bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous identification of specifically interacting paralogs and interprotein contacts by direct coupling analysis
Authors: Gueudré Thomas , Baldassi Carlo , Zamparo Marco , Weigt Martin , Pagnani Andrea
Published: October 2016

Significance

Most biological processes rely on specific interactions between proteins, but the experimental characterization of protein−protein interactions is a labor-intensive task of frequently uncertain outcome. Computational methods based on exponentially growing genomic databases are urgently needed. It has recently been shown that coevolutionary methods are able to detect correlated mutations between residues in different proteins, which are in contact across the interaction interface, thus enabling the structure prediction of protein complexes. Here we show that the applicability of coevolutionary methods is much broader, connecting multiple scales relevant in protein−protein interaction: the residue scale of interprotein contacts, the protein scale of specific interactions between paralogous proteins, and the evolutionary scale of conserved interactions between homologous protein families.
Quantum mechanics/molecular mechanics simulation of the ligand vibrations of the water-oxidizing Mn
4
CaO
5
cluster in photosystem II
Authors: Nakamura Shin , Noguchi Takumi
Published: October 2016

Significance

Photosystem II plays an important role in photosynthesis by oxidizing water; this process provides as an electron source to fix CO
2
during photosynthesis, which sustains life on Earth by liberating molecular oxygen. Although the catalytic site, the water-oxidizing center (WOC), is known to consist of an Mn
4
CaO
5
cluster, six carboxylate ligands, and one imidazole ligand, its detailed structure and reaction mechanism have not yet been resolved. In this study, we successfully simulated the carboxylate stretching region of the experimental IR spectra of WOC by calculating WOC vibrations using the quantum mechanics/molecular mechanics method. Our simulations show the significant role that carboxylate groups bridging Mn and Ca play in tuning the water oxidation reaction.
Reading intervention with a growth mindset approach improves children’s skills
Authors: Andersen Simon Calmar , Nielsen Helena Skyt
Published: October 2016

Significance

Many large-scale parent interventions turn out to be ineffective, particularly for socioeconomically disadvantaged families—possibly because some parents believe that their children’s reading skills are relatively fixed and unresponsive to practicing. This study shows large and consistent effects on both reading and writing skills of second-grade children whose parents received a few children’s books and information about the value of supporting children when learning to read. Effects are at least as large for children with immigrant background or low-educated mothers as for other children—and biggest for those children whose parents before the intervention believed reading abilities to be relatively fixed. The study thereby shows a direction for effective parent interventions.
Fast fMRI can detect oscillatory neural activity in humans
Authors: Lewis Laura D. , Setsompop Kawin , Rosen Bruce R. , Polimeni Jonathan R.
Published: October 2016

Significance

A major challenge in neuroscience is our limited ability to image neural signals noninvasively in humans. Oscillations in brain activity are important for perception, attention, and awareness, and progress in cognitive neuroscience depends on localizing these patterns. fMRI is thought to be too slow to measure brain oscillations because it depends on slow changes in blood flow. Here, we use recently developed imaging techniques to show that fMRI can measure faster neural oscillations than previously thought, and responses are 10 times larger than expected. With computational modeling and simultaneous electroencephalography we show that vascular responses are surprisingly fast when brain activity fluctuates rapidly. These results suggest that fMRI can be used to track oscillating brain activity directly during human cognition.
Efficient CRISPR-mediated mutagenesis in primary immune cells using CrispRGold and a C57BL/6 Cas9 transgenic mouse line
Authors: Chu Van Trung , Graf Robin , Wirtz Tristan , Weber Timm , Favret Jeremy , Li Xun , Petsch Kerstin , Tran Ngoc Tung , Sieweke Michael H. , Berek Claudia , Kühn Ralf , Rajewsky Klaus
Published: October 2016

Significance

Efficient clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9)-mediated mutagenesis is necessary for robust genetic screening in primary cells and requires sufficiently high levels of Cas9 and reliable single guide RNAs (sgRNAs). We provide a sgRNA design tool that selects high-fidelity sgRNAs and a Cas9 transgenic mouse line that expresses Cas9 at high levels in all cells analyzed. Using this system, we achieved an average knockout efficiency of 80% in primary B cells and established a robust CRISPR/Cas9-mediated genetic screening system that can be adapted to other primary cell types.
Anti-allergic effects of His-Ala-Gln tripeptide in vitro and in vivo
Authors: Tanaka Mamoru , Watanabe Hiroyuki , Yoshimoto Yoshinobu , Kozai Hana , Okamoto Takeaki
Published: October 2016

We examined the inhibitory effects of HAQ (His-Ala-Gln) peptide on type-1 allergy in vitro and in vivo. HAQ peptide inhibited β-hexosaminidase release and intracellular Ca2+ levels of rat basophilic leukemia RBL-2H3 cells. Oral administration of a HAQ peptide-added diet (1 mg/mouse/administration) to C3H/HeJ mice for 14 days led to significant suppression of allergic symptoms, but did not reduce allergen-specific IgE or IgG1.
Do constitutions guarantee equal rights across socioeconomic status? A half century of change in the world's constitutions
Authors: Cassola Adèle , Raub Amy , Heymann Jody
Published: October 2016

