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International audience; Ischaemic heart disease (IHD) remains the leading cause of death and disability worldwide. As a result, novel therapies are still needed to protect the heart from the detrimental effects of acute ischaemia-reperfusion injury, in order to improve clinical outcomes in IHD patients. In this regard, although a large number of novel cardioprotective therapies discovered in the research laboratory have been investigated in the clinical setting, only a few of these have been demonstrated to improve clinical outcomes. One potential reason for this lack of success may have been the failure to thoroughly assess the cardioprotective efficacy of these novel therapies in suitably designed preclinical experimental animal models. Therefore, the aim of this Position Paper by the European Society of Cardiology Working Group Cellular Biology of the Heart is to provide recommendations for improving the preclinical assessment of novel cardioprotective therapies discovered in the research laboratory, with the aim of increasing the likelihood of success in translating these new treatments into improved clinical outcomes.

Conventional microfluidic devices are typically complex and expensive. The devices require the use of pneumatic control systems or highly precise pumps to control the flow in the devices. This work investigates an alternative method using paper based microfluidic devices to replace conventional microfluidic devices. Size based separation and extraction experiments conducted were able to separate free dye from a mixed protein and dye solution. Experimental results showed that pure fluorescein isothiocyanate could be separated from a solution of mixed fluorescein isothiocyanate and fluorescein isothiocyanate labeled bovine serum albumin. The analysis readings obtained from a spectrophotometer clearly show that the extracted tartrazine sample did not contain any amount of Blue-BSA, because its absorbance value was 0.000 measured at a wavelength of 590nm, which correlated to Blue-BSA. These demonstrate that paper based microfluidic devices, which are inexpensive and easy to implement, can potentially replace their conventional counterparts by the use of simple geometry designs and the capillary action. These findings will potentially help in future developments of paper based microfluidic devices.

In the first instalment of the Words of Advice series, we feature the essentials of good manuscript writing with practical tips on how to plan, organise and write a standout scientific paper.

The quantitative determination of small molecules by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI TOF MS) was always challenging, due to low sensitivity and interferences of matrix and other contaminants on sample plates. Here we report a disposable paper-array (PA) plate in MALDI TOF MS analysis for quantitative analysis of serum free fatty acids (FFAs) with less interference and higher sensitivity, compared with conventional stainless steel (SS) plate. The disposable PA plate was low cost and environmentally friendly. In particular, it was more sensitive in FFAs detection with ~8–34-fold sensitivity increase for eight FFAs as compared to SS plate. Eight serum FFAs in gout patients were investigated using this disposable PA plate. The quantitative results showed good linearity of all eight FFAs between 0.1 and 2.5 mM with correlation coefficients between 0.994 and 0.999 and limits of detection (LODs) between 8.6 and 104.2 μM. Mann-Whitney U test, principal component analysis (PCA) and random forest categorizer allowed the clear separation of gout patients from healthy controls, according to eight FFAs levels in serum detected by disposable PA plate based MALDI TOF MS.

Nobel laureate Aziz Sancar writes about his decades-long relationship with the Journal of Biological Chemistry. Since 1984, he has published 100 papers in JBC, including this "Reflections."

Peer review can seem like a barrier we have to scale in order to publish. In this Perspective, we ask what would happen if, instead, the focus of peer review was to help everyone in the field improve the quality of their papers.

Low oxygen tension, or hypoxia, is a common occurrence in solid tumors. Hypoxia is a master regulator of cellular phenotype, and is associated with increased tumor invasion and aggressiveness as well as adverse patient prognosis. Oxygen has recently been linked with the selective movement of different cancer cell types in three-dimensional invasion assays utilizing paper-based scaffolds. It has remained unclear, however, if cells in these paper-based invasion assays are experiencing hypoxia. In this manuscript, we adapted cell-based methods to measure oxygen tension in our 3D invasion assays: the adduction of pimonidazole to free thiols in the cell, indicative of a reducing environment; the localization of hypoxia inducible factors to the nucleus; and the expression of hypoxia-regulated gene products. We utilized each method to compare the oxygen tension in different locations of the paper-based invasion stacks and found an oxygen gradient is indeed forming. Specifically, we found that the extent of pimonidazole binding, as well as the levels and activities of nucleus-localized HIF-α proteins, increase as the distance between the cells and the source of fresh medium increases. These complementary cell-based readouts not only confirm the selective invasion we observe is due to an oxygen gradient, they also show the gradient is temporal in nature and evolves with increasing culture period.

