Role of matrix metalloproteinases in mitral valve regurgitation: Association between the of MMP-1, MMP-9, TIMP-1, and TIMP-2 expression, degree of mitral valve insufficiency, and pathologic etiology.

BACKGROUND: The pathogenesis of mitral valve insufficiency is not yet fully understood. Several studies stressed the role of matrix metalloproteinases (MMPs) in the emergence of valvular pathologies. The primary objective of the present study is to analyze the role of selected MMPs and their inhibitors in mitral valve insufficiency. PATIENTS AND METHODS: Eighty patients (33 female/47 male, mean age 67 years) underwent cardiopulmonary bypass surgery for mitral valve reconstruction between 2007 and 2015. All patients suffered from mitral insufficiency (MI) Stages iii and iv. When tissue resection was acquired specimens were taken immediately frozen and used for histological examination. Expression of MMP-1, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 was examined immunohistochemically and distribution was analyzed in regard to preoperative clinical, echocardiographic, and histopathological findings. RESULTS: A clear correlation between the MMP expression and the MI degree of severity could be shown. The expression of MMPs proved to be high in relation to mild insufficiencies and relatively weak in the case of severe ones. Additionally, the etiology of the MI was considered in the analysis and a significant difference in the expression of MMPs between the mitral valves with endocarditis and the ones featuring a degenerative disease could be shown. Within the group of valves with degenerative diseases, no significant difference could be established between the subgroups (myxoid and sclerosed valves). CONCLUSION: The increased expression of MMPs and their inhibitors in mild insufficiencies could prove that the molecular changes in the valve precede the macroscopical and thus the echocardiographically diagnosable changes. Hence, new options for early diagnosis and therapy of MIs should be examined in further studies, respectively. Herein, the correlation of the MMP blood levels with MMP tissue expression should be addressed for surgical therapeutical decisions.

Forecasting the daily deaths caused by COVID-19 using ARIMA model.

Coronavirus disease (COVID-19) pandemic has recently become a global health crisis. On the basis of this study the data reported from ten different countries on confirmed daily deaths caused by COVID-19. By fitting the linear regression models based on the data from ten countries to find the relationship between the new cases and deaths reported daily. We also used the autoregressive integrated moving average model (ARIMA) to predict the potential number of daily deaths caused by COVID-19 in these countries in the next 3 Months. The R2 value obtained for Iran (0.24) implies that 24% of daily deaths correspond to the daily cases. The R2of Pakistan 0.662 which indicates that 66.2% of daily deaths are explained by our predictor variable. In Turkey 70.2% of daily deaths are explained by daily cases and India recorded the highest number of deaths while UAE had the lowest number of deaths. Our results suggest that the pandemic is under control in China, UAE and Australia. Pakistan, Iran, Germany and Italy however, showed an upward trend in the spread of the disease, which may correlate with a high increase in death rate as the data indicated.

Variants of human CLDN9 cause mild to profound hearing loss.

Hereditary deafness is clinically and genetically heterogeneous. We investigated deafness segregating as a recessive trait in two families. Audiological examinations revealed an asymmetric mild to profound hearing loss with childhood or adolescent onset. Exome sequencing of probands identified a homozygous c.475G>A;p.(Glu159Lys) variant of CLDN9 (NM_020982.4) in one family and a homozygous c.370_372dupATC;p.(Ile124dup) CLDN9 variant in an affected individual of a second family. Claudin 9 (CLDN9) is an integral membrane protein and constituent of epithelial bicellular tight junctions (TJs) that form semipermeable, paracellular barriers between inner ear perilymphatic and endolymphatic compartments. Computational structural modeling predicts that substitution of a lysine for glutamic acid p.(Glu159Lys) alters one of two cis-interactions between CLDN9 protomers. The p.(Ile124dup) variant is predicted to locally misfold CLDN9 and mCherry tagged p.(Ile124dup) CLDN9 is not targeted to the HeLa cell membrane. In situ hybridization shows that mouse Cldn9 expression increases from embryonic to postnatal development and persists in adult inner ears coinciding with prominent CLDN9 immunoreactivity in TJs of epithelia outlining the scala media. Together with the Cldn9 deaf mouse and a homozygous frameshift of CLDN9 previously associated with deafness, the two bi-allelic variants of CLDN9 described here point to CLDN9 as a bona fide human deafness gene.

