Interaction of sperm with endometrium can regulate genes involved in endometrial receptivity pathway in mice: An experimental study

Background: Many researchers consider implantation and endometrial receptivity as pertinent issues in reproductive science. Although, several experiments have been performed and their results evaluated, yet there is no confirmed evidence about the related factors and the role of sperm in endometrial receptivity. Objective: To investigate the effect of the sperm-endometrium interaction in regulating genes involved in the endometrial receptivity pathway. Materials and Methods: In this experimental study, 10 male and 30 female NMRI mice were included, and half of the male cases were vasectomized. The subjects were divided into two groups as follows; group 1 (case) comprised of 15 females mated with 5 non-vasectomized male mice, while group 2 (control) consisted of 15 females mated with 5 vasectomized males. Cases were sacrificed and assessed after 36 hr and the endometrial tissue was extracted and kept at -80°C until the next use. The expression of the endometrial receptivity pathway genes, including VEGF, HBEGF, FGF2, EGF, LIF, LIFR, HOXA10, MUC1, PGR, and CSF, was examined in both groups. For statistical analysis, an independent samples test (Mean ± SD) was used. Results: The mRNA levels of LIF (p = 0.045), LIFR (p = 0.040), MUC1 (p = 0.032), VEGF (p = 0.022), EFG (p = 0.035), and FGF2 (p = 0.040) were significantly upregulated in the case group compared with the control group. Conclusion: Finally, seminal plasma was observed to be effective in expressing the involved genes in the successful implantation pathway, including LIF, LIFR, MUC1, VEGF, EGF, and FGF2. Key words: Endometrial receptivity, Sperm, Gene expression, Mice

A Memetic Algorithm for Hybrid Flowshops with Flexible Machine Availability Constraints

This paper considers the problem of scheduling hybrid flowshops with machine availability constraints (MAC) to minimize makespan. The paper deals with a specific case of MAC caused by preventive maintenance (PM) operations. Contrary to previous papers considering fixed or/and conservative policies, we explore a case in which PM activities might be postponed or expedited while necessary. Regarding this flexibility in PM activities, we expect to obtain more efficient schedule. A simple technique is employed to schedule production jobs along with the flexible MACs caused by PM. To solve the problem, we present a high performing metaheuristic based on memetic algorithm incorporating some advanced features. To evaluate the proposed algorithm, the paper compares the proposed algorithm with several wellknown algorithms taken from the literature. Finally, we conclude that the proposed algorithm outperforms other algorithms

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Update on Hyper IgE syndrome (HIES)

Hyper IgE Syndrome (HIES) is a rare primary immunodeficiency disease. Most of HIES cases are sporadic. HIES type AD is caused by mutation in signal transducer and activator of transcription-3 (STAT-3). A number of mosaicism HIES has been reported that is associated with intermediate phenotype. Autosomal recessive HIES (AR-HIES) is due to mutation in Dock-8 or cytokine sis 8 and TYK2 or tyrosine kinase 2. The common manifestations are atopic eczema, staphylococcal dermatitis, cellulitis and folliculitis (cold dermal abscesses that are not warm, painful and without redness), recurrent pneumonia and pulmonary abscesses, osteopenia and recurrent bone fracture. The diagnosis of standard HIES is based on clinical suspicion. There is no specific treatment for HIES. The treatment should be based on the prevention of developing infections. Prophylactic antibiotics such as cotrimoxazole and IVIG are administered. Hematopoietic stem cell transplantation was done for all types of HIES, but there is a little information and experience about the long term results of this therapy

Update on Hyper IgE syndrome (HIES)

Hyper IgE Syndrome (HIES) is a rare primary immunodeficiency disease. Most of HIES cases are sporadic. Autosomal dominant HIES is caused by mutation in signal transducer and activator of transcription-3 (STAT-3). A number of mosaicism HIES has been reported that is associated with intermediate phenotype. Autosomal recessive HIES is due to mutation in Dock-8 or cytokine sis 8 and TYK2 or tyrosine kinase 2. The common anifestations are atopic eczema, staphylococcal dermatitis, cellulitis and folliculitis (cold dermal abscesses that are not warm, painful and without redness), recurrent pneumonia and pulmonary abscesses, osteopenia and recurrent bone fracture. The diagnosis of standard HIES is based on clinical suspicion. There is no specific treatment for HIES. The treatment should be based on the prevention of developing infections. Prophylactic antibiotics such as cotrimoxazole and IVIG are administered. Hematopoietic stem cell transplantation was done for all types of HIES, but there is a little information and experience about the long term results of this therapy

