bluuebunny/crossref_metadata_2025 huggingface dataset:
Review on Epidemiology and Public Health Importance of Goat Tuberculosis in Ethiopia
Authors: Ayana Dibessa Zelalem
Published: September 2020

Small ruminant is an important and integral part of livestock in Ethiopia. Especially, goats are attractive to people of Ethiopia because of the ability to resist challenges, easily adapt to different ecological regions, and need small land to rearing and small initial capital in which poor people can engaged in the production system. In spite of the presence of large number of goat population in Ethiopia, it fails to utilize expected productivity due to many factors. Among the factors, which limit the economic returns of goats, diseases stand frontline. Tuberculosis is one the diseases that affect goats’ health and production in Ethiopia. Goat tuberculosis is a chronic disease, which is characterized by the development of granulomas, essentially in the respiratory tract and related lymph nodes, from which the mycobacteria are discharged and contaminate other susceptible animals. Goat tuberculosis has a public health implication in Ethiopia because of the farmers’ habit of consuming raw goat milk and its products, and they do have consistent or day-to-day contact with their goats. The etiological agents also transmitted to humans through the aerogenous route from those animals with active cases in the herd. The infection has been reported from several parts of different areas of the country dependent on the abattoir inspections. Therefore, attention should be given towards the control of tuberculosis in livestock; public health education on zoonotic importance of the disease or awareness creation and the national tuberculosis control needs to consider the one health approach, and further epidemiological studies should be undertaken.
Proanthocyanidins-Mediated Nrf2 Activation Ameliorates Glucocorticoid-Induced Oxidative Stress and Mitochondrial Dysfunction in Osteoblasts
Authors: Chen Liang , Hu Sun-Li , Xie Jun , Yan De-Yi , Weng She-Ji , Tang Jia-Hao , Wang Bing-Zhang , Xie Zhong-Jie , Wu Zong-Yi , Yang Lei
Published: September 2020

The widespread use of therapeutic glucocorticoids has increased the frequency of glucocorticoid-induced osteoporosis (GIOP). One of the potential pathological processes of GIOP is an increased level of oxidative stress and mitochondrial dysfunction, which eventually leads to osteoblast apoptosis. Proanthocyanidins (PAC) are plant-derived antioxidants that have therapeutic potential against GIOP. In our study, a low dose of PAC was nontoxic to healthy osteoblasts and restored osteogenic function in dexamethasone- (Dex-) treated osteoblasts by suppressing oxidative stress, mitochondrial dysfunction, and apoptosis. Mechanistically, PAC neutralized Dex-induced damage in the osteoblasts by activating the Nrf2 pathway, since silencing Nrf2 partly eliminated the protective effects of PAC. Furthermore, PAC injection restored bone mass and promoted the expression of Nrf2 in the distal femur of Dex-treated osteoporotic rats. In summary, PAC protect osteoblasts against Dex-induced oxidative stress and mitochondrial dysfunction via the Nrf2 pathway activation and may be a promising drug for treating GIOP.
Generalized Additive Mixed Modeling of Longitudinal Tumor Growth Reduces Bias and Improves Decision Making in Translational Oncology
Authors: Forrest William F. , Alicke Bruno , Mayba Oleg , Osinska Magdalena , Jakubczak Michal , Piatkowski Pawel , Choniawko Lech , Starr Alice , Gould Stephen E.
Published: September 2020

Scientists working in translational oncology regularly conduct multigroup studies of mice with serially measured tumors. Longitudinal data collected can feature mid-study dropouts and complex nonlinear temporal response patterns. Parametric statistical models such as ones assuming exponential growth are useful for summarizing tumor volume over ranges for which the growth model holds, with the advantage that the model's parameter estimates can be used to summarize between-group differences in tumor volume growth with statistical measures of uncertainty. However, these same assumed growth models are too rigid to recapitulate patterns observed in many experiments, which in turn diminishes the effectiveness of their parameter estimates as summary statistics. To address this problem, we generalized such models by adopting a nonparametric approach in which group-level response trends for logarithmically scaled tumor volume are estimated as regression splines in a generalized additive mixed model. We also describe a novel summary statistic for group level splines over user-defined, experimentally relevant time ranges. This statistic reduces to the log-linear growth rate for data well described by exponential growth and also has a sampling distribution across groups that is well approximated by a multivariate Gaussian, thus facilitating downstream analysis. Real-data examples show that this nonparametric approach not only enhances fidelity in describing nonlinear growth scenarios but also improves statistical power to detect interregimen differences when compared with the simple exponential model so that it generalizes the linear mixed effects paradigm for analysis of log-linear growth to nonlinear scenarios in a useful way.

Significance:

This work generalizes the statistical linear mixed modeling paradigm for summarizing longitudinally measured preclinical tumor volume studies to encompass studies with nonlinear and nonmonotonic group response patterns in a statistically rigorous manner.
Examining COVID-19 Preventive Behaviors among Cancer Survivors in the United States: An Analysis of the COVID-19 Impact Survey
Authors: Islam Jessica Y. , Camacho-Rivera Marlene , Vidot Denise C.
Published: September 2020

Background:

The COVID-19 pandemic has impacted adults with chronic diseases, and their health care delivery. Patterns of COVID-19–related preventive behaviors practiced by cancer survivors are unknown, including practices related to canceling doctor's appointments. We evaluated COVID-19–related preventive behaviors among cancer survivors in the United States.

Methods:

We used nationally representative data of 10,760 U.S. adults from the COVID-19 Impact Survey. We defined cancer survivors as those with a self-reported diagnosis of cancer (n = 854, 7.6%). We present frequencies and χ2 tests to evaluate COVID-19–related preventive behaviors among cancer survivors. We estimated determinants of canceling doctor's appointments among cancer survivors using Poisson regression models.

Results:

Cancer survivors were more likely to practice preventive behaviors, including social distancing (93%, χ2 P < 0.001), wearing a face mask (93%, χ2 P < 0.001), and avoiding crowded areas (84%, χ2 P < 0.001) compared with adults without cancer. Cancer survivors were more likely to cancel doctor's appointments (41%, χ2 P < 0.001), whereas they were less likely to cancel other social activities such as work (19%, χ2 P < 0.001) and school-related (13%, χ2 P < 0.001) activities. After adjustment for covariates, while non-Hispanic (NH)-Black cancer survivors were less likely to cancel a doctor's appointment compared with NH-White cancer survivors, cancer survivors aged 18 to 29, who were female, and who had least one comorbid condition were more likely.

Conclusions:

Cancer survivors are adhering to recommended preventive behaviors. Cancer survivor's continuity of care may be impacted by COVID-19, specifically young adults, females, and those with existing comorbid conditions.

Impact:

Insights into cancer survivors whose care may be most impacted by COVID-19 will be valuable toward surveillance and survivorship of U.S. cancer survivors.
An Epigenetic Mechanism Underlying Chromosome 17p Deletion–Driven Tumorigenesis
Authors: Chen Mei , Chen Xuelan , Li Shujun , Pan Xiangyu , Gong Yanqiu , Zheng Jianan , Xu Jing , Zhao Chengjian , Zhang Qi , Zhang Shan , Qi Lu , Wang Zhongwang , Shi Kaidou , Ding Bi-Sen , Xue Zhihong , Chen Lu , Yang Shengyong , Wang Yuan , Niu Ting , Dai Lunzhi , Lowe Scott W. , Chen Chong , Liu Yu
Published: September 2020

Chromosome copy-number variations are a hallmark of cancer. Among them, the prevalent chromosome 17p deletions are associated with poor prognosis and can promote tumorigenesis more than TP53 loss. Here, we use multiple functional genetic strategies and identify a new 17p tumor suppressor gene (TSG), plant homeodomain finger protein 23 (PHF23). Its deficiency impairs B-cell differentiation and promotes immature B-lymphoblastic malignancy. Mechanistically, we demonstrate that PHF23, an H3K4me3 reader, directly binds the SIN3–HDAC complex through its N-terminus and represses its deacetylation activity on H3K27ac. Thus, the PHF23–SIN3–HDAC (PSH) complex coordinates these two major active histone markers for the activation of downstream TSGs and differentiation-related genes. Furthermore, dysregulation of the PSH complex is essential for the development and maintenance of PHF23-deficient and 17p-deleted tumors. Hence, our study reveals a novel epigenetic regulatory mechanism that contributes to the pathology of 17p-deleted cancers and suggests a susceptibility in this disease.

Significance:

We identify PHF23, encoding an H3K4me3 reader, as a new TSG on chromosome 17p, which is frequently deleted in human cancers. Mechanistically, PHF23 forms a previously unreported histone-modifying complex, the PSH complex, which regulates gene activation through a synergistic link between H3K4me3 and H3K27ac.

This article is highlighted in the In This Issue feature, p. 1
Metabolomics and Proteomics Reveal the Variation of Substances in Apheresis Platelets during Storage and Their Effects on Cancer Cell Proliferation
Authors: Li Xiaofei , Zhang Yuan , Cheng Fu , Yu Yang , Wang Deqing
Published: September 2020

Introduction: Apheresis platelets (APs) are clinically and crucially important in the prevention and treatment of bleeding in patients with thrombocytopenia or cancer. However, few researchers have addressed the variation of supernatant metabolites and exosome proteins in APs during storage and their effects on cancer cell proliferation. Objective: This study was designed to explore the change rules of the metabolites and exosomal proteins of APs during storage and their effects on cancer cell proliferation. Methods: Metabolomics and proteomics were separately applied to analyze the variation of AP supernatant metabolites and exosomal proteins between freshly prepared day-0 and day-5 terminal-stored APs. Cell counting kit (CCK)-8 assay was performed to detect the effects of AP supernatants and exosomes on the proliferation of cancer cells. Results: We found that the supernatant metabolites and exosomal proteins in APs were significantly different on day 0 and day 5, and that many differential metabolites and exosomal proteins were associated with cancer characteristics. Furthermore, the day-5 AP supernatants had a greater inhibition of the proliferation of K562, HepG2, and HCT116 cancer cells, but the day-5 AP exosomes had no significant effect on the proliferation of these cancer cells. Conclusion: The variant terminal-stored AP supernatants may inhibit the proliferation of cancer cells but the variant terminal AP exosomes have no effect on cancer cell proliferation.
Effects of Cellular Senescence on Dental Follicle Cells
Authors: Morsczeck Christian
Published: September 2020

The dental follicle is part of the tooth germ, and isolated stem cells from this tissue (dental follicle cells; DFCs) are considered, for example, for regenerative medicine and immunotherapies. However somatic stem cells can also improve pharmaceutical research. Cell proliferation is limited by the induction of senescence, which, while reducing the therapeutic potential of DFCs for cell therapy, can also be used to study aging processes at the cellular level that can be used to test anti-aging pharmaceuticals. Unfortunately, very little is known about cellular senescence in DFCs. This review presents current knowledge about cellular senescence in DFCs.
Carotid Intima‐Media Thickness and the Risk of Sudden Cardiac Death: The ARIC Study and the CHS
Authors: Suzuki Takeki , Wang Wanmei , Wilsdon Anthony , Butler Kenneth R. , Adabag Selcuk , Griswold Michael E. , Nambi Vijay , Rosamond Wayne , Sotoodehnia Nona , Mosley Thomas H.
Published: September 2020

Background

Sudden cardiac death (SCD) is associated with severe coronary heart disease in the great majority of cases. Whether carotid intima‐media thickness (C‐IMT), a known surrogate marker of subclinical atherosclerosis, is associated with risk of SCD in a general population remains unknown. The objective of this study was to investigate the association between C‐IMT and risk of SCD.

Methods and Results

We examined a total of 20 862 participants: 15 307 participants of the ARIC (Atherosclerosis Risk in Communities) study and 5555 participants of the CHS (Cardiovascular Health Study). C‐IMT and common carotid artery intima‐media thickness was measured at baseline by ultrasound. Presence of plaque was judged by trained readers. Over a median of 23.5 years of follow‐up, 569 participants had SCD (1.81 cases per 1000 person‐years) in the ARIC study. Mean C‐IMT and common carotid artery intima‐media thickness were associated with risk of SCD after adjustment for traditional risk factors and time‐varying adjustors: hazard ratios (HRs) with 95% CIs for fourth versus first quartile were 1.64 (1.15–2.63) and 1.49 (1.05–2.11), respectively. In CHS, 302 participants developed SCD (4.64 cases per 1000 person‐years) over 13.1 years. Maximum C‐IMT was associated with risk of SCD after adjustment: HR (95% CI) for fourth versus first quartile was 1.75 (1.22–2.51). Presence of plaque was associated with 35% increased risk of SCD: HR (95% CI) of 1.37 (1.13–1.67) in the ARIC study and 1.32 (1.04–1.68) in CHS.

Conclusions

C‐IMT was associated with risk of SCD in 2 biracial community‐based cohorts. C‐IMT may be used as a marker of SCD risk and potentially to initiate early therapeutic interventions to mitigate the risk.
Camellia zhaiana (sect. Longipedicellata), a new species of Theaceae from Guangxi, China

Authors: LIU ZHENWEN , YE PINMING , LI ZHIHUI , WEI XIAOJUAN , LIU ENDE , ZHANG ZHIRONG , MA JIN-LIN , YANG SHIXIONG
Published: September 2020

Camellia zhaiana is described and illustrated as a new species from Guangxi, China. It is morphologically related to C. longipedicellata, but can be easily distinguished by its pink and puberulent petals as well as its larger thinly leathery leaves. It is accessed to be Critically Endangered (CR) according to the IUCN Red List Categories and Criteria.
Connecting Land–Atmosphere Interactions to Surface Heterogeneity in CHEESEHEAD19
Authors: Butterworth Brian J. , Desai Ankur R. , Townsend Philip A. , Petty Grant W. , Andresen Christian G. , Bertram Timothy H. , Kruger Eric L. , Mineau James K. , Olson Erik R. , Paleri Sreenath , Pertzborn Rosalyn A. , Pettersen Claire , Stoy Paul C. , Thom Jonathan E. , Vermeuel Michael P. , Wagner Timothy J. , Wright Daniel B. , Zheng Ting , Metzger Stefan , Schwartz Mark D. , Iglinski Trevor J. , Mauder Matthias , Speidel Johannes , Vogelmann Hannes , Wanner Luise , Augustine Travis J. , Brown William O. J. , Oncley Steven P. , Buban Michael , Lee Temple R. , Cleary Patricia , Durden David J. , Florian Christopher R. , Lantz Kathleen , Riihimaki Laura D. , Sedlar Joseph , Meyers Tilden P. , Plummer David M. , Guzman Eliceo Ruiz , Smith Elizabeth N. , Sühring Matthias , Turner David D. , Wang Zhien , White Loren D. , Wilczak James M.
Published: September 2020

The Chequamegon Heterogeneous Ecosystem Energy-Balance Study Enabled by a High-Density Extensive Array of Detectors 2019 (CHEESEHEAD19) is an ongoing National Science Foundation project based on an intensive field campaign that occurred from June to October 2019. The purpose of the study is to examine how the atmospheric boundary layer (ABL) responds to spatial heterogeneity in surface energy fluxes. One of the main objectives is to test whether lack of energy balance closure measured by eddy covariance (EC) towers is related to mesoscale atmospheric processes. Finally, the project evaluates data-driven methods for scaling surface energy fluxes, with the aim to improve model–data comparison and integration. To address these questions, an extensive suite of ground, tower, profiling, and airborne instrumentation was deployed over a 10 km × 10 km domain of a heterogeneous forest ecosystem in the Chequamegon–Nicolet National Forest in northern Wisconsin, United States, centered on an existing 447-m tower that anchors an AmeriFlux/NOAA supersite (US-PFa/WLEF). The project deployed one of the world’s highest-density networks of above-canopy EC measurements of surface energy fluxes. This tower EC network was coupled with spatial measurements of EC fluxes from aircraft; maps of leaf and canopy properties derived from airborne spectroscopy, ground-based measurements of plant productivity, phenology, and physiology; and atmospheric profiles of wind, water vapor, and temperature using radar, sodar, lidar, microwave radiometers, infrared interferometers, and radiosondes. These observations are being used with large-eddy simulation and scaling experiments to better understand submesoscale processes and improve formulations of subgrid-scale processes in numerical weather and climate models.
Antecedents for the Shapiro–Keyser Cyclone Model in the Bergen School Literature
Authors: Schultz David M. , Keyser Daniel
Published: September 2020

