Inheritance Factors Research Articles

Теория и кейсы креативного туризма

The pertinence of the study stems from the need to develop the domestic tourism market and creative tourism as one of its areas. Creativity has become a place build-ing strategy as cities and regions seek to increase their appeal to the middle class, support the creative industries, or become “creative cities.” The article analyzes the conceptual apparatus of the creative industry, trends in the development of the crea-tive economy. The practical connection between creativity and the creative economy is represented by specific examples of creative tourism associated with various festi-vals and events. The most famous are the Kunqu opera (Hangzhou, China), the birth-place of Hieronymus Bosch (Hertogenbosch, the Netherlands), Frevo-style music concerts (Recife, Brazil), the CounterPlay festival (Denmark), the #Urbanana project (North Rhine-Westphalia, Germany). In Russia, creative tours are a niche type of tourism and are not yet arranged in all regions, for example, in the Sverdlovsk and Ivanovo regions, the Perm Territory, and the Khanty-Mansiysk Autonomous District. Thus, the purpose of the study is to analyze the theory of creative tourism and identi-fy the most successful examples of the implementation of creative tours. On the one hand, festivals and events serve to stimulate commercial activities, create new jobs and increase attendance, on the other hand, cultural events have become a common means by which creative spaces are created. The presence of creative events shows a growing relationship between the tourism industry and strategies for creating and promoting tourist destinations. The ability of a tourist destination to compete de-pends on its ability to transform basic inherited factors into created assets with a higher symbolic or iconic value.

Correlation between Slope 2 in Clot Waveform Analysis of Activated Partial Thromboplastin Time with Factor VIII Activity in Hemophilia A

Hemophilia A is an inherited factor VIII deficiency disease, related to X chromosome. Diagnosis of Hemophilia A is made based on Factor VIII assay. Nowadays, Hemophilia A therapy is by giving factor VIII concentrate, so that monitoring of this therapy must be done by examine Factor VIII activity, but examination of Factor VIII activity is currently still limited in facilities and quite expensive. One of activated partial thromboplastin time (aPTT) optical methods can provide information about every stage of coagulation through clot waveform analysis. Factor VIII activity can describe in slope 2 of clot waveform analysis, which deficiency of factor VIII will cause slope 2 slighter than normal, because the clot form is not optimal and the light transmission recorded at clot waves do not decrease maximally. The aim of this study was to analyze the correlation between slope 2 on the clot waveform analysis of the optical method on aPTT test with Factor VIII activity in hemophilia A subjects. This was a correlative observational study cross sectional study, conducted at Hasan Sadikin General Hospital Bandung in August 2018-September 2019. The subjects were member of Hemophilia A sufferers of West Java Hemophilia Society. The research subjects were assesed for Factor VIII activity and optical method of aPTT. Slope 2 calculated from the clot waveform analysis that formed in aPTT examination. This study involved 43 subjects, with a median age of 6 years, an age range of 1-45 years, and 51.2% of patients aged 6-17 years. The results of Factor VIII activity in this study had a median 0% with a range 0-25.9%, and the value of slope 2 had a median 1.0%T/sec with a range 0.5-3.5%T/sec. The correlation test between slope 2 and Factor VIII activity with 95% confidence interval using Spearman's correlation test showed very strong positive correlation which statistically significant (r = 0.854 and p <0.001). Conclusion: there was a statistically significant very strong positive correlation between slope 2 on the clot waveform analysis of aPTT optical method test with the activity of Factor VIII in Hemophilia A.

Inheritance factor on the physical properties in metallic glasses

Material genetic engineering can significantly accelerate the development of new materials. As an important topic in material science and condensed matter physics, the development of metallic glasses (MGs) with specific properties has largely been the result of trial and error since their discovery in 1960. Yet, property design based on the physical parameters of constituent elements of MGs remains a huge challenge owing to the lack of an understanding of the property inheritance from constitute elements to the resultant alloys. In this work, we report the inherent relationships of the yield strength σ y, Young’s modulus E, and shear Modulus G with the valence electron density. More importantly, we reveal that the electronic density of states (EDOSs) at the Fermi surface (E F) is an inheritance factor for the physical properties of MGs. The physical properties of MGs are inherited from the specific element with the largest coefficient of electronic specific heat (γi ), which dominates the value of the EDOS at E F. This work not only contributes to the understanding of property inheritances but also guides the design of novel MGs with specific properties based on material genetic engineering.

