Routine immunization in Pakistan: comparison of multiple data sources and identification of factors associated with vaccination.

Background: Within Pakistan, estimates of vaccination coverage with the pentavalent vaccine, oral polio vaccine (OPV) and measles vaccine (MV) in 2011 were reported to be 74%, 75% and 53%, respectively. These national estimates may mask regional variation. The reasons for this variation have not been explored. Methods: Data from the Multiple Indicator Cluster Surveys (MICS) for Balochistan and Punjab (2010-2011) are analysed to examine factors associated with receiving three or more doses of the pentavalent vaccine and one or more MVs using regression modelling. Pentavalent and OPV estimates from the MICS were compared to vaccine dose histories from surveillance for acute flaccid paralysis (AFP; poliomyelitis) to ascertain agreement. Results: Adjusted coverage of children 12-23 months of age were estimated to be 16.0%, 75.5% and 34.2% in Balochistan and 58.0%, 87.7% and 72.6% in Punjab for the pentavalent vaccine, OPV and MV, respectively. Maternal education, healthcare utilization and wealth were associated with receiving the pentavalent vaccine and the MV. There was a strong correlation of district estimates of vaccination coverage between AFP and MICS data, but AFP estimates of pentavalent coverage in Punjab were biased toward higher values. Conclusions: National estimates mask variation and estimates from individual surveys should be considered alongside other estimates. The development of strategies targeted towards poorly educated parents within low-wealth quintiles that may not typically access healthcare could improve vaccination rates

Assessment of Human Health Risk of Zinc and Lead by Consuming Food Crops Supplied with Excessive Fertilizers

For the study of heavy metals impact on human beings, areas in Sargodha city that were supplied with various types of fertilizers were chosen. The three industrial areas; (Bhalwal, Sillanwali, and Sahiwal) of this city were explored for research reasons. The researchers wanted to know how much heavy metal was in the soil, food crops, and human. Excess fertilizer use contributes to global pollution. Farmyard manure, urea, and potassium chloride were used on Site 1; urea phosphate, manure, and ammonium sulphate were used on Site 2; and super phosphate, ammonium phosphate, and nitrate phosphate were used on Site 3. Samples of commonly used food crops, their respective soils and blood of residents who ingested the food crops of the studied area were collected. The zinc and lead levels in soil (8.30-16.80 and 1.80-12.71 mg/kg) and food crops (0.26-2.02 and 2.26-4.70 mg/kg) were far lower than WHO permitted limits. Blood mean concentration of both Zn (2.30-4.30 mg/L) and Ni (0.24-0.70 mg/L) were found maximum in residents of Site 3. The values of pollution load index, bioconcentration factor, enrichment factor for both zinc and lead were (0.18-0.37 and0.220-0.948), (0.027-0.138 and 0.316-1.705), (0.020-0.144 and 0.515-2.780), respectively. Daily intake of metal (0.004-0.008 and 0.001-0.002 mg/kg/day) and health risk index (0.0001-0.016 and 0.005-0.115) values were observed to be lower in individuals for Zn and Pb, respectively. In present work values of all pollution indices wereSo, there would be no human health hazard

Characterising the Initial Events of Herpes Simplex Virus Infection in Human Anogenital Tissue

