Biallelic Variants in MNS1 Are Associated with Laterality Defects and Respiratory Involvement.

Defects in motile cilia, termed motile ciliopathies, result in clinical manifestations affecting the respiratory and reproductive system, as well as laterality defects and hydrocephalus. We previously defined biallelic MNS1 variants causing situs inversus and male infertility, mirroring the findings in Mns1-/- mice. Here, we present clinical and genomic findings in five newly identified individuals from four unrelated families affected by MNS1-related disorder. Ciliopathy panel testing and whole exome sequencing identified one previously reported and two novel MNS1 variants extending the genotypic spectrum of disease. A broad spectrum of laterality defects including situs inversus totalis and heterotaxia was confirmed. Interestingly, a single affected six-year-old girl homozygous for an MNS1 nonsense variant presented with a history of neonatal respiratory distress syndrome, recurrent respiratory tract infections, chronic rhinitis, and wet cough. Accordingly, immunofluorescence analysis showed the absence of MNS1 from the respiratory epithelial cells of this individual. Two other individuals with hypomorphic variants showed laterality defects and mild respiratory phenotype. This study represents the first observation of heterotaxia and respiratory disease in individuals with biallelic MNS1 variants, an important extension of the phenotype associated with MNS1-related motile ciliopathy disorder.

Beta Thalassemia Carrier Rate: Problem Burden among High School Children.

Background & Aim of the Work: ß-Thalassemia (ßT) is highly prevalent in some countries like Egypt. Accurate data about actual disease prevalence and heavily prevalent geographic locations are essential to help in early detection and in setting up effective preventive programs. We aim for screening ßT carriers among Egyptian high school students in the Delta region. SUBJECTS AND METHODS: A cross-sectional multicenter study was carried out on 4320 randomly selected students from four governorates of the Nile Delta region, Egypt. All patients were to be tested for their complete blood count. Those with microcytic hypochromic anemia not caused by iron deficiency were tested for ßT carrier status using high-performance liquid chromatography. RESULTS: The total prevalence of ßT carrier rate was 6.13%. The highest prevalence was detected in Al-Sharkia Governorate, reaching 7.89%, followed by 6.90% in Al-Gharbia Governorate. Al- Dakahilia and Al-Menoufia showed lower rates of 4.86% and 3.73%, respectively. CONCLUSION: Despite the premarital national screening program for ßT in Egypt, the carrier rate is still high. More effort should be done into the proper implementation of national prevention programs.

Nano-insecticides against the black cutworm Agrotis ipsilon (Lepidoptera: Noctuidae): Toxicity, development, enzyme activity, and DNA mutagenicity.

Frequent applications of synthetic insecticides might cause environmental pollution due to the high residue. In addition, increasing insecticide resistance in many insect pests requires novel pest control methods. Nanotechnology could be a promising field of modern agriculture, and is receiving considerable attention in the development of novel nano-agrochemicals, such as nanoinsectticides and nanofertilizers. This study assessed the effects of the lethal and sublethal concentrations of chlorantraniliprole, thiocyclam, and their nano-forms on the development, reproductive activity, oxidative stress enzyme activity, and DNA changes in the black cutworm, Agrotis ipsilon, at the molecular level. The results revealed that A. ipsilon larvae were more susceptible to the nano-forms than the regular forms of both nano chlorine and sulfur within the chlorantraniliprole and thiocyclam insecticides, respectively, with higher toxicities than the regular forms (ca. 3.86, and ca.2.06-fold, respectively). Significant differences in biological parameters, including developmental time and reproductive activity (fecundity and hatchability percent) were also observed. Correspondingly, increases in oxidative stress enzyme activities were observed, as were mutagenic effects on the genomic DNA of A. ipsilon after application of the LC50 of the nano-forms of both insecticides compared to the control. These promising results could represent a crucial step toward developing efficient nanoinsecticides for sustainable control of A. ipsilon.

Screening for the Most Common Mutations of CFTR Gene among Egyptian Children with Difficult-to-Treat Asthma.

