bluuebunny/crossref_metadata_2025 huggingface dataset:
Acupuncture for chronic uncomplicated musculoskeletal pain associated with the spine
Authors: Xu Tao , Zhou Siyuan , Zhang Yutong , Yu Yang , Li Xiang , Chen Jiao , Du Jiarong , Wang Ziwen , Zhao Ling
Published: January 2019

Background:

Chronic uncomplicated neck pain, back pain, and lower back pain, with incidences of 18%, 17.7% and 36%, respectively. Although these three conditions occur in different parts of the body, we can summarize them as chronic uncomplicated musculoskeletal pain associated with the spine (CMPS) in accordance with the pathogenesis. Acupuncture is often used to treat them. We aim to conduct a systematic review to evaluate the efficacy of acupuncture for patients experiencing CMPS.

Methods:

The following electronic databases will be searched from inception to Mar 2019: Cochrane Central Register of Controlled Trials, Web of Science, ScienceDirect, PubMed, MEDLINE, EMBASE, Springer, WHO International Clinical Trials Registry Platform, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Chinese Science and Technology Periodical Database, and Wanfang Database. All randomized controlled trials published in English or Chinese related to acupuncture for CMPS will be included. The primary outcome will be the visual analog scale. Adverse events will be evaluated as secondary outcomes for safety evaluation. Study selection, data extraction, and assessment of study quality will be performed independently by two reviewers. RevMan V.5.3.5 software will be used for the assessment of risk of bias and data synthesis.

Results:

This study will provide a high-quality synthesis of current evidence of acupuncture for CMPS from visual analog scale.

Conclusion:

The conclusion of our study will provide an evidence to judge whether acupuncture is an effective intervention for patients suffered from CMPS.

Ethics and dissemination:

Formal ethical approval is not required, as the data are not individualized. The findings of this systematic review will be disseminated in a peer-reviewed publication and/or presented at relevant conferences.

PROSPERO registration number:

CRD42018114806.
Rechallenge capecitabine after fluoropyrimidine-induced cardiotoxicity in rectal cancer
Authors: Peng Tao , Ouyang Yulu , Tong Kanger
Published: January 2019

Rationale:

Fluoropyrimidine-induced cardiotoxicity is a rare but potentially serious toxicity. The most common symptom is anginal chest pain.

Patient concerns:

A 35-year-old woman was diagnosed with rectal cancer with metastasis to the liver.

Diagnosis:

A computed tomography scan showed a 9.3 × 4.5-cm predominantly hypodense lesion within the left lobe of the liver and thickening of the rectum. Liver biopsy showed moderately differentiated adenocarcinoma with necrosis involving the liver parenchyma, and immunohistochemistry for mismatch repair proteins indicated that the tumor was positive for MutL Homolog 1, MutS Homolog 2, MutS Homolog 6, and Protein Homolog 2. Rectal biopsy indicated moderately differentiated adenocarcinoma.

Interventions:

She received chemotherapy of fluorouracil 1600 mg/m2, leucovorin 500 mg/m2, and irinotecan 100 mg/m2every week. During the second cycle of chemotherapy, she developed severe anginal chest pain. We replaced fluorouracil with capecitabine 1500 mg (3 pills) a day every 2 weeks, with 1 week off, with irinotecan 100 mg/m2on day 1 and bevacizumab 5 mg/kg at 200 ml/h for 30 min every 2 weeks. She was treated with chemotherapy for approximately 6 months.

Outcomes:

The liver lesion showed a significant response to chemotherapy, so she underwent resection of the liver tumor and rectum. After the surgery, she received radiation therapy to the rectal area, and 3 months of chemotherapy were administered prior to colostomy reversal.

Lessons:

Although the mechanism of fluoropyrimidine-induced cardiotoxicity is still uncertain, our case provides clinical evidence that cardiotoxicity could be a dose-related complication. Reducing the dose of fluoropyrimidine should be considered as a strategy after fluoropyrimidine-induced cardiotoxicity. However, this must be discussed with a multidisciplinary team including oncologists and cardiologists. Close monitoring of serial biomarkers and echocardiography are necessary for early diagnosis of cardiotoxicity.
Efficacy and safety of pinaverium bromide combined with flupentixol-melitracen for diarrhea-type irritable bowel syndrome
Authors: Qin Lifeng , Qin Jinmei , Yang Qian , Lv Xiaoping , Huang Liyi
Published: January 2019

Background:

There are many trials on the combination of Pinaverium bromide (PB) and Flupentixol-melitracen (FM) in the treatment of diarrhea-type irritable bowel syndrome (IBS-D), but the sample sizes are small, and the research conclusions are inconsistent. Thus, a meta-analysis was performed, aiming to evaluate the efficacy and safety of this combination therapy in patients with IBS-D.

Methods:

A systematic literature search was conducted in 7 databases covering the period up to July 2018 to identify randomized controlled trials (RCTs) of PB combined with FM versus PB alone for IBS-D. The primary outcome was the total symptom relief rate. The other outcomes were the adverse events rate, HAMA/SAS score, and HAMD/SDS score. The methodological quality of the RCTs was assessed independently using 6 criteria according to the Cochrane Collaboration. All data were analyzed using Review Manager 5.3.

