Law matters - assessment of country-level code implementation and sales of breastmilk substitutes in South Asia.

Objectives: This study examines the status of implementation of the International Code of Marketing of Breast-milk Substitutes of eight countries in the South Asia region (Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka), and describes the sales value and volume of commercial milk formula (CMF) marketed as breastmilk substitutes (BMS) and baby food in four countries (Bangladesh, India, Pakistan, and Sri Lanka). Design: A mix of descriptive methods is used to assess national status of Code implementation, including a desk review of the 2022 WHO/UNICEF/IBFAN Code Status Report, systematic content analysis of national Code measures, and insights generated from the participation of key government and UNICEF/WHO actors in a regional workshop that aimed to identify each country's barriers, gaps, and the status of Code implementation. Data on the sales value and volume of CMF and baby food between 2007 to 2021 and with the prediction to 2026 in Bangladesh, India, Pakistan, and Sri Lanka were obtained from Global Data. Findings: There are major gaps in Code implementation in countries even with legal measures considered substantially aligned with the Code, such as the inadequate age range of CMF covered in the scope, insufficient safeguards against conflicts of interest in the health system, lack of warning of risks of intrinsic contamination of powdered milk formula, and an absence of effective monitoring and enforcement mechanisms. Data on CMF sales shows health facilities and pharmacies sustain the highest sales. Lower sales volume of infant formula (including special formula), compared to other CMF such as follow-up formula and growing-up milk, has been observed in three of the four countries (Bangladesh, India, and Sri Lanka). Overall, GUM, followed by baby cereals, accounted for a large portion of CMF and baby foods sales in the same three countries. Recommended actions include: (1) Closing the gaps between national measures and the Code, (2) Ensuring effective monitoring and enforcement mechanisms, (3) Strengthening conflicts of interest safeguards in the health system, (4) Tackling digital marketing, and (5) Galvanizing political support and support from in-country public health and women's rights jurist networks.

Association of Kaiso and partner proteins in oral squamous cell carcinoma.

Objectives: 1. Identification of protein expression and subcellular localization of E-cadherin (E-cad), p120 catenin (P120ctn), and Kaiso in oral cancer (OC). 2. To study the protein expression of cyclin D1 and c-Myc (Kaiso targets) and determine their relationship with the expression and localization of Kaiso. Methods: Histological grading was performed in accordance with Broder's criteria. Expression and localization data for E-cad, p120ctn, Kaiso, cyclin D1, and c-Myc were acquired using immunohistochemistry. Data were analyzed using SPSS version 21. The chi-square test was used to measure the statistical significance of associations, with p < 0.05 as statistically significant. Results: Of 47 OC cases, 36% showed low E-cad expression and 34% showed low p120ctn. Low Kaiso expression was recognized in 78% of tumor specimens. Aberrant cytoplasmic localization of p120ctn was seen in 80.8% cases. Cytoplasmic Kaiso localization was appreciated in 87% of tumor tissues, whereas 29.7% lacked any nuclear Kaiso. Kaiso expression was significantly associated with the expression of cyclin D1 but not with c-Myc. Conclusion: The present study identified a change in the localization of Kaiso in OC. The significance of this in relation to OC and tumor prognosis needs to be investigated with further studies using larger sample sizes and more sensitive molecular tools.

Analysis Of Common Somatic Mutations In Colorectal Carcinoma And Associated Dysregulated Pathwaysarts.

BACKGROUND: Identification of gene targets and biological pathways involved in colorectal carcinoma (CRC) is essential for better management of patients. Our study aims to highlight common somatic mutations in colorectal carcinoma and to identify dysregulated pathways and gene enrichment based on KRAS and BRAF interaction network analysis. METHODS: By using cancer browser tool in COSMIC database, mutation frequencies of the top 20 mutated genes listed for colorectal adenocarcinoma were identified. The most frequent variants of selected genes were explored with ClinVar database which led to identification of protein change along with its cytogenic location, variant type, variant length and the associated single nucleotide polymorphism (SNP). These identified SNPs were searched in Pakistani database using 1000genome in an attempt to identify common polymorphisms. Using the database ClinicalTrial.gov the number of clinical trials based upon these selected mutations was explored. Enrichment and protein interaction (PI) analysis of KRAS and BRAF was carried out to reveal significant biological pathways associated with these genes. RESULTS: In cumulative data, among all variants about 57% of substitution mutations are observed to be G>A including mutations in KRAS, Tp53, SMAD4, PI3K and NRAS. The mutations of KRAS (c.35G>A), TP53 (c.524G>A) and APC (c.4348C>T) were found to be pathogenic with single nucleotide variation and variant length of 1bp. Searching 1000genome database revealed that 100 % of alleles found in East Asian population studied are 'C'(frequency=1). Significant biological pathways (<0.05) identified by our search include Trk receptor signalling mediated by the MAPK pathway, signalling to p38 via RIT and RIN, signalling to ERKs, Frs2-mediated activation, ARMS-mediated activation and prolonged ERK activation events. CONCLUSIONS: Our study highlights the role of genetic profiling in CRC, with emphasis on mutations which may define treatment outcome. Targeting several collateral pathways simultaneously may be further explored to improve colorectal cancer therapeutics.

