Depth of focus and intensity distribution of a lensacon illuminated by a partially coherent Gaussian Schell vortex beam.

Using the extended Huygens-Fresnel principle, a cross-spectral density formula was developed for a Gaussian Schell model vortex (PCGSMV) beam diffracted through a lensacon (lens with an axicon). The intensity and depth of focus (DOF) shaped by the lensacon were calculated. Our numerical results show the relationship between the intensity distribution and depth of focus with the beam waist width as well as the spatial correlation of the coherence length. Furthermore, the relationship between the beam spot size and propagation distance was investigated. In the case of the lensacon tandem, the maximum intensity was greater than that attained by the axicon alone for the same beam parameters, and the DOF was smaller than that of the axicon alone. The vortex structure canceled out the low value of the spatial degree of coherence length. Our numerical model exhibited high-intensity values and high-quality Bessel rings along the DOF, which are critical for various applications.

General Population Awareness of Primary Immune Deficiency Disease in Children in the Arar Region, Saudi Arabia.

Background Primary immunodeficiency disorders (PIDD) are of various types and severities, and they are associated with a delay in diagnosis. Early diagnosis of PIDD helps to improve the quality of life of affected children and prevent permanent consequences such as organ damage. Hence, awareness of PIDD is a must in the community to aid in early detection. Objectives The study aims to investigate the general population's awareness of PIDD in children in Arar, Northern Saudi Arabia. Methods A cross-sectional design was utilized to determine the awareness of PIDD in children in Arar, Northern Saudi Arabia. The participants were selected through an online self-administered questionnaire. The collected data was analyzed using descriptive and inferential statistics. Results A total of 528 participants were involved in the current study. The majority of the sample population falls within the 20-30 age range. 9.1% of respondents know a child with primary immunodeficiency. Additionally, participants were aware of certain symptoms, such as delayed growth and chronic diarrhea, with rates of 47.0% and 34.1%, respectively. On the other hand, symptoms like otitis media and sinusitis have lower awareness rates of 25.8% and 33.3%, respectively. Conclusion This study can help in developing targeted awareness campaigns and educational programs to improve the understanding of primary immune deficiency disease among the general population in Saudi Arabia. This, in turn, can lead to earlier diagnosis and better management of the disease in children, ultimately improving their quality of life.

Micro/nanofluidic device for tamsulosin therapeutic drug monitoring in patients with benign prostatic hyperplasia at point of care.

Discovering the balance between toxicity and efficacy for many drugs requires therapeutic drug monitoring (TDM) of their concentrations in the blood. Here, a hot-embossed microfluidic device with a new design integrated to a nanofracture is presented for purification of blood samples from numerous proteins and cells, allowing to the separation of small molecules from blood matrix. The device was used to separate and quantitatively detect tamsulosin drug after derivatization with fluorescamine reagent, allowing converting it from a neutral molecule into a charged fluorescent complex under the experimental conditions, and thus its separation by electrophoresis. The device is portable and easy operated, and the presented method showed good linearity (R2 = 0.9948) over a concentration range of 0.1-1 µg/mL. The relative standard deviation (RSD%) was below 10% (n = 3), indicating good precisions, and the limit of detection (LOD) and limit of quantitation (LOQ) values were estimated to be 0.1 and 0.55 µg/mL, respectively. Whole blood samples from 10 patients with benign prostatic hyperplasia (BPH) were analyzed, showing good percentage recoveries of tamsulosin in whole blood. This point-of-care (POC), low-cost method could increase the convenience of patients and doctors, make therapies safer, and make TDM available in different regions and places.

Effect of high frequency repetitive transcranial magnetic stimulation (rTMS) on the balance and the white matter integrity in patients with relapsing-remitting multiple sclerosis: A long-term follow-up study.

