Evaluation of mandibular advancement device placement based on levels of TNF-alpha in participants with obstructive sleep apnea: A clinical study.

STATEMENT OF PROBLEM: Objective assessments of the effect of mandibular advancement device on patients with obstructive sleep apnea are lacking. PURPOSE: The purpose of this clinical study was to compare levels of serum tumor necrosis factor alpha (TNF-alpha), Epworth Sleepiness Scale score, and Berlin Questionnaire score in patients with mild to moderate obstructive sleep apnea before and after treatment with a mandibular advancement device. MATERIAL AND METHODS: Twenty participants diagnosed with mild to moderate obstructive sleep apnea based on polysomnography testing were enrolled. A custom nonadjustable mandibular advancement device with 70% mandibular protrusion was provided for each participant for management of the obstructive sleep apnea. Evaluation of TNF-alpha levels was performed before treatment (baseline) and 3 and 6 months after starting mandibular advancement device therapy by using a Human TNF-alpha enzyme-linked immunoassay (ELISA) sandwich kit. The Epworth Sleepiness Scale and Berlin Questionnaire were also filled out by the participants at the same time intervals (α=.05). RESULTS: A statistically significant decline in the levels of TNF-alpha was observed at 3 and 6 months compared with baseline (P<.001). The Epworth Sleepiness Scale scores showed a statistically significant reduction at 3 and 6 months compared with baseline (P<.001). The risk of obstructive sleep apnea assessed by using the Berlin Questionnaire was found to be significantly reduced at 6 months compared with baseline (P=.001). CONCLUSIONS: Patients with mild to moderate obstructive sleep apnea showed reduced levels of TNF-alpha and Epworth Sleepiness Scale and Berlin Questionnaire scores when treated with a mandibular advancement device.

Cadmium in Human Diseases: It's More than Just a Mere Metal.

Cadmium (Cd), poisoning has been reported from all around the World, causing many deaths annually. Cd is a toxic heavy metal, and is widely present in environment. It has been reported that chronic Cd exposure is associated with kidney disease, osteoporosis, cardiovascular diseases and cancer. Smoking causes exposure to significantly higher Cd levels in humans. Tobacco smoke transports Cd into the lungs. Blood then transport it to the rest of the body where it increases effects by potentiating Cd that is already present from Cd-rich food. Other high exposures of Cd can occur with people, who live near hazardous waste sites, or factories that release Cd into the air and people who work in the metal refinery industry. Breathing of Cd can severely damage the lungs and may even cause death. Multiple studies have shown an association between environmental exposure to hazardous chemicals including toxic metals and obesity, diabetes, and metabolic syndrome. At the same time, the existing data on the impact of Cd exposure on obesity and diabetes are contradictory. On the converse, results of epidemiologic studies linking Cd exposure and Osteoporosis, overweight or obesity are far less consistent and even conflicting, also depending on differences in exposure levels. In turn, laboratory studies demonstrated that Cd adversely affects adipose tissue physiopathology through several mechanisms, thus contributing to increased insulin resistance and enhancing diabetes. However, intimate biological mechanisms linking Cd exposure with human diseases are still to be adequately investigated. Therefore, the aim of the present review was to explore the impact of Cd exposure and status on the risk of Cd in human diseases.

Current and future therapeutic approaches of CFTR and airway dysbiosis in an era of personalized medicine.

Cystic fibrosis (CF) is a life-threatening genetic disorder caused by mutations in the CFTR gene. This leads to a defective protein that impairs chloride transport, resulting in thick mucus buildup and chronic inflammation in the airways. The review discusses current and future therapeutic approaches for CFTR dysfunction and airway dysbiosis in the era of personalized medicine. Personalized medicine has revolutionized CF treatment with the advent of CFTR modulator therapies that target specific genetic mutations. These therapies have significantly improved patient outcomes, slowing disease progression, and enhancing quality of life. It also highlights the growing recognition of the airway microbiome's role in CF pathogenesis and discusses strategies to modulate the microbiome to further improve patient outcomes. This review discusses various therapeutic approaches for cystic fibrosis (CFTR) mutations, including adenovirus gene treatments, nonviral vectors, CRISPR/cas9 methods, RNA replacement, antisense-oligonucleotide-mediated DNA-based therapies, and cell-based therapies. It also introduces airway dysbiosis with CF and how microbes influence the lungs. The review highlights the importance of understanding the cellular and molecular causes of CF and the development of personalized medicine to improve quality of life and health outcomes.

