Most dietary assessment methods are limited by self-report biases, how long they take for participants to complete, and cost of time for dietitians to extract content. Electronically recorded, supermarket-obtained transactions are an objective measure of food purchases, with reduced bias and improved timeliness and scale.The use, breadth, context, and utility of electronic purchase records for dietary research is assessed and discussed in this systematic review.Four electronic databases  were searched. Included studies used electronically recorded supermarket transactions to investigate the diet of healthy, free-living adults.Searches identified 3422 articles, of which 145 full texts were retrieved and 72 met inclusion criteria. Study quality was assessed using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.Purchase records were used in observational studies, policy evaluations, and experimental designs. Nutrition outcomes included dietary patterns, nutrients, and food category sales. Transactions were linked to nutrient data from retailers, commercial data sources, and national food composition databases.Electronic sales data have the potential to transform dietary assessment and worldwide understanding of dietary behavior. Validation studies are warranted to understand limits to agreement and extrapolation to individual-level diets.PROSPERO registration no. CRD42018103470 Population dietary surveillance is important for understanding temporal changes and variation between subgroups. The data contribute to the epidemiologic understanding of diet-related diseases,,,,Supermarkets dominate as the source of household food supplies in high-income countries. Thus, supermarket purchase records may offer insight into diets in high- and middle-income settings. Early work using paper cash-register receipts highlighted the feasibility of supermarket purchase data to contribute to population dietary surveillance.A previous review of both paper-based and electronically captured transaction records suggested that supermarket data could contribute to dietary research in 7 key areas; 1) dietary patterns, 2) longitudinal analysis, 3) nutrient availability, 4) validation of self-report, 5) identifying predictors of healthy food choices, 6) evaluating intervention effectiveness, and 7) exploring associations between diet and health outcomes.Similarly, Bandy et al,For this review, we synthesized information from existing studies to understand the utility of electronically captured supermarket purchase records in dietary research and offer a clearer understanding of benefits of these data as well as the methodological challenges faced. This understanding will facilitate methodological innovation in dietary assessment, in turn contributing to a better understanding of dietary behaviors worldwide. Thus, we used a narrative approach to address the following questions in this review:What types of studies use supermarket electronic-transaction records to assess diet-related behaviors in adults?Are supermarket transaction data a valid dietary assessment measure?What sources of nutrient data did the studies use?What nutritional outcomes did the studies report?This review is reported in line with guidance of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) . An example search strategy can be found in Studies of any design using electronically captured supermarket sales data to assess dietary outcomes (any measure) were included in this review. Studies using paper cash-register receipts or purchase data from market-research panels were excluded. Studies measuring non-nutritional aspects of diet  also were excluded. Purchase data had to have been captured at the individual or household level in the general, healthy, free-living population and studies exclusively capturing purchases made by children < 18 years were excluded. Dietary outcomes for inclusion were quantity of sales at a product or category level (expressed as expenditure or volume), purchased macro- and micronutrients, and dietary patterns. The full eligibility criteria are described in The 2 reviewers (V.L.J. and F.P.) piloted a data extraction form, which was adapted from the Cochrane Public Health Group Data Extraction and Assessment Template,The National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional StudiesGuidance on Narrative Synthesis in Systematic Reviews by the Economic and Social Research Council Methods Programme was followed.Because of the variability in study outcomes and methodologies, it was not possible to quantitatively synthesize the study data. Instead, a systematic narrative synthesis approach was used to explore findings and methods thematically, in line with the proposed research questions. The report As the PRISMA flow chart in n = 72 articles) to monitor dietary outcomes across 14 high-income countries between 1996 and 2019  were assessed as being of fair quality , including: financial incentives or penalties , community behavioral-change interventions , or environmental nudges ,such as changes to the in-store architecture   . Twelve 15; 21%) . Just 2 15; 21%) .Intervention studies were typically short term. Consequently, the majority of studies used no more than 12 months of transaction data . A few s,Transaction data provided evidence for success of in-store choice-architecture interventions,,,Electronic point-of-sale systems generate high-volume transaction data with a fine temporal granularity. Continuous transaction data revealed how dietary patterns change over time, including monthly trends in relation to payment in low-income groups,,,,,,,Two studies (3%) aggregated supermarket purchase data to the country level for observation of national market trendsIn 3 studies (4%), researchers disaggregated purchases to the transaction level. This increased data volume permitting novel data-driven approaches to hypothesis generation, even without linkage to individual customers. For example, unsupervised machine learning (k-means clustering) revealed differences in dietary quality by type of alcohol purchased.In total, 42 articles (58%), authors reported used loyalty card records to link transactions at the customer level via a unique customer identifier. Cohorts of loyalty card customers can be tracked over time, increasing confidence in observed temporal patterns and intervention effectiveness. Customer cohorts enable understanding of behavioral mechanisms and reveal within-population dietary differences and intervention responsiveness. For example, the link among socioeconomic factors, intervention effectiveness,n = 23; 32%), which enabled researchers to capture sensitive information, such as body mass index,,,,,In general, customer demographics were poorly described. More than half of articles did not report the socioeconomic status of participants . Of thos,,In the absence of customer demographic information, area-level proxies, based on store location., were used in 13 studies. For example, area geodemographics ,,,,Other socioeconomic proxies included store type (regular or discount),,,,Four studies (6%) used additional self-reported household purchase data. The findings suggested that among loyal customers, supermarkets may account for between 63% and 67% of total household food expenditure.One study (1%) compared purchase records with national expenditure surveys.,,,Additional data on self-reported individual dietary intake were collected in 17 studies (24%). None of the studies included in the present review attempted to extrapolate absolute dietary estimates from household purchases to the individual level. Instead, dietary estimates from purchase records were represented proportionally, such as percentage contribution to total energy or expenditure.t tests.,,,One study (1%) directly compared household purchase estimates with individual self-reported consumption, using Spearman correlation coefficients and paired Comparison with national dietary-intake surveys also revealed differences in agreement within the population, with a poorer association observed for children’s diets.n = 10 papers; 14%)  did not link transactions to any source of nutrient information . Four pars; 14%) , creatin,,The source of nutrient information influences the degree of error incorporated into dietary estimates at the nutrient level. National FCDBs are used to code dietary survey responses, because they contain detailed nutrient information for commonly consumed generic foods. Yet, matching to transaction records results in reduced dimensionality from several thousand retail products to just a couple of thousand generic foods and a loss of product-specific detail.,,,However, matching transaction data to FCDBs is challenging. Because of the large number and high turnover of retail products, there have been attempts to develop automated, scalable and repeatable FCDB-matching approaches. Although near-perfect matches for standard food groups may be possible, in the absence of commonly used product identifiers, there are barriers to mapping to detailed nutrient content.,,,Alternatively, nutrient data may be mapped at the category or subcategory level,,,,,,,,,,,,Where BOP nutrient information is available from the retailer, automated linkage to the transaction record may be achieved via the unique product code.,,,,n = 3),,,Nutrient-level analyses,,,,,,,,,,,,,,Because of challenges of data availability and linkage with nutrient data, most studies conducted analysis at the food category or subcategory level.,,,,,,The study of dietary patterns involves classifying customers into groups on the basis of their purchasing habits. Groups may be defined a priori on the basis of the purchase of a product of interest, in a deterministic approach. For example, Johansen et al,Alternatively, dietary patterns may be explored nondeterministically through unsupervised machine-learning algorithms. Hansel et alThe 2017 Review of Nutrition and Human Health ResearchThere is no gold standard method of dietary assessment that can answer all diet-related questions. The breadth of questions posed by the field of nutrition research, therefore, requires a suite of innovative methods to supplement existing approaches. This necessitates the harnessing of technology and secondary data sources, where they are available. Just as biomarkers complement surveys with an objective measure of nutrients within the body, supermarket transaction records provide a complementary objective measure of food purchases.,,,In this review, we found that supermarket electronic purchase records can be useful for longitudinal dietary surveillance,Large customer samples and passive data collection may improve representation of hard-to-reach groups. This was demonstrated by good diffusion across income groups within a single-retailer sample in the United Kingdom,Limitations of supermarket electronic transaction data are partial coverage of total food purchased or otherwise obtained, unknown distribution of food within households, and inability to account for food wasted or food consumed by visitors.,Statistical agreementBecause no studies in this review attempted to adjust household purchases to the individual level, it is unclear how well household purchases represent the diet of individuals within a household. Modelling individual diet from household purchases would require several assumptions and necessitate further study.There has been increasing recognition of the importance of engaging with the food industry to translate research insights into action. Effective research-industry partnerships, therefore, are vital, as explained by the guidance framework proposed by Birkin et al.,,New approaches to transparency and customer consent are warranted to enable greater utility of customer-level data. Efforts are needed to overcome issues of poor data quality,Another obstacle for the future of the method is the lack of centralized and up-to-date, product-level FCDBs, which may be linked to automatically.myfood24.Solutions could include the linkage of product data to close-matching generic foods in national FCDBs, which contain detailed micronutrient compositions, as performed by the dietary assessment app This review highlights 5 priority areas for research into the use of supermarket sales data for population dietary surveillance: 1) validation against established self-report methods and nutritional biomarkers; 2) extrapolation of household purchases to the individual level; 3) triangulation with other data sources; 4) exploration of spatial dietary patterns; and 5) development of suitable nutrient data sets for linkage.Our findings from this review suggest electronic purchase records have broad applicability for dietary surveillance, policy evaluation, and intervention research studies in high- and middle-income countries. The scale, temporality, and geocoded nature of electronic purchase records are notable advantages. However, there is a need for additional methodological assessment of utility; validation against self-reported dietary intake measures and nutritional biomarkers; required data volumes; extrapolation to the individual level; exploration of spatial dietary patterns; and assessment of generalizability. The potential for automated dietary coding is currently hindered by the availability of regularly updated, open product data. Web-scraping methods may address this need. However, this lack limits coverage to key BOP nutrients, which exclude micronutrients (with the exception of sodium). Product data alone account only for dietary availability; linkage with sales data is crucial for behavioral research.nuab089_Supplementary_DataClick here for additional data file.


Lactobacillus spp. during production of indigenous foods and beverages, the potential health benefit of probiotics, and the impact of these food-grade microorganisms on food safety and prolonged shelf life are discussed. During production of African indigenous foods , fermentation occurs in succession; the first group of microorganisms to colonize the fermenting substrates are lactic acid bacteria (LAB) with the diversity and dominance of Lactobacillus spp. The Lactobacillus spp. multiply rapidly in the fermentation matrix, by taking up nutrients from the surrounding environments, and cause rapid acidification in the fermenting system via the production of organic compounds that convert fermentable sugars into mainly lactic acid. Production of these compounds in food systems inhibits spoilage microorganisms, which has a direct effect on food quality and safety. The knowledge of microbial interaction and succession during food fermentation will assist the food industry in producing functional foods and beverages with improved nutritional profiling and technological attributes, as Lactobacillus strains isolated during fermentation of several African indigenous foods have demonstrated desirable characteristics that make them safe for use as probiotic microorganisms and even as a starter culture in small- and large-scale/industrial food production processes.The benefits derived from fermented foods and beverages have placed great value on their acceptability worldwide. Food fermentation technologies have been employed for thousands of years and are considered essential processes for the production and preservation of foods, with the critical roles played by the autochthonous fermenting food-grade microorganisms in ensuring food security and safety, increased shelf life, and enhanced livelihoods of many people in Africa, particularly the marginalized and vulnerable groups. Many indigenous fermented foods and beverages of Africa are of plant origin. In this review, the predominance, fermentative activities, and biopreservative role of  Bacillus spp., acetic acid bacteria, and molds have been reportedly isolated during production of some other fermented foods: legumes, wine, etc.  has been carried out for several decades. In the last 2–3 decades, with increasing research and development, discoveries in the use of industrial-scale technology are preferred, i.e., inoculation of “defined starter culture”  in controlled fermentation processes; the latter is becoming a necessary under-regulated process to increase automated production, leading to improved and consistent fermented food quality for commercial purposes.In Africa, production of several foods consumed by the populace relies on the fermentation processes; food security and shelf life are improved because of the biopreservative role played by the autochthonous microorganisms, which is advantageous to the community where there is poor access to electricity and refrigerating systems . FermentSeveral advantages of these fermented food products have been reviewed by various researchers , includi•Production of safe food products.•Reduction in cooking time.•Production of foods with extended shelf life.•Improvement of the organoleptic properties of fermented food products/enhancement of food sensorial characteristics.•Increases mineral and trace element bioavailability in food/enrichment of food nutritional contents and digestibility.•Elimination of cyanide compounds in cassava tubers and other harmful substances that may be present in cereals.•Prevention of diseases or infections such as diarrhea and salmonellosis.Lactobacillus microbiota during the production of African indigenous foods and the industrial importance of their interactions in cereal-based and cassava-based fermentation, their application in optimized or controlled food fermentation over mixed culture/uncontrolled fermentation, and the impact of Lactobacillus species co-occurrence in the fermenting food matrix on product development and safety.The population dynamics of microbes during fermentation using phenotypic and culture-dependent techniques have resulted in the understanding of different important roles that exist in the microbial consortia . The invLactobacillaceae  status; these characteristics displayed by LAB affect the storage quality, thereby extending the shelf life and safety of many fermented foods and beverages  are grouped under the same genus, Lactobacillus spp., with desirable probiotic attributes, and are now renamed, including the following: Lactobacillus casei (renamed as Lacticaseibacillus casei), Lactobacillus paracasei (renamed as Lacticaseibacillus paracasei), Lactobacillus rhamnosus (renamed as Lacticaseibacillus rhamnosus), Lactobacillus plantarum (renamed as Lactiplantibacillus plantarum), Lactobacillus brevis (renamed as Levilactobacillus brevis), Lactobacillus salivarius , Lactobacillus fermentum (renamed as Limosilactobacillus fermentum), and Lactobacillus reuteri (renamed as Limosilactobacillus reuteri) , Paralactobacillus, and 23 other novel genera. Lactobacilli are predominant organisms involved in the fermentation of cereal-based foods and beverages in Africa. During lactic acid fermentation, LAB at the initial stage of fermentation improve the flavor, shelf life, nutritional values, and digestibility of fermented foods. The predominance and the involvement of Lactobacilli especially [L. plantarum (Lactiplantibacillus plantarum) and L. fermentum (Limosilactobacillus fermentum)] during food fermentation have been reported by several researchers  and can also produce a wide range of metabolites . Lactic illaceae . These geverages . The mosobiotics  reportedreuteri) . Zheng eearchers .Lactobacillus species are widely applied in food production and are known for their fermentative ability, health, and nutritional benefits. The role of LAB in the safety and quality of fermented foods around the globe has been reviewed by several researchers .earchers . Strainsompounds . In AfriLactobacilli during indigenous food fermentation is commonly associated with cereal-based and cassava-based foods; these substrates are processed into different types of foods and beverages. Most of the fermented cereal-based foods are consumed as complementary infant food and as cereal beverages in adults, while the fermented cassava-based foods are consumed as main course meals. Different fermented foods from cereals and cassava tubers include mawé (Beninese fermented sour dough); gowé ; tchoukoutou (Beninese home-brewed beer from sorghum); ben-saalga ; dolo (Burkinabé fermented sorghum beer); Bikédi (Congolese fermented cassava tubers); poto poto (Congolese fermented maize dough); cingwada (East African retted cassava); kisk ; Bikédi, foufou, chikwangue, mbalampinda, tutu, tsaba, minsela, and tsiya borde (Ethiopian fermented beverages); injera (Ethiopian sour fermented flatbread); kocho (Ethiopian fermented bread); koko and koko sour water (Ghanaian fermented millet porridge and drink); agbelima and kenkey (Ghanaian fermented cassava-based food); kisra dégué ; wômi, baca, and doklu ; attiéké, placali, and attoupkou (Ivorian fermented cassava-based foods); uji (Kenyan millet-based fermented porridge); ogi ; gari, fufu, and lafun (Nigerian fermented retted cassava); pito and kunun zaki ; ikigage (Rwandan fermented sorghum beer); hussuwa (Sudanese fermented sorghum food); (Sudanese fermented sorghum bread); mbege, togwa, and kivunde (Tanzanian retted cassava); komé ; koko and bushera ; and mahewu   . Severalkoko and koko sour water), with L. fermentum as the predominant organisms. doklu (Ivorian maize dough). It was reported that after 24 h of fermentation, the percentage occurrence of L. plantarum was 64%, which was the highest, followed by other LAB: Weissella cibaria (22%), Pediococcus acidilactici (7%), and L. fermentum (7%); at 48 h fermentation time, L. plantarum spp. still predominate, having 56% of occurrence, and at the end of fermentation, the percentage of occurrence of L. fermentum was 100%. The predominance of LAB species especially L. plantarum in Nigeria traditional fermented foods and beverages is well documented  during fermentation of Dégué .Lactic acid bacteria have been reportedly isolated at different fermentation stages, and researchers have recommended that the quality of the final food products is dependent on the microbial diversity, dynamics, and frequency of occurrence of these LAB species. Lactobacilli constitute an important group of LAB, and the industrial importance of this Lactobacillus spp. cannot be overemphasized; they are commonly recommended as a starter culture for controlled fermentation of African indigenous fermented foods , and these sugars possess antioxidant properties that can be used as a substrate during Lactobacillus metabolism in cereal fermentation to produce vitamin-enriched foods and in combating nutritional deficiency in many African fermented cereal-based foods. During cereal-based fermentation, the dominance of Lactobacilli and other LAB with extracellular amylase production has resulted in the provision of metabolizable starch via hydrolysis and can be utilized for industrial fermentation processes, because of its acid production, which simultaneously improves the preservation and safety of fermented foods.The use of a carefully selected functional starter culture with added nutritional benefits during microbial fermentation will enhance the production of fermented foods with improved quality . The tecLactobacillus spp. in catalyzing the hydrolysis of amylose and amylopectin to yield fermentable maltose makes each strain desirable, important, and useful as a starter culture. In traditional food fermentation, using amylolytic lactic acid bacteria as a starter culture offers an advantage by combining both amylase production and acidification properties in a single strain. The raw starch binding ability of the α-amylase producing gene (amyA) of L. plantarum A6 (amylolytic strain isolated from retted cassava) with an unusual structure of the 3′ end of the α-amylase gene and the ability to break down raw starch has been successfully cloned and sequenced  and the potential of using these LAB strains for industrial processing of West African cereal-based foods and beverages, due to the probiotic function, amylase enzyme, and bacteriocin-producing ability exhibited by the strains  isolated from naturally fermented foods in Nigeria for effective control of spoilage and pathogenic microorganisms; the strains showed a broad range of activities and had a significant effect on the selected pathogenic microorganisms. Lactobacillus strain as a food preservative agent. The antifungal activity of L. fermentum YML014 isolated from cassava-based fermented foods against food spoilage molds using tomato puree was investigated by Lactobacillus fermentum YML104 showed strong antifungal activity against Aspergillus niger, Aspergillus flavus, and Penicillium expansum, and thus caused an increase in the shelf life of the tomato puree.Bacteriocins can be used as “biologically derived” preservatives; thus, food shelf life can be extended, and pathogenic organisms are inhibited without altering the product’s nutritional quality . Lactic in vivo . Many LaLactobacillus reuteri against protozoa and fungi. Other inhibitory compounds such as organic acids, bacteriocins, and antifungal peptides produced by L. plantarum have been reportedly isolated from silage (Lactobacillus species during the production of poto poto (Congolese fermented maize product) using species-specific PCR and 16S rRNA gene sequencing; 31 strains were identified as bacteriocin producers, and the bacteriocins produced by these LAB strains, L. plantarum (28) and L. fermentum (3), were identified as plantaricin and were found to display a broad spectrum of inhibition against the following pathogens: Escherichia coli, Salmonella enterica, Enterobacter aerogenes, Bacillus cereus, Staphylococcus aureus, Listeria monocytogenes, and Enterococcus faecalis. Lactobacillus spp. (L. plantarum F1 and L. brevis OG1) isolated from Nigerian fermented foods were reported to produce bacteriocins, which have a broad spectrum of inhibition against pathogenic and spoilage organisms; the Lactobacillus strains exhibited activities of 6,400 and 3,200 AU/ml, respectively, against Escherichia coli NCTC10418 and Enterococcus faecalis EF1, but did not inhibit Candida albicans ATCC10231 and Klebsiella sp. UCH15  produced bacteriocins that were able to inhibit both Gram-positive and Gram-negative bacteria, including species of the genera Lactobacillus, Streptococcus, Bacillus, Salmonella, Shigella, Pseudomonas, and Klebsiella and multidrug-resistant strains of the pathogens E. coli and S. aureus . It was observed that 12 strains out of the 21 LAB species were reported to display inhibitory substances to proteolytic enzymes (Trypsin and Proteinase K) and the bacteriocins produced showed broad inhibitory activity against pathogenic microbes.In another study, one . aureus . During Lactobacillus produces antimicrobial ribosomally synthesized peptides, or “bacteriocins.” The LAB-producing bacteriocin has been reported to possess biopreservative characteristics, which makes them ideal food biopreservatives; some of these characteristics include the bacteriocin proteinaceous nature, in vivo non-toxicity and non-immunogenicity, inactivity against eukaryotic cells, thermoresistance against heat treatment, and broadened bactericidal activity  by the Russian scientist and Nobel Prize winner Elie Metchnikoff while working in Bulgaria; he hypothesized that the longevity of the Bulgarian centenarians was a result of the improved health benefits conferred upon daily intake of fermented yogurt containing Lactobacillus bulgaricus  among diarrhea patients . The koko and koko sour water millet porridge and drink were reported to contain an abundance of viable LAB, which are responsible for the beneficial effect conferred when these beverages are consumed. A similar report was obtained among Tanzanian children that were fed with togwa   . A largeLactobacillus have been reported to have the ability to adhere to intestinal cells via coaggregation to form normal balanced flora and also produce compounds such as organic acids, hydrogen peroxides, and bacteriocins that are inhibitory to pathogenic organisms  by Lactobacillus spp. and the spectrum of antibacterial activity displayed by these species can find their wide applications in the food industry. As applications of Lactobacillus are enormous and wide usage as a probiotic and/or as a starter culture due to their ability to improve the product’s nutritional and technological features cannot be neglected, this LAB group occupies a central role during the fermentation process and significantly possesses many benefits as discussed in this review, with long and safe usage in the food industry. Lactobacillus species (those associated with African fermented foods) are described as key players during fermentation technology and have been reportedly involved in the enhancement of flavor, texture, and improved rheology with health-promoting characteristics, which can be applied in the production of functional foods, thus conferring beneficial attributes and consistency in food quality and thereby making the African food market/industry attractive. However, the use of appropriate metagenomic tools that will provide insights into the gene, structure, and functions of microbial strains with multi-functional properties during controlled fermentation will guarantee product quality and consistency, which will be accessible to all. In developing products with improved quality and safety, the inclusion of technologically relevant microorganisms (such as Lactobacillus strains) is crucial and will serve as sustainable interventions for the development of African-specific starter cultures. Development of starter culture technology for both small-scale and industrial-scale food production will lead to products of greater consistency, safe quality, and global acceptance, and all these should be the focus of African researchers and scientists. It can be observed that despite the rich diversity of food-grade microorganisms present in many African indigenous fermented foods, most of the well-defined starter cultures available in the shops and markets are not manufactured in Africa; therefore, there is a need to produce well-defined and well-characterized microbial cultures from autochthonous microorganisms peculiar to African foods.In Africa, the biotechnological application, development of bioreactor technology, and the use of a starter culture for food fermentation processes should be prioritized through technical skills training, provision of infrastructures, and government willingness in funding research in the area of upgrading fermentation processes and fortification of these foods with bio-enriched vitamins. Also, synergism among research institutes, universities, and manufacturing sectors will play a major role in bringing starter culture development and usage to the limelight in the food industry; this will guarantee consistent and safe food with improved shelf life. Several foods produced in Africa are fermented before consumption, and it is highly recommended that among the household food producers, good manufacturing practices should be effectuated from the point of collection of the raw materials/substrates because of the risks that are associated with improperly/unhygienically produced foods during the production of the final food products. The use of safe water should also be emphasized throughout the production/fermentation process; food should not be manufactured under poor hygienic conditions, and all these can be achieved by properly educating the food producers. The activities of fermentative LAB and most especially AA-D: conceptualization and writing—original draft preparation. TA: writing part of the primary draft. AA-D and SD: technical editing of the manuscript and reviewing the manuscript for submission. All authors have read and agreed to the published version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Hematopoietic homeostasis depends on the close regulation of hematopoietic stem cell (HSC) activity in the bone marrow. Quiescence and activation in response to stress, among other changes in state, are mediated by shifts in HSC metabolic activity. Although HSC steady-state metabolism is well established, the mechanisms driving HSC activation, proliferation, and differentiation in response to stress remain poorly understood. Here we discuss a study by Mistry et al. that describes a novel metabolic mechanism that fuels HSC activation and expansion. The authors show that to meet their metabolic needs in response to infection, hematopoietic stem and progenitor cells uptake free fatty acids from their microenvironment via CD36 to fuel fatty acid oxidation. These exciting findings suggest that in the context of infection, HSCs undergo a metabolic shift toward fatty acid metabolism that drives emergency hematopoiesis and raise questions about the role of the microenvironment in this process. The life-long production of blood depends on the ability of hematopoietic stem cells (HSCs) to self-renew, differentiate, and form all hematopoietic lineages. HSCs rely upon precisely controlled interactions with their local microenvironment in the bone marrow (or “niche”) to preserve quiescence and maintain normal blood output . These iCellular metabolism has emerged as a critical regulator of HSC homeostasis, dysregulation of which can trigger changes in HSC cell cycle dynamics, leading to functional decline . Quiesce(Ppard) results in disrupted HSC asymmetric division, which leads to symmetric commitment of daughter cells, exhaustion, and poor repopulation capacity [Fatty acid metabolism has emerged as a critical regulator of HSC self-renewal. Deletion of the fatty acid transport and oxidation regulator Peroxisome-proliferator activated receptor delta capacity ,11. The capacity  strengthcapacity . Furthercapacity . These scapacity . As the capacity –18. HoweS. typhimurium) or its outer membrane lipopolysaccharide (LPS), which led to rapid HSC and leukocyte expansion and elevation of free fatty acids (FFA) in the serum. Using a novel model to quantify fatty-acid uptake by hematopoietic cells, the authors revealed that challenging mice with either S. typhimurium or LPS triggered rapid uptake of FFA by hematopoietic stem and progenitor cells (HSPCs), and subsequent experiments confirmed that bacterial infection enhanced FAO in these activated HSPCs. Moreover, pharmacological inhibition of β-oxidation using etomoxir suppressed the expansion and proliferation of HSPCs in vivo. These findings establish that enhanced FAO induces metabolic remodeling that enables HSPCs to transition from steady-state to emergency hematopoiesis to combat infection. Fatty acid metabolism is thus a key mechanism supporting stem cell activation in response to infection-mediated physiological stress; however, it has yet to be determined whether this holds true for malignancies or stem cells in other tissues.In a recent study by Mistry et al. published in Nature Communications , the autBiorender.com.Schematic overview of the role of fatty acid metabolism and adipocytes in the maintenance of HSCs. Quiescent HSCs are kept in a low metabolic state and utilize glycolysis for energy production. HSC self-renewal and asymmetric division depend on FAO, mediated by PPARδ and PPARγ. To maintain homeostasis, bone marrow adipocytes negatively regulate HSC activity (orange box and arrows). Adipocyte-derived SCF has been shown to facilitate hematopoietic recovery following genotoxic stress, however, the role of FAO in hematopoietic regeneration is unknown (green box and arrows). Based on findings by Mistry et al. , bacteri−/− mice) results in reduced FFA uptake, lipid content, basal and maximal respiration, and HSPC proliferation. Moreover, specific deletion of CD36 in hematopoietic cells revealed an intrinsic role for FAO in inducing the metabolic switch needed to sustain activation and subsequent proliferation of HSCs.To further understand the mechanisms that facilitate FAO in HSCs, the authors quantified the transcript and protein levels of known lipid transporter proteins and identified that the fatty-acid translocase CD36 was consistently upregulated in response to infection. As CD36 facilitates fatty-acid uptake and oxidation –22, thesIn summary, Mistry et al. report a new mechanism of emergency hematopoiesis and highlight FAO as a central metabolic pathway fueling HSPC expansion in response to infection. These findings shed light on the role of lipid metabolism in stem cell maintenance and raise new questions about the role of the microenvironment in this process. What is the source of FFA? The present study does not address how infection reshapes the bone marrow microenvironment to accommodate the availability of FFA, nor does it explore the bone marrow AT as a source for circulating FFA. Furthermore, exploring how induction of FAO in HSCs relates to other stress conditions and pathologies associated with enhanced adipogenesis would be of great interest. For example, in both aging and obesity, there is an increase in bone marrow adipogenesis, which is accompanied by poor HSC maintenance ,24. Aged