Two widely accepted conceptual models of extratropical cyclone structure and evolution exist: the Norwegian and Shapiro–Keyser cyclone models. The Norwegian cyclone model was developed around 1920 by the Bergen School meteorologists. This model has come to feature an acute angle between the cold and warm fronts, with the reduction in the area of the warm sector during the evolution of the cyclone corresponding to the formation of an occluded front. The Shapiro–Keyser cyclone model was developed around 1990 and was motivated by the recognition of alternative frontal structures depicted in model simulations and observations of rapidly developing extratropical cyclones. This model features a right angle between the cold and warm fronts (T-bone), a weakening of the poleward portion of the cold front (frontal fracture), an extension of the warm or occluded front to the rear of and around the cyclone (bent-back front), and the wrapping around of the bent-back front to form a warm-core seclusion of post-cold-frontal air. Although the Norwegian cyclone model preceded the Shapiro–Keyser cyclone model by 70 years, antecedents of features of the Shapiro–Keyser cyclone model were apparent in observations, analyses, and conceptual models presented by the Bergen School meteorologists, their adherents, and their progeny. These “lost” antecedents are collected here for the first time to show that the Bergen School meteorologists were aware of them, although not all of the antecedents survived until their reintroduction into the Shapiro–Keyser cyclone model in 1990. Thus, the Shapiro–Keyser cyclone model can be viewed as a synthesis of various elements of cyclone structure and evolution recognized by the Bergen School meteorologists.
Family Caregiver Perspectives on Benefits and Challenges of Caring for Older Adults With Paid Caregivers
Authors: Shaw Amy L. , Riffin Catherine A. , Shalev Ariel , Kaur Harveen , Sterling Madeline R.
Published: September 2020

Background:

Many older adults receive help from both family caregivers and home care workers. We aimed to understand family caregivers’ perspectives on home care workers.

Methods:

This qualitative study took place at an academic medical center in New York, N.Y. We interviewed family caregivers of community-dwelling older adults about their experiences with home care workers. We analyzed transcripts thematically.

Results:

We interviewed 17 family caregivers and identified four major themes: (a) home care workers provide functional and emotional support; (b) home care is logistically challenging; (c) finding the right fit between home care workers, older adults, and families is essential; and (d) home care workers and family caregivers coordinate care well beyond the initiation of home care.

Conclusion:

Despite its logistical challenges, home care benefits patients and family caregivers. Given the growing prevalence of caregiving, clinicians and family caregivers might benefit from training and support about working with home care workers.
Safety Assessment of Lecithin and Other Phosphoglycerides as Used in Cosmetics
Authors: Johnson Wilbur , Bergfeld Wilma F. , Belsito Donald V. , Hill Ronald A. , Klaassen Curtis D. , Liebler Daniel C. , Marks James G. , Shank Ronald C. , Slaga Thomas J. , Snyder Paul W. , Gill Lillian J. , Heldreth Bart
Published: September 2020

The phosphoglycerides considered in this safety assessment are reported to function primarily as skin and hair conditioning agents, emulsifying agents, and surfactants in cosmetic products and are used up to a maximum reported concentration of 50%. Although phospholipids exert physiologic effects, these are not reproduced by application of phospholipid ingredients to the skin. Given the possibility that Lecithin may be derived from animal sources, it should be noted that the Food and Drug Administration does not permit the use of ingredients made from bovine specified risk materials in cosmetic products. The Expert Panel for Cosmetic Ingredient Safety concluded that the 17 phosphoglycerides are safe in the present practices of use and concentration in cosmetics, as described in this safety assessment.
Radical democracy and the imagination of the commons: Beyond cultural populism
Authors: Stevenson Nick
Published: September 2020

Until recently it has been argued that we live in the age of populism. Political parties, both Left and Right, have sought to take advantage of this moment to further their respective political projects. Here, I return to the seminal work of Jim McGuigan and his carefully judged critique of cultural populism that was prominent within cultural studies during the 1990s. Returning to many of the questions raised by McGuigan, I seek to argue that cultural studies needs to readdress these questions in the light of more ecosocialist concerns. Drawing on the work of both Herbert Marcuse and Raymond Williams, I argue that cultural studies needs to carefully question assumptions about so-called elitism and to think again about how different cultural forms (here I mostly focus upon writing) are able to open up crucial questions around the commons. I draw upon different arguments in relation to the commons before connecting them to a range of aesthetic responses. Overall, the argument is that cultural studies needs to develop a specifically anti-capitalist approach while being careful to steer clear of Left populism.
Photosensitivity During Quinolone Therapy in Diabetic Foot Patients May Falsely Indicate Treatment Failure
Authors: Loupa Chariclia V. , Meimeti Evangelia , Voyatzoglou Eleftherios D. , Donou Andriana , Kalantzi Sophia , Konsta Ekaterini
Published: September 2020

Acute bacterial skin and skin structure infections (ABSSSI), also referred to as skin and soft tissue infections, or skin and skin structure infections, with or without osteomyelitis (OM) in diabetic foot are complications of diabetes. Quinolones are a widely used class of antibiotics in ABSSSI and OM, and photosensitivity is among their adverse reactions. Its appearance may falsely indicate treatment failure. We describe 2 such cases. The first patient is a 49-year-old male with type 2 diabetes mellitus (DM), who presented with left lower limb ulcer with fever (39 °C) over a week. He began treatment with ciprofloxacin, clindamycin, and linezolid. Although his clinical condition and laboratory tests improved, the redness of the left lower limb increased. Clinical examination revealed redness on the face and the parts of the body that had been exposed to sunlight. The patient continued the same antimicrobial therapy and was given instructions to avoid exposure to sunlight. Redness and infection improved, and the patient was discharged. The second case is a 72-year-old male with a history of type 2 DM, admitted to hospital because of an infected ulcer of the first toe of the right limb. The patient received intravenous treatment with levofloxacin and clindamycin. On the fourth hospital day, the patient presented redness (with eczematous plaques) on his left lower limb. Clinical examination revealed that the patient’s bed was placed near a window and his left limb was exposed to direct sunlight. Patient’s bed was changed to avoid sun exposure. Symptoms began to improve over the next few days.
Secondary hemophagocytic lymphohistiocytosis versus cytokine release syndrome in severe COVID-19 patients
Authors: Hakim Nausheen N , Chi Jeffrey , Olazagasti Coral , Liu Johnson M
Published: September 2020

COVID-19 or SARS-CoV-2 infection can lead to severe acute respiratory distress syndrome/pneumonia with features of cytokine storm reminiscent of secondary hemophagocytic lymphohistiocytosis (HLH), which can be diagnosed by the calculated HScore. Recent reports have suggested favorable responses to the interleukin-1 receptor antagonist, anakinra in patients with COVID-19 associated secondary HLH. In our single institution study, we compared 14 COVID-19 cytokine storm patients with 10 secondary HLH patients seen immediately prior to the pandemic (non-COVID-19), to determine whether diagnostic features of secondary HLH were typically seen in COVID-19 patients presenting with cytokine storm. Although most of our COVID-19 patients did not fulfill diagnostic criteria for HLH, we hypothesize that identification of HLH may relate to the severity or timing of cytokine release. Based on our observations, we would suggest distinguishing between cytokine release syndrome and secondary HLH, reserving the latter term for cases fulfilling diagnostic criteria.

Impact statement

Severe COVID-19 associated pneumonia and acute respiratory distress syndrome has recently been described with life-threatening features of cytokine storm and loosely referred to as hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS). Although a recent report indicated favorable responses to the interleukin-1 receptor antagonist, anakinra in eight patients with COVID-19 secondary HLH diagnosed using the HScore calculation, others have suggested that the diagnosis of secondary HLH is uncommon and that the use of the HScore has limited value in guiding immunomodulatory therapy for COVID-19. Here, we provide additional perspective on this important controversy based upon comparisons between 14 COVID-19 cytokine storm patients and 10 secondary HLH patients seen immediately prior to the pandemic. We hypothesize that identification of HLH may relate to the severity or timing of cytokine release and suggest distinguishing between cytokine release syndrome and secondary HLH, reserving the latter term for cases fulfilling diagnostic criteria.
Management of severe asthma: summary of the European Respiratory Society/American Thoracic Society task force report
Authors: Khurana Sandhya , Bush Andrew , Holguin Fernando
Published: September 2020

Educational aims

This article is mainly intended for trainees and specialists who are interested in the management of severe asthma.

It aims to inform readers about the updated ERS/ATS recommendations for management of severe asthma, specifically on the topics of biologics, macrolides and long-acting muscarinic antagonists.

It also provides guidance on utilisation of available biomarkers in selecting advanced therapies in severe asthma.
Appropriateness of intensive care treatments near the end of life during the COVID-19 pandemic
Authors: Cardona Magnolia , Anstey Matthew , Lewis Ebony T. , Shanmugam Shantiban , Hillman Ken , Psirides Alex
Published: September 2020

The patient and family perspective on the appropriateness of intensive care unit (ICU) treatments involves preferences, values and social constructs beyond medical criteria. The clinician's perception of inappropriateness is more reliant on clinical judgment. Earlier consultation with families before ICU admission and patient education on the outcomes of life-sustaining therapies may help reconcile these provider–patient disagreements. However, global emergencies like COVID-19 change the usual paradigm of end-of-life care, as it is a new disease with only scarce predictive information about it. Pandemics can also bring about the burdensome predicament of doctors having to make unwanted choices of rationing access to the ICU when demand for otherwise life-saving resources exceeds supply. Evidence-based prognostic checklists may guide treatment triage but the principles of shared decision-making are unchanged. Yet, they need to be altered with respect to COVID-19, defining likely outcomes and likelihood of benefit for the patient, and clarifying their willingness to take on the risks inherent to being in an ICU for 2 weeks for those eligible. For patients who are admitted during the prodrome of COVID-19 disease, or those who deteriorate in the second week, clinicians have some lead time in hospital to have appropriate discussions about ceilings of treatments offered based on severity.

Key points

The patient and family perspective on inappropriateness of intensive care at the end of life often differs from the clinician's opinion due to the nonmedical frame of mind.

To improve satisfaction with communication on treatment goals, consultation on patient values and inclusion of social constructs in addition to clinical prediction is a good start to reconcile differences between physician and health service users’ viewpoints.

During pandemics, where health systems may collapse, different admission criteria driven by the need to ration services may be warranted.

Educational aims

To explore the extent to which older patients and their families are involved in decisions about appropriateness of intensive care admission or treatments

To understand how patients or their families define inappropriate intensive care admission or treatments

To reflect on the implications of decision to admit or not to admit to the intensive care unit in the face of acute resource shortages during a pandemic
In defence of extrapolation but not improvisation in SARS-CoV-2 lung disease
Authors: Epelbaum Oleg , Galperin Irene
Published: September 2020

Recently, the struggle against COVID-19 by respiratory and intensive care clinicians worldwide was punctuated by the sound of calls from a number of influential publications for an end to, as it were, improvisation and a return to principles of evidence-based medicine. The message was that management of SARS-CoV-2 lung disease needed to be guided strictly according to established dogma in acute respiratory distress syndrome unless supplanted by clinical trials specific to COVID-19. This position is predicated on the assumptions that knowledge about acute respiratory distress syndrome, and only about that entity, is directly translatable to SARS-CoV-2 lung disease, and that clinical trials enrolling COVID-19 patients will be completed in a sufficiently timely and rigorous fashion to influence empirical practice during the current pandemic. Clearly, there is room for an alternative perspective. In this Viewpoint, we aim to articulate a contrary point of view by resorting to arguments that are likely to resonate with frontline clinicians battling COVID-19.
Restoring pars intermedia dopamine concentrations and tyrosine hydroxylase expression levels with pergolide: evidence from horses with pituitary pars intermedia dysfunction
Authors: Fortin Jessica S. , Benskey Matthew J. , Lookingland Keith J. , Patterson Jon S. , Howey Erin B. , Goudreau John L. , Schott Harold C.
Published: September 2020

Background

Pituitary pars intermedia dysfunction (PPID) develops slowly in aged horses as degeneration of hypothalamic dopaminergic neurons leads to proliferation of pars intermedia (PI) melanotropes through hyperplasia and adenoma formation. Dopamine (DA) concentrations and tyrosine hydroxylase (TH) immunoreactivity are markedly reduced in PI tissue of PPID-affected equids and treatment with the DA receptor agonist pergolide results in notable clinical improvement. Thus, we hypothesized that pergolide treatment of PPID-affected horses would result in greater DA and TH levels in PI tissue collected from PPID-affected horses versus untreated PPID-affected horses.

To test this hypothesis, pituitary glands were removed from 18 horses: four untreated PPID-affected horses, four aged and four young horses without signs of PPID, and six PPID-affected horses that had been treated with pergolide at 2 µg/kg orally once daily for 6 months. DA concentrations and TH expression levels in PI tissues were determined by high performance liquid chromatography with electrochemical detection and Western blot analyses, respectively.

Results

DA and TH levels were lowest in PI collected from untreated PPID-affected horses while levels in the pergolide treated horses were similar to those of aged horses without signs of PPID.

Conclusions

These findings provide evidence of restoration of DA and TH levels following treatment with pergolide. Equine PPID is a potential animal model of dopaminergic neurodegeneration, which could provide insight into human neurodegenerative diseases.
Therapeutic effect and safety of stem cell therapy for chronic liver disease: a systematic review and meta-analysis of randomized controlled trials
Authors: Zhou Guang-Peng , Jiang Yi-Zhou , Sun Li-Ying , Zhu Zhi-Jun
Published: September 2020

Background

Stem cell therapy is becoming an emerging therapeutic option for chronic liver disease (CLD). However, whether stem cell therapy is more effective than conventional treatment remains questionable. We performed a large-scale meta-analysis of randomized controlled trials (RCTs) to evaluate the therapeutic effects and safety of stem cell therapy for CLD.

Methods

We systematically searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases for the period from inception through March 16, 2020. Primary outcomes were all-cause mortality and adverse events related to stem cell therapy. Secondary outcomes included the model for end-stage liver disease score, total bilirubin, albumin, alanine aminotransferase, prothrombin activity, and international normalized ratio. The standardized mean difference (SMD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a random-effects model.

Results

Twenty-four RCTs were included and the majority of these studies showed a high risk of bias. The meta-analysis indicated that compared with conventional treatment, stem cell therapy was associated with improved survival and liver function including the model of end-stage liver disease score, total bilirubin, and albumin levels. However, it had no obvious beneficial effects on alanine aminotransferase level, prothrombin activity, and international normalized ratio. Subgroup analyses showed stem cell therapy conferred a short-term survival benefit for patients with acute-on-chronic liver failure (ACLF), a single injection was more effective than multiple injections, hepatic arterial infusion was more effective than intravenous infusion, and bone marrow-derived stem cells were more effective than those derived from the umbilical cord. Thirteen trials reported adverse events related to stem cell therapy, but no serious adverse events were reported.

