bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue tolerance: an essential but elusive trait for salt-tolerant crops
Authors: Munns Rana , James Richard A. , Gilliham Matthew , Flowers Timothy J. , Colmer Timothy D.
Published: October 2016

For a plant to persist in saline soil, osmotic adjustment of all plant cells is essential. The more salt-tolerant species accumulate Na+ and Cl– to concentrations in leaves and roots that are similar to the external solution, thus allowing energy-efficient osmotic adjustment. Adverse effects of Na+ and Cl– on metabolism must be avoided, resulting in a situation known as ‘tissue tolerance’. The strategy of sequestering Na+ and Cl– in vacuoles and keeping concentrations low in the cytoplasm is an important contributor to tissue tolerance. Although there are clear differences between species in the ability to accommodate these ions in their leaves, it remains unknown whether there is genetic variation in this ability within a species. This viewpoint considers the concept of tissue tolerance, and how to measure it. Four conclusions are drawn: (1) osmotic adjustment is inseparable from the trait of tissue tolerance; (2) energy-efficient osmotic adjustment should involve ions and only minimal organic solutes; (3) screening methods should focus on measuring tolerance, not injury; and (4) high-throughput protocols that avoid the need for control plants and multiple Na+ or Cl– measurements should be developed. We present guidelines to identify useful genetic variation in tissue tolerance that can be harnessed for plant breeding of salt tolerance.
Knowledge-based soil type classification using terrain segmentation
Authors: Dornik Andrei , Drăguţ Lucian , Urdea Petru
Published: October 2016

Soil information covering regional, continental, or even global scales is needed for modelling, prediction, or estimation of environmental risks, crop yield estimation, carbon stock estimation, or research on climate change. This study aims to evaluate the extent to which geographic object-based image analysis and expert-knowledge, using digital maps of climate, topography, vegetation, and geology as soil covariates (GEOBIA approach), might model and reproduce a conventional soil map at a scale 1:1000000 in the south-west of Romania. The environmental variables were segmented with a region-growing algorithm, the resulting objects being subsequently classified into soil types using expert-knowledge fuzzy classification rules. To assess the geographical support of classification for the modelling of a conventional soil map, we quantitatively evaluated a pixel-based soil map produced using the same expert-knowledge classification rules, as an alternative to an object-based approach. To evaluate the source of soil information, we quantitatively assessed the map of the World Reference Base soil groups produced by the data-driven global soil information system, SoilGrids, as an alternative to expert-knowledge rules. The digital soil maps were quantitatively compared with the conventional soil map. Evidence was provided that the similarity of soil types with the conventional soil map was higher when the modelling was conducted through GEOBIA approach (general similarity of 65% and fuzzy kappa index of 0.58) than the pixel-based approach and SoilGrids. Furthermore, the results showed that the SoilGrids map achieved higher similarity to conventional soil map than the pixel-based soil map. When tested in another area, without modification to the knowledge-based methodologies, the same conclusions could be drawn, although the two maps recorded lower similarity values. The overall reduction in similarity values is explained by a high variability of some soil types under different environmental conditions.
Working stroke of the kinesin-14, ncd, comprises two substeps of different direction
Authors: Nitzsche Bert , Dudek Elzbieta , Hajdo Lukasz , Kasprzak Andrzej A. , Vilfan Andrej , Diez Stefan
Published: October 2016

Significance

Kinesin, dynein, and myosin motor proteins are best known for their production of linear force along the axes of cytoskeletal filaments. However, many of these motors can also generate torque manifesting itself by filament rotations around their longitudinal axes when gliding on motor-coated surfaces. By combining the measured longitudinal and angular velocities of microtubules gliding on nonprocessive kinesin-14 motors with a theoretical model we here show that the working stroke of this motor comprises at least two distinct conformational changes. Our observations clarify the temporal order of events in the hydrolysis cycle of kinesin-14, which has not been conclusive from previous structural and single-molecule data. Moreover, our results demonstrate how conformational changes in individual enzymes can be deduced from their ensemble properties.
Timescales and the management of ecological systems
Authors: Hastings Alan
Published: October 2016

Human management of ecological systems, including issues like fisheries, invasive species, and restoration, as well as others, often must be undertaken with limited information. This means that developing general principles and heuristic approaches is important. Here, I focus on one aspect, the importance of an explicit consideration of time, which arises because of the inherent limitations in the response of ecological systems. I focus mainly on simple systems and models, beginning with systems without density dependence, which are therefore linear. Even for these systems, it is important to recognize the necessary delays in the response of the ecological system to management. Here, I also provide details for optimization that show how general results emerge and emphasize how delays due to demography and life histories can change the optimal management approach. A brief discussion of systems with density dependence and tipping points shows that the same themes emerge, namely, that when considering issues of restoration or management to change the state of an ecological system, that timescales need explicit consideration and may change the optimal approach in important ways.
Human mitochondrial ribosomes can switch their structural RNA composition
Authors: Rorbach Joanna , Gao Fei , Powell Christopher A. , D’Souza Aaron , Lightowlers Robert N. , Minczuk Michal , Chrzanowska-Lightowlers Zofia M.
Published: October 2016