Herpes simplex virus (HSV) infection has a high prevalence globally and is associated with increased risk of HIV infection. Understanding HSV immunopathogenesis is key to developing successful treatments which may also reduce HIV acquisition rates. HSV directly interacts with keratinocytes and antigen presenting cells, mainly mononuclear phagocytes (MNPs) via the HSV entry receptor nectin-1. We recently discovered a novel population of epidermal type 2 conventional dendritic cells (Epidermal cDC2s) in anogenital skin and mucosae that express CD11c and are more susceptible to infection by HSV-1 in vitro compared to Langerhans Cells (LCs) (Bertram et al., 2021). Here, we developed a primary human foreskin model to study the early events of HSV infection in situ. To simulate microtrauma and the inflammatory environment during sexual transmission, we used microneedle patches (Nanopatch) to induce perforations into the epidermis. Coating the Nanopatches with virus prior to their application enhanced epidermal infection with HSV and was essential for infection of non-infant foreskins (aged 5 y.o+). Infection only occurred when perforations extended beyond one third of the thickness of the epidermis. GFP-labeled HSV-1 spread rapidly in local keratinocytes, away from the perforations. Nectin-1 expression was induced on cells surrounding the perforations and also surrounding foci of infection seemingly facilitating spread of the infection. Experiments with HaCaT cells showed that this paracrine induction of nectin-1 in response to HSV infection was due to soluble mediators from infected keratinocytes, currently being characterized. We also utilized highly sensitive RNAscope technology to visualise HSV DNA interactions with LCs and Epidermal cDC2s. We detected both nuclear and cytoplasmic HSV DNA in both LCs and Epidermal cDC2s, in addition to extracellular particles initially in the mid-epidermis. In vitro studies on the epidermal MNP subsets demonstrated that they also play a role in HSV-2/HIV-1 co-infection. Both subsets expressed HIV co-receptors CCR5, CD4 and CXCR4, with CCR5 highly constitutively expressed on Epidermal cDC2s. Surface expression of all HIV co-receptors increased further with HSV-2 infection. Both subsets produced TNF in response to HSV-2 infection, which can act on bystander cells to upregulate their CCR5 expression as shown by Marsden et al., (2015). Thus both types of MNPs play a significant role in the immune response to HSV infection, while also increasing the susceptibility of the tissue to co-infection with HIV. This data provides insight into the window of opportunity for intervention against infection with HSV, a crucial step in the development of vaccines and immunotherapies

Integrating MDT tumor board shadowing into the undergraduate medical curriculum: Perspective of medical students

Site-specific multidisciplinary team (MDT) tumor boards are valuable resources for medical students, enabling them to familiarize themselves with the latest evidence-based cancer management strategies and observe effective teamwork in action. In this study, we looked at the awareness and perceptions of medical students about incorporating MDT tumor boards in the medical curriculum. A cross-sectional study was conducted among medical students from year 1 to year 5 at the Aga Khan University after exemption from ethical review committee. A 20-item self-administered questionnaire was used to evaluate the awareness and perceptions of medical students regarding MDT tumor boards. A total of 285 medical students participated in this study, with their mean age (± standard deviation) being 21.91 ± 1.67 years. A majority of 183 (64.2%) had no prior knowledge of the existence of a site-specific MDT tumor board for cancer management. Of the 285 students, 252 (88.4%) demonstrated sufficient awareness of the effectiveness of MDT tumor boards; similarly, 232 (81.4%) responded positively to the idea of mandatory tumor board rotations being incorporated into the undergraduate curriculum. No significant association was found between the student\u27s year of study (χ2 = 6.03, p = 0.20) or gender (χ2 = 35, p = 0.84) and their perceptions of the effectiveness of MDT tumor boards. However, it was found that students who had prior knowledge of their existence had a stronger association with sufficient awareness (χ2 = 4.2, p = 0.04). The results indicate that while the majority of the medical students have no prior attendance or knowledge regarding MDT tumor boards, there is an overwhelming willingness among students to incorporate them into the medical curriculum

A Standardized Chemically Modified Curcuma longa Extract Modulates IRAK-MAPK Signaling in Inflammation and Potentiates Cytotoxicity

