bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuraxial Anesthesia in Parturients With Thrombocytopenia: A Multisite Retrospective Cohort Study
Authors: Goodier C.G. , Lu J.T. , Hebbar L. , Segal B.S. , Goetzl L.
Published: May 2016

(Anesth Analg. 2015;121:988–991)

Thrombocytopenia, defined as a platelet count <100,000/mm3 in this study, is a relative contraindication to neuraxial analgesia because of the unknown risk of hematoma. Although the risk of hematoma might outweigh the benefits of neuraxial anesthesia, withholding neuraxial anesthesia may result in suboptimal pain management and increased risk of general anesthesia-associated maternal morbidity. Consequently, the authors of the present study evaluated risk estimates of spinal-epidural hematoma after neuraxial anesthesia and of general anesthesia-associated complications in thrombocytopenic parturients. The primary goal was to determine a precise platelet threshold for withholding neuraxial anesthesia in thrombocytopenic parturients.
Is Cell Salvaged Vaginal Blood Loss Suitable for Reinfusion?
Authors: Teare K.M. , Sullivan I.J. , Ralph C.J.
Published: May 2016

(Int J Obstet Anesth. 2015;24(2):103–110)

Hemorrhage is one of the foremost direct causes of maternal death and critical care admission, often requiring allogeneic blood products. Because allogeneic blood is an increasingly scarce and expensive resource, and given the risks associated with donor blood transfusion, it is important to explore blood conservation strategies in order to reduce consumption of allogeneic blood.
Management of Postpartum Haemorrhage With Uterine Balloon Tamponade: The Way Forward
Authors: Marasinghe J.P. , Du Plessis J. , Epitawela D. , Umstad M.P.
Published: May 2016

(Aust N Z J Obstet Gynaecol. 2015;55(4):315–317)

Uterine atony is the leading cause of postpartum hemorrhage, which is the sixth most common cause of maternal death in the United Kingdom. There are many methods for managing postpartum hemorrhage, but if conservative treatment does not work, surgical intervention should be used before the situation becomes severe. Uterine balloon tamponade (UBT), introduced in 1991, is one of the most popular early surgical interventions, due to its relative simplicity and ease of use.
A NICE Delivery—The Cross-Atlantic Divide Over Treatment Intensity in Childbirth
Authors: Shah N.
Published: May 2016

(N Engl J Med. 2015;372(23):2181–2183)

This editorial examines the transatlantic debate over best labor and delivery practices for healthy women that arose following the results of an evidence-based review that prompted the United Kingdom’s National Institute for Health and Care Excellence (NICE) to conclude that it is safer for healthy women with straightforward pregnancies to give birth at home or in a midwife-led unit than in a hospital under the supervision of an obstetrician.
A Systematic Review of the Effects of Adding Neostigmine to Local Anesthetics for Neuraxial Administration in Obstetric Anesthesia and Analgesia
Authors: Cossu A.P. , De Giudici L.M. , Piras D. , Mura P. , Scanu M. , Cossu M. , Saba M. , Finco G. , Brazzi L.
Published: May 2016

(Int J Obstet Anesth. 2015;24:237–246)

Neostigmine, an acetyl-cholinesterase inhibitor, has been used for both epidural and intrathecal anesthesia in obstetric patients. In order to quantify its benefits and/or adverse effects as an adjuvant in neuraxial anesthesia, the authors of this meta-analysis reviewed randomized, placebo-controlled studies in which neostigmine was administered in combination with local anesthetics or other adjuvants.
The Nordic Obstetric Surveillance Study: A Study of Complete Uterine Rupture, Abnormally Invasive Placenta, Peripartum Hysterectomy, and Severe Blood Loss at Delivery
Authors: Colmorn L.B. , Petersen K.B. , Jakobsson M. , Lindqvist P.G. , Klungsoyr K. , Källen K. , Bjarnadottir R.I. , Tapper A.M. , Børdahl P.E. , Gottvall K. , Thurn L. , Gissler M. , Krebs L. , Langhoff-Roos J.
Published: May 2016

(Acta Obstet Gynecol Scand. 2015;94:734–744)

There is a lack of reliable research regarding severe complications at delivery, which is most likely due to the rarity of such complications. There is also the issue of interactions between different severe complications, questionable reporting, and the absence of precise terminology. The Nordic Obstetric Surveillance Study (NOSS) evaluated the rate of uterine rupture, placenta accreta, peripartum hysterectomy, and severe blood loss during delivery in Nordic countries as well as the characteristics of the women who suffered these complications. The aim was to provide valuable information that might help guide the management of obstetric emergencies.
The Consistency of Experts’ Evaluation of Obstetric Claims for Compensation
Authors: Andreasen S. , Backe B. , Lydersen S. , Øvrebø K. , Øian P.
Published: May 2016

(BJOG. 2015;122(7):948–953)

In Norway, patients who believe they have been injured by the health care system may apply for compensation to the Norwegian System of Compensation to Patients (NPE), a no-blame system which can dispense compensation without anyone being proven guilty of negligence.
The Effect of Co-administration of Intravenous Calcium Chloride and Oxytocin on Maternal Hemodynamics and Uterine Tone Following Cesarean Delivery: A Double-blinded, Randomized, Placebo-controlled Trial
Authors: Farber M.K. , Schultz R. , Lugo L. , Liu X. , Huang C. , Tsen L.C.
Published: May 2016

(Int J Obstet Anesth. 2015;24:217–224)

Oxytocin administration following cesarean delivery may be associated with significant adverse effects, such as cardiovascular instability (hypotension, tachycardia, myocardial ischemia). Intravenous (IV) calcium chloride (CaCl2) has been shown to increase mean arterial pressure (MAP) and cardiac contractility in patients undergoing anesthesia. Consequently, the authors of the present study hypothesized that IV co-administration of CaCl2 with oxytocin 5 U IV bolus would reduce the risk of hypotension and improve uterine tone in women undergoing elective cesarean delivery under spinal anesthesia. The primary outcome studied was blood pressure change after study drug administration. Secondary outcomes included the effect of CaCl2 on heart rate, uterine tone, need for additional uterotonic agent, vasopressor use, and blood loss.
Ondansetron Does Not Attenuate Hemodynamic Changes in Patients Undergoing Elective Cesarean Delivery Using Subarachnoid Anesthesia
Authors: Terkawi A.S. , Tiouririne M. , Mehta S.H. , Hackworth J.M. , Tsang S. , Durieux M.E.
Published: May 2016

(Reg Anesth Pain Med. 2015;40:344–348)

The most common side effect of subarachnoid (SA) anesthesia for cesarean delivery (CD) is hypotension, and the use of serotonin receptor-blocking drugs has been suggested as a possible treatment for this. One receptor antagonist that has been proposed for this use in both obstetric and nonobstetric settings is ondansetron. However, current studies regarding the use of ondansetron are either underpowered or have reported conflicting results. The purpose of this study was to determine how useful ondansetron actually is in the prevention of hypotension, particularly when it is administered intravenously and prophylactically to women undergoing elective CD.
Multidisciplinary Team Training Reduces the Decisions-to-delivery Interval for Emergency Cesarean Section
Authors: Fuhrmann L. , Pedersen T.H. , Atke A. , Møller A.M. , Østergaard D.
Published: May 2016

(Acta Anaesthesiol Scand. 2015;59(10):1287–1295)

A 30-minute period is a common practice benchmark for the decision-to-delivery interval (DDI) for emergency cesarean section (ECS) when the life of the mother or fetus is at risk. In Denmark, there is a national standard recommending that 95% of ECSs be performed within this 30-minute interval. A shorter, 15-minute goal is used when there is an immediate maternal or fetal threat, and a 60-minute goal for cases in which there is a need for an earlier-than-planned delivery, but no maternal or fetal compromise. Danish obstetrical results reported to a national database showed that only 34.4% of the ECSs performed at the study hospital in 2011 achieved the desired goal, indicating the need for improvement. This study implemented a simulation-based multidisciplinary team-training program and examined its effect on the DDI in a before-after study.
Cardiovascular Disease Risk is Only Elevated in Hypertensive, Formerly Preeclamptic Women
Authors: Breetveld N.M. , Ghossein-Doha C. , van Kuijk S. , van Dijk A.P. , van der Vlugt M.J. , Heidema W.M. , Scholten R.R. , Spaanderman M.E.
Published: May 2016

(BJOG. 2015;122(8):1092–1100)

Preeclampsia (PE) complicates 5% to 8% of all pregnancies and is associated with an increased risk for premature cardiovascular disease (CVD) later in life. Patients with a history of PE have a 2-fold to 7-fold risk of developing ischemic cardiac disease compared with healthy controls, depending on gestational age at delivery, and about a 4-fold risk of developing chronic hypertension within 15 years after pregnancy. Although it is unknown whether PE itself increases the risk of CVD independently or through risk factors associated with both PE and CVD, patients with a history of PE tend to exhibit components of the metabolic syndrome compared with patients with a history of uncomplicated pregnancy. Quantifying person-specific CVD risk could be useful in counseling these patients.
The Effect of Patient Warming During Cesarean Delivery on Maternal and Neonatal Outcomes: A Meta-Analysis
Authors: Sultan P. , Habib A. , Cho Y. , Carvalho B.
Published: May 2016

(Br J Anaesth. 2015;115(4):500–510)

The use of periperative warming is recommended for surgery under anesthesia, as it can help lower the risk of postoperative wound infection, myocardial ischemia, perioperative coagulopathy, blood loss, and transfusion requirements. However, there are currently no European or American national recommendations on the use of warming prior to and during cesarean delivery and it is not widely practiced. This study looked at the effect of active warming for elective cesarean deliveries on maternal temperature and comfort, neonatal temperature, umbilical cord pH, and Apgar scores.
The Effect of Adding a Background Infusion to Patient-Controlled Epidural Labor Analgesia on Labor, Maternal, and Neonatal Outcomes: A Systematic Review and Meta-Analysis
Authors: Heesen Michael , Böhmer Johannes , Klöhr Sven , Hofmann Thomas , Rossaint Rolf , Straube Sebastian
Published: May 2016

(Anesth Analg. 2015;121:149–158)

Epidural analgesia during labor can either be administered by means of a continuous infusion, bolus technique, or patient-controlled epidural analgesia (PCEA). PCEA gives patients the ability to administer a bolus themselves, which shortens the duration between the onset of patient discomfort and the administration of additional analgesia. This technique has been associated with less motor block, a reduced need for local anesthetic, and fewer physician-administered boluses compared with continuous infusion. Some clinicians prefer to combine a continuous infusion with a bolus technique even though it is uncertain if there are any real benefits to this method. The purpose of this review was to provide a meta-analysis that would hopefully guide clinical practice with respect to this combined method.
Pencil-point Needle Bevel Direction Influences ED50 of Isobaric Ropivacaine With Fentanyl in Spinal Anesthesia for Cesarean Delivery: A Prospective, Double-blind Sequential Allocation Study
Authors: Stroumpoulis K. , Stamatakis E. , Koutroumanis P. , Loukeri A. , Valsamidis D.
Published: May 2016

(Int J Obstet Anesth. 2015;24:225–229)

The authors of this study reported that their clinical experiences suggested that a cephalad orientation of the bevel of a Whitacre spinal needle decreased the amount of local anesthetic required for effective spinal anesthesia during cesarean delivery. To provide evidence supporting their anecdotal experience, they conducted a prospective, double-blind, sequential allocation study, in which they evaluated if the mean effective dose (ED50) of intrathecal isobaric 0.75% ropivacaine with fentanyl differed when the bevel direction of a 26-G Whitacre needle was changed.
A Perioperative Course of Gabapentin Does Not Produce a Clinically Meaningful Improvement in Analgesia After Cesarean Delivery
Authors: Monks D.T. , Hoppe D.W. , Downey K. , Shah V. , Bernstein P. , Carvalho J.C.
Published: May 2016

(Anesthesiology. 2015;123:320–326)

Gabapentin is an analgesic that has proven itself to be beneficial perioperatively for several surgeries, some of which, such as abdominal hysterectomy, are similar to cesarean delivery. There is also extensive information on this drug from its use as an anticonvulsant, in which it has been shown to be safe for use during pregnancy and breastfeeding. But while there have been studies evaluating its efficacy for pain management following cesarean delivery, studies evaluating use of a single preoperative dose for pain management following cesarean delivery have not produced definitive results. The authors of this trial sought to test the analgesic effect of gabapentin when given perioperatively for cesarean delivery.
Scheduled Acetaminophen With As-needed Opioids Compared With As-needed Acetaminophen Plus Opioids for Postcesarean Pain Management
Authors: Valentine A.R. , Carvalho B. , Lazo T.A. , Riley E.T.
Published: May 2016

(Int J Obstet Anesth. 2015;24:210–216)

Postoperative multimodal regimens like oral opioid-acetaminophen combination drugs can produce adverse maternal opioid-related side effects. Uncoupling these 2 drugs and administering them separately on a scheduled basis (acetaminophen plus as-needed opioids) may thereby be advantageous and lead to decreased opioid use. In the present study, the authors compared opioid use for scheduled acetaminophen plus as-needed opioid regimens with as-needed opioid-acetaminophen combination drug regimens.
Post-traumatic Stress Disorder Managed Successfully With Hypnosis and the Rewind Technique: 2 Cases in Obstetric Patients
Authors: Slater P.M.
Published: May 2016

(Int J Obstet Anesth. 2015;24:272–275)

Posttraumatic stress disorder (PTSD) occurs in 1% to 2% of women following childbirth and is associated with subjective distress in labor, obstetric emergencies, trait anxiety, and a history of psychological problems. PTSD itself is also a risk factor for the development of depressive and psychiatric disorders, and suicide remains a leading cause of maternal death. The rewind technique, in combination with hypnosis, is a specific treatment for PTSD. Patients are asked to rapidly fast-forward and rewind images associated with the event, to allow for reframing the event as nonthreatening. Currently, there are no reports focusing on the rewind technique and hypnosis as treatments for this disorder in the medical literature. In this present report, the authors describe 2 obstetric patients presenting with PTSD who underwent hypnosis with or without the rewind technique.
Chronic Adhesive Arachnoiditis After Repeat Epidural Blood Patch
Authors: Carlswärd C. , Darvish B. , Tunelli J. , Irestedt L.
Published: May 2016

(Int J Obstet Anesth. 2015;24:280–283)

An epidural blood patch (EBP) has variable efficacy in managing postdural puncture headache (PDPH). The authors of this case report describe a patient who developed chronic adhesive arachnoiditis (CAA), which might have resulted from a repeat EBP. The patient was a healthy, 29-year-old woman with an uncomplicated pregnancy who delivered vaginally. Upon epidural placement for labor analgesia, an accidental dural puncture occurred. The epidural catheter was placed intrathecally and effective labor analgesia was provided with intermittent doses of 0.25% bupivacaine. A total of 15 mg was administered throughout labor and delivery. She developed a severe PDPH 36 hours after the accidental dural puncture.
Microanalytic Assessment of Self-Regulated Learning During Clinical Reasoning Tasks: Recent Developments and Next Steps
Authors: Cleary Timothy J. , Durning Steven J. , Artino Anthony R.
Published: May 2016

Helping medical educators obtain and use assessment data to assist medical students, residents, and physicians in reducing diagnostic errors and other forms of ineffective clinical practice is of critical importance. Self-Regulated Learning–Microanalytic Assessment and Training is an assessment-to-intervention framework designed to address this need by generating data about trainees’ strategic processes (e.g., focusing on clinical task procedures), regulatory processes (e.g., planning how to do a task), and motivational processes (e.g., increasing confidence for performing a task) as they perform clinical activities. In this article, the authors review several studies that have used an innovative assessment approach, called self-regulated learning (SRL) microanalysis, to generate data about how trainees regulate their thinking and actions during clinical reasoning tasks. Across the studies, initial findings revealed that medical students often do not exhibit strategic thinking and action during clinical reasoning practice tasks even though some regulatory processes (e.g., planning) are predictive of important medical education outcomes. Further, trainees’ motivation beliefs, strategic thinking, and self-evaluative judgments tend to shift rapidly during clinical skills practice and may also vary across different parts of a patient encounter. Collectively, these findings underscore the value of dynamically assessing trainees’ SRL as they complete clinical tasks. The findings also set the stage for exploring how medical educators can best use SRL microanalytic assessment data to guide remedial practices and the provision of feedback to trainees. Implications and future research directions for connecting assessments to intervention in medical education are discussed.
Quality of Care Provided by Board-Certified Versus Non-Board-Certified Psychiatrists and Neurologists
Authors: Wallace Anna , McFarland Bentson H. , Selvam Nandini , Sahota Gurvaneet
Published: May 2016

Purpose

To examine associations between board certification of psychiatrists and neurologists and quality-of-care measures, using multilevel models controlling for physician and patient characteristics, and to assess feasibility of linking physician information with patient records to construct quality measures from electronic claims data.

Method

The authors identified quality measures and matched claims data from 2006 to 2012 with 942 board-certified (BC) psychiatrists, 868 non-board-certified (nBC) psychiatrists, 963 BC neurologists, and 328 nBC neurologists. Using the matched data, they identified psychiatrists who treated at least one patient with a schizophrenia diagnosis, and neurologists attending patients discharged with a principal diagnosis of ischemic stroke, and analyzed claims from these patients. For patients with schizophrenia who were prescribed an atypical antipsychotic, quality measures were claims for glucose and lipid tests, duration of any antipsychotic treatment, and concurrent prescription of multiple antipsychotics. For patients with ischemic stroke, quality measures were dysphagia evaluation; speech/language evaluation; and prescription of clopidogrel, low-molecular-weight heparin, intravenous heparin, and warfarin (for patients with co-occurring atrial fibrillation).

Results

Overall, multilevel models (patients nested within physicians) showed no statistically significant differences in quality measures between BC and nBC psychiatrists and neurologists.

Conclusions

The authors demonstrated the feasibility of linking physician information with patient records to construct quality measures from electronic claims data, but there may be only minimal differences in the quality of care between BC and nBC psychiatrists and neurologists, or there may be a difference that could not be measured with the quality measures used.
Influence of Complex Loading Conditions on Intervertebral Disc Failure
Authors: Berger-Roscher Nikolaus , Casaroli Gloria , Rasche Volker , Villa Tomaso , Galbusera Fabio , Wilke Hans-Joachim
Published: May 2016

Study Design.

High resolution imaging investigation of the failure of ovine lumbar intervertebral discs under complex loading.

Objective.

To investigate how different loading combinations influence the mechanism and extent of intervertebral disc failure.

Summary of Background Data.

Even though there has been extensive research on how an intervertebral disc fails under various conditions, failure mechanisms remain unclear. In addition, the influence of different loading directions on the mode and extent of failure under complex loading was never systematically investigated.

Methods.

Thirty ovine lumbar spinal segments were loaded in a newly developed, dynamic, 6-degree-of-freedom (6-DOF) disc loading simulator under five combinations of the following loading parameters: 0°–13° flexion, 0°–10° lateral bending, 0°–4° axial rotation, 0–800 N axial compression. A total of 1000 cycles at 2 Hz were done. After testing, imaging of the discs was performed in an ultra-high field magnetic resonance imaging (11.7 T) scanner and with a micro-computed tomography scanner.

Results.

A total of 13 large endplate junction failures (EPJFs) occurred, of which all but one maintained an intact cartilaginous endplate. Ten out of 13 EPJFs occurred caudally. Four solely annulus failures occurred affecting only the outer posterior annulus. A herniation was not observed. The maximum moments measured in any group (median) were 52.5 N · m flexion, 16.5 N · m lateral bending, and 14.0 N · m axial rotation.

Conclusion.

Complex loading protocols could lead to EPJFs (76%) and annulus failures (24%) in vitro. The combination of flexion, lateral bending, axial rotation, and axial compression bears the highest risk for caudal EPJF. Flexion without lateral bending and vice versa has the lowest risk for failure. Both axial compression and axial rotation seem to have a smaller influence than flexion and lateral bending. It seems that a herniation requires an additional failure of the cartilaginous endplate, likely initiated by further axial compressive load.

Level of Evidence: 4
Deletion of Opg Leads to Increased Neovascularization and Expression of Inflammatory Cytokines in the Lumbar Intervertebral Disc of Mice
Authors: Li Xiao-Feng , Xue Chun-Chun , Zhao Yong-Jian , Cheng Shao-Dan , Zhao Dong-Feng , Liang Qian-Qian , Chen Lin , Wang Qiang , Lu Sheng , Shi Qi , Wang Yong-Jun , Shu Bing
Published: May 2016

Study Design.

Neovascularization and expression of inflammatory cytokines were examined in Osteoprotegerin (Opg) knockout (KO) mice that show intervertebral disc (IVD) degeneration.

Objective.

The aim of this study was to clarify the pathological changes in lumbar IVD degeneration in Opg KO mice.

Summary of Background Data.

Osteoporosis is a controversial risk factor for IVD degeneration. Deletion of Opg resulted in IVD degeneration in mice. Neovascularization and inflammatory cytokines are key factors in IVD degeneration.

Methods.

