bluuebunny/crossref_metadata_2025 huggingface dataset:
Ensuring adequate health financing to prevent and control the COVID-19 in Iran
Authors: Behzadifar Masoud , Ghanbari Mahboubeh Khaton , Bakhtiari Ahad , Behzadifar Meysam , Bragazzi Nicola Luigi
Published: May 2020

On February 19th 2020, the Iranian Ministry of Health and Medical Education (MoHME) has announced the first 2 cases of SARS-CoV-2, a novel emerging coronavirus which causes an infection termed as COVID-19, in Qom city. As such, the Iranian government, through the establishment of the “National Headquarters for the management and control of the novel Coronavirus”, has started implementing policies and programs for the prevention and control of the virus. These measures include schools and universities closure, reduced working hours, and increased production and delivery of equipment such as masks, gloves and hygienic materials for sterile environments. The government has also made efforts to divulge high-quality information concerning the COVID-19 and to provide laboratories and hospitals with diagnostic kits and adequate resources to treat patients. However, despite such efforts, the number of cases and deaths has progressively increased with rising trends in total confirmed cases and deaths, as well as in new daily cases and deaths associated with the COVID-19. Iran is a developing country and its economic infrastructure has been hit hardly by embargo and sanctions. While developed countries have allocated appropriate funding and are responding adequately to the COVID-19 pandemics, Iran has experienced a serious surge of cases and deaths and should strive to provide additional resources to the health system to make healthcare services more accessible and to increase the fairness of that access. All relevant actors and stakeholders should work together to fight this disease.
Cholesterol reducer and thrombolytic therapy in acute ischemic stroke patients
Authors: Poupore Nicolas , Strat Dan , Mackey Tristan , Brown Katherine , Snell Ashley , Nathaniel Thomas I.
Published: May 2020

Background

Specific clinical risk factors may contribute to improving or worsening neurological functions in acute ischemic stroke (AIS) patients pre-treated with a combined cholesterol reducer and recombinant tissue plasminogen activator (rtPA) therapy. In this study, clinical risk factors associated with good or poor presenting neurological symptoms in ischemic stroke patients with prior cholesterol reducer use, specifically a statin and rtPA therapy was investigated.

Methods

Retrospective data for baseline clinical and demographic data for patients with AIS taking cholesterol reducers prior to rtPA treatment from January 2010 to June 2016 in a regional stroke center was analyzed. Improving (NIHSS score ≤ 7) or worsening (NIHSS score > 7) of neurologic functions were the determined measures of treatment outcome. Multivariate logistic regression models identified demographic and clinical factors associated with worsening or improving neurologic functions.

Results

Adjusted multivariate analysis showed that in an AIS population with a combined rtPA and cholesterol reducer medication history, increasing age (OR = 1.032, 95% CI, 1.015–1.048,P < 0.001) and atrial fibrillation (OR = 1.859, 95% CI, 1.098–3.149,P = 0.021) demonstrated a likely association with worsening neurologic functions, while direct admission (OR = 0.411, 95% CI, 0.246–0.686,P = 0.001) and being Caucasian (OR = 0.496, 95% CI, 0.297–0.827,P = 0.007) showed an association with improving or progressing neurologic functions.

Conclusion

A prior cholesterol reducer, namely a statin, plus rtPA combination may be associated with worsening neurological function for elderly AIS patients with atrial fibrillation, while Caucasians directly admitted to a neurology unit are more likely to show an association with progress or improvements in neurologic functions. While combining statin with rtPA treatment may facilitate worsening neurologic functions in elderly AIS patients with atrial fibrillation, they should not be denied of this therapy. The decision to combine statin and rtPA for AIS patients with atrial fibrillation can be done after clinical stabilization following appropriate clinical management.
Urticaria: recommendations from the Italian Society of Allergology, Asthma and Clinical Immunology and the Italian Society of Allergological, Occupational and Environmental Dermatology
Authors: Nettis Eustachio , Foti Caterina , Ambrifi Marina , Baiardini Ilaria , Bianchi Leonardo , Borghi Alessandro , Caminati Marco , Canonica Giorgio Walter , Casciaro Marco , Colli Laura , Colombo Giselda , Corazza Monica , Cristaudo Antonio , De Feo Giulia , De Pita’ Ornella , Di Gioacchino Mario , Di Leo Elisabetta , Fassio Filippo , Gangemi Sebastiano , Gatta Alessia , Hansel Katharina , Heffler Enrico , Incorvaia Cristoforo , Napolitano Maddalena , Patruno Cataldo , Peveri Silvia , Pigatto Paolo Daniele , Quecchia Cristina , Radice Anna , Ramirez Giuseppe Alvise , Romita Paolo , Rongioletti Franco , Rossi Oliviero , Savi Eleonora , Senna Gianenrico , Triggiani Massimo , Zucca Myriam , Maggi Enrico , Stingeni Luca
Published: May 2020

Background

Urticaria is a disorder affecting skin and mucosal tissues characterized by the occurrence of wheals, angioedema or both, the latter defining the urticaria-angioedema syndrome. It is estimated that 12–22% of the general population has suffered at least one subtype of urticaria during life, but only a small percentage (estimated at 7.6–16%) has acute urticaria, because it is usually self-limited and resolves spontaneously without requiring medical attention. This makes likely that its incidence is underestimated. The epidemiological data currently available on chronic urticaria in many cases are deeply discordant and not univocal, but a recent Italian study, based on the consultation of a national registry, reports a prevalence of chronic spontaneous urticaria of 0.02% to 0.4% and an incidence of 0.1–1.5 cases/1000 inhabitants/year.