Results:

Fifteen RCTs with 1487 participants were identified from 2005 to 2018. Compared with PB alone, 15 RCTs showed significant effects of PB plus FM in terms of improved symptom relief in patients with IBS-D (n = 1487, OR = 5.17, 95%CI, 3.79–7.07, P < .00001). Eleven RCTs reported adverse effects in both the PB plus FM and PB groups, there was no statistically significant difference in the adverse events rate between the 2 groups (n = 1207, OR = 2.91, 95%CI, 0.91–9.28, P = 0.07). Two RCTs and 3 RCTs reported HAMA and HAMD scores respectively, and 3 RCTs reported both SAS and SDS scores. After treatment, the above scores in the PB plus FM group were significantly lower than the PB group (all P < .01). However, the trials were deemed to have a medium risk of bias.

Conclusions:

The efficacy of PB combined with FM is superior to PB alone in the treatment of IBS-D, and it is safe for clinical use. However, the conclusions still need to be verified by conducting more large-scale and high-quality RCTs.
Pneumatosis intestinalis and hepatic portal venous gas associated with gas-forming bacterial translocation due to postoperative paralytic ileus
Authors: Tahara Sayumi , Sakai Yasuhiro , Katsuno Hidetoshi , Urano Makoto , Kuroda Makoto , Tsukamoto Tetsuya
Published: January 2019

Rationale:

Pneumatosis intestinalis (PI) and hepatic portal venous gas (HPVG) are rare but potentially lethal conditions in which gas pathologically accumulates in the portal vein and intestinal wall, respectively. Proposed mechanisms include flatus escaping through an injured intestinal mucosa into the submucosa and thence into the portal venous system, or bacterial translocation (BT) of gas-forming enteric microorganisms from the gut into and through the intestinal wall to other organs. However, there has been no clear histopathological evidence to support these hypotheses.

Patient concerns:

A 61-year-old man underwent sigmoidectomy for colonic adenocarcinoma. Postoperatively, he developed paralytic ileus and then had a sudden cardiopulmonary arrest.

Diagnoses:

PI and HPVG were found at autopsy, presumably caused by the postoperative paralytic ileus and associated with BT of gas-forming organisms.

Interventions:

Cardiopulmonary resuscitation was unsuccessful.

Outcomes:

Postmortem imaging indicated the presence of massive PI and HPVG. At autopsy, there was marked intestinal emphysema with diffuse ischemic mucosal necrosis and severe pneumatosis in the stomach and intestine and marked gaseous dilation of the intrahepatic portal veins. Postmortem bacterial cultures revealed enteric bacteria in the peripheral blood and liver tissue.

Lessons:

Postoperative ileus leading to intestinal mucosal damage may be associated with BT of gas-forming enteric bacteria and the rapid onset of PI and HPVG with a lethal outcome.
On-table extubation in neonates undergoing anoplasty: an experience of anesthetic management on the concept of fast-tracking anesthesia
Authors: Cui Yu , Wang Yu , Cao Rong , Liu Kai , Huang Qing-hua , Liu Bin
Published: January 2019

Fast-track anesthesia (FTA) is difficult to achieve in neonates due to immature organ function and high rates of perioperative events. As a high-risk population, neonates require prolonged postoperative mechanical ventilation, which may lead to contradictions in cases where neonatal intensive care unit resources and ventilator facilities are limited. The choice of anesthesia strategy and anesthetic can help achieve rapid postoperative rehabilitation and save hospitalization costs. The authors describe their experience with maintaining spontaneous breathing in neonates undergoing anoplasty without opioids or muscle relaxants.

This retrospective chart review included neonates who underwent anoplasty in the authors’ institution. Twelve neonates who underwent the procedure with atomized 5% lidocaine topical anesthesia around the glottis, combined with sevoflurane sedation and caudal anesthesia facilitating tracheal intubation without opioid and muscle relaxant comprised the FTA group. Ten neonates who underwent the intervention with routine anesthesia techniques in the same period comprised the control group (group C).

The surgical success rate in the FTA group was 91.7%. There were no severe complications related to lidocaine administered around the glottis. Extubation time was significantly shorter in the FTA group than in group C (4 [2.5, 5.2] vs 81.5 [60.6, 96.8], respectively; P < .01). The duration of stay in the surgical intensive care unit (SICU) was longer in group C than in the FTA group (2 [2.0, 2.6] vs 1 [0.9, 2.0], respectively; P = .006,). A statistically significant lower rate of extubation-cough was noted after endotracheal tube removal in the FTA group compared with group C (18% vs 90%, respectively; P < .001). There was no difference in the duration of anesthesia or hospitalization costs between the 2 groups. No neonates required re-intubation after extubation.

On-table extubation via 5% atomized lidocaine topical anesthesia around the glottis for tracheal intubation combined with sevoflurane sedation and caudal anesthesia without opioid and muscle relaxant was feasible in neonates undergoing anoplasty. This reduced time to extubation, length of SICU stay and saved resources. A similar trend in cost savings was also found; nevertheless, more studies are needed to confirm these results.
A case report of spontaneous coronary artery dissection and the role of intravascular imaging for accurate diagnosis and successful management
Authors: Chen Chun-Chao , Liu Ju-Chi , Sung Li-Chin
Published: January 2019

Rationale:

Acute myocardial infarction (AMI) secondary to spontaneous coronary artery dissection (SCAD) is a rare condition. SCAD can be underdiagnosed on a coronary angiography (CAG). Therefore, the application of intravascular imaging including intravascular ultrasound (IVUS) and optical coherence tomography (OCT) is crucial for ensuring an accurate diagnosis and treatment.