Value of Gluten Patch Test in Diagnosis of Celiac Disease

Objective:Celiac disease is an intestinal disorder identified by mucus inflammation, villous atrophy and crypt hyperplasia. This disorder can be controlled by elimination of gluten from daily diet. Patients with celiac disease are at greater risk of gastrointestinal malignancy and non- Hodgkin lymphoma than are the general population. This study tries to present the value of gluten patch test for diagnosis of celiac disease. Methods: In this investigation, the study population was divided into case and control groups. The case group consisted of patients with celiac disease. The control group were patients involved in celiac disease but suffering from other gastrointestinal disorders. Both gluten patch and placebo patch were attached to the skin between the scapulas. The results were read twice: 48 hours and 96 hours after the patch was applied. Patients who showed irritation reactions were withdrawn from this study. The results were analysed by SPSS software, Spearman’s test, chi square, and Mann–Whitney tests. Findings: The value obtained from the gluten patch test after 96 hours are as follows: specification at 95%, sensitivity at 8%, positive prediction value at 67%, and negative prediction value at 43%. Conclusion: It can be concluded that the gluten patch test is not an efficient test for screening of celiac disease, however, it can be useful for diagnosis of celiac disease if employed and studied with clinical symptoms and serologic and biopsy tests. Furthermore, we should doubt our judgment if the result of gluten patch test for the patient with celiac disease is positive

Clinical and Immunological Features of 65 Iranian Patients with Common Variable Immunodeficiency

Common variable immunodeficiency (CVID) is a primary immunodeficiency disease characterized by hypogammaglobulinemia and recurrent bacterial infections. The records of 65 patients with CVID (37 males and 28 females) in the age range of 24 to 537 months were reviewed. By the year 2003, 11 patients had died and seven patients could not be located. The total follow-up period was 221 patient-years. The median diagnostic delay (time between onset and diagnosis) in our patient group was 60 months. At the time of diagnosis, the baseline serum immunoglobulin G (IgG), IgM, and IgA levels were below the level normal for the patients' age; the medians for this group were 120, 10, and 0 mg/dl, respectively. All of the patients presented with infectious diseases at the time of onset, the most common of which were otitis media, diarrhea, pneumonia, and sinusitis. Acute and recurrent infections were also found in almost all of the patients, particularly involving respiratory and gastrointestinal systems. The most common infections, before diagnosis and during follow-up, were pneumonia, acute diarrhea, acute sinusitis, and otitis media. CVID should be considered in any patient with a history of recurrent infections and decreased levels of all serum immunoglobulin isotypes

Inheritance Pattern and Clinical Aspects of 93 Iranian Patients with Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is a rare immunodeficiency due to a genetic defect in one of the NADPH-oxidase components. We studied CGD inheritance forms (autosomal recessive (AR) or X-linked (XL)) and AR-CGD subtypes in Iran. Clinical and functional investigations were conducted in 93 Iranian CGD patients from 75 families. Most of the patients were AR-CGD (87.1%). This was related to consanguineous marriages (p = 0.001). The age of onset of symptoms and diagnosis were lower in XL-CGD compared with AR-CGD (p <0.0001 for both). Among AR-CGD patients, p47phox defect was the predominant subtype (55.5%). The most common clinical features in patients were lymphadenopathy (65.6%) and pulmonary involvement (57%). XL-CGD patients were affected more frequently with severe infectious manifestations. Although XL-CGD is the most common type of the disease worldwide, only 12 patients (12.9%) were XL-CGD in our study. The relatively high frequency of AR-CGD is probable due to widely common consanguineous marriages in Iran

Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort

Background: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses. Objective: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings. Methods: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID. Results: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase [BTK] and 6 μ heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with μ heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with μ heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008). Conclusions: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment