bluuebunny/crossref_metadata_2025 huggingface dataset:
Unusual neuromuscular presentation of a Wilson’s disease patient with one-stage surgical correction treatment: A case report
Authors: Lin Yi-Chen , Chen Ing-Ho , Yang Kai-Chiang , Wang Chen-Chie
Published: June 2020

Wilson’s disease (WD), an autosomal recessive disorder of copper metabolism, may develop complex foot and ankle deformity associated with gastrosoleus muscle complex spasticity. In this case report, we present a female WD patient with bilateral equinocavovarus foot deformity in which the right foot deformity was progressed with severe contracture of posteromedial hindfoot structures and manifested as a rigid deformed foot. One-stage correction surgery including modified Lambrinudi arthrodesis, posterior tibialis tendon transfer to the lateral column of the foot, plantar fascia release (Steindler release), and Achilles tendon lengthening procedures was performed. Shortening the treatment period and decreasing possible complications due to multiple procedures are the main benefits of this technique. Although the limitation is that only a single patient was enrolled, this study provides a practical and reasonable surgical procedure with a satisfactory outcome.
Prescription Patterns and Risk Factors for Prolonged Opioid Dependence in Elective Anterior Cruciate Ligament Reconstruction in a Military Population
Authors: Anderson Ashley B. , Balazs George C. , Brooks Daniel I. , Potter Benjamin K. , Forsberg Jonathan A. , Dickens Jonathan F.
Published: June 2020

Background:

Limited data are available regarding excessive opioid prescribing in the perioperative period after routine orthopaedic procedures in US military personnel.

Purpose:

To examine the demographic profile of the patients receiving these medications and to identify potential risk factors for prolonged opioid use after anterior cruciate ligament reconstruction (ACLR) in the active duty military population.

Study Design:

Case-control study; Level of evidence, 3.

Methods:

The Military Analysis and Reporting Tool (M2) was used to search the Military Health System Data Repository (MDR) for patients undergoing ACLR from 2012 through 2015 and specifically for active duty personnel with an arthroscopically assisted ACLR (Current Procedural Terminology [CPT] code 29888). Complete opioid prescription filling history was also obtained. This study had 2 primary outcomes: (1) use of opiate analgesics more than 90 days after surgery, representing prolonged opiate prescriptions, and (2) high levels of postoperative opiate use, defined as having filled prescriptions accounting for greater than the 95th percentile of morphine equivalents for patients in the study cohort. Data were analyzed via multivariate regression analysis to identify potential associations with the primary outcomes.

Results:

A total of 9474 patients met the inclusion criteria. Median patient age was 27 years, and the sample included 1316 (14%) female and 8158 (86%) male patients. A total of 66 (0.7%) patients had a preoperative diagnosis for substance abuse; 2656 (28%) patients continued to receive opioid prescriptions more than 90 days after surgery, and 502 (5%) patients were in the top 95th percentile of all opioid users within the study cohort. Total preoperative morphine equivalents per day and total perioperative morphine equivalents per day were highly important risk factors for both outcomes, although other demographic factors such as race, sex, and age may play minor roles.

Conclusion:

We identified total preoperative morphine equivalents, total perioperative morphine equivalents, sex, and race as potential predictors of prolonged opioid use after ACLR. This information may prove useful in developing a predictive model to identify at-risk patients before surgery. This could help mitigate future misuse or abuse and improve preoperative patient counseling regarding pain management expectations.
Cohabitation and Self-rated Health: The Role of Socioeconomic Status and Sexual Minority Status among U.S. Cohabitors
Authors: Spiker Russell L.
Published: June 2020

This study examines whether health disparities between same-sex and different-sex cohabitors differ depending on socioeconomic status (SES). Previous research showed that SES mediates health disparities between different-sex and same-sex cohabitors, but less is known about its role as a potential moderator. Using data on cohabitors from the Integrated Public Use Microdata Series (IPUMS) National Health Interview Surveys (2007–2018), this study examines how the SES-health gradient shapes health disparities for same-sex and different-sex cohabitors. Average adjusted predictions from multinomial logistic regression models show that higher income-to-needs ratio is associated with improvements in self-rated health for same-sex cohabiting women relative to different-sex cohabiting women. However, results are mixed for men. As income-to-needs ratio increases, same-sex cohabiting men have higher probabilities of “excellent” or “very good” health than different-sex cohabitors; however, their risk of “poor” health increases significantly with higher income-to-needs ratios. Potential explanations related to minority stress, stress proliferation, gendered meanings of self-rated health, and selection are explored. Overall, disparities between same-sex and different-sex cohabitors differ by gender and SES, suggesting socioeconomic diversity should be considered in the study of sexual minority health.
Health Professions Students’ Assessment of an Interprofessional Rural Public Health-Focused Rotation: A Pilot Study Based on the Community-Oriented Primary Care Approach
Authors: Johansson Patrik , Nickol Devin , Maloney Shannon , Grimm Brandon , Tibbits Melissa , Siahpush Mohammad , De Alba Rosales Armando , Lyden Elizabeth , Schneider Caitlin , Gofin Jaime
Published: June 2020

Using a community-oriented primary care (COPC) approach, the format for this interprofessional rural rotation was a public health focused team project based in a local health department and primary care setting. The target audience included fourth-year dental students, fourth-year undergraduate students in imaging science, second-year master of public health students, third-year medical students enrolled in the MD/MPH program, second-year nurse practitioner students, fourth-year pharmacy students, second-year MSN nursing students, and first-year PhD students. The specific learning objectives of the curriculum were drawn from emphasis areas of the Interprofessional Education Collaborative’s competency domains and included the development of students’ knowledge to function as a member of an interprofessional team to (1) engage diverse health care professionals, (2) communicate with team members to clarify each member’s responsibility in executing components of a public health intervention, (3) choose effective communication tools and techniques, (4) integrate knowledge and experience of other professions, and (5) engage themselves and others to constructively manage disagreements.

Additional learning objectives centered on 10 competencies from the Master’s Degree in Public Health Core Competency Project. Assessment of 13 student participants, as a group, showed increased perceived knowledge in 4 out of 5 selected interprofessional emphasis areas and 9 out of 10 public health competencies. Our curriculum provides promising evidence for one interprofessional rural education model with proven short-term effectiveness among six health professions disciplines, in increasing student knowledge in interprofessional emphasis areas and public health competencies.
Learning to Speak Up for Patient Safety: Interprofessional Scenarios for Training Future Healthcare Professionals
Authors: McCoy Lise , Lewis Joy H , Simon Harvey , Sackett Denise , Dajani Tala , Morgan Christine , Hunt Aaron
Published: June 2020

Background:

Preventable medical errors represent a leading cause of death in the United States. Effective undergraduate medical education (UME) strategies are needed to train medical students in error prevention, early identification of potential errors, and proactive communication. To address this need, a team of faculty from A.T. Still University’s School of Osteopathic Medicine in Arizona developed four digital patient safety case scenarios for second-year medical students. These scenarios were designed to integrate interprofessional collaboration and patient safety principles, increase student ability to identify potential errors, and promote proactive communication skills.

Methods:

Faculty used Qualtrics to create four digital case scenarios on patient safety covering the following domains: communicating about potential drug-to-drug interactions; effective handoffs; human factors errors, such as fatigue, illness, and stress; and conflicts with supervising resident. In fall 2018, 97 second-year medical students completed the entire safety module in dyad or triad teams. As they worked through each case study, student teams completed 11 assessment questions with instant feedback, and participated in short case debrief discussions. Next, each individual student took a 12-question post-test to assess learning. Descriptive statistics were reviewed for the assessment questions, and case critical thinking discussion answers were reviewed to evaluate student comprehension.

Results:

The mean score for the module was 95.5% (SD= 6.36%, range = 75%-100%). Seventy-eight students completed the post-test, which had a mean score of 96.5% (SD = 6.51%, range = 66.7%-100%). Student written responses to the four case critical thinking discussion prompts indicated a high level of comprehension.

Conclusion:

Our results demonstrated that digital case studies can provide an innovative mechanism to introduce key patient safety concepts and experiential practice of interprofessional communication in early UME. Our design and implementation of these engaging interprofessional patient safety training modules provided an opportunity for students to learn key communication and safety concepts in small teams. This training method was cost-effective and could be replicated in other online learning or blended learning environments for a wide range of health professions.
Rare manifestation of Waldenström macroglobulinemia with acute kidney injury secondary to cast nephropathy in a young woman
Authors: Ramaswami Arun Prakas , Nedumannil Rithin , Pawar Basant , Routledge David , Tam Constantine , Nayar Sajith , Thomas Sajan
Published: June 2020

A 28-year-old Caucasian woman presented with acute kidney injury secondary to cast nephropathy and was diagnosed with Waldenström macroglobulinemia. This was an unusual presentation, as the patient was both young and female. More over renal involvement in Waldenström macroglobulinemia is rare. Histology of this patient revealed the presence of tubular casts and electron microscopic evidence of monoclonal immune deposit disease. Targeted next-generation sequencing of bone marrow revealed a missense mutation in MYD88 (L265  P) along with a nonsense mutation in CXCR4 (S338*) confirming Waldenström macroglobulinemia. After failing to respond to two cycles of bortezomib-based chemoimmunotherapy and a further 2 months of ibrutinib monotherapy, the patient remained dialysis dependent but managed to achieve a partial response with a different chemoimmunotherapy. Following successful stem cell harvesting, she underwent a melphalan-conditioned autologous stem cell transplant to attain a complete remission with hematologic recovery but with persistent renal impairment.
The Long‐term Efficacy of Botulinum Toxin Injection to Treat Retrograde Cricopharyngeus Dysfunction
Authors: Hoesli Rebecca C. , Wingo Melissa L. , Bastian Robert W.
Published: June 2020

Objectives

To report the percentage of patients with symptom relief 6 or more months after botulinum toxin injection into the cricopharyngeus muscle for retrograde cricopharyngeus dysfunction (R‐CPD).

Study Design

Retrospective case series of consecutively treated patients.

Setting

Tertiary care laryngology clinic.

Subjects and Methods

A review was performed of the first 200 patients who were diagnosed with R‐CPD and treated with botulinum toxin injection into the cricopharyngeus muscle by a single surgeon. The study group was limited to those for whom a minimum of 6 months has elapsed since the injection. Items assessed were efficacy, safety, complications, and duration of benefit.

