoms, and discuss its first measurements of the local gravitational acceleration. In this context, we also ...describe an active vibration isolation system and a tip-tilt stage, which allow for a suppression of vibrational noise and systematic effects like the Coriolis force due to Earth’s rotation.
IMPORTANCE: Skin cancer is the most common cancer type and is a major cause of morbidity. OBJECTIVE: To systematically review the benefits and harms of screening for skin cancer to inform the US ...Preventive Services Task Force. DATA SOURCES: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from June 1, 2015, through January 7, 2022; surveillance through December 16, 2022. STUDY SELECTION: English-language studies conducted in asymptomatic populations 15 years or older. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently appraised the articles and extracted relevant data from fair- or good-quality studies; results were narratively summarized. MAIN OUTCOMES AND MEASURES: Morbidity; mortality; skin cancer stage, precursor lesions, or lesion thickness at detection; harms of screening. RESULTS: Twenty studies in 29 articles were included (N = 6 053 411). Direct evidence on screening effectiveness was from 3 nonrandomized analyses of 2 population-based skin cancer screening programs in Germany (n = 1 791 615) and suggested no melanoma mortality benefit at the population level over 4 to 10 years’ follow-up. Six studies (n = 2 935 513) provided inconsistent evidence on the association between clinician skin examination and lesion thickness or stage at diagnosis. Compared with usual care, routine clinician skin examination was not associated with increased detection of skin cancer or precursor lesions (5 studies) or stage at melanoma detection (3 studies). Evidence on the association between clinician skin examination and lesion thickness at detection was inconsistent (3 studies). Nine studies (n = 1 326 051) found a consistent positive association between more advanced stage at melanoma detection and increasing risk of melanoma-associated and all-cause mortality. Two studies (n = 232) found little to no persistent cosmetic or psychosocial harms associated with screening. CONCLUSIONS AND RELEVANCE: A substantial nonrandomized evidence base suggests a clear association between earlier stage at skin cancer detection and decreased mortality risk. However, nonrandomized studies suggest little to no melanoma mortality benefit associated with skin cancer screening with visual skin examination in adolescents or adults and no association between routine clinician skin examination and earlier stage at melanoma detection. Evidence is inconsistent regarding whether clinician skin examination is associated with thinner melanoma lesions at detection.
Access to protein substrates homogenously modified by ubiquitin (Ub) is critical for biophysical and biochemical investigations aimed at deconvoluting the myriad biological roles for Ub. Current ...chemical strategies for protein ubiquitylation, however, employ temporary ligation auxiliaries that are removed under harsh denaturing conditions and have limited applicability. We report an unprecedented aromatic thiol-mediated N-O bond cleavage and its application towards native chemical ubiquitylation with the ligation auxiliary 2-aminooxyethanethiol. Our interrogation of the reaction mechanism suggests a disulfide radical anion as the active species capable of cleaving the N-O bond. The successful semisynthesis of full-length histone H2B modified by the small ubiquitin-like modifier-3 (SUMO-3) protein further demonstrates the generalizability and compatibility of our strategy with folded proteins.
Despite the success of cervical cancer screening programs, questions remain about the appropriate time to begin and end screening. This review explores epidemiologic and contextual data on cervical ...cancer screening to inform decisions about when screening should begin and end. Cervical cancer is rare among women younger than 20 years. Screening for cervical cancer in this age group is complicated by lower rates of detection and higher rates of false-positive results than in older women. Methods used to diagnose and treat cervical intraepithelial neoplasia have important potential adverse effects. High-risk human papillomavirus infections and abnormalities on cytologic and histologic examination have relatively high rates of regression. Accordingly, cervical cancer screening in women younger than 20 years may be harmful. The incidence of, and mortality rates from, cervical cancer and the proportion of U.S. women aged 65 years or older who have had a Papanicolaou smear within 3 years have decreased since 2000. Available evidence supports discontinuation of cervical cancer screening among women aged 65 years or older who have had adequate screening and are not otherwise at high risk. Further reductions in the burden of cervical cancer in older women are probably best achieved by focusing on screening those who have not been adequately screened.