Significance

Mammalian mitoribosomes are idiosyncratic. They reversed the typical 70% RNA:30% protein ratio to generate a protein-rich ribosome, which lacks the conventional 5S transcript as a third rRNA component. Recent subnanometer-resolution structures revealed a further unexpected eccentricity: integration of a mitochondrially encoded tRNA into the large-subunit structure. However, mitochondrially encoded tRNA (mt-tRNA) selection varies with mt-tRNA
Val
integration into human mitoribosomes compared with porcine mitoribosomes favoring mt-tRNA
Phe
. Our analysis of mitoribosomes from multiple tissues isolated from different mammals found that of 22 mitochondrially encoded tRNAs, only mt-tRNA
Val
or mt-tRNA
Phe
is incorporated. Further, there was no evidence of tissue-specific selectivity. Remarkably, human mitoribosomes can exhibit adaptive plasticity when mt-tRNA
Val
levels are severely depleted by selectively integrating mt-tRNA
Phe
instead, to generate translationally competent mitoribosomes.
Germline replications and somatic mutation accumulation are independent of vegetative life span inArabidopsis
Authors: Watson J. Matthew , Platzer Alexander , Kazda Anita , Akimcheva Svetlana , Valuchova Sona , Nizhynska Viktoria , Nordborg Magnus , Riha Karel
Published: October 2016

Significance

In contrast to animals, plants lack a segregated germline. Instead, all plant tissue is derived from small clusters of meristematic cells that throughout development give rise to vegetative tissues and only late in development to reproductive organs. Hence, mutations acquired during vegetative growth can be passed on to offspring; it is generally believed that older plants will acquire more such mutations over their lifetimes due to replication during cell division. Here we measure the number of DNA replications occurring in the cell lineage leading to gametes and demonstrate that the number of replications is independent of life span, suggesting that older plants may not be passing on more mutations to their offspring relative to younger plants.
L3 acquisition of English attributive adjectives
Authors: Fallah Nader , Jabbari Ali Akbar
Published: October 2016

This study examines three L3 transfer proposals, namely the L1 Factor (Hermas, 2010, 2014a, 2014b), the CEM (Flynn et al., 2004) and the TPM (Rothman, 2010, 2011, 2013, 2015) as well as investigates the role of the language of dominance in L3 acquisition of English attributive adjectives. Three groups of bilinguals took part in this study: L1 Mazandarani/L2 Persian, with Mazandarani as the dominant language of communication, L1 Mazandarani/L2 Persian, with Persian as the dominant language of communication and L1 Persian/L2 Mazandarani, with Persian as the dominant language of communication. The results of a grammaticality judgment task and an element rearrangement task show that the predictions of the above-mentioned L3 transfer proposals were not realized. Instead, the dominant language of communication turns out to be the main source of syntactic crosslinguistic influence at the initial stages of L3 acquisition, irrespective of its status as an L1 or L2.
Simulation of primary dendrite arm spacing in an Al–Cu welding molten pool
Authors: Wang L. , Wei Y. , Yu F.
Published: October 2016

Primary dendrite arm spacing in tungsten inert gas welding pool for Al–4wt%Cu alloys is predicted by a quantitative phase-field model. Transient conditions are obtained by functions of thermal gradient and solidification rate. When the same welding power is given by 3500 W and different welding velocities are given by 1.5, 2.0 and 2.5 mm s−1, the primary dendrite arm spacing obtained by simulation results is the largest under the welding velocity of 2.0 mm s−1. When the same welding velocity is given by 2.5 mm s−1 and different welding power is given by 3500, 4000 and 5000 W, the primary dendrite arm spacing acquired by simulation results is the largest under the welding power of 5000 W. Primary dendrite arm spacing and morphology obtained by simulation results agrees well with experimental findings.
Rabifier2: an improved bioinformatic classifier of Rab GTPases
Authors: Surkont Jaroslaw , Diekmann Yoan , Pereira-Leal José B
Published: October 2016

The Rab family of small GTPases regulates and provides specificity to the endomembrane trafficking system; each Rab subfamily is associated with specific pathways. Thus, characterization of Rab repertoires provides functional information about organisms and evolution of the eukaryotic cell. Yet, the complex structure of the Rab family limits the application of existing methods for protein classification. Here, we present a major redesign of the Rabifier, a bioinformatic pipeline for detection and classification of Rab GTPases. It is more accurate, significantly faster than the original version and is now open source, both the code and the data, allowing for community participation.

Availability and Implementation

Rabifier and RabDB are freely available through the web at http://rabdb.org. The Rabifier package can be downloaded from the Python Package Index at https://pypi.python.org/pypi/rabifier, the source code is available at Github https://github.com/evocell/rabifier.

Supplementary information

Supplementary data are available at Bioinformatics online.
Recommendations for high-risk clinical target volume definition with computed tomography for three-dimensional image-guided brachytherapy in cervical cancer patients
Authors: Ohno Tatsuya , Wakatsuki Masaru , Toita Takafumi , Kaneyasu Yuko , Yoshida Ken , Kato Shingo , Ii Noriko , Tokumaru Sunao , Ikushima Hitoshi , Uno Takashi , Noda Shin-ei , Kazumoto Tomoko , Harima Yoko ,   , the Working Group of the Gynecological Tumor Committee of the Japanese Radiation Oncology Study Group (JROSG)
Published: October 2016

