bluuebunny/crossref_metadata_2025 huggingface dataset:
Amyloid fibrils from the N-terminal prion protein fragment are infectious
Authors: Choi Jin-Kyu , Cali Ignazio , Surewicz Krystyna , Kong Qingzhong , Gambetti Pierluigi , Surewicz Witold K.
Published: November 2016

Significance

Prion diseases are a group of transmissible neurodegenerative disorders. The protein-only hypothesis asserts that transmission of these diseases does not require nucleic acids and that a misfolded, aggregated form of the prion protein represents a self-perpetuating infectious agent. Even though this model is supported by a large body of experimental data, there is a dispute regarding the role of specific cofactors in prion infectivity as well as the structural basis of prion formation. In this work, we show that structurally well-characterized amyloid fibrils generated from bacterially expressed prion protein fragment 23-144 cause prion disease in transgenic and wild-type mice, demonstrating that cofactors are not obligatory for prion formation and providing insight into the structural basis of prion propagation.
Heparanase is required for activation and function of macrophages
Authors: Gutter-Kapon Lilach , Alishekevitz Dror , Shaked Yuval , Li Jin-Ping , Aronheim Ami , Ilan Neta , Vlodavsky Israel
Published: November 2016

Significance

The tumor microenvironment is now considered to play a major role in cancer growth and metastasis. Heparanase is the only enzyme in mammals capable of cleaving heparan sulfate, an activity that is highly implicated in tumor growth, metastasis, and inflammation. Here we provide evidence that heparanase is critically required for the activation and function of macrophages, an important constituent of the tumor microenvironment. Mechanistically, we describe a linear cascade by which heparanase activates Erk, p38, and JNK signaling in macrophages, leading to increased c-Fos levels and induction of cytokine expression in a manner that apparently does not require heparanase enzymatic activity. These results identify heparanase as a key mediator of macrophage activation and function in tumorigenesis and cross-talk with the tumor microenvironment.
Two familial ALS proteins function in prevention/repair of transcription-associated DNA damage
Authors: Hill Sarah J. , Mordes Daniel A. , Cameron Lisa A. , Neuberg Donna S. , Landini Serena , Eggan Kevin , Livingston David M.
Published: November 2016

Significance

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which progressive dysfunction of motor neurons leads to paralysis and death. There is currently no known pathway of disease pathogenesis. However, many genes with varying functions have been linked to familial and sporadic forms of ALS suggesting multiple possible disease mechanisms. One set of gene products, including ALS-linked FUS and TDP43, functions in transcription and RNA processing. We find that defects in transcription due to loss of function of FUS or TDP43 can lead to DNA damage, including in primary human neuronal cells, and hypothesize that dysfunction in their RNA processing roles leads to DNA damage in motor neurons that, if incompletely resolved, could contribute to motor neuron death and ALS.
Mg
2+
regulates transcription of
mgtA
in
Salmonella
Typhimurium via translation of proline codons during synthesis of the MgtL peptide
Authors: Gall Aaron R. , Datsenko Kirill A. , Figueroa-Bossi Nara , Bossi Lionello , Masuda Isao , Hou Ya-Ming , Csonka Laszlo N.
Published: November 2016

Significance

Mg
2+
is an important signal for the regulation of virulence and thermotolerance in
Salmonella enterica
. Transcription of the
mgtA
gene, which encodes a transporter for Mg
2+
, is highly induced by Mg
2+
limitation. The 5′ leader of the
mgtA
mRNA encodes
mgtL
, a 17-codon, proline-rich open reading frame, whose translation controls the transcription of
mgtA
: efficient translation of
mgtL
results in termination of transcription upstream of the
mgtA
protein-coding region, whereas slow or incomplete translation of
mgtL
antagonizes this termination. We show that the proline codons in
mgtL
present an impediment to translation at low but not high Mg
2+
concentrations, and thereby, we provide a model for how Mg
2+
is coupled to the regulation of
mgtA
transcription.
Arabidopsis thaliana
GH3.5 acyl acid amido synthetase mediates metabolic crosstalk in auxin and salicylic acid homeostasis
Authors: Westfall Corey S. , Sherp Ashley M. , Zubieta Chloe , Alvarez Sophie , Schraft Evelyn , Marcellin Romain , Ramirez Loren , Jez Joseph M.
Published: November 2016

Significance

Plants require precise control over growth regulators during development and in their responses to biotic and abiotic stresses. One strategy for modulating levels of bioactive phytohormones is to conjugate these molecules to amino acids using acyl acid amido synthetases of the Gretchen Hagen 3 (GH3) protein family. Typically, GH3 proteins modify one type of phytohormone. Structural studies, along with in vitro and
in planta
biochemical analyses, reveal that the GH3.5 protein from the model plant
Arabidopsis thaliana
conjugates multiple molecules from various phytohormone pathways. This activity mediates crosstalk between auxin developmental and pathogen response pathways.
Standing genetic variation in a tissue-specific enhancer underlies selfing-syndrome evolution in
Capsella
Authors: Sicard Adrien , Kappel Christian , Lee Young Wha , Woźniak Natalia Joanna , Marona Cindy , Stinchcombe John R. , Wright Stephen I. , Lenhard Michael
Published: November 2016