Behavioral genetics and genomics: Mendel’s peas, mice, and bees

The question of the heritability of behavior has been of long fascination to scientists and the broader public. It is now widely accepted that most behavioral variation has a genetic component, although the degree of genetic influence differs widely across behaviors. Starting with Mendel’s remarkable discovery of “inheritance factors,” it has become increasingly clear that specific genetic variants that influence behavior can be identified. This goal is not without its challenges: Unlike pea morphology, most natural behavioral variation has a complex genetic architecture. However, we can now apply powerful genome-wide approaches to connect variation in DNA to variation in behavior as well as analyses of behaviorally related variation in brain gene expression, which together have provided insights into both the genetic mechanisms underlying behavior and the dynamic relationship between genes and behavior, respectively, in a wide range of species and for a diversity of behaviors. Here, we focus on two systems to illustrate both of these approaches: the genetic basis of burrowing in deer mice and transcriptomic analyses of division of labor in honey bees. Finally, we discuss the troubled relationship between the field of behavioral genetics and eugenics, which reminds us that we must be cautious about how we discuss and contextualize the connections between genes and behavior, especially in humans.

Dopamine-transporter heterozygous rats carrying maternal wild-type allele are more vulnerable to the development of compulsive behavior.

Compulsivity is defined as an unstoppable tendency toward repetitive and habitual actions, which are reiterated despite negative consequences. Polydipsia is induced preclinically by intermittent reward, leading rodents to ingest large amounts of fluids. We focused on the role of dopamine transporter (DAT) and inheritance factors in compulsive behavior. Our sample consisted of DAT heterozygous (HET) rats with different genetic inheritance (MAT-HET, born from WT-dams×KO-fathers; MIX-HET, born from HET-dams × KO-fathers). As controls, we used both wild-type (WT) rats and their socially-isolated (WTi) siblings. We ran the schedule-induced polydipsia (SIP) protocol, to induce compulsive behavior; then the Y-maze and marble-burying tests, to verify its actual development. Only MAT-HET (who inherited the functional DAT allele from the WT mother) is vulnerable to developing compulsive behavior. MAT-HET rats drank increasingly more water during SIP; they showed significant perseverance in the Y-maze test and exhibited compulsive actions in the marble-burying test. Interestingly, compulsive behaviors of MAT-HET rats correlated with expression ex vivo of different genes in different areas. Regarding the prefrontal cortex (PFC), D2R correlatedwith Y-maze "perseverance" in addition to BDNF; considering the amygdala (AMY), both D3R and OXTR correlated with SIP "licks." Indeed, compulsivity may be linked to D2R and BDNF in PFC, while extreme anxiety in MAT-HET rats may be associated with D3R and OXTR in the AMY. These results confirm some similarities between MAT-HET and DAT-KO subjects, and link the epigenetic context of the DAT gene to the development of compulsive behavior.

Analysis of Technological Heredity in the Production of Rolling Bearing Rings Made of AISI 52100 Steel Based on Waviness Measurements.