Opg KO mice and their wild-type (WT) littermates were euthanized. Lumbar IVDs were harvested. Safranin O/Fast Green staining was performed to examine the pathological changes. Microcomputed tomographic (micro-CT) analysis was performed to determine the structural changes at the junction of lumbar IVD cartilage and vertebrae. Tartrate-resistant acid phosphatase (TRAP) staining was performed to evaluate osteoclast formation. Protein expression of vascular endothelial growth factor A (VEGF-A), CD31, VE-cadherin, CD 34, interleukin-1β (IL-1β), and tumor necrosis factors α (TNF-α) were analyzed by immunohistochemistry (IHC) assays. Gene expressions of IL-1β, IL-6, and TNF-α were analyzed by real-time polymerase chain reaction (RT-PCR).

Results.

In 12-week-old Opg KO mice, new bone was formed in the endplate cartilage of lumbar IVDs and this became more obvious in 24-week-old Opg KO mice. Three-dimensional (3D) μCT reconstruction analyses showed that the edges of the L4 and L5 vertebrae were rugged with bone marrow cavities in it. Protein expression of VEGF-A, CD31, VE-cadherin, and CD34 was increased in the endplate and growth plate of lumbar IVDs of Opg KO mice. Gene expression of IL-1β, IL-6, and TNF-α as well as protein expression of IL-1β and TNF-α were highly expressed in the lumbar IVDs of Opg KO mice.

Conclusion.

Deletion of Opg leads to increased neovascularization and expression of inflammatory cytokines in the lumbar disc in Opg KO mice, which may play important roles in IVD degeneration.

Level of Evidence: N/A
Inhibition of TNF-α–mediated NF-κB Activation by Ginsenoside Rg1 Contributes the Attenuation of Cardiac Hypertrophy Induced by Abdominal Aorta Coarctation
Authors: Tang Futian , Lu Meili , Yu Lan , Wang Qiuning , Mei Meng , Xu Chonghua , Han Ronghui , Hu Jin , Wang Hongxin , Zhang Yingjie
Published: May 2016

Ginsenoside Rg1 (Rg1), a protopanaxadiol saponin extracted from Chinese medicine Panax ginseng C.A. Meyer, has been demonstrated to inhibit the cardiac hypertrophy. However, the molecular mechanisms underlying the inhibition remain poorly understood. Activation of nuclear factor-kappa B (NF-κB) mediated by tumor necrosis factor α (TNF-α) gets involved in the cardiac hypertrophy. This study is designed to investigate the effects and the potential mechanism of Rg1 on the abdominal aorta coarctation (AAC)-induced cardiac hypertrophy with focus on TNF-α/NF-κB signaling pathway. The results showed that oral administration of Rg1 dose-dependently improved the pathological changes, decreased the ratios of left ventricular weight/body weight (LVW/BW) and heart weight/BW (HW/BW), corrected the dysfunction of the cardiac hemodynamics by decreasing the left ventricular systolic pressure and left ventricular end-diastolic pressure and increasing the maximal rate of left ventricular systolic and diastolic pressure (±dp/dtmax) compared with the AAC alone. Rg1 also downregulated the atrial natriuretic peptide mRNA expression and decreased the mRNA and protein expression of TNF-α in the heart tissue of rats compared with the AAC alone. In addition, Rg1 and BAY, the specific inhibitor of NF-κB, decreased the protein content and downregulated the mRNA expression of atrial natriuretic peptide in neonatal rat ventricular myocytes treated with TNF-α. Furthermore, Rg1 increased the protein expression of p65, the subunit of NF-κB, in cytoplasm and decreased the expression p65 in nucleus of the heart tissue of rats undergoing the AAC and of neonatal rat ventricular myocytes treated with TNF-α. The results suggested that Rg1 attenuates the AAC-induced cardiac hypertrophy through inhibition of TNF-α/NF-κB signaling pathway.
Exercise training reduces the frequency of menopausal hot flushes by improving thermoregulatory control
Authors: Bailey Tom G. , Cable N. Timothy , Aziz Nabil , Dobson Rebecca , Sprung Victoria S. , Low David A. , Jones Helen
Published: May 2016

Objective:

Postmenopausal hot flushes occur due to a reduction in estrogen production causing thermoregulatory and vascular dysfunction. Exercise training enhances thermoregulatory control of sweating, skin and brain blood flow. We aimed to determine if improving thermoregulatory control and vascular function with exercise training alleviated hot flushes.

Methods:

Twenty-one symptomatic women completed a 7-day hot flush questionnaire and underwent brachial artery flow-mediated dilation and a cardiorespiratory fitness test. Sweat rate and skin blood flow temperature thresholds and sensitivities, and middle cerebral artery velocity (MCAv) were measured during passive heating. Women performed 16 weeks of supervised exercise training or control, and measurements were repeated.

Results:

There was a greater improvement in cardiorespiratory fitness (4.45 mL/kg/min [95% CI: 1.87, 8.16]; P = 0.04) and reduced hot flush frequency (48 hot flushes/wk [39, 56]; P < 0.001) after exercise compared with control. Exercise reduced basal core temperature (0.14°C [0.01, 0.27]; P = 0.03) and increased basal MCAv (2.8 cm/s [1.0, 5.2]; P = 0.04) compared with control. Sweat rate and skin blood flow thresholds occurred approximately 0.19°C and 0.17°C earlier, alongside improved sweating sensitivity with exercise. MCAv decreased during heating (P 
< 0.005), but was maintained 4.5 cm/s (3.6, 5.5; P < 0.005) higher during heating after exercise compared with control (0.6 cm/s [−0.4, 1.4]).