To Study the ß-Globin Haplotype Pattern of Descent of a Set of Linked Alleles Occurring on the Same Chromosome in the Northern Province of India.

OBJECTIVE: To study the five mutations commonly prevalent in North India, i.e., IVS-I-5 (G→C), 619 bp deletion, IVS-I-1 (G→T), codon 41/42 (-TTCT), and codon 8/9 (+G), in the beta thalassemia (ß-thalassemia) major children. The specific ß-thalassemia mutations of different haplotype patterns of the ß-globin gene cluster will also be determined. METHODS: A total of 125 children diagnosed with ß-thalassemia major visiting the Department of Pediatrics of King George's Medical University were involved in the study. As per the QIAamp (Qiagen, Hilden, Germany) manufacturer guidelines, genomic DNA was isolated from whole blood. To identify the haplotype pattern within the ß-globin gene cluster, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used. The respective restriction endonucleases used were Hind III/GƔ, Hinc II/Ψß, Hinf I/ß, Ava II/ß, and BamHI for the haplotype analysis in the ß-globin pattern of descent of a set of linked alleles occurring on the same chromosome. RESULTS: Among the five common mutations, 73 patients had IVS-I-5 (G→C), 28 patients had 619 bp deletion, 17 patients had IVS-I-1 (G→T), five patients had Cd 41/42 (-TTCT), and two patients had Cd 8/9 (+G) mutations. Fifteen haplotypes (haplotypes 1-15) were identified in 125 ß-thalassemia major children. Among the five haplotypes observed in the IVS-I-5 (G→C) mutation, the H1 haplotype was most predominant with a frequency of 27.2%, followed by the H2, H4, H3, and H10 haplotypes in the given population. In 619 bp deletion, IVS-I-1 (G→T), codon 41/42, and codon 8/9, haplotype H9, H12, H11, and H5 were seen, respectively. CONCLUSION: ß-thalassemia was found to be the most common in the northern province of Uttar Pradesh. The linkage of ß-globin gene haplotypes with ß-thalassemia mutations was explored in the northern province of Uttar Pradesh. The population of different natives is being mixed up due to migration and industrialization. These were some reasons for the occurrence of haplotypic heterogeneity. This haplotype heterogeneity was correlated with the origin of these mutations found to be unlike the origin of common ones from different provinces.

Measuring impact of Covid-19 pandemic at a teaching hospital in north India.

Introduction: Government runs teaching hospitals to impart a high-quality medical education to budding medicos and paramedical students in training. The experiences these trainees at various tenure positions get then and there shape their worldview for rest of the life and have an indelible impression. The Covid-19 pandemic disrupted all the routines at the hospitals around the world-including ours-and we make an attempt to measure it in one dimension in this study. Materials and Methods: We obtained attendance data of patients at out patient department and in patient department of our hospital. During the pandemic for a certain duration offline (physical) registrations were closed and they were attended only by online ones. Hence that data (actually a part of it) got captured electronically and we analyzed it to get an idea of the traversed course of the scourge. Results: When the pandemic surged during the spring and summer of 2021, our hospital was turned into a Covid facility. Hence average routine attendance of patients got reduced to a significant extent, elective surgeries/interventions and procedures were postponed and this data is reflected in an electronic system, perhaps making a long-lasting effect on the budding trainees. This fact needs to be realized so as to take appropriate action. Conclusion: We need to realize that the effects of the viral communicable disease may be enduring, not only for the infected patients and their families but also for those who learn on those patients. Therefore, the transmissible diseases disabled not only our society, economy, and health care services when they ascended but pedagogy too. Online learning came to rescue but only up to a certain extent and with several caveats and limitations.

Analysis of Government website for web-registration to assess pattern of the Covid pandemic.

Introduction: Covid-19 is an unprecedented challenge in our times leaving a trail of destruction and mayhem affecting almost all of us during the last 2 years. Various data sources are available around the globe to measure its impact using various yardsticks. Material and Methods: By carefully looking at data available at the website maintained by Government of India, we can draw some useful conclusions. Results: There is a dip in the number of online registrations at our hospital coinciding with second wave and resultant lockdown. Conclusion: Tracing digital footprints of an event as huge as the Covid pandemic may help us for future planning when we learn its lessons well.

Altered pro-inflammatory and anti-inflammatory plasma cytokines levels in children with Down's syndrome: A meta-analysis.

BACKGROUND: Down syndrome (DS) is the commonest chromosomal anomalies at birth. DS is portrayed by the event of extra complete/deficient duplicate of chromosome number 21 (trisomy 21). Around the world, this disordered influencing roughly 1 out of 1000 infants. Pro-inflammatory and anti-inflammatory cytokines engaged with a few physiological procedures involving the guideline of inflammatory reactions. In DS kids, the creation of few important inflammatory and anti-inflammatory cytokines is altered. Different investigations shows that the cytokines are dysregulated in patients with DS. In this study, we led a meta-analysis to evaluate the connections of pro-inflammatory and anti-inflammatory cytokine changes in youngsters with DS patients. METHODOLOGY: We searched PubMed, Google and Web of Science for studies in exploring the association of pro-inflammatory and anti-inflammatory serum level with DS patients. Total 10 studies were included in the meta-analysis. The random effects were used to analyze the pooled data. All statistical tests were two-sided. RESULTS: High circulating level of serum MCP-1 was significantly associated with DS [Cohen's d = 143.91 95% confidence interval (CI) =110.38-177.43]. However, the other circulating cytokines IL-2 and IL-17 level were lower whereas IL-13 level was higher but not significantly different in DS as contrasted to healthy controls. The heterogeneity level was higher in IL-2, IL-13 and IL-17 cytokines. CONCLUSION: This meta-analysis shows that the higher circulating level of MCP-1 was associated with DS.

Paradise under siege: Healthcare elusive under Kashmir lockdown.

The famous poet, Amir Khusro, said of Kashmir: "If there is heaven on earth, it is here, it is here, it is here". That heaven and crown of India has been under siege now for over four months.

MTHFR C677T, Prothrombin G20210A, and Factor V Leiden (G1691A) Polymorphism and Beta-Thalassemia Risk: A Meta-Analysis.

Background Beta (ß)-thalassemia major patients frequently suffer from many vascular problems. Thrombophilia is a blood disorder that comprises imbalances in the blood coagulating factor due to ecological and hereditary components. Previous evidence shows that thrombosis is the commonest risk in beta-thalassemia patients. Several studies have examined that MTHFR C677T, prothrombin G20210A (PT G20210A), and Factor V Leiden G1691A (FVL G1691A) polymorphism play a crucial role in the development of ß-thalassemia major, yet the result was questionable and uncertain. Therefore, in this study, we executed the correlation between these gene polymorphisms with ß-thalassemia major patients. Methods Suitable keywords were used to search related articles in PubMed, Google Scholar, and Web of Science. In this random-effects meta-analysis, we analyzed the odds ratio (OR) for the estimation of risk. Results A total of nine research articles with 645 ß-thalassemia major patients and 989 healthy controls were incorporated in this meta-analysis. The pooled OR was assessed in MTHFR C677T, PT G20210A, and FVL G1691A polymorphism. This random-effects meta-analysis demonstrated that MTHFR C677T, PT G20210A, and FVL G1691A gene polymorphism did not significantly associate with ß-thalassemia major. Moreover, the heterogeneity was significantly found in genotype CC vs CT+TT C677T (I2=61%) and allele C vs T (I2=71%) of MTHFR and genotype GG vs GA (I2=95%), GG vs GA+AA (I2=95%), GA vs GG+AA (I2=95%), and allele G vs A (I2=93%) of FVL G1691A. Conclusion The results of this meta-analysis show that MTHFR C677T, prothrombin G20210A, and Factor V Leiden (G1691A) gene polymorphism are not a risk factor for ß-thalassemia major.