Cystic fibrosis (CF) is panethnic autosomal recessive disease that affects the exocrine glands of pancreas, lungs, and intestine. It is often misdiagnosed in developing countries as difficult-to-treat asthma. We enrolled 150 Egyptian families with one or more probands who were complaining of difficult-to-treat asthma, and 112 cases were studied extensively through history taking including pedigree construction and clinical examination. In addition, spirometry and computed tomography of the chest were done in selected cases. All cases were subjected to quantitative sweat chloride test and molecular screening for the three most common mutations of cystic fibrosis transconductance regulator ( CFTR ) gene ( ΔF508 , G542X , W1282X ) using amplification refractory mutation system (ARMS) technique. Probands of difficult-to-treat asthma comprised 66 males and 46 females; their age range was 1 to 14 years. Sixty-one probands (54.5%) were carriers of one or more of the studied mutations (36 cases and 25 carriers). Six carriers of single mutations had mild respiratory symptoms and negative sweat test. The most common allele was ΔF508 , 60 alleles in 56 individuals (4 were homozygous ΔF508 / ΔF508 ) followed by W1282X in 25 individuals and G542X in 12 individuals. Allele W1282X had an increased risk of recurrent chest infection and bronchiectasis. Moreover, cases with two mutations had more severe symptoms compared with those with a single mutation. CFTR mutations and CF-related syndromes are not rare as thought in Egypt, especially among the high-risk difficult-to-treat asthma. The readily available ARMS technique is recommended for ΔF508 and/or W1282X screening on priority basis among these children.

Unilateral Emphysema in Infancy, a Rare Presentation of Aberrant Bronchial Artery: Case Report and Review of Literature.

Aberrant bronchial arteries are rarely seen and may originate from various vascular structures. Hemoptysis is the most common clinical presentation of cases with anomalous bronchial artery. We report a case of a 1-month-old infant presented with respiratory distress and left lung emphysema. Radiologic investigations and bronchoscopy revealed that the cause is an aberrant left bronchial artery compressing the left main bronchus. Surgical division of the aberrant vessel was performed with gradual improvement of the emphysema and respiratory distress. Unilateral emphysema due to vascular compression was previously reported. However, to the best of our knowledge, this is the first reported case of aberrant bronchial artery presenting with external compression of a main bronchus and unilateral emphysema. Also, this is the youngest reported case with an aberrant bronchial artery.

Endobronchial inflammatory pseudotumor: a rare cause of a pneumothorax in children.

Inflammatory pseudotumors of the lung are a group of non-neoplastic tumors, which are mainly of parenchymal origin and rarely endobronchial. We report a case of a 9-year-old girl who presented with left-sided tension pneumothorax and subcutaneous emphysema. After emergency management, chest computed tomography revealed an ill-defined left lung mass. Rigid bronchoscopy revealed a mass occluding the left main bronchus at the origin of the left upper lobe bronchus. Initially, the mass was thought to be a foreign body granuloma. Few weeks later, the child presented with recurrence of the same clinical, radiologic, and bronchoscopic outcomes. Histologic examination after the repeat bronchoscopic excision revealed the lesion to be consistent with inflammatory pseudotumor. Left upper lobectomy was performed with a complete resolution of symptoms and no recurrence was observed during the 2 years of follow-up. To the best of our knowledge, this is the first reported case of inflammatory pseudotumor presenting with tension pneumothorax.

Migrating laryngeal foreign body.

We report the case of a 6-year-old boy who presented with a 2-month history of stridor and respiratory difficulty, preceded 1 month earlier by dry cough. The evaluation before admission revealed glottic narrowing due to diffuse inflammatory changes. On examination, the patient was seen to have biphasic stridor and respiratory distress with diminished breath sounds throughout both lung fields. Laryngoscopy revealed multiple polyps and granulation tissue causing marked laryngeal narrowing. No foreign body was detected in the larynx. Elective tracheostomy was performed before proceeding to bronchoscopy. The latter procedure revealed a foreign body in the left main bronchus. One week after the foreign body extraction, repeat bronchoscopy revealed nearly total disappearance of polyps and granulation tissues. The tracheostomy tube was removed and the patient recovered uneventfully. To our knowledge, this is the first reported case of stridor caused by a migrating laryngeal foreign body. A thorough endobronchial examination should be carried out in patients with unexplained laryngeal polyps and granulation tissue.

Steroid Phobia among Parents of Asthmatic Children: Myths and Truth.