For those disadvantaged by bias and barriers based on socioeconomic status (SES), constitutions can provide a defense against discrimination and a foundation for greater equality in social, economic, and political life. In light of the near-global commitment to a multi-dimensional poverty reduction agenda and the increased inclusion of marginalized groups in constitution-drafting processes, this article examines how 193 constitutions address SES and how this has changed over time. The majority of constitutions guarantee equal access to primary education across SES (59%) and prohibit discrimination on this basis (58%). Fewer guarantee access to healthcare (20%), equal rights in employment (15%), eligibility for legislative office (4%), and voting rights (4%) across SES. Constitutions adopted after 1990 are considerably more likely to protect equal rights across SES than older ones. However, 25% of constitutions – including 17% of those adopted since 1990 – restrict political participation based on socioeconomic characteristics.
SChloro: directing Viridiplantae proteins to six chloroplastic sub-compartments
Authors: Savojardo Castrense , Martelli Pier Luigi , Fariselli Piero , Casadio Rita
Published: October 2016

Motivation

Chloroplasts are organelles found in plants and involved in several important cell processes. Similarly to other compartments in the cell, chloroplasts have an internal structure comprising several sub-compartments, where different proteins are targeted to perform their functions. Given the relation between protein function and localization, the availability of effective computational tools to predict protein sub-organelle localizations is crucial for large-scale functional studies.

Results

In this paper we present SChloro, a novel machine-learning approach to predict protein sub-chloroplastic localization, based on targeting signal detection and membrane protein information. The proposed approach performs multi-label predictions discriminating six chloroplastic sub-compartments that include inner membrane, outer membrane, stroma, thylakoid lumen, plastoglobule and thylakoid membrane. In comparative benchmarks, the proposed method outperforms current state-of-the-art methods in both single- and multi-compartment predictions, with an overall multi-label accuracy of 74%. The results demonstrate the relevance of the approach that is eligible as a good candidate for integration into more general large-scale annotation pipelines of protein subcellular localization.

Availability and Implementation

The method is available as web server at http://schloro.biocomp.unibo.it
Lessons learned from practical approaches to reconcile mismatches between biological population structure and stock units of marine fish
Authors: Kerr Lisa A. , Hintzen Niels T. , Cadrin Steven X. , Clausen Lotte Worsøe , Dickey-Collas Mark , Goethel Daniel R. , Hatfield Emma M.C. , Kritzer Jacob P. , Nash Richard D.M.
Published: October 2016

Recent advances in the application of stock identification methods have revealed inconsistencies between the spatial structure of biological populations and the definition of stock units used in assessment and management. From a fisheries management perspective, stocks are typically assumed to be discrete units with homogeneous vital rates that can be exploited independently of each other. However, the unit stock assumption is often violated leading to spatial mismatches that can bias stock assessment and impede sustainable fisheries management. The primary ecological concern is the potential for overexploitation of unique spawning components, which can lead to loss of productivity and reduced biodiversity along with destabilization of local and regional stock dynamics. Furthermore, ignoring complex population structure and stock connectivity can lead to misperception of the magnitude of fish productivity, which can translate to suboptimal utilization of the resource. We describe approaches that are currently being applied to improve the assessment and management process for marine fish in situations where complex spatial structure has led to an observed mismatch between the scale of biological populations and spatially-defined stock units. The approaches include: (i) status quo management, (ii) “weakest link” management, (iii) spatial and temporal closures, (iv) stock composition analysis, and (v) alteration of stock boundaries. We highlight case studies in the North Atlantic that illustrate each approach and synthesize the lessons learned from these real-world applications. Alignment of biological and management units requires continual monitoring through the application of stock identification methods in conjunction with responsive management to preserve biocomplexity and the natural stability and resilience of fish species.
Comparing estimates of abundance trends and distribution shifts using single- and multispecies models of fishes and biogenic habitat
Authors: Thorson James T. , Barnett Lewis A. K.
Published: October 2016

Several approaches have been developed over the last decade to simultaneously estimate distribution or density for multiple species (e.g. “joint species distribution” or “multispecies occupancy” models). However, there has been little research comparing estimates of abundance trends or distribution shifts from these multispecies models with similar single-species estimates. We seek to determine whether a model including correlations among species (and particularly species that may affect habitat quality, termed “biogenic habitat”) improves predictive performance or decreases standard errors for estimates of total biomass and distribution shift relative to similar single-species models. To accomplish this objective, we apply a vector-autoregressive spatio-temporal (VAST) model that simultaneously estimates spatio-temporal variation in density for multiple species, and present an application of this model using data for eight US Pacific Coast rockfishes (Sebastes spp.), thornyheads (Sebastolobus spp.), and structure-forming invertebrates (SFIs). We identified three fish groups having similar spatial distribution (northern Sebastes, coastwide Sebastes, and Sebastolobus species), and estimated differences among groups in their association with SFI. The multispecies model was more parsimonious and had better predictive performance than fitting a single-species model to each taxon individually, and estimated fine-scale variation in density even for species with relatively few encounters (which the single-species model was unable to do). However, the single-species models showed similar abundance trends and distribution shifts to those of the multispecies model, with slightly smaller standard errors. Therefore, we conclude that spatial variation in density (and annual variation in these patterns) is correlated among fishes and SFI, with congeneric fishes more correlated than species from different genera. However, explicitly modelling correlations among fishes and biogenic habitat does not seem to improve precision for estimates of abundance trends or distribution shifts for these fishes.
Thermodynamics of Giant Planet Formation: Shocking Hot Surfaces on Circumplanetary Disks
Authors: Szulágyi J. , Mordasini C.
Published: October 2016