Patients concerns:

A 72-year-old woman had an evolving AMI with ST elevation in the inferior leads (II, III, and aVF).

Diagnoses:

An emergent CAG showed that a double lumen had developed in the middle portion of the left circumflex artery. An IVUS examination revealed a coronary artery dissection and intramural hematoma.

Interventions:

First, the patient was treated with conservative management. We later placed a stent in response to the progression of the intramural hematoma observed during the IVUS follow-up.

Outcomes:

The patient remained symptom free after discharge. CAG with OCT at the 1-year follow-up after stent implantation showed in-stent restenosis with dissection flap with residual false lumen at the proximal site of stent. We treated this lesion with another stent.

Lessons:

From this case, we learned that in patients with AMI, SCAD should be considered as a possible diagnosis and that intravascular imaging tool can successfully guide clinical decision making and the treatment strategies.
Rare acute abdominal condition caused by mesenteric fibromatosis perforation
Authors: Li Jian , Xu Run , Hu Deng-Min
Published: January 2019

Rationale:

Mesenteric fibromatosis is a rare benign neoplasm with a tendency to spread and recur locally, without metastasis. It may present with a wide spectrum of clinical features; however, onset as a perforation is extremely rare.

Patient concerns:

The present patient was an 18-year-old female with a 10-hour history of increasing abdominal pain that arose suddenly with nausea and vomiting. She had experienced an appendectomy 2 years before this admission.

Diagnoses:

A gastrointestinal perforation was initially suspected on the basis of complaints and physical examination. The patient was thoroughly investigated for further diagnosis. Computed tomography showed a large well-defined intra-abdominal mass measuring 7.1 × 6.7 × 5.9 cm in the right lower quadrant, with adjacent small intestine compression and free intraperitoneal air. Then, the patient underwent a laparotomy. Finally, postoperative pathology and immunohistochemistry confirmed mesenteric fibromatosis, with a consecutive perforation from ileum to the bottom of tumor.

Interventions:

The patient has been treated by a resection of the mass with the adhesive small intestine, without chemotherapy or radiotherapy postoperatively.

Outcomes:

The patient had an uneventful postoperative recovery. Three months after surgery, the patient reviewed the colonoscopy, no intestinal polyps were noted. The present case has been followed up for 17 months without tumor recurrence.

Lessons:

Our case illustrates another possible cause of acute abdominal pain. Although rare, treating physicians should maintain a high suspicion index while managing a patient with an abdominal mass and pain. Close follow-up is essential because of the high incidence of local tumor recurrence.
Size and Prevalence of Pediatric Aerodigestive Programs in 2017
Authors: Gumer Lindsey , Rosen Rachel , Gold Benjamin D. , Chiou Eric H. , Greifer Melanie , Cohen Sherri , Friedlander Joel A.
Published: January 2019

Objective:

Pediatric aerodigestive programs appear to be rapidly proliferating and provide multidisciplinary, coordinated care to complex, medically fragile children. Pediatric subspecialists are considered essential to these programs. This study evaluated the state of these programs in 2017 by surveying their size, composition, prevalence, and the number of patients that they serve.

Methods:

The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Aerodigestive Special Interest Group leadership distributed an 11‐question survey to the Pediatric Gastroenterology International Listserv. The mean time of the programs’ existence, number of half‐day clinics, number of procedure days, number of patients evaluated, and the lead primary specialty were evaluated.

Results:

Thirty‐four programs responded. Twenty‐five were based in academic centers. Thirty‐one programs were located across the United States. The average time of program existence was 5.3 years (standard deviation [SD] = 4.3; range 1–17 years). Approximately 64.7% were started in the past 5 years. Twelve programs were based in the division of gastroenterology. The average number of gastroenterologists serving aerodigestive programs was 2 (SD = 1.1). The mean number of half‐day clinic sessions and procedure days were 2.8 (SD = 2.9) and 2.6 (SD = 2), respectively. New and follow‐up visits per year in each program averaged 184 (SD = 168; range 10–750).

Conclusions:

Pediatric aerodigestive programs are prevalent, proliferating, and serve a large number of complex patients across North America and the world. This survey demonstrated that programs are predominantly based in academic settings. The number of patients cared for by aerodigestive centers varies widely depending on size and age of program.
Clinical and Endoscopy Findings in Children With Accidental Exposure to Concentrated Detergent Pods
Authors: Singh Avantika , Anderson Michael , Altaf Muhammad A.
Published: January 2019

Background:

Caustic ingestion with concentrated detergent pods (CDPs) is a common problem encountered in pediatric population. There is insufficient literature about endoscopic findings in CDP ingestion and hence no current consensus or guidelines regarding the need for endoscopic evaluation.

Objectives:

To review cases of children with exposure to CDPs from 2010 to 2016 at a tertiary care children's hospital and to identifying the possibility of a correlation between clinical presentation and the endoscopic findings.

Methods:

A retrospective review identified pediatric patients with accidental caustic exposure to CDPs. Data on demographics, type of exposure, clinical symptoms, physical examination, details of the hospital course were collected. Esophagogastroduodenoscopy (EGD) findings and direct laryngoscopy‐bronchoscopy findings were also collected. Descriptive statistics were computed for all demographic and clinical variables. The association between EGD findings and clinical presentation were tested using Fisher exact test.