Stem cells provided new opportunity to treat various diseases, including liver disorders. Stem cells are unspecialized cells, stimulating influential research interest be indebted to their multipotent self-renewal capacity and differentiation characteristics into several specialized cell types. Many factors contribute to their differentiation into different cell types such as insulin producing cells, osteoblast, and hepatocytes. Accordingly, wide range methods and materials have been used to transform stem cells into hepatocytes, but effectiveness of differentiation is different and depends on several factors such as cell-to-cell adhesion, cell-to-cell contact, and cell biological change. Search was done in PubMed, Scopus, and WOS to evaluate results of studies about stem cells differentiation for higher efficacy. Among more than 28000 papers, 51 studies were considered eligible for more evaluations. Results indicated that most studies were performed on mesenchymal stem cells compared with other types. Acute liver failure was the most investigated liver disorder, and tissue engineering was the most investigated differentiation methods. Also, functional parameters were the most evaluated parameters in assessing differentiation efficacy. We summarize recent advances in increasing efficiency of stem cells differentiation using varied materials, since promising results of this review, further studies are needed to assess efficiency and safety of these cells transplantation in some liver disease treatment. There are several treatment options to cure liver diseases and among them, hepatocyte transplantation therapy is an optional cure to replace dysfunctional hepatocytes in order to significantly restore liver diseases. Still, its clinical use is limited by the lack of donor tissue. Therefore, researchers are motivated to find other treatments; in vitro differentiation of different source of stem cells (SCs) into hepatocytes or in vivo generating mature liver cells from SCs could solve this limitation . SCs areLiver disorders include a wide range of both acute and chronic conditions, which are linked with remarkably morbidity and mortality across and differentiation into several specialized cell types. In vitro condition, several factors such as extracellular matrix (ECM) proteins, cell-to-cell adhesion, cell-to-cell contact, and soluble factors may affect their differentiation into specialized cell types, and play an important role in regulating the fate of stem cells . AccordiThis review was conducted in accordance with the PRISMA statement to address the following question: “Which intervention has the greatest effect on the differentiation efficacy of SCs into functional hepatocytes?”Two researchers performed a comprehensive search in the PubMed and Scopus databases in June 2020. The search encompassed all types of articles using the terms included (liver cell [Title/Abstract]) OR hepatocyte [Title/Abstract]) AND (Stem Cell [Title/Abstract] OR Progenitor Cells [Title/Abstract]) OR Mother Cell [Title/Abstract]) OR Colony-Forming Unit [Title/Abstract]). Two researchers independently removed duplicates by hand screening. Inclusion criteria were the English language publications, focusing on the in vitro and animal model studies. Two researchers independently assessed all the articles by screening the title and abstracts, if necessary, the full texts were reviewed. The review articles or the SC therapy studies for diseases other than liver disorders were excluded. No data limitation regarding animal, age group, and cell type imposed. Two researchers independently inspected full texts of the potentially eligible articles. Data were collected from the full-text articles as follows: (i) the source of SCs, (ii) type of the study (in vitro or in vivo), (iii) methods used for the evaluation of SCs differentiation efficacy, and (iv) the obtained results. Efficiencies of stem cells differentiation toward functional hepatocytes were systematically reviewed and retrieved data, as the study authors had originally reported without using any specific or additional analyses were included in the manuscript. The searches were repeated in October 2022 to identify any new reports that emerged during the time to develop the manuscript and two new related articles were found and added.A total of 28312 articles were initially identified; after deleting duplications (5334 articles) by two authors using hand-screening. Among remained 22978 papers, 3714 papers were reviewed and excluded .Among remained original articles (19264), 19213 were excluded due to unrelated with efficacy. By studying these articles, only 51 articles included the results of efficiency of stem cells differentiation toward functional hepatocytes.By studying these article abstracts, only 40 articles included the results of the SC differentiation efficacy assay in vitro conditions , and 22 Results revealed that the investigated SC cells have different sources. The SCs derived from the embryo (ESCs) were used in ten studies. Mesenchymal stem cells from various sources were employed in twenty-three studies, including bone marrow mesenchymal stem cells (BM-MSCs) in ten studies, whereas four studies investigated adipose tissue-derived mesenchymal stem cells (ADMSCs), two papers examined umbilical cord-derived mesenchymal stem cells (UCMSCs), one study investigated WJMSCs, nine articles discussed liver mesenchymal stem cells, and just two studies used hematopoietic stem cells (HSCs). Induced pluripotent stem cells (iPSCs) were used in eight studies; only one study examined the mensural stem cells and one study investigated testis-derived stem cells. By all these source variation, only five other methods were used, and these different methods had important effects on the SCs differentiation efficacy. In the following section, these studies are discussed according to the used method.Application and research of different differentiation methods.Tissue engineering strategies based on the cocultivation of SCs with different cells, growth, and soluble factors , on the (1) Use of Coculture Method. Regarding this method, different materials were used in eight studies to increase the differentiation of SCs into hepatocytes. Carraro et al. cultured human liver stem cells (HLSCs) with hepatic stellate cells, and after seven days, this in vitro condition promoted the functional differentiation of HLSCs into mature hepatocytes  SCs were transplanted to patient or animals and exhibited liver regeneration, also, their liver function improved.In summary, the results obtained from this systematic review provide better understanding about the efficacy of SC differentiation into hepatocytes for treating liver disorders. The obtained results showed that the hepatocytes derived from SCs by using tissue engineering and imitating in vivo microenvironment showed a better efficacy than the other methods of differentiation to restore liver regeneration and function. However, the obtained results indicate that more evaluation is needed about the efficacy of SC differentiation into hepatocytes for the treatment of liver disorders.


The challenges of childhood uveitis lie in the varied spectrum of its clinical presentation, the often asymptomatic nature of disease, and the evolving nature of the phenotype alongside normal physiological development. These issues can lead to delayed diagnosis which can cause significant morbidity and severe visual impairment. The most common ocular complications include cataracts, band keratopathy, glaucoma, and macular oedema, and the various associated systemic disorders can also result in extra-ophthalmic morbidity. Pediatricians have an important role to play. Their awareness of the various presentations and etiologies of uveitis in children afford the opportunity of prompt diagnosis before complications arise. Juvenile Idiopathic Arthritis (JIA) is one of the most common associated disorders seen in childhood uveitis, but there is a need to recognize other causes. In this review, different causes of uveitis are explored, including infections, autoimmune and autoinflammatory disease. As treatment is often informed by etiology, pediatricians can ensure early ophthalmological referral for children with inflammatory disease at risk of uveitis and can support management decisions for children with uveitis and possible underling multi-system inflammatory disease, thus reducing the risk of the development of irreversible sequelae. Pediatric uveitis is rare condition, which accounts for 5–10% of all-age uveitis .Diagnosis of pediatric uveitis can be challenging due to insidious  presentation, lack of symptom reporting in early childhood, and difficulties in examining young children. Pediatric uveitis is also characterized by frequent complications and comorbidities such as cataract, glaucoma or amblyopia .The focus of this review is the role of the pediatrician in all stages, including recognition of the signs or symptoms (or lack thereof) of uveitis in the child at risk due to their rheumatological condition; advising on possible etiology; and co-managing systemic therapy in the child with uveitis and systemic disorders.The parts of the normal globe (anterior to posterior) are the cornea, anterior chamber, iris (anterior segment), lens, ciliary body, vitreous humor (intermediate structures), retina, choroid, and sclera (posterior segment). Uveitis can be described using this anatomy: anterior uveitis refers to inflammation of focused on anterior chamber; intermediate uveitis involves the vitreous cavity; posterior uveitis affects the retina and choroid; and panuveitis is characterized by the involvement of all layers of the eye  4)..4).The most common causes of red eye in childhood are ocular surface conditions such viral, bacterial or allergic conjunctivitis, but other causes include ocular inflammatory conditions such as uveitis or inflammation of the sclera, scleritis. It is useful for the pediatrician to understand the “red flags” which warrant timely referral to the ophthalmologist. These comprise photophobia (adverse response to light stimulation) or significant pain, disturbed or reduced vision, and pupil or other structural abnormalities . It shouUveitis is a descriptive term rather than a diagnosis and may have an infective or non-infective cause. In the following section, we describe the infective causes of uveitis. Note that since there is limited data published on pediatric infective uveitis, some references have been taken from the adult literature.Infectious uveitis should be excluded as the cause for childhood uveitis (particularly panuveitis) as the treatment differs significantly from that for non-infectious disease. The details of infections known to cause or be associated with uveitis are mentioned in Globally, Toxoplasmosis is a common parasitic cause of infectious uveitis, and can be either a congenital or acquired infection (the latter being a less common presentation). Eye inflammation can resolve without any sequalae, but often leaves a chorioretinal scaring. In 70–80%, this occurs as a unilateral focal chorioretinal lesion. Reactivation may cause eye pain, blurred vision and can lead to permanent eye damage and blindness. Although