Results

Of 200 patients treated, (99.5%) gained the ability to burp and 95% experienced relief of the cardinal symptoms of R‐CPD: inability to belch, socially awkward gurgling noises, abdominal/chest pressure and bloating, and excessive flatulence. For those who experienced relief, 159 (79.9%) maintained a satisfactory ability to burp after 6 months. Of those who did not maintain the ability, 12 underwent a second injection, 1 patient underwent 3 subsequent injections, and 3 patients underwent partial myotomy. No patients experienced complications of botulinum toxin injection itself, and 4 patients had complications from esophagoscopy or anesthesia.

Conclusion

In a case series of 200 patients with retrograde cricopharyngeus dysfunction, 99% experienced relief of the cardinal symptoms and 79.9% experienced lasting relief of their symptoms beyond pharmacologic duration of action after a single injection of botulinum toxin into the cricopharyngeus muscle. Relief can be reestablished in the remainder via additional injection or cricopharyngeus myotomy.
The normal distribution fitting method for frequency distribution characteristics of peak arrival time of earthquake
Authors: Han Xu , Liu Yunan , Wang Lihua
Published: June 2020

The physical meaning of phase difference controls the occurrence time of peak values of triangular series, which can be abbreviated as peak arrival time. This article describes a method for deducing the correspondence between the energy distribution characteristics in the time domain and the peak arrival time. The variation laws of acceleration time–history curve of natural seismic wave can be transformed into its energy distribution characteristics in time domain. Based on the needs of seismic engineering, this article proposes a conversion formula to describe the relationship between the peak arrival time and the energy distribution characteristics in the time domain. To ensure that the variation laws of acceleration time–history curve of artificial seismic waves are more consistent with those of natural seismic waves, a normal-fitting annealing algorithm is proposed based on the normal-fitting method. The proposed method not only considers the frequency distribution characteristics of the peak arrival time comprehensively but also optimizes the fitting parameters according to the actual situation. The results of all the experimental cases verify the rationality and reliability of the proposed method.
Serum estradiol levels in infertile men with non-obstructive azoospermia
Authors: Salama Nader , Blgozah Saeed
Published: June 2020

Purpose:

To report the different patterns of estradiol levels in infertile men with non-obstructive azoospermia and correlate these levels with their clinical and laboratory findings.

Materials and methods:

A retrospective study was launched, and a retrieval of data for infertile men with non-obstructive azoospermia ( n = 166) and fertile controls ( n = 40) was performed. The retrieved data included demographics, clinical findings, scrotal duplex, semen analysis, and hormonal assay (testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, and estradiol).

Results:

Our findings showed a wide spectrum of estradiol concentrations. The patients were arranged into three groups (high, normal, and low estradiol groups). The normal estradiol group was the most prevalent (71.1%). Testosterone, gonadotrophins, testicular volumes, and the number of patients with jobs in polluted workplaces showed significant differences among the study groups ( p = 0.001, <0.001, <0.001, and 0.004, respectively). Age, body mass index, varicocele prevalence, prolactin, and smoking habits did not show any significant differences among the groups. Obesity was lacking in the low estradiol group, but it had significantly higher prevalence in the normal ( p = 0.013) or high group ( p = 0.023) compared with the controls.

Conclusion:

Serum estradiol, in infertile men with non-obstructive azoospermia, may be present at different levels. It is recommended that estradiol be measured in infertile men with non-obstructive azoospermia when there is an alteration in testosterone concentration, obesity, a polluted workplace occupation, or before trying hormonal therapy. Extended studies are highly recommended to provide a clear clue whether alterations in estradiol concentrations in men with non-obstructive azoospermia are the cause or a consequence of the condition.
Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome
Authors: Middleton Elizabeth A. , He Xue-Yan , Denorme Frederik , Campbell Robert A. , Ng David , Salvatore Steven P. , Mostyka Maria , Baxter-Stoltzfus Amelia , Borczuk Alain C. , Loda Massimo , Cody Mark J. , Manne Bhanu Kanth , Portier Irina , Harris Estelle S. , Petrey Aaron C. , Beswick Ellen J. , Caulin Aleah F. , Iovino Anthony , Abegglen Lisa M. , Weyrich Andrew S. , Rondina Matthew T. , Egeblad Mikala , Schiffman Joshua D. , Yost Christian Con
Published: June 2020

COVID-19 affects millions of patients worldwide, with clinical presentation ranging from isolated thrombosis to acute respiratory distress syndrome (ARDS) requiring ventilator support. Neutrophil extracellular traps (NETs) originate from decondensed chromatin released to immobilize pathogens, and they can trigger immunothrombosis. We studied the connection between NETs and COVID-19 severity and progression. We conducted a prospective cohort study of COVID-19 patients (n = 33) and age- and sex-matched controls (n = 17). We measured plasma myeloperoxidase (MPO)-DNA complexes (NETs), platelet factor 4, RANTES, and selected cytokines. Three COVID-19 lung autopsies were examined for NETs and platelet involvement. We assessed NET formation ex vivo in COVID-19 neutrophils and in healthy neutrophils incubated with COVID-19 plasma. We also tested the ability of neonatal NET-inhibitory factor (nNIF) to block NET formation induced by COVID-19 plasma. Plasma MPO-DNA complexes increased in COVID-19, with intubation (P < .0001) and death (P < .0005) as outcome. Illness severity correlated directly with plasma MPO-DNA complexes (P = .0360), whereas Pao2/fraction of inspired oxygen correlated inversely (P = .0340). Soluble and cellular factors triggering NETs were significantly increased in COVID-19, and pulmonary autopsies confirmed NET-containing microthrombi with neutrophil-platelet infiltration. Finally, COVID-19 neutrophils ex vivo displayed excessive NETs at baseline, and COVID-19 plasma triggered NET formation, which was blocked by nNIF. Thus, NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.
Differences in lung clearance index and functional residual capacity between two commercial multiple-breath nitrogen washout devices in healthy children and adults
Authors: Zwitserloot Annelies M. , van den Born Evelyne J. , Raaijmakers Lena H.A. , Stalman Wouter E. , van Smaalen Marjanne , van den Berge Maarten , Gappa Monika , Koppelman Gerard H. , Willemse Brigitte W.M.
Published: June 2020