Our purpose was to develop recommendations for contouring the computed tomography (CT)-based high-risk clinical target volume (CTVHR) for 3D image-guided brachytherapy (3D-IGBT) for cervical cancer. A 15-member Japanese Radiation Oncology Study Group (JROSG) committee with expertise in gynecological radiation oncology initiated guideline development for CT-based CTVHR (based on a comprehensive literature review as well as clinical experience) in July 2014. Extensive discussions occurred during four face-to-face meetings and frequent email communication until a consensus was reached. The CT-based CTVHR boundaries were defined by each anatomical plane (cranial–caudal, lateral, or anterior–posterior) with or without tumor progression beyond the uterine cervix at diagnosis. Since the availability of magnetic resonance imaging (MRI) with applicator insertion for 3D planning is currently limited, T2-weighted MRI obtained at diagnosis and just before brachytherapy without applicator insertion was used as a reference for accurately estimating the tumor size and topography. Furthermore, utilizing information from clinical examinations performed both at diagnosis and brachytherapy is strongly recommended. In conclusion, these recommendations will serve as a brachytherapy protocol to be used at institutions with limited availability of MRI for 3D treatment planning.
On the metallicity dependance of the [Y/Mg] – age relation for solar type stars
Authors: Feltzing Sofia , Howes Louise M. , McMillan Paul J. , Stonkutė Edita
Published: October 2016

Several recent studies of Solar twins in the Solar neighbourhood have shown a tight correlation between various elemental abundances and age, in particular [Y/Mg]. If this relation is real and valid for other types of stars as well as elsewhere in the Galaxy it would provide a very powerful tool to derive ages of stars without the need to resort to determining their masses (evolutionary stage) very precisely. The method would also likely work if the stellar parameters have relatively large errors. The studies presented in the recent literature span a narrow range of [Fe/H]. By studying a larger sample of Solar neighbourhood dwarfs with a much larger range in [Fe/H], we find that the relation between [Y/Mg] and age depends on the [Fe/H] of the stars. Hence, it appears that the [Y/Mg] – age relation is unique to Solar analogues.
Internal Medicine Residency Program Directors’ Views of the Core Entrustable Professional Activities for Entering Residency: An Opportunity to Enhance Communication of Competency Along the Continuum
Authors: Angus Steven V. , Vu T. Robert , Willett Lisa L. , Call Stephanie , Halvorsen Andrew J. , Chaudhry Saima
Published: October 2016

Purpose

To examine internal medicine (IM) residency program directors’ (PDs’) perspectives on the Core Entrustable Professional Activities for Entering Residency (Core EPAs)—introduced into undergraduate medical education to further competency-based assessment—and on communicating competency-based information during transitions.

Method

A spring 2015 Association of Program Directors in Internal Medicine survey asked PDs of U.S. IM residency programs for their perspectives on which Core EPAs new interns must or should possess on day 1, which are most essential, and which have the largest gap between expected and observed performance. Their views and preferences were also requested regarding communicating competency-based information at transitions from medical school to residency and residency to fellowship/employment.

Results

The response rate was 57% (204/361 programs). The majority of PDs felt new interns must/should possess 12 of the 13 Core EPAs. PDs’ rankings of Core EPAs by relative importance were more varied than their rankings by the largest gaps in performance. Although preferred timing varied, most PDs (82%) considered it important for medical schools to communicate Core EPA-based information to PDs; nearly three-quarters (71%) would prefer a checklist format. Many (60%) would be willing to provide competency-based evaluations to fellowship directors/employers. Most (> 80%) agreed that there should be a bidirectional communication mechanism for programs/employers to provide feedback on competency assessments.

Conclusions

The gaps identified in Core EPA performance may help guide medical schools’ curricular and assessment tool design. Sharing competency-based information at transitions along the medical education continuum could help ensure production of competent, practice-ready physicians.
From Communication Skills to Skillful Communication: A Longitudinal Integrated Curriculum for Critical Care Medicine Fellows
Authors: Roze des Ordons Amanda L. , Doig Christopher J. , Couillard Philippe , Lord Jason
Published: October 2016

Problem

Communication with patients and families in critical care medicine (CCM) can be complex and challenging. A longitudinal curricular model integrating multiple techniques within classroom and clinical milieus may facilitate skillful communication across diverse settings.

Approach

In 2014–2015, the authors developed and implemented a curriculum for CCM fellows at the Cumming School of Medicine, University of Calgary, to promote the longitudinal development of skillful communication. A departmental needs assessment informed curriculum development. Five 4-hour classroom sessions were developed: basic communication principles, family meetings about goals and transitions of care, discussing patient safety incidents, addressing conflict, and offering organ donation. Teaching methods—including instructor-led presentations incorporating a consistent framework for approaching challenging conversations, simulation and clinical practice, and feedback from peers, trained facilitators, family members, and clinicians—supported integration of skills into the clinical setting and longitudinal development of skillful communication. Seven fellows participated during the first year of the curriculum.

Outcomes

CCM fellows engaged enthusiastically in the program, commented that the framework provided was helpful, and highly valued the opportunity to practice challenging communication scenarios, learn from observing their peers, and receive immediate feedback.