serological or intraocular diagnosis is useful, the initial suspicion is based on a typical chorioretinal lesion on eye examination. These lesions can be multiple, solitary or a satellite to an old chorioretinal scar –12.Both herpes simplex and herpes zoster can cause keratouveitis. Unilateral eye disease is more common . The preBartonella henselae is the principal cause of cat-scratch disease. Although the presentation of ocular inflammation can vary, optic nerve inflammation and macular star (“neuroretinitis”) is characteristic, although the most common initial manifestation is a unilateral anterior uveitis. Exploration of a history of contacts with domestic pets is thus important in childhood uveitis , 25.Ocular TB represents an extrapulmonary form of the disease which may occur in isolation, with no other evidence of pulmonary infection or active disease at any other site in the body  16)..16).One of the distinguishing features of the TB infection is the development of granulomatous uveitis with the incidence and prevalence depending on the region and endemic nature. Features that should raise suspicion are a history of TB exposure, pyrexia of unknown origin, night sweats, lymphadenopathy, or an immunosuppressed child, and granulomatous forms of ocular inflammation. Bilateral presentation and posterior uveitis are the most reported phenotypes. The Collaborative Ocular Tuberculosis (COTS−1) study reported that chest computed tomography (CT) was three times more sensitive than X ray in identifying old, inactive TB . Early aSyphilis can manifest in various forms, including posterior uveitis  and papillitis. The frequency of this uveitis is <1% of all uveitis . HIV posEye manifestations occur in 1–4% of infected patients, and whilst early disease can have transient non-specific conjunctivitis, later stages can preset with uveitis, typically intermediate  Anteriorvia small capillaries, leading to an endophthalmitis with typical “fluff balls” or vitreous abscesses. Other eye findings in endophthalmitis are hypopyon, optic nerve involvement or vitreous abscesses  may be associated with different types of ocular inflammation caused by various opportunistic or pathogenic viruses, parasites, or bacteria. A retrospective study from Congo reported a prevalence of 14.3% of uveitis in HIV patients. CMV is another frequently associated infection in this group of patients, causing posterior uveitis or retinitis which are considered as one of the most severe ocular complications of HIV associated with severe morbidity , 54. TheA simplified flowchart regarding the differential diagnosis of uveitis based on its location and etiology is shown in Drug induced uveitis may be triggered by topical, systemic, or intraocular medications. It is important to take a detailed drug history in patients with unexplained uveitis . The onsTopical medications such as Brimonidine and Prostaglandin analogs and intraocular injections with Vancomycin, Triamcinolone acetonide or anti-vascular endothelial growth factor (anti VEGF) agents can cause uveitis. Common systemic drugs which may cause uveitis are Cidofovir, Rifabutin, Fluoroquinolones, bisphosphonates, immune checkpoint inhibitors, protein kinase inhibitors and sulfonamides. Mechanism may be toxic or immune mediated , 60.Cidofovir-induced uveitis occurs mostly post-intravitreal injections. Non-granulomatous anterior uveitis and hypotony are two most common findings. Chances of uveitis are higher in patients on protease inhibitors, who have been previously treated for CMV retinitis, have recurrent retinitis, or immune recovery . PatholoProtein kinase inhibitors have been linked to all types of uveitis and are responsive to topical steroids. Drug-induced Vogt-Koyanagi-Harada syndrome has also been described in association with the use of some protein kinase inhibitors .Antibiotic use and Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) may cause Tubulointerstitial nephritis and uveitis (TINU) which is an immune mediated hypersensitivity reaction. The importance of NSAID as a risk factor varies greatly between the studies but may be present in up to 60–70% of the cases .There is emerging awareness of a potential link between vaccines and uveitis onset. It is possible that this is not causative, and simply an ascertainment bias with associations only posited because of an incidental temporal association. Post-vaccine uveitis has been described as a mild course of anterior uveitis which are usually responsive to topical steroids. The most common associations are with the Hepatitis B vaccine, but also HPV vaccine, influenza vaccine, BCG, MMR, and varicella vaccine –70. ReceNon-infectious uveitis causes or associated disorders span a wide range of conditions, the most significant of which are discussed here.JIA-associated uveitis, with a pooled prevalence of 11.8% (95%CI: 11.2–12.4%) amongst JIA patients, is the most common extra-articular manifestation of disease. In comparison, the prevalence uveitis in pediatric SLE is <1% . UveitisThe seven subtypes of Juvenile idiopathic arthritis (JIA) can be divided into JIA with low risk of uveitis (systemic arthritis and other unclassified arthritis), moderate risk  and higher risk of uveitis  , 74. ChrChronic anterior uveitis is the most common form seen in JIA associated uveitis, and in most cases, JIA precedes the onset of uveitis. Children are often asymptomatic at onset and can develop irreversible complications by the time of eventual diagnosis. Complications at diagnosis are highly predictive of later permanent loss of vision, and this underpins the importance of early detection and treatment initiation for JIA-associated uveitis. In the UK and USA, commencement of regular eye examinations is generally recommended to start as soon as possible after JIA is suspected for those at moderate or high risk, and to continue every 4 months until the age of 11–12 years, with the other key time for surveillance being the first few months after stopping systemic JIA treatment.The risk of developing uveitis appears to be highest in young females with oligoarticular JIA who are ANA antibody positive. As well as differing risk, clinical characteristics differ between JIA subtypes. In sharp contrast to the “silent uveitis” classically seen in early onset oligoarticular JIA, uveitis onset and recurrences in ERA and JPsA JIA can be acutely symptomatic (the “painful red eye”) .Children with juvenile psoriatic arthritis  , 77 can Predictors of uveitis incidence in children with JIA include clinical subtype, as above, inflammatory markers, autoantibodies and genetic susceptibility. Several disease activity biomarkers are used routinely , but there are also emerging biomarkers which are still undergoing validation, including S100A12, S100A8/A9  and soluble IL-2 . The main genetic factor identified in JIA is MHC class II HLA-DRB1 that is involved in antigen presentation being a predictor of JIA or, in some cases, JIA associated uveitis .Sarcoidosis can affect almost any portion of the eye or surrounding tissue.Sarcoidosis associated uveitis can present as anterior, intermediate, posterior or panuveitis. Anterior uveitis may be asymptomatic or painful, but presentation may be with visual symptoms, dependent on the extent, severity and location of ocular inflammation . The manAs well as bilateral and chronic, the uveitis associated with sarcoid is usually clinically granulomatous: large “greasy” keratic precipitates, iris nodules, choroidal granuloma, which may encircle the optic nerve, and/or various degree of vitreous opacities, snowballs and snowbanks in the vitreous cavity –85.Sarcoidosis can be included on the differential diagnosis of almost any presentation of uveitis. Diagnostic criteria for sarcoidosis associated uveitis have been proposed at first International Workshop on Ocular Sarcoidosis (IWOS) in 2009. To make a diagnosis of ocular sarcoidosis, 3 conditions must be met—First, patient must have clinical findings consistent with sarcoidosis by IWOS criteria. Second, evidence of non-caseating granulomas must be demonstrated histologically on a tissue biopsy. Third, other causes of granulomatous inflammation must be excluded such as tuberculosis or syphilis. Many patients with clinical features of ocular sarcoidosis are unable to undergo biopsy or do not have an appropriate site for biopsy. In these cases, a diagnosis of probable or presumed ocular sarcoidosis is made based on clinical features, laboratory findings and chest imaging results according to the IWOS criteria. The IWOS criteria have been recently validated in several countries and shown high reliability for the clinical diagnosis of ocular sarcoidosis .Recommended laboratory investigations in suspected ocular sarcoidosis include chest x-ray to look for bilateral hilar lymphadenopathy, liver function tests, Angiotensin converting enzyme and other sarcoidosis biomarkers in the blood such as lysozyme, neopterin levels and sCD163 serum levels .TINU is a rare benign autoimmune condition of unknown etiology characterized by combined ocular and renal damage. Usually, the eye inflammation precedes or is diagnosed soon after the accidental finding of renal abnormalities and associated systemic features –89.TINU is diagnosed in ~1–2% of pediatric and adolescent patients attending uveitis clinics . A JapanMain clinical and laboratory features of TINU include sudden onset of bilateral non-granulomatous anterior uveitis (rare posterior uveitis or panuveitis) associated with typical anterior uveitis symptoms  and mildly to moderately abnormal renal function, in particular elevated Creatinine with or without raised urea, high inflammatory markers , abnormal urinalysis . To confirm the renal involvement, kidney biopsy can be considered demonstrating tubulointerstitial inflammatory infiltrations containing lymphocytes and non-specific histiocytes with vessels and glomeruli being typically spared , 90, 92.Response to treatment is usually good although patients may develop chronic relapsing course of uveitis. Escalation of treatment should be considered without delays to avoid irreversible ocular damage, including, cataract and loss of vision.Uveitis can be associated with systemic vasculitis. Broadly, pediatric vasculitis is classified as large, medium, small, or variable vessel vasculitis.BD comes under an overlapping category of autoimmune and autoinflammatory diseases as both adaptive and innate immune systems play a role in its pathogenesis. The prevalence of BD is exclusively high in countries across the Old “Silk Road”, the area between the Mediterranean and East Asia. The highest prevalence is reported in Turkey, Iran, Israel, Northern Jordan, Korea, Northern China and Japan , 94. TheA type of large vessel vasculitis and defined as panarteritis involving all layers of large vessels of the neck, thorax and abdomen, Takayasu arteritis frequently leads to ischaemic events. The incidence of ocular involvement is rare and includes retinopathy, ischaemic optic neuropathy and much less frequently anterior uveitis. It usually occurs late in the disease course and may be associated with severe involvement of the aortic arch and carotid arteries –102.A medium vessel vasculitis, KD is typically associated with bilateral non-exudative bulbar conjunctivitis sparing the limbus and seen in ~85% of children but can also manifest as anterior uveitis in up to 66% of children. Uveitis is usually mild, resolving within 2–8 weeks and maybe associated with keratic precipitates , 104.HSP typically