Multiple-breath nitrogen washout (MBNW) and its clinical parameter lung clearance index (LCI) are gaining increasing attention for the assessment of small airway function. Measurement of LCI relies on accurate assessment of functional residual capacity (FRC). The EasyOne Pro LAB (ndd) and Exhalyzer D (EM) are two commercially available MBNW devices. The aim of the study was to compare these two devicesin vitroandin vivoin healthy subjects with regard to FRC, LCI and secondary outcome parameters and to relate FRCMBNWto FRC measured by body plethysmography (pleth) and helium dilution technique. MBNW measurements were performed using a lung model (FRC between 500 and 4000 mL)in vitroand in 38 subjects aged 6–65 years followed by helium dilution and plethin vivousing fixed and relaxed breathing techniques.In vitroaccuracy within 5% of lung model FRC was 67.3% for ndd, FRC was >5% higher for EM in all tests.In vivo, FRCplethranged from 1.2 to 5.6 L. Mean differences (limits of agreement) between FRCplethand FRCMBNWwere −7.0%, (−23.2 to 9.2%) and 5.7% (−11.2 to 22.6%) using ndd and EM, respectively. FRCnddwas consistently lower than FRCEM(−11.8% (−25.6 to 2%)). LCI was comparable between the two devices (−1.3% (−21.9 to 19.3%)). There was a difference of >10 % in LCI in 12 of 38 subjects. Using the most recent software updates, both devices show relevant deviations in FRC measurement bothin vitroandin vivoand individual differences in LCI in a significant proportion of subjects. The devices are therefore not interchangeable.
The α7 nicotinic acetylcholine receptor agonist, GTS-21, attenuates hyperoxia-induced acute inflammatory lung injury by alleviating the accumulation of HMGB1 in the airways and the circulation
Authors: Sitapara Ravikumar A. , Gauthier Alex G. , Valdés-Ferrer Sergio I. , Lin Mosi , Patel Vivek , Wang Mao , Martino Ashley T. , Perron Jeanette C. , Ashby Charles R. , Tracey Kevin J. , Pavlov Valentin A. , Mantell Lin L.
Published: June 2020

Background

Oxygen therapy, using supraphysiological concentrations of oxygen (hyperoxia), is routinely administered to patients who require respiratory support including mechanical ventilation (MV). However, prolonged exposure to hyperoxia results in acute lung injury (ALI) and accumulation of high mobility group box 1 (HMGB1) in the airways. We previously showed that airway HMGB1 mediates hyperoxia-induced lung injury in a mouse model of ALI. Cholinergic signaling through the α7 nicotinic acetylcholine receptor (α7nAChR) attenuates several inflammatory conditions. The aim of this study was to determine whether 3–(2,4 dimethoxy-benzylidene)-anabaseine dihydrochloride, GTS-21, an α7nAChR partial agonist, inhibits hyperoxia-induced HMGB1 accumulation in the airways and circulation, and consequently attenuates inflammatory lung injury.

Methods

Mice were exposed to hyperoxia (≥99% O2) for 3 days and treated concurrently with GTS-21 (0.04, 0.4 and 4 mg/kg, i.p.) or the control vehicle, saline.

Results

The systemic administration of GTS-21 (4 mg/kg) significantly decreased levels of HMGB1 in the airways and the serum. Moreover, GTS-21 (4 mg/kg) significantly reduced hyperoxia-induced acute inflammatory lung injury, as indicated by the decreased total protein content in the airways, reduced infiltration of inflammatory monocytes/macrophages and neutrophils into the lung tissue and airways, and improved lung injury histopathology.

Conclusions

Our results indicate that GTS-21 can attenuate hyperoxia-induced ALI by inhibiting extracellular HMGB1-mediated inflammatory responses. This suggests that the α7nAChR represents a potential pharmacological target for the treatment regimen of oxidative inflammatory lung injury in patients receiving oxygen therapy.
Combination of TLR agonist and miR146a mimics attenuates ovalbumin-induced asthma
Authors: Wang Xinhua , Lu Xiaoxian , Ma Chenhui , Ma Lihong , Han Shuguang
Published: June 2020

Background

microRNA-146a has been reported to be a regulator in the process of attenuating asthma by inhibiting Toll-like receptor 2 (TLR2) pathway. This study aimed to investigate how miR146a-inhibitor affect the symptom of asthma and the underlying mechanisms.

Methods

Ovalbumin (OVA)-induced allergic asthma mice model was established by intraperitoneal injection with 20 μg of OVA. Total cells and differential inflammatory cells in bronchoalveolar lavage fluid were counted by flow cytometry. The expression levels of molecules and cytokines in TLR2 signaling pathway were detected by Q-PCR and ELISA.