For scientific research to have an impact, its findings need to be communicated. Usually, such communications take the form of published papers in a journal. Given that most papers are rarely cited, yet consume a great deal of a scientist’s time, treasure, and talent, the value of scientific publication as an enterprise merits consideration. What is a paper really worth? In this Perspective, I consider three potential values: career, science, and society.

Over the last 20 years, there has been increasing focus on the development of novel stem cell based therapies for the treatment of disorders and diseases affecting the enteric nervous system (ENS) of the gastrointestinal tract (so-called enteric neuropathies). Here, the idea is that ENS progenitor/stem cells could be transplanted into the gut wall to replace the damaged or absent neurons and glia of the ENS. This White Paper sets out experts’ views on the commonly used methods and approaches to identify, isolate, purify, expand and optimize ENS stem cells, transplant them into the bowel, and assess transplant success, including restoration of gut function. We also highlight obstacles that must be overcome in order to progress from successful preclinical studies in animal models to ENS stem cell therapies in the clinic.

In the above paper, some basic equations are wrong.

Translating to the Community (T2C) is a social biorepository designed to advance new diagnostic tools and realign community–clinical processes, with the aim to mitigate the short- and long-term impacts of fetal alcohol spectrum disorder (FASD) as well as prenatal alcohol exposure and its co-morbidities and behaviors. In this paper, we describe the evolution of this repository as a new translational partnership to advance a precision-medicine approach to FASD. Key to its evolution was a partnership between academic researchers, Indigenous communities, families, and a regional diagnostic clinic. We further describe the rationale for social biobanking, the type of banking, ethical engagement of families, communities, and clinics, their roles in repository design, governance, translation, and research activities, types of data collected from families, and how the study data are managed, reported, and accessed. The repository design includes biological samples, social-contextual health-survey data, and clinical data (which are linkable to administrative data) from community and clinical cohorts of diagnosed children, children prenatally exposed but not diagnosed, children suspected to have had a prenatal exposure, and related siblings, biological parents, and unrelated children and their parents. From these cohorts and families, potential studies drawing on this data will shed light on various risk factors, social and biological pathways, and service utilization issues, with the aim to implement primary and secondary prevention and intervention strategies.

This week’s papers address the involvement of TGF-β signaling in the differentiation of T H 17 cells, a checkpoint that restrains the antitumor and antivirus activities of natural killer cells, and a mechanism for erasing a parental epigenetic memory in plant embryos.

How many of the authors who publish in Cell Stem Cell dream that their work will eventually wind up in the clinic? Probably quite a few. In the 10 years since its launch, Cell Stem Cell has featured many innovative discoveries, and several of them have gone on to become the seeds of burgeoning biotechnology companies with therapeutic aspirations. Two scientists who have seen that happen are Benjamin Reubinoff (Figure 1) and Derrick Rossi (Figure 2), both of whom led the clinical translation of technologies that made their public debut in Cell Stem Cell.

Nephrotoxicity is one of the more common causes of attrition in nonclinical drug development. Like most tissues, the kidney has a limited number of ways of responding to toxicological insults from diverse mechanistic pathways, which can limit the ability to determine mechanisms of renal injury using the assays routinely performed in preclinical toxicologic studies. In situations where the renal injury is unusual in morphology or if a therapeutic margin is low, additional investigative techniques may be needed to identify a potential mechanism of toxicity in order to inform clinical risk assessment or establish human relevance and translatability of the toxicity. While routine microscopic evaluation can suggest a specific pathogenesis, understanding the mechanism of renal injury often requires additional hypothesis-driven investigations and specialized techniques to obtain the data necessary to identify a nephrotoxic mechanism. Nonclinical mechanistic investigations can be resource-intensive and often yield limited new information. Although there are multiple avenues to investigate renal toxicity, no single mechanistic study or prescriptive battery of tests will identify the pathophysiologic basis for every potential mechanism of renal injury. To aid the nonclinical investigator, we outline a tiered approach for prioritizing investigations to provide a rational and linear road map for the exploration of mechanisms of drug-induced kidney injury. [Box: see text]