Significance

Flower size can change rapidly in evolution; in particular, the frequent transition from animal-mediated out-crossing to self-pollination is often associated with a dramatic, yet rapid and specific, reduction in flower size. Here we demonstrate that the small petals of the selfing red Shepherd’s Purse (
Capsella rubella
) are because of a specific reduction in the activity of a general growth factor in petals. Different-strength versions of this growth gene were already present in the ancestral out-breeding population, and capture of a weak version from this pool can explain the rapid reduction of petal size in
C. rubella
. The additive effects of segregating small-effect mutations with low pleiotropy allowed specific modulation of petal size to enable adaptation to a new mode of reproduction.
Phylogenetic approach to the evolution of color term systems
Authors: Haynie Hannah J. , Bowern Claire
Published: November 2016

Significance

A major question in the study of both anthropology and cognitive science is why the world’s languages show recurrent similarities in color naming. Here we examine this inherently evolutionary question–the evolution of color systems in language–using phylogenetic methods. We track the evolution of color terms across a large language tree in order to trace the history of the systems. We provide further validation of phylogenetic approaches to culture, and provide an explicit history of color terms across a large language sample, the Pama-Nyungan languages of Australia. Our work is of relevance to anthropologists, psychologists, and linguists.
Multiple mechanisms contribute to double-strand break repair at rereplication forks in
Drosophila
follicle cells
Authors: Alexander Jessica L. , Beagan Kelly , Orr-Weaver Terry L. , McVey Mitch
Published: November 2016

Significance

Repeated activation of the same DNA replication origin, termed “rereplication,” is one developmental strategy to increase gene copies for high levels of protein production. However, it also generates DNA double-strand breaks and can lead to genome instability. We present evidence for competition between different pathways of double-strand break repair during rereplication in
Drosophila
follicle cells. Loss of DNA polymerase θ (Pol θ), which operates in an error-prone repair mechanism named “microhomology-mediated end joining,” impedes the progress of rereplication forks at a specific genomic locus. Pol θ-mediated repair is also used in the absence of classical end joining, but only at certain regions. Our findings suggest that genomic context has a major impact on genomic stability and mutagenesis in rereplicating DNA.
When imperfections are perfect
Authors: D'Alessandro Roberta , van Oostendorp Marc
Published: November 2016

Vocatives are often considered as exceptions to the regularity of language, and therefore often put “outside” of grammar, and pertaining instead to speech. In this paper, we wish to show that this conceptualization of vocatives is wrong: not only are they perfectly regular, but they give us important insights on the grammatical architecture of language. We will consider a case-study, namely central and southern Italian vocatives, which are obtained by truncation, to show that: 1. Deixis and reference are to be kept separate. 2. Speech-act related information is encoded in syntax, but on a different dimension than core argumental syntax. 3. This dimension is targeted by prosody. 4. There would be no other way that grammar could be built, given the inviolable constraint imposed by prosody because of the fact that it cannot apply without underlying phonological segmental material.
Why are distributive readings dispreferred?
Authors: Dobrovie-Sorin Carmen , Ellsiepen Emilia , Hemforth Barbara
Published: November 2016

The paper reports the results of four experiments that were meant to investigate the availability of distributive readings in three types of French sentences, which involved singular indefinite DPs in the object position but differed with respect to the syntax of the subject DP (def-plDP, groupDP,
most of
DP). Our results show a clear contrast between def-plDP and groupDP vs.
most of
DP: the collective reading is preferred with the former, and the distributive reading is preferred with the latter. We will propose complexity-based explanations, which attribute dispreferred readings to an increase in processing load.
Focus and the syntacticization of discourse
Authors: Poole Geoffrey
Published: November 2016

This paper examines two pairs of phenomena: Quantifier Fronting in Old Spanish and Modern Spanish (Mackenzie 2010; Leonetti and Escandell-Vidal 2009) and declarative verb-clitic orders in Old Spanish and ‘Conservative’ Asturian (Fontana 1993; Fernández Rubiera 2009). While the syntax of each construction does not change diachronically, the information-structure interpretation does. The medieval constructions both exhibit wide focus, but the modern counterparts exhibit verum focus. I argue that this change is the result of a ‘syntacticization of discourse’, in which the syntactic mechanism for left-peripheral displacement changes from a formal EPP feature to information-structure specific syntactic features (e.g., [+focus]) as a consequence of changes to the locus of EPP and Tense features (Biberauer and Roberts 2010; Poole 2014).
Intervention or phasal locality?
Authors: Rouveret Alain
Published: November 2016

The Minimalist Program claims that only two notions of locality are necessary: phasal locality and intervention locality (in the form of the Minimal Link Condition). This paper asks whether the unification of the two is possible or desirable. An argument against unification would consist in showing that a process A obeys one locality condition and doesn’t obey the other and that another process B does exactly the reverse. Two phenomena are considered, which fit this description – respectively interpretation (R-I) and clitic placement (CL-PL). Their contrasting behavior in the French faire-construction indicates that each one obeys a locality condition that the other does not: CL-PL obeys phasal locality, R-I some form of minimality. The theoretical implications of these findings for the theory of locality and the architecture of grammar are examined in the conclusion.
Variation and change in the Romance faire-par causative
Authors: Sheehan Michelle , Cyrino Sonia M. L.
Published: November 2016

This chapter considers the extent to which the faire-par causative (FP) is available in Italian, French, Catalan, and varieties of Spanish and Portuguese. While French and Italian (like some Spanish varieties) permit FP with an optional by-phrase, Catalan permits FP only where the by-phrase is supressed. Although some Spanish and Portuguese varieties display something superficially resembling the Catalan FP, closer consideration reveals the construction in question to have quite distinct properties. Taking Portuguese as a case study, we trace the diachronic development of FP, proposing that the obligatory suppression of the by-phrase combined with the possibility of ECM/inflected causative complements permitted reanalysis, leading to the loss of FP in some Portuguese (and Spanish) varieties.
Burkina Faso: from Thomas Sankara to popular resistance
Authors: Zeilig Leo
Published: November 2016