Next Steps

More detailed accounts of fellows’, patients’, and family members’ experiences will be obtained to guide curricular development. The curriculum will be expanded to involve other members of the multidisciplinary intensive care unit team, and faculty education initiatives will be offered to enhance the quality of the feedback provided. The impact of the curriculum on initial skill development, retention, and progression will be assessed.
Acquired Exchange Protein Directly Activated by Cyclic Adenosine Monophosphate Activity Induced by p38 Mitogen-activated Protein Kinase in Primary Afferent Neurons Contributes to Sustaining Postincisional Nociception
Authors: Matsuda Megumi , Oh-hashi Kentaro , Yokota Isao , Sawa Teiji , Amaya Fumimasa
Published: October 2016

Background

The molecular mechanisms responsible for sustained pain after tissue injury are largely unknown. The aim of this study was to clarify the role of exchange protein directly activated by cyclic adenosine monophosphate (EPAC) in sustained postincisional nociception, using tissue injury-induced nociceptor priming, and involvement of p38 mitogen-activated protein kinase (p38MAPK) in EPAC-mediated nociceptor priming.

Methods

Plantar incisions were made in the hind paws of Sprague–Dawley rats (n = 144). Nociceptor priming was confirmed by behavior testing followed by prostaglandin E2 injection 14 to 21 days after the incision. ESI-09, a selective EPAC inhibitor, was administered to assess its effects on nociceptor priming. Expression of two isoforms of EPAC (EPAC1/EPAC2) in dorsal root ganglions from naive rats and those 14 days after the incision was detected by immunohistochemistry and Western blotting. Separately, FR167653, a selective p38MAPK inhibitor, was administered to assess its effect on EPAC1/EPAC2 expression and the development of nociceptor priming.

Results

Prostaglandin E2 injection 14 to 21 days after the plantar incision induced persistent mechanical hyperalgesia for 7 days. EPAC1/EPAC2 expression in dorsal root ganglion neurons was trivial in naive rats (7.7 ± 4.8% for EPAC1; 6.3 ± 4.1% for EPAC2) but markedly increased 14 days after the incision (21.0 ± 9.4% and 20.1 ± 3.8%, respectively). ESI-09 treatment inhibited prostaglandin E2-induced persistent mechanical hypersensitivity but had no effect on incision-induced acute nociceptive hypersensitivity. Treatment with FR167653 before the incision inhibited the development of nociceptor priming and incision-induced EPAC1/EPAC2 expression (8.5 ± 5.4% and 7.6 ± 3.3%, respectively).

Conclusions

Transient inflammatory stimulation causes long-lasting nociceptive hypersensitivity via nociceptor priming during the subacute period after incision. Acquired EPAC activity by p38MAPK in the dorsal root ganglion neurons is a key for this event.
Intra-fetal Compared With Intra-amniotic Digoxin Before Dilation and Evacuation
Authors: White Katharine O'Connell , Nucatola Deborah L. , Westhoff Carolyn
Published: October 2016

OBJECTIVE:

To compare the effectiveness of 1.0 mg intra-fetal or intra-amniotic digoxin to achieve fetal asystole before second-trimester surgical pregnancy termination.

METHODS:

In a randomized trial, women received 1.0 mg transabdominal intra-fetal or intra-amniotic digoxin on the day of laminaria placement before dilation and evacuation between 20 and 24 weeks of gestation. The primary outcome was incidence of fetal asystole, documented immediately before dilation and evacuation. We planned to analyze the primary outcome by original group assignment as well as by as-treated and per-protocol populations. A sample size of 270 was needed to detect an 8% difference in failure rates between groups. Prespecified secondary outcomes included the incidence of adverse events, side effects, and procedural differences.

RESULTS:

Between January 2012 and January 2013, we screened 381 women and randomized 270 women to receive intra-fetal (n=136) or intra-amniotic (n=134) digoxin. Characteristics were similar across groups; the mean gestational age was 21.6 weeks (standard deviation 1.2). The proportion of fetal asystole was higher in the intra-fetal group (128/135 [94.8%]) than the intra-amniotic group (107/130, 82.3%; relative risk of failure to achieve asystole 3.41, 95% confidence interval 1.52–7.68). Results were similar in the as-treated and per-protocol populations. There were no significant differences in adverse events or side effects and no differences in injection duration, operative time, or estimated blood loss.

CONCLUSION:

Administration of intra-fetal injection of digoxin led to a higher proportion of participants achieving fetal asystole within 24 hours than intra-amniotic injection.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, https://clinicaltrials.gov, NCT01047748.
Pregnancy Outcomes in Women With a History of Previable, Preterm Prelabor Rupture of Membranes
Authors: Monson Martha A. , Gibbons Karen J. , Esplin M. Sean , Varner Michael W. , Manuck Tracy A.
Published: October 2016

OBJECTIVE:

To characterize subsequent pregnancy outcomes among women with a history of previable, preterm prelabor rupture of membranes (PROM) and assess factors associated with recurrent preterm birth.

METHODS:

This was a retrospective cohort study of women cared for with a history of one or more singleton pregnancy complicated by preterm PROM at less than 24 weeks of gestation between 2002 and 2013 who were cared for in two tertiary care health systems by a single group of maternal-fetal medicine specialists. Women were identified using International Classification of Diseases, 9th Revision codes and obstetric databases. Those with iatrogenic preterm PROM and those whose index preterm PROM at less than 24 weeks of gestation was preceded by advanced cervical dilation were excluded. All women with one or more pregnancies reaching the second trimester after an index previable, preterm PROM pregnancy were included. The primary outcome was recurrent preterm birth at less than 37 weeks of gestation. Data were analyzed by χ2, Fisher exact,ttest, Wilcoxon rank-sum, and logistic regression.

RESULTS:

Two hundred ninety-four women had one or more pregnancies complicated by previable, preterm PROM. One hundred eight of 294 (37%) had one or more subsequent pregnancies in our health care systems and 50 of 108 (46%) had two or more. In the pregnancy immediately after the index delivery, the risk of prematurity was high: 50 (46%) delivered at less than 37 weeks of gestation, 31 (30%) at less than 34 weeks of gestation, 25 (23%) at less than 28 weeks of gestation, and 18 (17%) before 24 weeks of gestation. Fewer than half (n=49 [45%]) of women received preterm birth prophylaxis (progesterone or cerclage) in a subsequent pregnancy; rates of recurrent preterm birth were similar among women who received preterm birth prophylaxis compared with those who did not. In regression models, the only factor significantly associated with recurrent preterm birth at less than 37 weeks of gestation was a history of preterm birth preceding previable, preterm PROM delivery (adjusted odds ratio 3.23, 95% confidence interval 1.32–7.93).

CONCLUSION:

Patients with a history of previable, preterm PROM are at high risk of recurrent preterm birth.
Laparoscopically Confirmed Endometriosis and Breast Cancer in the Nurses' Health Study II
Authors: Farland Leslie V. , Tamimi Rulla M. , Eliassen A. Heather , Spiegelman Donna , Hankinson Susan E. , Chen Wendy Y. , Missmer Stacey A.
Published: October 2016

OBJECTIVE:

To investigate the association between laparoscopically confirmed endometriosis and the risk of breast cancer. Previous research on endometriosis and breast cancer has reported mixed results.

METHODS:

Our prospective cohort study included 116,430 women from the Nurses' Health Study II cohort followed from 1989 until 2013. Our primary analysis investigated the association between self-reported laparoscopically confirmed endometriosis and the risk of breast cancer. Breast cancer diagnosis was verified through medical records. Multivariable adjusted Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Breast cancer was further classified by menopausal status at the time of diagnosis and tumor hormone receptor status verified through tissue microarrays when available and medical records.

RESULTS:

At baseline, 5,389 (5%) women reported laparoscopically confirmed endometriosis. Over 24 years of follow-up, 4,979 (3%) incident breast cancer cases were diagnosed. Women with endometriosis were not at higher risk for overall (adjusted HR 0.96, 95% CI 0.88–1.06), premenopausal (adjusted HR 1.05, 95% CI 0.89–1.23), or postmenopausal breast cancer (adjusted HR 0.93, 95% CI 0.80–1.07). However, associations varied by tumor hormone receptor status (P value, test for heterogeneity: .001), although women with endometriosis were not at increased risk of estrogen- and progesterone receptor-positive (ER+/PR+) tumors (adjusted HR 1.00, 95% CI 0.87–1.14) or ER− and PR− tumors (adjusted HR 0.90, 95% CI 0.67–1.21). Women with endometriosis reported 2.87 ER+/PR− breast cancer cases per 10,000 person-years compared with women without endometriosis (1.32/10,000 person-years), which resulted in nearly a twofold increased risk of ER+/PR− breast cancers (adjusted HR 1.90, 95% CI 1.44–2.50).

CONCLUSION:

Endometriosis was not found to be associated with overall risk of breast cancer in this study; however, endometriosis was significantly associated with an increased risk of ER+/PR− breast tumors, which should be interpreted cautiously.
Identifying Patients With Vesicovaginal Fistula at High Risk of Urinary Incontinence After Surgery
Authors: Bengtson Angela M. , Kopp Dawn , Tang Jennifer H. , Chipungu Ennet , Moyo Margaret , Wilkinson Jeffrey
Published: October 2016

OBJECTIVE:

To develop a risk score to identify women with vesicovaginal fistula at high risk of residual urinary incontinence after surgical repair.

METHODS:

We conducted a prospective cohort study among 401 women undergoing their first vesicovaginal fistula repair at a referral fistula repair center in Lilongwe, Malawi, between September 2011 and December 2014, who returned for follow-up within 120 days of surgery. We used logistic regression to develop a risk score to identify women with a high likelihood of residual urinary incontinence, defined as incontinence grade 2–5 within 120 days of vesicovaginal fistula repair, based on preoperative clinical and demographic characteristics (age, number of years with fistula, human immunodeficiency virus status, body mass index, previous repair surgery at an outside facility, revised Goh classification, Goh vesicovaginal fistula size, circumferential fistula, vaginal scaring, bladder size, and urethral length). The sensitivity, specificity, and positive and negative predictive values of the risk score at each cut point were assessed.

RESULTS:

Overall, 11 (3%) women had unsuccessful fistula closure. Of those with successful fistula closure (n=372), 85 (23%) experienced residual incontinence. A risk score cut point of 20 had sensitivity of 82% (95% confidence interval [CI] 72–89%) and specificity 63% (95% CI 57–69%) to potentially identify women with residual incontinence. In our population, the positive predictive value for a risk score cut point of 20 or higher was 43% (95% CI 36–51%) and the negative predictive value was 91% (95% CI 86–94%). Forty-eight percent of our study population had a risk score 20 or greater and, therefore, would have been identified for further intervention.