The production of rolling bearings is a complicated process that requires the use of many operations. The manufactured elements of rolling bearings should be of high quality while minimizing production costs. Despite many research studies related to the analysis of technological processes, there is still a lack of research and tools allowing us to satisfactorily assess the relationships between individual operations of the rolling bearing ring process of production and the quality. To perform such an assessment, one can use the concept of technological heredity phenomenon analysis. As the surface waviness of the bearing race is of key importance, the present paper aims at evaluating how the individual technological operations of the rolling bearing ring production process affect the formation of their surface waviness. The surface waviness of the bearing race was measured in both directions (two sections), i.e., along the circumference using the Talyrond 365 measurement system and across the circumference of the race using Talysurf PGI. The production of 6308-2z rolling bearings made of AISI (American Iron and Steel Institute) 52100 bearing steel was analyzed. The occurrence of the phenomenon of technological heredity in the production of rolling bearings was observed. The research results indicate that the turning operation reduces the surface waviness of the bearing rings obtained after forging, while the heat treatment causes a slight increase in surface waviness. On the other hand, grinding operation significantly reduces the waviness, with this reduction being greater for the outer ring. Furthermore, the research has shown that the waviness of the surface is an inheritance factor caused by individual operations of the rolling bearing rings manufacturing process.

Integrative therapies for amyotrophic lateral sclerosis disease using dynamic physiological systems

BackgroundAmyotrophic Lateral Sclerosis (ALS) is a fatal motor neuron condition that is characterized by progressive loss of upper and lower motor neurons at the spinal or bulbar level with an incidence of about 1/100,000. ALS is categorized in two forms. The most common form is sporadic (90–95% of cases) which has no obvious genetically inherited component. The familial type of ALS (FAL5, represents ~10% of cases) is due to associated genetic dominant inheritance factors. The first onset of symptoms of ALS usually occurs between the ages of 50 and 65. The pathogenesis of ALS is unknown. There are two approved medications for ALS treatment: riluzole and edaravone, both of which have many reported side effects. ALS patients and their family members seek an effective therapy for treating the symptoms and/or delaying the progression of ALS.MethodA comprehensive literature search consisting of 12 peer reviewed studies was conducted using PubMed, Medline and Nature review from inception to 2019, and meta‐analysis used to evaluate the findings. Amyotrophic Lateral Sclerosis diagnosis was determined using El Escorial criteria. Exposures to agriculture chemicals, heavy metals, electrical magnetic fields, types of diet, and physical activity were all examined for association with ALS. Also, use of integrative therapies (IT) were evaluated among the treatment options reviewed.ResultsThe results of the study did not indicate that factors of diet, smoking or cardiovascular disease increase the risk of developing ALS. Vitamins and Chinese herbal decoctions, Chinese herbal compounds, massage therapy, and acupuncture were the 5 most commonly used IT reported. In the meta‐analysis reviewed, the most common reason for using IT was to treat weakness and fatigue in males (68.72% of males were IT users) and muscle atrophy in females (66.35% of females were IT users). Most of the effects of the IT therapies reported were improvements in subjective symptoms of the disorder.ConclusionThis study could not identify smoking, physical activity, environmental exposure, occupational factors, or dietary habits as risk factors or protective factors for the onset or progression of ALS. ALS has multiple pathological mechanisms. Since integrative therapy contains various components which display multiple effects, it would be helpful in alleviating the pathological events affecting patients with ALS, thereby increasing the quality of life for the individuals and families of patients. However, more research must be performed regarding the efficacy and safety of integrative therapy or complementary and alternative therapy and clinical studies will be required to demonstrate the complimentary beneficial effects of integrative therapies in the management and treatment of ALS.

Secure User Authentication Leveraging Keystroke Dynamics via Wi-Fi Sensing

User authentication plays a critical role in access control of a man-machine system, where the knowledge factor, such as a personal identification number, constitutes the most widely used authentication element. However, knowledge factors are usually vulnerable to the spoofing attack. Recently, the inheritance factor, such as fingerprints, emerges as an efficient alternative resilient to malicious users, but it normally requires special equipment. To this end, in this article, we propose WiPass, a device-free authentication system only leveraging the pervasive Wi-Fi infrastructure to explore keystroke dynamics (manner and rhythm of keystrokes) captured by the channel state information to recognize legitimate users while rejecting spoofers. However, it remains an open challenge to characterize the behavioral features hidden in the human subtle motions, such as keystrokes. Therefore, we build a signal enhancement model using Ricean distribution to amplify user keystroke dynamics and a hybrid learning model for user authentication, which consists of two parts, i.e., convolutional neural network based feature extraction and support vector machine based classification. The former relies on visualizing the channel responses into time-series images to learn the behavioral features of keystrokes in energy and spectrum domains, whereas the latter exploits such behavioral features for user authentication. We prototype WiPass on the low-cost off-the-shelf Wi-Fi devices and verify its performance. Empirical results show that WiPass achieves on average 92.1% authentication accuracy, 5.9% false accept rate, and 6.3% false reject rate in three real environments.

Collaboration of vessel speed optimization with berth allocation and quay crane assignment considering vessel service differentiation

Green shipping and efficient information sharing deepen the collaboration between shipping companies and ports, enabling vessel speed optimization (VSO) to be integrated with the berth allocation and quay crane assignment problem (BACAP). However, the literature presented to date usually considers all vessels as a whole and only addresses the vertical conflict between the two levels of the BACAP and the VSO but neglects the horizontal conflict among vessels in each level of the collaborative planning. To describe and address the conflicts within and between levels, we consider the vessel service differentiation (VSD) and propose a BACAP-VSO with VSD (BACAP-VSO-w/-VSD) collaboration mode. To this end, we set up a bi-level multi-objective optimization model. In the upper-level BACAP model, the VSD is implemented by separating vessels into different preferential groups. Multi-objectives are formulated to minimize the service delays of vessels in preferential groups and all vessels. In the lower-level VSO model, the VSD is realized by grouping vessels based on their shipping companies. Multi-objectives are solved to minimize the fuel consumption costs of each shipping company. We develop a nested genetic algorithm incorporated with an inheritance factor and jumping operations for the solution approach. Experimental results show that the proposed collaboration mode can analyze trade-offs among multiple conflicting objectives in any and between both planning levels. Compared to the existing collaboration mode, the proposed collaboration mode further reduces service delays of vessels and fuel consumption costs of shipping companies, improves customer satisfaction, and effectively reduces vessel emissions.

Numerical analysis of the strip crown inheritance in tandem cold rolling by a novel 3D multi-stand FE model

The strip shape inheritance model is widely applied to improve the strip shape quality in tandem cold rolling (TCR). However, the inheritance mechanism is still currently unclear. To bridge this gap, this paper presents a new numerical method for calculating the strip crown inheritance factor. In addition, the effects of the entry strip crown on exit strip crown and flatness were quantitatively analysed at each stand in the TCR using a novel three-dimensional (3D) multi-stand elastic–plastic finite element (FE) model. The results show that the strip crown inheritance factor increases slowly from S1 (stand 1) to S3 (stand 3), while rising sharply from S3 to S5 (stand 5), reaching a peak value of 0.495 μm/μm at S5. This trend coincides with that of strip plastic rigidity, which verifies that the strip crown inheritance factor is dependent on the strip plastic rigidity. Furthermore, the variation of strip crown and flatness under different entry strip crowns from S1 to S5 is jointly influenced by the pass reduction and strip plastic rigidity. Moreover, the strip crown inheritance factor increases with the deformation resistance of the strip at both S1 and S5. These findings not only offer a fresh perspective to understand the mechanism of strip crown inheritance, but also provide an important basis for optimising the strip shape control in the TCR process.

Germline testing in haematology – who and why

With the inclusion for the first time of ‘Myeloid Neoplasms with Germline Predisposition’ in the most recent iteration of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, consideration of whether an underlying inherited factor may have contributed to malignancy development has become an essential part of the diagnostic work up. The disease groups which fall under this heading are broad; from the traditional inherited bone marrow failures such as Fanconi anaemia and dyskeratosis congenita, to the more recently described GATA2 deficiency syndrome and also some ‘non-syndromal’ conditions such as the predisposition to myeloid malignancy conferred by germline mutations in DDX41.

Genomic instability is enriched in localized prostate cancers from men of African ancestry.