Arguably the résistance populaire across Burkina Faso in September 2015 against the coup led by members of the old regime was as significant as the uprising that toppled Blaise Compaoré in October 2014. This Briefing attempts to unpick the significance and extent of the popular resistance.
In-situ microscopy study of grain refinement in the simulated heat-affected zone of high-strength low-alloy steel by TiN particle
Authors: Wan X. , Zhou B. , Nune K. C. , Li Y. , Wu K. , Li G.
Published: November 2016

High-strength low-alloy steels subjected to high heat input welding are susceptible to failure due to low toughness caused by grain coarsening. The effect of TiN on grain refinement in the simulated heat-affected zone (HAZ) was investigated. Because of small amount of Ti addition, abundant dispersed nanoscale TiN precipitates were formed. The TiN precipitates tended to be stable at high temperature and effectively retarded the austenite grain growth by refining the grain size during thermal cycle. Furthermore, the TiN also covered on the surface of Al–Ti complex oxide with MnS and caused low interface energy with ferrite. The acicular ferrite grains nucleated on complex inclusion in austenite grains at intermediate temperature and induced the austenite grain transform to the fine-grained mixed microstructure of acicular ferrite and bainite. The crystallographic grain size became small in the simulated HAZ due to the effective pinning effect and acicular ferrite formation.
Hypoxia‐induced pulmonary hypertension in type 2 diabetic mice
Authors: Pan Minglin , Han Ying , Si Rui , Guo Rui , Desai Ankit , Makino Ayako
Published: November 2016

Hypoxia‐induced pulmonary hypertension (HPH) is a progressive disease that is mainly caused by chronic exposure to high altitude, chronic obstructive lung disease, and obstructive sleep apnea. The increased pulmonary vascular resistance and increased pulmonary arterial pressure result in increased right ventricular afterload, leading to right heart failure and increased morbidity. There are several clinical reports suggesting a link between PH and diabetes, insulin resistance, or obesity; however, it is unclear whether HPH is associated with diabetes as a progressive complication in diabetes. The major goal of this study is to examine the effect of diabetic “preconditioning” or priming effect on the progression of HPH and define the molecular mechanisms that explain the link between diabetes and HPH. Our data show that HPH is significantly enhanced in diabetic mice, while endothelium‐dependent relaxation in pulmonary arteries is significantly attenuated in chronically hypoxic diabetic mice (DH). In addition, we demonstrate that mouse pulmonary endothelial cells (MPECs) isolated from DH mice exhibit a significant increase in mitochondrial reactive oxygen species (ROS) concentration and decreased SOD2 protein expression. Finally, scavenging mitochondrial ROS by mitoTempol restores endothelium‐dependent relaxation in pulmonary arteries that is attenuated in DH mice. These data suggest that excessive mitochondrial ROS production in diabetic MPECs leads to the development of severe HPH in diabetic mice exposed to hypoxia.
Challenging the 4- to 5-minute Rule: From Perimortem Cesarean to Resuscitative Hysterotomy
Authors: Rose C.H. , Faksh A. , Traynor K.D. , Cabrera D. , Arendt K.W. , Brost B.C.
Published: November 2016

(Am J Obstet Gynecol 2015;213(5):653–656. 653.e1)

About 1/12,500 deliveries are complicated by antepartum maternal cardiac arrest, causative factors of which include hemorrhage, amniotic fluid embolism, heart failure, sepsis, anesthetic complications, and trauma. The maternal survival rate ranges from 17% to 59% and fetal survival rates from 61% to 80%. This article is a review of current practices for maternal cardiopulmonary arrest (MCPA) management and also proposes a maternofetal management strategy that differs from the current 4 to 5 minute rule for perimortem cesarean delivery (PMCD).
The Placenta is the Center of the Chronic Disease Universe
Authors: Thornburg K.L. , Marshall N.
Published: November 2016

(Am J Obstet Gynecol 2015;213(suppl):S14–S20)

This review article explores the potential role of the placenta in the development of chronic diseases later in life. It discusses studies reporting an inverse relationship between birthweight and chronic disease, leading to a better understanding of health and longevity in offspring. Researchers have long studied the mechanism by which compromised fetal development leads to the onset of certain diseases in adulthood. They refer to this as process as “programming.” Research has shown that there are links between early life development and the incidence of obesity, diabetes, and heart disease. One study by Barker and colleagues estimated that diabetes could be reduced by approximately 60% in a generation if children were born at the lowest risk birthweight and did not cross body mass index percentiles in childhood.
#37: Diagnosis and Management of Vasa Previa
Authors: Sinkey R.G. , Odibo A.O. , Dashe J.S.
Published: November 2016

(Am J Obstet Gynecol 2015;213(5):615–619)

Vasa previa is a condition that occurs in approximately 1 per 2500 deliveries when fetal blood vessels that are unprotected by the umbilical cord or placenta run through the amniotic membranes and pass across the cervix. Rupture of membranes causes these vessels to rupture, resulting in fetal hemorrhage, exsanguination, fetal asphyxia, or even death. Type I vasa previa occurs when a velamentous cord insertion between the umbilical cord and placenta is present, and fetal vessels that run freely within the amniotic membranes overlie the cervix. Type II vasa previa occurs when the placenta has a succenturiate lobe or is multilobed, and fetal vessels that connect the 2 placental lobes pass over or are near the cervix.
Conservative Management of Morbidly Adherent Placenta: Expert Review
Authors: Fox K.A. , Shamshirsaz A.A. , Carusi D. , Secord A.A. , Lee P. , Turan O.M. , Huls C. , Abuhamad A. , Simhan H. , Barton J. , Wright J. , Silver R. , Belfort M.A.
Published: November 2016

