Lissotriton vulgaris) is one of the most widely distributed amphibians species across Eurasia and forms a species complex with a partially overlapping distribution and morphology. In the present study, we explored the population genomic structure of smooth newt lineages in the Carpathian Basin (CB) relying on single‐nucleotide polymorphisms. Our dataset included new and previously published data to study the secondary contact zone between lineages in the CB and also tested for the barrier effect of rivers to gene flow between these lineages. We confirmed the presence of the South L. v. vulgaris Lineage distributed in Transdanubia and we provided new distribution records of L. v. ampelensis inhabiting the eastern territories of the CB. High genetic diversity of smooth newts was observed, especially in the North Hungarian Mountains and at the interfluves of the main rivers in the South with four distinct lineages of L. v. vulgaris and one lineage of L. v. ampelensis showing a low level of admixture with the spatially closest L. v. vulgaris lineage. Moreover, admixture detected at the interfluve of the main rivers (i.e. Danube and Tisza) suggested a secondary contact zone in the area. Finally, we found that the river Danube has a very weak effect on population divergence, while the river Tisza is a geographical barrier limiting gene flow between smooth newt lineages. As the range boundaries of L. v. vulgaris and L. v. ampelensis in the CB coincide with the river Tisza, our study underpins the influence of rivers in lineage diversification.Species with wide‐range distributions usually display high genetic variation. This variation can be partly explained by historical lineages that were temporally isolated from each other and are back into secondary reproductive contact, and partly by local adaptations. The smooth newt  relying on single‐nucleotide polymorphism. High genetic diversity of smooth newts was observed with four distinct lineages of  Finally, an unrooted phylogenetic tree was reconstructed based on the genetic distance matrix (Fst) and neighbour‐joining method implemented in MEGA software  was performed in Plink 1.9  analysis with the ‘BEDASSLE’ package in R  additional clusters  1 (explaining 26% of the variance), 2 (8%) and 3 (6%) is presented in Figure s Figure . This wa Figures .Fst statistics showed high differentiation (0.266) between L. v. ampelensis and the South L. v. vulgaris Lineage, and also between L. v. ampelensis and all the four South L. v. vulgaris Lineage (Lvv1–4) clusters (0.266–0.31). Lower differentiation was found among the South L. v. vulgaris Lineage clusters (0.103–0.157), cluster Lvv1 being the most differentiated from the others   Figure .L. vulgaris populations, while the median geographical distance between populations in our dataset is 279 km  towards the tributaries of the Danube to the tributaries of the Tisza, with an admixture of lineages through the interfluves of the rivers. Second, according to the fine‐scale scenario, the Transdanubian populations of L. v. vulgaris were clustering into four different genetic clusters; in contrast, L. v. ampelensis populations remained to be represented by a single cluster with some admixture from the closest cluster of the South L. v. vulgaris Lineage  adds L. vulgaris to the list of amphibian species where pronounced genetic diversity is present within the CB. The genetic distance between the four clusters shows that cluster Lvv1 might represent the most distantly related one and that clusters Lvv2–Lvv4 might have differentiated approximately at the same time, being now separated by rivers and lakes  suggest that one or multiple northerly refugia in the CB cannot be ruled out for the smooth newt as well.Smooth newt populations reached the highest genetic diversity in the Balkans , the northern Transdanubia (Lvv2) and the Danube–Tisza Interfluve (Lvv3 and Lvv4) show that landscape features—such as the river Danube or the Lake Balaton—might shape also the population structure within L. v. vulgaris in the CB. The interfluve of the rivers (i.e. from the Great Plains of Hungary towards northern Serbia) serves as a contact zone for lineages, which was confirmed by the presence of admixed populations in the area. This population structure is corresponding to the distributional pattern of the Danube crested newts that showed a weak but significant genetic structure between tributaries of the three main river systems of Danube, Sava, and Tisza in the CB ; writing – original draft (lead); writing – review and editing (lead). Gemma Palomar: Formal analysis (lead); methodology ; software (lead); writing – review and editing . Piotr Zieliński: Formal analysis (supporting); methodology ; writing – review and editing . Isolde van Riemsdijk: Formal analysis (supporting); methodology ; writing – review and editing . Wiesław Babik: Methodology ; writing – review and editing . Róbert Dankovics: Investigation . Bálint Halpern: Investigation . Milena Cvijanović: Investigation . Judit Vörös: Conceptualization (lead); funding acquisition (lead); supervision (lead); writing – original draft (supporting); writing – review and editing .The authors declare no conflicts of interest.Data S1Click here for additional data file.


This study evaluated the burden and manifestations of genetic eye diseases in children in Ibadan, Nigeria.this was a hospital-based cross-sectional study in which new and follow-up paediatric eye clinic patients were recruited consecutively at the University College Hospital, Ibadan. Children with genetic eye diseases had comprehensive ocular and systemic examinations, and their pedigrees were charted to determine the probable modes of inheritance. The main outcome variables were the proportion of study participants with genetic eye diseases, the probable modes of inheritance, and the clinical diagnoses. Summary statistics were performed using means and standard deviations for numerical variables and proportions for categorical variables.fifty-two (12%) of 444 children had genetic eye diseases, and their mean (SD) age was 88.8 ± 50.4 months. Thirteen different phenotypic diagnoses were made following the evaluation of the 52 children, including primary congenital glaucoma  and familial non-syndromic cataracts . The probable modes of inheritance were derived from the pedigree charts, and 30 (58%) conditions were presumed to be sporadic.this study demonstrated a significant burden and a wide range of paediatric genetic eye diseases in this tertiary referral centre in Nigeria. This information provides invaluable evidence for planning ophthalmic genetic services. There has been a gradual shift in the aetiology of childhood blindness in developing countries such as Nigeria from communicable diseases such as measles with corneal scarring ,2, to noThe molecular diagnosis of genetic eye diseases holds much promise in ophthalmology practice through accurate diagnosis and understanding of recurrence risk and prognosis . ConsequThere has been remarkable advancement globally in the field of ophthalmic genetics in terms of clinical and molecular diagnoses, genetic counselling, clinical trials, and gene therapies for inherited diseases such as Leber congenital amaurosis, achromatopsia, choroideraemia, X-linked retinitis pigmentosa, and Stargardt disease ,8. Howevet al. [et al. [Although various studies in Nigeria have examined the burden of congenital ocular anomalies, these studies were largely retrospective and made no distinction between anomalies of genetic origin and those of other aetiologies -18. In tet al.  assessed [et al.  examinedStudy design and setting: the study was a hospital-based, cross-sectional, descriptive study carried out at the eye clinic of the University College Hospital (UCH), Ibadan, a major referral tertiary centre in Southwest Nigeria. Participants were recruited from April to July 2021.Participants: the study population comprised new and follow-up patients below 18 years of age who presented to the eye clinic, UCH, Ibadan, during the study period. Participants were recruited consecutively using a total sampling approach till the study sample size was achieved. Patients with genetic eye diseases according to the study definition were further evaluated. Their family and clinical histories were obtained and their pedigrees were charted up to at least three generations to determine their probable inheritance pattern. Subsequently, they underwent further comprehensive ocular and systemic examinations as appropriate. The ocular examination involved anterior segment slit-lamp examination (Haag-Streit), intraocular pressure measurement (Goldman Applanation Tonometry), dilated fundoscopy with 78D lens, and/or binocular indirect ophthalmoscope as applicable. Appropriate systemic examinations were also carried out. A clinical (phenotypic) diagnosis was then made based on the history and clinical evaluation.Variables: the main outcome variables of interest were the proportion of study participants with genetic eye diseases, the modes of inheritance of the genetic eye diseases and the clinical diagnoses.Study definitions and diagnostic criteria: the study definition of genetic eye disease was restricted to chromosomal and single gene (Mendelian) but not complex or multifactorial diseases since routine genetic testing for the latter is not currently recommended till benefits can be demonstrated for specific types of therapy and surveillance [eillance . Chromoseillance . Mendelieillance .Inheritance patterns were described as autosomal dominant or autosomal recessive. Genetic diseases that are not known to be inherited, or which were thought to be due to de novo mutations were categorised as "sporadic". The basic definitions used for these inheritance patterns are as follows :Autosomal dominant: the phenotype occurs in every generation and is transmitted from either parent to offspring of either sex.Autosomal recessive: the phenotype may occur in siblings of the proband but not in parents, offspring or other relations, affects both sexes equally, and parents may be consanguineous.Sporadic: the disease is not the result of the inheritance of a