Results

miR146a-inhibitor attenuated OVA-induced allergic asthma by increasing Th1 cytokines in OVA-induced allergic asthma model, and the treatment of miR146a-inhibitor can reduce the inflammation caused by asthma, followed by the down-regulation of IL-5 and IL-13 in sorted ILC2. The inhibition of miR-146a significantly reduced symptoms of asthma model with TLR2-related molecules being up-regulated.

Conclusion

It was found that miR-146a is an important regulator in OVA-induced allergic asthma model, which can relieve symptoms of asthma through regulating TLR2 pathway. These findings provide a theoretical basis for solving asthma in clinical treatment.
RETRACTED ARTICLE: Long Non-coding RNA MALAT1/microRNA-143/VEGFA Signal Axis Modulates Vascular Endothelial Injury-Induced Intracranial Aneurysm
Authors: Gao Ge , Zhang Yang , Yu Jian , Chen Yu , Gu Daqun , Niu Chaoshi , Fu Xianming , Wei Jianjun
Published: June 2020

The roles of some long non-coding RNAs (lncRNAs) in intracranial aneurysm (IA) have been investigated in many studies. The aim of this study is to elucidate the mechanism of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-143 (miR-143)/vascular endothelial growth factor-A (VEGFA) signal axis in vascular endothelial injury-induced IA. MALAT1, miR-143, and VEGFA expression in IA tissues and normal arterial tissues were detected. Matrix metalloproteinase 9 (MMP-9) in tissues, von Willebrand factor (vWF) in serum and tissues, and endothelin-1 (ET-1) in serum were detected. The modeled IA rats were injected with silenced or overexpressed MALAT1 for detecting vascular endothelial injury. Vascular endothelial cells from patients with IA were abstracted and transfected with silenced or overexpressed MALAT1 to verify the impacts of MALAT1 on cell viability and apoptosis. The connections among MALAT1, miR-143, and VEGFA were verified by online prediction, luciferase activity, and RNA-pull down assays. Overexpression of MALAT1 and VEGFA and poor expression of miR-143 were found in IA tissues. Downregulation of MALAT1 inhibited blood pressure, the expression of ET-1, vWF, and MMP-9, as well as the apoptotic index of vascular endothelial cells of rats with IA. Downregulated MALAT1 inhibited apoptosis and promoted viability of vascular endothelial cells in IA. MALAT1 bound to miR-143 and miR-143 targeted VEGFA. This study suggests that MALAT1 elevates VEGFA expression through competitive binding to miR-143, thereby boosting apoptosis and attenuating viability of vascular endothelial cells in IA.
Design of experiments for fine-mapping quantitative trait loci in livestock populations
Authors: Wittenburg Dörte , Bonk Sarah , Doschoris Michael , Reyer Henry
Published: June 2020

Background

Single nucleotide polymorphisms (SNPs) which capture a significant impact on a trait can be identified with genome-wide association studies. High linkage disequilibrium (LD) among SNPs makes it difficult to identify causative variants correctly. Thus, often target regions instead of single SNPs are reported. Sample size has not only a crucial impact on the precision of parameter estimates, it also ensures that a desired level of statistical power can be reached. We study the design of experiments for fine-mapping of signals of a quantitative trait locus in such a target region.

Methods

A multi-locus model allows to identify causative variants simultaneously, to state their positions more precisely and to account for existing dependencies. Based on the commonly applied SNP-BLUP approach, we determine the z-score statistic for locally testing non-zero SNP effects and investigate its distribution under the alternative hypothesis. This quantity employs the theoretical instead of observed dependence between SNPs; it can be set up as a function of paternal and maternal LD for any given population structure.

Results

We simulated multiple paternal half-sib families and considered a target region of 1 Mbp. A bimodal distribution of estimated sample size was observed, particularly if more than two causative variants were assumed. The median of estimates constituted the final proposal of optimal sample size; it was consistently less than sample size estimated from single-SNP investigation which was used as a baseline approach. The second mode pointed to inflated sample sizes and could be explained by blocks of varying linkage phases leading to negative correlations between SNPs. Optimal sample size increased almost linearly with number of signals to be identified but depended much stronger on the assumption on heritability. For instance, three times as many samples were required if heritability was 0.1 compared to 0.3. An R package is provided that comprises all required tools.

Conclusions

Our approach incorporates information about the population structure into the design of experiments. Compared to a conventional method, this leads to a reduced estimate of sample size enabling the resource-saving design of future experiments for fine-mapping of candidate variants.
Detection of tetracycline and streptomycin in beef tissues using Charm II, isolation of relevant resistant bacteria and control their resistance by gamma radiation
Authors: Araby Eman , Nada Hanady G. , Abou El-Nour Salwa A. , Hammad Ali
Published: June 2020

Background

Misuse of antibiotics in veterinary medicine has the potential to generate residues in animal derived products, which could contributing to the development of an important health risk either through the exposure to antibiotic residues or the transfer of antibiotic resistance among foodborne pathogens as well. Tetracycline (TE) and eptomycin (ST) are commonly used as antibiotics in the Egyptian animal husbandry. The objective of this study, quick detection of TE and ST in fresh local beef tissue samples using radioimmunoassay Charm II technique, isolation and identification of relevant highly resistant bacterial strains. In addition to investigating the effect of gamma radiation on the susceptibility of such resistant strains to TE and ST.