OBJECTIVES: Repetitive Transcranial Magnetic Stimulation (rTMS) is considered as a safe and non-invasive developing technique used as a therapeutic method for patients with Relapsing-Remitting Multiple Sclerosis (RRMS) who suffer from disturbances in gait and balance. The aim of our study is to evaluate the long-term effect of high frequency rTMS as a therapeutic option for truncal ataxia in RRMS patients and to assess its impact on the integrity of the white matter (WMI), measured in the form of anisotropy metrics using diffusion tensor imaging (DTI). METHODS: The study was conducted in two phases: phase I; a randomized, single-blind, sham-controlled phase and phase II was a 12 months longitudinal open-label prospective phase. Phase I of the trial involved the randomization of 43 patients with RRMS and truncal ataxia to either real (n = 20) or sham (n = 19) rTMS (2 participants from each treatment group were excluded from the study; one developed a relapse before treatment, 2 declined to participate, and one did not show up). Phase II involved providing 12 actual treatments cycles to all patients; each cycle length is 4 weeks, repeated four times on a trimonthly basis, forming a total of 48 sessions. DTI was used for assessment of the WMI. All patients performed DTI 3 times: Imaging sessions were conducted at the screening visit, at the end of phase I, and after the last session in phase II for the first, second and third sessions respectively. A figure-of-8-shape coil, employing rTMS protocol and located over the cerebellum, was used. rTMS protocol is formed of 20 trains formed of 50 stimuli with 20 s apart (5 Hz of 80 % of resting Motor Threshold "MT"). The Berg Balance Scale (BBS), Time up and go (TUG) test, and 10-m walk test (10MWT) were first evaluated at the start of each cycle and just after the final rTMS session. RESULTS: The genuine rTMS group's 10MWT, TUG, and BBS showed substantial improvement (p < 0.01), which is continued to be improved throughout the study Timeline, with a significant difference observed following the final rTMS session (P< 0.001). A longitudinal increase in FA was observed in both the Cerebello-Thalamo-Cortical (CTC) and Cortico-Ponto-Cerebellar (CPC) bilateral, as indicated by means of Fractional Anisotropy (FA) measures (p < 0.05). CONCLUSION: In ataxic RRMS patients, high frequency rTMS over the cerebellum has a long-term beneficial impact on both balance and WMI.

Unveiling detection probability for multi-Gaussian correlated anomalous vortex modes in maritime atmospheric turbulence.

In this study, we employ the Rytov approximation to investigate the detection probability of orbital angular momentum (OAM) in multi-Gaussian correlated anomalous vortex (MGCAV) beams under non-Kolmogorov maritime atmospheric turbulence. Our results demonstrate that the OAM detection probability of a MGCAV beam is influenced by various factors, including beam parameters and the characteristics of maritime atmospheric turbulence. Specifically, an increase in propagation distance, beam order, and beam index, or a decrease in inner scale, spatial coherence width, and non-Kolmogorov parameter, leads to a decrease in the OAM detection probability. The phase characteristics of partially coherent vortex modes are affected by both atmospheric turbulence phase and initial random phase, resulting in reduced robustness compared to fully coherent vortex modes. Furthermore, a comparative analysis between Gaussian-Schell correlated anomalous vortex (GSCAV) beams and MGCAV beams reveals the superior resilience of GSCAV beams in mitigating the impact of maritime atmospheric turbulence. Moreover, specific combinations of beam order, topological charge, and beam waist, or the optimal beam width, yield maximum OAM detection probability or minimum scintillation. These findings provide valuable insights applicable to optical communication, particularly in scenarios above sea and ocean levels.

HNF1α upregulation and promoter hypermethylation as a cause of glucose dysregulation: a case-control study of Kashmiri MODY population.