presents with a triad of symptoms including palpable purpura, abdominal pain and arthritis. Uveitis is a rare complication of HSP that can be associated with the development of bilateral granulomatous anterior uveitis and keratitis, commonly reported in adult patients or those with HSP-related nephritis . The eyeOrbital involvement is one of the most frequently diagnosed types of ocular manifestations occurring in up to two third of patients with GPA, and in some cases can be the initial presentation of the disease. More broadly, disease tends to affect the respiratory tract and kidneys and is characterized by necrotizing vasculitis of small arteries and veins. A small number of cases of ocular inflammation in GPA can also be associated with uveitis that can be unilateral or bilateral, anterior, intermediate or posterior, with or without vitritis. Granulomatous panuveitis has also been described –110.IBD is characterized by chronic remitting-relapsing inflammatory disease of gastro-intestinal tract (GIT) and refers to as Crohn's disease (CD) and ulcerative colitis (UC), where CD is characterized by non-contiguous disturbed, granulomatous inflammation of any part of GIT, while UC is a diffuse, non-specific inflammation of the colonic mucosa, mainly the end part of the GIT, resulting in erosions and ulcer formation . The etiBoth, CD and UC have recognized extra-intestinal manifestations (EIMs) that include skin involvement, arthritis (in particular spondylarthritis) and development of ocular inflammation. The muscular-skeletal manifestations may be associated with concomitant eye involvement. The prevalence of eye inflammation is higher in patients with CD than in patients with UC and ranges from 0.6 to 1.8% of all EIMs in the pediatric population –115.Ocular inflammation usually manifests as episcleritis, scleritis but children can also present with a bilateral acute or chronic anterior uveitis. The uveitis can be primary, i.e., manifests before the intestinal symptoms, or secondary .SAIDs are a broad spectrum of rare inherited disorders caused by genetic mutations leading to upregulation of key innate immune mediators and characterized by recurrent episodes of self-limiting inflammation without evidence of infection and autoimmunity . SAIDs share common features, particularly recurrent fevers, typical skin rash and multisystemic involvement affecting almost all organ systems depending on the subtype of SAID –118.Depending on the underlying immune mechanisms, SAIDs can be categorized into inflammasomopathies and interferonopathies. Both categories are associated with uveitis, but the most commonly associated SAIDs comprise cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), TNF receptor associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MVKD), Blau's syndrome (BS), deficiency of adenosine deaminase 2 (DADA2) and haploinsufficiency of A20 (HA20), Aicardi-Goutieres syndrome (AGS), and chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) , 119.According to the literature reports, nearly all SAIDs are associated with transient or chronic recurrent ocular inflammation of varying severity and diversity and in some cases leading to severe ocular impairment. CAPS and Blau's syndrome are more frequently associated with moderate to severe eye inflammation .CAPS is associated with a gain-of-function missense mutation of the NLRP3 gene and include three overlapping clinical phenotypes: familial cold autoinflammatory syndrome , Muckle-Wells syndrome  and neonatal-onset multisystem inflammatory disease . Ocular involvement is reported in all phenotypes with conjunctivitis being the most frequently reported, typically occurring during flares. However, a chronic anterior non-granulomatous uveitis is seen roughly in half of CAPS patients, and other uveitis types may develop. Patients with NOMID may also develop papilledema related to high intracranial pressure secondary to CNS involvement , 120.Blau's Syndrome, NFkB activation disorders caused by mutation in NOD2/CARD15 gene, share common clinical features with early-onset sarcoidosis, including recurrent fever, granulomatous dermatitis, sterile arthritis, and ocular inflammation, particularly granulomatours anterior and panuveitis , 120.Ocular inflammation is a recognized feature of the other SAIDS, but occur at a much lower frequency . The clinical presentation of FMF and TRAPS is similar and characterized by recurrent fever, erysipelas-like or erythematous skin rash, serositis, arthralgia, myalgia, and lymphadenopathy. The most frequent ocular findings are choroidal thickening, retinal vasculitis and anterior uveitis , 121–126- MVKD is determined by mutation of MVK gene resulting in metabolic defect leading to recurrent fever, rash, painful adenopathy, arthralgia, mouth and genital ulcerations, hepatosplenomegaly, and abdominal pain. MVKD ranges from a milder form known as Hyper IgD syndrome (HIDS), to the most severe phenotype, mevalonic aciduria (MA). The ocular manifestation is less frequently reported with anterior uveitis being the dominant ocular finding, followed by retinal dystrophy and cataract formation in severe cases. The latter is explained by a direct toxicity of mevalonic acid on the retina and lens , 118.- Other rare inflammasomopathies, such as deficiency in ADA2 and interferonopathies, including HA20 haploinsufficiency, Aicardi-Gouttieres syndrome (AGS) and CANDLE can also present with ocular inflammation. This can be associated with severe involvement of choroid, retina, and cornea with high intraocular pressure in some cases . InterfeReA may also be associated with a various ocular involvement with mild bilateral conjunctivitis being the most frequently diagnosed in the affected patients. The symptoms of conjunctivitis may vary from mild and painless with spontaneous recovery, to severe inflammation including blepharospasm and photophobia requiring topical and sometimes systemic treatment . The secOcular manifestation has been described in a third of patients with Juvenile SLE affecting various parts of the eye . The mosVKHD is described as multisystemic autoimmune sight-threatening disease and is characterized by granulomatous ocular inflammation related to T-cell mediated dysregulation targeting melanocyte-containing tissue in the eye, the CNS, the inner ear, and the skin. The incidence of VKH in pediatric population is rare and race-dependent varying between 0.5 and 3% of all pediatric uveitides –136. The*0405 may play a role. The high prevalence of VKHD is seen among Hispanic and Asian population with young females being more affected and relatively rare in pediatric cohort  in 2001, VKHD may present as complete, incomplete, or probable. In its complete form, VKHD is defined as a non-traumatic bilateral panuveitis and is associated with integumentary, neurological/auditory signs. Patients with the incomplete form of the disease usually present with bilateral ocular involvement with either integumentary features or neurologic/auditory manifestations. Probable (ocular) VKHD is characterized by the presence of ocular features with the absence of extraocular manifestations. In all forms of the disease, a history of ocular surgery and clinical or laboratory evidence suggestive of other ocular diseases make the diagnosis of VKH unlikely .Therefore, VKH should be considered if, there is no history of ocular surgery and no clinical or laboratory evidence suggestive of other ocular diseases having similar disease course. There is no single pathognomonic sign or highly specific laboratory tests that could reliably help with the diagnosis of VKHD. Initial step toward the diagnosis of VKHD is a thorough medical history, including history of eye trauma or intraocular surgery, family history of uveitis, detailed systems and medication history.Multiple Sclerosis (MS) is a chronic inflammatory CNS disorder of the white matter. The reported frequency of MS following uveitis diagnosis ranges from 0.4 to 26.9%. Intermediate uveitis and retinal vasculitis are the most common ocular manifestations, usually occurring bilaterally and most frequently affecting females , 141.Pars planitis is a form of idiopathic intermediate uveitis that primarily affects children. The incidence of pars planitis has been reported to be 1.5–2 cases per 100,000 persons  accountiCS is a rare autoimmune vasculitis of unknown etiology that is classically presented with interstitial keratitis and sensorineural hearing loss with tinnitus, vertigo and constitutional symptoms . DevelopTreatment of CS includes corticosteroids and immunosuppressive agents. It has been proposed recently that early treatment with biologic DMARDs, including TNFα blockers such as Adalimumab and Infliximab or anti-CD20 monoclonal antibody Rituximab, may improve hearing function and significantly reduce eye inflammation , 145.SS is a rare self-limiting autoimmune endotheliopathy characterized by the clinical triad: CNS dysfunction, sensorineural hearing loss and retinal vaso-occlusive disease. Branched retinal artery occlusion (BRAO) is the classical ocular involvement in patients with SS resulting in the irreversible visual loss by the occlusions of arterioles supplying the retina. The process can be unilateral or bilateral, characterized by altitudinal defects or central/paracentral scotomas; however, patients may remain asymptomatic if the occlusions are in the peripheral retina , 147. BlHigh dose of corticosteroids and intravenous immunoglobulins (IVIG) are the mainstay of the treatment of SS and have shown high effectiveness. Other treatment options including plasma exchange may be considered as alternative treatment in corticosteroid-resistant cases .Although management of uveitis is led by ophthalmologists, multi-disciplinary care teams which involve pediatricians are needed for holistic care of these inflammatory, chronic, relapsing and remitting disorders , 151. ThFirst line of treatment of anterior chamber involvement is topical steroids, but its use is associated with a risk of ocular complication such as raised intraocular pressure, glaucoma and cataract , 154. LoPediatric investigations prior to commencement of biologic DMARDs treatment should include work up to rule out tuberculosis , serology for varicella zoster virus (VZV), hepatitis B, and hepatitis C (and HIV when appropriate). Immunizations should be updated prior to starting immunosuppression, according to national recommendations including live attenuated vaccines such as MMR and varicella vaccine when patient is seronegative , 156. MoVZV non-immune children who are exposed to chickenpox and not eligible for vaccine should be offered post-exposure prophylaxis (PEP). Although there is no standardized PEP, anti-VZV immunoglobulins (V-ZIG) and oral acyclovir are both used. Varicella immunization of seronegative family members is recommended –160. MosAlthough there is little evidence in pediatric uveitis, immunizations are safe and effective in children with Rheumatic diseases on immunosuppression but in one third of the patients, response to vaccine may be decreased and this can be confirmed by measuring antibody levels so timing to boosters can be adjusted , 163. ItMost patients with non-JIA-associated uveitis will have a baseline work-up to identify extra-ocular involvement. The identification of an underlying autoimmune or autoinflammatory disease may tailor management. Extra-ocular involvement may need monitoring that can be undertaken by the pediatrician alongside the tertiary care center. In the absence of