Asthma is one of the most common chronic diseases of childhood. Inhaled corticosteroids (ICS) are the recommended controller drug for asthma treatment. The aim of our study was to determine concerns and fears of parents of children with asthma towards the use of ICS. One hundred parents of asthmatic children were interviewed using structural questionnaire. Airway inflammation was reported by only 6% of interviewed parents, whereas airway narrowing was addressed by 34%. Interesting data, 71% of parents were concerned with the role of steroids in asthma treatment, but more than half (53%) of them addressed fears from side effects. Apparent gaps were found in knowledge of parents of asthmatic children about ICS as controller asthma medication. So, physician and health providers should explain to asthmatic parents that airway inflammation is the core for asthma management. This may remove fears about ICS and thus improve adherence to treatment.

Gene polymorphisms of IL-6(-174) G/C and IL-1Ra VNTR in asthmatic children.

OBJECTIVE: To check for the association of genetic polymorphisms of IL-6-(-174)G/C and IL-1RaVNTR with the susceptibility and severity of asthma in Egyptian children. METHODS: Subjects included 69 asthmatic children and 98 healthy unrelated controls from the Nile Delta of Egypt. Cases consisted of 20 males and 49 females with an age mean +/- SD is 7.5 +/- 2.1 ranging between 2-13 years. DNA amplification using PCR with sequence-specific primers was done for detection of promotor single nucleotide polymorphism of IL-6 gene as well as intron 2 VNTR of IL-1Ra gene. Frequency of case-genotypes or alleles were compared to controls using Fisher exact test and Odds ratio. RESULTS: Cases showed significant higher frequency of the genotypes: IL-6-174 GG (P<0.05, OR=3.2, 95% CI=1.09-10) that was evident mainly in the uncontrolled asthma subgroup indicative of the possibility of being a severity genotype. All cases as well as case-subgroups showed high significant frequency of IL-1Ra A1A1 (p<0.0001, OR=1.5, 95% CI=1.3-1.8). This may be considered a susceptibility genotype. Cases have also shown significant lower frequency of IL-6(-174) GC and IL-1Ra A1A2 genotypes (P<0.001 and P<0.0001 respectively). CONCLUSION: IL-6 and IL-1Ra polymorphisms can be considered genetic markers for bronchial asthma susceptibility and/or severity among Egyptian children. This may have a potential impact on family counseling and management.

Gene polymorphisms of tumor necrosis factor alpha-308 and interleukin-10-1082 among asthmatic Egyptian children.

Tumor necrosis factor (TNF) alpha-308 and interleukin (IL)-10(-1082) have potent inflammatory responses in the process of airway inflammation in asthma. The purpose of this study was to check for association of polymorphisms related to cytokine genes with susceptibility and severity of bronchial asthma in Egyptian children. Blood samples of 69 asthmatic children receiving treatment and follow-up at the Allergy and Respiratory Medicine Unit, Mansoura University Children Hospital, Mansoura, Egypt, were subjected to DNA extraction and amplification using polymerase chain reaction with sequence-specific primers for detection of single nucleotide polymorphisms in the promoter regions of cytokine genes TNF-alpha(-308(G-->A)), IL-10(-1082(G-->A)). Compared with normal controls, Egyptian asthmatic children showed a significant higher frequency of IL-10(-1082) G/G homozygosity genotype (p < 0.001; odds ratio [OR] = 7) with lower frequency of G/A heterozygosity genotype among cases. This finding also was detected in cases with persistent asthma and eczema. These cases showed significant lower frequency of TNF-alpha-308 G/A heterozygosity (p < 0.05; OR = 0.44). Also, male cases, cases with positive family history, and those patients with persistent types of asthma showed a higher frequency of TNF-alpha-308 G/G homozygosity. IL-10(-1082(G-->A)) G/G and TNF-alpha-308(G-->A) G/G may be a contributing factor in susceptibility as well as severity of asthma among Egyptian children. Separate studies should be specified relating these cytokine genotypes to response to various modalities in asthma therapy. This study reports that IL-10(-1082(G-->A)) G/G and TNF-alpha-308(G-->A) G/G genotypes may be contributing factors in susceptibility as well as in severity of asthma among Egyptian children. Separate studies may be specified relating these cytokine genotypes to response to various modalities in asthma therapy.