disease-causing allele but is often due to a new germline or a somatic mutation.The study definition for childhood cataracts of genetic origin was based on the presence of a definite family history, in the absence of any history or finding suggestive of any other known aetiology. These criteria were necessary to avoid misclassification because of the complexity of accurately diagnosing the underlying aetiology of congenital cataracts in the absence of a molecular diagnosis ,23, whicData source and measurements: data were collected with a pre-designed proforma. The proportion with genetic eye diseases was calculated as a proportion of the total number of participants recruited. The modes of inheritance for each participant with a genetic eye disease was determined from the participant's pedigree chart which was constructed up to at least three generations. The clinical diagnoses were determined following careful clinical examination.Bias: care was taken to ensure that participants were recruited only once in the course of the study.Study size: this was based on the proportion of suspected ocular genetic diseases among children in a general paediatric ophthalmology clinic catering for an ethnically diverse inner-city area in the United Kingdom of 13% [m of 13% . The samwhere n was the estimated minimum sample size, Z was the standard normal variate at 95% confidence interval (1.96) and 80% power (0.84), proportion of children with genetic eye diseases in a clinical setting from a previous study (13%) , and d wQuantitative variables and statistical methods: data management was done using the IBM Statistical Package for Social Sciences (SPSS) version 20.0 . Summary statistics were performed using means and standard deviations for numerical variables and proportions for categorical variables. The proportion of participants who had genetic eye diseases was calculated from the total number of participants recruited for the study.Ethical considerations: ethical approval was obtained from the Ethics Review Committee of the University College Hospital, Ibadan (UI/EC/20/0368). Informed consent was obtained from the parents of participants, and assent from participants > seven years old if they were mentally capable of granting it.Participants and demographic data: a total of 444 children were recruited over a period of four months. Their ages ranged from one to 204 months with a mean (SD) of 88.8 ± 50.4 months, and 244 (55%) were males.Proportion of children with genetic eye diseases: the proportion of children that were presumed to have genetic eye diseases was 12% . Their ages ranged from five to 168 months with a mean (SD) of 74.4 (49.2) months. There was no history of consanguinity in any of the parents.Clinical diagnoses and modes of inheritance: overall, 13 different phenotypic diagnoses were made following the evaluation of the 52 children with presumed genetic eye diseases. Their modes of inheritance were presumed to be sporadic in 30 (58%), autosomal dominant in 19 (36%), and autosomal recessive in 3 (6%) children, respectively, based on their clinical histories and pedigrees. The demographic details, clinical features and probable modes of inheritance of the children with genetic eye diseases are shown in The children with familial non-syndromic cataracts  included three sibling trios - a pair of female twins aged 22 months and their four-year-old female older sibling; two stepsisters aged six and seven years; and three other unrelated children. They were all presumed to have autosomal dominant mode of inheritance because of a positive family history of the condition in a parent and other family members in multiple generations. The pedigree for the step sisters is shown in Six (11%) children had isolated bilateral aniridia with autosomal dominant pattern of inheritance based on their pedigrees and lack of systemic associations. They included a sibling trio comprising a six-year-old female, an eight-year-old male, and a 12-year-old female; a sibling pair comprising a five-year-old female and a 13-month-old male; and an 11-year-old male. The 11-year-old male child had bilateral aniridia and cataracts (pseudophakic), had an eight-year-old sister with bilateral developmental cataracts but no aniridia, a history of bilateral aniridia and cataract in his father, and poor vision in an aunt and two male cousins from his paternal side .Four (8%) children had intraocular retinoblastoma - one bilateral and three unilateral. Three of them were considered to have sporadic or new mutations . The remaining child with unilateral disease was presumed to have an autosomal dominant pattern of inheritance because of a positive history of bilateral disease in an elder sibling, and probable history of retinoblastoma in six deceased step siblings (father's children with previous partners . The fatThree (6%) children had Marfan syndrome - a male and female sibling pair aged 14 and 13 years, respectively, who were presumed to have an autosomal dominant pattern of inheritance because of a strong family history in a parent and in multiple relatives . The thiFurthermore, a nine-year-old male child with familial, non-syndromic retinal detachment was presumed to have an autosomal dominant pattern of inheritance . He was et al. [This study assessed the proportion, pedigrees, probable modes of inheritance and clinical profiles of children with genetic eye diseases at the University College Hospital, Ibadan. The proportion of children with genetic eye diseases was 12% (52), similar to the 13% reported by Reddy et al.  who alsoPedigree charts served as a guide in this study to determine a probable pattern of inheritance for each patient with a genetic eye disease, and whether a systemic association was expected for conditions with multiple patterns of inheritance such as aniridia. The conditions were presumed to be sporadic in a majority  of the children, autosomal dominant in 19 (36%), and autosomal recessive in 3 (6%). This served as a basis for counselling the parents of these children on the possible risks of recurrence in future offspring as well as risks to other family members. Comprehensive pedigree charting is a vital component of the genetic evaluation process, and can save both time and money in reaching a diagnosis . It alsoFurthermore, clinical evaluation, comprising comprehensive family history, pedigree charting, clinical examination, and investigation, is still a fundamental aspect and the first step of any genetic evaluation, even when sophisticated cytogenetic and molecular genetic tests are available. Clinical diagnosis is an important aspect of genetic evaluation as it can help guide the choice of genetic testing. Likewise, genetic test results should be interpreted in light of clinical findings . In resoet al. [The most common of the 13 forms of phenotypic diagnoses encountered in this study were primary congenital glaucoma  and non-syndromic familial cataracts . Reddy et al.  in Londoet al.  while caet al. .et al. [et al. [et al. [et al. [Olowoyeye et al.  and Gilb [et al.  reported [et al. . Mirrori [et al. . The diset al. [Though consanguinity may be linked to an increased prevalence of genetic eye diseases as highlighted by Kemmanu et al.  in the Pet al. -32.Limitations: a limitation of this study is a probable underestimation of the proportion of children with genetic eye diseases because of the strict criteria employed for the diagnosis of cataracts of genetic origin. Molecular diagnosis was beyond the scope of this study. Furthermore, being a hospital-based study, the proportion reported only accounts for the population of people who have access to, and have been able to seek health care. This may therefore represent only the tip of the iceberg of the burden of genetic eye diseases in the general population.This study showed that, indeed, there is a significant burden of paediatric genetic eye diseases in Nigeria. It included both new and follow-up patients and, therefore, represents the likely burden of genetic eye diseases in a paediatric ophthalmology eye clinic. This may be useful in terms of policy and planning for ophthalmic genetic services. Furthermore, though routine genetic testing for ocular diseases is not yet available in Nigeria, this study has demonstrated that careful pedigree charting and clinical evaluation can provide invaluable information that can aid clinical diagnosis and counselling. Finally, this study underscores the importance of incorporating genetic services into paediatric ophthalmic care in lower-income countries like Nigeria as this would ensure that more accurate diagnoses can be made in a timelier and cost-effective manner. It would also enable better counselling of parents of children with genetic eye diseases so that they can make informed management and reproductive choices going forward. We recommend the incorporation of routine pedigree charting in the evaluation of children suspected to have ocular genetic diseases, and ophthalmic genetics services as part of paediatric ophthalmology care in Nigeria to ensure a more holistic evaluation that would guide management and enhance outcomes in these children. A national genetic eye disease register will be vital in providing evidence of the burden in Nigeria for policy making and will ensure easy communication with patients in case of future opportunities for genetic testing, clinical trials, and other technological advancements. Finally, a large collaborative hospital-based study with molecular diagnosis across Nigeria may be necessary to provide more comprehensive evidence on the burden and manifestations of paediatric ocular genetic diseases in the country to aid policy and planning.Despite the recent advances in the field of ophthalmic genetics globally, much of sub-Saharan Africa is still underrepresented in this field of research;Little is known about the burden and manifestations of genetic eye diseases children in the region.This study demonstrates a significant burden and variety of genetic eye diseases among children in a clinical setting in Nigeria;It provides evidence to aid planning of ophthalmic genetic services in similar settings.