Conclusions:

Exercise training that improves cardiorespiratory fitness reduces self-reported hot flushes. Improvements are likely mediated through greater thermoregulatory control in response to increases in core temperature and enhanced vascular function in the cutaneous and cerebral circulations.
Estrogen therapy may counterbalance eutrophic remodeling of coronary arteries and increase bradykinin relaxation in a rat model of menopausal hypertension
Authors: Matrai Mate , Hetthéssy Judit R. , Nadasy Gyorgy L. , Szekacs Bela , Mericli Metin , Acs Nandor , Monos Emil , Arbib Nissim , Varbiro Szabolcs
Published: May 2016

Objective:

Hypertension causes adverse remodeling and vasomotor alterations in coronaries. Hormones such as estrogen may help counterbalance some of these effects. The aim of this study was to analyze the effects of ovariectomy and estrogen therapy in a rat model of menopausal hypertension induced by angiotensin II (AII).

Methods:

We investigated diameter, tone, and mechanics of intramural coronaries taken from ovariectomized female rats (n = 11) that received chronic AII treatment to induce hypertension, and compared the results with those found in female rats that were also given estrogen therapy (n = 11). The “hypertensive control” group (n = 11) underwent an abdominal sham operation, and received AII. After 4 weeks of AII treatment, side branches of left anterior descendent coronary (approximately 200 μm in diameter) were isolated, cannulated with plastic microcannulas at both ends, and studied in vitro in a vessel chamber. The inner and outer diameter of the arteries were measured by microangiometry, and spontenuous tone, wall thickness, wall cross-sectional area, tangential stress, incremental distensibility, circumferential incremental elastic modulus, thromboxane agonist-induced tone, and bradykinin-induced dilation were calculated.

Results:

In hypertension, intramural small coronaries show inward eutrophic remodeling after ovariectomy comparing with hypertensive controls. Estrogen therapy had an opposite effect on vessel diameter. Hormone therapy led to an increase in spontaneous tone, allowing for greater dilatative capacity.

Conclusions:

Estrogen may therefore be considered to counterbalance some of the adverse changes seen in the wall of intramural coronaries in the early stages of chronic hypertension.
Histologic types of gastric cancer among migrants from the former Soviet Union and the general population in Germany: what kind of prevention do we need?
Authors: Jaehn Philipp , Holleczek Bernd , Becher Heiko , Winkler Volker
Published: May 2016

Objective

The incidence of gastric cancer (GC) is high among migrants from Eastern Europe and Asia, but a detailed picture of disease characteristics is missing. Our study examined the incidence of histologic types among resettlers from the former Soviet Union and the general population in Germany to draw conclusions on risk factors and possible prevention strategies.

Methods

Between 1990 and 2009, all GC diagnoses among a cohort of 18 619 resettlers residing in the Saarland were identified in the Saarland Cancer Registry database. Age-standardized incidence rates (ASRs) of the entire Saarland population and standardized incidence ratios (SIRs) of resettlers compared with the Saarland population were calculated for types according to Laurén. In addition, ASRs and SIRs were modeled using Poisson’s regression to investigate time trends.

Results

The ASR of intestinal GC in the Saarland population decreased over time, whereas the ASR of diffuse GC remained unchanged. Resettlers’ incidence of intestinal GC was elevated among men [SIR: 3.04, 95% confidence interval (CI): 2.05–4.50] and women (SIR: 2.78, 95% CI: 1.61–4.79), whereas diffuse GC was elevated only among women (SIR: 1.98, 95% CI: 1.07–3.69). No time trends for SIRs could be observed in regression analysis.

Conclusion

Different trends of diffuse GC incidence in Germany and the USA underline the importance of environmental risk factors. The continuously elevated risk of GC among male resettlers is probably associated with risk factors affecting exclusively the intestinal type such as a low intake of fruit and vegetables and heavy alcohol consumption. Future prevention programs for resettlers should include dietary measures.
Clinical implications of new mechanistic insights into atopic dermatitis
Authors: Leung Donald Y.M.
Published: May 2016

Purpose of review

The review will examine recent advances in our understanding of atopic dermatitis and how these mechanisms provide a framework for new approaches to the management of this common skin disease.

Recent findings

The mechanisms by which epithelial skin barrier and immune responses contribute to the complex clinical phenotypes found in atopic dermatitis are being elucidated. Atopic dermatitis often precedes food allergy because reduced skin barrier function allows environmental food allergens to penetrate the skin leading to systemic allergen sensitization. There is increasing evidence that atopic dermatitis is a systemic disease. New treatments are focused on intervention in polarized immune responses leading to allergic diseases. This includes antagonism of IL-4 and IL-13 effects. Prevention strategies involve maintaining normal skin barrier function with emollients to prevent allergens and microbes from penetrating the skin.

Recent work on the pathogenesis of atopic dermatitis has important implications for its clinical management, including the development of effective barrier creams and biologicals targeting specific polarized immune pathways resulting in skin inflammation.
Understanding autoimmunity of vitiligo and alopecia areata
Authors: Rork Jillian F. , Rashighi Mehdi , Harris John E.
Published: May 2016

Purpose of review

Vitiligo and alopecia areata are common, disfiguring skin diseases. Treatment options are limited and include nontargeted approaches, such as corticosteroids, topical calcineurin inhibitors, narrow band ultraviolet B phototherapy, and other immune-modifying agents. The purpose of this article is to review shared, novel mechanisms between vitiligo and alopecia areata, as well as discuss how they inform the development of future targeted treatments.

