bluuebunny/crossref_metadata_2025 huggingface dataset:
Nicotinic Acetylcholine Receptor Signaling in the Hypothalamus: Mechanisms Related to Nicotine’s Effects on Food Intake
Authors: Calarco Cali A , Picciotto Marina R
Published: January 2019

Despite health risks associated with smoking, up to 20% of the US population persist in this behavior; many smoke to control body weight or appetite, and fear of post-cessation weight gain can motivate continued smoking. Nicotine and tobacco use is associated with lower body weight, and cessation yields an average weight gain of about 4 kg, which is thought to reflect a return to the body weight of a typical nonsmoker. Nicotine replacement therapies can delay this weight gain but do not prevent it altogether, and the underlying mechanism for how nicotine is able to reduce weight is not fully understood. In rodent models, nicotine reduces weight gain, reduces food consumption, and alters energy expenditure, but these effects vary with duration and route of nicotine administration. Nicotine, acting through nicotinic acetylcholine receptors (nAChRs), increases the firing rate of both orexigenic agouti-related peptide and anorexigenic proopiomelanocortin neurons in the arcuate nucleus of the hypothalamus (ARC). Manipulation of nAChR subunit expression within the ARC can block the ability of nicotine and the nicotinic agonist cytisine from decreasing food intake; however, it is unknown exactly how this reduces food intake. This review summarizes the clinical and preclinical work on nicotine, food intake, and weight gain, then explores the feeding circuitry of the ARC and how it is regulated by nicotine. Finally, we propose a novel hypothesis for how nicotine acts on this hypothalamic circuit to reduce food intake.

Implications: This review provides a comprehensive and updated summary of the clinical and preclinical work examining nicotine and food intake, as well as a summary of recent work examining feeding circuits of the hypothalamus. Synthesis of these two topics has led to new understanding of how nAChR signaling regulates food intake circuits in the hypothalamus.
Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens
Authors: De La Cruz Justin , Vardhanbhuti Saran , Sahoo Malaya K , Rovner Robert , Bosch Ronald J , Manasa Justen , Katzenstein David A , Pinsky Benjamin A
Published: January 2019

Background

Efavirenz (EFV)-based regimens select broad drug resistance to nonnucleoside reverse-transcriptase inhibitors (NNRTIs), limiting the effectiveness of EFV and other NNRTIs. The duration, persistence, and decay of drug resistance mutations (DRMs) in the proviral reservoir is not well defined.

Methods

Participants with virologic failure of EFV-based regimens and drug-resistant viremia with the K103N mutation in plasma ribonucleic acid (RNA) were identified from AIDS Clinical Trials Group (ACTG) studies A364 and A5095. These individuals received a second-line, boosted protease inhibitor-based regimen with suppression of viremia for up to10 years during long-term follow-up (median = 3.6 years; interquartile range, 2.1–6.9 years). Proviral deoxyribonucleic acid (DNA) from cryopreserved peripheral blood mononuclear cells was sequenced to identify the persistence of DRM.

Results

Twenty-eight participants from ACTG 364 and ACTG 5095 were evaluated. Sanger sequencing of proviral DNA detected K103N as well as additional reverse-transcriptase inhibitor (RTI) mutations. Ultradeep sequencing confirmed persistence of K103N in 71% of participants with minimal decay over time. In an adjusted model including years since suppression, persistent proviral K103N was 2.6 times more likely (95% confidence interval, 1.0–6.4) per log10 higher human immunodeficiency virus RNA at EFV failure.

Conclusions

Persistence of RTI mutations in proviral DNA after virologic failure has implications for the effectiveness of future drug regimens and the recycling of RTI drugs.
Early Cardiac Mitochondrial Molecular and Functional Responses to Acute Anthracycline Treatment in Wistar Rats
Authors: Pereira Gonçalo C , Pereira Susana P , Pereira Francisco B , Lourenço Nuno , Lumini José A , Pereira Claudia V , Bjork James A , Magalhães José , Ascensão António , Wieckowski Mariusz R , Moreno António J , Wallace Kendall B , Oliveira Paulo J
Published: January 2019

Doxorubicin (DOX) is an anticancer drug widely used to treat human and nonhuman tumors but the late and persistent cardio-toxicity reduces the therapeutic utility of the drug. The full mechanism(s) of DOX-induced acute, subchronic and delayed toxicity, which has a preponderant mitochondrial component, remains unclear; therefore, it is clinically relevant to identify early markers to identify patients who are predisposed to DOX-related cardiovascular toxicity. To address this, Wistar rats (16 weeks old) were treated with a single DOX dose (20 mg/kg, i.p.); then, mRNA, protein levels and functional analysis of mitochondrial endpoints were assessed 24 h later in the heart, liver, and kidney. Using an exploratory data analysis, we observed cardiac-specific alterations after DOX treatment for mitochondrial complexes III, IV, and preferentially for complex I. Conversely, the same analysis revealed complex II alterations are associated with DOX response in the liver and kidney. Interestingly, H2O2 production by the mitochondrial respiratory chain as well as loss of calcium-loading capacity, markers of subchronic toxicity, were not reliable indicators of acute DOX cardiotoxicity in this animal model. By using sequential principal component analysis and feature correlation analysis, we demonstrated for the first time alterations in sets of transcripts and proteins, but not functional measurements, that might serve as potential early acute markers of cardiac-specific mitochondrial toxicity, contributing to explain the trajectory of DOX cardiac toxicity and to develop novel interventions to minimize DOX cardiac liabilities.
A Real-Time PCR Differentiating Pantoea stewartii subsp. stewartii From P. stewartii subsp. indologenes in Corn Seed
Authors: Pal Narinder , Block Charles C. , Gardner Candice A. C.
Published: January 2019