The luminosity of young giant planets can inform about their formation and accretion history. The directly imaged planets detected so far are consistent with the “hot-start” scenario of high entropy and luminosity. If nebular gas passes through a shock front before being accreted into a protoplanet, the entropy can be substantially altered. To investigate this, we present high resolution, 3D radiative hydrodynamic simulations of accreting giant planets. The accreted gas is found to fall with supersonic speed in the gap from the circumstellar disk's upper layers onto the surface of the circumplanetary disk and polar region of the protoplanet. There it shocks, creating an extended hot supercritical shock surface. This shock front is optically thick, therefore, it can conceal the planet's intrinsic luminosity beneath. The gas in the vertical influx has high entropy which when passing through the shock front decreases significantly while the gas becomes part of the disk and protoplanet. This shows that circumplanetary disks play a key role in regulating a planet's thermodynamic state. Our simulations furthermore indicate that around the shock surface extended regions of atomic – sometimes ionized – hydrogen develop. Therefore circumplanetary disk shock surfaces could influence significantly the observational appearance of forming gas-giants.
Sleep Enhancement Training for Pregnant Women
Authors: Lee Kathryn A. , Gay Caryl L. , Alsten Christopher R.
Published: October 2016

OBJECTIVE:

To evaluate the feasibility and efficacy of a home-based cognitive–behavioral training program for sleep during late pregnancy.

METHODS:

A nonrandomized quasiexperimental sample of nulliparous women who received the intervention during pregnancy (n=25) was compared with two control groups (n=76 and n=48) from other intervention studies at similar postintervention time points: approximately 1 month before childbirth and 1–2 months after childbirth. The home-based Sleep Enhancement Training System for Pregnancy consisted of 4 weeks of sound-enhanced audio relaxation programs, readings, and daily sleep diaries. Both control groups received dietary recommendations for improving sleep. Sleep duration (total sleep time) and sleep disruption (wake after sleep onset) were measured using wrist actigraphy for a minimum of 48 hours on consecutive weekdays.

RESULTS:

The intervention group had significantly longer sleep duration and less sleep disruption than both control groups, particularly at the postpartum assessment. Intervention participants slept an average of 430 (95% confidence interval [CI] 397–464) minutes during pregnancy compared with 420 (95% CI 403–438) and 417 (95% CI 395–439) minutes for the two control groups. At the postpartum assessment, the intervention group slept 446 (95% CI 415–478) minutes compared with 390 (95% CI 373–408) and 370 (95% CI 348–393) minutes for those in the control groups. In terms of sleep disruption, women in the intervention group had 16.1% (95% CI 11.9–20.2%) wake after sleep onset during pregnancy, whereas women in the control groups had 13.4% (95% CI 11.2–15.5%) and 20.4% (95% CI 17.7–23.0%). Postpartum, the intervention group had 20.3% (95% CI 16.4–24.1%) wake after sleep onset compared with 26.6% (95% CI 24.5–28.8%) and 28.7% (95% CI 26.0–31.5%) among women in the control groups. Participant feedback about the intervention was generally positive, although intervention adherence was variable.

CONCLUSION:

This study provides evidence of the feasibility and efficacy of the Sleep Enhancement Training System for Pregnancy intervention for enhancing sleep that typically worsens during late pregnancy and after childbirth.
Progestogens as Maintenance Treatment in Arrested Preterm Labor
Authors: Palacio Montse , Ronzoni Stefania , Sánchez-Ramos Luis , Murphy Kellie E.
Published: October 2016

OBJECTIVE:

To evaluate the efficacy of maintenance tocolysis with progestogens compared with placebo or no treatment in women with singleton pregnancies and arrested preterm labor.

DATA SOURCES:

Studies without language restrictions were identified from MEDLINE, EMBASE, PubMed, Scopus, the Cochrane Pregnancy and Childbirth Group's Trials Register, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to June 2015. MeSH headings for progestogens were combined with terms regarding labor, tocolysis, or preterm birth. Reference lists of included studies and GoogleSearch were also reviewed.

METHODS OF STUDY SELECTION:

Randomized controlled trials that compared progestogens as a maintenance treatment after arrested preterm labor in singleton pregnancies with placebo or no treatment were identified. Selected studies evaluated delivery before 37 or 34 weeks of gestation or the latency period from randomization to delivery. Excluded studies used progestogens as prevention in asymptomatic women at risk. Risk of bias assessment, subgroup analysis on type of progestogens used, and sensitivity analysis by high-quality studies were performed.

TABULATION, INTEGRATION, AND RESULTS:

Sixteen randomized controlled trials consisting of 1,917 participants were included. Study characteristics and quality were recorded. Preterm delivery at less than 37 weeks of gestation was decreased (38.2% compared with 44.3%; relative risk 0.79, 95% confidence interval [CI] 0.65–0.97) and pregnancy was prolonged (mean difference 8.1 days; 95% CI 3.8–12.4) when women treated with progestogens were compared with placebo or no treatment. There were no differences in the outcome of delivery at less than 34 weeks of gestation (15.6% compared with 18.3%; relative risk 0.77, 95% CI 0.53–1.12). However, sensitivity analysis including five high-quality studies showed no significant differences for preterm delivery at less than 37 weeks of gestation (37.2% compared with 36.9%; relative risk 0.91, 95% CI 0.67–1.25) or latency period (mean difference 0.6 days; 95% CI −3.7 to 4.9).