Helicase-like transcription factor is regulated by alternative mRNA splicing. Global deletion of Hltf causes perinatal lethality, i.e. 75% die of hypoglycemia

Background Heavy menstrual bleeding (HMB) is the most common symptom for women with bleeding disorders. Major barriers to performing research in this field are difficulties in quantifying and tracking changes in menstrual bleeding, particularly in adolescents. The Pictorial Blood Assessment Chart (PBAC) score is often used to quantify severity of menstrual bleeding1. However, the traditional paper diary PBAC score is fraught with recall bias and compliance issues in adolescents. Utilizing mobile applications (apps) has great potential for improving health by assisting with behavior modification and disease self-management. Additionally, mobile apps can serve as a valuable medical research tool by facilitating rapid reporting. Objectives We developed a mobile app version of the PBAC score to enable adolescents to report and quantify menstrual bleeding. We evaluated patient satisfaction and compliance with mobile app reporting as compared to paper reporting. We hypothesized that adolescents would be compliant with mobile app reporting and would prefer this method over paper reporting. Methods This study was a randomized cross-over study of 25 post-menarchal females ages 13-21 years seen in the Hematology Clinics at Nationwide Children's Hospital, Columbus, Ohio. Inclusion criteria included: history of regularly occurring menstrual cycle and possession of a mobile application capable device (smart phone) with continuous service expected. Non-English speaking patients and patients intending to start a hormonal agent that may fully suppress menstrual bleeding were excluded. Subjects agreed to track menstrual bleeding in two consecutive menstrual cycles and were randomized to using the PBAC paper diary or the PBAC mobile app format first. At the end of each cycle, a 10-point response scale satisfaction questionnaire and a system usability scale (mobile app only) assessed the acceptability of the format of the diary used. Weekly email reminders were sent in both groups. Mobile device notifications and reminders were used in the mobile app group. To compare the satisfaction survey results, the Hills and Armitage method for analyzing cross-over data was used which included evaluation of period effect, group effect, and their interaction using a series of independent t-tests. Results The 25 subjects enrolled had a median age of 15 years (range 13-21 years). Eleven (44%) had identified bleeding disorders. Twenty-two (88%) could use phones in school. Subjects' PBAC scores did not have significant variability between the paper diary (median PBAC=95) and the mobile app (median PBAC=114). There was a median number of 2 entry times per day in both groups. There was no significant difference in the number of app entries subjects reported to study staff and the actual number recorded in the app. For the mobile app, twenty subjects (80%) had high compliance for reporting bleeding symptoms (app entries for >80% of cycle duration). There were no subjects with low compliance (app entries for Discussion This study demonstrated that a PBAC mobile app as compared to the PBAC paper diary was the preferred method of recording menstrual bleeding in adolescents and demonstrated feasibility as a research data collection tool. The app received stronger satisfaction scores and overall compliance was high. A PBAC mobile app is unique compared to publicly available apps because it allows girls and women to quantify their heaviness of flow during menses. Most menstrual tracking apps only track length of cycles or use qualitative assessments of bleeding. In a clinical setting, data from the PBAC app can allow providers to see real-time bleeding symptoms allowing for adjustments in therapy. 1Higham JM, O'Brien PM, Shaw RW. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol 1990:97(8):734-739. Disclosures No relevant conflicts of interest to declare.

This week’s articles describe ways to treat scleroderma and schizophrenia.

This week’s articles showed that enhancing a mitochondrial stress response reduced amyloid aggregation in mice; solved the structure of the ion channel TRPM4; found a role for NOTCH1 in the assembly of adherens junctions and endothelial barrier maintenance; and showed that RNA polymerase III limits life span in worms and flies.

This week’s articles report that inhibiting the ion channel TRPC5 prevents the loss of podocytes in rat models of kidney disease.

This month’s articles show how a hypha-associated fungal peptide triggers an antifungal immune response and how the lipid PIP 2 sustains B cell receptor signaling.

Wenbing Wan,1–3,* Shiwen Zhang,2–4,* Liangpeng Ge,2,3,5 Qingtao Li,1 Xingxing Fang,1 Quan Yuan,4 Wen Zhong,6 Jun Ouyang,1 Malcolm Xing1,2,7 1Department of Anatomy, Guangdong Provincial Medical Biomechanical Key Laboratory, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Mechanical Engineering, University of Manitoba, Winnipeg, MB, Canada; 3Manitoba Institute of Child Health, Winnipeg, MB, Canada; 4Sichuan University, Chengdu, People’s Republic of China; 5Chongqing Academy of Animal Sciences, Chongqing, People’s Republic of China; 6Department of Textile Sciences, University of Manitoba, Winnipeg, MB, Canada; 7Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada *These authors contributed equally tothis work Abstract: Bone tissue engineering through seeding of stem cells in three-dimensional scaffolds has greatly improved bone regeneration technology, which historically has been a constant challenge. In this study, we researched the use of adipose-derived stem cell (ADSC)-laden layer-by-layer paper-stacking polycaprolactone/gelatin electrospinning nanofibrous membranes for bone regeneration. Using this novel paper-stacking method makes oxygen distribution, nutrition, and waste transportation work more efficiently. ADSCs can also secrete multiple growth factors required for osteogenesis. After the characterization of ADSC surface markers CD29, CD90, and CD49d using flow cytometry, we seeded ADSCs on the membranes and found cells differentiated, with significant expression of the osteogenic-related proteins osteopontin, osteocalcin, and osteoprotegerin. During 4 weeks in vitro, the ADSCs cultured on the paper-stacking membranes in the osteogenic medium exhibited the highest osteogenic-related gene expressions. In vivo, the paper-stacking scaffolds were implanted into the rat calvarial defects (5 mm diameter, one defect per parietal bone) for 12 weeks. Investigating with microcomputer tomography, the ADSC-laden paper-stacking membranes showed the most significant bone reconstruction, and from a morphological perspective, this group occupied 90% of the surface area of the defect, produced the highest bone regeneration volume, and showed the highest bone mineral density of 823.06 mg/cm3. From hematoxylin and eosin and Masson staining, the new bone tissue was most evident in the ADSC-laden scaffold group. Using quantitative polymerase chain reaction analysis from collected tissues, we found that the ADSC-laden paper-stacking membrane group presented the highest osteogenic-related gene expressions of osteocalcin, osteopontin, osteoprotegerin, bone sialoprotein, runt-related transcription factor 2, and osterix (two to three times higher than the control group, and 1.5 times higher than the paper-stacking membrane group in all the genes). It is proposed that ADSC-laden layer-by-layer paper-stacking scaffolds could be used as a way of promoting bone defect treatment. Keywords: paper-stacking, layer-by-layer membrane, bone regeneration, adipose-derived stem cells, calvarial defect

Due to its availability, low cost, flat geometry, and transparency, the ex ovo chick embryo has become a major vertebrate animal model for the study of morphogenetic events, such as gastrulation2, neurulation3-5, somitogenesis6, heart bending7,8, and brain formation9-13, during early embryogenesis. Key to understanding morphogenetic processes is to follow them dynamically by time-lapse imaging. The acquisition of time-lapse movies of chick embryogenesis ex ovo has been limited either to short time windows or to the need for an incubator to control temperature and humidity around the embryo14. Here, we present a new technique to culture chick embryos ex ovo for high-resolution time-lapse imaging using transmitted light microscopy. The submerged filter paper sandwich is a variant of the well-established filter paper carrier technique (EC-culture)1 and allows for the culturing of chick embryos without the need for a climate chamber. The embryo is sandwiched between two identical filter paper carriers and is kept fully submerged in a simple, temperature-controlled medium covered by a layer of light mineral oil. Starting from the primitive streak stage (Hamburger-Hamilton stage 5, HH5)15 up to at least the 28-somite stage (HH16)15, embryos can be cultured with either their ventral or dorsal side up. This allows the acquisition of time-lapse movies covering about 30 hr of embryonic development. Representative time-lapse frames and movies are shown. Embryos are compared morphologically to an embryo cultured in the standard EC-culture. The submerged filter paper sandwich provides a stable environment to study early dorsal and ventral morphogenetic processes. It also allows for live fluorescence imaging and micromanipulations, such as microsurgery, bead implantation, microinjection, gene silencing, and electroporation, and has a strong potential to be combined with immersion objectives for laser-based imaging (including light-sheet microscopy).