Results:

A total of 23 (28%) cases of CDP ingestion were identified out of 83 total cases of caustic ingestion between January 2010 and June 2016. Median age was 15 months. gastrointestinal symptoms were present in 21 (91%) patients. Examination findings were present in 8 of 23 (35%) patients. EGD (done by gastroenterologists) evaluation was done in 21 (91%) patients and positive findings were seen in 5 of 21 (24%). The proportion of patients with positive examination findings was significantly higher in patients with positive EGD findings (80% vs 20%, respectively; P = 0.0307). Direct laryngoscopy‐bronchoscopy (done by otolaryngologists) evaluation was done in 6 (26%) patients and positive findings were seen in 4 of 6 (67%).

Conclusions:

Our results suggest that oropharyngeal examination findings increase the likelihood of endoscopy findings; hence, we recommend endoscopic evaluation of patients who have examination findings secondary to exposure to CDPs. In other patients, it will be reasonable to evaluate the need for endoscopy on a case‐by‐case basis.
Hand Assessment for Elderly People in the Community
Authors: Leow Mabel Qi He , Teo Wendy , Low Tzuemn Ling , Tay Shian Chao
Published: January 2019

BACKGROUND:

Hand conditions are common in elderly persons.

PURPOSE:

To assess the prevalence of common hand conditions in elderly persons in a community setting, specifically osteoarthritis of the hand, trigger finger, and carpal tunnel syndrome.

METHODS:

The elderly persons were recruited from community groups for elderly persons. Data collection included participants' demographic and clinical data; quick disability, arm, shoulder, and hand (QuickDASH) questionnaire; and presence of hand conditions.

RESULTS:

Of the 55 elderly persons recruited, almost a third of them presented with a hand condition (n = 17, 30.8%). Hand conditions were more common in females (39% in females, 7% in males; χ2 = 4.97, p = .04). Quick-DASH scores were higher in those with hand conditions, indicating lower levels of function (greater disability) (t =−4.61, p = .002).

CONCLUSIONS:

Most elderly persons did not seek medical attention for their hand condition until the late stages. Nurses can play an important role in providing community hand assessment, education on hand symptoms, information about available treatment, and adaptive approaches to maximize functioning.
Summary: NAON's Best Practice Guideline, Total Hip Replacement (Arthroplasty)
Authors: Gabbert Tandy , Filson Rebekah , Bodden Janine , Coppola Carrie
Published: January 2019

This article summarizes the Best Practice Guideline for Total Hip Replacement (Arthroplasty) recently released by the National Association of Orthopaedic Nurses (NAON). The summary highlights the process of content development utilizing a systematic literature review and resulting recommendations for nursing care strategies throughout the patient care continuum. The authors of the Best Practice Guideline are expert nurses working in Joint Commission Disease Specific Certified clinical settings. The Summary concludes reminding readers of the purpose and focus of the guideline to enhance clinician knowledge and to improve patient care pathways and, ultimately, patient outcomes.
Variant Creutzfeldt-Jakob Disease Presenting as New-onset Psychosis
Authors: PATNIYOT NICHOLAS S. , PATNIYOT IRENE R.
Published: January 2019

The case of a patient with a first presentation psychotic episode secondary to variant Creutzfeldt-Jakob Disease (vCJD) is presented. While psychiatric symptoms are considered a prominent feature of vCJD, they may precede characteristic neurological symptoms, which can delay diagnosis. The psychotic symptoms in this case differed in quality from typical psychotic presentations, which could have helped with earlier diagnosis. The patient’s symptomatology suggested that errors in cognition and perception were largely contributing to his psychiatric symptoms. These errors appeared to be the result of prion destruction of relevant brain structures that may either be directly or secondarily involved in psychiatric disorders. The findings in this case can help elucidate how vCJD symptoms deviate from established guidelines for diagnosing primary psychiatric disorders.
An Overview of Reviews on the Safety of Electroconvulsive Therapy Administered During Pregnancy
Authors: COSHAL SHANA , JONES KRISTIN , COVERDALE JOHN , LIVINGSTON ROBIN
Published: January 2019

Objective:

To inform obstetricians and psychiatrists about the safety of electroconvulsive therapy (ECT) administration during pregnancy and to reconcile conflicting recommendations concerning this treatment.

Methods:

A systematically conducted overview was undertaken on the safety of ECT during pregnancy. The Cochrane Library, MEDLINE/PubMed, PsycINFO, and Ovid were independently searched by 2 of the authors from January 2015 to March 2017 using the following search terms: electroconvulsive therapy, ECT, and electroshock combined with pregnancy and reviews. Articles were reviewed and critically appraised using components of the PRISMA and AMSTAR systematic review assessment tools.

Results:

Of the 9 articles that were identified, 5 publications of varying methodological quality met inclusion criteria and involved a range of 32 to 339 patients. The most common problems that occurred in association with ECT were fetal arrhythmia, fetal bradycardia, premature birth, developmental delay, abdominal pain, uterine contraction, vaginal bleeding, placental abruption, and threatened abortion. The number of fetal deaths in each of the reviews ranged from 2 to 12. The authors of 1 of the 5 reviews recommended that ECT only be used as a last resort, whereas the authors of the other reviews took the stance that the administration of ECT during pregnancy was relatively safe. Differences in recommendations among reviews were in part due to inclusion criteria and how adverse events were attributed to ECT.