CONCLUSION:

There is insufficient high-quality data to inform clinicians and patients about the use of progestogens as maintenance treatment after arrested preterm labor to reduce the incidence of preterm birth or pregnancy prolongation.
Prenatally Diagnosed Vasa Previa
Authors: Catanzarite Val , Cousins Larry , Daneshmand Sean , Schwendemann Wade , Casele Holly , Adamczak Joanna , Tith Tevy , Patel Ami
Published: October 2016

OBJECTIVE:

To describe outcomes for a large cohort of women with prenatally diagnosed vasa previa, determine the percentage in patients without risk factors, and compare delivery timing and indications for singletons and twins.

METHODS:

This was a retrospective case series of women with prenatally diagnosed vasa previa delivered at a single tertiary center over 12 years. Potential participants were identified using hospital records and perinatal databases. Patients were included if vasa previa was confirmed at delivery and by pathologic examination. Maternal and newborn data were gathered from medical records.

RESULTS:

There were 77 singleton and 19 twin pregnancies with a prenatal diagnosis of vasa previa. There was one neonatal death from congenital heart disease. Perinatal management of recommended elective hospitalizations with corticosteroid administration and elective early delivery resulted in average gestational age for delivery in singletons at 34.7±1.6 weeks and 32.8±2.2 weeks for twins. Among the 77 singletons, delivery was elective in 48, as a result of contractions or labor in 21, bleeding in four, nonreassuring tracing in two, asymptomatic cervical shortening in one, and preeclampsia in one. Among 19 twins, delivery was elective in six and for contractions or labor in 13. Sixty-eight percent of twins compared with 37% of singletons had nonelective delivery (P<.05). Delivery occurred by 32 weeks of gestation in 6.4% of singletons and 26% of twins (P<.05) and by 34 weeks of gestation in 11% of singletons and 58% of twins (P<.001). Six neonates (5.2%) had major anomalies, all prenatally detected. Respiratory distress syndrome occurred in 57.1% of singletons and 65.7% of twins. Nineteen singletons (24.7%) had no risk factors for vasa previa.

CONCLUSION:

Planned preterm delivery for women with prenatally diagnosed vasa previa resulted in elective delivery for singletons in 62% and for twins 32%. Gestational age at birth on average was 34.7 weeks for singletons and 32.8 weeks of gestation for twins. Major anomalies were frequent as was respiratory distress syndrome. Elective delivery between 34 and 35 weeks of gestation for singletons is reasonable. As a result of the high rate of nonelective delivery in twins, delivery at 32–34 weeks of gestation may be risk-beneficial. The high rate of singletons without risk factors for vasa previa reinforces the recommendation to screen routinely for cord insertion site.
Maternal and Neonatal Outcomes With Early Compared With Delayed Pushing Among Nulliparous Women
Authors: Yee Lynn M. , Sandoval Grecio , Bailit Jennifer , Reddy Uma M. , Wapner Ronald J. , Varner Michael W. , Caritis Steve N. , Prasad Mona , Tita Alan T. N. , Saade George , Sorokin Yoram , Rouse Dwight J. , Blackwell Sean C. , Tolosa Jorge E. ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network
Published: October 2016

OBJECTIVE:

To describe factors associated with delayed pushing and evaluate the relationship between delayed pushing and perinatal outcomes in nulliparous women with singleton term gestations.

METHODS:

This was a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Assessment of Perinatal Excellence cohort of 115,502 women and their neonates born in 25 U.S. hospitals from 2008 to 2011. Nulliparous women with singleton, cephalic, nonanomalous term births who achieved 10-cm cervical dilation were included. Women in whom pushing was delayed by 60 minutes or greater (delayed group) were compared with those who initiated pushing within 30 minutes (early group). Multivariable regression analyses were used to assess the independent association of delayed pushing with mode of delivery, length of the second stage, and other maternal and perinatal outcomes (significance defined as P<.05).

RESULTS:

Of 21,034 women in the primary analysis sample, pushing was delayed in 18.4% (n=3,870). Women who were older, privately insured, or non-Hispanic white as well as those who had induction or augmentation of labor, diabetes, or epidural analgesia were more likely to have delayed pushing. Delayed pushing was more common when the second stage began during daytime hours or in hospitals with dedicated 24-hour obstetric anesthesia, although differences were small. After adjusting for differences in baseline and labor characteristics including center, women in the delayed group had longer mean durations of the second stage (191 compared with 84 minutes, P<.001) and of active pushing (86 compared with 76 minutes, P<.001). Delayed pushing was associated with greater rates of cesarean delivery (11.2% compared with 5.1%; adjusted odds ratio [OR] 1.86, 95% confidence interval [CI] 1.63–2.12), operative vaginal delivery (adjusted OR 1.26, 95% CI 1.14–1.40), postpartum hemorrhage (adjusted OR 1.43, 95% CI 1.05–1.95), and blood transfusion (adjusted OR 1.51, 95% CI 1.04–2.17). Delayed pushing was not associated with increased odds of adverse neonatal outcomes compared with early pushing.

CONCLUSION:

In this large birth cohort, delayed pushing was associated with longer second stage duration, increased odds of cesarean delivery, and increased odds of postpartum hemorrhage, but was not associated with neonatal morbidity.
Simultaneous Administration Compared With a 24-Hour Mifepristone–Misoprostol Interval in Second-Trimester Abortion
Authors: Abbas Dina Fatima , Blum Jennifer , Ngoc Nguyen Thi Nhu , Nga Nguyen Thi Bach , Chi Huynh Thi Kim , Martin Roxanne , Winikoff Beverly
Published: October 2016

OBJECTIVE:

To compare outcomes with simultaneous administration of mifepristone and misoprostol with a regimen in which the drugs are administered at a 24-hour interval for second-trimester abortion.