CONCLUSION:

A risk score of 20 or higher was associated with an increased likelihood of residual incontinence with satisfactory sensitivity and specificity. If validated in alternative settings, the risk score could be used to refer women with a high likelihood of postoperative incontinence to more experienced surgeons.
T-Cell Therapy Enabling Adenoviruses Coding for IL2 and TNFα Induce Systemic Immunomodulation in Mice With Spontaneous Melanoma
Authors: Tähtinen Siri , Blattner Carolin , Vähä-Koskela Markus , Saha Dipongkor , Siurala Mikko , Parviainen Suvi , Utikal Jochen , Kanerva Anna , Umansky Viktor , Hemminki Akseli
Published: October 2016

The immunosuppressive microenvironment of solid tumors renders adoptively transferred T cells hypofunctional. However, adenoviral delivery of immunostimulatory cytokines IL2 and TNFα can significantly improve the efficacy of adoptive T-cell therapy. Using ret transgenic mice that spontaneously develop skin malignant melanoma, we analyzed the mechanism of action of adenoviruses coding for IL2 and TNFα in combination with adoptive transfer of TCR-transgenic TRP-2-specific T cells. Following T-cell therapy and intratumoral virus injection, a significant increase in antigen-experienced, tumor-reactive PD-1+ CD8+ T cells was seen in both cutaneous lesions and in metastatic lymph nodes. A reverse correlation between tumor weight and the number of tumor-reactive PD-1+ tumor-infiltrating lymphocytes (TILs) was observed, suggesting that these T cells could target and kill tumor cells. It is interesting to note that, local expression of cytokines did not affect intratumoral levels of T-regulatory cells (Tregs), which had previously been associated with systemic IL2 therapy. Instead, Ad5-IL2 induced upregulation of IL2 receptor α-chain (CD25) on conventional CD4+CD25+Foxp3− cells, indicating that these CD4+ T cells may contribute to CD8+ T-cell activation and/or homing. Signs of therapy-induced resistance were also observed as the expression of PD-L1 on tumor-infiltrating granulocytic myeloid-derived suppressor cells was upregulated as a reaction to PD-1+ TILs. Finally, beneficial ratios between tumor-reactive PD-1+ CD8+ TILs and immunosuppressive cell subsets (Tregs and nitric oxide–producing myeloid-derived suppressor cells) were observed in primary and secondary tumor sites, indicating that local delivery of IL2 and TNFα coding adenoviruses can systemically modify the cellular composition of the tumor microenvironment in favor of adoptively transferred T cells.
Sleep-disordered breathing and the menopausal transition among participants in the Sleep in Midlife Women Study
Authors: Mirer Anna G. , Young Terry , Palta Mari , Benca Ruth M. , Rasmuson Amanda , Peppard Paul E.
Published: October 2016

Objective:

Menopause is widely believed to be an established cause of sleep disorders, but evidence for this theory is inconclusive. Attributing any sleep problem to normal processes of menopause may lead to underdiagnosis of treatable sleep disorders in midlife women. This study uses detailed longitudinal data on sleep and menopausal health from participants in the Sleep in Midlife Women Study to investigate whether risk and severity of sleep-disordered breathing increase with progression through menopause, accounting for changes in age and body habitus.

Methods:

A total of 219 women aged 38 to 62 years were recruited from participants in the Wisconsin Sleep Cohort Study. Menopause status was determined from daily diaries in which participants reported menstrual flow, hot flashes, and use of hormonal medications. Each participant underwent in-home polysomnography studies every 6 months, to measure the apnea-hypopnea index (AHI) (N = 1,667 studies). Linear models with empirical standard errors were fit for logarithm of AHI on menopause status and years in menopause, adjusting for age, body mass index, waist girth, and neck girth.

Results:

Compared with women in premenopause, AHI was 21% higher among participants in perimenopause (95% CI, −4 to 54), 31% higher among participants in postmenopause (95% CI, 2-68), and 41% higher among participants whose menopausal stage could not be distinguished between peri- and postmenopause (95% CI, 8-82). Among women who had begun perimenopause, each additional year in menopause was associated with 4% greater AHI (95% CI, 2-6).

Conclusions:

Progression through menopause is associated with greater sleep-disordered breathing severity. This association is independent of aging and changes in body habitus.
Efficacy of Tribulus terrestris for the treatment of hypoactive sexual desire disorder in postmenopausal women: a randomized, double-blinded, placebo-controlled trial
Authors: de Souza Karla Zanolla Dias , Vale Fabiene Bernardes Castro , Geber Selmo
Published: October 2016

Objective:

The objective of this study was to evaluate the efficacy of Tribulus terrestris for the treatment of hypoactive sexual desire disorder in postmenopausal women and evaluate its effect on the serum levels of testosterone.

Methods:

We performed a prospective randomized, double-blinded, placebo-controlled study, during 18 months. A total of 45 healthy sexually active postmenopausal women reporting diminished libido were selected to participate in the study and were randomly assigned to receive 750 mg/d of T terrestris or placebo for 120 days. Randomization was performed using sealed envelopes. All participants answered the Female Sexual Function Index and the Sexual Quotient—female version questionnaires and had their serum levels of prolactin, thyroid-stimulating hormone, total testosterone, and sex hormone-binding globulin measured.

Results:

A total of 36 participants completed the study, because 3 from each group were excluded due to side effects and 3 dropped out due to personal reasons. FSFI questionnaire results demonstrated an improvement in all domains in both groups (P < 0.05) except for lubrication which was improved only in the study group. QS-F results showed a significant improvement in the domains of desire (P < 0.01), arousal/lubrication (P = 0.02), pain (P = 0.02), and anorgasmia (P < 0.01) in women who used T terrestris, whereas no improvement was observed in the placebo group (P > 0.05). Moreover, free and bioavailable testosterone levels showed a significant increase in the T terrestris group (P < 0.05).

