bluuebunny/crossref_metadata_2025 huggingface dataset:
Acetylsalicylic acid inhibits intravascular coagulation during Staphylococcus aureus–induced sepsis in mice
Authors: Carestia Agostina , Davis Rachelle P. , Grosjean Heidi , Lau Matthew W. , Jenne Craig N.
Published: January 2020

Antiplatelet therapies have been proposed for the treatment of sepsis, a syndrome resulting from a dysregulated immune response and inappropriate activation of coagulation. Acetylsalicylic acid (ASA) may serve as a potential therapeutic strategy to prevent infection-induced coagulopathy and associated tissue damage. Using intravital microscopy, we found that Staphylococcus aureus infection induced neutrophil recruitment, platelet aggregation, and neutrophil extracellular trap (NET) release in the liver. Mice pretreated with ASA, or animals receiving ASA 3 hours postinfection, had significantly reduced platelet aggregation and NET release. Additionally, ASA-treated mice had reduced intravascular thrombin activity and microvascular occlusion as compared with untreated S aureus–infected mice. This inhibition of coagulation was accompanied by decreased levels of alanine aminotransferase and aspartate aminotransferase in the plasma, indicating less liver damage. Finally, bacterial loads (colony-forming units per milliliter) in liver, lung, and spleen were not different between groups, and the phagocytic capacity of Kupffer cells was preserved following ASA treatment. These results suggest that ASA may serve as a therapeutic approach to sepsis through its ability to reduce the deleterious action of immunothrombi while maintaining innate immune functions.
Multiple BCL2 mutations cooccurring with Gly101Val emerge in chronic lymphocytic leukemia progression on venetoclax
Authors: Blombery Piers , Thompson Ella R. , Nguyen Tamia , Birkinshaw Richard W. , Gong Jia-nan , Chen Xiangting , McBean Michelle , Thijssen Rachel , Conway Thomas , Anderson Mary Ann , Seymour John F. , Westerman David A. , Czabotar Peter E. , Huang David C. S. , Roberts Andrew W.
Published: January 2020

The BCL2 inhibitor venetoclax has complete response rates of up to 50% in chronic lymphocytic leukemia patients, but secondary resistance reflecting acquired mutations in BCL2 can lead to treatment failure. Blombery et al report that an unexpectedly large number of patients carry multiple BCL2 mutations with subclonal variation in their occurrence.
Accumulation of genetic variants associated with immunity in the selective breeding of broilers
Authors: Zou Angela , Nadeau Kerry , Wang Pauline W. , Lee Jee Yeon , Guttman David S. , Sharif Shayan , Korver Doug R. , Brumell John H. , Parkinson John
Published: January 2020

Background

To satisfy an increasing demand for dietary protein, the poultry industry has employed genetic selection to increase the growth rate of broilers by over 400% in the past 50 years. Although modern broilers reach a marketable weight of ~ 2 kg in a short span of 35 days, a speed twice as fast as a broiler 50 years ago, the expedited growth has been associated with several negative detrimental consequences. Aside from heart and musculoskeletal problems, which are direct consequences of additional weight, the immune response is also thought to be altered in modern broilers.

Results

Given that identifying the underlying genetic basis responsible for a less sensitive innate immune response would be economically beneficial for poultry breeding, we decided to compare the genomes of two unselected meat control strains that are representative of broilers from 1957 and 1978, and a current commercial broiler line. Through analysis of genetic variants, we developed a custom prioritization strategy to identify genes and pathways that have accumulated genetic changes and are biologically relevant to immune response and growth performance. Our results highlight two genes, TLR3 and PLIN3, with genetic variants that are predicted to enhance growth performance at the expense of immune function.

Conclusions

Placing these new genomes in the context of other chicken lines, reveal genetic changes that have specifically arisen in selective breeding programs that were implemented in the last 50 years.
Trait-based mapping to identify the genetic factors underlying anaerobic germination of rice: Phenotyping, GXE, and QTL mapping
Authors: Ghosal Sharmistha , Quilloy Fergie Ann , Casal Carlos , Septiningsih Endang M. , Mendioro Merlyn S. , Dixit Shalabh
Published: January 2020

Background

Anaerobic germination is one of the most important traits for rice under direct-seeded conditions. The trait reduces risk of crop failure due to waterlogged conditions after seeding and allows water to be used as a means of weed control. The identification of QTLs and causal genes for anaerobic germination will facilitate breeding for improved direct-seeded rice varieties. In this study, we explored a BC1F2:3 population developed from a cross between BJ1, an indica landrace, and NSIC Rc222, a high-yielding recurrent parent. The population was phenotyped under different screening methods (anaerobic screenhouse, anaerobic tray, and aerobic screenhouse) to establish the relationship among the methods and to identify the most suitable screening method, followed by bulk segregant analysis (BSA) to identify large-effect QTLs.

Results

The study showed high heritability for survival (SUR) under all three phenotyping conditions. Although high correlation was observed within screening environments between survival at 14 and 21 days after seeding, the correlation across environments was low. Germination under aerobic and anaerobic conditions showed very low correlation, indicating the independence of their genetic control. The results were further confirmed through AMMI analysis. Four significant markers with an effect on anaerobic germination were identified through BSA. CIM analysis revealed qAG1–2, qAG6–2, qAG7–4, and qAG10–1 having significant effects on the trait. qAG6–2 and qAG10–1 were consistent across screening conditions and seedling age while qAG1–2 and qAG7–4 were specific to screening methods. All QTLs showed an effect when survival across all screening methods was analyzed. Together, the QTLs explained 39 to 55% of the phenotypic variation for survival under anaerobic conditions. No QTL effects were observed under aerobic conditions.