Deubiquitylating enzymes (DUBs) remove ubiquitin (Ub) from various cellular proteins and render eukaryotic ubiquitylation a dynamic process. The misregulation of protein ubiquitylation is associated ...with many human diseases, and there is an urgent need to identify specific DUBs associated with therapeutically relevant targets of Ub. We report the development of two facile selenocysteine-based strategies to generate the DUB probe dehydroalanine (Dha). Optimized oxidative or alkylative elimination of Se yielded Dha at the C-terminus of Ub. The high utility of alkylative elimination, which is compatible with multiple thiols in Ub targets, was demonstrated by generating a probe derived from the Ub ligase tripartite motif protein 25 (TRIM-25). Successful capture of the TRIM-25-associated DUB, ubiquitin-specific protease 15, demonstrated the versatility of our chemical strategy for identifying target-specific DUBs.
Background: We aimed to evaluate a comparative analysis of the prognostic value of the metastatic lymph node ratio (LNR) and pN (TNM) in stage III gastric cancer. Patients and Methods: A total of 159 ...stage III gastric cancer patients with curative gastrectomy were retrospectively analyzed. Cutoff values for LNR were designated according to 25%, 50% and 75% percentiles, 0.07, 0.20 and 0.44 respectively. The LNR was divided into four groups as 0 > LNR1 ≤ 0.07; 0.07 > LNR2 ≤0.20; 0.20 > LNR3 ≤0.44; 0.44 > LNR4 ≤1. Results: The mean age of the patients was 61.1 ± 11.3 years. Male predominance was apparent (73.6%). The 1-year overall survival and recurrence rates were 73.6% and 33.6%, respectively. The univariate cox regression analysis demonstrated age and LNR were the main variables that affected overall survival (OS) (p < 0.05). Harvested lymph nodes less than 16 did not affect OS (p = 0.255). The results of the multivariate cox regression analysis revealed that only LNR was an independent prognostic factor (P < 0.001), while pN was not (p > 0.05). Similar results, as with overall survival, could not be revealed clearly for disease free survival (DFS). Conclusions: LNR was an independent significant prognostic factor and superior to pN staging in predicting OS but not for DFS in stage III gastric cancer patients. The high LNR levels in our research were found to be associated with poor survival rates. The percentile system we used to determine cutoff values may be considered as a reliable method. Similarly, LNR also provides a reliable prognostic parameter in future staging systems to help guide treatment algorithm plans.
The “element effect” in nucleophilic aromatic substitution reactions (SNAr) is characterized by the leaving group order, F > NO2 > Cl ≈ Br > I, in activated aryl halides. Multiple causes for this ...result have been proposed. Experimental evidence shows that the element effect order in the reaction of piperidine with 2,4-dinitrophenyl halides in methanol is governed by the differences in enthalpies of activation. Computational studies of the reaction of piperidine and dimethylamine with the same aryl halides using the polarizable continuum model (PCM) for solvation indicate that polar, polarizability, solvation, and negative hyperconjugative effects are all of some importance in producing the element effect in methanol. In addition, a reversal of polarity of the C–X bond from reactant to transition state in the case of ArCl and ArBr compared to ArF also contributes to their differences in reactivity. The polarity reversal and hyperconjugative influences have received little or no attention in the past. Nor has differential solvation of the different transition states been strongly emphasized. An anionic nucleophile, thiolate, gives very early transition states and negative activation enthalpies with activated aryl halides. The element effect is not established for these reactions. We suggest that the leaving group order in the gas phase will be dependent on the exact combination of nucleophile, leaving group, and substrate framework. The geometry of the SNAr transition state permits useful, qualitative conceptual distinctions to be made between this reaction and other modes of nucleophilic attack.
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