Recent findings

Vitiligo and alopecia areata are both autoimmune diseases, and striking similarities in pathogenesis have been identified at the level of both the innate and adaptive immune system. Increased reactive oxygen species and high cellular stress level have been suggested as the initiating trigger of the innate immune system in both diseases, and genome-wide association studies have implicated risk alleles that influence both innate and adaptive immunity. Most importantly, mechanistic studies in mouse models of vitiligo and alopecia areata have specifically implicated an interferon (IFN)γ-driven immune response, including IFNγ, IFNγ-induced chemokines, and cytotoxic CD8+ T cells as the main drivers of disease pathogenesis. These recent discoveries may reveal an effective strategy to develop new treatments, and several proof-of-concept clinical studies support this hypothesis.

The identification of IFNγ-driven immune signaling pathways has enabled discoveries of potential new treatments for vitiligo and alopecia areata, and supports initiation of larger clinical trials.
Therapist Adherence to Good Psychiatric Practice in a Short-Term Treatment for Borderline Personality Disorder
Authors: Kolly Stéphane , Despland Jean-Nicolas , de Roten Yves , Marquet Pierre , Kramer Ueli
Published: May 2016

Therapist adherence describes the quality of interventions according to the imperatives of a treatment model. We examined the relationship between therapist adherence and symptom change in the context of a short-term treatment with respect good psychiatric management (GPM) principles. Based on a parent trial, borderline personality disorder patients (N = 40) benefited from a 10-session intervention. Adherence to GPM was assessed using a GPM Adherence Scale (GPMAS). The psychometric properties of the GPMAS were excellent, and the adherence to GPM explained 16% of the general symptom improvement (t(1) = 2.38, β = 0.40, p = 0.02) and 23% of the borderline symptom improvement (t(1) = 2.46, β = 0.48, p = 0.02). Because GPM adherence predicts the outcome after only 10 sessions, GPMAS is a valuable measure early on in psychiatric practice as part of an initial step to longer-term treatment, to quickly detect problems and correct them.
Assessing p16 Status of Oropharyngeal Squamous Cell Carcinoma by Combined Assessment of the Number of Cells Stained and the Confluence of p16 Staining
Authors: Barasch Samuel , Mohindra Pranshu , Hennrick Kenneth , Hartig Gregory K. , Harari Paul M. , Yang David T.
Published: May 2016

Human papillomavirus–related oropharyngeal squamous cell carcinoma (OPSCC) has favorable prognosis relative to other head and neck squamous cell carcinomas. Criteria for predicting human papillomavirus status based upon p16 staining, including difficult cases with partial staining patterns, have been developed; however, clinical validation of these criteria and the clinical significance of partial p16 staining have not been reported. Eighty-one archival OPSCC cases were initially stained for p16 by immunohistochemistry with clone G175-405. The percentage of p16+ cells and percentage of confluence of p16+ cells were categorized as 25%, 26% to 75%, or >75%. Of all cases, 16 (20%) had partial p16 expression, with 26% to 75% p16+ cells. Applying previously developed criteria of >75% p16+ cells or >50% positive cells with >25% confluence, 48 (59%) patients were categorized p16+ and demonstrated expected clinical characteristics and superior disease-free survival and overall survival (P<0.001) compared with p16− patients. By themselves, the partial staining patients had intermediate outcomes; however, separating the partial staining cases by degree of confluence showed that those with >75% confluence had superior disease-free survival (P=0.042). When the 16 original partial staining cases were re-stained with the alternative anti-p16 E6H4 clone, p16 status remained concordant for all cases, but only 3 of the 16 were interpreted as demonstrating partial staining. This report shows that the prevalence of partial p16 staining varies with the antibody utilized and clinically validates the application of a graded evaluation of both the number as well as confluence of positive cells for risk stratification of patients with OPSCC.
Explicit Facial Emotion Processing in Patients With Dissociative Seizures
Authors: Pick Susannah , Mellers John D.C. , Goldstein Laura H.
Published: May 2016

Objective

There have, as yet, been few experimental studies of explicit facial affect recognition in patients with dissociative seizures (DS). The aim of the study was to examine explicit recognition and physiological responses to facial expressions in this group, relative to healthy controls.

Methods

Forty patients with DS and 43 controls completed a computerized test of facial affect recognition, including five basic expressions (happiness, anger, disgust, fear, neutral). Recognition accuracy, emotional intensity judgements, and skin conductance levels and responses were dependent measures. Analyses controlled for a range of potentially confounding variables, including anxiety, depression, and medication effects.

Results

The DS group was less accurate at identifying facial expressions than controls (p = .005, η
2
p = 0.10). No group difference emerged for intensity judgements (p = .72, η
2
p = 0.002). Mean skin conductance levels were higher in the DS group relative to controls (p = .046, η
2
p = 0.053). However, a subgroup of DS patients showed attenuated skin conductance responses to the facial stimuli, compared with controls (p = .015, η
2
p = 0.18). These differences could not be accounted for by possible confounding variables. Recognition accuracy for neutral faces correlated negatively with trauma scores (r = −0.486, p = .002) and abandonment concerns (r = −0.493, p = .002) in the DS group.