The TLR/IL-1R pathway is a critical signaling module that is misregulated in pathologies like inflammation and cancer. Extracts from turmeric (Curcuma longa L.) enriched in curcumin and carbonyls like turmerones have been shown to exert potent anti-inflammatory effects. The present study evaluated the anti-inflammatory activity, cytotoxic effect and the underlying mechanism of a novel chemically modified, non-carbonyl compound enriched Curcuma longa L. (C. longa) extract (CMCE). CMCE (1 or 10 µg/mL; 14 h) significantly decreased LPS (50-100 ng/mL) induced TNF-α and IL-1β production in THP-1 cells, human, and mouse whole blood as measured by ELISA. LPS-induced IRAK1, MAPK activation, TLR4 expression, TLR4-MyD88 interaction and IκBα degradation were significantly reduced in CMCE pre-treated THP-1 cells as assessed by Western blotting. CMCE (30, 100 and 300 mg/kg; 10 days p.o.) pre-treated and LPS (10 mg/kg) challenged Swiss mice exhibited attenuated plasma TNF-α, IL-1β, nitrite, aortic iNOS expression and vascular dysfunction. In a PI permeability assay, cell lines derived from acute myeloid leukemia were most sensitive to the cytotoxic effects of CMCE. Analysis of Sub-G1 phase, Annexin V-PI positivity, loss of mitochondrial membrane potential, increased caspase-3 and PARP-1 activation confirmed CMCE induced apoptosis in HL-60 cells. IRAK inhibition also sensitized HL-60 cells to CMCE induced cytotoxicity. The present study defines the mechanism underlying the action of CMCE and suggests a therapeutic potential for its use in sepsis and leukemia

Tumors Presenting as Multiple Cranial Nerve Palsies

Cranial nerve palsy could be one of the presenting features of underlying benign or malignant tumors of the head and neck. The tumor can involve the cranial nerves by local compression, direct infiltration or by paraneoplastic process. Cranial nerve involvement depends on the anatomical course of the cranial nerve and the site of the tumor. Patients may present with single or multiple cranial nerve palsies. Multiple cranial nerve involvement could be sequential or discrete, unilateral or bilateral, painless or painful. The presentation could be acute, subacute or recurrent. Anatomic localization is the first step in the evaluation of these patients. The lesion could be in the brain stem, meninges, base of skull, extracranial or systemic disease itself. We present 3 cases of underlying neoplasms presenting as cranial nerve palsies: a case of glomus tumor presenting as cochlear, glossopharyngeal, vagus and hypoglossal nerve palsies, clivus tumor presenting as abducens nerve palsy, and diffuse large B-cell lymphoma presenting as oculomotor, trochlear, trigeminal and abducens nerve palsies due to paraneoplastic involvement. History and physical examination, imaging, autoantibodies and biopsy if feasible are useful for the diagnosis. Management outcomes depend on the treatment of the underlying tumor

Automated Pavement Cracks Detection and Classification Using Deep Learning

Monitoring asset conditions is a crucial factor in building efficient transportation asset management. Because of substantial advances in image processing, traditional manual classification has been largely replaced by semi-automatic/automatic techniques. As a result, automated asset detection and classification techniques are required. This paper proposes a methodology to detect and classify roadway pavement cracks using the well-known You Only Look Once (YOLO) version five (YOLOv5) and version 8 (YOLOv8) algorithms. Experimental results indicated that the precision of pavement crack detection reaches up to 67.3% under different illumination conditions and image sizes. The findings of this study can assist highway agencies in accurately detecting and classifying asset conditions under different illumination conditions. This will reduce the cost and time that are associated with manual inspection, which can greatly reduce the cost of highway asset maintenance.</p

Advancing Roadway Sign Detection with YOLO Models and Transfer Learning

Roadway signs detection and recognition is an essential element in the Advanced Driving Assistant Systems (ADAS). Several artificial intelligence methods have been used widely among of them YOLOv5 and YOLOv8. In this paper, we used a modified YOLOv5 and YOLOv8 to detect and classify different roadway signs under different illumination conditions. Experimental results indicated that for the YOLOv8 model, varying the number of epochs and batch size yields consistent MAP50 scores, ranging from 94.6% to 97.1% on the testing set. The YOLOv5 model demonstrates competitive performance, with MAP50 scores ranging from 92.4% to 96.9%. These results suggest that both models perform well across different training setups, with YOLOv8 generally achieving slightly higher MAP50 scores. These findings suggest that both models can perform well under different training setups, offering valuable insights for practitioners seeking reliable and adaptable solutions in object detection applications.</p