Conclusions

The study helped us understand the effect of phenotyping method on anaerobic germination, which will lead to better phenotyping for this trait in future studies. The QTLs identified through this study will allow the improvement of breeding lines for the trait through marker-assisted selection or through forward breeding approaches such as genomic selection. The high frequency of the BJ1 allele of these QTLs will enhance the robustness of germination under anaerobic conditions in inbred and hybrid rice varieties.
In-stent restenosis and longitudinal stent deformation: a case report
Authors: Si Daoyuan , Tong Yaliang , Yu Bo , He Yuquan , Liu Guohui
Published: January 2020

Background

Longitudinal stent deformation (LSD) is an infrequent complication of percutaneous coronary intervention (PCI), and it may lead to catastrophic clinical outcomes. However, reports of cardiac adverse events associated with LSD are rare.

Case presentation

A 55-year-old man with chest pain was treated for a severe left anterior descending branch (LAD)-diagonal 1 (D1) bifurcation lesion by PCI with two stents in the proximal LAD. LSD occurred during the withdrawal of the trapped D1 wire. High-pressure balloon dilatation was performed in the deformed stent, and the end-angiographic appearance was acceptable, but no additional corrective measures were implemented. Ten months later, the patient represented with acute coronary syndrome. Severe in-stent restenosis (ISR) had suboccluded the proximal LAD, and optical coherence tomography (OCT) visualized multilayered stent struts protruding into the lumen at the compressed segment of the stent. Following complete apposition with balloon dilation, a drug-coated balloon (DCB) was used to avoid an additional permanent metallic layer. He remained angina free, and the angiographic result demonstrated no residual stenosis at the six-month follow-up. To our knowledge, this case demonstrates the first report of ISR triggered by LSD in patients treated with DCBs under the guidance of OCT.

Conclusions

The current report underscores the importance of awareness of LSD, and OCT seems to be the preferred modality to confirm complete apposition. If left without performing additional corrective measures, LSD may be associated with a risk of ISR. Complete apposition with balloon dilation followed by a DCB is a feasible treatment option.
Antifungal resistance in patients with Candidaemia: a retrospective cohort study
Authors: Aldardeer Namareq F. , Albar Hadiel , Al-Attas Majda , Eldali Abdelmoneim , Qutub Mohammed , Hassanien Ashraf , Alraddadi Basem
Published: January 2020

Background

Candidaemia is the most common form of invasive candidiasis. Resistant Candida blood stream infection (BSI) is rising, with limitations on the development of broader-spectrum antifungal agents worldwide. Our study aimed to identify the occurrence of antifungal-resistant candidaemia and the distribution of these species, determine the risk factors associated with antifungal resistance and evaluate the association of antifungal-resistant candidaemia with the length of intensive care unit (ICU) and hospital stay and with 30-day mortality.

Methods

A retrospective cohort study was conducted at King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia. Adult patients diagnosed with candidaemia from January 2006 to December 2017 were included.

Results

A total of 196 BSIs were identified in 94 males (49.74%) and 95 females (50.26%). C. glabrata was the most commonly isolated Candida species, with 59 (30%), followed by C. albicans with 46 (23%). Susceptibility data were available for 122/189 patients, of whom 26/122 (21%) were resistant to one or more antifungals. C. parapsilosis with available sensitivity data were found in 30/122 isolates, of which 10/30 (33%) were resistant to fluconazole. Risk factors significantly associated with antifungal-resistant candidaemia included previous echinocandin exposure (odds ratio (OR) =1.38; 95% confidence interval (CI) (1.02–1.85); P = 0.006) and invasive ventilation (OR = 1.3; 95% CI (1.08–1.57); P = 0.005). The median length of ICU stay was 29 days [range 12–49 days] in the antifungal-resistant group and 18 days [range 6.7–37.5 days] in the antifungal-sensitive group (P = 0.28). The median length of hospital stay was 51 days [range 21–138 days] in the antifungal-resistant group and 35 days [range 17–77 days] in the antifungal-sensitive group (P = 0.09). Thirty-day mortality was 15 (57.7%) and 54 (56.25%) among the antifungal-resistant and antifungal-sensitive groups, respectively (OR = 1.01; 95% CI (0.84–1.21); P = 0.89).

Conclusions

Our results indicate a high frequancy of non- C. albicans candidaemia. The rise in C. parapsilosis resistance to fluconazole is alarming. Further studies are required to confirm this finding.
Clinical experience with a novel assay measuring cytomegalovirus (CMV)-specific CD4+ and CD8+ T-cell immunity by flow cytometry and intracellular cytokine staining to predict clinically significant CMV events
Authors: Rogers Ralph , Saharia Kapil , Chandorkar Aditya , Weiss Zoe F. , Vieira Kendra , Koo Sophia , Farmakiotis Dimitrios
Published: January 2020

Background

Cytomegalovirus (CMV) infection is one of the most common opportunistic infections following organ transplantation, despite administration of CMV prophylaxis. CMV-specific T-cell immunity (TCI) has been associated with reduced rates of CMV infection. We describe for the first time clinical experience using the CMV T-Cell Immunity Panel (CMV-TCIP), a commercially available assay which measures CMV-specific CD4+ and CD8+ T-cell responses, to predict clinically significant CMV events.