Stewart’s wilt of corn caused by the bacterium Pantoea stewartii subsp. stewartii is a seed-borne disease of major phytosanitary importance. Many countries have imposed restrictions on corn seed imports from regions where the disease occurs to prevent the potential introduction of the pathogen. Current laboratory testing methods (enzyme-linked immunosorbent assay [ELISA] and polymerase chain reaction [PCR]) cannot readily distinguish P. stewartii subsp. stewartii from the closely related subspecies Pantoea stewartii subsp. indologenes. However, P. stewartii subsp. indologenes, a nonpathogen on corn, is occasionally found on corn seed as part of the resident bacterial population and can yield false positive test results. A real-time PCR targeting the cpsAB intergenic sequence was developed to specifically detect P. stewartii subsp. stewartii from corn seeds and distinguish it from P. stewartii subsp. indologenes. The assay successfully detected P. stewartii subsp. stewartii from corn seed, and P. stewartii subsp. indologenes-contaminated seed lots, which previously yielded false positives by ELISA and published PCR methods, were negative. The absence of P. stewartii subsp. stewartii and the presence of P. stewartii subsp. indologenes in this seed were confirmed by size differentiation of the cpsAB amplicons in a conventional PCR. By distinguishing the two subspecies, the assays described would avoid false positive results and help prevent unnecessary restrictions on international movement of corn seed.
Managing Ulcers Associated with Pyoderma Gangrenosum with a Urinary Bladder Matrix and Negative-Pressure Wound Therapy
Authors: Dillingham Claire Sanger , Jorizzo Joseph
Published: January 2019

Pyoderma gangrenosum (PG) is a rare disease that presents as painful ulcerations with inflammation and undermining at the borders. The ulcers can occur anywhere on the body but are most commonly seen on the lower extremities. The etiology of PG is unknown, and there are no definitive diagnostic criteria; PG is a diagnosis of exclusion, which can present serious delays in treatment.

Patients should be treated with an interdisciplinary approach with aggressive immunosuppression, treatment of any comorbidities, maximization of nutrition status, reconstructive surgery for treatment of the wound, and physical therapy for deconditioning.

This article presents a case study of one patient treated with a porcine urinary bladder matrix and negative-pressure wound therapy; this treatment combination provided pain relief, coverage of the wound, an acceptable aesthetic outcome, and long-term stability.
Implementing a Chronic Wound Care Workshop for Internal Medicine Residents
Authors: White-Chu Elizabeth Foy , Le Tri , Cordrey Renee
Published: January 2019

OBJECTIVE:

To determine the feasibility of a piloted wound care curriculum within a busy internal medicine (IM) curriculum.

METHODS:

This prospective pilot study was conducted with 89 IM residents at an academic teaching hospital. The residents were provided a 90-minute workshop in chronic wound care. They anonymously completed a clinical vignette to target practice behavior prior to the workshop. The workshop was mixture of didactic and hands-on practice of sharp debridement and wound dressing selection. Three months later, the residents completed the same clinical vignette along with questions on changes and barriers to change in their practice.

MAIN OUTCOME MEASURES:

Change in behavior of chronic wound care management, measurements of barriers to change in participant continuity clinics.

MAIN RESULTS:

Of the participants, 57 residents (64%) and 25 residents (28%) completed a pre- and postvignette, respectively. Ten (40%) of the postvignette respondents stated that they had made changes in their care. Barriers to change included having a supervising attending physician who is not comfortable with wound care, a lack of wound care resources available in clinic, and a lack of confidence even after the session.

CONCLUSIONS:

It is feasible to insert a chronic wound care education into a busy IM curriculum. Future efforts will be aimed at assessing the wound care needs/resources of the IM outpatient clinics, addressing the comfort of the supervising attending physicians and residents with wound care, and focusing the curriculum on high-yield interventions.
Martorell’s Ulcer Successfully Treated by Wireless Microcurrent Stimulation Technology
Authors: Wirsing Peter G. , Konstantakaki Maria , Poulas Konstantinos A.
Published: January 2019

Martorell’s ulcers are hard-to-heal leg ulcers typically accompanied by a significant elevation of blood pressure and severe pain. This case study examines the use of an innovative technology, wireless microcurrent stimulation, for the healing of a Martorell’s ulcer. Using wireless microcurrent stimulation, study authors managed to reduce the size of a large Martorell’s ulcer by 90% within 8 weeks. In this article, the case of a 65-year-old woman is discussed in detail, and this new, contactless method is compared with traditional ulcer healing methods.
Allogeneic Versus Autologous Injectable Mesenchymal Stem Cells for Knee Osteoarthritis: Review and Current Status
Authors: Mautner Kenneth , Carr Devon , Whitley Jeremy , Bowers Robert
Published: January 2019

Background:

Osteoarthritis (OA) is the leading cause of joint disease in the United States. Conventional conservative interventions are often ineffective in providing long-term improvements in pain and function, and mesenchymal stem cell (MSC) therapy provides a promising treatment option. The traditional source of MSCs was of autologous origin; however, allogeneic MSC treatments are gaining popularity.

Objectives:

To review the current literature and perform a best evidence synthesis regarding the use of injectable allogeneic and autologous MSCs for the treatment of knee OA.

Results:

Although many studies were limited by sample size and lack of a control group, there were 19 studies that assessed injectable MSC therapy for knee OA, and most shown potential to improve pain and function. There were no studies that compared autologous versus allogeneic MSC injections, and only 1 study that compared adipose-derived versus bone marrow–derived MSC injections that showed significant improvements in pain and function but no significant differences between injection groups.

Conclusions:

MSC therapies in the treatment of knee OA are safe and have shown promising results but the available studies are limited. At this time, no definitive recommendations can be made regarding which MSC source to use. Allogeneic MSCs offer theoretical advantages over autologous MSCs, especially in ease of use and consistency of product, but there are concerns regarding cell viability and vitality, as well as the body’s response to nonautologous products. Future clinical trials should focus on randomized head-to-head comparisons of MSC sources as well as the use of multiple injections for patients with knee OA.
The Gastrointestinal Subsyndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose-response Relationship With and Without Medical Management
Authors: MacVittie Thomas J. , Farese Ann M. , Parker George A. , Jackson William , Booth Catherine , Tudor Gregory L. , Hankey Kim G. , Potten Christopher S.
Published: January 2019

Well-characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the US Food and Drug Administration’s Animal Rule. Development of a model for the gastrointestinal acute radiation syndrome requires knowledge of the radiation dose-response relationship and time course of mortality and morbidity across the acute and prolonged gastrointestinal radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that has been used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality relative to the hematopoietic acute radiation syndrome, gastrointestinal acute radiation syndrome, and lung injury. It can be used to assess the natural history of gastrointestinal damage, concurrent multiple organ injury, and aspects of the mechanism of action for acute radiation exposure and treatment. A systematic review of relevant studies that determined the dose-response relationship for the gastrointestinal acute and prolonged radiation syndrome in the rhesus macaque relative to radiation dose, quality, dose rate, exposure uniformity, and use of medical management has never been performed.
Proteomic Evaluation of the Acute Radiation Syndrome of the Gastrointestinal Tract in a Murine Total-body Irradiation Model
Authors: Huang Weiliang , Yu Jianshi , Jones Jace W. , Carter Claire L. , Pierzchalski Keely , Tudor Gregory , Booth Catherine , MacVittie Thomas J. , Kane Maureen A.
Published: January 2019

Radiation exposure to the gastrointestinal system contributes to the acute radiation syndrome in a dose- and time-dependent manner. Molecular mechanisms that lead to the gastrointestinal acute radiation syndrome remain incompletely understood. Using a murine model of total-body irradiation, C57BL/6J male mice were irradiated at 8, 10, 12, and 14 Gy and assayed at day 1, 3, and 6 after exposure and compared to nonirradiated (sham) controls. Tryptic digests of gastrointestinal tissues (upper ileum) were analyzed by liquid chromatography-tandem mass spectrometry on a Waters nanoLC coupled to a Thermo Scientific Q Exactive hybrid quadrupole-orbitrap mass spectrometer. Pathway and gene ontology analysis were performed with Qiagen Ingenuity, Panther GO, and DAVID databases. A number of trends were identified in our proteomic data including pronounced protein changes as well as protein changes that were consistently up regulated or down regulated at all time points and dose levels interrogated. Time- and dose-dependent protein changes, canonical pathways affected by irradiation, and changes in proteins that serve as upstream regulators were also identified. Additionally, proteins involved in key processes including inflammation, radiation, and retinoic acid signaling were identified. The proteomic profiling conducted here represents an untargeted systems biology approach to identify acute molecular events that will be useful for a greater understanding of animal models and may be potentially useful toward the development of medical countermeasures and/or biomarkers.
Dosimetric Comparison of Four Different Techniques for Supraclavicular Irradiation in 3D-conformal Radiotherapy of Breast Cancer
Authors: Firouzjah Razzagh Abedi , Banaei Amin , Farhood Bagher , Bakhshandeh Mohsen
Published: January 2019

This study aimed to compare and evaluated the dosimetric characteristics of esophagus, spinal cord, carotid artery, lungs, and brachial plexus in patients with breast cancer undergoing four various techniques of supraclavicular irradiation. By keeping unchanged the breast tangential radiotherapy fields, four different treatment field arrangements were created to irradiate the supraclavicular region as follows: (1) four field (4F; 1 anterior-posterior and 1 posterior-anterior), (2) six field (6F; 2 anterior-posterior and 2 posterior-anterior), (3) five field-1 (5F-1; 2 anterior-posterior and 1 posterior-anterior), and (4) five field-2 (5F-2; 1 anterior-posterior and 2 posterior-anterior). Then, the dosimetric parameters for the above-mentioned organs were evaluated. The mean dose (D
mean) of the esophagus had significant difference between 6F and 5F-2 techniques. For the spinal cord, the D
mean dosimetric parameter demonstrated significant difference between the 4F and 6F techniques, and between the 4F and 5F-1 techniques, with lower values for the 4F technique. There was no significant difference between the different irradiation techniques in all the dosimetric parameters for the carotid artery. The D
mean of the left lung significantly differed between the 4F and 5F-2 techniques, with lower values for the 5F-2 technique. Furthermore, the V
20Gy dosimetric parameter had significant difference between the 4F and 6F, and also 4F and 5F-2, techniques with lower values for 5F-2. The maximum dose (D
max) of the brachial plexus showed significant difference between the two techniques of 5F. The V
45Gy dosimetric parameter of the brachial plexus revealed significant difference between the 4F and 6F techniques, and also between the 4F and 5F-1 techniques, with lower values for 5F-1. In general, these techniques had similar dosimetric results, with little differences. The dosimetric parameters for the esophagus and lung showed better results with the 5F-2 technique in comparison with other techniques. Dosimetric results for the brachial plexus and spinal cord improved with the 5F-1 and 4F techniques, respectively, against other techniques. Dose distribution for the carotid artery did not differ in the four irradiation techniques.
Integrating Patient Education Into the Glaucoma Clinical Encounter: A Lean Analysis
Authors: Newman-Casey Paula A. , Musser John A. , Niziol Leslie M. , Heisler Michele M. , Kamat Shivani S. , Shah Manjool M. , Patel Nish , Cohn Amy M.
Published: January 2019

Purpose:

The main purpose of this study was to use Lean analysis to identify how often and when wait times occur during a glaucoma visit to identify opportunities for additional patient engagement.

Methods:

This prospective observational time-motion study measured process and wait times for 77 patient visits from 12 ophthalmologists at an academic glaucoma clinic over a 3-month period. Value stream maps visually diagramed the process of a clinical visit from the patient’s perspective. Descriptive statistics were calculated for process times, wait times, and the frequency of 10+ minute wait times during each part of the visit. Key stakeholders participated in a root cause analysis to identify reasons for long wait times. The main outcome measure was average times (hours: minutes: seconds) for process times and wait times.

Results:

Twenty-nine new visit (NV) patients and 48 return visit (RV) patients were included. Total time in clinic was 187.1±44.5 (mean±SD) minutes for NV patients and 102.0±44.7 minutes for RV patients. Wait time for NV patients was 63.7±33.4 minutes (33.1% of total appointment time) and for RV patients was 52.6±31.6 minutes (49.4% of the total appointment time). All NV patients and 87.5% of RV patients had at least one 10+ minute wait time during their clinic visit and the majority (75.9% NV, 60.4% RV) had >1.

Conclusions:

Currently, sufficient wait time exists during the visit for key portions of glaucoma education such as teaching eye drop instillation.
Coverage rate of ADME genes from commercial sequencing arrays
Authors: Zaid Nabil , Limami Youness , Senhaji Nezha , Errafiy Nadia , Khalki Loubna , Bakri Youssef , Zaid Younes , Amzazi Saaid
Published: January 2019

Pharmacogenomics offers remarkable potential for the rapid translation of discoveries into changes in clinical practice. In the present work, we are interested in evaluating the ability of commercially available genome-wide association sequencing chips to cover genes that have high pharmacogenomics potential.

We used a set of 2794 variations within 369 absorption, distribution, metabolism, and elimination (ADME) genes of interest, as previously defined in collaboration with the Pharma ADME consortium. We have compared the Illumina TrueSeq and both Agilent SureSelect and HaloPlex sequencing technologies. We have developed Python scripts to evaluate the coverage for each of these products. In particular, we considered a specific list of 155 allelic variants in 34 genes which present high pharmacogenomics potential. Both the theoretical and practical coverage was assessed.

Given the need to have a good coverage to establish confidently the functionality of an enzyme, the observed rates are unlikely to provide sufficient evidence for pharmacogenomics studies. We assessed the coverage using enrichment technology for exome sequencing using the Illumina Trueseq exome, Agilent SureSelectXT1 V4 and V5, and Haloplex exome, which offer a coverage of 96.12%, 91.61%, and 88.38%, respectively.

Although pharmacogenomic advances had been limited in the past due in part to the lack of coverage of commercial genotyping chips, it is anticipated that future studies that make use of new sequencing technologies should offer a greater potential for discovery.
Solitary colonic metastasis from primary lung adenocarcinoma first presenting as intestinal obstruction
Authors: Choi Sang-ji , Hong Seong Kweon , Chae Gibong , Ryu Young-Joon , Park Sung-Bae , Kim Yang Hee , Moon Suk-Bae , Kim Song-Yi , Kim Hwansoo
Published: January 2019

Rationale:

The brain, liver, adrenal glands, and bone are the most common sites of metastatic disease in patients with lung cancer. Symptomatic gastrointestinal metastases are rare. In the present report, we describe a rare case of a patient with intestinal obstruction due to solitary colonic metastasis from primary lung adenocarcinoma, wherein the intestinal obstruction was the first symptom of lung cancer.

Patient concerns:

A 74-year-old man was admitted to the emergency room with abdominal pain and vomiting, and abdominal computed tomography (CT) indicated obstruction of the ascending colon due to a huge mass.

Diagnosis:

The ascending colon cancer was found to be a metastatic adenocarcinoma based on the results of the pathology report. Chest CT and positron emission tomography-CT were performed to identify the cancer origin site. Moreover, immunohistochemical staining of the tissue specimen for thyroid transcription factor 1, cytokeratin 7 (CK7), and CK20 and CT-guided gun biopsy of the lung mass confirmed the presence of an adenocarcinoma that originated from the lung.

Intervention:

Right hemicolectomy was performed as the primary treatment.

Outcomes:

The patient recovered without any problems due to the surgery itself. However, malignant pleural effusion deteriorated, and no additional palliative chemotherapy was performed.

