Boston biorepository, recruitment and integrative network (BBRAIN): A resource for the Gulf War Illness scientific community.

AIMS: Gulf War Illness (GWI), a chronic debilitating disorder characterized by fatigue, joint pain, cognitive, gastrointestinal, respiratory, and skin problems, is currently diagnosed by self-reported symptoms. The Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) is the collaborative effort of expert Gulf War Illness (GWI) researchers who are creating objective diagnostic and pathobiological markers and recommend common data elements for GWI research. MAIN METHODS: BBRAIN is recruiting 300 GWI cases and 200 GW veteran controls for the prospective study. Key data and biological samples from prior GWI studies are being merged and combined into retrospective datasets. They will be made available for data mining by the BBRAIN network and the GWI research community. Prospective questionnaire data include general health and chronic symptoms, demographics, measures of pain, fatigue, medical conditions, deployment and exposure histories. Available repository biospecimens include blood, plasma, serum, saliva, stool, urine, human induced pluripotent stem cells and cerebrospinal fluid. KEY FINDINGS: To date, multiple datasets have been merged and combined from 15 participating study sites. These data and samples have been collated and an online request form for repository requests as well as recommended common data elements have been created. Data and biospecimen sample requests are reviewed by the BBRAIN steering committee members for approval as they are received. SIGNIFICANCE: The BBRAIN repository network serves as a much needed resource for GWI researchers to utilize for identification and validation of objective diagnostic and pathobiological markers of the illness.

WITHDRAWN: Fighting for access: Research at the National Abortion Federation's 43rd Annual Meeting.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Continuous versus cyclic use of combined oral contraceptives for contraception: systematic Cochrane review of randomized controlled trials.

BACKGROUND: With the recent US Food and Drug Administration approval of a combination oral contraceptive that causes a withdrawal bleed every 3 months instead of monthly, avoidance of menstruation through extended or continuous administration (>28 days of active pills) of combined oral contraceptives may become more commonplace for reasons of personal preference rather than limited to treatment of menstrual-associated medical disorders. METHODS: The review aimed to compare contraceptive efficacy, compliance, continuation, satisfaction, bleeding profiles, and menstrual symptoms of combined oral contraceptives with continuous dosing (>28 days of active pills) versus traditional cyclic dosing (21 days of active pills and 7 days of placebo). We searched five computerized databases as well as reference lists of relevant articles for randomized controlled trials (RCT) using continuous or extended combined oral contraceptives for contraception. Two reviewers independently extracted data from eligible articles. RESULTS: Six RCT met inclusion criteria and were of good quality. Contraceptive efficacy and compliance were similar between groups. Discontinuation overall, and for bleeding problems, was not uniformly higher in either group. When studied, participants reported high satisfaction with both dosing regimens. Five out of the six studies found that bleeding patterns were either equivalent or improved with continuous-dosing regimens. The continuous-dosing group had greater improvement of menstrual-associated symptoms (headaches, genital irritation, tiredness, bloating, and menstrual pain). CONCLUSIONS: The variations in pill type and time-interval for continuous dosing make direct comparisons between regimens unfeasible. To allow for comparisons, future studies should choose a previously researched pill and dosing regimen. More attention needs to be directed towards participant satisfaction and menstruation-associated symptoms.

Continuous or extended cycle vs. cyclic use of combined oral contraceptives for contraception.

BACKGROUND: The avoidance of menstruation through extended or continuous administration (greater than 28 days of active pills) of combination oral contraceptives (COCs) has gained legitimacy through its use in treating endometriosis, dysmenorrhea, and menstruation-associated symptoms. Avoidance of menstruation through continuous use of COCs for reasons of personal preference may have additional advantages to women, including improved compliance, greater satisfaction, fewer menstrual symptoms, and less menstruation-related absenteeism from work or school. OBJECTIVES: To determine the differences between COCs dosed continuously (greater than 28 days of active pills) compared with traditional cyclic dosing (21 days of active pills and 7 days of placebo). Our hypothesis was that continuously administered COCs have equivalent efficacy and safety but improved bleeding profiles, amenorrhea rates, adherence, continuation, participant satisfaction, and menstrual symptoms compared with cyclic COCs. SEARCH STRATEGY: We searched computerized databases (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, POPLINE, LILACS) for trials using continuous or extended COCs during the years 1966 to 2005. We also searched the references in review articles and publications identified for inclusion in the protocol. Investigators were contacted regarding additional references. SELECTION CRITERIA: All randomized controlled trials in any language comparing continuous (greater than 28 days of active pills) versus traditional cyclic administration (21 days of active pills and 7 days of placebo) of COCs for contraception. DATA COLLECTION AND ANALYSIS: Titles and abstracts identified from the literature searches were assessed for potential inclusion. Data were extracted onto data collection forms and then entered into RevMan 4.2. Peto odds ratios with 95% confidence intervals were calculated for all outcomes for dichotomous outcomes. Weighted mean difference was calculated for continuous outcomes. The trials were critically appraised by examining the following factors: study design, blinding, randomization method, group allocation concealment, exclusions after randomization, loss to follow-up, and early discontinuation. Because the included trials did not have a standard treatment (type of pill and time length for continuous dosing), we could not aggregate data into meta-analysis. MAIN RESULTS: Six randomized controlled trials met our inclusion criteria. Study findings were similar between 28-day and extended cycles in regard to contraceptive efficacy (i.e., pregnancy rates) and safety profiles. When compliance was reported, no difference between 28-day and extended cycles was found. Participants reported high satisfaction with both dosing regimens, but this was not an outcome universally studied. Overall discontinuation and discontinuation for bleeding problems were not uniformly higher in either group in most studies. The few studies that reported menstrual symptoms found that the extended cycle group fared better in terms of headaches, genital irritation, tiredness, bloating, and menstrual pain. Five out of the six studies found that bleeding patterns were either equivalent between groups or improved with continuous-dosing regimens. Endometrial lining assessments by ultrasound were done in a small number of participants but all endometrial stripe measurements were less than 5 mm. AUTHORS' CONCLUSIONS: Evidence from existing randomized control trials comparing COCs given continuously (greater than 28 days of active pills) to traditional monthly cyclic dosing (21 days of active pills and 7 days of placebo) is of good quality. However, the variations in type of pill and time length for continuous dosing make direct comparisons between regimens impossible. Future studies should choose a previously described type of pill and dosing regimen. More attention needs to be directed towards participant satisfaction and menstruation-associated symptoms.

Comparing the acceptability of manual vacuum aspiration and electric vacuum aspiration as methods of early abortion.

OBJECTIVE: to compare the acceptability of manual vacuum aspiration (MVA) and electric vacuum aspiration (EVA) as methods of early (< or = 77 days' gestation) abortion. METHODS: We interviewed 42 women who had been randomly assigned to either MVA or EVA and compared their perceptions of the two procedures. RESULTS: The experiences and perceptions of women in the two groups were similar in many ways. The majority of women in both procedure groups were very satisfied with the method used, and most indicated that they would prefer the same method if they were to have another abortion. CONCLUSION: This study found no major differences in the acceptability of MVA and EVA among women undergoing early abortions.

Comparison of pain and time of procedures with two first-trimester abortion techniques performed by residents and faculty.

OBJECTIVES: We compared pain perception and procedure time in abortions performed by residents and faculty using a manual vacuum aspirator and electric vacuum curettage devices. STUDY DESIGN: We conducted a randomized trial of 114 women undergoing first-trimester abortions. Patients assessed the level of pain with visual analog scales. RESULTS: The mean procedure times were 5.7 and 6.9 minutes, respectively, with electric vacuum curettage and manual vacuum aspirator. Faculty took less time than residents to perform both procedures. Patients reported a higher pain level with cervical dilatation before resident electric vacuum curettage procedures. Patients undergoing electric vacuum curettage thought that the procedure noise increased their pain. CONCLUSIONS: First-trimester abortion procedures can be performed more quickly by experienced surgeons. The procedure time for the manual vacuum aspirator is greater than that for the electric vacuum curettage. Patient pain perception with aspiration by these two techniques is not different. The level of pain after aspiration did not vary significantly in patients who had abortions performed by residents or faculty.

Structure and function of an archaeal topoisomerase VI subunit with homology to the meiotic recombination factor Spo11.

In all organisms, type II DNA topoisomerases are essential for untangling chromosomal DNA. We have determined the structure of the DNA-binding core of the Methanococcus jannaschii DNA topoisomerase VI A subunit at 2.0 A resolution. The overall structure of this subunit is unique, demonstrating that archaeal type II enzymes are distinct from other type II topoisomerases. However, the core structure contains a pair of domains that are also found in type IA and classic type II topoisomerases. Together, these regions may form the basis of a DNA cleavage mechanism shared among these enzymes. The core A subunit is a dimer that contains a deep groove that spans both protomers. The dimer architecture suggests that DNA is bound in the groove, across the A subunit interface, and that the two monomers separate during DNA transport. The A subunit of topoisomerase VI is homologous to the meiotic recombination factor, Spo11, and this structure can serve as a template for probing Spo11 function in eukaryotes.

Outcomes of suction curettage and mifepristone abortion in the United States. A prospective comparison study.

A prospective, nonconcurrent cohort analysis of 178 mifepristone/misoprostol and 199 suction curettage abortion subjects, ages > or = 18 years, with intrauterine pregnancies < or = 63 days estimated gestational age, was conducted to compare the outcomes of suction curettage abortion to those of medical abortion. The medical abortion subjects received 600 mg of mifeprisone orally, followed by 400 micrograms of oral misoprostol 2 days later. Surgical abortion subjects underwent electronic vacuum aspiration. All subjects were followed for 2 weeks or until the absence of clinical bleeding. Outcome measures included a successful abortion (complete abortion without a surgical intervention), duration of bleeding, and morbidity. Overall, 18.3% medical and 4.7% surgical patients failed their primary procedure and received an unanticipated suction curettage (RR 3.93, 95% CI 1.87, 8.29). Four mifepristone subjects required curettage for acute bleeding, nine to manage ongoing pregnancy, and five for incomplete abortion. Fourteen mifepristone and eight surgical subjects required curettage for persistent bleeding. The median time delay for therapeutic curettage was significantly longer in the medical abortion group (35 versus 8 days; Mann-Whitney U = 17.0, p = 0.008). Medical subjects experienced significantly longer bleeding (mean difference = 9.6 days, 95% CI 6.8, 12.4). No significant change in hemoglobin occurred in either group. Mifepristone patients reported significantly greater pain (77.1% vs 10.5%; RR 7.4, 95% CI 4.7, 11.5), and nausea or vomiting (68.6% vs 0.6%; RR 117.9, 95% CI 16.7, 834.7). Women receiving mifepristone/misoprostol are more likely to require an unplanned surgical intervention than women who undergo suction curettage. They experience more discomfort with their procedure and in the follow-up interval, bleed for a longer period, and remain at risk for surgical completion curettage for several weeks.

PIP: A prospective, nonconcurrent cohort analysis was conducted to compare the outcomes of suction curettage abortion to those of medical abortion in the US. The study included 178 mifepristone/misoprostol and 199 curettage abortion subjects, ages 18 years or older, with intrauterine pregnancies of 63 or fewer days. Medical abortion subjects received 600 mg of mifepristone orally, followed by 400 mcg of oral misoprostol 2 days later. Surgical abortion subjects underwent electronic vacuum aspiration. Results showed that 18.3% of medical and 4.7% of surgical patients failed their primary procedure and received an unanticipated suction curettage. Medical subjects experienced significantly longer bleeding; however, no significant change in hemoglobin occurred in either group. While, mifepristone patients reported significantly greater pain, nausea or vomiting. Thus, women receiving mifepristone/misoprostol are more likely to require an unplanned surgical intervention than women who undergo curretage. Medical abortion patients have more discomfort, they bleed longer, and remain at risk for surgical completion curettage for several weeks.

