Acceptance, availability, and feasibility of RTS, S/AS01 malaria vaccine: A review.

INTRODUCTION: In malaria-stricken regions, malaria continues to be one of the primary causes of mortality for children. The number of malaria-related fatalities has drastically decreased because of artemisinin-based pharmacological regimens. METHODS: Two independent researchers did a comprehensive literature search using PubMed/MEDLINE and Google Scholar from its inception to September 2022. RESULTS: After evaluating RTS, S/AS01 for its safety, effectiveness, and feasibility, the European Medicines Agency (EMA) issued a favorable conclusion. It was suggested that the RTS, S malaria vaccine be used extensively by the World Health Organization on October 6, 2021. The successful pilot program testing the malaria vaccine in Ghana, Kenya, and Malawi served as the basis for this proposal. CONCLUSION: Several challenges need to be addressed to ensure the success of vaccination programs. From the acceptability perspective, issues such as inadequate community engagement, concerns about side effects, and issues with the delivery and quality of healthcare services can affect the acceptance of the vaccine. From the feasibility standpoint, factors such as lack of transportation or long distances to healthcare facilities and the perception of completion of the vaccination calendar can affect the feasibility of the vaccine. Lastly, the availability of the vaccine is also a major concern as it may not be readily available to meet the demands.

Factors leading to delayed and challenging presentation of benign breast lumps in young females.

Background and Objective: A delayed presentation of benign breast diseases may lead to a therapeutic challenge when they enlarge enormously or become multiple. Aim of this study was to evaluate the factors leading to delayed presentation of benign breast lumps. Methods: This cross-sectional study was conducted at Madinah Teaching Hospital and Allied Hospital, Faisalabad from January 2019 to October 2021. One hundred and forty five female patients were selected by non-probability purposive sampling. Patients with large size (>5cm) or multiple benign breast lumps were included. An interview was conducted using structured questionnaire translated in Urdu. Factors leading to delayed presentation and social impact scale for stigma were evaluated. Results: Patients had a mean age of 26.52 ± 6.90 years. The average delay of seeking medical care was 8.48 ± 8.41 months. Factors leading to delayed presentation were; lack of knowledge n=112 (77.2%) and parda (religious issues) n=112 (77.2%), followed by poverty n=109 (75.2%), and fear of cancer n=90 (62.1%). All the sub-scales of stigma, i.e., social rejection, financial insecurity, internalized shame and social isolation were high in late presenters, though, only financial insecurity was significantly high in late presenters (p=0.03). Conclusion: Lack of awareness, socioeconomic factors and disease related stigma were the main factors related to delayed presentation in young females with benign breast diseases. Addressing these factors may improve timely diagnosis and management of delayed and challenging cases.

Genetic Inheritance of Stripe Rust (Puccinia Striiformis) Resistance in Bread Wheat Breeding Lines at Seedling and Maturity Stages.

One hundred and five (105) bread wheat (Triticum aestivum L.) genotypes, including five commercial checks, were screened for stripe rust resistance at seedling and adult plant stages. Seedlings grown under controlled conditions were screened for disease resistance after 12 days concerning disease incidence percentage after inoculation. K-means cluster analysis divided the genotypes into five different classes according to the presence of virulence/avirulence profile, i.e., class 1, 2, 3, 4 and 5. The same set of genotypes was grown under field conditions for adult plant resistance. Data for disease scoring and different yield and yield-related parameters was recorded. A comparison of breeding lines indicated that all studied traits were negatively affected by disease incidence. Further cluster analysis ranked the genotypes into three distinct groups with Group I and III being the most diverse. Thirteen stripe rust resistance lines were identified using seedling and adult plant resistance strategies. Correlation analysis indicated a negative association between stripe rust incidence and yield and yield-related traits, particularly grains per spike, grain weight per spike, thousand-grain weight, and grain yield per plant. These findings suggested that stripe rust resistance negatively affects yield and yield related traits. The breeding programs aiming at the development of high yielding varieties must also focus on stripe rust resistance.

Body Mass Index and Other Risk Factors Effects on Colon Cancer Prognosis in Pakistan.

Introduction: Asian developing countries share the burden of colorectal cancer (CRC) with rising mortality rates. This prospective study aims to apprehend the clinical relevance of age, gender, lifestyle choices (dietary habits and addiction) and body mass index (BMI) to the occurrence and progression of colon cancer (CC). Methods: A cohort of non-cancer (NC) and CC patients of South-Central Asian origin registered for screening colonoscopy or surgery at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH and RC), Lahore, Pakistan, from 2015 to 2020 was identified. BMI (Kg/m2) was classified according to the World Health Organization criteria as underweight (<18.5 Kg/m2), normal weight (18.5-24.9 Kg/m2) and overweight (≥25 Kg/m2). Results: Among 236 participants, 99 (41.9%) belonged to the NC group, and 137 (58.1 %) participants had CC Overall, participants included 74 women and 162 men aged 20-85 years (mean ± SD; 49.9 ± 14.9). Notably, 46.0% of cancer patients had a family history of cancer. There was a direct relationship between CC with abnormal BMI (underweight and overweight), positive smoking history and positive family history of cancer. Conclusion: Being underweight or overweight is a potential risk factor for CC patients. The overall survival in patients with CC is clinically associated with lifestyle choices before CC diagnosis. A balanced diet, walking and other forms of exercise should be strongly recommended to the community and those undergoing screening colonoscopy.