270 Background: Whole genome sequencing (WGS) of prostate cancers (PC) from American men of African ancestry (AA) is limited despite AA men having twice the incidence of and mortality from PC as compared to their European ancestry (EA) men. Herein we describe analysis of AA PC WGS to identify genomic contributions to incidence and outcome disparities. Methods: WGS data from AA localized hormone naïve (HN) PCs (n = 23) from our institution were combined with publicly available WGS HNPC datasets (n = 5); quantitative predominant genome-wide ancestry was approximated via RFMix. A comparable EA cohort (n = 224) was similarly assembled. Ancestry groups were compared via regression models correcting for Gleason grade, PSA, and pathologic stage. Results: Analysis of known HNPC driver genes revealed lower frequency of PTEN (2/28 v 70/224, 7% v 31%, p = 0.006) and higher frequency of MYC (5/28 v 13/224, 18% v 5%, p = 0.014) and FOXA1 (7/28 v 24/224, 25% v 11%, p = 0.018) alterations in AA tumors relative to EA. An unbiased search for coding and noncoding drivers uncovered recurrent FOXA1 promoter (n = 8, p = 1.1e-8, RR = 3.92) and gene body protein-coding (n = 5, p = 1.2e-6, RR = 7.83) mutations, as targets of somatic selection and affecting nearly half of AA cases. Despite comparable tumor mutational burdens in each group, analysis of genome-wide mutational signatures revealed an AA-specific enrichment of SNVs in trinucleotide contexts associated with mismatch repair deficiency (SBS6, p = 1.68e-2, RR = 49.1). AA tumors also had significantly more small deletions (sig. ID2) relative to EA samples (p = 2.25e-31, RR = 9.47), implying replication slippage at lagging strands. Finally, AA PC genomes had consistently higher MSI scores relative to EA (median [IQR]: 4.03 [3.8-4.53] v 1.52 [1.21-1.85], p = 2.95e-44), yet lower than MSI-H colon cancers. These associations were independent of tissue preservation method or source, suggesting they reflect an ancestry-specific mutational process. Comparison of germline and somatic variants between AA and EA uncovered candidate DNA damage response genes (DDR) for further functional validation. Conclusions: Analysis of the largest AA cohort to date of WGS HNPC has revealed an ancestry-specific somatic mutational processes resulting in elevated rate of MMR-linked SNVs, replication-slippage associated small deletions, and MSI, relative to EA. The uniformity of these data suggest that AAs may harbor an inherited factor contributing to increased somatic genomic instability in the HNPC context. These results are compatible with published analyses demonstrating lower expression of DDR genes in AA versus EA PCs. Greater MSI and indels (via neoantigen formation) may explain the higher response proportions in AA PC patients treated with immune- and radiotherapies. Studies are ongoing to define mechanisms via associations between germline predisposition, somatic modification, and transcriptional outcome.

Genotype-Phenotype Relationship Among 1200 Unrelated White Patients with Inherited FVII Deficiency: A Three-Center Database Study

▪Background: Congenital factor VII (FVII) deficiency is a rare bleeding disorder caused by mutations in F7 gene with autosomal recessive inheritance. A clinical heterogeneity with poor correlation with FVII:C levels has been described. Aim of this study was to identify genetic defects and to evaluate their relationships with clinical phenotype in a large cohort of 1228 white patients with FVII:C below the age-dependent cut-off %.Methods: Probands with confirmed inherited factor VII deficiency were i) genotyped (Sanger method & multiplex ligation-dependent probe amplification [MLPA]) for F7 mutations including common polymorphic variants and were ii) classified according to clinical bleeding scores (BC). In addition, common thrombophilic variants and blood groups were determined. Results: Probands included asymptomatic subjects (referred for laboratory work up of recurrent prolonged prothrombin time; n=415; mean age 30 + 19 yrs.; female 52%) and patients who presented with mild, moderate or severe bleeding episodes (n=805; mean age 34 + 18 yrs.; female 70%). Bleeding symptoms included epistaxis, gum bleeding, GI bleeding, hematuria, postoperative and gynecologic hemorrhage. Median FVII activity (entire cohort) measured with clotting-based assays (ACL TOP 750 and/or BCS-XP) was 49% (range 5-78%) and the median ISTH BS recorded within a period of two years prior to work-up was 1(0-17). The latter was significantly higher in women compared with males (2 versus 1; p < 0.001). The corresponding PBAC-Score prior to hormonal treatment was 163 (25-1200). Blood group 0 was present in 40.6% of cases. Known and novel mutations in the F7 gene, including coding regions, exon/intron boundaries and the promoter region, are found in 534 patients (44%) and common polymorphisms were detected in 666 subjects (95%). Logistic regression analysis adjusted for clinical and laboratory data (blood group, FVII activity, presence of F7 gene mutations and /or polymorphisms, thrombophilia status and further factor deficiencies) revealed that older age (increase per year) at referral (odds/95% CI: 1.01/1.007-1.025) and female gender (odds/95% CI: 3.25/2.35-4.50) in part explain differences in clinical bleeding phenotype associated with FVII deficiency.Conclusion: Overall there is poor correlation between the FVII level and the bleeding phenotype. Older patients and females are more likely to have symptomatic disease as a result of gynecological or muco-cutaneous bleeding. DisclosuresKenet: Alnylam: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Opko Biologics: Research Funding; Pfizer: Consultancy, Research Funding; Shire: Research Funding; Novo Nordisk: Consultancy; Roche: Consultancy; Takeda: Consultancy.

Dopaminergic modulation of the circadian activity and sociability: Dissecting parental inheritance versus maternal styles as determinants of epigenetic influence

In mammalians, social life and circadian rhythms find their neurobiological basis in a network that includes the dopaminergic system. The malfunctioning of dopamine pathways can lead to various disorders such as Attention-Deficit/Hyperactivity and Obsessive/compulsive disorders. A useful research approach is to exploit animal models that carry a functional silencing of SLC6A3 gene, encoding the dopamine transporter (DAT). Hyperactivity, working memory deficits, and asocial tendencies are core features in truncated-DAT rats, for example. We investigated how inheritance and maternal caring style influence circadian rhythms and social behaviours in DAT heterozygous (HET) rats, belonging to four groups: Mat-P, Mat-M, Mix-P, and Mix-M (Mat label stands for care from wild-type dam, Mix label stands for care by heterozygous dam; M label stands for maternal wild-DAT and P label stands for paternal wild-DAT). In Experiment 1, we monitored 24/7 the spontaneous locomotor activity of peri-adolescent subjects. Hyperactivity occurred only in P-asset subjects (with maternal-origin truncated-DAT allele) at specific bins of the day. In Experiment 2, we observed social interactions of the same rats. Mix-M subjects (raised by HET dams and/or inheriting the wild-DAT allele from mothers) tend to interact with all rats; Mat-P (cared by WT dams and/or inheriting the truncated-DAT allele from mothers) seem to be ignored, when acting as stimulus subjects. Overall, results confirm complex modulations for circadian cycle and social life: flexible DAT expression in HET subjects depends on epigenetic combinations of parental inheritance and early experiential factors. Once confirmed, these data could shed light on trans-generational contributions to dopaminergic-related disorders.

Bladder stone in children: literature review

Bladder stones affecting children, especially in low-resource countries. Dietary, environmental, genetic inheritance, and socio-economic factors affecting the composition of bladder stones. Even though the etiology of bladder stones is unknown, recent research has identified many risk factors that may assist this pathological condition. Even though cystolithotripsy has now become the standard of care, many other approaches are indicated in specific conditions. Surgeons should diagnose and investigate the etiology of the diseases properly, thus a surgical approach is only used when it is needed. Therefore, this study aims to review bladder stones in children based on current literature to refer to other researchers and clinicians.