Chicken breast meat is one of the most sustainable and affordable sources of animal protein making it one of the most popular protein sources globally. As such, maintaining consistency in product quality is of the utmost importance. Over the last decade three novel myopathies have been identified in broilers (White striping (WS), Wooden breast (WB) and Spaghetti breast (SB)) ; there hThe exact aetiology of the myopathies is still not fully understood however a wide range of studies have used gene expression , proteomGenetic selection for broiler performance traits such as bodyweight (BW) and breast yield (BY) has been a core theory as a cause of the myopathies. Published data of large populations of broiler pure lines have estimated low genetic correlation between the three myopathies and performance traits (BY and BW), this indicates there is little shared genetic background between the myopathies and broiler performance traits ; 2020. HThere are many non-genetic factors that can influence broiler growth rates such as incubation, brooding, nutrition, temperature and ventilation . A key aOxidative stress and hypoxia have been highlighted as a key feature of all three myopathies  thereforWhilst genetic correlations indicate that there are no significant links between the myopathies and bird growth at the genetic level, phenotypically it is often the larger birds in a flock which express the myopathies. This phenotypic relationship is not always the case however, as some studies report that WS and WB are not linked to bird weight . Wooden One approach to influencing growth is reducing nutrient intake by diluting or limiting the availability of feed; these methods ultimately impact upon the efficiency of production through poor bird growth or the birds compensate by eating more food and thus do not offer a suitable solution . By targvia the intermediate guanidinoacetic acid (GAA)   but thisid (GAA) . Exogenoid (GAA) ; 2018b.Increasing dietary antioxidants such as vitamin E and selenium have been used to reduce oxidative stress and myopathies but results have been mixed and may depend upon the quality of fat in the diet . A novelpost mortem, the authors stated that SB was not and thus not described fully due to the uncertainty; this raises the question of whether SB is present in the live bird (post mortem change in the muscle. Immediately post mortem, muscle pH drops as a result of lactic acid production which is accompanied by the release of proteolytic enzymes (post mortem changes in the muscle and thus increase SB incidence in a flock. The rate of cooling of carcases post mortem has an influence on the rate of lactic acid production and the activity of the proteolytic enzymes (Spaghetti breast is probably the least understood myopathy  and its ive bird  or only  enzymes . This pr enzymes  and, in  enzymes —the slow enzymes . The useBreast myopathies remain an important focus for the poultry industry and the poultry science community, and it is clear that there is still a lot to understand. The reduction in breast myopathies relies on a holistic approach to control: Balanced breeding by poultry breeders can target the genetic component but the larger influence from non-genetic factors remains an important focus area. Understanding the biological needs of the muscle and ongoing physiology in the modern broiler provides key time-points for strategies to reduce the myopathies and gain more insight into their aetiology .


Tourette syndrome (TS) and obsessive-compulsive disorder (OCD) are two neuropsychiatric disorders that frequently co-occur. Previous evidence suggests a shared genetic diathesis underlying the comorbidity of TS and OCD. This review aims to comprehensively summarize the current literature on the genetic factors linked with TS and its comorbidities, with a focus on OCD. Family studies, linkage analysis, cytogenetic studies, and genome-wide association studies (GWAS) have played a pivotal role in identifying common and rare genetic variants connected with TS and OCD. Although the genetic framework of TS and OCD is complex and multifactorial, several susceptibility loci and candidate genes have been identified that might play a crucial role in the pathogenesis of both disorders. Additionally, post-infectious environmental elements have also been proposed to contribute to the development of TS-OCD, although the dynamics between genetic and environmental factors is not yet fully understood. International collaborations and studies with well-defined phenotypes will be crucial in the future to further elucidate the genetic basis of TS and OCD and to develop targeted therapeutic strategies for individuals suffering from these debilitating conditions. Genetic studies indicate a complex interplay of multiple genes contributing to TS and OCD, with a potential shared genetic diathesis in certain families leading to the manifestation of either or both disorders. GWAS have identified significant genetic overlap between TS and OCD, including SNPs in the LINC01122 gene, suggesting a common genetic nexus for both conditions. Environmental factors such as post-infection autoimmune reactions (GABHS) and psychosocial stressors play a role in exacerbating TS and OCD symptoms, highlighting the need for a holistic approach to understanding these disorders. The evolving field of pharmacogenomics in TS and OCD treatment was discussed, with emphasis placed on the importance of personalized pharmacological interventions tailored to individual genetic variations, particularly in drug metabolism pathways. The emerging role of epigenetic modulation in TS and OCD comorbidity was explored, with emphasis placed on the need for comprehensive research into epigenetic mechanisms and their potential impact on diagnosis and treatment approaches in the future. GABHS, Group a beta-hemolytic streptococci; GWAS, Genome-wide associated studies; LINC01122, Long intergenic non-protein coding RNA 1122; SNP, Single nucleotide polymorphism; OCD, obsessive-compulsive disorder; TS, Tourette syndrome. More than a hundred years ago, the pioneering French neurologist, Gilles de la Tourette, delineated Tourette syndrome (TS) in nine individuals exhibiting repetitive motor and vocal tics during their childhood . For a cTourette syndrome (TS), attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and OCD are intricate neurodevelopmental disorders with a myriad of common and rare genetic factors influencing their onset –9. AlthoThis concise review endeavors to elucidate the prevailing understanding of the most prominent concepts associated with the genetic underpinnings of TS and OCD. Moreover, the review accentuates the conceivable influence of environmental risk factors on the manifestation of these neuropsychiatric conditions. Lastly, the review contemplates the directions for forthcoming research on TS and OCD genetics, encompassing the potential identification of novel therapeutic targets. Ultimately, a more profound comprehension of the complex interplay between genetic and environmental determinants precipitating the onset of these disorders is imperative for devising more efficacious interventions and enhancing the prognosis for affected individuals.Robust evidence underscores the heritability of TS, a neurodevelopmental condition. Family studies have invariably demonstrated the familial aggregation of TS and associated tic disorders, evidenced by a higher prevalence of the disorder among immediate relatives relative to the general population . For insWhile the familial distribution of TS suggests a genetic association, other determinants, such as infectious or environmental risk factors, might also be contributory . Twin stNumerous investigations have endeavored to elucidate the mode of TS’s inheritance, with segregation analyses proposing its transmission as an autosomal dominant trait with incomplete penetrance –25. ConvInterestingly, the paradox of pronounced heritability without identified definitive mutations is not unique to TS. Essential Tremor (ET) is another classical example where, despite clear heritability and extensive research, the responsible mutations remain elusive . SeveralDRD2, HRH3, MAOB, BDNF, SNAP25, and SLC6A4, have been identified in the pathogenesis of both TS and ADHD, hinting at a shared pathogenic pathway  among TS patients compared to those without TS . The undStudies conducted globally have estimated that OCD affects 2–3% of the population throughout their lifetime . family The implication of genetics in disorders was elucidated through research on families and twins, which necessitated identifying specific genetic loci involved. The autosomal dominant inheritance pattern observed in studies marked TS as a prime candidate for linkage analysis. Yet, despite years of parametric linkage studies, no specific genetic locus, except for the HDC gene, which codes for the enzyme L-histidine decarboxylase, has been pinpointed in the etiology of this neurodevelopmental disorder. L-histidine decarboxylase is the rate-limiting enzyme in histamine biosynthesis . A rare Histamine (HA) signaling within the central nervous system is mediated by four 7-transmembrane G protein-coupled receptors, both pre-synaptically (predominantly H3 and H4) and post-synaptically (H1–H3), with presynaptic HA receptors being responsible for regulating the release of HA and dopamine . ExistinInvestigating the potential contribution of recessive genetic variations to reduced penetrance of TS is a complex task. However, autozygosity, which occurs when both alleles at a genetic location are inherited from a single ancestor, allows the application of homozygosity mapping even in small families. This technique has been used to detect recessive variations in highly consanguineous populations . Motlaghin situ hybridization, and array comparative genomic hybridization are valuable tools for detecting chromosomal irregularities like translocations, deletions, and duplications. By identifying genes located near these disrupted regions, potential genes that may increase susceptibility can be identified for further study. Notable chromosomal abnormalities linked with TS familes have been found on several chromosomes, including 2p12, 3p21.3, 7q35-36, 8p21.4, partial trisomy 9, 13q31, and 18q22.3  and OCD, who displayed a specific inversion on chromosome 18q22 . The telCuker et al. described a translocation t , 18p12;. InteresCNTNAP2 gene, a massive gene in our genome  stress response. Notably, pronounced maternal stress during gestation has been linked to a more complex form of TS . In tandToday, physicians are moving away from a “one size fits all” model to one that considers individual patient differences. The ultimate goal of pharmacogenomics is to maximize efficacy and minimize adverse effects. Practice parameters have suggested a difference in pharmacological interventions between tic-associated and non-tic-associated OCD. For example, while selective serotonin reuptake inhibitors (SSRIs), metabolized by the CYP2D6 and CYP2C19 enzymes, are efficacious for treating OCD, their response appears to be less favorable for tic-associated OCD , 82. ConResearch spanning over the past 40 years has shown that the genetic landscape of TS is considerably more diverse and intricate than previously perceived. Significant strides in discerning the genetic underpinnings of TS and its concurrent disorders like OCD have been achieved by leveraging family-based studies, segregation analyses, linkage analysis, GWAS, and investigations into rare genetic variants. Existing data indicates a genetic overlap between TS and OCD. The susceptibility to TS-OCD may be shaped by the cumulative impact of several genes interplaying with distinct environmental determinants, such as psychosocial and infectious stressors. Larger international genetic, epigenetic, and pharmacogenomic studies with well-defined phenotypes in the current era of novel genetic discoveries, will have tremendous ramifications for the tailored diagnosis and therapeutic approaches to comorbid TS and OCD.MK: Writing – original draft, Writing – review & editing, Conceptualization, Methodology, Funding acquisition. FA: Visualization, Writing – review & editing. YK: Writing – review & editing. FM: Funding acquisition, Resources, Supervision, Writing – original draft, Writing – review & editing.