Conclusions

Stem cell therapy is a safe and effective therapeutic option for CLD, while patients with ACLF benefit the most in terms of improved short-term survival. A single injection administration of bone marrow-derived stem cells via the hepatic artery has superior therapeutic effects.
RETRACTED ARTICLE:Indirubin exerts anticancer effects on human glioma cells by inducing apoptosis and autophagy
Authors: Li Zhaohui , Wang Han , Wei Jun , Han Liang , Guo Zhigang
Published: September 2020

Glioma causes significant mortality across the world and the most aggressive type of brain cancer. The incidence of glioma is believed to increase in the next few decades and hence more efficient treatment strategies need to be developed for management of glioma. Herein, we examined the anticancer effects of Indirubin against a panel of human glioma cells and attempted to explore the underlying mechanisms. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay showed that Indirubin could inhibit the growth of all the glioma cells but the lowest IC50 of 12.5 µM was observed against the U87 and U118 glioma cells. Additionally, the cytotoxic effects of Indirubin were comparatively negligible against the normal astrocytes with an IC50 of > 100 µM. Investigation of mechanism of action, revealed that Indirubin exerts growth inhibitory effects on the U87 and U118 glioma cells by autophagic and apoptotic cell death. Annexin V/PI staining assay showed that apoptotic cell percentage increased dose dependently. Apoptosis was associated with increase in Bax decrease in Bcl-2 expressions. Additionally, the expression of autophagic proteins such as LC3II, ATG12, ATG15 and Beclin 1 was also increased. Wound heal assay showed that Indirubin caused remarkable decrease in the migration of the U87 and U118 cells indicative of anti-metastatic potential of Indirubin. Taken together, these results suggest that Indirubin exerts potent anticancer effects on glioma cells and may prove essential in the management of glioma.
Correction to: The analysis of the Saltzman Collection of Peruvian dyes by high performance liquid chromatography and ambient ionisation mass spectrometry
Authors: Armitage Ruth Ann , Fraser Daniel , Degano Ilaria , Colombini Maria Perla
Published: September 2020

An amendment to this paper has been published and can be accessed via the original article.
Quantitative carbon distribution analysis of hydrocarbons, alcohols and carboxylic acids in a Fischer-Tropsch product from a Co/TiO2 catalyst during gas phase pilot plant operation
Authors: Partington Roy , Clarkson Jay , Paterson James , Sullivan Kay , Wilson Jon
Published: September 2020

Comprehensive two-dimensional gas chromatography (GCxGC) analysis for 1-alcohols and gas chromatography–mass spectrometry (GC-MS) analysis for carboxylic acids, derivatised as their methyl esters, have been applied to liquid and wax Fischer-Tropsch (FT) hydrocarbon products. These methods in combination with conventional one-dimensional gas chromatography (GC) analysis of the aqueous, gaseous, liquid hydrocarbon and wax products plus conventional high-performance liquid chromatography (HPLC) analysis of the aqueous phase has allowed a quantitative distribution analysis of FT hydrocarbon and oxygenated products to be demonstrated for a Co/TiO2 catalyst operating in a fixed bed gas phase pilot plant utilising CANSTM catalyst carrier devices. The GC-MS method used is, to the best of our knowledge, the first application of this derivatisation route for the quantification of individual carboxylic acids in FT hydrocarbon product streams.

Whilst the hydrocarbons and oxygenates that were identified are known compounds formed during the low temperature, Co catalysed, FT process the combination of the multiple analysis techniques used has allowed a level of detail to be gained on the product composition that is seldom reported.

Additionally, 1H nuclear magnetic resonance spectroscopy (NMR) and 13C NMR analyses were used to quantify the average concentration of 1-olefin, cis- and trans-2-olefins, 1-alcohol and aldehyde as appropriate for the technique used. Comparison of GCxGC versus 1H NMR and GC-MS versus a KOH titration confirmed the applicability of the chromatographic methods for the quantitative analysis of FT oxygenated compounds. Long-chain 1-alcohols and carboxylic acids, ≥ C3, were found to be present at levels of 1/10th and 1/1000th that of hydrocarbons of equivalent carbon chain length respectively. The 1-olefin:n-paraffin ratio in the hydrocarbon liquid and wax products was found to decrease significantly with increasing carbon chain length and much more so than those of the 2-olefin or 1-alcohol.
Development of Wernicke’s encephalopathy long after subtotal stomach-preserving pancreatoduodenectomy: a case report
Authors: Tsutsumi Chikanori , Abe Toshiya , Shinkawa Tomohiko , Watanabe Hideyuki , Nishihara Kazuyoshi , Nakano Toru
Published: September 2020

Background

Wernicke’s encephalopathy (WE) is an acute neuropsychiatric disorder resulting from thiamine (vitamin B1) deficiency, frequently associated with chronic alcoholism and total parenteral nutrition without thiamine. However, only a few reports have focused on the relationship between WE and subtotal stomach-preserving pancreatoduodenectomy (SSPPD).

Case presentation

A 71-year-old woman underwent SSPPD for an adenocarcinoma of the ampulla of Vater. Although there had been no evidence of recurrence, the patient was treated with antibiotics for cholangitis at 12 and 31 months, respectively, post-surgery. Thereafter, the patient presented with vomiting and disorientation 33 months after surgery. Although she was admitted and underwent closer inspection by a neurologist and a psychiatrist, the exact cause of these syndromes remained unknown. The psychiatrist measured thiamine concentration to examine the cause of disorientation. After 6 days, her level of consciousness worsened. Magnetic resonance imaging of the head showed symmetrically multiple abnormal hyperintense signals on fluid-attenuated inversion-recovery and diffusion weighted image, compatible with WE. An administration of intravenous thiamine was immediately initiated. After 8 days of the measurement of the thiamine level, the patient’s serum thiamine level was found to be 6 µg/mL (reference range, 24–66 µg/mL). Accordingly, the patient was diagnosed with WE. Shortly after starting the treatment, blood thiamine value reached above normal range with significant improvement of her confusional state. However, short-term memory and ataxia remained.

