bluuebunny/crossref_metadata_2025_split huggingface dataset:
Niacinamide mitigates SASP‐related inflammation induced by environmental stressors in human epidermal keratinocytes and skin
Authors: Bierman John C. , Laughlin Timothy , Tamura Makio , Hulette Ben C. , Mack Catherine E. , Sherrill Joseph D. , Tan Christina Y.R. , Morenc Malgorzata , Bellanger Sophie , Oblong John E. 
Published: July 2020

AbstractObjectiveTo evaluate whether niacinamide (Nam) can mitigate production of inflammatory and senescence‐related biomarkers induced by environmental stressors.MethodsHuman epidermal keratinocytes were exposed to UVB, urban dust, diesel exhaust and cigarette smoke extract and treated with Nam or vehicle control. Full thickness 3‐D skin organotypic models were exposed to a combination of UVB and PM2.5 and treated with Nam or vehicle control. Quantitation of the SASP‐related inflammatory mediators PGE2, IL‐6 and IL‐8 was performed on cultured media. UVB‐exposed keratinocytes treated with and without Nam were immunostained for the senescence biomarker Lamin B1 (LmnB1). Transcriptomics profiling of cigarette smoke extract effects on keratinocytes was performed. A double‐blind, placebo‐controlled clinical was conducted on 40 female panellists that were pretreated on back sites for two weeks with 5% Nam or vehicle and then exposed to 1.5 minimal erythemal dose (MED) solar‐simulated radiation (SSR). Treated sites were compared with non‐treated exposed sites for erythema and the skin surface IL‐1αRA/IL‐1α inflammatory biomarkers.ResultsUltraviolet B induced synthesis of PGE2, IL‐8 and IL‐6 and reduced LmnB1 levels in keratinocytes. Urban dust and diesel exhaust only stimulated synthesis of IL‐8 whereas cigarette smoke extract only stimulated levels of PGE2. In all exposures, treatment with Nam significantly mitigated synthesis of the inflammatory mediators and restored levels of UVB‐reduced LmnB1. In the 3D skin equivalent model, Nam reduced IL‐8 levels stimulated by a combination of topical PM2.5 and UV exposure. In a UV challenge clinical, pretreatment with 5% Nam reduced erythema and skin surface IL‐1αRA/IL‐1α inflammatory biomarkers that were induced by SSR.ConclusionSince it is known that Nam has anti‐inflammatory properties, we tested whether Nam can inhibit environmental stress‐induced inflammation and senescence‐associated secretory phenotype (SASP) biomarkers. We show Nam can reduce PGE2, IL‐6 and IL‐8 levels induced by environmental stressors. Additionally, in vivo pretreatment with Nam can reduce UV‐induced erythema and skin surface inflammatory biomarkers. These findings add to the body of evidence that Nam can mitigate the skin’s inflammatory response elicited by environmental stressors. This supports Nam can potentially inhibit senescence and premature ageing and thereby maintain skin’s functionality and appearance.
The role of host genetics in the immune response to SARS‐CoV‐2 and COVID‐19 susceptibility and severity
Authors: Ovsyannikova Inna G. , Haralambieva Iana H. , Crooke Stephen N. , Poland Gregory A. , Kennedy Richard B. 
Published: July 2020

AbstractThis article provides a review of studies evaluating the role of host (and viral) genetics (including variation in HLA genes) in the immune response to coronaviruses, as well as the clinical outcome of coronavirus‐mediated disease. The initial sections focus on seasonal coronaviruses, SARS‐CoV, and MERS‐CoV. We then examine the state of the knowledge regarding genetic polymorphisms and SARS‐CoV‐2 and COVID‐19. The article concludes by discussing research areas with current knowledge gaps and proposes several avenues for future scientific exploration in order to develop new insights into the immunology of SARS‐CoV‐2.
The microbiome and cytosolic innate immune receptors
Authors: Liwinski Timur , Zheng Danping , Elinav Eran 
Published: July 2020