Lessons:

Patients with malignant bowel obstruction along with lung infiltration should be suspected of not only colon cancer with lung metastasis, but also lung cancer with colon metastasis.
Characteristics and proposed classification system of posterior pilon fractures
Authors: Zhang Jianzheng , Wang Hao , Pen Cheng , Qu Wen-chun , Duan Lida , Ren Jixin , Li Lianhua , Liu Zhi , Sun Tiansheng
Published: January 2019

Posterior pilon fractures involve the medial malleolus (MM). Our purpose was to define the characteristics of posterior pilon fractures, and propose a classification system based on fracture morphology and type of management.

The records of patients with posterior pilon fractures treated from 2011 to 2015 were retrospectively reviewed. The injury mechanism, fracture morphology, surgical approach, and follow-up results were reviewed and analyzed. This study was approved by the Institutional Review Board of PLA Army General Hospital.

Thirty-six patients, 18 males and 18 females (mean age: 48.9 years) were included in the study. Four characteristics were used to define posterior pilon fractures. A simple posterolateral approach or a combined posterolateral and posteromedial approach was used for reduction and fixation in all patients. The mean follow-up time was 28.2 months, and at the end of follow-up, the mean American Orthopedic Foot and Ankle Society Score (AOFAS) was 82.5 points (range: 35–100 points). Based on injury mechanism and fracture morphology, we classified posterior pilon fractures into 3 types that suggest the optimal surgical approach: type I, a single complete fracture fragment; type II, a posterior malleolus fracture with 2 subtypes; type III, a posterior malleolus fracture associated with complete MM fracture with 2 subtypes.

The proposed classification system based on injury mechanism and fracture morphology can guide the surgical approach to maximize outcomes.
Population pharmacokinetics and individualized lobaplatin regimen for the treatment of Chinese small cell lung cancer in the elderly
Authors: Cheng Ying , Wu Lin , Liu Xiaoqing , Zhao Yanqiu , Liu Chunling , Chen Qun , Sun Tao , Zheng Qingshan
Published: January 2019

Background:

Lobaplatin (LBP) is a third-generation platinum compound.

Material and methods:

This prospective study was performed in 7 institutions in 2014–2016. Elderly small cell lung cancer (SCLC) patients (≥65 years old) were divided into 2 groups to receive LBP regimens according to endogenous creatinine clearance rate (Ccr). LBP was administered at 30 and 20 mg/m2 in groups A (Ccr ≥ 80 ml/min) and B (60 ml/min ≤ Ccr < 80 ml/min), respectively. The primary endpoint was plasma LBP concentrations. Secondary endpoints were safety and efficacy parameters, including progression-free survival (PFS) and overall survival (OS).

Results:

One-hundred patients were enrolled. Median PFS and OS in groups A and B were 155 vs170 days and 306 vs 272 days, respectively. The rates of grade III/IV AEs in groups A and B were 60.8% (n = 31) and 51.0% (n = 25), respectively. In population pharmacokinetics, the area under the curve (AUC) value for group B was 39% lower than that of group A. With LBP administration based on body surface area (BSA), AUC differences between individuals were small.

Conclusion:

With Ccr ≥ 60 ml/min, BSA based administration is necessary. Meanwhile, LBP-based regimens are reliable in treating elderly patients with SCLC.
Acupotomy for the treatment of lumbar spinal stenosis
Authors: Kwon Chan-Young , Yoon Sang-hoon , Lee Boram , Leem Jungtae
Published: January 2019

Introduction:

This systematic review protocol describes the methods that will be used to evaluate the efficacy and safety of acupotomy for the treatment of lumbar spinal stenosis.

Methods and analysis:

The following electronic databases will be searched until December 2018 without language or publication status restrictions: five English databases, that is Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Allied and Complementary Medicine Database (AMED), and Cumulative Index to Nursing and Allied Health Literature (CINAHL); three Korean databases, that is Oriental Medicine Advanced Searching Integrated System (OASIS), Research Information Service System (RISS), and Korea Citation Index (KCI); and three Chinese databases, that is China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP. Any clinical, randomized controlled trials using acupotomy for lumbar spinal stenosis treatment will be included. Changes in the degrees of pain and function will be assessed as primary outcomes. The total effective rate, changes in quality of life, adverse events, and amount of rescue medication used will be evaluated as secondary outcomes. Two independent researchers will perform study selection, data extraction, and risk of bias assessment. If applicable, a meta-analysis will be performed using RevMan version 5.3, with the results expressed as risk ratios or mean differences with 95% confidence intervals. According to a heterogeneity test or the number of studies included, fixed effects or random effects model will be used. The risk of bias tool from the Cochrane group will be used to evaluate the methodological quality of the included studies.

Ethics and dissemination:

Ethical approval is not required because individual patient data will not be included in this study. The findings of this systematic review will be disseminated through a peer-reviewed publication or conference presentations.

PROSPERO registration number:

CRD42018116567.
Marfan syndrome with type 2 diabetes mellitus
Authors: Zhou Yingyi , Du Xuan , Chen Chao , Shi Bimin , Chen Ke
Published: January 2019

Rationale:

Marfan syndrome (MFS) is a genetic disorder of the connective tissue. MFS has an incidence of about 2 to 3 persons per 10,000 population. MFS is characterized majorly by the involvement of the eyes, skeletal muscles, and cardiovascular system. There are limited case reports of co-existence of MFS and type 2 diabetes mellitus (T2DM).

Patient concerns:

A 16-year-old male patient who got admitted to our hospital with complaints of loss of vision from left eye for the last 3 days.

Diagnosis of MFS along with luxation of left eye lens, and T2DM were made according to the patient's symptoms, signs, biochemical results, and ultrasonography.

Interventions:

The patient received “vitrectomy (posterior approach (left eye)) + cataract extraction (left eye) + intraocular lens implantation (left eye) surgery” for luxation of left eye lens. The patient received “Bentall Operation” for MFS, and was prescribed warfarin 5 mg qod and spironolactone 20 mg bid during the follow-up period. The patient received continuous subcutaneous insulin infusion (CSII) during hospitalization, and then changed to insulin glargine preparation during the follow-up period.

Outcomes:

The vision was restored after the eye surgery and the patient also recovered well after the Bentall Operation. Additionally, there were no obvious complications during hospitalization and the follow-up period. Blood glucose levels were within normal range.

Lessons:

There is a need to improve the recognition of MFS among school and community doctors. Early detection, diagnosis, and treatment of this rare disease can improve the quality of patient's life.
A novel self-expanding biflanged metal stent vs tubular metal stent for EUS-guided transmural drainage of pancreatic pseudocyst
Authors: Yao Yao , Zhang Dingguo , Guo Jiefang , Qi Ke , Li Feng , Zhu Jianwei , Wang Dong , Chen Jie , Xu Can , Wang Luowei , Wang Kaixuan , Jin Zhendong , Li Zhaoshen
Published: January 2019

Although endoscopic ultrasound (EUS)-guided transmural drainage of pancreatic fluid collections with metal stents is generally preferred over plastic stents, its superiority among different types of metal stents has not yet been well studied. We conducted this study to compare clinical outcomes and complications of a novel self-expanding biflanged metal stent (BFMS) and a traditional-shaped tubular metal stent (TMS) in treating pancreatic pseudocyst (PPC).

This was a retrospective analysis on consecutive patients with PPC underwent EUS-guided transmural drainage with either TMS or BFMS in a single tertiary center with expertise in management of complex biliary and pancreatic problems. The technical and functional success rate, reintervention, complications, and recurrence rate were evaluated.

From September 2013 to January 2018, 125 patients (66.4% male, median age 47 years) underwent EUS-guided transmural drainage for PPC. Among them, 49 used TMS and 76 used BFMS. All patients met the inclusion criteria that cyst diameter was >6 cm or the distance between cyst and stomach wall was shorter than 1 cm. There was no difference in technical success (98% vs 97.4%, P = 1.0) or functional success rate (87.8% vs 92.1%, P = .54) using 2 types of metal stents. However, more procedure related complications occurred in TMS than in BFMS group. TMS group had a much higher migration rate than BFMS group (14.6% vs 0, P = .001), even though there was no significant difference in bleeding, infection, or death rate between 2 groups. With similar clinical outcomes, TMS group required more additional plastic stent placement than BFMS group for better drainage.

TMS and BFMS placement can both be considered as methods of endoscopic transmural PPC drainage with equal efficacy, whereas BFMS could be preferred for fewer complications or less need of additional plastic stent placement.
A pathological toe fracture as the first presentation of cervical cancer
Authors: Zhang Jinming , Li Ze , Ma Xiaotong , Feng Helin
Published: January 2019

Rationale:

Cervical cancer is one of the most common gynecologic malignancies worldwide, and it spreads mainly through direct extension. Distinct metastases are less common and usually spread to distant lymph nodes, lungs, and bones. Bone metastases from cervical cancer are most commonly observed in the pelvis and spine. Thus, a pathological toe fracture as the initial presentation of cervical cancer is extremely rare.

Patient concerns:

We report a patient with a toe metastasis that first presented with pain caused by a pathological fracture.

Diagnoses:

The patient underwent surgery to remove the right great toe, and the histopathology revealed squamous carcinoma that originated from the cervix.

Interventions:

The patient then underwent cervical cancer surgery, chemotherapy, and radiotherapy.

Lessons:

A pathological toe fracture as the initial presentation of cervical cancer is extremely rare, but clinicians need to be aware that we should not exclude cancer when patients come to the hospital for pathological fractures.
Triple Premasseteric Branches of Facial Artery
Authors: Nayak Satheesha B.
Published: January 2019

Facial artery is known to show variations in its origin, course, termination, and branching pattern. One of its reported variant branch is called premasseteric branch. During our dissection classes, it was observed that an elderly male cadaver had 3 premasseteic branches arising from the facial artery. The first and second premasseteric branches passed deep to masseter under its anterior border, whereas the third premasseteric branch terminated by anastomosing with the infraorbital artery. This case could be of importance to maxillofacial surgeons, craniofacial surgeons, and plastic surgeons.
Reconstruction of Mohs Defects Located in the Head and Neck
Authors: Egeler Sabine A. , Johnson Anna Rose , Ibrahim Ahmed M.S. , Bucknor Alexandra , Chen Austin , Malyar Masoud , Tobias Adam M. , Lin Samuel J. , Mureau Marc A.M. , Lee Bernard T.
Published: January 2019

Background:

Defects following Mohs micrographic surgery (MMS) can range in size from small defects requiring linear closure to large defects needing flap coverage. Reconstruction is dependent on defect size and facial aesthetic unit involvement. The aim of this study was to review the types of facial reconstruction per aesthetic unit involvement and describe their outcomes.