Methods

Adult (> 18-year-old) patients with CMV-TCIP results and ≥ 1 subsequent assessment for CMV DNAemia were included at Brown University and the University of Maryland Medical Center-affiliated hospitals between 4/2017 and 5/2019. A clinically significant CMV event was defined as CMV DNAemia prompting initiation of treatment. We excluded indeterminate results, mostly due to background positivity, allogeneic hematopoetic cell transplant (HCT) recipients, or patients who were continued on antiviral therapy against CMV irrespective of the CMV-TCIP result, because ongoing antiviral therapy could prevent a CMV event.

Results

We analyzed 44 samples from 37 patients: 31 were solid organ transplant recipients, 4 had hematologic malignancies, 2 had autoimmune disorders. The CMV-protection receiver operating characteristic (ROC) area under the curve (AUC) was significant for %CMV-specific CD4+ (AUC: 0.78, P < 0.001) and borderline for CD8+ (AUC: 0.66, P = 0.064) T-cells. At a cut-off value of 0.22% CMV-specific CD4+ T-cells, positive predictive value (PPV) for protection against CMV was 85% (95%CI 65–96%), and negative predictive value (NPV) was 67% (95%CI 41–87%).

Conclusions

The CMV-TCIP, in particular %CMV-specific CD4+ T-cells, showed good diagnostic performance to predict CMV events. The CMV-TCIP may be a useful test in clinical practice, and merits further validation in larger prospective studies.
The prevalence of lower urinary tract symptoms based on individual and clinical parameters in patients with multiple sclerosis
Authors: Nazari Fatemeh , Shaygannejad Vahid , Mohammadi Sichani Mehrdad , Mansourian Marjan , Hajhashemi Valiollah
Published: January 2020

Background

Most patients with multiple sclerosis (MS) suffer from bladder dysfunction during the course of the disease. This study was conducted to examine the prevalence of these complications among patients with MS.

Methods

This cross-sectional study was performed on 602 patients with MS who referred to the neurology clinics of Kashani and Alzahra Hospitals affiliated to Isfahan University of Medical Sciences, Isfahan, Iran. Multistage random cluster sampling was performed and the informed consent form was signed by the subjects. Then, all the data were collected through interviews using the Lower Urinary Tract Symptom Score (LUTSS) developed in accordance with the definitions presented by the International Continence Society (ICS) and the International Prostate Symptom Score (I-PSS) and DASS-21 questionnaire. The data were analyzed using descriptive and inferential statistical tests in SPSS.

Results

The prevalence rate of lower urinary tract symptoms (LUTS) was 87.6% among all the subjects, with a similar rate among women (88.0%) and men (86.0%). There was a significant difference between men and women in terms of the prevalence of stress urinary incontinence (SUI), intermittent urine flow, hesitancy, straining, and dribbling (P <  0.050). There was no significant difference between women and men in terms of the prevalence of other symptoms (P > 0.050). A significant difference was observed in the degree of LUTS with age, marital status, marriage duration, education, illness duration, clinical course, disability, anxiety, depression, and stress (P<  0.05). Moreover, logistic regression analysis revealed that there was a higher probability of a urinary problems among patients with MS and a high EDSS score [0.67 (0.507–0.903),P = 0.008].

Conclusions

A high prevalence of LUTS was found among patients with MS. There was a higher probability of a urinary tract problem among patients with MS and a high EDSS score. Therefore, it is recommended that the health system take the necessary measures regarding timely detection and treatment of LUTS among these patients in order to prevent secondary outcomes and improve the quality of life (QOL) of patients with MS.
Secondary cardiac involvement in anti-SRP-antibody-positive myopathy: an 87-year-old woman with heart failure symptoms as the first clinical presentation
Authors: Hara Arika , Amano Ryota , Yokote Hiroaki , Ijima Masahide , Zeniya Satoshi , Uchihara Toshiki , Yada Sawako , Masumura Mayumi , Takei Hidenobu , Nishino Ichizo , Toru Shuta
Published: January 2020

Background

Necrotizing myopathy (NM) is defined by the dominant pathological feature of necrosis of muscle fibers without substantial lymphocytic inflammatory infiltration. Anti-signal recognition particle (SRP)-antibody-positive myopathy is related to NM. Anti-SRP-antibody-positive myopathy can comorbid with other disorders in some patients, however, comorbidity with malignant tumor and myopericarditis has still not been reported.

Case presentation

An 87-year-old woman with dyspnea on exertion and leg edema was referred to our hospital because of suspected heart failure and elevated serum creatine kinase level. Upon hospitalization, she developed muscle weakness predominantly in the proximal muscles. Muscle biopsy and immunological blood test led to the diagnosis of anti-SRP-antibody-positive myopathy. A colon carcinoma was also found and surgically removed. The muscle weakness remained despite the tumor resection and treatment with methylprednisolone. Cardiac screening revealed arrhythmia and diastolic dysfunction with pericardial effusion, which recovered with intravenous immunoglobulin (IVIg) treatment.

Conclusions

We reported the first case of anti-SRP-positive myopathy comorbid with colon carcinoma and myopericarditis. This case is rare in the point that heart failure symptoms were the first clinical presentation. The underlying mechanism is still not clear, however, physicians should be carefully aware of the neoplasm and cardiac involvement in anti-SRP-antibody positive-myopathy patients and should consider farther evaluation and management.
Inflammation biomarker discovery in Parkinson’s disease and atypical parkinsonisms
Authors: Santaella Anna , Kuiperij H. Bea , van Rumund Anouke , Esselink Rianne A. J. , van Gool Alain J. , Bloem Bastiaan R. , Verbeek Marcel M.
Published: January 2020

Background

Parkinson’s disease (PD) and atypical parkinsonisms (APD) have overlapping symptoms challenging an early diagnosis. Diagnostic accuracy is important because PD and APD have different prognosis and response to treatment. We aimed to identify diagnostic inflammatory biomarkers of PD and APD in cerebrospinal fluid (CSF) using the multiplex proximity extension assay (PEA) technology and to study possible correlations of biomarkers with disease progression.

Methods

CSF from a longitudinal cohort study consisting of PD and APD patients (PD, n = 44; multiple system atrophy (MSA), n = 14; vascular parkinsonism (VaP), n = 9; and PD with VaP, n = 7) and controls (n = 25) were analyzed.

Results

Concentrations of CCL28 were elevated in PD compared to controls (p = 0.0001). Five other biomarkers differentiated both MSA and PD from controls (p < 0.05) and 10 biomarkers differentiated MSA from controls, of which two proteins, i.e. beta nerve growth factor (β-NGF) and Delta and Notch like epidermal growth factor-related receptor (DNER), were also present at lower levels in MSA compared to PD (both p = 0.032). Two biomarkers (MCP-1 and MMP-10) positively correlated with PD progression (rho > 0.650; p < 0.01).

Conclusions

PEA technique identified potential new CSF biomarkers to help to predict the prognosis of PD. Also, we identified new candidate biomarkers to distinguish MSA from PD.
Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine clinical studies
Authors: Bangs Mark E. , Kudrow David , Wang Shufang , Oakes Tina M. , Terwindt Gisela M. , Magis Delphine , Yunes-Medina Laura , Stauffer Virginia L.
Published: January 2020

Background

Galcanezumab, a humanized monoclonal antibody that selectively binds to calcitonin gene-related peptide, has demonstrated a significant reduction in monthly migraine headache days in phase 2 and 3 trials. In these analyses, we aimed to evaluate the safety and tolerability of galcanezumab compared with placebo for prevention of episodic or chronic migraine.

Methods

Data were integrated from three double-blind clinical studies for the up to 6-month galcanezumab exposure group (N = 1435), and from five clinical studies for the up to 1-year all-galcanezumab exposure group (N = 2276). Patients received a monthly 120 mg subcutaneous injection of galcanezumab (with a 240 mg loading dose in month 1), 240 mg galcanezumab, or placebo. Outcomes measured were treatment-emergent adverse events (TEAEs), serious AEs (SAEs), and discontinuation due to AEs (DCAEs). Laboratory results, vital signs, electrocardiogram (ECG), suicidal ideation and behavior results were evaluated.

Results

TEAEs that occurred more frequently in galcanezumab-treated patients included injection site pain, injection site reactions excluding pain, constipation, vertigo, and pruritus. The proportion of DCAEs among galcanezumab-treated patients ranged between 1.8 and 3.0%, and differed from placebo group for galcanezumab 240 mg (P < 0.05). Fewer than 2.0% of patients in either galcanezumab dose-group compared with 1.0% of placebo-treated patients reported a SAE. There were no clinically meaningful differences between galcanezumab and placebo in laboratory measures, vital signs including blood pressure, ECGs, cardiovascular-related AEs, or suicidal ideation and behavior.

Conclusions

Galcanezumab demonstrated a favorable safety and tolerability profile for up to 1 year of treatment for the prevention of migraine.

Trial registration

Clinical Trials CGAB = NCT02163993, EVOLVE-1 = NCT02614183, EVOLVE-2 = NCT02614196, REGAIN = NCT02614261, and CGAJ = NCT02614287. All were first posted on 25 November 2015, except CGAB posted on 16 June 2014, and before enrolling the first patient.
Correction to: Cellular immunotherapy using irradiated lung cancer cell vaccine co-expressing GM-CSF and IL-18 can induce significant antitumor effects
Authors: Tian Hongwei , Shi Gang , Yang Guoyou , Zhang Junfeng , Li Yiming , Du Tao , Wang Jianzhou , Xu Fen , Cheng Lin , Zhang Xiaomei , Dai Lei , Chen Xiaolei , Zhang Shuang , Yang Yang , Yu Dechao , Wei Yuquan , Deng Hongxin
Published: January 2020

Following publication of the original article [1], the authors reported an error in Fig 5 of this article, graphs presenting FCM and immunofluorescent for CD4T, CD8T and NK cell of the Control Groups (LL2, LL2-irradation, MCS-irradiation) were inadvertently duplicated from another parallel experiment.
Povidone-iodine pharmacokinetics and study design
Authors: Koerner Jagger , Grzybowski Andrzej
Published: January 2020

Dr. Gnanasekaran et al. reported the bactericidal activity of various concentrations of povidone iodine (PI) solution in an agar plate experiment of respiratory flora. The study design and the pharmacokinetic properties of PI solution ensured that dilute PI would not be effective in this study. These results may not replicate the typical clinical situation and are significantly different than a previously reported agar plate experiment, again owing to subtle but very significant differences in methodology.
Determinants of healthcare seeking for childhood illnesses among caregivers of under-five children in urban slums in Malawi: a population-based cross-sectional study
Authors: Lungu Edgar Arnold , Darker Catherine , Biesma Regien
Published: January 2020

Background

There is considerable evidence that health systems, in so far as they ensure access to healthcare, promote population health even independent of other determinants. Access to child health services remains integral to improving child health outcomes. Cognisant that improvements in child health have been unevenly distributed, it is imperative that health services and research focus on the disadvantaged groups. Children residing in urban slums are known to face a health disadvantage that is masked by the common view of an urban health advantage. Granted increasing urbanisation rates and proliferation of urban slums resulting from urban poverty, the health of under-five children in slums remains a public health imperative in Malawi. We explored determinants of healthcare-seeking from a biomedical health provider for childhood symptoms of fever, cough with fast breathing and diarrhoea in three urban slums of Lilongwe, Malawi.