AbstractThe discovery of innate immune sensors (pattern recognition receptors, PRRs) has profoundly transformed the notion of innate immunity, in providing a mechanistic basis for host immune interactions with a wealth of environmental signals, leading to a variety of immune‐mediated outcomes including instruction and activation of the adaptive immune arm. As part of this growing understanding of host‐environmental cross talk, an intimate connection has been unveiled between innate immune sensors and signals perceived from the commensal microbiota, which may be regarded as a hub integrating a variety of environmental cues. Among cytosolic PRRs impacting on host homeostasis by interacting with the commensal microbiota are nucleotide‐binding domain, leucine‐rich repeat‐containing protein receptors (NLRs), together with a number of cytosolic DNA sensors and the family of absent in melanoma (AIM)–like receptors (ALRs). NLR sensors have been a particular focus of research, and some NLRs have emerged as key orchestrators of inflammatory responses and host homeostasis. Some NLRs achieve this through the formation of cytoplasmic multiprotein complexes termed inflammasomes. More recently discovered PRRs include retinoic acid‐inducible gene‐I (RIG‐I)–like receptors (RLRs), cyclic GMP‐AMP synthase (cGAS), and STING. In the present review, they summarize recent advancements in knowledge on structure and function of cytosolic PRRs and their roles in host‐microbiota cross talk and immune surveillance. In addition, we discuss their relevance for human health and disease and future therapeutic applications involving modulation of their activation and signaling.
Hypertension burden and challenges across the hypertension treatment cascade among adults enrolled in HIV care in northern Tanzania
Authors: Manavalan Preeti , Madut Deng B. , Hertz Julian T. , Thielman Nathan M. , Okeke Nwora Lance , Mmbaga Blandina T. , Watt Melissa H. 
Published: July 2020

AbstractFailure to address hypertension among people living with HIV (PLWH) may undermine the significant progress made toward reducing mortality among this high‐risk population in sub‐Saharan Africa (SSA). Here, the authors report hypertension prevalence, diagnosis, and treatment among patients enrolled in HIV care in Tanzania. Patients attending an HIV clinic were consecutively screened for hypertension. Hypertension was defined as follows: a single blood pressure measurement ≥160 mm Hg systolic or ≥100 mm Hg diastolic, two measurements at separate visits ≥140 mm Hg systolic or ≥90 mm Hg diastolic, or self‐reported hypertension diagnosis. The authors screened 555 patients, and 19.6% met hypertension criteria. Among a subset of 91 hypertensive participants, 44 (48.4%) reported previous blood pressure measurements, 32 (35.2%) were aware of diagnosis, 10 (11.0%) reported current antihypertensive use, and none had controlled blood pressure. Addressing barriers along the hypertension treatment cascade must be a top priority to improve cardiovascular outcomes among PLWH in SSA.
Sotrastaurin, a PKC inhibitor, attenuates RANKL‐induced bone resorption and attenuates osteochondral pathologies associated with the development of OA
Authors: Pang Cong , Wen Liangbao , Qin Haikuo , Zhu Bikang , Lu Xuanyuan , Luo Shixing 
Published: July 2020