Expression of cornulin in tongue squamous cell carcinoma.

The aim of the study is to identify cornulin (CRNN) protein expression associated with advancement of tongue squamous cell carcinoma (TSCC). A comparison of addictive (containing potential carcinogens) versus non-addiction causative agents was expected to allow detection of differences in CRNN expression associated with TSCC. Bespoke tissue microarrays (TMAs) were prepared and immunohistochemistry (IHC) performed to determine the changes in CRNN expression in epithelial cells of node-negative (pN-), node-positive (pN+) TSCC and non-cancer patients' oral tissues. TMAs were validated by performing IHC on whole diagnostic tissues. Chi-square test or Fisher's-exact tests were used to establish significant expression differences. Analogous analyses were performed for biomarkers previously associated with TSCC, namely collagen I alpha 2 (COL1A2) and decorin (DCN) to compare the significance of CRNN. Keratinisation and its level (low, extensive) were studied in relation to CRNN so that the extent of squamous differentiation could better be assessed. IHC immunoreactive score (IRS) clustered the patients based on weak/moderate (Low (IRS ≤ +3)) or strong (High (IRS ≥ +4)) expression groups. A low expression was observed in a larger number of patients in control proteins COL1A2 (77.3%), DCN (87.5%) and target protein CRNN (52.3%), respectively. Low CRNN expression was observed in TSCC where nodes were involved (pN+: mean 1.4 ± 2.1) (p = 0.248). Keratinisation (%) was low (0% ≤ 50%) in 42.2% and extensive (1% ≥ 50.0%) in 57.8% patients. In conclusion, our study suggested that Low CRNN expression was associated with grade and lymph node metastasis in TSCC. CRNN expression is independent of addiction, however potentially carcinogenic addictive substances might be aiding in the disease progression.

Proteomics analysis of colon cancer progression.

BACKGROUND: The aim of this pilot study was to identify proteins associated with advancement of colon cancer (CC). METHODS: A quantitative proteomics approach was used to determine the global changes in the proteome of primary colon cancer from patients with non-cancer normal colon (NC), non-adenomatous colon polyp (NAP), non-metastatic tumor (CC NM) and metastatic tumor (CC M) tissues, to identify up- and down-regulated proteins. Total protein was extracted from each biopsy, trypsin-digested, iTRAQ-labeled and the resulting peptides separated using strong cation exchange (SCX) and reverse-phase (RP) chromatography on-line to electrospray ionization mass spectrometry (ESI-MS). RESULTS: Database searching of the MS/MS data resulted in the identification of 2777 proteins which were clustered into groups associated with disease progression. Proteins which were changed in all disease stages including benign, and hence indicative of the earliest molecular perturbations, were strongly associated with spliceosomal activity, cell cycle division, and stromal and cytoskeleton disruption reflecting increased proliferation and expansion into the surrounding healthy tissue. Those proteins changed in cancer stages but not in benign, were linked to inflammation/immune response, loss of cell adhesion, mitochondrial function and autophagy, demonstrating early evidence of cells within the nutrient-poor solid mass either undergoing cell death or adjusting for survival. Caveolin-1, which decreased and Matrix metalloproteinase-9, which increased through the three disease stages compared to normal tissue, was selected to validate the proteomics results, but significant patient-to-patient variation obfuscated interpretation so corroborated the contradictory observations made by others. CONCLUSION: Nevertheless, the study has provided significant insights into CC stage progression for further investigation.

Risk factors associated with poor outcome in diabetic foot ulcer patients.

BACKGROUND/AIM: Diabetic foot ulcers and related complications are a major cause of morbidity and hospital admissions. Our aim was to evaluate the risk factors associated with poor outcome in diabetic foot ulcers. MATERIALS AND METHODS: A prospective study was conducted on patients with diabetic foot ulceration attending the Madinah Teaching Hospital from June 2014 to December 2015. Potential risk factors and laboratory test results at presentation were recorded and their association with outcome (healing vs. amputation) was analyzed using IBM SPSS Statistics for Windows, Version 22.0. RESULTS: In total, 112 patients were studied during our study period. The majority of the patients were male (60.7%) and aged 50 years and older (62.5%). Regarding the outcome, 68% healed completely, 27.7% underwent amputation, and 4.5% died during this period. Patient age of 50 and older, long duration of diabetes (>10 years), rural origin, and heel ulcers were significantly associated with poor outcome (P < 0.05). CONCLUSION: Patients with diabetes should have a detailed annual foot examination; those having risk factors for poor outcome require more frequent foot care, patient education, and early referral to tertiary care centers.

Patterns of cancer cell sphere formation in primary cultures of human oral tongue squamous cell carcinoma and neck nodes.