Methods

We reviewed the recent international guidelines about urticaria and we described a methodologic approach based on classification, pathophysiology, impact on quality of life, diagnosis and prognosis, differential diagnosis and management of all the types of urticaria.

Conclusions

The aim of the present document from the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) is to provide updated information to all physicians involved in diagnosis and management of urticaria and angioedema.
Blood cell count indexes as predictors of anastomotic leakage in elective colorectal surgery: a multicenter study on 1432 patients
Authors: Paliogiannis Panagiotis , Deidda Simona , Maslyankov Svilen , Paycheva Tsvetelina , Farag Ahmed , Mashhour Abdrabou , Misiakos Evangelos , Papakonstantinou Dimitrios , Mik Michal , Losinska Joanna , Scognamillo Fabrizio , Sanna Fabio , Feo Claudio Francesco , Cherchi Giuseppe , Xidas Andreas , Zinellu Angelo , Restivo Angelo , Zorcolo Luigi
Published: May 2020

Background

The aim of this study was to evaluate a series of blood count inflammation indexes in predicting anastomotic leakage (AL) in elective colorectal surgery.

Methods

Demographic, pathologic, and clinical data of 1432 consecutive patients submitted to colorectal surgery in eight surgical centers were retrospectively evaluated. The neutrophil to lymphocyte (NLR), derived neutrophil to lymphocyte (dNLR), lymphocyte to monocyte (LMR), and platelet to lymphocyte (PLR) ratios were calculated before surgery and on the 1st and 4th postoperative days, in patients with or without AL.

Results

There were 106 patients with AL (65 males, mean age 67.4 years). The NLR, dNLR, and PLR were significantly higher in patients with AL in comparison to those without, on both the 1st and 4th postoperative days, but significance was greater on the 4th postoperative day. An NLR cutoff value of 7.1 on this day showed the best area under the curve (AUC 0.744; 95% CI 0.719–0.768) in predicting AL.

Conclusions

Among the blood cell indexes of inflammation evaluated, NLR on the 4th postoperative day showed the best ability to predict AL. NLR is a low cost, easy to perform, and widely available index, which might be potentially used in clinical practice as a predictor of AL in patients undergoing elective colorectal surgery.
Long-term survival among patients with gastrointestinal stromal tumors diagnosed after another malignancy: a SEER population-based study
Authors: Shen Chaoyong , Wang Chengshi , He Tao , Cai Zhaolun , Yin Xiaonan , Yin Yuan , Lu Donghao , Zhang Bo , Zhou Zongguang
Published: May 2020

Background

To explore overall survival (OS) and GISTs-specific survival (GSS) among cancer survivors developing a second primary gastrointestinal stromal tumors (GISTs).

Methods

We conducted a cohort study, where patients with GISTs after another malignancy (AM-GISTs, n = 851) and those with only GISTs (GISTs-1, n = 7660) were identified from the Surveillance, Epidemiology, and End Results registries (1988–2016). Clinicopathologic characteristics and survival were compared between the two groups.

Results

The most commonly diagnosed first primary malignancy was prostate cancer (27.7%), followed by breast cancer (16.2%). OS among AM-GISTs was significantly inferior to that of GISTs-1; 10-year OS was 40.3% vs. 50.0%, (p < 0.001). A contrary finding was observed for GSS (10-year GSS 68.9% vs. 61.8%, p = 0.002). In the AM-GISTs group, a total of 338 patients died, of which 26.0% died of their initial cancer and 40.8% died of GISTs. Independent of demographics and clinicopathological characteristics, mortality from GISTs among AM-GISTs patients was decreased compared with their GISTs-1 counterparts (HR, 0.71; 95% CI, 0.59–0.84; p < 0.001), whereas OS was inferior among AM-GISTs (HR, 1.11; 95% CI, 0.99–1.25; p = 0.085).

Conclusions

AM-GISTs patients have decreased risk of dying from GISTs compared with GIST-1. Although another malignancy history does not seemingly affect OS for GISTs patients, clinical treatment of such patients should be cautious.
The relationships between neuroinflammation, beta-amyloid and tau deposition in Alzheimer’s disease: a longitudinal PET study
Authors: Ismail Rola , Parbo Peter , Madsen Lasse Stensvig , Hansen Allan K. , Hansen Kim V. , Schaldemose Jeppe L. , Kjeldsen Pernille L. , Stokholm Morten G. , Gottrup Hanne , Eskildsen Simon F. , Brooks David J.
Published: May 2020

Background

The aim of this longitudinal study was to assess with positron emission tomography (PET) the relationship between levels of inflammation and the loads of aggregated β-amyloid and tau at baseline and again after 2 years in prodromal Alzheimer's disease.

Methods

Forty-three subjects with mild cognitive impairment (MCI) had serial11C-PK11195 PET over 2 years to measure inflammation changes, and11C-PiB PET to determine β-amyloid fibril load; 22 also had serial18F-Flortaucipir PET to determine tau tangle load. Cortical surface statistical mapping was used to localise areas showing significant changes in tracer binding over time and to interrogate correlations between tracer binding of the tracers at baseline and after 2 years.