Conclusions

Patients with DS showed reduced recognition accuracy for facial affect, despite accurately perceiving its intensity. Elevated autonomic arousal may characterize patients with DS in general, alongside reduced phasic autonomic responses to facial expressions in some patients with the disorder.
The role of multiplex molecular panels for the diagnosis of gastrointestinal infections in immunocompromised patients
Authors: Liesman Rachael M. , Binnicker Matthew J.
Published: May 2016

Purpose of review

An increasing number of laboratories have implemented multiplex molecular panels for the diagnosis of gastrointestinal infections. This review focuses on recent data addressing the performance of US Food and Drug Administration-cleared multiplex gastrointestinal panels and discusses the advantages and limitations of these tests in the immunocompromised population.

Recent findings

Testing for gastrointestinal pathogens using multiplex molecular panels increases sensitivity and detection of coinfections compared with routine testing methods. Furthermore, multiplex panels reduce turnaround time and may allow for more informed decisions regarding treatment and infection control measures. However, the routine use of multiplex gastrointestinal panels has led to an increase in the detection of certain organisms, such as enteroaggregative Escherichia coli and sapovirus, which many clinical laboratories did not specifically test for in the past. This has created a degree of confusion on how to best interpret the results of multiplex panels, especially in the immunocompromised host.

Multiplex molecular panels provide a rapid and sensitive tool for the diagnosis of infectious diarrhea, and may allow for more timely decisions regarding the management of immunosuppressed patients. However, there are limitations associated with multiplex panels, including the interpretation of results and the cost associated with testing. Clinical microbiologists should work closely with clinicians to develop evidence-based algorithms to guide test utilization in this area.
Stochastic simulation tools and continuum models for describing two-dimensional collective cell spreading with universal growth functions
Authors: Jin Wang , Penington Catherine J. , McCue Scott W. , Simpson Matthew J.
Published: May 2016

Two-dimensional collective cell migration assays are used to study cancer and tissue repair. These assays involve combined cell migration and cell proliferation processes, both of which are modulated by cell-to-cell crowding. Previous discrete models of collective cell migration assays involve a nearest-neighbour proliferation mechanism where crowding effects are incorporated by aborting potential proliferation events if the randomly chosen target site is occupied. There are two limitations of this traditional approach: (i) it seems unreasonable to abort a potential proliferation event based on the occupancy of a single, randomly chosen target site; and, (ii) the continuum limit description of this mechanism leads to the standard logistic growth function, but some experimental evidence suggests that cells do not always proliferate logistically. Motivated by these observations, we introduce a generalised proliferation mechanism which allows non-nearest neighbour proliferation events to take place over a template ofr≥ 1 concentric rings of lattice sites. Further, the decision to abort potential proliferation events is made using acrowding function, f(C), which accounts for the density of agents within a group of sites rather than dealing with the occupancy of a single randomly chosen site. Analysing the continuum limit description of the stochastic model shows that the standard logistic source term, λC(1 –C), where λ is the proliferation rate, is generalised to a universal growth function, λCf(C). Comparing the solution of the continuum description with averaged simulation data indicates that the continuum model performs well for many choices off(C) andr. For nonlinearf(C), the quality of the continuum-discrete match increases withr.
MODA: MOdule Differential Analysis for weighted gene co-expression network
Authors: Li Dong , Brown James B. , Orsini Luisa , Pan Zhisong , Hu Guyu , He Shan
Published: May 2016

1

Gene co-expression network differential analysis is designed to help biologists understand gene expression patterns under different conditions. We have implemented an R package called MODA (Module Differential Analysis) for gene co-expression network differential analysis. Based on transcriptomic data, MODA can be used to estimate and construct condition-specific gene co-expression networks, and identify differentially expressed subnetworks as conserved or condition specific modules which are potentially associated with relevant biological processes. The usefulness of the method is also demonstrated by synthetic data as well as Daphnia magna gene expression data under different environmental stresses.
Markov models of the apo-MDM2 lid region reveal diffuse yet two-state binding dynamics and receptor poses for computational docking
Authors: Mukherjee Sudipto , Pantelopulos George A. , Voelz Vincent A.
Published: May 2016

MDM2 is a negative regulator of p53 activity and an important target for cancer therapeutics. The N-terminal lid region of MDM2 modulates interactions with p53 via competition for its binding cleft, exchanging slowly between docked and undocked conformations in the absence of p53. To better understand these dynamics, we constructed Markov State Models (MSMs) from large collections of unbiased simulation trajectories ofapo-MDM2, and find strong evidence for diffuse, yet two-state folding and binding of the N-terminal region to the p53 receptor site. The MSM also identifiesholo-like receptor conformations highly suitable for computational docking, despite initiating trajectories from closed-cleft receptor structures unsuitable for docking. Fixed-anchor docking studies using a test set of high-affinity small molecules and peptides show simulated receptor ensembles achieve docking successes comparable to cross-docking studies using crystal structures of receptors bound by alternative ligands. For p53, the best-scoring receptor structures have the N-terminal region lid region bound in a helical conformation mimicking the bound structure of p53, suggesting lid region association induces receptor conformations suitable for binding. These results suggest that MD+MSM approaches can sample binding-competent receptor conformations suitable for computational peptidomimetic design, and that inclusion of disordered regions may be essential to capturing the correct receptor dynamics.