A Timeline of Discovery and Current Research on Primary Open-Angle Glaucoma and Emergence of Potentially Permanent Treatment Solutions

This research examines the timeline of the discovery and research of Primary Open-Angle Glaucoma (POAG). By reviewing the literature on genetic and molecular mechanisms, we aim to emphasize a long-term treatment solution (iSTENT) to mitigate intraocular pressure (IOP) related to POAG etiology and disease progression. POAG is a multifactorial, autosomal dominant, adult-onset eye disease wherein the optic nerve cells become damaged due to a buildup of excess aqueous humor, resulting in increased IOP. Consequently, POAG leads to progressive loss of peripheral vision and is the leading cause of blindness in the US. Due to the multifactorial nature of glaucoma’s inheritance pattern and disease pathology, over 20 disease-associated loci have been implicated with POAG and its mechanisms remain relatively obscure. POAG remains a hotbed for multifactorial genetic research and the relationships between heterogeneity and environmental/genetic factors. To develop a more permanent solution for Glaucoma, we highlight a surgical insertion of a stent in the trabecular meshwork providing long-lasting dilation to the blocked drainage channels implicated with increased IOP and POAG progression. This procedure would allow for aqueous humor outflow from the eye and subsequent reduction of pressure-induced retinal ganglion cell damage. POAG’s progressive loss of vision due to polygenic inheritance and environmental factors is currently experienced by over 2.25 million Americans and will continue to grow as POAG-associated genes are maintained in subsequent generations. Therefore, a complete understanding of the history, etiology, and genetic mechanisms is critical for the development of effective and long-lasting treatment options.

Benzophenone-3 induced abnormal development of enteric nervous system in zebrafish through MAPK/ERK signaling pathway

Hirschsprung disease (HSCR) is a congenital disease characterized by the absence of enteric neurons, which is derived from the failure of the proliferation, differentiation or migration of the enteric neural crest cells (ENCCs). HSCR is associated with multiple risk factors, including polygenic inheritance factors and environmental factors. Genetic studies have been extensively performed, whereas studies related to environmental factors remain insufficient. Benzophenone-3 (BP-3), one important component of the ultraviolet (UV) filters, has been proved to have cytotoxicity and neurotoxicity which might be associated with HSCR. In this study, we used zebrafish as a model to investigate the relationship between BP-3 exposure and the development of the enteric nervous system (ENS) in vivo. Embryos exposed to BP-3 showed an average of 46% reduction of the number of the enteric neurons number. Besides, the ENCCs specific markers (ret and hand2) were downregulated upon BP-3 exposure. Moreover, we identified potential targets of BP-3 through Network Pharmacology Analysis and Autodock and demonstrated that the attenuation of the MAPK/ERK signaling might be the potential mechanism underlying the inhibition of the ENS development by BP-3. Importantly, MAPK/ERK signaling agonist could be used to rescue the ENS defects of zebrafish induced by BP-3. Overall, we characterized the influence of BP-3 on ENS development in vivo and explored possible molecular mechanisms.

Risk factors for major external structural birth defects among children in Kiambu County, Kenya: a case-control study.

Background: Although major external structural birth defects continue to occur globally, the greatest burden is shouldered by resource-constrained countries with no surveillance systems. To our knowledge, many studies have been published on risk factors for major external structural birth defects, however, limited studies have been published in developing countries. The objective of this study was to identify risk factors for major external structural birth defects among children in Kiambu County, Kenya. Methods: A hospital-based case-control study was used to identify the risk factors for major external structural birth defects. A structured questionnaire was used to gather information retrospectively on maternal exposure to environmental teratogens, multifactorial inheritance, and sociodemographic-environmental factors during the study participants' last pregnancies. Descriptive analyses (means, standard deviations, medians, and ranges) were used to summarize continuous variables, whereas categorical variables were summarized as proportions and percentages in frequency tables. Afterward, logistic regression analyses were conducted to estimate the effects of the predictors on the odds of major external structural birth defects in the country. Results: Women who conceived when residing in Ruiru sub-county (adjusted odds ratio [aOR]: 5.28; 95% CI: 1.68-16.58; P<0.01), and Thika sub-county (aOR: 0.27; 95% CI; 0.076-0.95; P =0.04); and preceding siblings with history of birth defects (aOR: 7.65; 95% CI; 1.46-40.01; P =0.02) were identified as the significant predictors of major external structural birth defects in the county. Conclusions: These findings pointed to MESBDs of genetic, multifactorial inheritance, and sociodemographic-environmental etiology. Thus, we recommend regional defect-specific surveillance programs, public health preventive measures, and treatment strategies to understand the epidemiology and economic burden of these defects in Kenya. We specifically recommend the integration of clinical genetic services with routine reproductive health services because of potential maternal genetic predisposition in the region.