Conclusions:

Our overview supports the conclusion, which has also been endorsed by the American College of Obstetricians and Gynecologists and the American Psychiatric Association, that administration of ECT during pregnancy is relatively safe. Conclusions about safety, however, will become better established with the availability of more data.
One-Stage versus Two-Stage Arteriovenous Loop Reconstructions: An Experience on 103 Cases from a Single Center
Authors: Henn Dominic , Wähmann Matthias S. T. , Horsch Miriam , Hetjens Svetlana , Kremer Thomas , Gazyakan Emre , Hirche Christoph , Schmidt Volker J. , Germann Günter , Kneser Ulrich
Published: January 2019

Background:

The optimal time for flap anastomosis to an arteriovenous loop remains controversial. Whether perforator flaps and axially vascularized muscle or fasciocutaneous flaps lead to comparable outcomes in conjunction with arteriovenous loops has not been investigated.

Methods:

Medical records from 103 patients undergoing arteriovenous loop reconstruction (76 one-stage and 27 two-stage) between 2007 and 2017 were reviewed. Postoperative outcomes were compared between one- and two-stage arteriovenous loop reconstructions and different types of free flaps.

Results:

Rates of flap thrombosis, major wound complications, and flap failure did not differ significantly between one- and two-stage arteriovenous loop reconstructions (14.47 percent versus 11.11 percent, p = 1.00; 30.26 percent versus 25.93 percent, p = 0.67; and 10.53 percent versus 7.41 percent, p = 1.00). For two-stage arteriovenous loop reconstructions, the time interval between arteriovenous loop placement and flap anastomosis was a predictor for thrombotic events (OR, 1.31; p < 0.05). Anterolateral thigh flaps in conjunction with arteriovenous loops showed higher failure rates (33.33 percent) compared with all other flaps (6.59 percent) (p < 0.05) and combined latissimus dorsi and parascapular flaps (0 percent) (p < 0.05). Thrombosis rates were higher in anterolateral thigh flaps (33.33 percent) compared with all other flaps (10.99 percent; p = 0.056), and combined latissimus dorsi and parascapular flaps (0 percent; p < 0.05).

Conclusions:

Two-stage arteriovenous loop reconstructions do not lead to increased postoperative complications compared to one-stage arteriovenous loop reconstructions and may be favorable in complicated cases because of shorter operative times. To avoid an increased thrombosis risk, flap anastomosis should not be delayed beyond 10 days in two-stage arteriovenous loop reconstructions. Anterolateral thigh flaps are less suitable for arteriovenous loop reconstructions because of higher complication rates.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Synovial Biopsy in the Diagnosis of Crystal-Associated Arthropathies
Authors: Moses Viju , Asirvatham Jaya Ruth , McHugh Jonathan , Ike Robert
Published: January 2019

Background/ Objective

This study seeks to assess the utility of synovial biopsy in the diagnosis of crystal-associated arthropathies (CAAs) in a clinical setting.

Methods

In this retrospective study, we reviewed biopsy reports involving synovial tissue between 1988 and 2015. We then reviewed the records of patients where the biopsy was performed for a clinical suspicion of CAA—the clinical group—and calculated the frequency of a positive diagnosis. The t test, Mann-Whitney-Wilcoxon test, and Fisher test were used to compare clinical characteristics of patients with and without a tissue diagnosis of CAA. We also reviewed cases of unexpected detection of crystalline disease involving synovial tissue—the incidental group.

Results

Among 2786 biopsies involving the synovium, we identified 65 cases in the clinical group and 33 cases in the incidental group. In the clinical group, a relevant diagnosis was obtained from synovial tissue in 36.9%, and a CAA was diagnosed in 20%. Restricting analysis to clinical biopsies performed for a primary suspicion of CAA, a relevant diagnosis was obtained in 61.3%, and a CAA was diagnosed in 38.7%. The incidental group comprised 1.2% of all synovial biopsies and included 7 mass lesions. Basic calcium phosphate was not reported on any biopsy in the study period.

Conclusions

Synovial biopsy is a diagnostic option when suspected CAA is resistant to conventional modes of diagnosis. Crystalline diseases should be considered in the differential diagnosis of musculoskeletal mass lesions mimicking neoplasms.
Sensory and auditory evoked responses mimic synchronization of cortical oscillations induced by Transcranial Magnetic Stimulation
Authors: Krawinkel Lutz A. , Forisch Julia , Feldheim Jan F. , Backhaus Winifried , Quandt Fanny , Gerloff Christian
Published: January 2019

Background

Entrainment of cortical oscillations by repetitive Transcranial Magnetic Stimulation (rTMS) is an attractive approach to modulate brain function non-invasively in humans. Here, we applied rTMS in order to modulate oscillatory activity in ventral premotor cortex (PMv), primary motor cortex (M1), and anterior intraparietal sulcus (aIPS). These areas are thought to contribute to recovery after motor stroke and our overarching goal is to enhance their impact by rTMS. To this end, we established a setup with bifocal, neuronavigated rTMS combined with EEG and tested its technical feasibility.

Methods

Bifocal zero-phase lag synchronized rTMS at 11Hz was applied in seven young healthy volunteers to the target pairs (i) PMv and M1 and (ii) aIPS and M1. Adapting to the close vicinity between target areas, we used two small, commercially available coils and applied subthreshold stimuli in order to avoid motor evoked potentials (MEPs). Besides a parieto-occipital sham stimulation, we also included auditory and sensory stimulation in a further control experiment.