Results

Those MCI subjects with high11C-PiB uptake at baseline (classified as prodromal Alzheimer’s disease) had raised inflammation levels which significantly declined across cortical regions over 2 years although their β-amyloid levels continued to rise. Those MCI cases who had low/normal11C-PiB uptake at baseline but their levels then rose over 2 years were classified as prodromal AD with low Thal phase 1-2 amyloid deposition at baseline. They showed levels of cortical inflammation which correlated with their rising β-amyloid load. Those MCI cases with baseline low11C-PiB uptake that remained stable were classified as non-AD, and they showed no correlated inflammation levels. Finally, MCI cases which showed both high11C-PiB and18F-Flortaucipir uptake at baseline (MCI due to AD) showed a further rise in their tau tangle load over 2 years with a correlated rise in levels of inflammation.

Conclusions

Our baseline and 2-year imaging findings are compatible with a biphasic trajectory of inflammation in Alzheimer’s disease: MCI cases with low baseline but subsequently rising β-amyloid load show correlated levels of microglial activation which then later decline when the β-amyloid load approaches AD levels. Later, as tau tangles form in β-amyloid positive MCI cases with prodromal AD, the rising tau load is associated with higher levels of inflammation.
Integrin CD11b mediates locus coeruleus noradrenergic neurodegeneration in a mouse Parkinson’s disease model
Authors: Hou Liyan , Qu Xingyue , Qiu Xiaofei , Huang Ruixue , Zhao Xiulan , Wang Qingshan
Published: May 2020

Background

The loss of locus coeruleus noradrenergic (LC/NE) neurons in the brainstem is reported in multiple neurodegenerative disorders, including Parkinson’s disease (PD). However, the mechanisms remain unclear. Strong evidence suggested that microglia-mediated neuroinflammation contributes to neurodegeneration in PD. We recently recognized integrin CD11b, the α-chain of macrophage antigen complex-1 (Mac-1, also called CR3), as a key regulator for microglial activation. However, whether CD11b is involved in LC/NE neurodegeneration in PD remains to be investigated.

Methods

LC/NE neurodegeneration and microglial activation were compared between wild type (WT) and CD11b KO mice after treated with paraquat and maneb, two pesticides that widely used to create PD model. The role of NLRP3 inflammasome in CD11b-mediated microglial dysfunction and LC/NE neurodegeneration was further explored. LC/NE neurodegeneration, microglial phenotype, and NLRP3 inflammasome activation were determined by using Western blot, immunohistochemistry, and RT-PCR technologies.

Results

Paraquat and maneb co-exposure elevated the expressions of CD11b in the brainstem of mice, and CD11b knockout significantly reduced LC/NE neurodegeneration induced by paraquat and maneb. Mitigated microglial activation and gene expressions of proinflammatory cytokines were also observed in paraquat and maneb-treated CD11b−/− mice. Mechanistically, CD11b-mediated NLRP3 inflammasome activation contributes to paraquat and maneb-induced LC/NE neurodegeneration. Compared with WT controls, CD11b deficiency reduced paraquat and maneb-induced NLRP3 expression, caspase-1 activation, and interleukin-1β production in mice. Furthermore, inhibition of NLRP3 inflammasome by glybenclamide, a sulfonylurea inhibitor of NLRP3 inflammasome, was found to be able to suppress microglial proinflammatory activation and nuclear factor-κB activation induced by paraquat and maneb. Moreover, reduced reactive oxygen species production, NADPH oxidase, and inducible nitric oxide synthase expressions as well as 4-hydroxynonenal and malondialdehyde levels were detected in combined glybenclamide and paraquat and maneb-treated mice compared with paraquat and maneb alone group. Finally, we found that glybenclamide treatment ameliorated LC/NE neurodegeneration and α-synuclein aggregation in paraquat and maneb-treated mice.

Conclusion

Our findings suggested that CD11b mediates LC/NE neurodegeneration through NLRP3 inflammation-dependent microglial proinflammatory activation in a two pesticide-induced mouse PD model, providing a novel insight into the immune pathogenesis of LC/NE neuronal damage in related disorders.
Identification of the distribution of human endogenous retroviruses K (HML-2) by PCR-based target enrichment sequencing
Authors: Xue Bei , Zeng Tiansheng , Jia Lisha , Yang Dongsheng , Lin Stanley L. , Sechi Leonardo A. , Kelvin David J.
Published: May 2020

Background

Human endogenous retroviruses (HERVs), suspected to be transposition-defective, may reshape the transcriptional network of the human genome by regulatory elements distributed in their long terminal repeats (LTRs). HERV-K (HML-2), the most preserved group with the least number of accumulated of mutations, has been associated with aberrant gene expression in tumorigenesis and autoimmune diseases. Because of the high sequence similarity between different HERV-Ks, current methods have limitations in providing genome-wide mapping specific for individual HERV-K (HML-2) members, a major barrier in delineating HERV-K (HML-2) function.

Results

In an attempt to obtain detailed distribution information of HERV-K (HML-2), we utilized a PCR-based target enrichment sequencing protocol for HERV-K (HML-2) (PTESHK) loci, which not only maps the presence of reference loci, but also identifies non-reference loci, enabling determination of the genome-wide distribution of HERV-K (HML-2) loci. Here we report on the genomic data obtained from three individuals. We identified a total of 978 loci using this method, including 30 new reference loci and 5 non-reference loci. Among the 3 individuals in our study, 14 polymorphic HERV-K (HML-2) loci were identified, and solo-LTR330 and N6p21.32 were identified as polymorphic for the first time.