AIM: HNF1α transcription factor regulates a network of genes involved in the development of ß-cells and also serves as a model for transcription defects in pancreatic ß-cells; mutations in this gene cause MODY. The goal of this study was to assess the promoter methylation and expression profile of the most common MODY causing gene, HNF1α, in Kashmiri MODY patients, as factors responsible for glucose dysregulation, as no such study had been performed on MODY patients in Kashmir previously. METHODS: The study included 85 Kashmiri subjects. Samples were extracted for DNA and RNA using standard protocols. The HNF1α promoter methylation profile was assessed by bisulfite conversion of the DNA followed by MSP, whereas qPCR was used for expression analysis. RESULTS: The expression of HNF1α was found to be upregulated (p value 0.0349*) in majority of MODY (60%) and T1D (72%) cases (p value 0.0349*). HNF1α expression was 1.33-fold higher in MODY cases with hypermethylated HNF1α promoters (p value 0.0360*). HNF1α expression was upregulated by 2.3-fold in MODY patients with HbA1c levels > 7% (p value 0.0025**). MODY cases with FBS levels > 7.7 mmol/l were upregulated by 0.646-fold than those with FBS levels ≤ 7.7 mmol/l (p value 0.0161*). CONCLUSION: In this study, we found that as glucose dysregulation progresses, blood FBS, RBS, and HbA1c levels rise, and that at higher levels, HNF1α expression rises as well. From the results obtained, we may conclude that HNF1α is strongly upregulated in MODY, thus indicating the deleterious effect of over expression of HNF1α gene on glucose regulation.

Prevalence of Ventilator-Associated Pneumonia in Children Admitted to Pediatric Intensive Care Units in the Middle East: A Systematic Review.

Ventilator-associated pneumonia (VAP) is a common healthcare-associated disease in intensive care units, leading to significant morbidity and mortality. This systematic review aims to investigate the prevalence, risk factors, and prevention strategies for VAP in the Middle East. PubMed, SCOPUS, Web of Science, Science Direct, and Google Scholar were systematically searched to include the relevant literature. Rayyan QCRI was used throughout this systematic approach. Ten studies, involving a total of 6295 patients diagnosed with VAP, were included in this review. Among these patients, 336 (5.3%) developed VAP. The prevalence of VAP in children and neonates in the Middle East was relatively low. Risk factors associated with VAP development included prematurity, low birth weight, prolonged mechanical ventilation, enteral feeding, intrusive devices such as umbilical catheters, and cardiac operations. All reviewed studies emphasized the importance of infection control measures in reducing the risk of VAP.

Determination of morpho-physiological and yield traits of maize inbred lines (Zea mays L.) under optimal and drought stress conditions.

Globally, climate change could hinder future food security that concurrently implies the importance of investigating drought stress and genotype screening under stressed environments. Hence, the current study was performed to screen 45 diverse maize inbred lines for 18 studied traits comprising phenological, physiological, morphological, and yield characters under optimum and water stress conditions for two successive growing seasons (2018 and 2019). The results showed that growing seasons and water regimes significantly influenced (p < 0.01) most of the studied traits, while inbred lines had a significant effect (p < 0.01) on all of the studied traits. The findings also showed a significant increase in all studied characters under normal conditions compared to drought conditions, except chlorophyll content, transpiration rate, and proline content which exhibited higher levels under water stress conditions. Furthermore, the results of the principal component analysis indicated a notable distinction between the performance of the 45 maize inbred lines under normal and drought conditions. In terms of grain yield, the drought tolerance index (DTI) showed that Nub60 (1.56), followed by Nub32 (1.46), Nub66 (1.45), and GZ603 (1.44) were the highest drought-tolerant inbred lines, whereas Nub46 (0.38) was the lowest drought-tolerant inbred line. These drought-tolerant inbred lines were able to maintain a relatively high grain yield under normal and stress conditions, whereas those drought-sensitive inbred lines showed a decline in grain yield when exposed to drought conditions. The hierarchical clustering analysis based on DTI classified the forty-five maize inbred lines and eighteen measured traits into three column- and row-clusters, as inbred lines in cluster-3 followed by those in cluster-2 exhibited greater drought tolerance in most of the studied traits. Utilizing the multi-trait stability index (MTSI) criterion in this study identified nine inbred lines, including GZ603, as stable genotypes in terms of the eighteen studied traits across four environments. The findings of the current investigation motivate plant breeders to explore the genetic potential of the current maize germplasm, especially in water-stressed environments.

Inheritance of resistance against northern leaf blight of maize using conventional breeding methods.

Maize (Zea mays L.) is one of the important cereal crops along with wheat and rice worldwide. The purpose of this study was to use classical genetic approaches to assess the resistance of various maize parents and hybrids to the northern corn leaf blight (NCLB) disease in two different locations in Egypt. Eight parents, 28 F1, and 2 check hybrids were evaluated. The analysis of variance showed high significant variations between maize parents and their hybrids for the studied parameters and NCLB disease, besides there are significant variations between both locations. Results of maize parents showed that Sids 63, Giza 602, and Giza 628 cultivars exhibited the highest values and were resistant to NCLB in both locations comparing with Nubaria 39 and Gemmiza 18 that were susceptible to NCLB disease. Concerning the maize hybrids, analysis of variance and mean squares of growth characters in both locations indicated high significant variations between the maize hybrids including the check hybrids. When combined between the two locations for current parameters against NCLB, the data pointed that the Sakha location values for maize hybrids were much closed to the combining data in parents and the hybrids detected high resistance to this disease comparing with Nubaria location. All tested maize lines (38 lines), including parents and hybrids were classified as follows, two lines were rated as 1 (highly resistant), three were rated as 2 (resistant), sixteen were rated as 3 (moderate resistant), eight were rated 4 (moderately susceptible) and nine were rated 5 (susceptible). The data explaining that the crossing between high resistant maize cultivars produced high levels of resistance to NCLB disease. Therefore, our results verified that classical breeding could efficiently increase the resistance levels of maize germplasm against NCLB disease by developing new cultivars with superior performance in terms of grain yield, disease resistance and grain quality.

Metamaterial-Inspired Electrically Compact Triangular Antennas Loaded with CSRR and 3 × 3 Cross-Slots for 5G Indoor Distributed Antenna Systems.

In this article, two distinct kinds of metamaterial (MTM) antennas are proposed for fifth-generation (5G) indoor distributed antenna systems (IDAS). Both antennas operate in the sub-6 GHz 5G band, i.e., 3.5 GHz. The antenna's radiating structure is based on a combination of triangular and rectangular patches, as well as two complementary split-ring resonators (CSRR) unit-cells etched on the top layer. The bottom layer of the first MTM antenna is a complete ground plane, while the bottom layer of the second MTM antenna is etched by a 3 × 3 cross-slot MTM structure on the ground plane. The use of these structures on the ground plane improves the antenna bandwidth. The proposed antennas are designed using two different substrates i.e., a high-end Rogers thermoset microwave materials (TMM4) substrate (h = 1.524 mm/εr = 4.5/tan δ = 0.002) and a low-end flame-resistant (FR4) epoxy glass substrate (h = 1.6 mm/εr = 4.3/tan δ = 0.025), respectively. The antenna designs are simulated using CST microwave studio, and in the end, the antenna fabrication is performed using FR4 substrate, and the results are compared. Furthermore, parametric analysis and comparative studies are carried out to investigate the performance of the designed antennas. The simulated and measured results are presented for various parameters such as return-loss, gain, and radiation pattern. The two MTM antennas have an overall dimension of 18 × 34 mm2, demonstrating that the proposed design is 60 percent smaller than a standard microstrip patch antenna (MPA). The two proposed MTM antenna designs with complete ground plane and 3 × 3 cross-slot MTM on the bottom layer using FR4 substrate have a measured gain/bandwidth characteristic of 100 MHz/2.6 dBi and 700 MHz/2.3 dBi, respectively.

Natural Ghee Enhances the Biochemical and Immunohistochemical Reproductive Performance of Female Rabbits.