Histochemistry continues to be widely applied in biomedical research, being nowadays mostly addressed to detect and locate single molecules or molecular complexes inside cells and tissues, and to relate structural organization and function at the high resolution of the more advanced microscopical techniques. In the attempt to see whether histochemical novelties may be found in the recent literature, the articles published in the European Journal of Histochemistry in the period 2014-2016 have been reviewed. In the majority of the published papers, standardized methods have been preferred by scientists to make their results reliably comparable with the data in the literature, but many papers (approximately one fourth of the published articles) described novel histochemical methods and procedures. It is worth noting that there is a growing interest for minimally-invasive in vivo techniques (magnetic resonance imaging, autofluorescence spectroscopy) which may parallel conventional histochemical analyses to obtain information not only on the morphological features of living organs and tissues, but also on their functional, biophysical and molecular characteristics. Thanks to this unceasing methodological refinement, histochemistry will continue to provide innovative applications in the biomedical field.

Introduction: Sickle cell disease (SCD) is a common inherited blood disorder caused by sickle hemoglobin (HbS) which, unlike normal adult hemoglobin (HbA), becomes insoluble and polymerizes under hypoxic conditions. Patients with SCD experience chronic hemolytic anemia, episodic pain crises and abnormal blood flow to critical organs that cumulatively result in significant illness and shortened lifespans for many. The severity of SCD varies significantly between patients, but for individuals the rate of adverse events is strongly correlated with intraerythrocytic concentration of HbS (%HbS). High per test costs and long turnaround times make conventional laboratory methods (e.g. Hb electrophoresis, HPLC, IEF) impractical for quantifying %HbS in real-time (e.g. during transfusion therapy). The objective of this study was to demonstrate that %HbS in blood could be quantified using our recently developed rapid, low-cost paper-based SCD assay [1]. Methods: Blood samples were obtained from SCD and sickle cell trait (SCT) patients at the Texas Children’s Hematology Center (Houston, TX). To perform the SCD assay a 20μL droplet of blood mixed with Hb solubility buffer (1:10 by volume) was dropped on chromatography paper. The resulting blood stain was digitized with a flatbed scanner (Canon USA Inc, Melville, NY) and analyzed using a custom image analysis code (The MathWorks Inc, Natick, MA). Conventional Hb electrophoresis was performed with the semi-automated Sebia Hydrasys 2 Scan system (Sebia Inc, Norcross, GA). Results: The difference in transport of Hb through the paper produced a blood stain with two parts: the area of the initial drop where polymerized HbS is retained (center spot) and the area where soluble Hb is wicked laterally (peripheral ring). The relative color intensity of the center spot and peripheral ring is related to the blood sample %HbS (Fig. 1). The image analysis code automatically isolates and calculates the ratio of the average color intensities of each area (S-index). A series of reconstituted blood samples with artificially adjusted %HbS from 0 to 60% was used to calibrate the assay so that %HbS could be estimated based on blood stain color intensities (Fig. 2a). The values of %HbS estimated for patient samples using our paper-based SCD assay and actual values measured using conventional Hb electrophoresis were highly correlated with R2 = 0.898 (Fig. 2b). The estimated and actual %HbS values also showed strong agreement with the standard deviation of the difference between the two measurements = 5.5 %HbS (Fig. 2c). The majority of the differences between actual and estimated %HbS (96.67%) are within 2 standard deviations of the mean of the differences. The assay could be performed in under 35 minutes and multiple assays could be performed and analyzed in parallel. The cost of consumable materials and reagents for the paper-based SCD assay is less than $0.03. Conclusions: This study demonstrates the feasibility of using our recently developed paper-based assay to quantify %HbS in blood samples in real-time. The ability to rapidly, inexpensively measure %HbS will be particularly useful for monitoring the effectiveness of chronic transfusion or hydroxyurea therapy for long-term control of HbS content in blood of SCD patients. The ability to measure %HbS in real-time could also potentially facilitate more aggressive prophylactic therapy to intervene rapidly and significantly reduce the rate of life-threatening complications in SCD patients, including stroke. Figure 1: Figure 1:. Figure 2: Figure 2:. Acknowledgments: This work was supported in part by a 2012 NIH Director's Transformative Research Award (NHLBI R01HL117329, PI: SSS). References: [1] Yang X, et al. Lab Chip, 2013, 13, 1464-1467. Disclosures Piety: Tulane University: PCT/US2012/064856 Patents & Royalties. Yang:Tulane University: PCT/US2012/064856 Patents & Royalties. Shevkoplyas:Tulane University: PCT/US2012/064856 Patents & Royalties; Halcyon Biomedical Incorporated: Equity Ownership.