Risk factors for major external structural birth defects among children in Kiambu County, Kenya: a case-control study

Background: Although major external structural birth defects continue to occur globally, the greatest burden is shouldered by resource-constrained countries with no surveillance systems. To our knowledge, many studies have been published on risk factors for major external structural birth defects, however, limited studies have been published in developing countries. The objective of this study was to identify risk factors for major external structural birth defects among children in Kiambu County, Kenya. Methods: A hospital-based case-control study was used to identify the risk factors for major external structural birth defects. A structured questionnaire was used to gather information retrospectively on maternal exposure to environmental teratogens, multifactorial inheritance, and sociodemographic-environmental factors during the study participants' last pregnancies. Descriptive analyses (means, standard deviations, medians, and ranges) were used to summarize continuous variables, whereas categorical variables were summarized as proportions and percentages in frequency tables. Afterward, logistic regression analyses were conducted to estimate the effects of the predictors on the odds of major external structural birth defects in the country. Results: Women who conceived when residing in Ruiru sub-county (adjusted odds ratio [aOR]: 5.28; 95% CI; 1.68-16.58; P<0.01), and Kiambu sub-county (aOR: 0.27; 95% CI; 0.076-0.95; P=0.04), and preceding siblings with history of birth defects (aOR: 7.65; 95% CI; 1.46-40.01; P=0.02) were identified as the significant predictors of major external structural birth defects in the county. Conclusions: These findings pointed to MESBDs of genetic, multifactorial inheritance, and sociodemographic-environmental etiology. Thus, we recommend regional defect-specific surveillance programs, public health preventive measures, and treatment strategies to understand the epidemiology and economic burden of these defects in Kenya. We specifically recommend the integration of clinical genetic services with routine reproductive health services because of potential maternal genetic predisposition in the region.

Risk factors for major external structural birth defects among children in Kiambu County, Kenya: a case-control study

Background: Although major external structural birth defects continue to occur globally, the greatest burden is shouldered by resource-constrained countries largely with no surveillance systems. To the best of our knowledge, few studies have been published on the risk factors for these defects in developing countries. The objective of this study was to identify the risk factors for major external structural birth defects among children in Kiambu County, Kenya. Methods: A hospital-based case-control study was used to identify the risk factors for major external structural birth defects in Kiambu County. A structured questionnaire was used to gather information retrospectively on exposure to environmental teratogens, multifactorial inheritance, and sociodemographic-environmental factors during the study participants' last pregnancies.Descriptive analyses (means, standard deviations, medians, and ranges) were used to summarize continuous variables, whereas, categorical variables were summarized as proportions and percentages in frequency tables. Afterward, logistic regression analyses were conducted to estimate the effects of the predictors on major external structural birth defects in the county. Results: From the multivariable analyses, maternal age ≤34 years old, (aOR: 0.41; 95% CI: 0.18-0.91; P=0.03), and preceding siblings with history of birth defects (aOR: 5.21; 95% CI; 1.35-20.12; P =0.02) were identified as the significant predictors of major external structural birth defects. Conclusions: Maternal age ≥35 years old, and siblings with a history of birth defects were identified as the risk factors for major external structural birth defects in Kiambu County, Kenya. This pointed to a need to create awareness among couples against delaying childbearing beyond 35 years of age and the need for clinical genetic services for women of reproductive age with history of births affected by congenital anomalies.