Conclusions

Interestingly, PTESHK provides an approach for the identification of the genome-wide distribution of HERV-K (HML-2) and can be used for the identification of polymorphic loci. Since polymorphic HERV-K (HML-2) integrations are suspected to be related to various diseases, PTESHK can supplement other emerging techniques in accessing polymorphic HERV-K (HML-2) elements in cancer and autoimmune diseases.
Measuring intracranial pressure by invasive, less invasive or non-invasive means: limitations and avenues for improvement
Authors: Evensen Karen Brastad , Eide Per Kristian
Published: May 2020

Sixty years have passed since neurosurgeon Nils Lundberg presented his thesis about intracranial pressure (ICP) monitoring, which represents a milestone for its clinical introduction. Monitoring of ICP has since become a clinical routine worldwide, and today represents a cornerstone in surveillance of patients with acute brain injury or disease, and a diagnostic of individuals with chronic neurological disease. There is, however, controversy regarding indications, clinical usefulness and the clinical role of the various ICP scores. In this paper, we critically review limitations and weaknesses with the current ICP measurement approaches for invasive, less invasive and non-invasive ICP monitoring. While risk related to the invasiveness of ICP monitoring is extensively covered in the literature, we highlight other limitations in current ICP measurement technologies, including limited ICP source signal quality control, shifts and drifts in zero pressure reference level, affecting mean ICP scores and mean ICP-derived indices. Control of the quality of the ICP source signal is particularly important for non-invasive and less invasive ICP measurements. We conclude that we need more focus on mitigation of the current limitations of today’s ICP modalities if we are to improve the clinical utility of ICP monitoring.
Choroid plexus and the blood–cerebrospinal fluid barrier in disease
Authors: Solár Peter , Zamani Alemeh , Kubíčková Lucie , Dubový Petr , Joukal Marek
Published: May 2020

The choroid plexus (CP) forming the blood–cerebrospinal fluid (B-CSF) barrier is among the least studied structures of the central nervous system (CNS) despite its clinical importance. The CP is an epithelio-endothelial convolute comprising a highly vascularized stroma with fenestrated capillaries and a continuous lining of epithelial cells joined by apical tight junctions (TJs) that are crucial in forming the B-CSF barrier. Integrity of the CP is critical for maintaining brain homeostasis and B-CSF barrier permeability. Recent experimental and clinical research has uncovered the significance of the CP in the pathophysiology of various diseases affecting the CNS. The CP is involved in penetration of various pathogens into the CNS, as well as the development of neurodegenerative (e.g., Alzheimer´s disease) and autoimmune diseases (e.g., multiple sclerosis). Moreover, the CP was shown to be important for restoring brain homeostasis following stroke and trauma. In addition, new diagnostic methods and treatment of CP papilloma and carcinoma have recently been developed. This review describes and summarizes the current state of knowledge with regard to the roles of the CP and B-CSF barrier in the pathophysiology of various types of CNS diseases and sets up the foundation for further avenues of research.
Fine needle biopsy of malignant tumors of the liver: a retrospective study of 624 cases from a single institution experience
Authors: Zhang Lin , Cai Zhenjian , Rodriguez Joe , Zhang Songlin , Thomas Jaiyeola , Zhu Hui
Published: May 2020

Background

Liver is one of the most common organs involved by metastatic neoplasms. In addition, a number of primary tumors can arise in the liver. Fine needle biopsy (FNB) is the most commonly used method for diagnosis of liver masses. Not much literature is available during the past 10 years about FNB of liver tumors. All large studies were performed more than 15 years ago. With the introduction of new disease entities, new tumor classification systems, and new diagnostic methods, updated documentation of FNB of liver neoplasms is much needed.

Methods

Liver FNB cases that were diagnosed as “Positive for Malignancy” between 2010 and 2018 were retrieved from the cytopathology database in our institution. Patient medical records, cytopathology and surgical pathology reports, and slides from selected cases were retrieved and reviewed.

Results

Over 30 different types of malignant tumors were identified in 624 malignant FNB cases, with the most common tumors being metastatic colorectal and pancreatic adenocarcinomas. Rare tumors include EBV-positive leiomyosarcoma, mesothelioma, and paraganglioma, among others. A subset of patients presented with widespread metastases involving liver with no known history. Identifying the primary sites in those cases can be challenging. We also found that in our practice, a significant number of hepatocellular carcinoma were diagnosed by FNB in recent years.

Conclusions

A tremendous variety of neoplasms can occur in liver. Accurate diagnosis is essential for proper patient management. Familiarization with morphological features and judicious usage of ancillary studies are essential for accurate diagnosis.
Concomitant EGFR mutation and ALK rearrangement in multifocal lung adenocarcinoma: a case report
Authors: Fan Jun , Wu Junhua , Huang Bo , Zhu Yili , Shi Heshui , Dai Xiaofang , Nie Xiu
Published: May 2020

Background

The prevalence of EGFR/ALK co-alterations in patients with NSCLC was low. The several previous studies focused on the simultaneous occurrence of EGFR mutations and ALK rearrangements in a unifocal lung cancer. However, the incidence of multifocal pulmonary adenocarcinomas was increasingly encountered in clinical practice, due to the increased availability and improvement of the thoracic imaging. The clinical relevance of EGFR/ALK co-alterations in multifocal adenocarcinomas required detailed investigation as well.

Case presentation

We present the case of a 57-year-old woman with solid nodule in the left upper lung and a ground glass nodule in the left lower lobe, who underwent radical operation. Pathological examination confirmed multifocal adenocarcinoma, molecular tests revealed that the left upper lung lesion was positive for ALK rearrangement but the left lower lobe displayed EGFR mutation positive separately. The patient pulmonary lesions were well controlled by adjuvant chemotherapy and radiation therapy. When brain metastases occurred, EGFR-TKI was not effective after firstly administration, while subsequent ALK inhibitors were efficient. We retrospective evaluated the oncogenic status of metastatic lymph nodes and found that the driver gene was ALK rearrangement rather than EGFR mutation.

Conclusions

The status of the oncogenic mutations in lymph node metastasis may provide some effective hints for metastasis lesion in other organ or tissue. Therefore, it is recommended to fully evaluate the driver genes in lymph node metastasis after radical resection.
Parametric mapping of cellular morphology in plant tissue sections by gray level granulometry
Authors: Legland David , Guillon Fabienne , Devaux Marie-Françoise
Published: May 2020

Background

The cellular morphology of plant organs is strongly related to other physical properties such as shape, size, growth, mechanical properties or chemical composition. Cell morphology often vary depending on the type of tissue, or on the distance to a specific tissue. A common challenge in quantitative plant histology is to quantify not only the cellular morphology, but also its variations within the image or the organ. Image texture analysis is a fundamental tool in many areas of image analysis, that was proven efficient for plant histology, but at the scale of the whole image.

Results

This work presents a method that generates a parametric mapping of cellular morphology within images of plant tissues. It is based on gray level granulometry from mathematical morphology for extracting image texture features, and on Centroidal Voronoi Diagram for generating a partition of the image. Resulting granulometric curves can be interpreted either through multivariate data analysis or by using summary features corresponding to the local average cell size. The resulting parametric maps describe the variations of cellular morphology within the organ.

Conclusions

We propose a methodology for the quantification of cellular morphology and of its variations within images of tissue sections. The results should help understanding how the cellular morphology is related to genotypic and / or environmental variations, and clarify the relationships between cellular morphology and chemical composition of cell walls.
The effect of hyperbaric oxygen therapy on bone macroscopy, composition and biomechanical properties after ionizing radiation injury
Authors: Júnior Luiz Henrique Ferreira , Limirio Pedro Henrique Justino Oliveira , Soares Priscilla Barbosa Ferreira , Dechichi Paula , de Souza Castro Filice Letícia , Quagliatto Paulo Sérgio , Rocha Flaviana Soares
Published: May 2020

Background

Radiotherapy used in tumor treatment compromises vascularization of bone tissue. Hyperbaric oxygenation (HBO) increases oxygen availability and improves vascularization, minimizing the deleterious effects of ionizing radiation (IR). Therefore, the aim of this study was to evaluate HBO therapy effect on bone macroscopy, composition and biomechanical properties after IR damage.

Methods

Twenty male Wistar rats weighing 300 ± 20 g (10 weeks of age) were submitted to IR (30 Gy) to the left leg, where the right leg was not irradiated. After 30 days, ten animals were submitted to HBO therapy, which was performed daily for 1 week at 250 kPa for 90-min sessions. All animals were euthanized 37 days after irradiation and the tibia were separated into four groups (n = 10): from animals without HBO - right tibia Non-irradiated (noIRnoHBO) and left tibia Irradiated (IRnoHBO); and from animals with HBO - right tibiae Non-irradiated (noIRHBO) and left tibia Irradiated (IRHBO). The length (proximal-distal) and thickness (anteroposterior and mediolateral) of the tibiae were measured. Biomechanical analysis evaluated flexural strength and stiffness. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) was used to calculate the amide I ratio, crystallinity index, and matrix to mineral ratios.

Results

In the macroscopic and ATR-FTIR analysis, the IRnoHBO showed lower values of length, thickness and amide I ratio, crystallinity index and matrix to mineral ratios compared to noIRnoHBO (p < 0.03). IRnoHBO showed no statistical difference compared to IRHBO for these analyses (p > 0.05). Biomechanics analysis showed that the IRnoHBO group had lower values of flexural strength and stiffness compared to noIRnoHBO and IRHBO groups (p < 0.04). In addition, the noIRHBO group showed higher value of flexural strength when compared to noIRnoHBO and IRHBO groups (p < 0.02).

Conclusions

The present study concluded that IR arrests bone development, decreases the collagen maturation and mineral deposition process, thus reducing the flexural strength and stiffness bone mechanical parameters. Moreover, HBO therapy minimizes deleterious effects of irradiation on flexural strength and the bone stiffness analysis.
Feasibility of hippocampus-sparing VMAT for newly diagnosed glioblastoma treated by chemoradiation: pattern of failure analysis
Authors: Wee Chan Woo , Kim Kyung Su , Kim Chae-Yong , Han Jung Ho , Kim Yu Jung , Kim In Ah
Published: May 2020

Background

To identify the pattern of failure and oncological safety of hippocampus (HC)-sparing IMRT (HSRT) in newly diagnosed glioblastoma (GBM) patients.

Materials and methods

Eighty-two GBM patients treated with temozolomide-based chemoradiation using HSRT between 2014 and 2018 were retrospectively reviewed. HSRT consisted of a sparing of Dmax of the contralateral HC < 17 Gy. Fifteen patients were unable to achieve the dose-constraints for adequate target coverage. The dose to ipsilateral HC was kept as low as possible. The pattern of failure was investigated, focusing on the area in the vicinity of the spared HC (organ and + 1 cm area). The median HSRT dose was 60 Gy in 30 fractions.

Results

The median follow-up for survivors was 11.7 months. The median progression-free and overall survival were 9.7 and 23.5 months, respectively. Six (7.3%) and eight (9.8%) patients eventually demonstrated progressive disease at the contralateral HC and HC + 1 cm, respectively. The 12-month contralateral HC and HC + 1 cm failure-free rate were 97.2 and 93.4%, respectively. However, no patient (0%) and two patients (2.4%) showed failure at contralateral HC and HC + 1 cm at initial progression, respectively. The dominant pattern of failure at the contralateral HC was by subependymal seeding (66.7%).

Conclusion

The incidence of failure at the contralateral HC and HC + 1 cm is very low and mostly accompanied by disseminated disease progression after HSRT. Since HSRT does not compromise oncological outcomes, it could be considered especially for GBM patients who are expected to have favorable survival outcomes.
Rapidly vanishing left atrial dissection following mitral valve replacement: a case report
Authors: Morishita Atsushi , Katahira Seiichiro , Hoshino Takeshi , Hanzawa Kazuhiko , Tomioka Hideyuki
Published: May 2020

Background

Left atrial dissection is an extremely rare complication of mitral valve replacement. Because of its severity, its prompt diagnosis and treatment is mandatory. The most effective treatment (i.e. surgical vs. non-surgical) for left atrial dissection has not been fully established yet.

Case presentation

Herein, we have reported left atrial dissection after mitral valve replacement in a 68-year-old obese woman. After closing the thorax, transesophageal echocardiography (TEE) revealed an atrial mass of 3 cm × 2 cm, visualized as an oval hypoechoic appearance extending from the posterior annulus of the mitral valve to the posterior wall of the left atrium. Because hemodynamic conditions were stable, surgery was ruled out and conservative treatment with close observation was selected. On postoperative day 2, TEE revealed that the atrial mass had vanished and the broken piece of the endocardium merely remained fluttering in the atrium. On postoperative day 6, the appearance of the left atrium was normalized completely, leaving no traces of left atrial dissection. The patient recovered uneventfully. Serial TEE was a very effective imaging modality during the non-surgical treatment of left atrial dissection.

Conclusions

It is crucial to accurately define diagnosis and optimally consider therapeutic strategies for left atrial dissection based on the hemodynamic conditions of the patient and serial TEE follow-up examinations. In our case study, left atrial dissection was successfully treated with conservative treatment; therefore, we believe that TEE could be a feasible modality for the early diagnosis of this condition.
The nature of youth in the eyes of mental-health care workers: therapists’ conceptualization of adolescents coming to therapy at others’ initiative
Authors: Barca Tonje Børseth , Moltu Christian , Veseth Marius , Fjellheim Gro , Stige Signe Hjelen
Published: May 2020

Background

Adolescent clients often come to therapy at the initiative of others and show a higher drop-out rate compared to adult clients. Therapeutic relationships are critical for preventing drop-outs and attaining good outcomes, yet few empirical studies have investigated how therapists conceptualize and meet adolescent clients who come reluctantly to therapy.

Methods

We conducted ten focus-group interviews in this study with a total of 51 therapists at different Norwegian specialist outpatient clinics for children and adolescents with mental-health problems to explore how therapists view and understand adolescents who come to therapy at the initiative of someone else. We used a reflexive approach to thematic analysis to analyze the transcripts.

Results

We found five main themes, expressing variations in participants’ understanding: The hurt and distrustful adolescent; The adolescent lacking hope for the future; The adolescent engulfed in the burden of mental-health suffering; The adolescent as something more than a psychiatric patient; and The adolescent meeting a system with varying flexibility and space for engagement.

Conclusions

Several conceptualizations of the adolescent client coexist within and between clinics, resulting in variability of services for adolescents even within the frames of a strong welfare system.
Effects of metatarsal domes on plantar pressures in older people with a history of forefoot pain
Authors: Landorf Karl B. , Ackland Claire A. , Bonanno Daniel R. , Menz Hylton B. , Forghany Saeed
Published: May 2020

Background

Forefoot pads such as metatarsal domes are commonly used in clinical practice for the treatment of pressure‐related forefoot pain, however evidence for their effects is inconsistent. This study aimed to evaluate the effects on plantar pressures of metatarsal domes in different positions relative to the metatarsal heads.

Methods

Participants in this study included 36 community‐dwelling adults aged 65 or older with a history of forefoot pain. Standardised footwear was used and plantar pressures were measured using the pedar®‐X in‐shoe plantar pressure measurement system. Peak pressure, maximum force and contact area were analysed using an anatomically‐based masking protocol that included three forefoot mask sub‐areas (proximal to, beneath, and distal to the metatarsal heads). Data were collected for two different types of prefabricated metatarsal domes of different densities (Emsold metatarsal dome and Langer PPT metatarsal pad) in three different positions relative to the metatarsal heads. Seven conditions were tested in this study: (i) control (no pad) condition, (ii) Emsold metatarsal dome positioned 5 mm proximal to the metatarsal heads, (iii) Emsold metatarsal dome positioned in‐line with the metatarsal heads, (iv), Emsold metatarsal dome positioned 5 mm distal to the metatarsal heads, (v) Langer PPT metatarsal pad positioned 5 mm proximal to the metatarsal heads, (vi) Langer PPT metatarsal pad positioned in‐line with the metatarsal heads, and (vii) Langer PPT metatarsal pad positioned 5 mm distal to the metatarsal heads.

Results

When analysed with the mask that was distal to the metatarsal heads, where the plantar pressure readings were at their highest, all metatarsal dome conditions led to significant reductions in plantar pressure at the forefoot compared to the control (no pad) condition (F3.9, 135.6 = 8.125, p < 0.001). The reductions in plantar pressure were in the order of 45–60 kPa. Both the Emsold metatarsal dome and the Langer PPT metatarsal pad, when positioned proximal to the metatarsal heads, managed to achieve this without adversely increasing plantar pressure proximally where the pad was positioned, however the Emsold metatarsal dome was most effective.

Conclusions

Metatarsal domes reduce plantar pressure in the forefoot in older people with a history of forefoot pain. All metatarsal dome conditions significantly reduced peak pressure in the forefoot, however metatarsal domes that were positioned 5 mm proximal to the metatarsal heads provided the best balance of reducing plantar pressure distal to the metatarsal heads, where the pressure is at its greatest, but not adversely increasing plantar pressure proximally, where the bulk of the pad is positioned. In this proximal position, the Emsold metatarsal dome was more effective than the Langer PPT metatarsal pad and we cautiously recommend this forefoot pad for alleviating forefoot pressure in older people with forefoot pain.
Pretreatment thrombocytosis as an independent predictive factor for chemoresistance and poor survival in epithelial ovarian cancer
Authors: Nakao Sari , Minaguchi Takeo , Itagaki Hiroya , Hosokawa Yoshihiko , Shikama Ayumi , Tasaka Nobutaka , Akiyama Azusa , Ochi Hiroyuki , Matsumoto Koji , Satoh Toyomi
Published: May 2020

Background

Thrombocytosis is related to tumor stage and survival in ovarian cancer in addition to the common complications of malignant diseases, such as anemia and inflammation. The aim of our study was to clarify the precise prognostic impact of pretreatment thrombocytosis in epithelial ovarian cancer.

Methods

We retrospectively analyzed 280 consecutive patients who were treated for epithelial ovarian cancer at our institution between 2001 and 2011.

Results

Pretreatment thrombocytosis was observed in 18.9% of all patients and was associated with advanced FIGO stage, primary treatment, operation achievement, histologic subtype, microcytic hypochromic anemia (MHA), and nonmalignant inflammatory condition (P = 0.0018, 0.0028, 0.00050, 0.034, 0.00090 and 0.0022). In the patients who relapsed after primary adjuvant chemotherapy (n = 126), thrombocytosis was associated with a shorter treatment-free interval (TFI) (P = 0.0091). The univariate and multivariate analyses revealed that thrombocytosis was independently associated with TFI and MHA (P = 0.021 and 0.0091). Patients with thrombocytosis had worse progression-free survival (PFS) and overall survival (OS) than those without thrombocytosis (P <  0.0001 and <  0.0001). The multivariate analyses for prognostic factors demonstrated that thrombocytosis was significant for poor PFS and OS (P = 0.0050 and 0.022) independent of stage, histology, primary treatment, operation achievement, nonmalignant inflammatory condition and MHA.

Conclusions

The current findings indicate that the detrimental survival impact of pretreatment thrombocytosis in epithelial ovarian cancer may be independent of tumor extent but rather attributed to chemoresistance, further supporting the therapeutic potential of targeting thrombopoietic cytokines in the disease.
Heating, ventilation and air conditioning (HVAC) in intensive care unit
Authors: Saran Sai , Gurjar Mohan , Baronia Arvind , Sivapurapu Vijayalakshmi , Ghosh Pralay S. , Raju Gautham M. , Maurya Indubala
Published: May 2020

The aim of this review is to describe variation in standards and guidelines on ‘heating, ventilation and air-conditioning (HVAC)’ system maintenance in the intensive care units, across the world, which is required to maintain good ‘indoor air quality’ as an important non-pharmacological strategy in preventing hospital-acquired infections. An online search and review of standards and guidelines published by various societies including American Institute of Architects (AIA), American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE), Centers for Disease Control and Prevention (CDC), Department of Health Estates and Facilities Division, Health Technical Memorandum 2025 (HTM) and Healthcare Infection Control Practices Advisory Committee (HICPAC) along with various national expert committee consensus statements, regional and hospital-based protocols available in a public domain were retrieved. Selected publications and textbooks describing HVAC structural aspects were also reviewed, and we described the basic structural details of HVAC system as well as variations in the practised standards of HVAC system in the ICU, worldwide. In summary, there is a need of universal standards for HVAC system with a specific mention on the type of ICU, which should be incorporated into existing infection control practice guidelines.
Quantitative stain-free imaging and digital profiling of collagen structure reveal diverse survival of triple negative breast cancer patients
Authors: Gole Laurent , Yeong Joe , Lim Jeffrey Chun Tatt , Ong Kok Haur , Han Hao , Thike Aye Aye , Poh Yong Cheng , Yee Sidney , Iqbal Jabed , Hong Wanjin , Lee Bernett , Yu Weimiao , Tan Puay Hoon
Published: May 2020

Background

Stromal and collagen biology has a significant impact on tumorigenesis and metastasis. Collagen is a major structural extracellular matrix component in breast cancer, but its role in cancer progression is the subject of historical debate. Collagen may represent a protective layer that prevents cancer cell migration, while increased stromal collagen has been demonstrated to facilitate breast cancer metastasis.