Methods:

All data were retrieved for patients ≥18 years who underwent multidisciplinary treatment including dermatological MMS and plastic surgical reconstruction at a single tertiary hospital center (2001–2017). Patient characteristics, tumor pathology, surgical specifics, reconstructive modalities, and surgical outcomes were analyzed.

Results:

A total of 418 patients were included. Patients were predominantly White, non-Hispanic (97%) and female (58%) with a mean age of 60 ± 13.9 years. Tumor pathology was predominantly basal cell carcinoma in 73% of all cases followed by squamous cell carcinoma in 14%. The nasal aesthetic unit was mostly affected (50%). Local advancement flaps and different types of grafts were used in 51% and 25% of reconstructions, respectively. Complications were observed in 3% and local cancer recurrence in 4% of the patients. Scar revision was needed in 6% of the patients.

Conclusion:

Reconstruction of facial defects after Mohs micrographic surgery can be challenging due to its technical complexity and aesthetic implications. There were differences in complications in reconstructions performed within the same day versus 1 week, with a majority of complications occurring within same-day Mohs reconstructions. A multidisciplinary structured approach, which incorporates patient-reported outcomes, may be needed to optimize surgical results.
Cone-Beam Computed Tomography Study on Morphologic Characteristics of the Posterior Region in Hard Palate
Authors: Ling Chuangliang , Jiang Qian , Ding Xiaojun
Published: January 2019

Background:

The goal of this study is to evaluate the morphologic characteristics of the posterior palatine region among the Chinese population, more specifically, the greater palatine grooves, crests, bridges, and torus palatinus structures and make comparisons between different ethnic groups and minorities.

Methods:

A total of 323 cone-beam computed tomography (CBCT) scans were collected for analysis on the presence of grooves, crests, bridges, or torus palatinus (TP). Data were collected through recognizing the grooves, crests, bridges, and TPs and calculating the number of those anatomy structures. The statistics index, including average, standard deviation, were adopted to describe the subjects and Wilcoxon test, Mann–Whitney test, and Chi-squared test were all carried out by SPSS.

Results:

Three different morphologic manifestations of the greater palatine groove (GPG) found in the upper 1st and 2nd molar regions are as follows: no groove, 1 groove, and 2 grooves. The number of crests ranged from 0 to 3. And the incidence of torus palatines was 29%. Moreover, a positive correlation was found between the presence of crests/GPGs and age in the 2nd molar region.

Conclusion:

The results in this study reveal that GPGs in the upper 1st and 2nd molar regions have 3 different morphologic manifestations among Chinese people and the number of crests can vary from 0 to 3 crests. Although the proportion of GPG or crest and the incidence of TP are different from the proportions of other studies, this may be due to the fact that different ethnic groups and sample sizes were used in the course of this study. Information about the anatomy structures of the posterior region in hard palate directly contributed to a decrease in potential complications during palatal implant surgery and periodontal surgery.
Two critical N-terminal epitopes of the nucleocapsid protein contribute to the cross-reactivity between porcine epidemic diarrhea virus and porcine transmissible gastroenteritis virus
Authors: Xie Wenting , Ao Chaojie , Yang Yilin , Liu Yinan , Liang Rui , Zeng Zhe , Ye Gang , Xiao Shaobo , Fu Zhen F. , Dong Wanyu , Peng Guiqing
Published: January 2019

Both porcine epidemic diarrhoea virus (PEDV) and porcine transmissible gastroenteritis virus (TGEV), which cause high mortality in piglets and produce similar clinical symptoms and histopathological morphology, belong to the genus Alphacoronavirus. Serological diagnosis plays an important role in distinguishing pathogen species. Together with the spike (S) protein, the nucleocapsid (N) protein is one of the immunodominant regions among coronaviruses. In this study, two-way antigenic cross-reactivity between the N proteins of PEDV and TGEV was observed by indirect immunofluorescence assay (IFA) and Western blot analysis. Furthermore, the PEDV N protein harbouring truncations of amino acids (aa) 1 to 170 or aa 125 to 301 was demonstrated to cross-react with the anti-TGEV N polyclonal antibody (PAb), whereas the truncation-expressing aa 302 to 401 resulted in a specific reaction with the anti-PEDV N PAb but not with the anti-TGEV N PAb. Mutants of the PEDV N protein were generated based on sequence alignment and structural analysis; we then confirmed that the N-terminal residues 58-RWRMRRGERIE-68 and 78-LGTGPHAD-85 contributed to the cross-reactivity. All the results provide vital clues for the development of precise diagnostic assays for porcine coronaviruses.
Black sea cucumber (Holothuria atra Jaeger, 1833) rescues Pseudomonas aeruginosa-infected Caenorhabditis elegans via reduction of pathogen virulence factors and enhancement of host immunity
Authors: Lee Wan-Ting , Tan Boon-Khai , Eng Su-Anne , Yuen Gan Chee , Chan Kit Lam , Sim Yee Kwang , Sulaiman Shaida Fariza , Shu-Chien Alexander Chong
Published: January 2019

A strategy to circumvent the problem of multidrug resistant pathogen is consumption of functional food rich in anti-infectives targeting bacterial virulence or host immunity. The black sea cucumber (Holothuria atra) is a tropical marine sea cucumer species traditionally consumed as remedy for many ailments. There is a paucity of knowledge the anti-infectives capacity of H. atra and the underlying mechanisms involved. The objectives of this study were to utilize the Caenorhabditis elegans-P. aeruginosa infection model to assess the anti-infective properties of H. atra. We first showed the capacity of a H. atra extract and fraction in promoting survival of C. elegans during a customarily lethal P. aeruginosa infection. The same chemical entities also attenuate the production of several P. aeruginosa virulence factors and biofilm. Treatment of infected transgenic lys-7::GFP worms with H. atra fraction restored the repressed expression of lys-7, a defense enzyme, indicating improved host immunity. QTOF-LCMS analysis revealed the presence of aspidospermatidine, an indole alkaloid and inosine. Collectively, our finding shows that H. atra confers survival advantage in C. elegans against P. aeruginosa infection through inhibition of pathogen virulence and eventually, the restitution of host lys-7 expression.
Carriage of a single strain of non-toxigenic Corynebacterium diphtheriae biovar Belfanti (Corynebacterium belfantii) in four patients with cystic fibrosis
Authors: Pivot Diane , Fanton Annlyse , Badell-Ocando Edgar , Benouachkou Marion , Astruc Karine , Huet Frederic , Amoureux Lucie , Neuwirth Catherine , Criscuolo Alexis , Aho Serge , Toubiana Julie , Brisse Sylvain
Published: January 2019

Cystic fibrosis (CF) patients are commonly colonized by bacterial pathogens, which can induce persistent lung inflammation and may contribute to clinical deterioration. Colonization of CF patients and cross-transmission by Corynebacterium diphtheriae has not been reported so far. The aim of this article was to investigate the possibility of a cross transmission of C. diphtheriae biovar Belfanti between four patients of a CF center. C. diphtheriae biovar belfanti (now formally called C. belfantii) isolates were collected from four patients in a single CF care center over a 6 years period and analyzed by microbiological methods and whole genome sequencing. Epidemiological links among patients were investigated. Ten isolates were collected from 4 patients. Whole genome sequencing of one isolate from each patient showed that a single strain was shared among them. In addition, one patient had the same strain on two consecutive samplings nine months apart. The strain was non-toxigenic and was susceptible to most antimicrobial agents. Ciprofloxacin resistance was observed in one patient. Transmission of the strain among patients was supported by the occurrence of same-day visits to the CF center. This study demonstrates colonization of CF patients by C. diphtheriae biovar Belfanti (C. belfantii) and shows persistence and transmission of a unique strain during at least six years in a single CF patient care center.

Previous meeting presentations

The information in this work was not previously presented in any meeting.

Accession numbers

The genomic sequence data generated in this work were submitted to the European Nucleotide Archive and are available from the International Nucleotide Sequence Database Collaboration (NCBI/ENA/DDBJ) databases under project accession number PRJEB28372 and run data accession numbers ERR2757916 to ERR2757921.
RPA phosphorylation regulates DNA resection
Authors: Soniat Michael M. , Myler Logan R. , Paull Tanya T. , Finkelstein Ilya J.
Published: January 2019

Genetic recombination in all kingdoms of life initiates when helicases and nucleases process (resect) the free DNA ends to expose single-stranded (ss) DNA overhangs. Resection termination in bacteria is programmed by a DNA sequence but the mechanisms limiting resection in eukaryotes have remained elusive. Using single-molecule imaging of reconstituted human DNA repair factors, we identify a general mechanism that limits DNA resection. BLM helicase together with EXO1 and DNA2 nucleases catalyze kilobase-length DNA resection on nucleosome-coated DNA. The resulting ssDNA is rapidly bound by RPA, which is in turn phosphorylated as part of the DNA damage response (DDR). Remarkably, phosphorylated RPA (pRPA) inhibits DNA resection via regulation of BLM helicase. pRPA suppresses BLM initiation at DNA ends and promotes the intrinsic helicase strand-switching activity. These findings establish that pRPA is a critical regulator of DNA repair enzymes and provides a feedback loop between the DDR and DNA resection termination.
Molecular and functional heterogeneity of cancer associated fibroblasts in high-grade serous ovarian cancer
Authors: Hussain Ali , Voisin Veronique , Poon Stephanie , Dmytryshyn Julia , Richman Cory , Meens Jalna , Ho Victor W , Tang Kwan Ho , Paterson Joshua , Clarke Blaise , Bernardini Marcus Q , Bader Gary D , Neel Benjamin G , Ailles Laurie E
Published: January 2019

Recent studies indicate that cancer-associated fibroblasts (CAFs) are phenotypically and functionally heterogeneous. However, little is known about CAF subtypes and the roles they play in cancer progression. Here we identify and characterize two CAF subtypes that coexist within high grade serous ovarian cancers: Fibroblast activation protein (FAP)-high (FH) CAFs resemble the classical myofibroblast-type CAF, whereas FAP-low (FL) CAFs possesses a preadipocyte-like molecular signature. Patients with predominantly FH CAFs have significantly worse outcomes than patients with predominantly FL CAFs. FH CAFs contract collagen gels and aggressively promote proliferation, invasion and therapy resistance of cancer cells, whereas FL CAFs do not. Overexpression of the FL-specific transcription factor TCF21 in FH CAFs decreases their ability to promote gel contraction, invasion, and in vivo tumor growth. Understanding CAF subtypes in more detail could lead to better patient stratification and novel therapeutic strategies.