Lactococcus lactis, Lactobacillus helveticus, Pseudoalteromonas nigrifaciens, Streptococcus thermophiles, and Lactobacillus acetotolerans were retrieved from the shotgun sequencing representing the dominant taxa in the studied fermented foods. Additionally, 33 genes that cause antimicrobial resistance (ARGs) against ten different antibiotic classes were detected. Metabolic pathways were abundant in the studied metagenomes, such as amino acid metabolism, carbohydrate metabolism, cofactors, and vitamin biosynthesis. Metagenomic evaluation of Arabian fermented foods, including the identification of probiotics, pathogenic bacteria, and ARGs, illustrates the importance of microbiological analysis in evaluating their health effects.This study uncovered microbial communities and evaluated the microbiological safety of traditional fermented foods consumed in the Arab region. Samples of dairy and non-dairy fermented foods—mish, jibneh, zabadi, and pickles—were collected from local markets in Saudi Arabia. Using the MiSeq system, samples were sequenced using 16S amplicons and shotgun metagenomics. Alpha and beta diversity indicated inter- and intra-variation in the studied fermented foods’ bacterial communities. In the case of mish, the replicates were clustered. Twenty-one genera were found to be significantly different (FDR < 0.05) in abundance in pairwise comparison of fermented foods. Five high-quality, metagenome-assembled genomes (MAGs) of  Saudi Arabia occupies most of the Arabian Peninsula, and most of its population descended from nomadic tribes who historically lived throughout the region. Saudi Arabian society has rapidly shifted from nomadic to urban life in the last fifty years. Despite the modern advancements that have come with this transformation, many people continue to raise goat, sheep, and camel herds. Their daily meals consist of fermented milk products such as laban, mish, cheese, and yogurt, as well as non-dairy, traditional vegetable pickles ,2. AlthoLactobacillus delbrueckii and Streptococcus thermophilus, but may also harbor harmful pathogens, including Salmonella, Listeria monocytogenes, and Staphylococcus aureus  were collected aseptically in sterilized containers. The samples were kept in an icebox during transportation and then stored at a temperature of −80 °C in the laboratory.g. The top fatty layer and supernatant were discarded, and the pellet was used for DNA extraction with the beads-beating method of DNeasy PowerSoil Pro Kit . The beads-beating method is efficient at extracting DNA from a wide variety of microorganisms, and the selected kit also removes PCR inhibitors. DNA extraction from pickle samples was performed following the removal of the vegetable debris using cheesecloth as described previously , bacterial secretion system [PATH:ko03070], and phosphotransferase system [PATH:ko02060] in the studied metagenomes . The cardamX gene for an inner membrane protein involved in bile resistance, and mdtABCD (multidrug resistance protein) were found in mish. The enzymes involved in horizontal gene transfer, including integrase, DNA primase, and phage lysin, were detected in all the fermented foods metagenomes.Relative to pickle, a higher abundance of genes responsible for the glycine, serine, and threonine [PATH:ko00260], arginine and proline [PATH:ko00330], cysteine and methionine [PATH:ko00270], lysine biosynthesis [PATH:ko00300], histidine [PATH:ko00340], phenylalanine, tyrosine and tryptophan biosynthesis [PATH:ko00400], and valine, leucine and isoleucine biosynthesis [PATH:ko00290] were detected in the dairy fermented food samples . HoweverMarinomonas genus from Gammaproteobacteria and Lactococcus and Leuconostoc from Firmicutes were predominantly found in mish samples. These genera were found in lower abundance in most of the other fermented foods that were examined. Limited studies have evaluated the microbiology of mish, and the available culture analysis reported Staphylococcus aureus, psychotropic bacteria, yeast, and lactobacilli from mish samples mainly conducted in Sudan [E. coli, S. aureus, Streptococcus spp., and Salmonella spp. in a study of characterizing microbial hazards associated with mish and other fermented milk [In this study, a combinatorial sequencing approach of 16S amplicon sequencing and shotgun sequencing was employed to study the microbial diversity and the functional potential of the traditional Arabian fermented milk foods and non-dairy fermented foods commonly consumed in the Arabian Peninsula. We identified microbial diversity, probiotics, and variations in relatively dominant bacterial taxa in the studied fermented foods metagenomes. Consistent with previous studies for fermented foods, Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria were commonly found in the studied samples ,34,35. Tin Sudan ,37. Abdated milk .Streptococcus and Lactobacillus were found in relatively high abundance in zabadi and jibneh samples. However, genera of Bacillus, Calothrix, Weissella, and Lactobacillus were abundantly found in pickle samples indicates variation in bacterial community composition among different fermented food types as observed in previous studies and could be linked to the fermented foods substrates, production recipes, environment influence, and manufacturing conditions [Bacillus, Lactobacillus, Clostridium, and Streptococcus were the most prevalent taxa in pickles, and our findings were consistent with the studies from fermented soybeans and vegetables [Lactococcus lactis and Lactobacillus helveticus from jibneh, Streptococcus thermophiles from zabadi, and Lactobacillus acetotolerans were identified from the pickle sample. However, Pseudoalteromonas nigrifaciens genome was retrieved from mish along with Lactococcus species. The source of Pseudoalteromonas nigrifaciens in mish sample is not known, but a previous study by Kothe et al. retrieved P. nigrifaciens from the cheese sample using a metagenomic approach [Taxa of nditions ,6,7. A rnditions . Bacillugetables ,41. Overapproach . FurtherStreptococcus thermophilus and Lactococcus lactis were identified in dairy fermented foods, mainly in zabadi (59.1%) and jibneh (59.7%), respectively. Streptococcus thermophiles and Lactococcus lactis are the prominent probiotics in the dairy industry and possess health beneficial immunomodulatory ability [Lactobacilli strains were also reported in traditional Polish vegetable fermented food [n = 11) followed by in mish (n = 8) samples. The safety of food is a major concern for consumers. Several PORPB were found in the studied samples, mainly in mish (n = 23) metagenome, but the relative abundance of those clinically important pathogenic bacteria was less than 0.1% as previously reported [Vibrio parahaemolyticus (0.06%) and Clostridium botulinum (0.01%) were detected in pickle metagenome. Similarly, an increased number of ARGs were found in mish (26 ARGs) metagenome conferring resistance to lincosamide, tetracycline, pleuromutilin, aminoglycoside, glycopeptide, and beta-lactam antibiotics. Genes causing glycopeptide, beta-lactam antibiotic, and multidrug resistance were also found in the jibneh and zabadi metagenomes. ARGs have been found in fermented vegetables and dairy products at varying levels, reducing the effectiveness of clinically important antibiotics such as aminoglycosides, fluoroquinolones, beta-lactams, tetracycline, lincosamides, fosfomycin, nitrofurans, nitroimidazoles, phenicols, macrolides, and rifamycin [The probiotic species reported in dairy fermented foods were different relative to the beneficial taxa of non-dairy fermented food, probably due to the nature of food substrates. In this study, the enhanced level of  ability ,44,45. Tted food ; in linemish n = 3 metagenibneh 59.%, respecticus 0.0% and Cloifamycin ,48. As aifamycin .Lactobacilli species in dairy and non-dairy fermented foods and encoding the genes for vitamin biosynthesis, fermentation, and secondary metabolites production [Propionibacterium freudenreichii, Bifidobacteria, and Lactobacilli in the gut that could synthesize most of the water-soluble vitamins, including biotin, cobalamin, riboflavin, folates, pyridoxine and thiamine, thus able to fulfill the requirement of the vitamins for the host [Humans fail to synthesize several metabolites, including SCFAs and vitamins, whereas an exogenous supply is needed for the overall development ,50,51. Moduction ,7,53. Vioduction . Moreovethe host ,55,56. Sthe host . Cofactothe host . OverallMarinomonas, Lactococcus, and Leuconostoc were predominantly identified in mish samples, whereas their presence was relatively less pronounced in most other studied fermented food samples. Streptococcus and Lactobacillus were found in relatively high abundance within zabadi and jibneh samples. The mish metagenome exhibited an increased number of ARGs and pathogenic bacteria; however, these were in minor relative abundance. Furthermore, the outcomes of this study suggest that Arabian fermented foods serve as significant sources of probiotic bacteria, fostering carbohydrate and amino acid metabolism, as well as vitamin biosynthesis. Presently, the overall risk to human health stemming from the consumption of these foods is assessed to be low. Nevertheless, responsible production practices and ongoing research are imperative to oversee the safety, nutritional advantages, and potential implications for public health associated with these fermented foods.This study provided an integrated analysis of dairy and non-dairy fermented foods in the Arabian Peninsula, linking microbial diversity and functional gene content. Noticeably distinct bacterial diversity was observed among dominant taxa at lower taxonomic levels in traditional fermented milk mish, when compared to other dairy and pickle samples. Genera such as