Methods

Stromal remodeling is characterized by collagen fiber restructuring and realignment in stromal and tumoral areas. The patients in our study were diagnosed with triple-negative breast cancer in Singapore General Hospital from 2003 to 2015. We designed novel image processing and quantification pipelines to profile collagen structures using numerical imaging parameters. Our solution differentiated the collagen into two distinct modes: aggregated thick collagen (ATC) and dispersed thin collagen (DTC).

Results

Extracted parameters were significantly associated with bigger tumor size and DCIS association. Of numerical parameters, ATC collagen fiber density (CFD) and DTC collagen fiber length (CFL) were of significant prognostic value for disease-free survival and overall survival for the TNBC patient cohort. Using these two parameters, we built a predictive model to stratify the patients into four groups.

Conclusions

Our study provides a novel insight for the quantitation of collagen in the tumor microenvironment and will help predict clinical outcomes for TNBC patients. The identified collagen parameters, ATC CFD and DTC CFL, represent a new direction for clinical prognosis and precision medicine. We also compared our result with benign samples and DICS samples to get novel insight about the TNBC heterogeneity. The improved understanding of collagen compartment of TNBC may provide insights into novel targets for better patient stratification and treatment.
Where do we go from here? – Opportunities and barriers to the career development of trial managers: a survey of UK-based trial management professionals
Authors:   on behalf of the UK Trial Managers’ Network Executive Group, Mitchell Eleanor , Goodman Kirsteen , Hartley Suzanne , Hickey Helen , McDonald Alison M. , Meadows Helen M. , Rhodes Shelley , Taylor Jodi , Wakefield Natalie , Farrell Barbara
Published: May 2020

Background

Clinical trials commonly have a dedicated trial manager and effective trial management is essential to the successful delivery of high-quality trials. Trial managers have diverse experience and currently there is no standardised structured career pathway. The UK Trial Managers’ Network (UKTMN) surveyed its members to understand what is important to them with respect to career development since this would be important in the development of any initiative intended to develop a skilled workforce.

Methods

We conducted an online survey of UKTMN members, who are trial management professionals, working on academic-led trials in the UK. Members were asked what they perceive as opportunities and barriers to career development. Two reminders were sent to facilitate completion of the survey, and responders were offered the opportunity to enter a prize draw for waived fees at the UKTMN annual meeting. Data were analysed descriptively by using Stata (version 15.1), and free-text responses were reviewed for themes.

Results

The survey was sent to 819 UKTMN members; 433 responses were received, although 13 were from non-UKTMN members; thus 420 respondents' data were included in analyses. Respondents were representative of UKTMN membership; however, more responses were received by trial managers based in registered clinical trials units (CTUs). The top three opportunities for career development were (i) training, (ii) helping design trials and (iii) undertaking relevant qualifications. The top three barriers were (i) funding, (ii) few opportunities to get involved in development activities aside from managing a trial and (iii) unclear organisational career pathway. Almost all respondents (401/420, 95.4%) considered career development either very or quite important. Although all respondents had a day-to-day role in managing trials, there was huge disparity between job titles.

Conclusion

Career development is important to trial managers yet there is a lack of a structured pathway. The enablers and disablers to career development for trial managers should be clearly considered by the clinical trial community and, in particular, employers, sponsors and funders in order to develop a highly skilled workforce of trial managers, who are key to the delivery of trials.
Acyl-lipid desaturases and Vipp1 cooperate in cyanobacteria to produce novel omega-3 PUFA-containing glycolipids
Authors: Poole Leslie B. , Parsonage Derek , Sergeant Susan , Miller Leslie R. , Lee Jingyun , Furdui Cristina M. , Chilton Floyd H.
Published: May 2020

Background

Dietary omega-3 (n-3), long chain (LC-, ≥ 20 carbons), polyunsaturated fatty acids (PUFAs) derived largely from marine animal sources protect against inflammatory processes and enhance brain development and function. With the depletion of natural stocks of marine animal sources and an increasing demand for n-3 LC-PUFAs, alternative, sustainable supplies are urgently needed. As a result, n-3 18-carbon and LC-PUFAs are being generated from plant or algal sources, either by engineering new biosynthetic pathways or by augmenting existing systems.

Results

We utilized an engineered plasmid encoding two cyanobacterial acyl-lipid desaturases (DesB and DesD, encoding Δ15 and Δ6 desaturases, respectively) and “vesicle-inducing protein in plastids” (Vipp1) to induce production of stearidonic acid (SDA, 18:4 n-3) at high levels in three strains of cyanobacteria (10, 17 and 27% of total lipids in Anabaena sp. PCC7120, Synechococcus sp. PCC7002, and Leptolyngbya sp. strain BL0902, respectively). Lipidomic analysis revealed that in addition to SDA, the rare anti-inflammatory n-3 LC-PUFA eicosatetraenoic acid (ETA, 20:4 n-3) was synthesized in these engineered strains, and ~ 99% of SDA and ETA was complexed to bioavailable monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) species. Importantly, novel molecular species containing alpha-linolenic acid (ALA), SDA and/or ETA in both acyl positions of MGDG and DGDG were observed in the engineered Leptolyngbya and Synechococcus strains, suggesting that these could provide a rich source of anti-inflammatory molecules.

Conclusions

Overall, this technology utilizes solar energy, consumes carbon dioxide, and produces large amounts of nutritionally important n-3 PUFAs and LC-PUFAs. Importantly, it can generate previously undescribed, highly bioavailable, anti-inflammatory galactosyl lipids. This technology could therefore be transformative in protecting ocean fisheries and augmenting the nutritional quality of human and animal food products.