METHODS:

In this placebo-controlled, double-blind trial, participants were randomized to receive mifepristone either 24 hours before or at the same time as misoprostol. Participants were hospitalized to receive 400 micrograms buccal misoprostol at 3-hour intervals up to 48 hours or until uterine expulsion. The primary outcome was the proportion of women who experienced uterine expulsion within 24 hours after the first misoprostol dose and this required 504 women to examine our hypothesis that this rate would be 85% in the 24-hour interval arm compared with 70% in the simultaneous arm. Secondary outcomes included total abortion time from mifepristone and misoprostol.

RESULTS:

From February 2013 to April 2014, 509 women were enrolled. Women in the 24-hour interval arm were more likely to abort within 24 hours (94.4% compared with 85.0%, relative risk 1.11, 95% confidence interval [CI] 1.05–1.18). At 48 hours, the rate was similar in the two arms (96.8% [24-hour interval] and 95.7% [simultaneous], relative risk 1.01, 95% CI 0.97–1.04). Median misoprostol dosing time was shorter in the 24-hour interval arm (7.7 compared with 13 hours; P<.001) and consistent with the median misoprostol doses required (three compared with five; P<.001). Median time from mifepristone to uterine expulsion was longer in the 24-hour interval arm (32.3 compared with 13 hours; P<.001). Both regimens had high acceptability rates and reported similar side effects and pain scores.

CONCLUSION:

Administering mifepristone and misoprostol simultaneously results in lower expulsion rates within 24 hours of taking misoprostol, longer median misoprostol treatment times, and requires more misoprostol doses. At 48 hours, both regimens work equally well. Simultaneous dosing results in less total time from the first clinical contact to complete abortion.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, https://clinicaltrials.gov, NCT01768299.
Psychotherapy With Somatosensory Stimulation for Endometriosis-Associated Pain
Authors: Meissner Karin , Schweizer-Arau Annemarie , Limmer Anna , Preibisch Christine , Popovici Roxana M. , Lange Isabel , de Oriol Barbara , Beissner Florian
Published: October 2016

OBJECTIVE:

To evaluate whether psychotherapy with somatosensory stimulation is effective for the treatment of pain and quality of life in patients with endometriosis-related pain.

METHODS:

Patients with a history of endometriosis and chronic pelvic pain were randomized to either psychotherapy with somatosensory stimulation (ie, different techniques of acupuncture point stimulation) or wait-list control for 3 months, after which all patients were treated. The primary outcome was brain connectivity assessed by functional magnetic resonance imaging. Prespecified secondary outcomes included pain on 11-point numeric rating scales (maximal and average global pain, pelvic pain, dyschezia, and dyspareunia) and physical and mental quality of life. A sample size of 30 per group was planned to compare outcomes in the treatment group and the wait-list control group.

RESULTS:

From March 2010 through March 2012, 67 women (mean age 35.6 years) were randomly allocated to intervention (n=35) or wait-list control (n=32). In comparison with wait-list controls, treated patients showed improvements after 3 months in maximal global pain (mean group difference −2.1, 95% confidence interval [CI] −3.4 to −0.8; P=.002), average global pain (−2.5, 95% CI −3.5 to −1.4; P<.001), pelvic pain (−1.4, 95% CI −2.7 to −0.1; P=.036), dyschezia (−3.5, 95% CI −5.8 to −1.3; P=.003), physical quality of life (3.8, 95% CI 0.5–7.1, P=.026), and mental quality of life (5.9, 95% CI 0.6–11.3; P=.031); dyspareunia improved nonsignificantly (−1.8, 95% CI −4.4 to 0.7; P=.150). Improvements in the intervention group remained stable at 6 and 24 months, and control patients showed comparable symptom relief after delayed intervention.

CONCLUSION:

Psychotherapy with somatosensory stimulation reduced global pain, pelvic pain, and dyschezia and improved quality of life in patients with endometriosis. After 6 and 24 months, when all patients were treated, both groups showed stable improvements.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, https://clinicaltrials.gov, NCT01321840.
Guillain-Barré Syndrome in Pregnancy
Authors: Pacheco Luis D. , Saad Antonio F. , Hankins Gary D. V. , Chiosi Giuseppe , Saade George
Published: October 2016

Guillain-Barré syndrome has been reported in pregnancy and is a potentially lethal condition. It affects the nervous system with acute onset of symmetric ascending weakness and may result in frank respiratory failure and autonomic dysfunction. Most patients recall symptoms of a respiratory or gastrointestinal illness in the weeks preceding the onset of weakness. Recent evidence suggests a potential role of the Zika virus as a trigger for the syndrome. The diagnosis of Guillain-Barré is clinical. Supportive measures include venous thromboembolism prophylaxis, aggressive physical therapy, pressure ulcer prevention, enteral nutrition, and respiratory support. The mainstay of management comprises plasmapheresis or administration of intravenous immunoglobulins. Affected patients must be closely monitored for development of respiratory failure and autonomic dysfunction. Treatment during pregnancy should follow the same principles as for nonpregnant individuals.
Safety of Local Intracutaneous Lidocaine Anesthesia Used by Dermatologic Surgeons for Skin Cancer Excision and Postcancer Reconstruction: Quantification of Standard Injection Volumes and Adverse Event Rates
Authors: Alam Murad , Schaeffer Matthew R. , Geisler Amelia , Poon Emily , Fosko Scott W. , Srivastava Divya
Published: October 2016

BACKGROUND

Intracutaneous lidocaine is used for anesthesia in dermatologic surgery for skin cancer excision and repair with exceedingly low incidence of reported adverse events.