(Am J Obstet Gynecol 2015;213(6):755–760)

Morbidly adherent placenta (MAP) includes the spectrum of placenta accreta, increta, and percreta and is a cause of major morbidity and mortality in pregnant women. In the last century, the incidence of MAP has risen from approximately 1 in 20,000 live births in 1928 to 1 in 533 in 2002.
Tranexamic Acid for Preventing Postpartum Blood Loss After Cesarean Delivery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Simonazzi G. , Bisulli M. , Saccone G. , Moro E. , Marshall A. , Berghella V.
Published: November 2016

(Acta Obstet Gynecol Scand 2016;95:28–37)

The World Health Organization defines postpartum hemorrhage (PPH) as “blood loss from the birth canal in excess of 500 mL during the first 24 hours after delivery,” although currently there is a debate about what definition to use for PPH. PPH is responsible for about 25% of maternal deaths worldwide, and 12% of survivors will develop severe anemia. Although there are several published clinical trials of the use of tranexamic acid (TXA) in an obstetric setting, there is no consensus on its use or guidelines for management. The aim of this meta-analysis of randomized controlled trials (RCTs) was to evaluate the effectiveness of TXA in reducing blood loss when given before cesarean delivery (CD).
Maternal Deaths in Iceland Over 25 Years
Authors: Birgisdottir H. , Bjarnadottir R.I. , Kristjansdottir K. , Geirsson R.T.
Published: November 2016

(Acta Obstet Gynecol Scand 2016;95:74–78)

An account of the incidence, causes, and cofactors of maternal mortality in every nation would enable the minimization of such events. This study in Iceland gathered information on deaths of women in the fertile age group (15 to 49 y), linked this information with data from the birth and hospital discharge diagnostic registries, and performed additional searches to estimate maternal mortality over a period of 25 years.
Association Between Hypertensive Disorders of Pregnancy and Later Risk of Cardiomyopathy
Authors: Behrens Ida , Basit Saima , Lykke Jacob Alexander , Ranthe Mattis Flyvholm , Wohlfahrt Jan , Bundgaard Henning , Melbye Mads , Boyd Heather A.
Published: November 2016

(JAMA 2016;315(10):1026–1033)

Hypertensive disorders of pregnancy (HDP), including preeclampsia and gestational hypertension, are common, occurring in approximately 10% of parturients worldwide. Women with preeclampsia have been shown to be at increased risk for peripartum cardiomyopathy as well as cardiovascular disease later in life. It has not yet been determined if these women are also at greater risk for developing cardiomyopathy beyond the peripartum period. However, recent research has suggested women with preeclampsia may undergo some degree of cardiac remodeling that results in persistent cardiac dysfunction. The aim of this study was to investigate the association between HDP and cardiomyopathy after the peripartum period.
Maternal and Neonatal Outcomes of Pregnancy in Women With Chronic Hypertension: A Retrospective Analysis of a National Register
Authors: Broekhuijsen K. , Ravelli A.C. , Langenveld J. , van Pampus M.G. , van den Berg P.P. , Mol B.W. , Franssen M.T.
Published: November 2016

(Acta Obstet Gynecol Scand 2015;94(12):1337–1345)

Increased risk of adverse pregnancy outcomes (preeclampsia/eclampsia, placental abruption, preterm delivery, growth restriction, and maternal and perinatal mortality) is noted in pregnancies complicated by chronic hypertension. The objective of this study was to assess whether planned early delivery may prevent some of these adverse outcomes. To achieve this objective, maternal and neonatal outcomes of pregnancy in women with chronic hypertension, including gestational-age–specific outcomes were studied.
Intrapartum Epidural Fixation Methods: A Randomized Controlled Trial of 3 Different Epidural Catheter Securement Devices
Authors: Odor P.M. , Bampoe S. , Hayward J. , Chis Ster I. , Evans E.
Published: November 2016

(Anaesthesia. 2016;71:298–305)

When placing an epidural for labor analgesia, one goal is to minimize epidural catheter migration during labor and delivery. However, there is no consensus among obstetric anesthesiologists as to the best method to use for epidural catheter fixation. Techniques used vary from simple adhesive dressings to specifically designed fixation devices such as Epi-Fix, LockIt Plus, and Tegaderm. The primary objective of this current study was to determine which of the devices listed above would result in the least amount of epidural catheter migration.
Success Factors for Bakri Balloon Usage Secondary to Uterine Atony: A Retrospective, Multicentre Study
Authors: Vintejoux E. , Ulrich D. , Mousty E. , Masia F. , Marès P. , de Tayrac R. , Letouzey V.
Published: November 2016

(Aust N Z J Obstet Gynaecol. 2015;55(6):572–577)

Postpartum hemorrhage (PPH), defined as bleeding exceeding 500 mL within 24 hours after vaginal delivery or a reduction of hematocrit level by at least 10% between admission and the postpartum period, is a major cause of maternal mortality and morbidity. Conventional surgical procedures and invasive treatments pose complications as well as difficulties with regard to access, hence, noninvasive techniques such as intrauterine tamponade using various balloons and catheters have been recommended.
Risk Factors for Retained Placenta
Authors: Coviello E.M. , Grantz K.L. , Huang C.C. , Kelly T.E. , Landy H.J.
Published: November 2016

(Am J Obstet Gynecol. 2015;213:864.e1–e.11)