The structural basis for terminator recognition by the Rho transcription termination factor.

The E. coli Rho protein disengages newly transcribed RNA from its DNA template, helping terminate certain transcripts. We have determined the X-ray crystal structure of the RNA-binding domain of Rho complexed to an RNA ligand. Filters that screen both ligand size and chemical functionality line the primary nucleic acid-binding site, imparting sequence specificity to a generic single-stranded nucleic acid-binding fold and explaining the preference of Rho for cytosine-rich RNA. The crystal packing reveals two Rho domain protomers bound to a single RNA with a single base spacer, suggesting that the strong RNA-binding sites of Rho may arise from pairing of RNA-binding modules. Dimerization of symmetric subunits on an asymmetric ligand is developed as a model for allosteric control in the action of the intact Rho hexamer.

Localization of contraceptive implant capsules for removal.

Implanted contraceptive capsules occasionally cannot be removed by means of palpation with local dissection, and imaging guidance is necessary. The authors report obtaining a single antero-posterior radiograph of the upper arm followed by sonography to localize the capsule and to allow precise marking of the skin over the capsules. The method can be performed quickly and is inexpensive and effective, allowing the localization and removal procedures to be scheduled independently.

PIP: In Oregon, since some physicians could not remove contraceptive implant (Norplant) capsules, they referred three patients to Oregon Health Sciences University or the Kaiser Sunnyside Medical Center in Clackamas for implant removal. The physician was able to initially remove five of the six capsules in a 21-year-old mother of three. One month later, the physician tried again to remove the remaining capsule and did not succeed. Anteroposterior and lateral radiographs of the upper left arm could not detect the 6th capsule. The referral institution obtained a single anteroposterior radiograph (about 55 kVp and 10 mAs) that revealed the capsule in the subcutaneous tissue. Using landmarks on the radiograph, the capsule's location was estimated and scanned with a high frequency linear ultrasound probe that found the exact location of the capsule. The physicians marked the patient's skin along the length of the capsule and asked her to renew the mark every day until her own physician could remove it two days later. The complete imaging procedure lasted only 12 minutes. Two different surgeons attempted removal of three capsules in one woman. The second surgeon even used 15 minutes of intraoperative fluoroscopy. Another case was referred for imaging because her physician could not palpate one capsule. The referral institution used the same localization method (radiograph and ultrasound) to locate the capsule and mark its location. These cases show that clinicians can perform this inexpensive and effective localization method for undetectable implant capsules quickly. Localization of capsules and removal procedures can be scheduled at different times.

Assay of retinoids in biological samples by reverse-phase high-pressure liquid chromatography.

A separation procedure for retinoids based on reversephase high-pressure liquid chromatography with solvent mixtures of acetonitrile and water is described. The method may be applied to the screening of synthetic retinoids, which have potential for use in the prevention of cancer. It is easily adapted to a variety of biological samples and can be applied to other conventional retinoid assays in liver and plasma, detecting as little as 1 nmol retinyl esters and less than 0.3 nmol retinol per g tissue. The one-step chromatography results in separation and simultaneous determination of many of the synthetic retinoids and all of the natural retinoids, including the retinyl esters that are separated into their major fatty acid components. The method has been applied to the analysis of retinoid levels in the liver and intestine of vitamin A-deficient hamsters following a p.o. dose (0.5 mg/day for 2 days) of retinyl acetate or of a synthetic vitamin A analog and is predictive of the degree to which various synthetic retinoids can be converted to retinol and stored in the liver as retinyl esters. Because of its speed, excellent recoveries, and high resolution, the method offers significant advantages over previous, more lengthy procedures.