Mutations of GJB2 encoding connexin 26 contribute to non-syndromic moderate and severe hearing loss in Pakistan.

Mutations of GJB2 which encode connexin 26, contribute to 6-7 % of profound deafness in Pakistan. We investigated the involvement of GJB2 mutations in a cohort of 84 pedigrees and 86 sporadic individuals with moderate or severe hearing loss. Individuals in eight consanguineous families and four sporadic cases (9.52 and 4.65 %, respectively) were homozygous or compound heterozygous for p.W24X or p.W77X mutations in GJB2. These two variants are also among the most common mutations known to cause profound deafness in South Asia. The association of identical mutations with both profound and less severe phenotype of hearing loss suggests that alleles of other genes modify the phenotype due to these GJB2 nonsense mutations. Our study demonstrates that GJB2 mutations are an important contributor to aetiology of moderate to severe hearing loss in Pakistan.

Preliminary study on mitochondrial DNA analysis from different sports items.

Criminals often attempt to conceal blood-stained weapons used in violent crimes, making forensic evidence crucial in solving cases. This study explores the recovery and extraction of trace DNA from sports equipment, including cricket bats, table tennis racquets, and hockey sticks, which are frequently implicated in such incidents. Our research evaluates various double swab collection methods for retrieving trace DNA from these sports items, emphasizing those associated with blunt force trauma. We also compare presumptive and confirmatory tests to establish a direct correlation. This research consistently demonstrated robust DNA recovery, surpassing a 50 % threshold across all tests. Specifically, DNA recovery from buried samples reached an impressive 87 %, while washed samples still yielded a substantial 80 % efficiency. We conducted a comparative analysis between presumptive and confirmatory testing methods, establishing a direct correlation between the two. Variability in DNA recovery efficiency was observed and attributed to factors like the type of surface the items contacted, and ambient humidity levels. In addition to presenting robust DNA recovery rates, statistical analyses were employed to compare methods, establishing correlations and highlighting the influence of environmental factors on DNA recovery efficiency. These findings have significant implications for forensic investigations involving silent weapons crafted from sports equipment, emphasizing the need for standardized protocols and consideration of environmental factors in DNA analysis.

In-field deployable and facile nanosensor for the detection of pesticides residues.

Local air and water should be first priority to understand the environment of any area. Different categories of contaminants behave like bottleneck situation in collection and analysis of data about abiotic factors for the understanding and resolving the environmental issues. In digital age the emerging nano technology enroll its role to meet the needs of hour. Due to increase in pesticides residues, the global health threats are on bloom because it inhibits the functionality of acetylcholinesterase (AChE) enzyme. Smart nanotechnology based system can tackle this issue and sense the pesticides residues in environment and vegetables as well. Here Au@ZnWO4 composite is reported, for accurate detection of pesticides residues in biological food and environmental samples. The fabricated unique nanocomposite was characterized by SEM, FTIR, XRD and EDX. The characterized material used for the electrochemical detection of organophosphate pesticide (chlorpyrifos), with 1 pM LoD at a signal to noise ratio of 3. The main concern of study is to help out in disease prevention, food safety and ecosystem protection.

Spectrum of genetic variants in moderate to severe sporadic hearing loss in Pakistan.

Hearing loss affects 380 million people worldwide due to environmental or genetic causes. Determining the cause of deafness in individuals without previous family history of hearing loss is challenging and has been relatively unexplored in Pakistan. We investigated the spectrum of genetic variants in hearing loss in a cohort of singleton affected individuals born to consanguineous parents. Twenty-one individuals with moderate to severe hearing loss were recruited. We performed whole-exome sequencing on DNA samples from the participants, which identified seventeen variants in ten known deafness genes and one novel candidate gene. All identified variants were homozygous except for two. Eleven of the variants were novel, including one multi-exonic homozygous deletion in OTOA. A missense variant in ESRRB was implicated for recessively inherited moderate to severe hearing loss. Two individuals were heterozygous for variants in MYO7A and CHD7, respectively, consistent with de novo variants or dominant inheritance with incomplete penetrance as the reason for their hearing loss. Our results indicate that similar to familial cases of deafness, variants in a large number of genes are responsible for moderate to severe hearing loss in sporadic individuals born to consanguineous couples.