According to the World Health Organization, in developing countries, postpartum hemorrhage is the primary cause of maternal mortality, responsible for 25% of maternal fatalities. About 2% to 3% of vaginal deliveries are complicated by postpartum hemorrhage for which the treatment includes manual or operative placental extraction and this often results in increased risks of hemorrhage, infection, and prolonged hospital stays. The objective of this study was to evaluate the risk factors for retained placenta (defined as >30 min between the delivery of the fetus and placenta).
Treatments for Pregnancy-related Lumbopelvic Pain: A Systematic Review of Physiotherapy Modalities
Authors: Gutke A. , Betten C. , Degerskär K. , Pousette S. , Olsén M.F.
Published: November 2016

(Acta Obstet Gynecol Scand. 2015;94(11):1156–1167)

Pelvic girdle pain (PGP) during pregnancy occurs between the posterior iliac crests and the gluteal folds, and may radiate down the thighs, while low back pain (LBP) is localized beneath the ribs, but above the gluteal folds, and may or may not radiate down the legs. Lumbopelvic pain, which denotes the absence of distinction between PGP and LBP, is experienced by 50% of parturients and its prevalence increases as pregnancy advances. The distinction between PGP and LBP is important in order to select appropriate targeted treatment options. Earlier studies have reported that the majority of pregnant women with lumbopelvic pain have PGP (50% with PGP, 17% with lumbar pain, and 33% with combined PGP and LBP). Various treatments have been recommended by physiotherapists for lumbopelvic pain, including mobilization, exercises, use of pelvic belts, acupuncture, and manipulative therapy.
A Large Head Circumference is More Strongly Associated With Unplanned Cesarean or Instrumental Delivery and Neonatal Complications Than High Birthweight
Authors: Lipschuetz M. , Cohen S.M. , Ein-Mor E. , Sapir H. , Hochner-Celnikier D. , Porat S. , Amsalem H. , Valsky D.V. , Ezra Y. , Elami-Suzin M. , Paltiel O. , Yagel S.
Published: November 2016

(Am J Obstet Gynecol. 2015;213:833.e1–e.12)

Perinatal outcomes are known to be affected by fetal size. A cross-sectional study based on electronic medical records was undertaken to study whether obstetric outcomes are affected more by fetal head circumference (HC) than by birthweight (BW).
Cervical Pessary to Prevent Preterm Birth in Women With Twin Gestation and Sonographic Short Cervix: A Multicentre Randomized Controlled Trial (PECEP-Twins)
Authors: Goya M. , de la Calle M. , Pratcorona L. , Merced C. , Rodó C. , Muñoz B. , Juan M. , Serrano A. , Llurba E. , Higueras T. , Carreras E. , Cabero L.
Published: November 2016

(Am J Obstet Gynecol. 2016;214(2):145–152)

The primary risk factor for perinatal morbidity and mortality is noted to be spontaneous preterm birth (SPB) and the risk increases in twin gestations. Early and very early birth among twins is attributed to mothers having short cervical length (CL). It is also seen that 15% of women with twin gestations have CL≤25 mm. This measurement has become the benchmark for identifying women at risk of preterm delivery. Vaginal progesterone, cervical cerclage, and cervical pessary are the choices available for the management of patients with short CL. Use of vaginal progesterone did not reduce the rate of preterm delivery but the rate of neonatal morbidity decreased. Adverse outcome in twin gestations has been associated with cervical cerclage. Cervical pessary—a small ring shaped device made of silicone—was introduced in 1960 as a preventive measure for short CL. This device is inserted around the cervix, and a considerable fall in the preterm birth rate was recorded after this device came in use. Although, earlier clinical trial reports showed favorable results, the evidence came from nonrandomized study designs. Thus, further evidence supporting the role of cervical pessary in reducing the preterm birth rate was sought.
Intermittent Screening and Treatment or Intermittent Preventive Treatment With Dihydroartemisinin-Piperaquine Versus Intermittent Preventive Treatment With Sulfadoxine-Pyrimethamine for the Control of Malaria During Pregnancy in Western Kenya: An Open-label, 3-Group, Randomized Controlled Superiority Trial
Authors: Desai Meghna , Gutman Julie , L’lanziva Anne , Otieno Kephas , Juma Elizabeth , Kariuki Simon , Ouma Peter , Were Vincent , Laserson Kayla , Katana Abraham , Williamson John , ter Kuile Feiko O.
Published: November 2016

(Lancet. 2015;386:2507–2519)

In sub-Saharan Africa, there are >32 million pregnancies annually. As this is a malaria-endemic region, it is estimated approximately 12 million women who have live births (45% of live births) would be exposed to malaria infection each year. The World Health Organization (WHO) recommends intermittent preventive treatment with sulfadoxine-pyrimethamine during the second and third trimester for parturients living in malaria-endemic areas. Although this strategy has been effective, concerns are being raised due to an increase in parasite resistance. The aim of this current study was to assess the efficacy and safety of 2 alternative strategies: intermittent screening with malaria rapid diagnostic tests and treatment of women who test positive with dihydroartemisinin-piperaquine, and intermittent preventive treatment with dihydroartemisinin-piperaquine.
Angiogenic Factor Imbalance Early in Pregnancy Predicts Adverse Outcomes in Patients With Lupus and Antiphospholipid Antibodies: Results of the PROMISSE Study
Authors: Kim M.Y. , Buyon J.P. , Guerra M.M. , Rana S. , Zhang D. , Laskin C.A. , Petri M. , Lockshin M.D. , Sammaritano L.R. , Branch D.W. , Porter T.F. , Merrill J.T. , Stephenson M.D. , Gao Q. , Karumanchi S.A. , Salmon J.E.
Published: November 2016

(Am J Obstet Gynecol. 2016;214:108.e1–e.14)

Systemic lupus erythematosus (SLE) predominantly affects women and commonly presents during their childbearing years. Pregnancy in patients with SLE, particularly those with antiphospholipid (APL) antibodies, and in patients with APL alone, is associated with an increased risk for maternal and fetal morbidity due to preeclampsia (PE) and insufficient placental support of the developing fetus. PE and placental insufficiency are, in turn, associated with adverse pregnancy outcomes (APOs), including maternal complications of PE, intrauterine fetal death, and fetal growth restriction, as well as indicated preterm delivery. Hence the ability to identify patients who are destined for poor outcomes, early in pregnancy, would significantly impact care of this high-risk population.
Neonatal Outcomes After the Obstetric Near-miss Events Uterine Rupture, Abnormally Invasive Placenta and Emergency Peripartum Hysterectomy: Prospective Data From the 2009 to 2011 Finnish NOSS Study
Authors: Jakobsson M. , Tapper A.M. , Palomäki O. , Ojala K. , Pallasmaa N. , Ordén M.R. , Gissler M.
Published: November 2016

(Acta Obstet Gynecol Scand. 2015;94:1387–1394)

The objective of this study was to assess fetal and neonatal outcomes in women with the obstetric near-miss complications of abnormally invasive placenta (AIP), uterine rupture, and emergency peripartum hysterectomy using the Finnish Nordic Obstetric Surveillance Study (NOSS) population.
Complications of 761 Short-term Intrathecal Macrocatheters in Obstetric Patients: A Retrospective Review of Cases Over a 12-Year Period
Authors: Cohn J. , Moaveni D. , Sznol J. , Ranasinghe J.
Published: November 2016

(Int J Obstet Anesth. 2016;25:30–36)

Continuous spinal anesthesia may have some advantages over epidural catheter and single-shot spinal techniques in obstetrics, particularly in certain groups of high-risk parturients. However, use of intrathecal catheters (ITCs) seems underutilized on many obstetric units, with anesthesiologists citing the fear of infection, nerve damage or postdural puncture headache (PDPH). At the authors’ institution, which is a tertiary care hospital, ITCs are placed intentionally in specific high-risk obstetric patients, including those with morbid obesity, severe cardiopulmonary disease or spinal abnormalities. They also used ITCs following accidental dural puncture (ADP) with a 17-G epidural needle. This study reviewed retrospectively the complications experienced by 761 parturients who received an ITC for labor analgesia and/or anesthesia for cesarean delivery (CD) during the time period of 2001 to 2012 period.
Effect of Neuraxial Technique After Inadvertent Dural Puncture on Obstetric Outcomes and Anesthetic Complications
Authors: Jagannathan D.K. , Arriaga A.F. , Elterman K.G. , Kodali B.S. , Robinson J.N. , Tsen L.C. , Palanisamy A.
Published: November 2016

(Int J Obstet Anesth. 2016;25:23–29)

Epidural analgesia is a popular technique for labor pain management. A relatively common complication of this procedure is inadvertent dural puncture (IDP), which will lead to postdural puncture headache (PDPH) in some patients. The objective of this current study was to evaluate whether there was a difference in labor outcomes when IDP was managed with insertion of an intrathecal catheter versus resiting of an epidural catheter. The authors hypothesized that patients who received an intrathecal catheter would be less likely to have a prolonged second stage of labor with no difference in cesarean delivery rate compare with patients who had another epidural catheter placed.
The Effects of Prophylactic Bolus Phenylephrine on Hypotension During Low-dose Spinal Anesthesia for Cesarean Section
Authors: Lee H.-M. , Kim S.-H. , Hwang B.-Y. , Yoo B.-W. , Koh W.-U. , Jang D.-M. , Choi W.-J.
Published: November 2016

(Int J Obstet Anesth. 2016;25:17–22)

Spinal anesthesia for cesarean section is preferred in order to avoid the serious maternal complications that can occur during general anesthesia. However, spinal anesthesia is not without complications. Spinal anesthesia-induced hypotension occurs commonly and may have deleterious effects on both mother and fetus. To decrease the risk of hypotension a continuous infusion of phenylephrine is frequently administered, but there are limited data about the use of prophylactic boluses of the drug. The objective of this study was to evaluate the effects of 3 prophylactic bolus doses of phenylephrine during low-dose spinal anesthesia for cesarean section, including adverse hemodynamic effects and neonatal outcome.
Spinal Fentanyl Versus Sufentanil for Postoperative Analgesia After C-section: A Double-blinded Randomized Trial
Authors: Wilwerth M. , Majcher J.L. , Van der Linden P.
Published: November 2016

(Acta Anaesthesiol Scand 2016) [Epub ahead of print]

Several studies have shown that the addition of opioids, such as morphine, to an intrathecal (IT) local anesthetic solution prolongs the effective postoperative analgesia in women undergoing cesarean section. Two of the most commonly administered lipophilic opioids are fentanyl and sufentanil. As there are few studies that compare these 2 agents, the authors of the present study investigated the effective analgesia duration, postoperative morphine requirement, and incidence of side effects for both IT fentanyl and sufentanil.
Osteosarcoma
Authors: Hiller Chelsea , Wegler Jennifer L. , Forest Christopher P.
Published: November 2016