Mean corpuscular volume/mean corpuscular hemoglobin values are not reliable predictors of the ß-thalassemia carrier status among healthy diverse populations of Himachal Pradesh, India.

BACKGROUND: Himachal Pradesh is a hill state in North India in the Western Himalayas. ß-thalassemia is a genetic disorder of hemoglobin inherited in an autosomal recessive manner that results in defective globin production leading to the early destruction of red blood cells. ß-thalassemia has long been neglected in Himachal Pradesh due to popular belief that it runs along "Lahore-Gujarat-Punjab" belt in India. Therefore, there is no ß-thalassemia testing facility currently in the state. METHODS: To estimate the prevalence of ß-thalassemia carriers, we calculated the sample size based on probability proportional to size self-weighing design. In each of 20 selected colleges, 111 students having an age of 18-25 were tested for high-performance liquid chromatography (HPLC) and complete blood count. Some were further tested for the mutations. We computed sensitivity, specificity, positive predictive value (PPV) and negative predictive value, and receiver operating characteristic curve for mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) red cell parameters. RESULTS: Of the 2220 students, 57 were found to be ß-thalassemia carrier by HPLC. The overall prevalence rate was 2.6% which translates to probable 180,000 ß-thalassemia carriers in Himachal Pradesh. Six districts bordering highly endemic Punjab had a higher prevalence. Hemoglobin D-Punjab, Heterozygous-Iran Trait, and raised fetal hemoglobin were found. Thalassemia major and sickle cell disease were not found. Anemic status or MCV/MCH parameters were not found to be reliable predictors of thalassemia carrier status among the healthy populations of HP. The predominant mutation found was IVS 1-5 G > C. CONCLUSION: Popular ongoing strategy for screening with MCV and MCH has low-PPV and can miss upto 37% of true thalassemia carriers. HPLC is better strategy for screening carriers and reduces further spread of thalassemia.

A demographic prevalence of ß Thalassemia carrier and other hemoglobinopathies in adolescent of Tharu population.

BACKGROUND AND AIMS: Hemoglobinopathies and thalassemias are the commonest single gene disorders in India. In Terai region of India, Hemoglobinopathies and thalassemias are the most common in the Tharu community. Therefore, in this study, we aim to evaluate the Hb variant analysis of hemoglobinopathies and thalassemias in a Tharu population in Lakhimpur Kheri Districts of Uttar Pradesh, India. MATERIALS AND METHODS: Total 493 individuals were recruited in this study. The demographic details and blood samples were collected from different location at Kheri district during mega health camp. Hb variant analysis was performed by high performance liquid chromatography (HPLC) system beta thalassemia short program in BIO-RAD VARIANT. RESULTS: Out of 493, 108 (21.9%) individual suffers with abnormal haemoglobinopathies. In which ß-thalassemia trait is the commonest haemoglobinopathy (12.98%), followed by HbE trait (7.50%), and compound heterozygous HbS/ß-Thalassemia trait (1.42%) in overall population. The HbF was significantly greater in HbS heterozygous (1.45 ± 1.41), whereas mean HbA2 was significantly greater in ß-Thalassemia trait (5.17 ± 1.36). CONCLUSION: The high incidence of hemoglobinopathies and thalassemias were observed in Tharu community in Lakhimpur Kheri districts of Uttar Pradesh, Indian.