Recently a sub-population of cells with stem cell characteristics, reported to be associated with initiation, growth, spread and recurrence, has been identified in several solid tumors including oral tongue squamous cell carcinoma (OTSCC). The aim of our pilot study was to isolate CD44+ cancer stem cells from primary cultures of OTSCC and neck node Level I (node-I) biopsies, grow cell spheres and observe their characteristics in primary cultures. Parallel cultures of hyperplastic lesions of tongue (non-cancer) were set up as a control. Immunohistochemistry was used to detect CD44/CD24 expression and magnetic activated cell sorting to isolate CD44+ cell populations followed by primary cell culturing. Both OTSCC and node-I biopsies produced floating spheres in suspension, however those grown in hyperplastic and node-I primary cultures did not exhibit self-renewal properties. Lymph node metastatic OTSCC, express higher CD44/CD24 levels, produce cancer cell spheres in larger number and rapidly (24 hours) compared to node negative OTSCC (1 week) and non-cancer specimens (3 weeks). In addition, metastatic OTSCC have the capacity for proliferation for up to three generations in primary culture. This in vitro system will be used to study cancer stem cell behavior, therapeutic drug screening and optimization of radiation dose for elimination of resistant cancer cells.

Use of matrix-assisted laser desorption/ionisation mass spectrometry in cancer research.

Cancer significantly affects millions of people worldwide. It is possible to use proteomic techniques to aid in detection, monitoring of treatment and progression, as well as gaining an increased understanding of cancer. Matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry can be utilised to detect the presence of proteins and peptides within various samples from the body, including blood, biological fluids and tumour tissue. This review aims to introduce MALDI mass spectrometry and discuss a range of applications in the field of cancer research, from quantitative to qualitative methods. Also described is MALDI imaging mass spectrometry which differs from typical sample preparation methods, as analytes are ionised directly from the tissue. Finally, presented is a brief summary of the status of biomarker discovery using blood/serum and biological fluids samples, and the implications in the clinic.

c-Kit and stem cell factor regulate PANC-1 cell differentiation into insulin- and glucagon-producing cells.

Recent evidence has shown that stem cell factor (SCF) and its receptor, c-Kit, have an important role in pancreatic islet development by promoting islet cell differentiation and proliferation. In this study, we examined the role of c-Kit and SCF in the differentiation and proliferation of insulin- and glucagon-producing cells using a human pancreatic duct cell line (PANC-1). Our study showed that increased expression of endocrine cell markers (such as insulin and glucagon) and transcription factors (such as PDX-1 and PAX-6) coincided with a decrease in CK19(+) and c-Kit(+) cells (P<0.001) during PANC-1 cell differentiation, determined by immunofluorescence and qRT-PCR. Cells cultured with exogenous SCF showed an increase in insulin(+) (26%) and glucagon(+) (35%) cell differentiation (P<0.01), an increase in cell proliferation (P<0.05) and a decrease in cell apoptosis (P<0.01). siRNA knockdown of c-Kit resulted in a decrease in endocrine cell differentiation with a reduction in PDX-1 and insulin mRNA, as well as the number of cells immunostaining for PDX-1 and insulin. Taken together, these results show that c-Kit/SCF interactions are involved in mediating islet-like cluster formation and islet-like cell differentiation in a human pancreatic duct cell line.

beta1 integrin/FAK/ERK signalling pathway is essential for human fetal islet cell differentiation and survival.

beta1 integrin and collagen matrix interactions regulate the survival of cells by associating with focal adhesion kinase (FAK) and initiating MAPK/ERK signalling, but little is known about these signalling pathways during human fetal islet ontogeny. The purpose of this study was to investigate whether beta1 integrin/FAK activation of the MAPK/ERK pathway regulates human fetal islet cell expression of endocrine cell markers and survival. Isolated human (18-21 weeks fetal age) islet-epithelial cell clusters, cultured on collagen I, were examined using beta1 integrin blocking antibody, beta1 integrin siRNA and FAK expression vector. Perturbing beta1 integrin function in the human fetal islet-epithelial cell clusters resulted in a marked decrease in cell adhesion, in parallel with a reduction in the number of cells expressing PDX-1, insulin and glucagon (p < 0.05). beta1 integrin blockade disorganized focal adhesion contacts in the PDX-1(+) cells and decreased activation of FAK and ERK1/2 signalling in parallel with an increase in expression of cleaved caspases 9 and 3 (p < 0.01). Similar results were obtained following an siRNA knock-down of beta1 integrin expression. In contrast, over-expression of FAK not only increased phospho-ERK and the expression of PDX-1, insulin and glucagon (p < 0.05) but also abrogated the decreases in phospho-ERK and PDX-1 by beta1 integrin blockade. This study demonstrates that activation of the FAK/ERK signalling cascade by beta1 integrin is involved in the differentiation and survival of human fetal pancreatic islet cells.

Compound palmar ganglion with carpal tunnel syndrome.

Compound palmer ganglion is an uncommon condition characterized by a swelling in the distal part of volar aspect of wrist and communicating with another swelling over palm across the flexor retinaculum. It commonly results from tuberculous tenosynovitis. It may lead to carpal tunnel syndrome and need surgical excision with division of flexor retinaculum.