AbstractOsteoarthritis (OA) is a common degenerative disease that affects the musculoskeletal structure of the whole joint, which is characterized by progressive destruction of both articular cartilage and subchondral bone. Treatment of the bone pathologies, particularly osteoclast‐mediated subchondral bone loss in the early stages of OA, could prevent subsequent cartilage degeneration and progression of OA. In the present study, the PKC inhibitor, Sotrastaurin, was found to inhibit RANKL‐induced osteoclast formation in vitro in a dose‐ and time‐dependent manner. In particular, SO exerted its anti‐osteoclastic effect predominantly at the early stages of RANKL stimulation, suggesting inhibitory effects on precursor cell fusion. Using mature osteoclasts cultured on bovine bone discs, we showed that SO also exerts anti‐resorptive effects on mature osteoclasts bone resorptive function. Mechanistically, SO attenuates the early activation of the p38, ERK and JNK signalling pathways, leeding to impaired induction of crucial osteoclast transcription factors c‐Jun, c‐Fos and NFATc1. We also showed that SO treatment significantly inhibited the phosphorylation of PKCδ and MARCKS, an upstream regulator of cathepsin K secretion. Finally, in animal studies, SO significantly alleviates the osteochondral pathologies of subchondral bone destruction as well as articular cartilage degeneration following DMM‐induced OA, markedly improving OARSI scores. The reduced subchondral bone loss was associated with marked reductions in TRAP(+) osteoclasts in the subchondral bone tissue. Collectively, our data provide evidence for the protective effects of SO against OA by preventing aberrant subchondral bone and articular cartilage changes. Thus, SO demonstrates potential for further development as an alternative therapeutic option against OA.
Ageing‐associated increase in SGLT2 disrupts mitochondrial/sarcoplasmic reticulum Ca2+ homeostasis and promotes cardiac dysfunction
Authors: Olgar Yusuf , Tuncay Erkan , Degirmenci Sinan , Billur Deniz , Dhingra Rimpy , Kirshenbaum Lorrie , Turan Belma 
Published: July 2020

AbstractThe prevalence of death from cardiovascular disease is significantly higher in elderly populations; the underlying factors that contribute to the age‐associated decline in cardiac performance are poorly understood. Herein, we identify the involvement of sodium/glucose co‐transporter gene (SGLT2) in disrupted cellular Ca2+‐homeostasis, and mitochondrial dysfunction in age‐associated cardiac dysfunction. In contrast to younger rats (6‐month of age), older rats (24‐month of age) exhibited severe cardiac ultrastructural defects, including deformed, fragmented mitochondria with high electron densities. Cardiomyocytes isolated from aged rats demonstrated increased reactive oxygen species (ROS), loss of mitochondrial membrane potential and altered mitochondrial dynamics, compared with younger controls. Moreover, mitochondrial defects were accompanied by mitochondrial and cytosolic Ca2+ ([Ca2+]i) overload, indicative of disrupted cellular Ca2+‐homeostasis. Interestingly, increased [Ca2+]i coincided with decreased phosphorylation of phospholamban (PLB) and contractility. Aged‐cardiomyocytes also displayed high Na+/Ca2+‐exchanger (NCX) activity and blood glucose levels compared with young‐controls. Interestingly, the protein level of SGLT2 was dramatically increased in the aged cardiomyocytes. Moreover, SGLT2 inhibition was sufficient to restore age‐associated defects in [Ca2+]i‐homeostasis, PLB phosphorylation, NCX activity and mitochondrial Ca2+‐loading. Hence, the present data suggest that deregulated SGLT2 during ageing disrupts mitochondrial function and cardiac contractility through a mechanism that impinges upon [Ca2+]i‐homeostasis. Our studies support the notion that interventions that modulate SGLT2‐activity can provide benefits in maintaining [Ca2+]i and cardiac function with advanced age.
MiR‐101 promotes pain hypersensitivity in rats with chronic constriction injury via the MKP‐1 mediated MAPK pathway
Authors: Qiu Shuang , Liu Benjuan , Mo Yanshuai , Wang Xueqin , Zhong Lina , Han Xiao , Mi Fuli 
Published: July 2020