Exploring Therapeutic Potential of 1,3,4-Oxadiazole Nucleus as Anticancer Agents: A Mini-review.

Cancer is an uncontrolled, abnormal growth of cells and the second cause of death after cardiovascular disease. At present, chemotherapy and related drugs have three major categories. All three have characteristic action and toxicity levels of antitumor activity. Due to indications of unwanted side effects, the exploration of novel and selective anticancer agents is crucially required. Heterocyclic compounds have always played a major role in research for new drug discovery and development. 1,3,4-oxadiazole derivatives are heterocyclic isomers having pharmacological properties and play an important role as antiproliferative agents. The present review summarizes anticancer activities of 1,3,4-oxadiazole derivatives against different cell lines, such as HCT-116, MCF-7, HeLa, SMMC-7721, and A549. The results showed that 1,3,4-oxadiazole and its derivatives have the potential to play a major role as an anticancer agent with fewer side effects.

Frequency And Risk Factors Of Microscopic Colitis As A Cause Of Chronic Watery Diarrhoea.

BACKGROUND: Microscopic colitis (MC) is one of the most underdiagnosed conditions leading to chronic watery diarrhoea in patients worldwide. This is the first study of this kind in Pakistan and we aimed to calculate the frequency as well as study the risk factors behind the disease. METHODS: This was a prospective cross-sectional study in a tertiary care hospital in Pakistan. A total of 58 participants with chronic watery diarrhoea who had normal colonoscopy were recruited for the study and biopsies were obtained for diagnosing MC. RESULTS: 2 participants out of 58 (3.4%) had biopsy proven microscopic colitis; one patient had a lymphocytic colitis variant and the other had a collagenous colitis variant. The average score based on the MC scoring system was 7.53 in the entire study group. The patient with lymphocytic colitis had a score of 06 while the patient with collagenous colitis had a score of 8. CONCLUSIONS: The frequency of microscopic colitis was found to be 3.4% of all cases of chronic watery diarrhoea. A link between MC and autoimmune diseases was also observed. However, we had a limited sample size and encouraged future studies to employ a larger sample size to get a multifaceted look at the disease process.

Expressional variations of Kaiso: an association with pathological characteristics and field cancerization of OSCC.

BACKGROUND: A group of genetically altered cells that have not transformed into a clinical or histologically identifiable state of malignancy but contains a higher risk of transforming into one is known as the field of cancerization. Numerous molecules are being investigated for their significance in the development of this phenomenon. One such protein of this family is Kaiso also known as ZBTB33 (Zinc Finger and BTB Domain containing 33). This protein belongs to the POZ-ZF family of transcription factors and may have functional tasks similar to its other siblings such as the growth and development of vertebrates and the pathogenesis of neoplastic diseases. Nevertheless, its role in the pathogenesis, progression, epithelial mesenchyal transition and field cancerization in case of oral cancer still needs exploration. Hence, this study was designed to explore the expressional differences between the mucosa of controls and those diagnosed with oral squamous cell carcinoma (OSCC). METHODS: Soft tissue samples were obtained from the main tumor, tumor periphery and opposite buccal mucosa of 50 oral cancer patients, whereas normal mucosa was taken from 50 volunteers undergoing elective tooth removal. The acquired samples were subjected to Immunohistochemical exploration for expression of Kaiso and E-Cadherin. The expression was measured using Image-J IHC profiler and summed as Optical density. The Optical density values were then subjected to statistical analysis. RESULTS: Results revealed a significant differential expression of Kaiso between the mucosal tissues taken from oral cancer patients and controls (p-value: < 0.0001), showing almost 50% down-regulation of Kaiso in all three tissue samples taken from oral cancer patients as compared to normal mucosa. CONCLUSION: Kaiso has a significant difference of expression in the mucosa of oral cancer patients as compared to the mucosa of normal patients, making it a probable contributor to disease pathogenesis and field cancerization.

Production of hyperimmune anti-SARS-CoV-2 intravenous immunoglobulin from pooled COVID-19 convalescent plasma.