Obstructive Sleep Apnea (OSA) is characterized by repetitive collapse of the upper airway during sleep. Drug-Induced Sleep endoscopy (DISE) is used to identify the collapse site. Among the possible sites of collapse, the epiglottis occurs more frequently than previously described. In this study, we reviewed DISE findings and classified different epiglottic collapse patterns. We found 104 patients (16.4%) with epiglottis collapse (primary 12.5% and secondary 3.9%). We described the following patterns of epiglottis collapse: Anterior–Posterior (AP) collapse with rigid component “trapdoor type” (48%); AP collapse with lax component “floppy type” (13.5%); Lateral– Lateral (LL) collapse with omega shape component “book type” (14.5%); and secondary due to lateral pharyngeal wall or tongue base collapse (24%). The identification of the epiglottic collapse pattern is crucial in decision-making when attempting to ameliorate OSA. These findings in OSA phenotyping could influence the type of treatment chosen. Obstructive Sleep Apnea (OSA) is the most prevalent chronic sleep-related breathing disorder ,2,3. It Airway obstruction in OSA patients are commonly multilevel and includes the Velopharynx, Oropharyngeal lateral walls, Tongue base, and Epiglottis (VOTE) classification . Among tIn 1998, Catalfumo et al.  estimateLan et al.  observedIt is important to note that the prevalence of epiglottic collapse was found to be significantly higher when evaluating patients with OSA who have previously failed upper airway surgery, ranging from 44% to 72.9% ,25.The aim of this study is to review DISE findings in our tertiary center and classify the different epiglottic collapse patterns (Francia-Lugo classification).This study was retrospectively performed in the Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE), Clínica Hospital Constitución, Monterrey, Nueva León, México—Sleep Disorders Clinic. All DISE videos performed and data obtained between January 2012 and December 2019 were reviewed by our team.The inclusion criteria were as follows: (1) adult patients (18 to 64 years old); (2) OSA diagnosed (Apnea-Hypopnea Index—AHI > 10) by a non-attended polysomnography type 3, according to The American Academy of Sleep Medicine (AASM) standard ; (3) witAn informed consent was conducted prior to enrollment and authorization was given from the director and main professor of the Sleep Disorders Clinic to review the videos and necessary data in the files.DISE was performed by an otolaryngologist and anesthesia was provided by an anesthesiologist in an ambulatory operating room or in an endoscopic area. We performed a positional exploration in all our patients, starting with supine position. A loading infusion of dexmedetomidine was started at 1 to 1.5 mcg/kg over 10–15 min followed by a maintenance infusion of 1–1.5 mcg/kg/h until completion of the DISE as recently described by Han et al. .Inclusion criteria for DISE examination were as follows: poor adherence to CPAP therapy, defining “adherence” according to US MEDICARE criteria as the use of CPAP at least 4 h each night for 70% of nights during a consecutive 30-day period, during the first 3 months of initial usage , and altVOTE classification . The site, type, and degree of obstruction were recorded.We categorized the obstructive site using In this study we focused on patients with more than 50% of epiglottis collapse (defined as complete) and described their visual characteristics.Anterior–Posterior (AP) primary collapse with rigid component “trapdoor type” in 50 patients (48%);AP primary collapse with lax component “floppy type” in 14 patients (13.5%);Lateral–Lateral (LL) primary collapse with omega shape component “book type” in 15 patients (14.5%).Secondary collapse due to base tongue or lateral pharyngeal walls collapse in 25 patients (24%).We reviewed 634 DISE in which 104 patients (16.4%) were found with epiglottis collapse. We found that 79 patients had primary isolated epiglottis collapse (12.5%) and 25 patients had secondary collapse due to base tongue or lateral pharyngeal walls (3.9%). We describe 4 different types of collapse:Examples of the four types of collapse is shown in The epiglottis is an important anatomical structure that was mainly ignored and/or underestimated in the early research in obstructive breathing disorders .Recent studies, have shown that it plays a pivotal role, either on when it is alone or in combination with other pharyngeal structures .Before the advent of DISE, epiglottis collapse was found on the basis of awake examinations. Its prevalence is thought to be 11.5% . DISE haSpinowitz et al. described in a series of 54 patients included in DISE with upper airway resistance syndrome (UARS) non OSA, that 39% had complete epiglottis collapse without mentioning an isolated or multilevel type of obstruction .In our paper we encountered 16.4% of epiglottis collapse, described as primary 12.5% and secondary due to tongue base or lateral walls collapse 3.9%; we included strictly patients with more than 50% of collapse (VOTE classification) and performed the DISE with dexmedetomidine drug, it may play an important fact in the incidence of our findings. In addition, it has also been shown that AP epiglottis collapse is more frequently than lateral epiglottis collapse and is more common in patients who do not respond to upper airway surgery for OSA ,33.VOTE classification is one of the most used classification in DISE . Other cThere are a few studies describing epiglottis collapse patterns in OSA patients. Torre et al. in a systematic review done in 2015 described two types of epiglottis collapse: AP and lateral (AP being predominant) . RavesloAccording to our findings, we summarized the different epiglottic collapses in two major categories named the Francia–Lugo Classification:Primary or intrinsic epiglottic collapse (76%): where the collapse is due to a structural defect of epiglottic. There are three types of primary epiglottic collapse, as follows:AP collapse with a rigid component (trapdoor).AP collapse with a hyperlax epiglottis (floppy).LL collapse with an omega-shaped epiglottis (book type).Secondary or extrinsic epiglottic collapse (24%): due to compression by other structures .Identification of the epiglottic collapse pattern is crucial in order to solve or improve sleep apnea. The first line of treatment for OSA continues to be CPAP. Actually, previous evidence suggests that CPAP may push the epiglottis further down into the entrance of the larynx, thus being ineffective in treating OSA patients who present with epiglottis collapse. Furthermore, it has been hypothesized that in the presence of a “floppy epiglottis”, the forced pressure generated by CPAP could cause the epiglottis to move backward to the point of complete occlusion at the laryngeal entrance ,37. ThisInterestingly, OSA patients with epiglottis collapse appear to be thinner than common patients with OSA. HY Kim et al. in a case–control study encountered that patients with epiglottic collapse (AP type) showed significantly lower BMI and obstructive sleep apnea severity  .Another factor that predisposes patients to OSA is craniofacial deformity. Similarly, epiglottis collapse is usually unrelated to this characteristic.In our experience we have seen more young and slim patients with epiglottic collapse with different degree of OSA. Therefore, it is crucial to look about these kind of collapse in these type of patients ,39,40.2 laser and robotic surgery are used for the reduction of epiglottic.According to the technique described in the literature, to date, the COEpiglottic with lateral or book cracking, partial resection superior to 75%.Epiglottis with AP collapse “floppy” collapse, partial resection of 50% with epiglottopexy.Epiglottis with AP crack rigid collapse “trapdoor”, partial resection less than 50% with or without epiglottopexy.For the treatment of primary epiglottic collapse confirmed by DISE, Lugo et al.  suggesteTo date, different surgical approaches have been described with the aim of treating this peculiar region, but some of these are technically complex and associated with complications, such as bleeding, edema, persistent dysphagia or dysgeusia ,43.Recently, Salamanca et al.  describeFurthermore, in the case of the omega-shaped epiglottis, horizontally extended cauterization leads to a simultaneous epiglottis opening and stiffening.It is crucial to take into account the functions of the epiglottis. Indeed, the epiglottis is involved in the prevention of food aspiration in two ways: by mechanically closing the laryngeal aditus during swallowing, and by contributing to swallowing through its sensitive receptors distributed on its surface. The main contraindications for the epiglottic surgical procedures are as follows: (1) secondary collapse or extrinsic collapse; (2) concomitant laryngeal pathology with risk of aspiration; (3) inadequate DISE technique; (4) lack of DISE before the surgical procedure. To prevent these unwanted complications, it is important from a technical point of view to leave a 3–4 mm rim of healthy mucosa along the entire profile of the epiglottis .OSA is commonly presented with multilevel obstructions, and identification of epiglottic collapse may improve the surgical success rate. The Francia–Lugo classification findings reviewed in DISE, assists to understand OSA phenotypes. It could have a major impact on the type of treatment or surgery chosen. Additional research is needed to measure the outcomes of these patients depending on the type of collapse, isolated or multilevel concomitant treatment and the relationship between the clinical characteristics and collapse patterns.


Reports on fermented, animal-sourced foods made by Inuit around the circumpolar North have lacked consideration for their unique microbiota and the geo-socio-cultural contexts in which they are made, often resulting in reinforced negative stereotypes. Deficit-based approaches to studying Inuit fermented foods overlook the fact that they have long been considered healthy and integral to Inuit diets. Inuit have deep knowledge on the harvesting, preparation, sharing, and consumption of fermented foods that research efforts must learn from and acknowledge. Our preliminary research into Inuit animal-sourced fermented foods expands current knowledge about the microorganisms needed to make them, and points to a potential to understand how these and other fermented foods impact the human gut microbiome. We provide recommendations for microbiological research on Inuit fermented foods that centers Inuit knowledge within the specific geographic, social, and cultural contexts in which these foods are made. Opportunities are developing in this new paradigm for revisiting existing views on microorganisms, with the understanding that the vast majority of microbes have either neutral or beneficial contributions to human health. In this perspective piece, our goal is to convey that this new paradigm in microbiological research should be put into practice by intentionally and appropriately collaborating with the people who stand to be most impacted by the outcomes of these important studies. We illustrate both the necessity and opportunities that lie in this approach through our work on fermented, animal-sourced foods made by Inuit in Nunavut, Canada.The notion that bacteria and other microbes are pathogens to be controlled and eliminated provided the framework for major advances in microbiology and prevention of infectious diseases over the past two centuries. With the emergence of high-throughput DNA sequencing and related methodologies, as well as enhanced computational power in the past few decades, microbiology has advanced into a new era in which scientists are able to survey all of the microbes in an environment and gain a more complete awareness for the ways that microbial communities and individual microbes promote human health. The importance of fermented foods as staples in human diets is profound as they are estimated to comprise approximately one-third of global food intake. Many thousands of different fermented foods are being made today. For example, over a thousand different types of cheeses and cheese-like products have been documented. Several different groups of microorganisms are recognized as necessary for making fermented foods, and are most commonly defined as members of the lactic acid bacteria and acetic acid bacteria along with certain mold and yeast species. The microbial composition in ready-to-consume fermented foods are determined by many factors, but most prominently by differences in food substrates and production practices. The primary ingredients in many fermented foods are from either plant or animal sources, and despite how fermented foods are frequently portrayed as being carbohydrate-rich and made via fermentative metabolism, this compositional profile is not required to meet the definition. Although there have been intensive efforts to understand the metabolic processes and traits desirable for certain industrial fermentations, only a few traditional fermented foods have been characterized in terms of their microbial and nutritional contents.Fermented foods are defined as foods and beverages that are made through desired microbial growth and enzymatic conversions of food components. Animal-sourced foods  from marine and terrestrial environments in Inuit homelands are consumed raw, frozen, cooked, or fermented. Inuit fermented foods are characterized by minimal human control. Among the publications describing the production processes and cultural significance of traditional fermented foods in greater depth, most are focused on fermented walrus (igunaq) and fermented seal and whale. Other examples of Inuit fermented meats include fermented trout, arctic char, narwhal, and caribou. Cultural research on Inuit food fermentation is otherwise limited and contains mainly brief descriptions of the fact that Inuit make and consume fermented foods. Nutritional and microbiological research focused on Inuit fermented foods are also very limited. Andersen (2005) provides an overview of the nutritional content of a large selection of Inuit foods including some aged foods. There is most often no addition of salt, no use of starter cultures, and no direct control of temperature, as these foods are traditionally prepared in the natural environment. We suspect that the minimal employment of control will result in highly variable and microbially diverse ferments, but more research is needed to start to understand how Inuit fermentation processes impact the microbial communities of the final products.We were recently commissioned by the Government of Nunavut to prepare a literature review and perform preliminary microbiological research on homemade, fermented, animal-sourced foods prepared by Inuit in communities in Nunavut, Canada. Inuit around the circumpolar North have traditionally consumed a protein- and fat-rich diet primarily from marine and terrestrial animals and fermented meats from other geographic regions,14. Members of the Clostridium genus constituted the majority of bacteria found on walrus and seal meat. Narwhal contained high levels of Clostridium and Bacteroidales. The high fraction of Clostridium in these fermented meats is unique and contrasts with previous studies on fermented meat products. These foods were different from trout and arctic char fermentations, which were enriched in Pseudomonas and Photobacterium species [Pseudomonas and Photobacterium are also found in hákarl, fermented shark, and these taxa colonize fish and other marine animals. For any given animal type, the predominant taxa on the muscle tissue also constituted the majority of bacteria found on fat and skin (data not shown). Overall these findings are in keeping with the understanding that the type of substrate determines the dominant bacteria in the fermented food [Our examination of the microbial contents of fermented muscle tissue meats using 16S rRNA gene amplicon DNA sequencing showed that those foods contain a unique microbiota, distinct from dried meats prepared by Inuit in Greenland species . Both Psted food .Clostridium and Bacteroidales was notable because these bacterial taxa are generally not understood to be abundant in fermented and other food products. Clostridia encompass diverse endospore forming bacteria and are found in soils and both clostridia and Bacteroidales inhabit animal and human digestive tracts. Clostridia in foods are mainly understood for their pathogenic or food spoilage properties. Importantly, the microorganisms identified on the Inuit fermented, animal-sourced foods were abundant. Across the 47 food samples tested, there was a median amount of 2.75 × 108 cells/g according to quantitative real-time PCR, ranging from a low of 4.0 × 104 cells/g on a sample of walrus meat, to a high of 1.6 × 1011 cells/g on a sample of arctic char. Although cell viability was not measured, it is clear that these foods, which are commonly not cooked before consumption, provide a rich source of dietary microorganisms.Finding , scientific publications on Inuit fermented meats thus far have primarily emphasized potential safety concerns for foodborne illness, including those caused by certain clostridia species,21. Raw and fermented walrus, seal, caribou, and whale were the most commonly-reported traditional foods tied to foodborne illness,21 and in particular, walrus consumption was primarily associated with botulism and trichinosis among Canadian Inuit populations. To understand and prevent foodborne illness from fermented meats, a holistic approach is needed. For example, botulism is associated with igunaq consumption, but has only been observed when it is not properly prepared,23. In one study, the causative agent of trichinosis in the Arctic Trichinella nativa from fermented walrus, igunaq, was found to be rendered non-infective, while larvae from non-fermented walrus were infective. A different study on a different species of Trichinella (T. patagoniensis) found larvae to be infective for several weeks in decomposing meat under different environmental conditions. These studies as well as the experiences from the current projects shows us that we lack an understanding of the interplay between fermented foods and food-borne parasites in the Arctic.While Inuit-led initiatives such as the Alaskan Inuit Food Security Conceptual Framework by the Inuit Circumpolar Council Alaska have identified the importance of Inuit fermentation practices for communities. Although the health benefits of fermented foods are best understood for those foods made using lactic acid bacteria, this view is biased towards foods more frequently represented in the scientific literature. While the mechanistic basis for how fermented foods support human health beyond basic nutrition remains to be fully understood, there is evidence that fermented food consumption alters the human gut microbiome . Moreover, the intake of fermented foods containing viable microorganisms may support human health. Fermented foods that do not have a microbial inactivation step  may account for the ingestion of 108 to 1011 microorganisms per day,30. These ingested microbes may transiently constitute greater than 0.1% of the bacteria in the digestive tract. Such numbers have prompted broader inquiries on the potentially far-reaching ways in which consuming live microorganisms improve human health. Thus, our findings lead us to acknowledge that there is a scientific knowledge-gap around fermentation of animal-sourced foods, where emphasis has previously been on potential food safety issues rather than how those foods and the large number of microorganisms they contain have benefited and continue to benefit Inuit. Our investigation broadens the diversity of microorganisms known to be consumed safely in human diets, and opens new opportunities to appreciate and understand the importance of commensal microorganisms in food production and potentially even in the prevention of non-communicable diseases. In order to further explore this new diversity of food-fermenting microorganisms, the employment of metagenomic approaches that allow for strain-level detection is recommended. Optimally, well-planned and comprehensive sampling schemes followed by high-coverage shotgun sequencing and whole-genome assembly of high-quality metagenome-assembled genomes will allow an assessment of the diversity within fermenting Clostridium species, potentially pointing towards species with yet unrecognized capacities. Collaborative research with Inuit, centering Inuit knowledge, and including metabolomic and metatranscriptomic data, are also key to new studies to reveal connections to nutritional and beneficial health properties.This emphasis on food safety neglects to consider the fact that these foods have been and continue to be dietary staples consumed by Inuit without adverse health effects. The production of these foods may actually increase food safety. Perception of food safety risk is contrary to the increasing appreciation that fermented foods in general are beneficial for human health to increased reliance on imported and processed, store-bought foods. This reliance has not only significantly altered population health but also heightens concerns for both food security and food sovereignty among Inuit.Before attempting to undertake further studies on Inuit traditional fermented foods, it is essential to first approach fermentation practices within their specific geo-socio-cultural contexts. For example, cultural changes occurring among Inuit populations due to the impacts of colonialism have resulted in a transition away from a traditional, hunter-gatherer dietFor research efforts to support health and food sovereignty among Inuit in their homelands, the following approaches are proposed:(1) Understand the context of fermented food production and consumption practices from a community and Inuit perspective: in addition to learning about the food material itself through microbial and nutritional analyses, visiting scientists must work collaboratively with Inuit, respect Inuit knowledge on an equal footing, respect Inuit language, and invest in learning about Inuit culture and the local context. This includes the socio-cultural context of these foods, the connections between people, and people and the land that is expressed through these foods, the roles of the animals consumed, the geographical context, as well as the nutritional decision-making context of these foods.(2) Investigate the microbial ecology and processes in fermented food production to support Inuit food safety, food security, and food sovereignty. Understanding the microorganisms and the enzymatic and other properties required for the making of local and traditional fermented meats may expand opportunities for continuing these healthy practices and with the same sensory attributes. Studies may then, in close collaboration with Inuit knowledge-holders and communities, flag any local changes to harvesting/hunting and preparation practices (such as preparing these foods indoors as opposed to outdoors) that could alter the microbial contents in ways that may negatively affect safety and sensory aspects of those foods. The altered microbial signature may or may not correspond to common microbes of interest in current food science.. Although previous work has documented Inuit seasonal changes in gut microbiota, any health and wellness benefits associated with these changes have not been described; nor has any published work covered the impacts of Inuit fermented food consumption in particular on gut microbiota and health. Growing evidence, for example, supports the hypothesis that gut microbiota manipulation via diet may have benefits to mental health and wellness, but we lack knowledge about how specific foods and microbial components might achieve this.(3) In research there is an opportunity to focus on the academic knowledge-gaps around the health and wellness benefits of preparing and consuming local and/or traditional fermented foods, including benefits to physical and mental health as well as social, cultural, and environmental health: a recent dietary intervention study found positive changes in immunity when people consumed a diet enriched in fermented foods from plant and dairy sourcesIn conclusion, combining new microbiological techniques with projects both led and informed by Inuit who make and consume fermented foods will provide for new ways of understanding the value of these traditional animal-sourced foods. The full benefits of making, sharing, and consuming these local and traditional fermented, animal-sourced foods are only understood within their geographical, social, and cultural contexts. By respecting the equal value of Inuit knowledge to Western scientific techniques and co-producing knowledge in support of microbial observations about traditional fermented foods, we can enhance understandings of these foods and their nutritional and bioactive constituents, and also potentially expand global discussions on what constitutes a healthy human diet.


Birds fed diets containing GLC showed an identical different growth rate to the control group. However, the total feed intake (TFI) increased quadratically in the GLC50 and GLC100 groups as compared to that in the control group. GLC addition had no significant effect on the weights of internal and immune organs, except for a decrease in bursal weight in the GLC150 group (p = 0.01). Dietary GLC addition increased the feed cost and total cost at 50 and 100 mg kg−1 doses. The percentages of n-3 and n-6 PUFA in the breast muscle of broiler chickens fed GLC-supplemented diets increased linearly in a dose-dependent manner (p < 0.01). The serum alanine aminotransferase (ALT) level and the uric acid level were quadratically increased in the GLC150 group. The serum levels of total antioxidant capacity, catalase, superoxide dismutase, interleukin-1β, and interferon-gamma linearly increased, while the MDA level decreased in the GLC-fed groups in a dose-dependent manner. Normal histological characterization of different liver structures in the different groups with moderate round cells was noted as a natural immune response around the hepatic portal area. The different experimental groups showed an average percentage of positive immunostaining to the proinflammatory marker transforming growth factor-beta with an increase in the dose of GLC addition. The results suggest that GLC up to 100 mg kg−1 concentration can be used as a feed additive in the diets of broiler chickens and shows no adverse effects on their growth, dressing percentage, and internal organs. GLC addition in diets improves the antioxidant activity and immune response in birds. GLC help enrich the breast muscle with n-3 and n-6 polyunsaturated fatty acids.Recently, researchers have been intensively looking for novel, safe antibiotic alternatives because of the prevalence of many clinical and subclinical diseases affecting bird flocks and the risks of using antibiotics in subtherapeutic doses as feed additives. The present study intended to evaluate the potential use of 1,3-β-glucans (GLC) as antibiotic alternative growth promotors and assessed the effect of their dietary inclusion on the growth performance, carcass traits, chemical composition of breast muscles, economic efficiency, blood biochemical parameters, liver histopathology, antioxidant activity, and the proinflammatory response of broiler chickens. This study used 200 three-day-old ROSS broiler chickens . They were assigned to four experimental groups with four dietary levels of GLC, namely 0, 50, 100, and 150 mg kg The economic production of broiler chickens is critical for sustained meat supply, and feed is a crucial factor that influences the economic and productive performance of broiler chickens ,2. Antibβ-glucans (GLC) are glucan polymers derived from the cell walls of yeast, fungi, and bacteria as well as cereal grains such as barley and oat . 1,3 β-gThe addition of GLC to feed enhanced gut health and disease resistance in birds challenged with necrotic enteritis by stimulating the gene expression of antimicrobial peptides . By enhaEuglena gracilis) with more than 50% content of 1,3 β-glucan, unlike yeast-based GLC that contain 5–15% 1,3 β-glucan. The high digestibility of algal cells makes GLC more bioavailable without extraction. Therefore, the aim of the present study was to assess the potential effects of the dietary addition of algae-based GLC as antibiotic alternative growth promoters on some production performance and health aspects of broiler chickens such as growth, carcass traits, economic efficiency, chemical composition of breast muscles, blood biochemical parameters, liver histopathology, antioxidant activity, and proinflammatory responses in broiler chickens.In the present study, we used algae-based GLC produced from a unique species of microalgae .2). The experiment lasted for 35 days. During the first week, the building temperature was set at 34 °C and gradually reduced until it reached 25 °C at the end of the experiment. The illumination regime was set to 23:1 h light/dark, then 20:4 h light/dark until the end of the experiment. The birds were exposed to a 3-day adaptation period prior to the experiment to achieve an average body weight (BW) of 98.71 ± 0.17 g. They were then randomly assigned to four treatment groups with five replicates for each group (10 chicks/replicate). Chicks were fed basal diets supplemented with four concentrations of GLC : 0, 50, 100, and 150 mg kg−1 of diet. The treatment groups were designated as GLC0, GLC50, GLC100, and GLC150, respectively. The birds were fed the experimental diets on three feeding periods: starter (4th–10th day), grower (11th–23rd day), and finisher period (24th–35th day). The GLC was mechanically mixed with other feed ingredients and offered to the birds in a mash form. The proximate composition of the basal diet is shown in A total of 200 one-day-old mixed chicks (Ross 308 broiler) were obtained from a commercial chick producer . Chicks were reared in an open, well-ventilated house with sawdust bedding , and feed intake (FI) were then recorded at 10, 23, and 35 days. The feed conversion ratio (FCR) was calculated by dividing FI by BWG.The protein efficiency ratio (PER) was calculated according to McDonald et al. .