Osteosarcoma is the most common primary bone malignancy in children and adolescents. Because the incidence of osteosarcoma is low and the disease occurs in physically active patients, it may be misdiagnosed as a more benign condition, thus leading to late diagnosis. This article describes the disease's most frequent presenting complaints and initial radiographic findings, as well as its risk factors and common misdiagnoses. Clinicians should consider osteosarcoma in young patients with persistent bone pain, especially pain with weight-bearing.
Dual Semitendinosus Allograft Reconstruction of Large Achilles Tendon Defects
Authors: Hsu Nigel N. , Tan Eric W. , Miller Stuart D.
Published: November 2016

Patients with chronic midsubstance Achilles tendinopathy who do not respond to nonoperative management often require surgical intervention. Debridement of the diseased and dysfunctional tendon may result in a gap >5 cm. A number of previously described techniques to bridge the defect include V-Y lengthening, turndown procedures, local tendon transfers, synthetic grafts, and hamstring autograft and allograft. This article describes a novel technique using 2 semitendinosus allografts to reconstruct Achilles tendinopathy with large defects. There are 2 options for distal fixation depending upon the residual amount of Achilles tendon that remains distally on the heel. This technique offers another option for the surgeon in the face of a difficult reconstructive procedure. Early outcomes have been excellent.

Level of Evidence: Diagnostic Level 5. See Instructions for Authors for a complete description of levels of evidence.
Mini-Open In Situ Cubital Tunnel Release
Authors: Samora Julie Balch , Awan Hisham M.
Published: November 2016

Cubital tunnel syndrome is the second most common nerve entrapment syndrome of the upper extremity. Patients typically present with numbness and paresthesias in the ring and small fingers, elbow pain, and intrinsic weakness. There are several surgical treatment options, including in situ decompression, medial epicondylectomy, subcutaneous transposition, and submuscular transposition. Potential complications include incomplete release, hematoma formation, and medial antebrachial cutaneous nerve injury. Recently, many authors have described an endoscopic cubital tunnel release that is performed through a smaller incision, is less invasive, and results in a faster recovery time. We describe a simple mini-open in situ release for ulnar nerve compression at the elbow. A 1 cm incision just posterior to the medial epicondyle is made and blunt dissection is utilized. The ulnar nerve is released on its posterior aspect under direct visualization. A Langenbeck retractor and Jameson tenotomy scissors are used to release the nerve proximally. The superficial and deep flexor carpi ulnaris fascia are released distally. This mini-open technique uses a smaller incision than the endoscopic technique, without the added cost of the endoscopic equipment.
The Opioid Epidemic and Orthopedic Outcomes: Implications and Strategies
Authors: Morris Brent J. , Mir Hassan R.
Published: November 2016

There has been a recent rise in efforts to recognize and curtail the detrimental effects of nontherapeutic opioid use. Diversion of prescribed opioids for nontherapeutic use has led to many unforeseen consequences at the individual and societal levels, and has led many to term our current state as an opioid epidemic. It is important to address the consequences of opioid use in the setting of both therapeutic and nontherapeutic use. The downside of nontherapeutic opioid use is very clear with a striking increase in addiction and unintentional overdose deaths in our country. The subtler features of the opioid epidemic are unexpected consequences of therapeutic opioid use. Perhaps in an effort to better identify and treat pain, opioids are increasingly prescribed without an awareness of the potential detrimental impact of therapeutic opioid usage. Recent studies have highlighted the negative consequences of preoperative opioid use. Therapeutic opioid use before orthopedic surgery is now recognized to be associated with worse clinical outcomes after surgery. This article addresses the disproportionate use of opioids in the United States, the role of physicians and orthopedic surgeons, individual and societal impacts, and some potential ways to address the opioid epidemic.
Cognitive Impairment After Trauma and Orthopedic Injury: Key Issues, Identification, and Treatment
Authors: Jackson James C. , Kiehl Amy L. , Jutte Jennifer E.
Published: November 2016

Individuals experiencing significant orthopedic trauma that requires intensive care unit treatment frequently demonstrate a number of adverse outcomes. Chief among these adverse outcomes is cognitive impairment, characterized by functional decrements as well as deficits in a wide range of domains including attention, executive functioning, memory, processing speed, among other domains. Cognitive impairment is often unrecognized, although the consequences of failing to recognize it are potentially very significant. Although questions pertaining to the prevention of cognitive impairment remain, it may be that neuropsychological deficits can be remediated with cognitive rehabilitation.
Current management of patients with chronic myelomonocytic leukemia
Authors: Alfonso Ana , Montalban-Bravo Guillermo , Garcia-Manero Guillermo
Published: November 2016

Purpose of review

The present review will focus on the current management of patients with chronic myelomonocytic leukemia (CMML) as well as in future therapeutic perspectives.

Recent findings

CMML is a clonal hematopoietic stem cell disorder characterized by peripheral blood monocytosis and myelodysplastic and myeloproliferative alterations in the bone marrow. Clinical behavior of the disease can be heterogeneous, with some patients having an indolent form of the disease, whereas others experience an aggressive course with decreased survival and eventual transformation to leukemia. Multiple studies have helped define the clinical, cytogenetic and mutational prognostic features of the disease. In addition, several prognostic scoring systems have been developed for patients with CMML. Incorporation of mutation data, particularly presence of frameshift and nonsense ASXL1 mutations, into these models seems to be allowing to further improve our ability to predict patient outcomes.