Introduction: Global health research is hampered by the lack of inexpensive and reliable assays to annotate clinical study cohorts for geographically localized endemic genetic disorders. The most prevalent modifier in Africa is sickle cell disease (SCD, HbSS). In SCD, sickling of erythrocytes by polymerization of hemoglobin S (HbS) causes vaso-occlusion and hemolysis, leading to significant morbidity/mortality and constituting a major healthcare and economic burden. The inhomogeneity bias introduced into the clinical data of patient cohorts by the changes associated to undiagnosed SCD is a significant challenge. Thus, our aims were to: a) optimize a paper-based screening test for SCD for its application in suboptimal and resource-limited conditions, b) demonstrate the feasibility of retrospective SCD annotation of a large cohort of children enrolled in a global health research study, and c) extract novel evidence on potential differences in clinical presentation between febrile children with and without SCD enrolled in this cohort. Materials & Methods: First, we adapted and simplified a paper-based SCD assay (Piety et al. 2017) for suboptimal sample conditions (frozen EDTA-whole blood) and limited-resource settings. Five microlitres of thawed EDTA-whole blood was solubilized (high phosphate buffer with saponin/sodium hydrosulfite), and blotted on standard blotting paper. Dots formed by capillarity, and their aspect depended on HbS%. A high-resolution scanner and two smartphone brands were compared for image capture. An algorithm for visual calling of the presence an HbS allele was developed, and the freeware ImageJ determined peripheral/central pixel intensities. An HbS dosimetric curve was determined after identification of optimal parameter correlations by scatter plot matrix. Second, blood samples from 1103 children aged 9 to 35 months enrolled in a randomized open prospective non-inferiority pediatric cohort study on algorithm-based management of febrile illnesses in Tanzania (ePOCT Trial, 2014-6, NCT02225769, Swiss/Tanzanian IRB approval, Keitel et al.2017) were assayed with the optimized paper test. In parallel, confirmation by gold-standard alkaline Hb electrophoresis (Helena Biosciences, UK) was performed. Third, clinical data from the newly SCD-annotated ePOCT database was analyzed (STATA software suite) to identify clinical features associated with febrile illnesses in the HbAA/AS/SS groups. Results: All EDTA-blood samples frozen onsite in Tanzania (shipped and then stored for >1 year) could be assayed. The test was rapid (5'), inexpensive (0.05 USD/test) and accessible (widely available reagents, no requirement for costly equipment, open-source freeware). Determination of HbS status (homozygous HbSS/AA or heterozygous HbSA) was effective both visually and by informatic means. Smartphone cameras yielded identical results (R2=0.96 & 0.97) when compared to a high-definition scanner. Local prevalence was at 1.6% and 13.6% for HbSS and HbAS respectively, in line with previously published data. By visual sorting of blood dots, the assay was 100% sensitive and 75.8% specific for the determination of HbSS-SCD and 97.6% sensitive and 87.5% specific for the identification of an HbS allele (in an hetero- or homozygous state). After analysis of the annotated ePOCT multiparametric clinical dataset, we observed that cough as the main complaint was more prevalent in children with HbSS (OR 3.1, 95% CI: 1.1-8.3). HbSS children were more severely malnourished (MUAC/age average z-scores -0.7 vs 0.0, p=0.01) and slightly more anemic (Hb 9.1 vs 9.8 g/dL, p=0.06) when compared to HbAA counterparts. Interestingly, children with HbAS had a better nutrition status than those with HbAA (MUAC/age average z-score 0.14, p Conclusions: We demonstrated that the retrospective annotation of clinical cohorts for SCD with an optimized paper-based assay is feasible, straightforward and inexpensive. Our approach has the potential to eliminate the interpretation bias associated with SCD, and thus facilitate the downstream analysis of valuable datasets in other studies. As a proof of principle, we examined a properly annotated dataset highlighting novel features of febrile illness in children with SCD and HbAS carriers in Africa. Disclosures No relevant conflicts of interest to declare.