Results

First, subthreshold TMS led to a phase synchronization and evoked time-averaged potentials in the EEG. However, the same findings could be elicited by peripheral, somatosensory stimulation combined with auditory stimulation. Second, despite the small coils neuronavigation analysis showed that in most participants aIPS and M1 or PMv and M1 could not precisely be targeted due to their vicinity and restriction in coil positioning. Third, bifocal subthreshold rTMS tended to sum up where the induced fields showed the greatest overlap resulting in overt MEPs and thus raising potential safety issues.

Conclusions

The presented data show refinements for bifocal rTMS studies regarding (i) spurious entrainment or resetting effects on brain oscillations, (ii) precise anatomical targeting of areas in close vicinity, and (iii) summing up of overlapping induced electrical fields.
Development and Characterization of a Fixed Repertoire of Blood Transcriptome Modules Based on Co-expression Patterns Across Immunological States
Authors: Altman Matthew C , Rinchai Darawan , Baldwin Nicole , Toufiq Mohammed , Whalen Elizabeth , Garand Mathieu , Kabeer Basirudeen Ahamed , Alfaki Mohamed , Presnell Scott , Khaenam Prasong , Benitez Aaron Ayllon , Mougin Fleur , Thébault Patricia , Chiche Laurent , Jourde-Chiche Noemie , Phillips J Theodore , Klintmalm Goran , O’Garra Anne , Berry Matthew , Bloom Chloe , Wilkinson Robert J , Graham Christine M , Lipman Marc , Lertmemongkolchai Ganjana , Bedognetti Davide , Thiebaut Rodolphe , Kheradmand Farrah , Mejias Asuncion , Ramilo Octavio , Palucka Karolina , Pascual Virginia , Banchereau Jacques , Chaussabel Damien
Published: January 2019

As the capacity for generating large scale data continues to grow the ability to extract meaningful biological knowledge from it remains a limitation. Here we describe the development of a new fixed repertoire of transcriptional modules. It is meant to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome profiling data. It is supported by customized resources, which include analysis workflows, fingerprint grid plots data visualizations, interactive web applications providing access to a vast number of module-specific functional profiling reports, reference transcriptional profiles and give users the ability to visualize of changes in transcript abundance across the modular repertoire at different granularity levels. A use case focusing on a set of six modules comprising interferon-inducible genes is also provided. Altogether we hope that this resource will also serve as a framework for improving over time our collective understanding of the immunobiology underlying blood transcriptome profiling data.
Trophic complexity alters the diversity-multifunctionality relationship in experimental grassland mesocosms
Authors: Anujan Krishna , Heilpern Sebastian A. , Prager Case M. , Naeem Shahid
Published: January 2019

Higher levels of diversity within trophic levels are necessary to sustain multiple ecosystem functions, but this diversity-multifunctionality relationship peaks at intermediate percent-function thresholds. The presence of multiple trophic levels, or trophic complexity, affects ecosystem multifunctionality but its effect on the diversity-multifunctionality relationship has not been experimentally tested. To test the sensitivity of the diversity-multifunctionality relationship to trophic complexity, we simultaneously manipulated plant diversity and trophic complexity in a multifactorial tall-grass prairie mesocosm experiment at Cedar Creek, Minnesota, USA. Trophic complexity altered the diversity-multifunctionality relationship, by lowering the height of the peak as well as by shifting to a negative effect at lower thresholds. These outcomes are consistent with decreases in both the “jack-of-all-trades” effect and complementarity among plant species. Our findings suggest that trophic complexity, which is experiencing widespread declines on a global scale, is important for sustaining ecosystem multifunctionality in the face of equally widespread declines in biodiversity.
Sulcal organization in the medial frontal cortex reveals insights into primate brain evolution
Authors: Amiez Céline , Sallet Jérome , Hopkins William D. , Meguerditchian Adrien , Hadj-Bouziane Fadila , Ben Hamed Suliann , Wilson Charles R.E. , Procyk Emmanuel , Petrides Michael
Published: January 2019

Although the relative expansion of the frontal cortex in primate evolution is generally accepted, the nature of the human uniqueness, if any, and between-species anatomo-functional comparisons of the frontal areas remain controversial. To provide a novel interpretation of the evolution of primate brains, sulcal morphological variability of the medial frontal cortex was assessed in old-world monkeys (macaque, baboon) and Hominoidea (chimpanzee, human). We discovered that both Hominoidea do possess a paracingulate sulcus, which was previously thought to be uniquely human and linked to higher cognitive functions like mentalizing. Also, we revealed systematic sulcal morphological organisations of the medial frontal cortex that can be traced from multiple old-world monkey to Hominoidea species, demonstrating an evolutionary conserved organizational principle. Our data provide a new framework to compare sulcal morphology, cytoarchitectonic areal distribution, connectivity, and function across the primate order, leading to clear predictions on how other primate brains might be anatomo-functionally organized.
Quantification and Isolation ofBacillus subtilisSpores using Cell Sorting and automated Gating
Authors: Karava Marianna , Bracharz Felix , Kabisch Johannes
Published: January 2019