Prognosis of patients with CMML is heterogeneous. Incorporation of mutational data into current clinical prognostic models has allowed to improve our ability to predict patient outcomes. Allogeneic stem cell transplantation remains the only potentially curative treatment for patients with CMML but is only an option for a subset of patients. For this reason, hypomethylating agents such as 5-azacitidine and decitabine have become the backbone of current therapy for patients with CMML, but new therapeutic strategies are required to improve their outcomes.
Role of the unfolded protein response in tumor cell characteristics and cancer outcome
Authors: Galmiche Antoine , Sauzay Chloé , Chevet Eric , Pluquet Olivier
Published: November 2016

Purpose of review

In the present review, we discuss the possible role of the unfolded protein response (UPR) in the acquisition of tumor cell characteristics and in the prognosis of cancer outcome, which could assist and contribute to the development of more promising therapeutic strategies.

Recent findings

Accumulating evidence supports the idea that alteration of endoplasmic reticulum proteostasis is a key player in cancer development and aggressiveness. Some UPR components were reported as independent prognostic biomarker. Recent evidence supports a relationship between the UPR activation status and prognosis of tumors. This may represent an interesting avenue for better characterization of carcinogenesis and tumor type.

The contribution of the UPR to the characteristics of malignant tumors is complex and dependent on both intrinsic (e.g. oncogene addiction) and extrinsic (e.g. hypoxia) contexts. Through adaptation to severe microenvironmental conditions, UPR branches are generally a survival strategy for cancer cells, which are able to cope with this challenging context. We address the question of whether the activation status of the UPR is related to tumor properties and discuss the role of the UPR in the clinical context.
Does low-dose aspirin use for cardiovascular disease prevention reduce colorectal cancer deaths? A comparison of two cohorts in the Florence district, Italy
Authors: Ventura Leonardo , Miccinesi Guido , Barchielli Alessandro , Manneschi Gianfranco , Puliti Donella , Mantellini Paola , Orso Francesco , Zappa Marco
Published: November 2016

Aspirin has been associated with reduced incidence and mortality of colorectal and a few other cancers. The aim of our paper was to study the effect of low-dose aspirin intake on cancer mortality in a population-based cohort study. The study included inhabitants of the Florence district (Italy) at the beginning of 2007. We considered two cohorts: patients who received prescriptions of low-dose aspirin for the whole year and patients who did not have any prescriptions over the same period. We followed the two cohorts until 31 December 2013. By linking with the Tuscany Mortality Registry, we analysed cause-specific mortality. We used a Cox semiparametric model to compare the mortality of the two cohorts. There was an 18% higher probability [hazard ratio (HR)=1.18, 95% confidence interval (CI): 1.12–1.23] for all causes of death among the cohort of aspirin users, almost completely caused by cardiovascular diseases (CVDs) (HR=1.39, 95% CI: 1.29–1.49). Colorectal cancer mortality was reduced by almost 30% (HR=0.71, 95% CI: 0.52–0.97). Death caused by major bleeding was 11% higher (HR=1.11, 95% CI: 0.86–1.44), but not statistically significant. Our results support the hypothesis that the use of low-dose aspirin for CVD prevention reduces colorectal cancer mortality. Given the growing ability to identify subgroups of individuals with an increased risk of developing cancer, further studies are needed to study the effectiveness of different cancer screening strategies tailored to these specific subgroups. Our study suggests the importance of focusing on this issue from the opposite perspective, that is, considering subgroups of individuals at decreased risk, such as the subgroup of individuals who take low-dose aspirin for CVD prevention. Thus, further assessments are needed to possibly identify subgroup-specific screening strategies that would be more effective than those developed for average-risk individuals.
Sequencing Treatment in BRAF V600 Mutant Melanoma: Anti-PD-1 Before and After BRAF Inhibition
Authors: Johnson Douglas B. , Pectasides Eirini , Feld Emily , Ye Fei , Zhao Shilin , Johnpulle Romany , Merritt Ryan , McDermott David F. , Puzanov Igor , Lawrence Donald , Sosman Jeffrey A. , Buchbinder Elizabeth , Sullivan Ryan J.
Published: November 2016

Novel agents targeting immune checkpoint molecules or mutated BRAF are active therapeutic options for patients with BRAF
V600-mutant melanoma. However, the most effective first-line treatment and the optimal sequencing of these agents have not been well characterized. To explore this, we retrospectively assessed 114 patients from 4 centers with advanced, BRAF
V600-mutant melanoma who received anti-programmed cell death-1 (PD-1)/PD-L1 antibodies. We evaluated clinical outcomes, including objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) to initial and subsequent therapies in patients that received anti-PD-1 first (n=56) versus those that received BRAF±MEK inhibitors (BRAFi) first (n=58). Median OS was similar between these groups (27.5 vs. 40.3 mo, P=0.71). Patients who progressed on anti-PD-1 during the study timeframe had worse outcomes after starting subsequent BRAFi than those who had not received prior anti-PD-1 (median PFS 5 vs. 7.4 mo, median OS 10.6 vs. 40.3 mo). Similarly, patients who previously progressed on BRAFi had seemingly inferior outcomes after starting anti-PD-1 compared with those without prior BRAFi, including ORR (25% vs. 41%), median PFS (2.8 vs. 10.6 mo) and median OS (8.2 vs. 27.6 mo). Notably, patients who benefited >6 months from BRAFi had superior ORR to subsequent anti-PD-1 compared with those with more rapid progression (<6 mo) on BRAFi (34% vs. 15%, P=0.04). We conclude that either BRAFi or anti-PD-1 may be effective regardless of treatment sequence in patients with BRAF
V600-mutant melanoma, but clinical outcomes to front-line therapy are superior. In addition, we suggest a shared “responder phenotype” between BRAFi and anti-PD-1.