Cathelicidins, like other antimicrobial peptides, exhibit direct antimicrobial activities against a broad spectrum of microbes, including both Gram-positive and Gram-negative bacteria, enveloped viruses, and fungi. These host-derived peptides kill the invaded pathogens by perturbing their cell membranes and can neutralize biological activities of endotoxin. Nowadays, more and more data indicate that these peptides, in addition to their antimicrobial properties, possess various immunomodulatory activities. Cathelicidins have the potential to influence and modulate, both directly and indirectly, the activity of various cell populations involved in inflammatory processes and in host defense against invading pathogens. They induce migration of neutrophils, monocytes/macrophages, eosinophils, and mast cells and prolong the lifespan of neutrophils. These peptides directly activate inflammatory cells to production and release of different pro-inflammatory and immunoregulatory mediators, cytokines, and chemokines, however cathelicidins might mediate the generation of anti-inflammatory cytokines as well. Cathelicidins also modulate epithelial cell/keratinocyte responses to infecting pathogens. What is more, they affect activity of monocytes, dendritic cells, keratinocytes, or epithelial cells acting in synergy with cytokines or β-defensins. In addition, these peptides indirectly balance TLR-mediated responses of monocytes, macrophages, dendritic cells, epithelial cells, and keratinocytes. This review discusses the role and significance of cathelicidins in inflammation and innate immunity against pathogens.

This week’s papers describe therapies for myeloid cancers and a kinase to inhibit in order to prevent pathogenic bone destruction.

Objective The aim of this study was to investigate the association of tongue brushing with the number of fungiform taste buds and taste perception using a confocal laser scanning microscopy in combination with a filter-paper disc method (FPDM). Methods Twenty-four subjects with or without a habit of tongue brushing (11 males and 13 females, 20–46 years old) participated in this study. Nine of the 24 subjects had no habit of tongue brushing (Group 1, n = 9). Fifteen subjects had a habit of tongue brushing, and the brushing regions of the tongue were as follows: central region (Group 2, n = 7), or entire region (Group 3, n = 8) of the tongue dorsum. Using confocal laser scanning microscopy, the average number of taste buds per fungiform papilla (FP) was counted. Taste perception was evaluated using an FPDM. These observations were performed in the midlateral region of the tongue since the distribution of fungiform papillae is large in the midlateral region compared to that in the central region. Results The subjects in Group 3 showed a significantly decreased number of fungiform taste buds compared to Group 1 and Group 2. Group 3 also showed significantly higher FPDM scores than the other two groups. Conclusions Excessive tongue brushing of the entire tongue dorsum, including the midlateral region, may have an association with the decreased number of FP and taste buds and decreased taste sensation. To avoid these conditions, instituting proper tongue brushing methods, such as limiting it to the central region of the tongue and using a light touch, is suggested and is important for the subjects who are eager to participate in tongue brushing.