Conclusions

Development of WE after SSPPD is uncommon. However, to prevent an after-effect, the possibility of development of WE after SSPPD should be recognized.
Pancreaticoduodenectomy with malrotation following reoperation due to torsion of efferent loop: a case report
Authors: Kageyama Yumiko , Yamaguchi Ryuzo , Watanabe Shinya , Aizu Keiji , Kobayashi Shinichiro , Sato Fumiya , Fujieda Hironori , Toyoda Yoshitaka , Iwata Tsutomu
Published: September 2020

Background

Malrotation is a congenital anomaly during the development of the embryonic intestine. Although it is generally considered a pediatric surgical condition, it can have significant implications for adult surgery in terms of reconstruction.

Case presentation

The patient was an 85-year-old man with pancreatic cancer and intestinal malrotation. He underwent pancreaticoduodenectomy with modified Child’s reconstruction. Because the ascending colon and efferent loop twisted easily, we fixed the ascending colon to the abdominal wall. Thereafter, right twist and stenosis of the efferent loop occurred. On the 22nd day after the initial surgery, detorsion and Braun anastomosis were performed for efferent loop fixation. Postoperative oral intake was good, and the patient was discharged from our hospital on the 24th day after the reoperation.

Conclusions

This is a rare case of pancreaticoduodenectomy with malrotation following reoperation due to a complication after Child’s reconstruction. In similar cases of intestinal malrotation, it is important to consider avoiding coaxial positioning of intestinal parts and an upper abdominal space while selecting a reconstruction method.
Anorectal injury related to a personal watercraft: a case report and literature review
Authors: Katano Kaoru , Furutani Yuichiro , Hiranuma Chikashi , Hattori Masakazu , Doden Kenji , Hashidume Yasuo
Published: September 2020

Background

Douche injury is a rare consequence of water recreation activities. Generally, this type of trauma occurs when people fall into the water in a sitting position during high-speed activities such as using a personal watercraft (PWC). Here, we report a rare case of anorectal injury caused by water jets from a PWC during sudden acceleration from rest.

Case presentation

A 21-year-old male passenger on a PWC fell off backward from the rear seat when the craft suddenly accelerated. He fell into the water in a supine position with his legs open, and the water jets of the PWC struck his perineum directly. Thereafter, bleeding from the anus was seen, and he was transferred to our hospital. On physical examination, there was a deep laceration interrupting the external anal sphincter in the posterior rectal wall. Abdominal computed tomography revealed a full-layer perforation of the posterior rectal wall and leakage of feces into the extraperitoneal space, but intraperitoneal free air was not seen. Laparoscopic sigmoid loop colostomy and primary suturing of the sphincter and mucosa were performed. He did not have any complications and was discharged from our hospital 16 days after the surgery. His anal function was almost perfectly preserved, and his diverting colostomy was closed 4 months later.

Conclusion

Anorectal injuries related to PWCs can occur not only while traveling at high speeds, but also when suddenly accelerating from rest. A diverting colostomy should be performed for this type of trauma. In these trauma cases, clinicians must suspect complex and life-threatening anorectal injuries early.
Variation in clinical outcomes and process of care measures in community acquired pneumonia: a systematic review
Authors: Lawrence H. , Lim W. S. , McKeever T. M.
Published: September 2020

Background

Variation in outcomes of patients with community acquired pneumonia (CAP) has been reported in some, but not all, studies. Although some variation is expected, unwarranted variation in healthcare impacts patient outcomes and equity of care. The aim of this systematic review was to: i) summarise current evidence on regional and inter-hospital variation in the clinical outcomes and process of care measures of patients hospitalised with CAP and ii) assess the strength of this evidence.

Methods

Databases were systematically searched from inception to February 2018 for relevant studies and data independently extracted by two investigators in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Included studies enrolled adults hospitalised with CAP and reported a measure of variation between two or more units in healthcare outcomes or process of care measures. Outcomes of interest were mortality, length of hospital stay (LOS) and re-admission rates. A structured synthesis of the studies was performed.

Results

Twenty-two studies were included in the analysis. The median number of units compared across studies was five (IQR 4–15). Evidence for variation in mortality between units was inconsistent; of eleven studies that performed statistical significance testing, five found significant variation. For LOS, of nine relevant studies, all found statistically significant variation. Four studies reported site of admission accounted for 1–24% of the total observed variation in LOS. A shorter LOS was not associated with increased mortality or readmission rates. For readmission, evidence was mixed; of seven studies, 4 found statistically significant variation. There was consistent evidence for variation in the use of intensive care, obtaining blood cultures on admission, receiving antibiotics within 8 h of admission and duration of intravenous antibiotics. Across all outcome measures, only one study accounted for natural variation between units in their analysis.

Conclusion

There is consistent evidence of moderate quality for significant variation in length of stay and process of care measures but not for in-patient mortality or hospital re-admission. Evidence linking variation in outcomes with variation in process of care measures was limited; where present no difference in mortality was detected despite POC variation. Adjustment for natural variation within studies was lacking; the proportion of observed variation due to chance is not quantified by existing evidence.