AbstractThis study was performed to characterize the effect of microRNA‐101 (miR‐101) on the pain hypersensitivity in CCI rat models with the involvement of mitogen‐activated protein kinase phosphatase 1 (MKP‐1) in spinal cord microglial cells. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in the developed CCI models were determined to assess the hypersensitivity of rats to mechanical stimulation and thermal pain. To assess inflammation, the levels of interleukin (IL)‐1β, IL‐6 and tumour necrosis factor‐α (TNF‐α) in the spinal dorsal horns of CCI rats and lipopolysaccharide (LPS)‐activated microglial cells were examined. miR‐101 and MKP‐1 gain‐ and loss‐of‐function experiments were conducted in in vivo and in vitro settings to examine the roles of miR‐101 and MKP‐1 in CCI hypersensitivity and inflammation. The results showed that miR‐101 was highly expressed in the spinal dorsal horn and microglial cells of CCI rat models. Furthermore, overexpression of miR‐101 promoted the pain hypersensitivity in CCI rat models by reducing MWT and TWL. The overexpression of miR‐101 also promoted inflammation in LPS‐exposed microglial cells, as indicated by increased levels of IL‐1β, IL‐6 and TNF‐α. MiR‐101 was shown to target MKP‐1, inhibiting its expression. Moreover, miR‐101 promoted pain hypersensitivity in CCI rat models by inhibiting MKP‐1 expression and activating the mitogen‐activated protein kinase (MAPK) signalling pathway. Taken together, miR‐101 could potentially promote hypersensitivity and inflammatory response of microglial cells and aggravate neuropathic pain in CCI rat models by inhibiting MKP‐1 in the MAPK signalling pathway.
Dichloroacetate reveals the presence of metabolic inertia at the start of exercise in rainbow trout (Oncorhynchus mykiss, Walbaum 1792)
Authors: Wood Chris M. , Pane Eric F. , Heigenhauser George J. F. 
Published: July 2020

AbstractA lag in the increase in oxygen consumption (MO2) occurs at the start of sustainable exercise in trout. Waterborne dichloroacetate (0.58 and 3.49 mmol l−1), a compound which activates pyruvate dehydrogenase (PDH) by inhibiting PDH kinase in muscle, accelerates the increase in MO2 during the first 10 min of sustainable exercise when velocity is elevated to 75% critical swimming speed in a swim tunnel. There are no effects on MO2 thereafter or at rest. This indicates that a delay in PDH activation (“metabolic inertia”) contributes to the lag phenomenon.
Cancer survival statistics for patients and healthcare professionals – a tutorial of real‐world data analysis
Authors: Eloranta S. , Smedby K. E. , Dickman P. W. , Andersson T. M. 
Published: July 2020

AbstractMonitoring survival of cancer patients using data collected by population‐based cancer registries is an important component of cancer control. In this setting, patient survival is often summarized using net survival, that is survival from cancer if there were no other possible causes of death. Although net survival is the gold standard for comparing survival between groups or over time, it is less relevant for understanding the anticipated real‐world prognosis of patients. In this review, we explain statistical concepts targeted towards patients, clinicians and healthcare professionals that summarize cancer patient survival under the assumption that other causes of death exist. Specifically, we explain the appropriate use, interpretation and assumptions behind statistical methods for competing risks, loss in life expectancy due to cancer and conditional survival. These concepts are relevant when producing statistics for risk communication between physicians and patients, planning for use of healthcare resources, or other applications when consideration of both cancer outcomes and the competing risks of death is required. To reinforce the concepts, we use Swedish population‐based data of patients diagnosed with cancer of the breast, prostate, colon and chronic myeloid leukaemia. We conclude that when choosing between summary measures of survival it is critical to characterize the purpose of the study and to determine the nature of the hypothesis under investigation. The choice of terminology and style of reporting should be carefully adapted to the target audience and may range from summaries for specialist readers of scientific publications to interactive online tools aimed towards lay persons.
Are Denture Adhesives Safe for Oral Cells?
Authors: López‐García Sergio , Pecci‐Lloret María P. , García‐Bernal David , Guerrero‐Gironés Julia , Pecci‐Lloret Miguel R. , Rodríguez‐Lozano Francisco J. 
Published: July 2020