Methods

This was a population-based cross-sectional study involving 543 caregivers of under-five children. Data on childhood morbidity and healthcare seeking in three months period were collected using face-to-face interviews guided by a validated questionnaire. Data were entered in CS-Pro 5.0 and analysed in SPSS version 20 using descriptive statistics and logistic regression analyses.

Results

61% of caregivers sought healthcare albeit 53% of them sought healthcare late. Public health facilities constituted the most frequently used health providers. Healthcare was more likely to be sought: for younger than older under-five children (AOR = 0.54; 95% CI: 0.30–0.99); when illness was perceived to be severe (AOR = 2.40; 95% CI: 1.34–4.30); when the presenting symptom was fever (AOR = 1.77; 95% CI: 1.10–2.86). Home management of childhood illness was negatively associated with care-seeking (AOR = 0.54; 95% CI: 0.36–0.81) and timely care-seeking (AOR = 0.44; 95% CI: 0.2–0.74). Caregivers with good knowledge of child danger signs were less likely to seek care timely (AOR = 0.57; 95% CI: 0.33–0.99).

Conclusions

Even in the context of geographical proximity to healthcare services, caregivers in urban slums may not seek healthcare or when they do so the majority may not undertake timely healthcare care seeking. Factors related to the child, the type of illness, and the caregiver are central to the healthcare decision making dynamics. Improving access to under-five child health services therefore requires considering multiple factors.
“A very humiliating illness”: a qualitative study of patient-centered Care for Rifampicin-Resistant Tuberculosis in South Africa
Authors: Furin Jennifer , Loveday Marian , Hlangu Sindisiwe , Dickson-Hall Lindy , le Roux Sacha , Nicol Mark , Cox Helen
Published: January 2020

Background

Patient-centered care is pillar 1 of the “End TB” strategy, but little has been documented in the literature about what this means for people living with rifampicin-resistant (RR-TB). Optimizing care for such individuals requires a better understanding of the challenges they face and the support they need.

Methods

A qualitative study was done among persons living with RR-TB and members of their support network. A purposive sample was selected from a larger study population and open-ended interviews were conducted using a semi-standard interview guide. Interviews were recorded and transcribed and the content analyzed using an iterative thematic analysis based in grounded theory.

Results

16 participants were interviewed from three different provinces. Four distinct periods in which support was needed were identified: 1) pre-diagnosis; 2) pre-treatment; 3) treatment; and 4) post-treatment. Challenges common in all four periods included: socioeconomic issues, centralized care, and the need for better counseling at multiple levels.

Conclusions

Beyond being a “very humiliating illness”, RR-TB robs people of their physical, social, economic, psychological, and emotional well-being far beyond the period when treatment is being administered. Efforts to tackle these issues are as important as new drugs and diagnostics in the fight against TB.
Effect of motorcycle helmet types on head injuries: evidence from eight level-I trauma centres in Taiwan
Authors: Lam Carlos , Wiratama Bayu Satria , Chang Wen-Han , Chen Ping-Ling , Chiu Wen-Ta , Saleh Wafaa , Pai Chih-Wei
Published: January 2020

Background

Motorcycle full-coverage helmet use may reduce fatalities and head injuries.

Methods

This retrospective cohort study extracted injury data from eight level-I trauma centres in Taiwan and performed a questionnaire survey to investigate injuries sustained by motorcyclists for the period between January 2015 and June 2017.

Results

As many as 725 patients participated in the questionnaire survey and reported their helmet types or phone use during crashes. The results of multivariate logistic models demonstrated that nonstandard helmet (half or open-face helmet) use was associated with an increased risk of head injuries and more severe injuries (injury severity score ≥ 8). Drunk riding and phone use appeared to be two important risk factors for head injuries and increased injury severity. Anaemia was also found to be a determinant of head injuries.”

Conclusions

Compared to full-coverage helmets, nonstandard provide less protection against head injuries and increased injury severity among motorcyclists.
Current infection control practices used in Australian and New Zealand cystic fibrosis centers
Authors: Stockwell Rebecca Elizabeth , Wood Michelle ELizabeth , Ballard Emma , Moore Vanessa , Wainwright Claire Elizabeth , Bell Scott Cameron
Published: January 2020

Background

The 2013 update of the Infection Prevention and Control (IP&C) Guideline outlined recommendations to prevent the spread of CF respiratory pathogens. We aimed to investigate the current infection control practices used in Australian and New Zealand (NZ) CF centers.

Methods

Two online surveys were distributed to Australian and NZ CF centers regarding the uptake of selected IP&C recommendations. One survey was distributed to all the Medical Directors and Lead CF Nurses and the second survey was distributed to all the Lead CF Physiotherapists.