Background: This study assesses the feasibility of producing hyperimmune anti-COVID-19 intravenously administrable immunoglobulin (C-IVIG) from pooled convalescent plasma (PCP) to provide a safe and effective passive immunization treatment option for COVID-19. Materials & methods: PCP was fractionated by modified caprylic acid precipitation followed by ultrafiltration/diafiltration to produce hyperimmune C-IVIG. Results: In C-IVIG, the mean SARS-CoV-2 antibody level was found to be threefold (104 ± 30 cut-off index) that of the PCP (36 ± 8.5 cut-off index) and mean protein concentration was found to be 46 ± 3.7 g/l, comprised of 89.5% immunoglobulins. Conclusion: The current method of producing C-IVIG is feasible as it uses locally available PCP and simpler technology and yields a high titer of SARS-CoV-2 antibody. The safety and efficacy of C-IVIG will be evaluated in a registered clinical trial (NCT04521309).

Thyroid carcinoma--experience at Jinnah Postgraduate Medical Centre Karachi.

OBJECTIVE: To evaluate the frequency and types of thyroid carcinoma with respect to age and sex groups. METHODS: This was a retrospective study conducted at the Department of Pathology, Basic Medical Sciences Institute, Jinnah postgraduate medical centre Karachi. A total of 998 thyroid lesions over a period of 05 years, from July 2000 to June 2005 were reviewed. H and E slides were studied to determine the types and frequencies of malignant lesions of thyroid. Special stains were performed whenever required. RESULTS: A total of 998 thyroid lesions were reviewed, of which 153 were found to be malignant. Papillary carcinoma was the commonest malignant lesion with a frequency of 90.2% followed by 4.5% medullary carcinoma, 2% follicular carcinoma, 2% undifferentiated carcinoma and 0.7% each of mixed medullary and papillary carcinoma and poorly differentiated carcinoma. Females were predominant 82.4% as compared to males 17.6% with female to male ratio 4.7:1. Maximum number of the patients were seen in 4th decade of life followed by 3rd and 2nd decades. CONCLUSION: The commonest malignant thyroid lesion was papillary carcinoma. Thyroid cancer was more common in females. Patients of papillary, medullary and follicular carcinomas were found in 3rd and 4th decades of life while poorly and undifferentiated carcinomas were diagnosed from 5th to 7th decades of life.

Differential expression of CK 19 in follicular adenoma, well-differentiated tumour of uncertain malignant potential (WDT-UMP) and follicular variant of papillary carcinoma.

OBJECTIVE: To see the expression of cytokeratin 19, a proven helpful marker for the differential diagnosis of neoplastic follicular patterned lesions of thyroid. METHODS: This was a retrospective study carried out in the Department of Pathology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi from 2000 to 2005. The haematoxylin and eosin (H&E) stained sections were reviewed and the cases were classified according to already published criteria. On the basis of the recent recommendations by Chemobyl Pathologists Group, encapsulated follicular patterned lesions with questionable nuclear changes were categorized as well - differentiated tumours of uncertain malignant potential (WDT-UMP). Formalin fixed paraffin embedded tissues of follicular adenoma, WDT-UMP and follicular variant of papillary carcinoma were obtained for CK 19 immunostaining. RESULTS: All (16) cases of follicular adenoma were negative for CK19. In a total of 35 cases of WDT- UMP, 10 cases scored 3+ positive for CK19, 15 were 2+ positive and remaining 10 cases were 1+ positive. There were 43 cases of follicular variant of papillary carcinoma with 4+ CK 19 positivity, 14 were 3+ positive and 3 were 2+ positive. CONCLUSION: CK19 is a good and useful diagnostic marker for differential diagnosis of follicular adenoma, WDT-UMP and follicular variant of papillary carcinoma. The recommendations by Chornobyl Pathologists Group need to be adopted and the cases of WDT-UMP require strict follow-up.

Thyroid carcinoma in Pakistan: a retrospective review of 998 cases from an academic referral center.

BACKGROUND AND OBJECTIVES: To address the need for epidemiologic data on thyroid carcinoma in Pakistan, we evaluated the frequency and types of thyroid carcinoma with respect to age and sex. METHODS: In a a retrospective study conducted at the Jinnah Postgraduate Medical Centre in Karachi, we reviewed thyroid lesions reported over a period of 5 years, from July 2000 to June 2005. Pathology slides were studied to determine the types and frequencies of malignant lesions of the thyroid. RESULTS: Of 998 thyroid lesions reviewed, 153 cases were malignant. Papillary carcinoma was the common- est malignant lesion with a frequency of 90.2%, followed by 4.5% for medullary carcinoma, 2% for follicular carcinoma, 2% for undifferentiated carcinoma and 0.7% each for mixed medullary and papillary carcinoma and poorly differentiated carcinoma. Females were predominant (82.4%) as compared with males (17.6%) for a female-to-male ratio 4.7:1. The maximum number of the patients were in the fourth decade of life followed by the third and second decades. CONCLUSION: The commonest malignant thyroid lesion was papillary carcinoma. Thyroid cancer was more com- mon in females. Papillary, medullary and follicular carcinomas were found in patients in the third and fourth decades of life, while poorly and undifferentiated carcinomas were diagnosed from the fifth to seventh decades of life.