The reproductive effects of several dietary fats (margarine, ghee, and olive oil) on female rabbits were studied. For that purpose, 40 mature female rabbits were designed into four groups of ten rabbits each. Group I was given a control diet, Group II received 10% margarine, Group III received 10% ghee, and Group IV received 10% olive oil; after two months, all rabbits were sacrificed. Lipid profile and reproductive hormones levels were assayed in serum besides ovarian antioxidant enzyme and lipid peroxidation. Furthermore, ovarian tissue was examined using hematoxylin−eosin staining and immunohistochemistry of estrogen, follicle-stimulating hormone (FSH), luteinizing hormone (LH) receptor, and caspase 3. Our data revealed that the margarine significantly (p < 0.05) increased lipid profile and malondialdehyde (MDA) level, which decreased in olive oil and ghee compared to the control. In addition, serum FSH and estrogen (estradiol (E2)) were significantly (p < 0.05) decreased in the group treated with margarine. Furthermore, there was a significant decrease in ovarian superoxide dismutase (SOD) and catalase activity in the margarine-treated group. In contrast, SOD and MDA showed a significant (p > 0.05) increase in the olive oil and ghee- treated group compared to the control group. At the same time, there was a significant increase in serum FSH and (estradiol (E2)) in the ghee and olive oil groups, respectively, compared to the control. The margarine feed group showed moderate immunoreaction of estrogen, FSH, LH receptor, and strong caspase 3, while ghee and olive oil showed strong immunoreaction of estrogen, FSH, LH receptor, and mild immunoreaction of caspase 3 in ovarian tissue. Photomicrograph of rabbit ovarian tissue showed vacuolation in small and growing follicles in the margarine group but appeared normal in ghee and the olive oil-treated group. In conclusion, based on these results, olive oil and ghee have a strong capability of enhancing lipid profile, antioxidant status, and female hormonal functions.

Indications of Keratoplasty and Outcomes of Deep Anterior Lamellar Keratoplasty Compared to Penetrating Keratoplasty.

Background Corneal diseases are a significant cause of visual impairment and blindness. Despite the treatable nature of many corneal diseases before visual demise, many cases of advanced disease necessitating keratoplasty for visual rehabilitation are encountered. A mismatch between the number of corneal donors and potential recipients also exists worldwide, with underutilization of certain types of keratoplasty techniques that may allow more efficient use of this limited resource. Methodology A retrospective cohort study of all cases of optical corneal transplantations performed from January 1, 2015 to October 31, 2020 was performed. Indications for keratoplasty, type of keratoplasty, complications, intraocular pressure elevation, and best corrected visual acuity (BCVA) by category and range at different time intervals were collected and analyzed. Findings were compared between penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK) for all indications, specifically for keratoconus (KCN). Results A total of 58 corneal transplants meeting our criteria were performed during the study period. PK was performed for 29 eyes, DALK for 28 eyes, and endothelial keratoplasty for one eye. The most frequently encountered indication was KCN (62.1%). The number of eyes with BCVA of 20/100 or better increased from preoperative BCVA, 37/58 eyes had BCVA worse than 20/100 before keratoplasty (63.8%), while at the time of last follow-up 45/58 eyes had BCVA of 20/100 or better (77.6%). At the time of last follow-up 16/58 had BCVA in the range of 20/20 to 20/40 (27.6%) and 29/58 eyes had BCVA in the range of 20/50 to 20/100 (50%). Comparison of all cases of PK to DALK for all indications showed significantly better BCVA by category at one year, at last follow-up, and BCVA range at last follow-up (p = 0.032, 0.001, and 0.014, respectively). Although better visual acuity results by category and range at one year and last follow-up, respectively, were observed in more patients undergoing DALK than PK, for KCN the results were not statistically significant (p = 1.00, 1.00, 0.417, and 0.374, respectively). Overall, 70% of recorded complications, intraocular pressure (IOP) elevations, and graft rejections were seen in eyes that underwent PK; however, these findings were not statistically significant (p = 0.297). Graft failures occurred more frequently with PK than deep anterior keratoplasty when analyzed for all indications of keratoplasty (p = 0.010). Conclusions Despite advancement and improvements in surgical techniques, statistics continue to show underutilization of the invaluable resource of donor corneas, with PK still being performed more than DALK for diseases that do not affect the endothelium. Our study found superior visual acuity outcomes of DALK as well as the advantages of less frequent complications, IOP elevations, graft rejections, and graft failures. We encourage ophthalmologists to utilize DALK in appropriate candidates to more fully utilize the scarce and potentially vision-restoring resource of donor corneal tissue.

[Epidemiological aspects and prognostic factors of severe traumatic brain injuries]. / Aspects épidemiologiques et facteurs pronostiques des traumatisés crâniens graves.

OBJECTIVE: To determine the severity factors in severe traumatic brain injuries. METHODS: A prospective descriptive study of severe head injuries admitted to the emergency department at Ibn Tofail Hospital at the University Hospital of Marrakech over a period of six months from May to October 2015. The following data was collected: circumstances, clinical, biology, radiology, treatment and evolution. RESULTS: One hundred and nineteen patients with severe traumatic brain injury were collected (101 males, 84,9%). The mean age was 37,73±15,7 years. Road accidents were the most common cause representing 84%. The median Glasgow coma scale (GCS) was 7±3. We noted 36 cases (30,3%) of anisocoria, 32 cases (26,9%) of bilateral mydriasis and 72 cases (60,5%) of hypoxia. Cerebral contusions (66,1%) and meningeal hemorrhage (66,6%) were the most frequent lesions on CT. Forty-seven patients (42%) had stage VI Marshall lesions. Twenty-four patients (20.1%) required a neurosurgical intervention, 12 extradural hematoma evacuations and 10 craniocerebral wounds. Mortality was 64.7% (77 deaths), the main cause was neurological (64,9%). In the latter group, we observed more frequently an older age (P=0.00001), a management delay (P=0.011), a low initial GCS (P=0.000001), a bilateral nonreactive mydriasis (P=0.0001), a hypoxia (P=0.0002), a subarachnoid hemorrhage (P=0.008), a high Marshall score (P=0.017) and an anemia (P=0.046). CONCLUSION: Head trauma is a public health problem. The victims are young, and the sequelae are frequently disabling. Several parameters are associated with a poorer prognosis including age, neurological state and the initial delay in management.

The Effects of Anthocyanins and Their Microbial Metabolites on the Expression and Enzyme Activities of Paraoxonase 1, an Important Marker of HDL Function.

High circulating HDL concentrations and measures of various HDL functions are inversely associated with cardiovascular disease (CVD) risk. Paraoxonase 1 (PON1) contributes to many of the athero-protective functions of HDL, such as promoting the reverse cholesterol transport process and reducing the levels of oxidized LDL. PON1 activities are influenced by several factors, the most important being diet and genetic polymorphisms. Reported data from randomized controlled trials have shown that anthocyanin consumption increased PON1 activity. However, the underlying molecular mechanisms by which anthocyanins increase PON1 activity are not understood. Therefore, the aim of this research was to investigate the ability of anthocyanins and their metabolites to increase PON1 gene expression and/or enzyme activities as potential mechanisms. The effect of the two predominant dietary anthocyanins and 18 of their recently identified microbial metabolites including their phase-II conjugates on PON1 gene expression was studied using a PON1-Huh7 stably-transfected cell line and reporter gene assay. The effects of these compounds on PON1 arylesterase and lactonase activities were investigated using two isoforms of the PON1 enzyme that are the phenotypes of the 192Q/R polymorphism. None of the compounds caused even modest changes in PON1 promoter activity (p ≥ 0.05). Further, none of the compounds at physiological concentrations caused any significant changes in the arylesterase or lactonase activity of either of the iso-enzymes. Cyanidin reduced the lactonase activity of the PON1-R192R enzyme at high concentrations (-22%, p < 0.001), but not at physiologically achievable concentrations. In conclusion, none of the data reported here support the notion that anthocyanins or their metabolites affect PON1 transactivation or enzyme activities.

Polyphenol Effects on Cholesterol Metabolism via Bile Acid Biosynthesis, CYP7A1: A Review.