Results

The response rate was 60% (60/100) for medical/nursing and 58% (14/24) for physiotherapy. Over 90% (55/60) of CF centers followed CF-specific infection control guidelines and consistent infection control practices were seen in most CF centers; 76% (41/54) had implemented segregation strategies for ambulatory care and no CF centers housed people with CF in shared inpatient accommodation. However, the application of contact precautions (wearing gloves and apron/gown) by healthcare professionals when reviewing a CF person was variable between CF center respondents but was most often used when seeing CF persons with MRSA infection in both ambulatory care and hospital admission (20/50, 40% and 42/45, 93% of CF centers, respectively). Mask wearing by people with CF was implemented into 61% (36/59) of centers. Hospital rooms were cleaned daily in 79% (37/47) of CF centers and the ambulatory care consult rooms were always cleaned between consults (49/49, 100%) and at the end of the clinic session (51/51, 100%); however the staff member tasked with cleaning changed with 37% (18/49) of CF centers responding that CF multidisciplinary team (MDT) members cleaned between patients whereas at the end of the clinic session, only 12% (6/51) of the CF MDT cleaned the consult room.

Conclusions

Overall, Australian and NZ CF centers have adopted many recommendations from the IP&C. Although, the application of contact precautions was inconsistent and had overall a low level of adoption in CF centers. In ~ 25% of centers, mixed waiting areas occurred in the ambulatory care. Given the variability of responses, additional work is required to achieve greater consistency between centers.
Surgical removal of part of an occluder to treat iatrogenic coarctation of the aorta: a case report
Authors: Sun Zhongwei , Li Dongxu , Wang Yabo , An Qi
Published: January 2020

Background

Iatrogenic aortic stenosis is a serious complication and potentially fatal due to erosion of the aortic wall. Timely management is necessary to prevent complications.

Case presentation

A 2-year-old boy underwent surgery to remove part of an Amplatzer occluder after patent ductus arteriosus (PDA) device embolization in the thoracic aorta. He exhibited moderate to severe obstruction with erosion of the intimal layer of the aorta caused by the device, part of which was retrieved surgically with restructuring of the thoracic aorta segment and occluder remnant. The patient’s postoperative course was uneventful.

Conclusions

When possible, retrieving only part of an embolized device can be advocated because it reduces the risk of aortic and pulmonary artery damage.
Development of a percutaneous coronary intervention patient level composite measure for a clinical quality registry
Authors: Ayton Darshini , Soh Sze-Ee , Morello Renata , Ahern Susannah , Earnest Arul , Brennan Angela , Lefkovits Jeffrey , Evans Susan , Reid Christopher , Ruseckaite Rasa , McNeil John
Published: January 2020

Background

Composite measures combine data to provide a comprehensive view of patient outcomes. Despite composite measures being a valuable tool to assess post-intervention outcomes, the patient perspective is often missing. The purpose of this study was to develop a composite measure for an established cardiac outcome registry, by combining clinical outcomes following percutaneous coronary interventions (PCI) with a patient-reported outcome measure (PROM) developed specifically for this population (MC-PROM).

Methods

Two studies were undertaken. Study 1: Patients who had undergone a PCI at one of the three participating registry hospital sites completed the 5-item MC-PROM. Clinical outcome data for the patients (e.g. death, myocardial infarction, repeat vascularisation, new bleeding event) were collected 30 days post-intervention as part of routine data collection for the cardiac registry. Exploratory factor analysis of clinical outcomes and MC-PROM data was conducted to determine the minimum number of constructs to be included in a composite measure. Study 2: Clinical experts participated in a Delphi technique, consisting of three rounds of online surveys, to determine the clinical outcomes to be included and the weighting of the clinical outcomes and MC-PROM score for the composite measure.

Results

Study 1: Routine clinical outcomes and the MC-PROM data were collected from 266 patients 30 days post PCI. The MC-PROM score was not significantly correlated with any clinical outcomes.

Study 2: There was a relatively consistent approach to the weighting of the clinical outcomes and MC-PROM items by the expert panel (n = 18) across the three surveys with the exception of the clinical outcome of ‘deceased at 30 days’. The final composite measure included five clinical outcomes within 30 days weighted at 90% (new heart failure, new myocardial infarction, new stent thrombosis, major bleeding event, new stroke, unplanned cardiac rehospitalisation) and the MC-PROM score (comprising 10% of the total weighting).

Conclusions

A single patient level composite score, which incorporates weighted clinical outcomes and a PROM was developed. This composite score provides a more comprehensive reported measure of individual patient wellbeing at 30 days post their PCI-procedure, and may assist clinicians to further assess and address patient level factors that potentially impact on clinical recovery.
Youth Depression Alleviation with Anti-inflammatory Agents (YoDA-A): a randomised clinical trial of rosuvastatin and aspirin
Authors: Berk Michael , Mohebbi Mohammadreza , Dean Olivia M. , Cotton Sue M. , Chanen Andrew M. , Dodd Seetal , Ratheesh Aswin , Amminger G. Paul , Phelan Mark , Weller Amber , Mackinnon Andrew , Giorlando Francesco , Baird Shelley , Incerti Lisa , Brodie Rachel E. , Ferguson Natalie O. , Rice Simon , Schäfer Miriam R. , Mullen Edward , Hetrick Sarah , Kerr Melissa , Harrigan Susy M. , Quinn Amelia L. , Mazza Catherine , McGorry Patrick , Davey Christopher G.
Published: January 2020

Background

Inflammation contributes to the pathophysiology of major depressive disorder (MDD), and anti-inflammatory strategies might therefore have therapeutic potential. This trial aimed to determine whether adjunctive aspirin or rosuvastatin, compared with placebo, reduced depressive symptoms in young people (15–25 years).

