Knowledge, Attitude and Practice Regarding Exclusive Breastfeeding Among Mothers Attending Tertiary Care Hospital

OBJECTIVES: To determine knowledge, attitude, and practice regarding exclusive breastfeeding among mothers attending tertiary care hospitals.  METHODOLOGY: A descriptive cross-sectional study was conducted at the Department of Pediatrics in Hayatabad Medical Complex, Peshawar. A total of 162 mothers were selected who were practicing breastfeeding of ages between 20 to 35 years, having a full-term baby of age up to 6 months old. The data is collected through a pre-planned questionnaire and then was analyzed using statistics version 24.0. The duration of the study was from 1st June 2020 to 30th October 2020. RESULTS: The results showed that no significant association was found between age groups, socio-economic status regarding knowledge, attitude, and practice (p>0.05). However, there was a significant difference between knowledge, attitude, and practice with respect to educational status (p<0.05). 123 (73.21%) mothers had unsatisfactory; whereas 39 (24.07%) mothers had excellent knowledge regarding breastfeeding. 39 (27.07%) of breast-feeding mothers had a positive attitude towards breastfeeding. 123 (73.21%) women showed a negative response regarding the practice of breastfeeding. CONCLUSION: Most of the mothers didn’t have adequate knowledge of exclusive breastfeeding (EBF) practice. As a result, it is suggested that media can be used as a medium to educate women about the benefits of exclusive breastfeeding (EBF)

Winner’s Curse on Malaysian IPOs: Does the Phenomenon Still Exist?

This study examines the winner’s curse phenomenon through Amihud and Yong’s winner’s curse measurements. Amihud’s allocation rate (ALLOCTJ) is the natural log of the reciprocal of investor demand or oversubscription ratio while Yong’s institutional investor participation is gauged based on a type of IPOs which is issued via private placement (DPRIVATE). Using data set from 560 initial public offerings (IPOs) issued from January 2000 until December 2022 for listing on Bursa Malaysia, the results of the cross-sectional multiple regression analyses show that ALLOCTJ and DPRIVATE are consistently significantly negative in influencing initial returns of the IPOs. The former relationship indicates that uninformed investors are more likely to win IPOs which are not demanded by the informed investors, and subsequently the IPOs produce low or negative initial returns. In the meantime, the latter relationship suggests that IPOs that are not offered to institutional investors are deliberately underpriced to allure all skeptical investors back into the new shares market

A Case of Adult-Onset Still’s Disease Caused by a Novel Splicing Mutation in TNFAIP3 Successfully Treated With Tocilizumab

TNFAIP3 encodes the NF-κB regulatory protein A20. High-penetrance heterozygous mutations in TNFAIP3 cause a haploinsufficiency of A20 (HA20), inadequate inhibition of NF-κB pathway, and an early onset autoinflammatory disorder. However, the clinical phenotype of patients with HA20 varies greatly and clinical diagnoses prior to establishing the genetic cause, included both autoimmune and autoinflammatory conditions. Here, we present the first patient with HA20, who was previously diagnosed with AOSD but was later found to have a novel heterozygous variant in TNFAIP3 and who was successfully treated with anti-IL6 receptor biologic tocilizumab (RoActemra). We discovered a novel heterozygous mutation in TNFAIP3 c.1906C>T, not previously found in ExAC database. Further analysis shows that this single-nucleotide variant at the terminal residue of TNFAIP3 exon 7 produces an alternatively spliced mRNA resulting in p.His636fsTer1. Additional genetic analysis of family members shows that this variant does segregate with the inflammatory clinical phenotypes. Subsequent functional test show that NF-κB activation, measured as intracellular phosphorylation of p65 in CD14 + monocytes, was more enhanced in the patient compared with healthy controls (HC) following stimulation with LPS. This was associated with higher production of inflammatory cytokines by the patients PBMC in response to LPS and ATP and enhanced activation of NLRP3 inflammasome complex. Furthermore, increased activation of NLRP3 inflammasome was evident systemically, since we detected higher levels of ASC specks in patients’ sera compared with HC. Finally, we used population genetics data from GnomAD to construct a map of both genetic conservation and most probable disease-causing variants in TNFAIP3 which might be found in future cases of HA20

An observational study on the expression levels of MDM2 and MDMX proteins, and associated effects on P53 in a series of human liposarcomas

Background: Inactivation of wild type P53 by its main cellular inhibitors (MDM2 and MDMX) is a well recognised feature of tumour formation in liposarcomas. MDM2 over-expression has been detected in approximately 80% of liposarcomas but only limited information is available about MDMX over-expression. To date, we are not aware of any study that has described the patterns of MDM2 and MDMX co-expression in liposarcomas. Such information has become more pertinent as various novel MDM2 and/or MDMX single and dual affinity antagonist compounds are emerging as an alternative approach for potential targeted therapeutic strategies. Methods. We analysed a case series of 61 fully characterized liposarcomas of various sub-types by immunohistochemistry, to assess the expression levels of P53, MDM2 and MDMX, simultaneously. P53 sequencing was performed in all cases that expressed P53 protein in 10% or more of cells to rule out mutation-related over-expression. Results: 50 cases over-expressed MDM2 and 42 of these co-expressed MDMX at varying relative levels. The relative expression levels of the two proteins with respect to each other were subtype-dependent. This apparently affected the detected levels of P53 directly in two distinct patterns. Diminished levels of P53 were observed when MDM2 was significantly higher in relation to MDMX, suggesting a dominant role for MDM2 in the degradation of P53. Higher levels of P53 were noted with increasing MDMX levels suggesting an interaction between MDM2 and MDMX that resulted in a reduced efficiency of MDM2 in degrading P53. Of the 26 cases of liposarcoma with elevated P53 expression, 5 were found to have a somatic mutation in the P53 gene. Conclusions: The results suggest that complex dynamic interactions between MDM2 and MDMX proteins may directly affect the cellular levels of P53. This therefore suggests that careful characterization of both these markers will be necessary in tumours when considering in vivo evaluation of novel blocker compounds for MDM proteins, as a therapeutic strategy to restore wild type P53 function