Results

Tetracycline (TE) was detected in all collected samples, while ST was detected in 38.46% (5/13) and 87.5% (7/8) of meat and liver samples, respectively.

Fifty-one bacterial isolates were isolated from the tested samples, among them, the highest resistant isolates to TE or ST were identified as Streptococcus thoraltensis, Proteus mirabilis (2 isolates) and E. coli (3 isolates). Among them, the highest D10-values in phosphate buffer; 0.807 and 0.480; kGy were recorded with S. thoraltensis and E. coli no.3, respectively. Such values increased to record 0.840 and 0.549 kGy, respectively after artificial inoculation into meat, indicating increased resistance to gamma radiation. Gamma radiation at dose 3 kGy increased the susceptibility of S. thoraltensis up to 50% to TE and ST, while the sensitivity of E. coli no.3 reached up 56% to both antibiotics at the same dose.

Conclusions

High prevalence of TE in all fresh collected tissue samples suggests an extensively use of TE as antimicrobial in conventional beef production as compared to ST in the Egyptian cows’ husbandry. Moreover, irradiation of food from animal origin by gamma radiation could potentially provide protection against resistant strains. In spite of limited samples used in this study, our data could raise the concerns of public health professionals about a withdrawal period before animals slaughtering, and address the importance of gamma radiation to minimize the hazards of foodborne resistant bacteria.
Putative alternative translation start site-encoding nucleotides of CPR5 regulate growth and resistance
Authors: Faisal Muhammad B. , Gechev Tsanko S. , Mueller-Roeber Bernd , Dijkwel Paul P.
Published: June 2020

Background

The Arabidopsis CONSTITUTIVE EXPRESSER of PATHOGENESIS-RELATED GENES 5 (CPR5) has recently been shown to play a role in gating as part of the nuclear pore complex (NPC). Mutations in CPR5 cause multiple defects, including aberrant trichomes, reduced ploidy levels, reduced growth and enhanced resistance to bacterial and fungal pathogens. The pleiotropic nature of cpr5 mutations implicates that the CPR5 protein affects multiple pathways. However, little is known about the structural features that allow CPR5 to affect the different pathways.

Results

Our in silico studies suggest that in addition to three clusters of putative nuclear localization signals and four or five transmembrane domains, CPR5 contains two putative alternative translation start sites. To test the role of the methionine-encoding nucleotides implicated in those sites, metCPR5 cDNAs, in which the relevant nucleotides were changed to encode glutamine, were fused to the CPR5 native promoter and the constructs transformed to cpr5–2 plants to complement cpr5-compromised phenotypes. The control and metCPR5 constructs were able to complement all cpr5 phenotypes, although the extent of complementation depended on the specific complementing plant lines. Remarkably, plants transformed with metCPR5 constructs showed larger leaves and displayed reduced resistance when challenged to Pseudomonas syringae pv Pst DC3000, as compared to control plants. Thus, the methionine-encoding nucleotides regulate growth and resistance. We propose that structural features of the CPR5 N-terminus are implicated in selective gating of proteins involved in regulating the balance between growth and resistance.

Conclusion

Plants need to carefully balance the amount of resources used for growth and resistance. The Arabidopsis CPR5 protein regulates plant growth and immunity. Here we show that N-terminal features of CPR5 are involved in the regulation of the balance between growth and resistance. These findings may benefit efforts to improve plant yield, while maintaining optimal levels of disease resistance.
Intraoperative hypotension is associated with shortened overall survival after lung cancer surgery
Authors: Huang Wen-Wen , Zhu Wen-Zhi , Mu Dong-Liang , Ji Xin-Qiang , Li Xue-Ying , Ma Daqing , Wang Dong-Xin
Published: June 2020

Background

Intraoperative hypotension is associated with increased morbidity and mortality after surgery. We hypothesized that intraoperative hypotension might also be associated with worse long-term survival after cancer surgery. Herein, we analyzed the correlation between intraoperative hyper−/hypotension and overall survival after lung cancer surgery.

Methods

In this retrospective cohort study, 676 patients who received lung cancer surgery between January 1, 2006 and December 31, 2009 were reviewed. Intraoperative hyper- and hypotension were defined according to their correlation with long-term survival. The primary endpoint was overall survival. The association between episodes of intraoperative hyper−/hypotension and overall survival was analyzed with multivariable Cox proportional hazard models.

Results

Long-term follow-ups were completed in 515 patients with a median duration of 5.2 years. The estimated 5-year survival rates were 66.5, 61.3, 56.5, and 41.2% in patients with only hypertension (systolic blood pressure > 140 mmHg for ≥5 min), with both hyper- and hypotension (systolic blood pressure < 100 mmHg for ≥5 min), with neither hyper- nor hypotension, and with only hypotension during surgery, respectively. After adjusting confounding factors, intraoperative hypotension was significantly associated with shortened overall survival (compared with patients with only intraoperative hypertension, those with both hyper- and hypotension: hazard ratio [HR]1.033, 95% confidence interval [CI] 0.709 to 1.507, p = 0.864; those with neither hyper- nor hypotension: HR 0.952, 95% CI 0.608 to 1.489, p = 0.829; those with only hypotension: HR 1.736, 95% CI 1.218 to 2.475, p = 0.002).