AbstractPurposeTo compare the cytotoxicity of six commercially available denture adhesives on human gingival cells: Poligrip Flavour Free Fixative Cream, Fixodent Pro Duo Protection, Novafix cream, FittyDent, Polident Total Action, and Fixodent Pro Plus Duo Protection.Material and MethodsEluates of denture adhesives were brought into contact with human gingival cells and compared to untreated cells (w/o any dental adhesive elute). Cell toxicity was assessed by measuring cell viability (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) (MTT) assays), cell morphology (immunofluorescence assays), induction of apoptosis/necrosis and production of reactive oxygen species (ROS) (flow cytometry assays). In addition, the pH of each sample was determined. Data were analyzed using one‐way analysis of variance (ANOVA) followed by Dunnett's multiple comparisons test.ResultsAll denture adhesives tested led to a reduction in pH, especially Fixodent Pro Duo Protection and Fixodent Pro Plus Duo Protection. The cell viability assays showed that Fixodent Pro Duo Protection (1:1 72 hours, p = 3.04 × 10−6; 1:2 72 hours, p = 2.07 × 10−6; 1:4 72 hours, p = 2.04 × 10−6) and Fixodent Pro Plus Duo Protection (1:1 72 hours, p = 2.01 × 10−6; 1:2 72 hours, p = 3.03 × 10−6; 1:4 72 hours, p = 2.02 × 10−6) significantly decreased cell viability at all dilutions. Compared to the control group and the rest of the adhesives, Poligrip Flavour Free Fixative Cream (PFF 1:1 72 hours, p = 2.24 × 10−6; 1:2 72 hours, p = 2.44 × 10−6; 1:4 72 hours, p = 2.04 × 10−6) showed a significantly higher cell viability score at all dilutions. Fixodent Pro Duo Protection and Fixodent Pro Plus Duo Protection, both adhesives containing zinc salts in their composition, were responsible for necrosis, and the number of cells was much reduced, with aberrant morphology and pyknotic nucleus. Finally, Fixodent (1:2, p = 2.04 × 10−6, 1:4, p = 0.00036; 1:2, p = 8.82 × 10−6, 1:4, p = 2.30 × 10−6) products significantly promoted ROS production in gingival cells.ConclusionsThe results suggest that denture adhesives containing zinc in their composition could be responsible of the decrease of cell viability, ROS production, aberrant cell morphology, and induction of apoptosis and cell death. However, other possible additional cytotoxic factors must be considered. Thus, more studies are necessary to confirm this hypothesis.
A retrospective study on prescribing pattern and cost analysis of proton-pump inhibitors used among adults of Saudi Arabia
Authors: Ali Mohammad Daud , Ahmad Ayaz 
Published: July 2020

Abstract

Objective
To evaluate the use of proton-pump inhibitors (PPIs) for treatment of different gastric disease in Saudi population and their related administration cost.

Materials and methods
It was a cross-sectional retrospective drug utilization study. The utilization rates and cost analysis of each PPIs class of drugs were compared. Study data were obtained from pharmacy database. Data between 1 January 2019 and 31 December 2019 were investigated, including incidence, prevalence and duration of use of proton-pump inhibitors among adults of Saudi Arabia.

Key findings
We observed 26 798 (4.27%) prescription of PPIs were dispensed in the in-patient and out-patient pharmacy department of Al-Mana Group of Hospital (AGH) Al khobar. Among all the PPIs user, more than the half ((53.01%, n = 14 208), 95% CI (52.42–53.62)) were male. 30–40 years age patients (24.57%, 95% CI (24.06–25.09) (n = 6585)) were highest number of PPI users. Nearly, equal number of PPI users belongs between 51–60 years ((20.88%, n = 5596), 95% CI (20.40–21.37)) and &gt;60 years ((20.36%, n = 5456), 95% CI (19.8–20.85)). Among all the dispensed PPIs drugs, Pantoprazole is dispensed to the highest number of patients (79.09% (95% CI, 78.61–79.58) (n = 21 197)) while their average duration of therapy was 18.86 days. Among all PPIs, pantoprazole average unit wise cost was highest SR 8.83 (USD 2.35) in comparison to other PPIs.

Conclusion
In our study, among all the PPIs Pantoprazole was prescribed to the highest number of patients also it was costliest; hence, their safe and effective use must be warranted. Current study will also help in to develop nation database regarding utilization of proton-pump inhibitors.
Diet diversity was limited in Malawi resulting in stunting despite availability of foods in markets
Authors: Adachi Motoi , Urabe Daisaku 
Published: July 2020

AbstractBackgroundStunting, the most common type of malnutrition, has been a big burden for developing countries such as the Republic of Malawi. The state of malnutrition and the eating behavior of children were surveyed at the border between Malawi and Zambia using anthropometrical measurements and Household Diet Diversity Scores.MethodsTwo rural sites were chosen to compare the impact of empowering communities with nutritional knowledge. Children between 6 months and 5 years old were randomly recruited to evaluate nutritional status. Their caregivers were interviewed to collect Household Dietary Diversity Scores.ResultsNutritional knowledge at the site where intervention had occurred was higher than at the site where intervention had not yet occurred. However, stunting prevalence at the site where intervention occurred was not statistically lower than site that had not experienced intervention. The Household Dietary Diversity Scores study revealed that some kinds of food groups were almost absent such as organ meat (kidney, liver, and heart), and dairy products but that cereals, spices, and other vegetables were almost 100% taken at both sites, and distance from market was not associated with diet diversity.ConclusionsThe fact that food diversity was not associated with distance from market would explain the limited food accessibility and poor utilization. Although animal resource foods are available at market, they were not been consumed. The profound challenge lays in their accessibility and utilization. A successful project would aim to introduce vitamin A‐rich vegetables and would explore the sustainable production of animal resource foods in the community.
COVID‐19 in kidney transplant recipients: A multicenter experience in Istanbul
Authors: Demir Erol , Uyar Murathan , Parmaksiz Ergun , Sinangil Ayse , Yelken Berna , Dirim Ahmet Burak , Merhametsiz Ozgur , Yadigar Serap , Atan Ucar Zuhal , Ucar Ali Riza , Demir Mehmet Emin , Mese Meral , Akin Emin Baris , Garayeva Nurana , Safak Seda , Oto Ozgur Akin , Yazici Halil , Turkmen Aydin 
Published: July 2020

AbstractIntroductionManagement of COVID‐19 in kidney transplant recipients should include treatment of the infection, regulation of immunosuppression, and supportive therapy. However, there is no consensus on this issue yet. This study aimed to our experiences with kidney transplant recipients diagnosed with COVID‐19.Material and MethodsKidney transplant recipients diagnosed with COVID‐19 from five major transplant centers in Istanbul, Turkey, were included in this retrospective cohort study. Patients were classified as having moderate or severe pneumonia for the analysis. The primary endpoint was all‐cause mortality. The secondary endpoints were acute kidney injury, the average length of hospital stay, admission to intensive care, and mechanical ventilation.ResultsForty patients were reviewed retrospectively over a follow‐up period of 32 days after being diagnosed with COVID‐19. Cough, fever, and dyspnea were the most frequent symptoms in all patients. The frequency of previous induction and rejection therapy was significantly higher in the group with severe pneumonia compared to the moderate pneumonia group. None of the patients using cyclosporine A developed severe pneumonia. Five patients died during follow‐up in the intensive care unit. None of the patients developed graft loss during follow‐up.DiscussionCOVID‐19 has been seen to more commonly cause moderate or severe pneumonia in kidney transplant recipients. Immunosuppression should be carefully reduced in these patients. Induction therapy with lymphocyte‐depleting agents should be carefully avoided in kidney transplant recipients during the pandemic period.