Identification and characterization of antibacterial compound(s) of cockroaches (Periplaneta americana)

Infectious diseases remain a significant threat to human health, contributing to more than 17 million deaths, annually. With the worsening trends of drug resistance, there is a need for newer and more powerful antimicrobial agents. We hypothesized that animals living in polluted environments are potential source of antimicrobials. Under polluted milieus, organisms such as cockroaches encounter different types of microbes, including superbugs. Such creatures survive the onslaught of superbugs and are able to ward off disease by producing antimicrobial substances. Here, we characterized antibacterial properties in extracts of various body organs of cockroaches (Periplaneta americana) and showed potent antibacterial activity in crude brain extract against methicillin-resistant Staphylococcus aureus and neuropathogenic E. coli K1. The size-exclusion spin columns revealed that the active compound(s) are less than 10 kDa in molecular mass. Using cytotoxicity assays, it was observed that pre-treatment of bacteria with lysates inhibited bacteria-mediated host cell cytotoxicity. Using spectra obtained with LC-MS on Agilent 1290 infinity liquid chromatograph, coupled with an Agilent 6460 triple quadruple mass spectrometer, tissues lysates were analyzed. Among hundreds of compounds, only a few homologous compounds were identified that contained isoquinoline group, chromene derivatives, thiazine groups, imidazoles, pyrrole containing analogs, sulfonamides, furanones, flavanones, and known to possess broad-spectrum antimicrobial properties, and possess anti-inflammatory, anti-tumour, and analgesic properties. Further identification, characterization and functional studies using individual compounds can act as a breakthrough in developing novel therapeutics against various pathogens including superbugs

Prevalence and clinical challenges among adults with primary immunodeficiency and recombination-activating gene deficiency.

Letter to the Edito

New Splicing Mutations in the Human Factor XIIIA Gene, Each Producing Multiple Mutant Transcripts of Varying Abundance

SummaryCoagulation factor XIII, a transglutaminase which stabilises blood clots by covalently cross-linking fibrin, is essential for normal haemostasis. FXIII deficiency results in a life-long bleeding disorder with added complications in wound healing and tissue repair. Sequence changes in the human FXIIIA gene, largely missense mutations, are primarily responsible for inherited FXIII deficiency. We have carried out molecular analysis of the FXIIIA gene in two unrelated FXIII deficient individuals and identified three splice site mutations; a g→a at the exon 6 acceptor splice site, a g→a at the exon 7 donor splice site and a coding sequence T→G at the exon 8 donor splice site. We have also examined the FXIIIA mRNA in these patients and find that each mutation gives rise to multiple transcripts which vary in their relative abundance. The precise molecular mechanisms which result in these variant transcripts, and their relative abundance in our FXIII deficient patients, are discussed.</jats:p

Identification of a Large Deletion, Spanning Exons 4 to 11 of the Human Factor XIIIA Gene, in a Factor XIII-Deficient Family

Inherited deficiency of factor XIIIA subunit (FXIIIA) is an autosomal recessive disorder that is characterized by a life-long bleeding tendency and complications in wound healing. Molecular genetic studies have shown the deficiency can be due to small sequence changes within the FXIIIA gene, such as point mutations or microdeletions. On molecular analysis of the FXIIIA gene in an FXIII-deficient patient, of United Kingdom origin, we identified a putative homozygous missense mutation, Arg408Gln. However, the father of this patient is homozygous normal for arginine at codon 408. Having proved paternity in this pedigree by microsatellite analysis, we examined the FXIIIA RNA of the patient by reverse transcriptase-polymerase chain reaction and found the paternal allele to lack exons 4 through 11 inclusive. Hence, a huge deletion extending from intron 3 to intron 11 and the Arg408Gln mutation are jointly responsible for FXIIIA deficiency in this family. This is the first finding of such a large deletion in the FXIIIA gene.</jats:p

Factor XIII Deficiency Causing Mutation, Ser295Arg, in Exon 7 of the Factor XIIIA Gene

SummaryInherited factor XIII (FXIII) deficiency is an autosomal recessive disorder which results in a serious bleeding diathesis, problems with wound healing and a very high risk of recurrent miscarriage in deficient females. We have analysed the molecular basis of factor XIII deficiency in two patients and their parents, who originate from the North of Pakistan. Four sequence changes were identified: an AGC→AGG (Ser→Arg) FXIII deficiency-causing mutation in codon 295; G→A at position -246 upstream of exon 1; T→C and C→T at positions -23 and -24, respectively, in intron 9. Using molecular modelling we predict that the Ser295Arg mutation would prevent the FXIIIA molecule from folding correctly and thus result in an unstable FXIIIA mutant polypeptide. The sequence changes −246G→A, −23T→C and −24C→T are normal polymorphisms. RT-PCR analysis demonstrates that the intronic sequence changes do not appear to affect the accuracy of FXIIIA RNA processing.</jats:p