Conclusions

For patients undergoing lung cancer surgery, intraoperative hypotension, but not hypertension, was associated with shortened overall survival.
Cardiac-specific methylation patterns of circulating DNA for identification of cardiomyocyte death
Authors: Liu Qin , Ma Jian , Deng Hua , Huang Shu-Jun , Rao Jiao , Xu Wei-Bin , Huang Jing-Si , Sun Shan-Quan , Zhang Liang
Published: June 2020

Background

Correct detection of human cardiomyocyte death is essential for definitive diagnosis and appropriate management of cardiovascular diseases. Although current strategies have proven utility in clinical cardiology, they have some limitations. Our aim was to develop a new approach to monitor myocardial death using methylation patterns of circulating cell-free DNA (cf-DNA).

Methods

We first examined the methylation status of FAM101A in heart tissue and blood of individual donors using quantitative methylation-sensitive PCR (qMS-PCR). The concentrations and kinetics of cardiac cf-DNA in plasma from five congenital heart disease (CHD) children before and after they underwent cardiac surgery at serial time points were then investigated.

Results

We identified demethylated FAM101A specifically present in heart tissue. Importantly, our time course experiments demonstrated that the plasma cardiac cf-DNA level increased quickly during the early post-cardiac surgery phase, peaking at 4–6 h, decreased progressively (24 h) and returned to baseline (72 h). Moreover, cardiac cf-DNA concentrations pre- and post-operation were closely correlated with plasma troponin levels.

Conclusions

We proposed a novel strategy for the correct detection of cardiomyocyte death, based on analysis of plasma cf-DNA carrying the cardiac-specific methylation signature. Our pilot study may lead to new tests for human cardiac pathologies.
Delay in treatment initiation and its association with clinical severity and infectiousness among new adult pulmonary tuberculosis patients in Tigray, northern Ethiopia
Authors: Tedla Kiros , Medhin Girmay , Berhe Gebretsadik , Mulugeta Afework , Berhe Nega
Published: June 2020

Background

Delayed treatment initiation of tuberculosis (TB) increases disease progression and development of complications which may lead to a higher level of infectiousness, clinical severity and increased mortality. But published evidences that investigated the effect of delayed initiation of treatment on clinical severity and level of infectiousness of pulmonary tuberculosis patients is scarce in Tigray, Northern Ethiopia.

Objective

To investigate the association of delayed treatment initiation of new adult Pulmonary Tuberculosis patients with clinical severity and level of infectiousness.

Methods

In this cross-sectional study design, a total of 875 newly diagnosed adult pulmonary tuberculosis patients were recruited from 21 health facilities from October 2018 to October 2019. Health facilities and study participants were selected by a simple random sampling method. Data were collected using questionnaires through face-to-face interviews of patients within the first 2 weeks of treatment initiation. Clinical severity was assessed by Bandim tuberculosis score and level of infectiousness was assessed by smear positivity or lung cavitations. Data were analyzed using SPSS version 21 software program. Logistic regression analysis was used to ascertain the association of delay with clinical severity and level of infectiousness. P-BMC Public Health of less than 0.05 was reported as being statistically significant.

Results

Those who had initiated treatment without delay and those who have initiated treatment after a medium delay of 31 to 60 days were significantly associated with decreased clinical score compared to those who initiated treatment after a delay of more than two months. Compared with patients who have initiated treatment within one month, the level of infectiousness was greater for delay of 30–60 days and above 60 days. Patients having more than 3 family members have higher level of infectiousness as compared to those who have a maximum of 3 family members. Whereas, patients having at least two rooms and being HIV negative had lower levels of infectiousness compared to their counter patients.

Conclusion

Narrowing the gap between their initial occurrence of TB symptoms and treatment initiation is the way forward to improve clinical courses of TB patients and to reduce the level of infectiousness of TB to other people from these patients.
Radiogenomics correlation between MR imaging features and mRNA-based subtypes in lower-grade glioma
Authors: Liu Zhenyin , Zhang Jing
Published: June 2020

Background

To investigate associations between lower-grade glioma (LGG) mRNA-based subtypes (R1-R4) and MR features.

Methods

mRNA-based subtyping was obtained from the LGG dataset in The Cancer Genome Atlas (TCGA). We identified matching patients (n = 145) in The Cancer Imaging Archive (TCIA) who underwent MR imaging. The associations between mRNA-based subtypes and MR features were assessed.

Results

In the TCGA-LGG dataset, patients with the R2 subtype had the shortest median OS months (P < 0.05). The time-dependent ROC for the R2 subtype was 0.78 for survival at 12 months, 0.76 for survival at 24 months, and 0.76 for survival at 36 months. In the TCIA-LGG dataset, 41 (23.7%) R1 subtype, 40 (23.1%) R2 subtype, 19 (11.0%) R3 subtype and 45 (26.0%) R4 subtype cases were identified. Multivariate analysis revealed that enhancing margin (ill-defined, OR: 9.985; P = 0.003) and T1 + C/T2 mismatch (yes, OR: 0.091; P = 0.023) were associated with the R1 subtype (AUC: 0.708). The average accuracy of the ten-fold cross validation was 71%. Proportion of contrast-enhanced (CE) tumour (> 5%, OR: 14.733; P < 0.001) and necrosis/cystic changes (yes, OR: 0.252; P = 0.009) were associated with the R2 subtype (AUC: 0.832). The average accuracy of the ten-fold cross validation was 82%. Haemorrhage (yes, OR: 8.55; P < 0.001) was positively associated with the R3 subtype (AUC: 0.689). The average accuracy of the ten-fold cross validation was 87%. Proportion of CE tumour (> 5%, OR: 0.14; P < 0.001) was negatively associated with the R4 subtype (AUC: 0.672). The average accuracy of the ten-fold cross validation was 71%. For the prediction of the R2 subtype, the nomogram showed good discrimination and calibration. Decision curve analysis demonstrated that prediction with the R2 model was clinically useful.