(1)PER=The relative growth rate (RGR) was calculated according to Brody .(2)RGR=At the end of the feeding period, the birds (10 birds/group) were euthanized by cervical dislocation . The bloTen birds from each group were randomly chosen, fasted, and euthanized by cervical dislocation . The weiv/v) for fatty acid analysis [At the end of the feeding period, five breast muscle samples were collected from each group. The proximate composition of the breast muscles  was determined. We also extracted the oils from the breast muscle by using a solvent mixture of chloroform/methanol  was used to measure serum creatinine and uric acid levels ,30. We aThe serum malondialdehyde (MDA) level was measured according to the method of Mcdonald and Hultin . We alsoFollowing the method of Omar et al. , samplesThe inflammatory response of broiler chickens fed GLC was investigated in the leucocytic populations of the liver and spleen by determining TGF-β levels according to the methods described by Amer et al. .The feed cost (FC), total cost (TC), total return (TR), and net profit (NP) were calculated according to the method of El-Telbany and Atallah  and DunnTC (USD) = Fixed cost + Variable cost ;FC/kg gain = Total FC/Total BWG;TR (USD)/bird = Price of kg × live BW/bird;NP (USD) = TR − TC;Economic efficiency (EE) = NP (USD)/total FC (USD).Performance index% (PI) was calculated according to the method of North and Bell  as folloPI% = final live BW (kg)/FCR × 100.p < 0.05. The normality of the data was verified using the Shapiro–Wilk test, and the homogeneity of variance among the components of the experimental treatments was confirmed by Levene’s test. The data were analyzed using one-way analysis of variance (ANOVA) and the GLM procedure in SPSS . By using orthogonal polynomial contrasts, the linear and quadratic effects of GLC were demonstrated. Tukey’s test was used to compare mean differences with a 5% probability. The data variation was represented as pooled SEM, and the significance level was established at p > 0.05). The only exception was the feed intake that quadratically increased in the GLC100 group during the grower period and in the GLC50 group during the finisher period relative to the GLC0 group (p < 0.01). The overall performance was nonsignificant among the groups for final BW, total BWG, FCR, RGR, and PER (p > 0.05). The total feed intake was quadratically augmented in the GLC50 and GLC100 groups as compared to that in the control group (GLC0) (p < 0.01).p > 0.05). However, the bursal weight was decreased in the GLC150 group (p = 0.01)  .p > 0.05). The breast muscles of birds fed GLC-supplemented diets showed a linear increase in the percentages of α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, linoleic acid, arachidonic acid, n-3 PUFA, and n-6 PUFA (p < 0.01)  .p = 0.03). The GLC150 group showed a linear increase in uric acid levels (p = 0.03). The serum AST and creatinine levels did not differ significantly between the groups. The liver and kidney function test results represented by the serum levels of ALT, AST, uric acid, and creatinine are shown in p < 0.01). In contrast, the MDA levels were linearly reduced in the GLC-fed groups (p < 0.01). The effects of GLC supplementation on the antioxidant and inflammatory indices are shown in The examined liver sections from the GLC0, GLC50, GLC100, and GLC150 groups showed the standard histomorphological structure of the liver. Mild portal vascular dilatation was observed in the GLC100 group. Moderate peri-portal lymphocytic aggregation were observed in GLC50, 100, and 150 I,II).TGF-β) (p < 0.01) in the different GLC-supplemented groups as follows: 0.15%, 0.995%, 2.22%, and 6.36% for GLC0, GLC50, GLC100, and GLC150 groups, respectively, in the liver sections . However, TR, NR, FC/kg gain, PI%, and EE were not affected by GLC supplementation (p > 0.05)  .−1 GLC (derived from Agrobacterium sp.) on birds’ growth. Cox et al. [−1 diet with or without an Eimeria challenge. Zhang et al. [−1 GLC (derived from Saccharomyces cerevisiae). In contrast, Kazempour et al. [−1) reduced feed intake and daily average gain and improved FCR in broiler chickens during the starter, grower, and finisher periods.GLC have important biological activities and play an important function in disease prevention and animal production performance . In the x et al.  showed ng et al.  demonstrg et al.  reportedg et al.  found inr et al.  reported−1; this may be due to increased inflammatory response. Similarly, Tang et al. [−1 concentration had no effect on the internal organs, namely the liver, spleen, and pancreas of broiler chickens; however, it decreased the abdominal fat and increased the weight of the small intestine and gizzards.In the current study, dietary GLC supplementation did not influence the carcass traits; dressing percentage; and the weights of the spleen, liver, intestine, and gizzard. These results indicate that GLC supplementation had no negative effects on the internal organs of birds. The bursal weight was decreased at the highest GLC concentration of 150 mg kgg et al.  reportedg et al. , GLC at Many factors affect meat quality, such as diet composition, genetic structure, sex, housing management, slaughter method, and the type of muscle fibers . The rec−1), as observed in the results of the liver histopathological examination, where normal liver histoarchitecture was found in all experimental groups with mild portal vascular dilatation and lymphoplasmacytic aggregations in the GLC100 group. A minimal number of inflammatory cells were recorded in the GLC0 and GLC50 groups. The GLC150 group showed moderate peri-portal lymphocytic aggregation.Regarding the liver and kidney function tests, the current study showed that the GLC150 group had higher serum ALT and uric acid levels, while their levels did not stray from the normal levels [Regarding the antioxidant status of broiler chickens in response to dietary GLC supplementation, the results showed increased serum levels of TAC, CAT, and SOD. The MDA levels in GLC-fed groups were decreased in a concentration-dependent manner. GLC can boost the antioxidant capacity of animals by enhancing the activity of the antioxidant enzymes CAT, SOD, and glutathione peroxidase, as well as by enhancing the scavenging activity of the superoxide anion and the hydroxyl radical and by preventing lipid peroxidation . The comEscherichia coli and Salmonella enterica [Regarding the inflammatory responses in broiler chickens fed with a GLC-supplemented diet, the results showed increased serum levels of IL-1β and IFN-γ in the GLC-fed groups in a concentration-dependent manner. Moreover, dietary GLC supplementation increased TGF-β immunoexpression in chicken liver and spleen tissues in a concentration-dependent manner. Proinflammatory cytokines (interferon-γ and IL-1β), which are essential immune proteins, are endogenous signaling molecules that facilitate cellular defense against inflammatory response . Broilerenterica ,57. GLC enterica . Immune enterica . The othFrom an economic point of view, dietary GLC supplementation did not affect the TR, NP, performance index, and EE of the treated groups. This effect was due to the increase in the amount of feed intake by birds in the GLC50 and GLC100 groups with no change in the growth rate of birds. However, birds fed GLC-enriched diets have the advantages of transferring energy to the development of immune response and antioxidant capability, which improves the health and performance of birds. These results have more economic value than weight gain in maintaining adequate health of chicken flocks because clinical and subclinical diseases result in reduced feed intake, weight, and severe morbidity and mortality, which consequently harm animal welfare and cause substantial economic problems to poultry producers ,59.−1 with no adverse effects on growth, carcass traits, and internal organs. The addition of GLC improves the antioxidant status of the fed birds by enhancing the activity of antioxidant enzymes, namely CAT, SOD, and glutathione peroxidase. GLC also boosts immunity by enhancing the release of proinflammatory cytokines. Furthermore, GLC supplementation helps enrich breast muscles with n-3 and n-6 PUFA. However, a limitation of this study is that it used mixed chickens and only five replicates per treatment. Therefore, using mono-sex chickens and a higher number of replications in future studies is recommended.Based on the study outcomes, we can conclude that dietary GLC can be used as a feed additive in the diet schedule of broiler chickens at a concentration of up to 100 mg kg