The Gram-positive bacteriumBacillus subtilisis able to form endospores which have a variety of biotechnological applications. Due to this ability,B. subtilisis as well a model organism for cellular differentiation processes. Sporulating cultures ofBacillus subtilisform sub-populations which include vegetative cells, spore forming cells and spores. In order to readily and rapidly quantify spore formation we employed flow cytometric and fluorescence activated cell sorting techniques in combination with nucleic acid fluorescent staining in order to investigate the distribution of sporulating cultures on a single cell level. Moreover we tested different fluorescent dyes as well as different conditions in order to develop a method for optimal separation of distinct populations during sporulation. Automated gating procedures using k-means clustering and thresholding by gaussian mixture modeling were employed to avoid subjective gating and allow for the simultaneous measurement of controls. We utilized the presented method for monitoring sporulation over time in strains harboring different genome modifications. We identified the different subpopulations formed during sporulation by employing sorting and microscopy. Finally, we employed the technique to show that a double knock-out mutant of the phosphatase gene encoding Spo0E and of the spore killing factor SkfA results in faster spore formation.
Intraoperative contrast-enhanced ultrasound for cerebral glioma resection and the relationship with microvessel density
Authors: Wang Jia , Liu Xi , Yang Yilin , Duan Yunyou
Published: January 2019

Purpose

We studied the value of intraoperative contrast-enhanced ultrasound (iCEUS) for real-time monitoring of resection of cerebral gliomas, and analyzed the relationship between CEUS parameters and microvessel density (MVD) of different pathologic grades of cerebral gliomas.

Materials and Methods

ICEUS was performed in 49 patients with cerebral gliomas. The enhancement characteristics of cerebral gliomas were observed before and after tumor resection. The number of microvessels was counted by immunostaining with anti-CD34. Differences in these quantitative parameters in cerebral gliomas were compared and subjected to a correlation analysis with MVD.

Results

The color Doppler flow classification within lesions were significantly different before and after iCEUS (p<0.05). The assessment of iCEUS parameters and tumor MVD showed that cerebral gliomas of different pathological grades had different characteristics. The time-to-peak (Tmax) was significantly shorter, the peak intensity (PI) and MVD were significantly higher in high-grade cerebral gliomas than in low-grade cerebral gliomas (p<0.05). According to the immunostaining, PI was positively (r=0.637) correlated with MVD and Tmax was negatively (r=–0.845) correlated with MVD.

Conclusion

ICEUS may determine the borders of lesions more clearly, indicate the microvascular perfusion in real time, and be helpful in understanding the cerebral gliomas grade.
Piezo1 is required for outflow tract and aortic valve development
Authors: Faucherre Adèle , Moha ou Maati Hamid , Nasr Nathalie , Pinard Amélie , Theron Alexis , Odelin Gaëlle , Desvignes Jean-Pierre , Salgado David , Collod-Béroud Gwenaëlle , Avierinos Jean-François , Lebon Guillaume , Zaffran Stéphane , Jopling Chris
Published: January 2019

Aims-

During embryogenesis, the onset of circulatory blood flow generates a variety of hemodynamic forces which reciprocally induce changes in cardiovascular development and performance. It has been known for some time that these forces can be detected by as yet unknown mechanosensory systems which in turn promote cardiogenic events such as outflow tract and aortic valve development. PIEZO1 is a mechanosensitive ion channel present in endothelial cells where it serves to detect hemodynamic forces making it an ideal candidate to play a role during cardiac development. We sought to determine whether PIEZO1 is required for outflow tract and aortic valve development.

Methods and results-

By analysing heart development in zebrafish we have determined thatpiezo1is expressed in the developing outflow tract where it serves to detect hemodynamic forces. In particular, we have found that mechanical forces generated during the cardiac cycle activate Piezo1 which triggers nitric oxide to be released in the outflow tract. Consequently, disrupting Piezo1 signalling leads to defective outflow tract and aortic valve development and indicates this gene may be involved in the etiology of congenital heart diseases. Based on these findings, we analysed genomic data generated from a cohort of bicuspid aortic valve patients and identified 3 probands who each harboured a novel variant inPIEZO1. Subsequentin vitroandin vivoassays indicates that these variants behave as dominant negatives leading to an inhibition of normal PIEZO1 mechanosensory activity and defective aortic valve development.

Conclusion-

These data indicate that the mechanosensitive ion channelpiezo1is required for OFT and aortic valve development and, furthermore, dominant negative variants ofPIEZO1appear to be associated with BAV in humans.
C/EBPδ demonstrates a dichotomous role in tumor initiation and promotion of epithelial carcinoma
Authors: Sowamber Ramlogan , Chehade Rania , Bitar Mahmoud , Dodds Leah , Milea Anca , Slomovitz Brian , Shaw Patricia A , George Sophia HL
Published: January 2019

C/EBPδ(CEBPD), a gene part of the highly conserved basic-leucine zipper (b-ZIP) domain of transcriptional factors, is downregulated in 65% of high grade serous carcinoma of the ovary (HGSC). Overexpression ofC/EBPδin different tumors as glioblastoma and breast cancer either promotes tumor progression or inhibits growth. Despite these contradictory roles in different cancer types, we show thatC/EBPδoverexpression has a consistent function of downregulating proliferation and promoting migration in fallopian tube epithelial cells (FTE). We show that the FTE have both mesenchymal and epithelial cell characteristics. Further, our data supports a role forC/EBPδas an early regulatory transcriptional factor that promotes a mesenchymal to epithelial (MET) phenotype by upregulating E-cadherin and downregulating vimentin and N-cadherin in FTE cells. We demonstrate that overexpression ofC/EBPδin ovarian and breast cancer cell lines have consistent effects and phenotype as the FTE cells. Our findings suggest a role forC/EBPδin the early events of ovarian serous carcinogenesis which may be used to help further understand how the disease develops from a premalignant cells.
Behavior influences range limits and patterns of coexistence across an elevational gradient in tropical bird diversity
Authors: Freeman Benjamin G , Tobias Joseph A , Schluter Dolph
Published: January 2019