Methods

YoDA-A, Youth Depression Alleviation with Anti-inflammatory Agents, was a 12-week triple-blind, randomised, controlled trial. Participants were young people (aged 15–25 years) with moderate to severe MDD (MADRS mean at baseline 32.5 ± 6.0; N = 130; age 20.2 ± 2.6; 60% female), recruited between June 2013 and June 2017 across six sites in Victoria, Australia. In addition to treatment as usual, participants were randomised to receive aspirin (n = 40), rosuvastatin (n = 48), or placebo (n = 42), with assessments at baseline and weeks 4, 8, 12, and 26. The primary outcome was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12.

Results

At the a priori primary endpoint of MADRS differential change from baseline at week 12, there was no significant difference between aspirin and placebo (1.9, 95% CI (− 2.8, 6.6), p = 0.433), or rosuvastatin and placebo (− 4.2, 95% CI (− 9.1, 0.6), p = 0.089). For rosuvastatin, secondary outcomes on self-rated depression and global impression, quality of life, functioning, and mania were not significantly different from placebo. Aspirin was inferior to placebo on the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) at week 12. Statins were superior to aspirin on the MADRS, the Clinical Global Impressions Severity Scale (CGI-S), and the Negative Problem Orientation Questionnaire scale (NPOQ) at week 12.

Conclusions

The addition of either aspirin or rosuvastatin did not to confer any beneficial effect over and above routine treatment for depression in young people. Exploratory comparisons of secondary outcomes provide limited support for a potential therapeutic role for adjunctive rosuvastatin, but not for aspirin, in youth depression.

Trial registration

Australian New Zealand Clinical Trials Registry, ACTRN12613000112763. Registered on 30/01/2013.
Temporal and anatomical distribution of 18F-flutemetamol uptake in canine brain using positron emission tomography
Authors: Yun Taesik , Lee Wonguk , Kang Ji-Houn , Yang Mhan-Pyo , Kang Byeong-Teck
Published: January 2020

Background

Positron emission tomography (PET) is increasingly being used as an imaging modality for clinical and research applications in veterinary medicine. Amyloid PET has become a useful tool for diagnosing Alzheimer’s disease (AD) in humans, by accurately identifying amyloid-beta (Aβ) plaques. Cognitive dysfunction syndrome in dogs shows cognitive and pathophysiologic characteristics similar to AD. Therefore, we assessed the physiologic characteristics of uptake of 18F-flutemetamol, an Aβ protein-binding PET tracer in clinical development, in normal dog brains, for distinguishing an abnormal state. Static and dynamic PET images of six adult healthy dogs were acquired after 18F-flutemetamol was administered intravenously at approximately 3.083 MBq/kg. For static images, PET data were acquired at 30, 60, and 90 min after injection. One week later, dynamic images were acquired for 120 min, from the time of tracer injection. PET data were reconstructed using an iterative technique, and corrections for attenuation and scatter were applied. Regions of interest were manually drawn over the frontal, parietal, temporal, occipital, anterior cingulate, posterior cingulate, and cerebellar cortices, cerebral white matter, midbrain, pons, and medulla oblongata. After calculating standardized uptake values with an established formula, standardized uptake value ratios (SUVRs) were obtained, using the cerebellar cortex as a reference region.

Results

Among the six cerebral cortical regions, the cingulate cortices and frontal lobe showed the highest SUVRs. The lowest SUVR was observed in the occipital lobe. The average values of the cortical SUVRs were 1.25, 1.26, and 1.27 at 30, 60, and 90 min post-injection, respectively. Tracer uptake on dynamic scans was rapid, peaking within 4 min post-injection. After reaching this early maximum, cerebral cortical regions showed a curve with a steep descent, whereas cerebral white matter demonstrated a curve with a slow decline, resulting in a large gap between cerebral cortical regions and white matter.

Conclusion

This study provides normal baseline data of 18F-flutemetamol PET that can facilitate an objective diagnosis of cognitive dysfunction syndrome in dogs in future.
Photoacoustic imaging of cells in a three-dimensional microenvironment
Authors: Liu Wei-Wen , Li Pai-Chi
Published: January 2020

Imaging live cells in a three-dimensional (3D) culture system yields more accurate information and spatial visualization of the interplay of cells and the surrounding matrix components compared to using a two-dimensional (2D) cell culture system. However, the thickness of 3D cultures results in a high degree of scattering that makes it difficult for the light to penetrate deeply to allow clear optical imaging. Photoacoustic (PA) imaging is a powerful imaging modality that relies on a PA effect generated when light is absorbed by exogenous contrast agents or endogenous molecules in a medium. It combines a high optical contrast with a high acoustic spatiotemporal resolution, allowing the noninvasive visualization of 3D cellular scaffolds at considerable depths with a high resolution and no image distortion. Moreover, advances in targeted contrast agents have also made PA imaging capable of molecular and cellular characterization for use in preclinical personalized diagnostics or PA imaging-guided therapeutics. Here we review the applications and challenges of PA imaging in a 3D cellular microenvironment. Potential future developments of PA imaging in preclinical applications are also discussed.
Immune-related gene signature for predicting the prognosis of head and neck squamous cell carcinoma
Authors: She Yangyang , Kong Xiangbo , Ge Yaping , Yin Ping , Liu Zhiyong , Chen Jieyu , Gao Feng , Fang Silian
Published: January 2020

Background

Immune-related genes (IRGs) were linked to the prognosis of head and neck squamous cell carcinoma (HNSCC). This study aimed to identify the effects of an immune-related gene signature (IRGS) that can predict the of HNSCC prognosis.