extra-ocular involvement at presentation, pediatricians may monitor extra-ocular involvement with history taking, clinical examination, and further investigations as indicated . In two Close monitoring of children with uveitis is recommended to prevent complications due to uncontrolled inflammation or long-term medication use such as steroids. For JIA-associated uveitis patients, the frequency of screening should be based on individual risk factors  and current immunosuppressive treatment even when the patient is in remission of uveitis –197. SimCorticosteroids are useful in acute inflammation for non-infectious ocular involvement .Their mechanism of action is by modulating the gene expression of pro-inflammatory cytokines. This anti-inflammatory action of steroids can be achieved either through topical or systemic administration of steroids depending on the location of ocular inflammation. Local treatments include topical steroid drops or periocular, intraocular injections or implants.Topical corticosteroids are usually the first-line treatment in anterior segment ocular inflammation and were used in about 90% of patients with idiopathic uveitis enrolled in the CARRA Registry. . DexametLocal injection of corticosteroids is a very useful modality for treating uveitis especially intermediate and posterior uveitis. Regional delivery of steroids is used to minimize systemic side-effects maximizing drug delivery to the target area. This can be done by either periocular (around the eye) or intravitreal (inside the eye) steroid injections or by using intraocular steroid implants.Periocular and intraocular steroid injections are most likely useful for severe presentations or flare up of remitting types of ocular inflammation and for non-chronic uveitis macular edema . Ocular Steroid implants were created to be used when long-term control of inflammation is desired with minimal relapses. These are approved for treatment of macular edema due to retinal vein occlusion and for treatment of non-infectious posterior uveitis. More studies are required to assess the long-term efficacy and safety profile of steroid implants in patients , but theSystemic Corticosteroids are very useful in children with intermediate, posterior or panuveitis, for urgent control of inflammation. According to the CARRA registry, roughly 94% of children with idiopathic uveitis were given systemic steroids during the disease course . Based oOcular complications of corticosteroids are mainly ocular hypertension/glaucoma and cataract. Ocular hypertension and secondary glaucoma have been reported with the use of systemic and topical steroids causing high incidence of blindness at 5 years. Early aggressive immunosuppression with DMARDs to control ocular inflammation may help prevent these ocular complications .Topical Dexamethasone (eye drops) and intravitreal implant (dexamethasone) are both associated with cataract formation and increased intraocular pressure , 207. AlIn JIA, growth is known to be affected by disease activity and prolonged high dose systemic corticosteroid use , 212. GrMedicines for long-term immunosuppression are Methotrexate (MTX) , and less commonly, mycophenolate mofetil (MMF), Azathioprine and cyclosporine A. MTX has a folic-acid analog mechanism of action inhibiting DNA replication and RNA transcription in B and T lymphocytes . Folic aIt is well known that withdrawal of Methotrexate may lead to flare of inactive JIA-associated uveitis. A longer period of uveitis inactivity prior to withdrawal may decrease the risk of flare .Since pro-inflammatory cytokines, such as TNFα, interferons and Interleukins (IL) are consistently elevated in aqueous fluid and serum of children with intraocular inflammation, targeting these molecules is an attractive and less toxic approach for children with uveitis refractory to steroids and conventional DMARDs. Targeted blocking these pro-inflammatory cytokines can represent a decent steroid-sparing alternative to treat uncontrolled ocular inflammation .Adalimumab, Infliximab, Golimumab and Certolizumab are widely used in patients with non-infectious uveitis . The effAlthough there is limited evidence mostly in JIA associated uveitis, Golimumab and Certolizumab appears to be off-label medications of interest , 229–231p = 0.09)  . Similar = 0.09) . Early M = 0.09) .Although limited to few case series, adalimumab and infliximab have been reported to be safe and efficacious in uveitis of several underlying causes including Behcet's disease, Blau's syndrome and sarcoidosis –242.Abatacept (CTLA4-Ig), a novel fusion protein that modulates the T cell co-stimulatory signal mediated through the CD28-CD80/86 pathway, Tocilizumab (IL-6 blockade), Rituximab (B cell blockade), Secukinumab  are some other off-label agents used in uveitis refractory to the above mentioned therapies , 243. AlTDM is not very much used in routine practice for the monitoring of conventional DMARDs such as Methotrexate, Azathioprine or MMF. It is becoming routine practice in the monitoring of biologic DMARDs, particularly anti-TNF. Adalimumab and infliximab are well known to be immunogenic in particular if they are not used in association with a conventional DMARD and therefore monitoring is recommended , 248. ThThere are limited data on the use of JAKi in the management of uveitis. It has been to date only used to rescue patients who failed biologic DMARDs in particular anti-TNF with improvement of the ocular inflammation and with no side-effects . A cliniACR (American College of Rheumatology) and SHARE initiative both recommend at least 2 years of uveitis remission on slit-lamp examination before tapering treatment intensity when uveitis is well controlled on DMARD and biologic therapy only , 197. EaVisual impairment is an important component of quality of life in children with uveitis and compounds the negative impact of reduced physical function due to associated rheumatological disease . Even amThis review on pediatric uveitis presents the case for the multi-disciplinary management of this complex childhood ocular inflammatory disease, in order to improve patient outcomes, patient experience and quality of life. Early recognition of ocular manifestations of established inflammatory disorders reduces the risk of sight loss. In the child who first presents with uveitis, prompt diagnosis of associated systemic conditions is supported by an understanding of the different uveitis types, and in turn supports the individualization of care and early escalation of treatment to reduce morbidity. Management of uveitis, whether it is isolated ocular disease treated with DMARDs, or as part of multisystem disease, involves ongoing surveillance for evolving extra-ocular disease, therapeutic drug monitoring, the management of side-effects of treatment and the psychosocial aspect of loss of vision and the underlying chronic disease.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.This work was supported by Biomedical Research Center, Great Ormond Street Hospital for Children, London, UK.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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Inspired by the successful application of Cas9 gene editing for “genome surgery,” we are looking back at what has been accomplished in the ten years of CRISPR editing. Intense effort is now focused on how to utilize the unique functions of CRISPR-Cas systems for molecular diagnostics and the next generation of therapeutic tools. CRISPR-Cas systems have two major advantages for gene editing that render them attractive for these new applications, specifically the ability to easily control their target recognition specificity and to couple this specificity to a targeted or secondary cleavage activity. However, despite the great potential of CRISPR/Cas for both gene editing and diagnosis, its medical applications have yet to be fully realized due factors that limit their delivery or utility for point-of-care (POC) applications. In this editorial note, we discuss how nanotechnology can address challenges associated with new CRISPR applications and what nanotechnology-specific advances are needed to circumvent remaining barriers that limit the development or use of new CRISPR/CAS-based genome editing and diagnostic approaches.in vivo delivery. Nanoparticle platforms exhibit strong potential to address issues associated with CRISPR reagent delivery, but several nanotechnology-specific considerations are needed to realize the potential of these delivery systems. For example, some nanomaterial-mediated delivery platforms are based on chemisorption of the polynucleotide cargo to the nanoparticle. Thus, at the most basic level, cationic lipid-based nanoparticles (NPs) can be used to encapsulate CRISPR components for cell delivery through charge interactions. However, this approach can have potential toxic effects and nonspecific NP uptake that can produce off-target effects and limit bioavailability to desired cell target cells. This can be remedied using lipid-based NPs that incorporate targeting molecules, including NPs derived from the plasma membranes of cells that express, or can be engineered to express, factors that target the cell of interest. Such membrane-derived NPs can also exhibit high biocompatibility to minimize immune reactions that can limit the effect of gene editing approaches.CRISPR/Cas-mediated gene editing approaches require a delivery system that efficiently delivers their reagents to target cells, but conventional delivery approaches  used in other gene editing methods can have limitations when applied to deliver CRISPR/Cas reagents . For exain vivo stability, targeting, and cell entry characteristics. NP platforms could also be employed to improve targeted release of CRISPR RNPs to better control spatiotemporal regulation of gene editing activity. Promising NP-based vectors employed for efficient delivery of CRISPR-Cas RNPs to date include liposomal/lipid-based NPs, polymeric NPs/polyplexes, gold NPs, synthetic and engineered exosomes, mesoporous silica nanoparticles (MSNPs), metal–organic frameworks (MOFs), and multiple cationic NPs -based dendrimers, polyethyleneimine (PEI), and chitosan NPs) [Aside from their these encapsulation and biocompatibility properties, NP delivery systems also needs to overcome physical barriers and direct carry CRISPR/Cas9 components to targeted cells and tissues for accurate and efficient genome editing. Synthetic NP designs should thus accommodate reactive chemical groups on their outer surfaces to permit modifications with factors that can be used to enhance their san NPs) . These nIntegrating nanotechnology with CRISPR assay approaches also provides a powerful new means for the fast, specific, and ultrasensitive detection of protein biomarkers, whole cells, and small molecules, in addition to nucleic acid targets . The detNew assay designs and device nanofabrication approaches are required to develop applications that simplify sample preparation, target preamplification, and provide multiplexed diagnostic capacity . The speCRISPR/Cas diagnostic platforms still have limitations, however, including a need for target amplification, short-term shelf life, nanomaterial degradation in biospecimens, and the potential complexity of the design and fabrication of their sensing systems. The incorporation of nanomaterials into CRISPR/Cas assay systems and devices has been limited thus far but there is significant potential for such applications to enhance the diagnostic performance of CRISPR/Cas assays.