Conclusions:

Tribulus terrestris might be a safe alternative for the treatment of hypoactive sexual desire disorder in postmenopausal women, because it was effective in reducing symptoms with few side effects. Its probable mechanism of action involves an increase in the serum levels of free and bioavailable testosterone.
Surgical Treatment of Tubular Breast Type II
Authors: Galych Sergey P. , Dabizha Oleksii Y. , Kostenko Alona A. , Gomolyako Irina V. , Samko Kristina A. , Borovyk Denys V.
Published: October 2016

Background:

Tubular breasts are caused by connective tissue malformation and occur in puberty. The main clinical characteristics of the tubular breast are breast asymmetry, dense fibrous ring around the areola, hernia bulging of the areola, megaareola, and hypoplasia of quadrants of the breast. Pathology causes great psychological discomfort to patients.

Methods:

This study included 17 patients, aged 18 to 34 years, with tubular breast type II who had bilateral pathology and were treated from 2013 to 2016. They had surgical treatment by method of the clinic. Correction technique consisted of mobilization of the central part of the gland and formation of a glandular flap with vertical and horizontal scorings, which looks like a “chessboard,” that was sufficient to cover the lower pole of the implant. The flap was fixed to the submammary folds with stitches that prevented its reduction and accented a new submammary fold. To underscore the importance of the method and to study the structural features of the vascular bed of tubular breast tissue, a morphological study was conducted.

Results:

Mean follow-up time was 25 months (range between 13 and 37 mo). The proposed technique achieved good results. Complications (hematoma, circumareolar scarring, and “double-bubble” deformity) were identified in 4 patients.

Conclusions:

Our morphological study confirmed that tubular breast tissue has increased vascularity due to the vessels with characteristic minor malformation and due to the high restorative potential of the vascular bed. Therefore, an extended glandular flap could be freely mobilized without damaging its blood supply; thus, the flap in most cases covered the implant completely and good aesthetic results were achieved.
Primary Gliosarcoma of the Optic Nerve: A Unique Adult Optic Pathway Glioma
Authors: Cimino Patrick J. , Sychev Yevgeniy V. , Gonzalez-Cuyar Luis F. , Mudumbai Raghu C. , Keene C. Dirk
Published: October 2016

A 90-year-old woman presented with 1-year history of right-sided progressive proptosis, neovascular glaucoma, blindness, and worsening ocular pain. No funduscopic examination was possible because of a corneal opacity. Head CT scan without contrast demonstrated a heterogeneous 4.1 cm (anterior–posterior) by 1.7 cm (transverse) cylindrical mass arising in the right optic nerve and extending from the retrobulbar globe to the optic canal. She underwent palliative enucleation with subtotal resection of the orbital optic nerve and tumor. Pathological examination showed effacement of the optic nerve by an infiltrative high-grade glial neoplasm with biphasic sarcomeric differentiation. Invasion into the uvea and retina was present. The neoplasm was negative for melan-A, HMB45, tyrosinase, synaptophysin, smooth muscle actin, and epithelial membrane antigen. The glioma had strongly intense, but patchy immunopositivity for glial fibrillary acidic protein. Multiple foci of neoplastic cells had pericellular reticulin staining. The overall features were diagnostic of a gliosarcoma (World Health Organization grade IV) of the optic nerve. Postoperative MRI demonstrated postsurgical changes and residual gliosarcoma with extension into the optic chiasm. The patient died 2 and a half months after her enucleation surgery at her nursing home. Autopsy was unavailable due to the caregiver wishes, making a definitive cause of death unknown. Gliosarcoma is a rare variant of glioblastoma, and this is the first documented case presenting as a primary neoplasm of the optic nerve.
Duloxetine Augmentation in Resistant Obsessive-Compulsive Disorder
Authors: Mowla Arash , Boostani Sanaz , Dastgheib Seyed Ali
Published: October 2016

Introduction

The aim of this study is to evaluate the efficacy of duloxetine augmentation in treatment of resistant obsessive-compulsive disorder (OCD).

Methods

This augmentation trial was designed as an 8-week randomized controlled, double-blind study. Forty-six patients experiencing OCD who had failed to respond to at least 12 weeks of treatment with a selective serotonin reuptake inhibitor (fluoxetine, citalopram, or fluvoxamine) were randomly allocated to receive duloxetine or sertraline plus their current anti-OCD treatment. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was the primary outcome measure. Treatment response was defined as 25% or more decrease in scores of Y-BOCS. The mean dosage of duloxetine was 44.4 mg/d (range, 20–60 mg/d), and the mean dosage of sertraline was 123.8 mg/d (range, 50–200 mg/d).

Results

Forty-six patients (24 of 30 in duloxetine group and 22 of 27 in sertraline group) completed the trial. Both groups showed improvement during the 8-week study period (mean Y-BOCS total score at week 8 as compared with baseline: P < 0.001 & P < 0.001) without significant difference (P = 0.861). Those receiving duloxetine plus their initial medications experienced a mean decrease of 33.0% in Y-BOCS score, and the patients with sertraline added to their initial medication experienced a mean decrease of 34.5% in Y-BOCS.