OBJECTIVE

To measure (1) the quantity of lidocaine typically used for facial skin cancer excision and reconstruction; and (2) the frequency and character of associated adverse events.

METHODS

Survey study of dermatologic surgeons with longitudinal reporting. Reported practice during 10 business days: (1) mean volume of 1% lidocaine per skin cancer excision; (2) maximum per excision; (3) mean per reconstruction; and (4) maximum per reconstruction.

RESULTS

A total of 437 of 1,175 subjects contacted (37.2%) responded. Mean per excision was 3.44 mL (SD: 2.97), and reconstruction 11.70 mL (10.14). Maximum per excision was 6.54 mL (4.23), and reconstruction was 15.85 mL (10.39). No cases of lidocaine toxicity were reported, diagnosed, or treated. Incidence of adverse events possibly anesthesia related was >0.15%, with most (0.13%) being mild cases of dizziness, drowsiness, or lightheadedness from epinephrine tachycardia.

CONCLUSION

Toxicity associated with local anesthesia other than lidocaine was not studied. Volumes of lidocaine in skin cancer excision and repair are modest and within safe limits. Lidocaine toxicity is exceedingly rare to entirely absent. For comparable indications, lidocaine is safer than conscious sedation or general anesthesia.
Sebaceous Carcinoma Treated With Mohs Micrographic Surgery
Authors: Brady Kimberly L. , Hurst Eva A.
Published: October 2016

BACKGROUND

Sebaceous carcinoma is a rare and potentially aggressive adnexal neoplasm with historic data indicating high rates of recurrence, metastasis, and cancer-specific mortality.

OBJECTIVE

To evaluate the incidence of local recurrence, metastasis, disease-specific mortality, and all-cause mortality and to identify work-up approaches.

PATIENTS AND METHODS/MATERIALS

Retrospective review of patients with sebaceous carcinoma treated with Mohs micrographic surgery between 2001 and 2013 at one institution.

RESULTS

Thirty-seven patients had 45 sebaceous carcinomas located on the periocular region (13%), non-periocular face (47%), scalp (7%), neck (4%), trunk (9%), and extremities (20%). The mean age was 66.1 years, and 24 (65%) patients were male. Five patients had Muir–Torre syndrome (MTS) or Lynch syndrome. Seven of 12 tumors showed loss of expression of ≥1 mismatch repair gene. The most common work-up involved taking a detailed personal and family medical history. No local recurrences, metastases, or disease-specific deaths occurred during an average follow-up of 3.6 years.

CONCLUSION

Mohs micrographic surgery is an effective treatment for sebaceous carcinoma. Detailed history taking, age-appropriate cancer screening, and immunohistochemical staining with MLH1, MSH2, or MSH6 is helpful in identifying which patients should be referred to a geneticist for work-up of MTS.
Association between maternal age at childbirth and metabolic syndrome in postmenopausal women: Korea National Health and Nutrition Examination Survey 2010 to 2012
Authors: Shin Jae Eun , Han Kyung Do , Shin Jong Chul , Lee Young , Kim Sa Jin
Published: October 2016

Objective:

The aim of this study was to evaluate the relationship between maternal age at childbirth and metabolic syndrome in postmenopausal women.

Methods:

We carried out a cross-sectional study on 3,956 Korean postmenopausal women who participated in the Korea National Health and Nutrition Examination Survey from 2010 to 2012. Multivariate logistic regression was used to evaluate the association between maternal age at first and last childbirth and metabolic syndrome, with adjustment for potential confounding variables.

Results:

Women with metabolic syndrome had younger age at first delivery (23.3 ± 0.1 vs 24.4 ± 0.1 y, P < 0.001) and an older age at last delivery (30.8 ± 0.1 vs 30.3 ± 0.1 y, P = 0.011) than those without metabolic syndrome. After adjustments for confounding factors, earlier ages of first and last childbirth were positively associated with metabolic syndrome. The odds ratio (OR) was 2.157 (95% CI 1.256-3.705) for age at first childbirth, and 1.639 (95% CI 1.118-2.403) for age at last childbirth. Among the components of metabolic syndrome, only fasting glucose was positively associated with early age at first childbirth (OR 1.86; 95% CI 1.065-3.249) and early age at last childbirth (OR 1.71; 95% CI 1.197-2.444).

Conclusions:

A younger maternal age at first and last childbirth was independently associated with a higher risk of metabolic syndrome in postmenopausal women. Advanced maternal age at last childbirth was, however, not an independent risk factor for metabolic syndrome.
Age at natural menopause genetic risk score in relation to age at natural menopause and primary open-angle glaucoma in a US-based sample
Authors: Pasquale Louis R. , Aschard Hugues , Kang Jae H. , Bailey Jessica N. Cooke , Lindström Sara , Chasman Daniel I. , Christen William G. , Allingham R. Rand , Ashley-Koch Allison , Lee Richard K. , Moroi Sayoko E. , Brilliant Murray H. , Wollstein Gadi , Schuman Joel S. , Fingert John , Budenz Donald L. , Realini Tony , Gaasterland Terry , Gaasterland Douglas , Scott William K. , Singh Kuldev , Sit Arthur J. , Igo Robert P. , Song Yeunjoo E. , Hark Lisa , Ritch Robert , Rhee Douglas J. , Gulati Vikas , Havens Shane , Vollrath Douglas , Zack Donald J. , Medeiros Felipe , Weinreb Robert N. , Pericak-Vance Margaret A. , Liu Yutao , Kraft Peter , Richards Julia E. , Rosner Bernard A. , Hauser Michael A. , Haines Jonathan L. , Wiggs Janey L.
Published: October 2016

Objective:

Several attributes of female reproductive history, including age at natural menopause (ANM), have been related to primary open-angle glaucoma (POAG). We assembled 18 previously reported common genetic variants that predict ANM to determine their association with ANM or POAG.