Does competition influence patterns of coexistence between closely related taxa? Here we address this basic question in ecology by analyzing patterns of range overlap between related bird species (“sister pairs”) distributed along a Neotropical elevational gradient. We explicitly contrast the behavioral dimension of interspecific competition (interference competition) with similarity in resource acquisition traits (exploitative competition). We find that behavioral interactions are generally important in setting elevational range limits and preventing coexistence of closely related species. Specifically, close relatives that defend year-round territories tend to live in non-overlapping elevational distributions, while close relatives that do not defend territories tend to broadly overlap in distribution. In contrast, neither similarity in beak morphology nor evolutionary relatedness was associated with patterns of range limitation. Our main result is that interference competition can be an important driver of species ranges at the scale of entire diverse assemblages. Consequently, we suggest that behavioral dimensions of the niche should be more broadly incorporated in macroecological studies.
Mutational Landscape of Spontaneous Base Substitutions and Small Indels in Experimental Caenorhabditis elegans Populations of Differing Size
Authors: Konrad Anke , Brady Meghan J. , Bergthorsson Ulfar , Katju Vaishali
Published: January 2019

Experimental investigations into the rates and fitness effects of spontaneous mutations are fundamental for our understanding of the evolutionary process. To gain insights into the molecular and fitness consequences of spontaneous mutations, we conducted a mutation accumulation (MA) experiment at varying population sizes in the nematode Caenorhabditis elegans, evolving 35 lines in parallel for 409 generations at three population sizes (N = 1, 10, 100 individuals). Here, we focus on nuclear SNPs and small indels under minimal influence of selection, as well as their accrual rates in larger populations under greater selection efficacy. The spontaneous rates of base substitutions and small indels are 1.84 × 10−9 substitutions and 6.84 × 10−10 changes /site/generation, respectively. Small indels exhibit a deletion-bias with deletions exceeding insertions by three-fold. Notably, there was no correlation between the frequency of base substitutions, nonsynonymous substitutions or small indels with population size. These results contrast with our previous analysis of mtDNA mutations and nuclear copy-number changes in these MA lines, and suggest that nuclear base substitutions and small indels are under less stringent purifying selection compared to the former mutational classes. A transition bias was observed in exons as was a near universal base substitution bias towards A/T. Strongly context-dependent base substitutions, where 5’–T and 3’–As increase the frequency of A/T → T/A transversions, especially at the boundaries of A or T homopolymeric runs, manifest as higher mutation rates in (i) introns and intergenic regions relative to exons, (ii) chromosomal cores versus arms and tips, and (iii) germline-expressed genes.
Comparative analysis of sfRNA in the genome of pre-epidemic and epidemic Zika viruses for host interacting proteins potentially related to the recent epidemic
Authors: Desingu P.A.
Published: January 2019

Zika virus (ZIKV), circulating in more than 70 countries since 2014, is causing severe developmental abnormality to compare to pre-epidemic infection. ZIKV related flaviviruses as the ability to produce subgenomic flaviviral RNAs (sfRNAs) which are associated with pathogenicity in foetal mice. This study, delineate the increased virulence of ZIKV through sfRNA mediated host protein interaction. Phylogenetically ZIKV sfRNA formed three distinct clades of African, Asian and American strains. Compare with preepidemic, the epidemic ZIKV sfRNA has genetic, RNA secondary structure and host protein interacting profile diversity. Interestingly this study found that ZIKV sfRNA interacting proteins involved in the neuronal development, differentiation, proliferation, and apoptosis along with spermatogenesis, host immunity and viral pathogenesis. The difference in the interaction profile and interaction strength between pre-epidemic and epidemic virus could be the reason for the increased virulence of the recent epidemic viruses. Targeting this protein will be the potent choice for antiviral drug designing.
On measuring selection in cancer from subclonal mutation frequencies
Authors: Bozic Ivana , Paterson Chay , Waclaw Bartlomiej
Published: January 2019

Recently available cancer sequencing data have revealed a complex view of the cancer genome containing a multitude of mutations, including drivers responsible for cancer progression and neutral passengers. Measuring selection in cancer and distinguishing drivers from passengers have important implications for development of novel treatment strategies. It has recently been argued that a third of cancers are evolving neutrally, as their mutational frequency spectrum follows a 1/f power law expected from neutral evolution in a particular intermediate frequency range. We study a stochastic model of cancer evolution and derive a formula for the probability distribution of the cancer cell frequency of a subclonal driver, demonstrating that driver frequency is biased towards 0 and 1. We show that it is difficult to capture a driver mutation at an intermediate frequency, and thus the calling of neutrality due to a lack of such driver will significantly overestimate the number of neutrally evolving tumors. Our approach provides precise quantification of the validity of the 1/f statistic across the entire range of all relevant parameter values. Our results are also applicable to the question of distinguishing driver and passenger mutations in a general exponentially expanding population.