Atherosclerosis, the main contributor to coronary heart disease, is characterised by an accumulation of lipids such as cholesterol in the arterial wall. Reverse cholesterol transport (RCT) reduces cholesterol via its conversion into bile acids (BAs). During RCT in non-hepatic peripheral tissues, cholesterol is transferred to high-density lipoprotein (HDL) particles and returned to the liver for conversion into BAs predominantly via the rate-limiting enzyme, cholesterol 7 α-hydroxylase (CYP7A1). Numerous reports have described that polyphenol induced increases in BA excretion and corresponding reductions in total and LDL cholesterol in animal and in-vitro studies, but the process whereby this occurs has not been extensively reviewed. There are three main mechanisms by which BA excretion can be augmented: (1) increased expression of CYP7A1; (2) reduced expression of intestinal BA transporters; and (3) changes in the gut microbiota. Here we summarise the BA metabolic pathways focusing on CYP7A1, how its gene is regulated via transcription factors, diurnal rhythms, and microRNAs. Importantly, we will address the following questions: (1) Can polyphenols enhance BA secretion by modulating the CYP7A1 biosynthetic pathway? (2) Can polyphenols alter the BA pool via changes in the gut microbiota? (3) Which polyphenols are the most promising candidates for future research? We conclude that while in rodents some polyphenols induce CYP7A1 expression predominantly by the LXRα pathway, in human cells, this may occur through FXR, NF-KB, and ERK signalling. Additionally, gut microbiota is important for the de-conjugation and excretion of BAs. Puerarin, resveratrol, and quercetin are promising candidates for further research in this area.

Null mutation of the endothelin receptor type B gene causes embryonic death in the GK rat.

The Hirschsprung disease (HSCR) is an inherited disease that is controlled by multiple genes and has a complicated genetic mechanism. HSCR patients suffer from various extents of constipation due to dysplasia of the enteric nervous system (ENS), which can be so severe as to cause complete intestinal obstruction. Many genes have been identified as playing causative roles in ENS dysplasia and HSCR, among them the endothelin receptor type B gene (Ednrb) has been identified to play an important role. Mutation of Ednrb causes a series of symptoms that include deafness, pigmentary abnormalities, and aganglionosis. In our previous studies of three rat models carrying the same spotting lethal (sl) mutation on Ednrb, the haplotype of a region on chromosome (Chr) 2 was found to be responsible for the differing severities of the HSCR-like symptoms. To confirm that the haplotype of the responsible region on Chr 2 modifies the severity of aganglionosis caused by Ednrb mutation and to recreate a rat model with severe symptoms, we selected the GK inbred strain, whose haplotype in the responsible region on Chr 2 resembles that of the rat strain in which severe symptoms accompany the Ednrbsl mutation. An Ednrb mutation was introduced into the GK rat by crossing with F344-Ednrbsl and by genome editing. The null mutation of Ednrb was found to cause embryonic death in F2 progeny possessing the GK haplotype in the responsible region on Chr 2. The results of this study are unexpected, and they provide new clues and animal models that promise to contribute to studies on the genetic regulatory network in the development of ENS and on embryogenesis.

Profiling of cellular immune responses to Mycoplasma pulmonis infection in C57BL/6 and DBA/2 mice.

Mycoplasma infections cause respiratory tract damages and atypical pneumonia, resulting in serious problems in humans and animals worldwide. It is well known that laboratory inbred mouse strains show various susceptibility to Mycoplasma pulmonis (M. pulmonis) infection, which causes murine respiratory mycoplasmosis. In this study, we aimed to demonstrate the difference in cellular immune responses between resistant strain, C57BL/6NCrSlc (B6) and susceptible strain, DBA/2CrSlc (D2) after challenging M. pulmonis infection. D2 mice showed higher amount of bacterial proliferation in lung, higher pulmonary infiltration of immune cells such as neutrophils, macrophages, and lymphocytes, and higher levels of interleukin (IL)-1ß, IL-6, IL-17A, and tumor necrosis factor-α in bronchoalveolar lavage fluid than did B6 mice. The results of this study suggest that D2 mice are more susceptible than B6 mice to M. pulmonis infection due to a hyper-immune inflammatory response.