Methods:

Using data from the Nurses’ Health Study (7,143 women), we validated the ANM weighted genetic risk score in relation to self-reported ANM. Subsequently, to assess the relation with POAG, we used data from 2,160 female POAG cases and 29,110 controls in the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (NEIGHBORHOOD), which consists of 8 datasets with imputed genotypes to 5.6+ million markers. Associations with POAG were assessed in each dataset, and site-specific results were meta-analyzed using the inverse weighted variance method.

Results:

The genetic risk score was associated with self-reported ANM (P = 2.2 × 10–77) and predicted 4.8% of the variance in ANM. The ANM genetic risk score was not associated with POAG (Odds Ratio (OR) = 1.002; 95% Confidence Interval (CI): 0.998, 1.007; P = 0.28). No single genetic variant in the panel achieved nominal association with POAG (P ≥0.20). Compared to the middle 80 percent, there was also no association with the lowest 10th percentile or highest 90th percentile of genetic risk score with POAG (OR = 0.75; 95% CI: 0.47, 1.21; P = 0.23 and OR = 1.10; 95% CI: 0.72, 1.69; P = 0.65, respectively).

Conclusions:

A genetic risk score predicting 4.8% of ANM variation was not related to POAG; thus, genetic determinants of ANM are unlikely to explain the previously reported association between the two phenotypes.
QUANTITATIVE ANALYSIS OF PIGMENT EPITHELIAL DETACHMENT RESPONSE TO DIFFERENT ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS IN WET AGE-RELATED MACULAR DEGENERATION
Authors: Balaskas Konstantinos , Karampelas Michael , Horani Mania , Hotu Oana , Keane Pearse , Aslam Tariq
Published: October 2016

Purpose:

To assess whether best-corrected visual acuity and pigment epithelial detachment (PED) height, volume, and reflectivity in patients with wet age-related macular degeneration are influenced by baseline anatomical and functional parameters, including quantifiable metrics of PED morphology and choice of treatment.

Methods:

One hundred two consecutive, treatment-naive wet age-related macular degeneration patients with PED (>50 μm) treated with aflibercept (52) or ranibizumab (50) were retrospectively included. Pigment epithelial detachment height, horizontal and vertical dimensions, and volume were recorded at baseline, 3 months, and 1 year, respectively. Bespoke image analysis software provided a quantifiable measure of reflectivity.

Results:

Best-corrected visual acuity at 3 months was influenced by baseline best-corrected visual acuity (P = 0.006). Pigment epithelial detachment height was influenced by baseline height (P = 0.009), subretinal fluid (P = 0.008), central macular thickness (P = 0.006), and use of aflibercept (P = 0.003) at 3 months and by baseline height (P = 0.018), volume (P = 0.017), vertical dimension (P = 0.0004), and aflibercept (P = 0.015) at 1 year. Pigment epithelial detachment reflectivity increased from 43.59 to 55.86 (3 months) and 57.35 (1 year) (P < 0.001) and was influenced by its baseline values and, interestingly, use of aflibercept at 3 months (P = 0.013).

Conclusion:

Quantifiable metrics of PED morphology improve with treatment, and PED content becomes hyperreflective, more so on aflibercept. Pigment epithelial detachments respond better in the context of more active disease. More hyporeflective PED content may predispose to better treatment response, especially with aflibercept.
CEFALIUM-INDUCED BILATERAL TRANSIENT MYOPIA, RETINAL FOLDS, AND FOCAL CHOROIDAL DELAY
Authors: Arana Luís Augusto , Bach Mariana Bolzani , Vedana Gustavo , Volkmann Mathias Alexandre , Arana Jayme
Published: October 2016

Purpose:

To describe a case of acute bilateral transient myopia, retinal folds, and island of choroidal delay associated with oral administration of Cefalium, a medication commonly prescribed in Brazil for migraine that combines acetaminophen 500 mg, caffeine 40 mg, dihydroergotamine mesylate 1 mg, and metoclopramide hydrochloride 10 mg.

Methods:

A 21-year-old woman with bilateral blurred vision 1 day after the use of Cefalium. The main outcomes measures were BCVA, ocular fundus, ocular coherence tomography, and angiography findings.

Results:

The patient developed bilateral myopia, retinal folds, and focus choroidal delay 1 day after the administration of oral cefalium. Ocular fundus examination and ocular coherence tomography revealed retinal folds in the internal surface of the retina. Angiography showed focus areas of hypofluorescence in both eyes. Seven days after Cefalium was suspended, all clinical symptoms had resolved, with full recovery from the abnormal findings on ocular fundus, ocular coherence tomography, and angiography.