Conclusions

Patients with the R2 subtype had the worst prognosis. We demonstrated that MRI features can identify distinct LGG mRNA-based molecular subtypes.
Potential enhancement of host immunity and anti-tumor efficacy of nanoscale curcumin and resveratrol in colorectal cancers by modulated electro- hyperthermia
Authors: Kuo I-Ming , Lee Jih-Jong , Wang Yu-Shan , Chiang Hsin-Chien , Huang Cheng-Chung , Hsieh Pei-Jong , Han Winston , Ke Chiao-Hsu , Liao Albert T. C. , Lin Chen-Si
Published: June 2020

Background

Modulated electro-hyperthermia (mEHT) is a form of hyperthermia used in cancer treatment. mEHT has demonstrated the ability to activate host immunity by inducing the release of heat shock proteins, triggering apoptosis, and destroying the integrity of cell membranes to enhance cellular uptake of chemo-drugs in tumor cells. Both curcumin and resveratrol are phytochemicals that function as effective antioxidants, immune activators, and potential inhibitors of tumor development. However, poor bioavailability is a major obstacle for use in clinical cancer treatment.

Methods

This purpose of this study was to investigate whether mEHT can increase anti-cancer efficacy of nanosized curcumin and resveratrol in in vitro and in vivo models. The in vitro study included cell proliferation assay, cell cycle, and apoptosis analysis. Serum concentration was analyzed for the absorption of curcumin and resveratrol in SD rat model. The in vivo CT26/BALB/c animal tumor model was used for validating the safety, tumor growth curve, and immune cell infiltration within tumor tissues after combined mEHT/curcumin/resveratrol treatment.

Results

The results indicate co-treatment of mEHT with nano-curcumin and resveratrol significantly induced cell cycle arrest and apoptosis of CT26 cells. The serum concentrations of curcumin and resveratrol were significantly elevated when mEHT was applied. The combination also inhibited the growth of CT26 colon cancer by inducing apoptosis and HSP70 expression of tumor cells while recruiting CD3+ T-cells and F4/80+ macrophages.

Conclusions

The results of this study have suggested that this natural, non-toxic compound can be an effective anti-tumor strategy for clinical cancer therapy. mEHT can enable cellular uptake of potential anti-tumor materials and create a favorable tumor microenvironment for an immunological chain reaction that improves the success of combined treatments of curcumin and resveratrol.
Prevalence and incidence of cancer related lymphedema in low and middle-income countries: a systematic review and meta-analysis
Authors: Torgbenu Eric , Luckett Tim , Buhagiar Mark A. , Chang Sungwon , Phillips Jane L.
Published: June 2020

Background

Little is known about the prevalence and incidence in low and middle-income countries (LMICs) of secondary lymphedema due to cancer. The purpose of the study is to estimate the prevalence and incidence in LMICs of secondary lymphedema related to cancer and/or its treatment(s) and identify risk factors.

Method

A systematic review and meta-analysis was conducted. Medline, EMBASE and CINAHL were searched in June 2019 for peer-reviewed articles that assessed prevalence and/or incidence of cancer-related lymphedema in LMICs. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies. Estimates of pooled prevalence and incidence estimates were calculated with 95% confidence intervals (CI), with sub-group analyses grouping studies according to: country of origin, study design, risk of bias, setting, treatment, and lymphedema site and measurement. Heterogeneity was measured usingX2and I2, with interpretation guided by the Cochrane Handbook for Systematic Reviews.

Results

Of 8766 articles, 36 were included. Most reported on arm lymphedema secondary to breast cancer treatment (n = 31), with the remainder reporting on leg lymphedema following gynecological cancer treatment (n = 5). Arm lymphedema was mostly measured by arm circumference (n = 16/31 studies), and leg lymphedema through self-report (n = 3/5 studies). Eight studies used more than one lymphedema measurement. Only two studies that measured prevalence of leg lymphedema could be included in a meta-analysis (pooled prevalence =10.0, 95% CI 7.0–13.0,I2 = 0%). The pooled prevalence of arm lymphedema was 27%, with considerable heterogeneity (95% CI 20.0–34.0,I2 = 94.69%,n = 13 studies). The pooled incidence for arm lymphedema was 21%, also with considerable heterogeneity (95% CI 15.0–26.0,I2 = 95.29%,n = 11 studies). There was evidence that higher body mass index (> 25) was associated with increased risk of arm lymphedema (OR: 1.98, 95% CI 1.45–2.70,I2 = 84.0%,P < 0.0001,n = 4 studies).

Conclusion

Better understanding the factors that contribute to variability in cancer-related arm lymphedema in LMICs is an important first step to developing targeted interventions to improve quality of life. Standardising measurement of lymphedema globally and better reporting would enable comparison within the context of information about cancer treatments and lymphedema care.