Background: Sarcopenia seems to be an emerging health issue worldwide, concerning the progressive loss of skeletal muscle mass, accompanied by adverse outcomes. Asthma is a chronic inflammatory respiratory condition that is widespread in the world, affecting approximately 8% of adults. Although data are scarce, we aim to shed light on the potential association between low muscle mass and asthma and point out any probable negative feedback on each other. Methods: We searched within the PubMed, Scopus, MEDLINE, and Google Scholar databases. Study selections: Three studies were included in our analysis. Only original studies written in English were included, while the references of the research articles were thoroughly examined for more relevant studies. Moreover, animal model studies were excluded. Results: 2% to 17% of asthmatics had sarcopenia according to the existent literature. Sarcopenic asthmatic patients seem to have reduced lung function, while their mortality risk may be increased. Furthermore, patients with asthma- chronic obstructive pulmonary disease (COPD) overlap syndrome phenotype and sarcopenia might have a higher risk of osteopenia and osteoporosis progression, leading consequently to an increased risk of fractures and disability. Conclusions: Emerging data support that pulmonologists should be aware of the sarcopenia concept and be prepared to evaluate the existence of low muscle mass in their asthmatic patients. Worldwide, it there is an emerging interest concerning the progressive loss of skeletal muscle mass and loss of muscle function, broadly known as sarcopenia . SarcopeAsthma is a chronic inflammatory disorder concerning the airways . It is cIn this non-systematic review, we aim to investigate the potential interplay between these two clinical entities, even though data are limited and further studies are needed to validate this interaction.The combination of low muscle mass and low muscle function is characterized as sarcopenia ,10. EvenSarcopenia is an important component of the syndrome of frailty, which is associated with increased vulnerability, a decline in the physiological reserves of several systems of the human body and augmented susceptibility to both endogenous and exogenous stressors ,18. FraiIn 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) published a sarcopenia definition. Still, in early 2018, the Working Group carried out a new meeting (EWGSOP2) to determine an update concerning the description of this condition. In its 2018 definition, EWGSOP2 uses low muscle strength as the basic parameter of sarcopenia . The updTo monitor sarcopenia among individuals, there are specific tools. One screening tool for sarcopenia is SARC-F, which is a questionnaire consisting of five questions: Strength (S), Assistance walking (A), Rising from a chair (R), Climbing stairs (C), and Falls (F) on a scale of 0 to 2. The cutoff value recommended is ≥4 points ,23. In aThe laboratory evaluation of skeletal muscle mass, or skeletal muscle quality, can be carried out by appendicular skeletal muscle mass (ASMM) by Dual-energy X-ray absorptiometry (DXA), muscle ultrasonography, neutron activation (NAA), electrical impedance myography (EIM), whole-body skeletal muscle mass (SMM) or ASMM predicted by Bioelectrical impedance analysis (BIA) and lumbar muscle cross-sectional area by CT or MRI ,24,25.Interventions concerning sarcopenia are also critical to prevent its progression and adverse outcomes. Among these interventions are dietary supplementation, exercise interventions, and combined diet and exercise interventions or lifestyle interventions .Both aerobic and resistance training seem to increase muscle strength and improve physical function in general . SpecifiIt is already well-established that malnutrition is related to the pathogenesis of low muscle mass, specifically in frail and vulnerable elderly patients ,18,27,28Bronchial asthma is a medical condition that may have detrimental effects, while its prevalence globally has demonstrated a rapid increase during the last century ,31. It iThe risk factors concerning the bronchial asthma are already validated and it seems that gene-environment interactions have a pivotal role ,33. As hThe pathophysiology of this clinical issue is closely linked to the inflammation of the lower airway. This is most likely to derive from the combination of environmental exposures, genetic profile of its individual and probably alterations in the microbiome and metabolites ,36. It iThere are four essential symptoms concerning individuals living with bronchial asthma. Among these symptoms are: wheezing, coughing, shortness of breath / dyspnea and chest tightness ,41, whilBronchial asthma classification concerns intermittent or persistent asthma, ranging from mild to severe, while certain asthmatic patients may have intermittent to persistent asthma . MoreoveAsthma management remains still quite intriguing, with acute asthma being a medical emergency that could be fatal . In addiAsthma treatment strategy is associated with the administration of inhaled corticosteroids (ICS), which have the ability to reduce asthma exacerbations and generally ameliorate the disease control . In addiIt is important to underline that, in severe conditions of bronchial asthma, there is availability of biologic therapies in the form of anti-IgE  and anti-IL5 therapies (mepolizumab and reslizumab) .Asthma and obesity, both of which are considered global health issues, tend to increase in parallel indicating a potential link between these two conditions ,51. TherIn this non-systematic review article, the current literature was retrieved using the PubMed, Scopus, MEDLINE, and Google Scholar databases from the date of the idea’s inception concerning this review from July 1975 until August 2022. We have searched for the following terms: “sarcopenia and asthma” OR “sarcopenia and bronchial asthma” OR “low muscle mass and asthma” OR “low muscle mass and bronchial asthma”. Only original studies written in English were included, while the references of the research articles were thoroughly examined for relevant studies. Animal model studies were excluded. In this study, we tried to highlight the existing literature concerning the interaction between these two entities .The association between sarcopenia and bronchial asthma seems to have been under medical investigation in recent years. Researchers worldwide tried to investigate the potential impact of these two entities on each other. Still, there is enough scientific space for a further and more thorough investigation.Won et al. tried to investigate the association between sarcopenia and asthma in the elderly, mainly concerning asthma control and lung function . The groBenz et al. focused on investigating the association between sarcopenia, higher systemic immune-inflammation index (SII), COPD or asthma, and all-cause mortality in a large-scale population-based setting, taking under serious consideration that SII and sarcopenia are associated with higher morbidity in patients with COPD or asthma . 4482 paLee et al. investigated the association between sarcopenia and bone mineral density (BMD) (which is related to osteopenia and osteoporosis) in asthma-COPD overlap (ACO), based on the existing hypothesis that sarcopenia and decreased BMD are common in the elderly and are significant comorbidities concerning obstructive airway disease (OAD) . A totalThis non-systematic review aims to demonstrate and highlight the potential interplay between bronchial asthma and low muscle mass, known as sarcopenia. These two entities play a pivotal role in respiratory and muscle health, respectively, while they are already linked to many other pathological conditions and adverse outcomes that could deteriorate the QoL among individuals. However, the existing literature is still scarce but quite promising.Certain limitations are related to this medical issue. These limitations are associated with the currently small number of studies investigating this intriguing interplay, while the number of patients participating in them is relatively limited.Nevertheless, it seems that it would be intriguing if further studies could include and investigate a more significant number of patients living with bronchial asthma, not only older but also of younger age, and evaluate the existence or not of a low muscle state by muscle mass assessment. In addition, it is important to study the effect of currently used treatment against asthma in sarcopenic individuals living with asthma and whether these agents could positively impact muscle mass, apart from their chronic respiratory disease.Another interesting approach concerning this medical topic and the potential interplay between these entities could be the development of specific indexes that could evaluate the prognosis of bronchial asthma among asthmatic sarcopenic patients, probably relying on their clinical image, along with laboratory parameters concerning both muscle mass and respiratory activity.In addition, using specific biomarkers that could assess sarcopenia phenotype in asthmatic subjects might be of great importance. It has already been analyzed the association with plasma biomarkers such as glycoprotein Dickkopf-3 (Dkk-3), c-terminal agrin fragment-22 (CAF22), and microRNAs miR-21, miR-134a, miR-133 and miR-206 with hand-grip strength (HGS) and appendicular skeletal mass index (ASMI) in male, 54–73-year-old individuals with COPD, bronchial asthma or pulmonary tuberculosis and it has been demonstrated a modest-to-significant increase in the plasma markers of oxidative stress, inflammation and muscle damage, which had varying degrees of correlations with Dkk-3, CAF22 and selected micro RNAs (miRs) in these respiratory diseases . This coLast but not least, it would be appealing if an interventional protocol could be established for sarcopenic individuals with bronchial asthma. This specific protocol could include a multimodal approach in which nutrition, exercise, and respiratory rehabilitation programs could beneficially coexist and positively affect the muscle mass, along with the asthmatic exacerbations. Ameliorating these conditions could have an upside effect on these individuals and improve their QoL.Sarcopenic patients living with a chronic respiratory disease, such as bronchial asthma, may have reduced lung function, while their mortality risk may increase. In addition, individuals with asthma-COPD overlap syndrome phenotype and low muscle mass may have a higher risk of osteopenia and osteoporosis progression, leading consequently to an increased risk of fractures, immobilization, and disability. Pulmonologists should be aware of the sarcopenia clinical condition and be prepared to evaluate low muscle mass in bronchial asthma patients using the existing screening tools for sarcopenia. Moreover, physicians who examine sarcopenic patients with bronchial asthma should be able to appropriately collaborate with specialists who deal with nutrition and exercise, giving their patients a multimodal approach concerning these entities’ interplay and the optimum treatment.


The applications of genetic, and later genomic, metagenomics and transcriptomic techniques to biofilm studies, begun by work on Escherichia coli surface adhesion factors [The first published observations that microorganisms associate to form microbial communities structured as biofilms in natural environments date back to the first half of the last century . However factors , of the  factors .As mentioned above, biofilm growth represents a major concern in microbial infections, since it can lead to tolerance to antimicrobial treatments. This issue is directly connected to the growing emergence of antibiotic resistance as well as to the lack of novel antimicrobial agents. These are issues that, if not addressed, might lead to an estimated staggering amount of 10 million deaths/year caused by pan-antibiotic resistant pathogens by 2050 . Lack ofMicrobial Biofilms: From Molecular Mechanisms and Structure to Antimicrobial Therapy, includes research articles tackling crucial issues in the field of microbial biofilms. One paper published in this Special Issue points to the relevance of the pyrimidine biosynthetic gene pyrD as suitable target for anti-virulence and anti-biofilm agents in adherent invasive Escherichia coli (AIEC), an intracellular pathogen implicated in the onset of Crohn’s disease [Pseudomonas aeruginosa isolates from cystic fibrosis patients, using a machine learning algorithm aimed at the understanding of those molecules that are more active against biofilm formation [Lactiplantibacillus plantarum CCFM8724 appears promising in this respect, being able to impair the formation of a Streptococcus mutans-Candida albicans mixed-species biofilm, with supernatants of L. plantarum cultures strongly affecting the expression of C. albicans adhesion and virulence genes [Staphylococcus aureus clinical isolates from prosthetic joint-associated infections showed the absence of mutations affecting expression of the icaABCD operon, encoding PIA/PNAG biosynthetic genes. Single aminoacid changes in the IcaR regulatory protein resulting in increased PIA/PNAG production led to decreased virulence in a Galleria mellonella model, suggesting that biofilm formation might be detrimental to S. aureus virulence [S. epidermidis clinical isolates, with no apparent role of PIA/PNAG in this process [This Special Issue,  disease . Anotherormation . Anotherce genes . Other wirulence . Surpris process . Thus, tAltogether, the papers featured in this Special Issue cover some of the main topics in biofilm studies, mainly focusing on biofilm control. We believe these studies represent an important contribution to our knowledge in this field.