Discussion

Our double-blind controlled clinical trial showed duloxetine to be as effective as sertraline in reducing obsessive and compulsive symptoms in patients with resistant OCD. However, it needs to be noted that our study is preliminary, and larger double-blind placebo-controlled studies are necessary to confirm the results.
The Effect of Geometry on the Efficiency and Hemolysis of Centrifugal Implantable Blood Pumps
Authors: Mozafari Sahand , Rezaienia Mohammad A. , Paul Gordon M. , Rothman Martin T. , Wen Pihua , Korakianitis Theodosios
Published: October 2016

The application of centrifugal pumps as heart assist devices imposes design limitations on the impeller geometry. Geometry and operating parameters will affect the performance and the hemocompatibility of the device. Among all the parameters affecting the hemocompatibility, pressure, rotational speed, blade numbers, angle, and width have significant impact on the blood trauma. These parameters directly (pressure, speed) and indirectly (geometry) affect the efficiency of the pump as well. This study describes the experimental investigation on geometric parameters and their effect on the performance of small centrifugal pumps suitable for Mechanical Circulatory Support (MCS) devices. Experimental and numerical techniques were implemented to analyze the performance of 15 centrifugal impellers with different characteristics. The effect of each parameter on the pump performance and hemolysis was studied by calculating the normalized index of hemolysis (NIH) and the shear stress induced in each pump. The results show five and six blades, 15–35° outlet angle, and the lowest outlet width that meets the required pressure rise are optimum values for an efficient hemocompatible pump.
Outcomes of Extracorporeal Life Support During Surgery for the Critical Airway Stenosis
Authors: Kim Seon Hee , Song Seunghwan , Kim Yeong Dae , I Hoseok , Cho Jeong Su , Ahn Hyo Yeong , Lee Jonggeun , Kim Do Hyung , Son Bong Soo
Published: October 2016

Anesthetic management of critical airway stenosis is often very challenging. Extracorporeal membrane oxygenation (ECMO) may provide adequate respiratory support when conventional approaches fail. We report our experience of ECMO support for critical airway surgery. Between April 2012 and March 2015, nine patients underwent ECMO-supported airway operation. The reason for surgery was tracheal stenosis in nine patients, and tracheomalacia, tracheal tumor, and external tracheal compression by mediastinal mass in one patient each. Resection and end-to-end anastomosis was performed in four patients; the remainder underwent diverse procedures, including tracheoplasty, tracheal ballooning, tracheostomy, and debulking of mediastinal mass. Extracorporeal membrane oxygenation support was sufficient for gas exchange during surgery and six patients were successfully weaned off intraoperatively. The median time on ECMO was 2.42 hours (range: 14.43−216 hours). No ECMO-related complications occurred. The median intensive care unit stay, median hospital stay, and mean follow-up period were 2 days (range: 1−61 days), 33 days (range: 9−303 days), and 17.1 ± 10.8 months, respectively. The rate of freedom from reintervention was 71.4%; the mean survival rates over 1 and 2 years were 76.2% and 63.5%, respectively. Our experience indicates that ECMO is a feasible and safe method for critical airway surgery.
Acceptability and Effectiveness of Assisted Human Immunodeficiency Virus Partner Services in Mozambique: Results From a Pilot Program in a Public, Urban Clinic
Authors: Myers R. Serene , Feldacker Caryl , Cesár Freide , Paredes Zulmira , Augusto Gerito , Muluana Chadreque , Citao Sinesia , Mboa-Ferrao Catarina , Karajeanes Esmeralda , Golden Matthew R.
Published: October 2016

Background

Assisted partner services (APS) involves offering persons with human immunodeficiency virus (HIV) assistance notifying and testing their sex partners. Assisted partner services is rarely available in sub-Saharan Africa. We instituted a pilot APS program in Maputo, Mozambique.

Methods

Between June and September 2014, community health workers (CHWs) offered APS to persons with newly diagnosed HIV (index patients [IPs]). Community health workers interviewed IPs at baseline, 4 and 8 weeks. At baseline, CHWs counseled IPs to notify partners and encourage their HIV testing, but did not notify partners directly. At 4 weeks, CHWs notified partners directly. We compared 4- and 8-week outcomes to estimate the impact of APS on partner notification, HIV testing and HIV case finding.

Results

Community health workers offered 223 IPs APS, of whom 220 (99%) accepted; CHWs collected complete follow-up data on 206 persons; 79% were women, 74% were married, and 50% named >1 sex partner. Index patients named 262 HIV-negative partners at baseline. At 4 weeks, before APS, IPs had notified 193 partners (74%), but only 82 (31%) had HIV tested; 43 (13%) tested HIV positive. Assisted partner services resulted in the notification of 22 additional partners, testing of 83 partners and 43 new HIV diagnoses. In relative terms, APS increased partner notification, testing, and HIV case finding by 13%, 101%, and 125%. Seventy-two (35%) of 206 IPs were in ongoing HIV serodiscordant partnerships. Only 2.5 IPs needed to receive APS to identify a previously undiagnosed HIV-infected partner or an ongoing HIV serodiscordant partnership. Two (1%) IPs reported APS-related adverse events.

Conclusions

Assisted partner services is acceptable to Mozambicans newly diagnosed with HIV, identifies large numbers of serodiscordant partnerships and persons with undiagnosed HIV, and poses a low risk of adverse events.