Methods

The expression data of 770 HNSCC patients from the TCGA database and the GEO database were used. To explore a predictive model, the Cox proportional hazards model was applied. The Kaplan–Meier survival analysis, as well as univariate and multivariate analyses were performed to evaluate the independent predictive value of IRGS. To explore biological functions of IRGS, enrichment analyses and pathway annotation for differentially expressed genes (DEGs) in different immune groups were applied, as well as the immune infiltration.

Results

A prognostic signature comprising 27 IRGs was generated. IRGS significantly stratified HNSCC patients into high and low immune risk groups in regard to overall survival in the training cohort (HR = 3.69, 95% CI 2.73–4.98, P < 0.001). Likewise, IRGS could be linked to the prognosis of HNSCC in patients of the validation cohort (HR = 1.84, 95% CI 1.21–2.81, P < 0.01). Even after adjusting for TNM stage, IRGS was maintained as an independent predictor in the multivariate analysis (HR = 3.62, 95% CI 2.58–5.09, P < 0.001), and in the validation cohort (HR = 1.73, 95% CI 1.12–2.67, P = 0.014). The IFN-α response, the IFN-γ response, IL-2/STAT5 signaling, and IL-6/JAK/STAT3 signaling were all negatively correlated with the immune risk (P < 0.01). Immune infiltration of the high-risk group was significantly lower than that of the low-risk group (P < 0.01). Most notably, the infiltration of CD8 T cells, memory-activated CD4 T cells, and regulatory T cells was strongly upregulated in the low immune risk groups, while memory resting CD4 T cell infiltration was downregulated (P < 0.01).

Conclusion

Our analysis provides a comprehensive prognosis of the immune microenvironments and outcomes for different individuals. Further studies are needed to evaluate the clinical application of this signature.
Molecular characteristics of odorant-binding protein 1 in Anopheles maculipennis
Authors: Ghavami Mohammad Bagher , Khoeini Sakineh , Djadid Navid Dinparast
Published: January 2020

Background

Anopheles maculipenniscomplex, the historic vector of malaria, causes serious medical problems worldwide and exhibits different behaviours. Studying the odorant-binding proteins (OBPs), which influence the chemosensory system and behavioural responses, is essential to understanding the population structure and developing effective control measures against this vector. The present study was designed to identify and analyse theobp1gene inAn. maculipennis.

Methods

Adults ofAn. maculipennissensu stricto were collected in Zanjan Province, northwest of Iran, and gDNAs of female mosquitoes were extracted. Fragments ofAn. maculipennis obp1(Amacobp1) gene were amplified using degenerate and specific primers, and some of amplicons were selected for sequencing.

Results

Analysis of amplified products identified that the sequence ofAmacobp1gene was 1341 bp long. This gene contains three exons (5′, internal, and 3′of 160, 256, and 18 bp, respectively) and encodes 144 amino acids. The sizes of introns I and II in deduced gene are 268 and 358 nucleotides, respectively. The amino acid sequence in the C-terminal of AmacOBP1 is similar to that of major malaria vectorAnophelesspecies. However, its N-terminal has a specific signal peptide with 19 amino acids. This peptide is conserved in different studied populations, and its sequence of amino acids shows the most variation among anopheline species.

Conclusions

Degenerate primers in this study are suggested for studyingobp1gene inAnophelesspecies.Amacobp1gene is proposed as a molecular marker for the detection of intraspecific ecotypes and diagnosis of different species within Maculipennis Group. Moreover, the N-terminal ofAmacOBP1peptide is recommended as a molecular marker to identify the Amacobp1 expression patterns in different chemosensory organs for assessing the molecular mechanisms and developing novel behavioural disturbance agents to controlAn. maculipennis.
The progress of gut microbiome research related to brain disorders
Authors: Zhu Sibo , Jiang Yanfeng , Xu Kelin , Cui Mei , Ye Weimin , Zhao Genming , Jin Li , Chen Xingdong
Published: January 2020

There is increasing evidence showing that the dynamic changes in the gut microbiota can alter brain physiology and behavior. Cognition was originally thought to be regulated only by the central nervous system. However, it is now becoming clear that many non-nervous system factors, including the gut-resident bacteria of the gastrointestinal tract, regulate and influence cognitive dysfunction as well as the process of neurodegeneration and cerebrovascular diseases. Extrinsic and intrinsic factors including dietary habits can regulate the composition of the microbiota. Microbes release metabolites and microbiota-derived molecules to further trigger host-derived cytokines and inflammation in the central nervous system, which contribute greatly to the pathogenesis of host brain disorders such as pain, depression, anxiety, autism, Alzheimer’s diseases, Parkinson’s disease, and stroke. Change of blood–brain barrier permeability, brain vascular physiology, and brain structure are among the most critical causes of the development of downstream neurological dysfunction. In this review, we will discuss the following parts:

Overview of technical approaches used in gut microbiome studies

Microbiota and immunity

Gut microbiota and metabolites

Microbiota-induced blood–brain barrier dysfunction

Neuropsychiatric diseases

■ Stress and depression

■ Pain and migraine

■ Autism spectrum disorders

Neurodegenerative diseases

■ Parkinson’s disease

■ Alzheimer’s disease

■ Amyotrophic lateral sclerosis

■ Multiple sclerosis

Cerebrovascular disease

■ Atherosclerosis

■ Stroke

■ Arteriovenous malformation

Conclusions and perspectives