Conclusion:

This is the first report that identified and described bilateral transient myopia, retinal folds, and focus choroidal delay secondary the use of Cefalium.
Allergic Eyelid Dermatitis as the Sole Manifestation of Gold Hypersensitivity
Authors: McDaniel Lindsey M. , Couch Steven M.
Published: October 2016

Gold hypersensitivity is a cause of periorbital dermatitis that often presents as a diagnostic challenge for many ophthalmologists. Six female patients are described as presenting with isolated bilateral periorbital dermatitis. Main symptoms included itching (3/6), eyelid redness (3/6), and drooping eyelids (3/6) for an average duration of 16.8 months prior to referral. All 6 patients failed conservative management. Recurrence of symptoms necessitated allergic patch testing, revealing a severe hypersensitivity reaction to gold in all cases. By discontinuing contact with gold, specifically gold jewelry, the allergic periorbital dermatitis completely resolved. No patients required surgical intervention for eyelid malposition. Increased awareness of this reversible cause of allergic periorbital dermatitis may improve patient outcomes.
Targeting the Endocannabinoid System in Psychiatric Illness
Authors: Katzman Martin A. , Furtado Melissa , Anand Leena
Published: October 2016

Prevalence of psychiatric disorders continues to rise globally, yet remission rates and patient outcome remain less than ideal. As a result, novel treatment approaches for these disorders are necessary to decrease societal economic burden, as well as increase individual functioning. The recent discovery of the endocannabinoid system has provided an outlet for further research into its role in psychiatric disorders, because efficacy of targeted treatments have been demonstrated in medical illnesses, including cancers, neuropathic pain, and multiple sclerosis. The present review will investigate the role of the endocannabinoid system in psychiatric disorders, specifically schizophrenia, depressive, anxiety, and posttraumatic stress disorders, as well as attention-deficit hyperactivity disorder. Controversy remains in prescribing medicinal cannabinoid treatments due to the fear of adverse effects. However, one must consider all potential limitations when determining the safety and tolerability of cannabinoid products, specifically cannabinoid content (ie, Δ9-tetrahydrocannabinol vs cannabidiol) as well as study design. The potential efficacy of cannabinoid treatments in the psychiatric population is an emerging topic of interest that provides potential value going forward in medicine.
A Systematic Review on the Pharmacological Treatment of Delusional Disorder
Authors: Muñoz-Negro José Eduardo , Cervilla Jorge A.
Published: October 2016

Background

Pharmacological treatment is the criterion standard in delusional disorder (DD). No second-generation antipsychotic (SGA) is specifically authorized for the treatment of DD.

Aims

To evaluate the evidence available on pharmacological treatments in adults with DD and to compare first-generation antipsychotics (FGA) versus SGA.

Methods

A systematic review on pharmacological treatment of DD following the PRISMA methodology was conducted. We selected the best evidence available and analyzed it critically assessing both, biases and quality, to finally perform a narrative and quantitative synthesis.

Results

The evidence available was mainly limited to observational studies and case series. There were no randomized clinical trials. Three hundred eighty-five DD cases were included (177 of which were on SGAs). Overall, antipsychotics achieved a good response in 33.6%% of the patients. As a group, FGAs showed significant superiority compared to SGAs (good response rates were 39% vs 28%, respectively). We did not find superiority of any specific antipsychotic over another.

Conclusions

There is no strong evidence to make definite recommendations, although antipsychotics in general seem to be an effective treatment for DD with a slight superiority in favor of FGAs as compared with SGAs. Existent data are, albeit, scarce and specific clinical trials on DD, are strongly recommended.
Yield of Endoscopy in Pediatric Gastroparesis
Authors: Altepeter Tara A. , Shaffer Stephen
Published: October 2016

Objectives:

The aim of the study was to quantify the diagnostic yield of upper endoscopy in children with gastroparesis and to develop a clinical model for gastroparesis using common symptoms and screening blood tests.

Methods:

We retrospectively reviewed charts of 196 patients of age 4 to 18 years evaluated for gastroparesis between 2009 and 2013. All patients completed a standard solid‐phase gastric emptying scan and upper endoscopy within a 12‐month period. We analyzed gross and histologic endoscopy findings. Symptom‐based data were collected on dyspeptic symptoms and classic “red‐flag” symptoms.

Results:

Seventy patients with gastroparesis and 126 controls were included. Clinically significant endoscopic findings were noted in 35% of controls (44/126) and 43% of gastroparetics (30/70), P = 0.345. Concordance between gross and histologic findings was low at 50%. Histologic findings included gastritis 60% (17/28), esophagitis 39% (11/28), and duodenitis 7% (2/28). In univariate and multivariate analyses, there was no meaningful correlation between symptoms and/or screening laboratory values and diagnosis of gastroparesis.

Conclusions:

Clinically significant endoscopy findings were common in both controls and gastroparetics. As more than one‐third of patients had findings on endoscopy, we conclude that upper endoscopy remains an important part of the evaluation process of patients with dyspeptic symptoms and suspected gastroparesis. As gross abnormalities were frequently not present with histologic changes, routine biopsy is required. There was no association between studied symptoms and the presence of gastroparesis. A comprehensive evaluation of children with dyspeptic symptoms requires endoscopy with biopsy and solid‐phase gastric emptying scan to determine the underlying diagnosis.
Intensive Care Management of Pediatric Acute Liver Failure
Authors: Lutfi Riad , Abulebda Kamal , Nitu Mara E. , Molleston Jean P. , Bozic Molly A. , Subbarao Girish
Published: October 2016

Pediatric acute liver failure is rare but life‐threatening illness that occurs in children without preexisting liver disease. The rarity of the disease, along with its severity and heterogeneity, presents unique clinical challenges to the physicians providing care for pediatric patients with acute liver failure. In this review, practical clinical approaches to the care of critically ill children with acute liver failure are discussed with an organ system‐specific approach. The underlying pathophysiological processes, major areas of uncertainty, and approaches to the critical care management of pediatric acute liver failure are also reviewed.