BackgroundMedical education curricula in developing countries should emphasize training in health research. This study compares the knowledge and attitudes towards health research between undergraduate medical students undertaking Problem Based Learning (PBL) versus conventional Lecture Based Learning (LBL).MethodsTwo groups comprising 66 (LBL) and 84 (PBL) 4th and 5th year students from the medical college of Aga Khan University were administered a structured and validated questionnaire. Knowledge and attitudes of the two groups were recorded on a scale (graduated in percentages) and compared for statistical difference.ResultsPBL students scored 54.0% while LBL students scored 55.5% on the knowledge scale [p-value; 0.63]. On the attitudes scale, PBL students scored 75.5% against a 66.7% score of LBL students [p-value; 0.021]. A higher proportion of PBL students (89%) had participated in research activities compared to LBL students (74%) and thus felt more confident in conducting research and writing a scientific paper.ConclusionThe PBL students showed slightly healthier attitudes towards health research compared to LBL students. Both groups demonstrated a similar level of knowledge about health research. The positive impact of the PBL curriculum on attitudes of medical students towards health research may help in improving research output from developing countries in future.

Background: Head and neck cancers are a major cancer burden in Pakistan. They share a common risk factor profile including regular consumption of products of betel, areca and tobacco. Use of paan, chaalia, gutka, niswar and tumbaku is acceptable in Pakistan and is considered a normal cultural practice. This cross-sectional study was carried out to understand the relation of sociodemographic factors for the consumption of paan, chaalia, gutka, niswar and tumbaku in Pakistani population. Through systematic sampling, 425 subjects from a squatter settlement in Karachi were interviewed using a structured questionnaire. High risk behavior was defined as Daily use of any of the above products.

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Natural killer (NK) cells are essential innate immune effectors with promising anti-leukemia activity in acute myeloid leukemia (AML). However, clinical success of applying NK cells in AML treatment has not been achieved. A better understanding of the regulatory mechanisms for NK cell function is important to optimize this therapeutic strategy. T cell immunoglobulin and ITIM domain (TIGIT) is a recently identified inhibitory receptor expressed on T cells and NK cells. Multiple studies including ours have demonstrated its suppressive effect in anti-tumor CD8 T cell response. However whether and how TIGIT impacts NK cells in AML is unknown. Here we performed phenotypic and functional studies on NK cells derived from patients with newly diagnosed AML (n=30). Cells collected from healthy individuals (n=18) were used as controls. TIGIT expression and their contributions to NK cell function in AML were assessed. Peripheral blood samples were first examined by flow cytometry for the frequency of NK cells (defined as CD56+CD3-). The percentage of NK cells among peripheral blood mononuclear cells (PBMCs) in AML patients is comparable with that of healthy controls. In contrast, when we performed functional analysis to assess NK cells for cytokine release upon in vitro stimulation with a human leukemia cell line K562, we observed significantly lower intracellular production of IFN-γ in cells from AML patients compared with that of healthy controls. Consistently NK cells from AML patients expressed less Perforin, indicating a compromised killing capacity. We next evaluated the expression of TIGIT on CD56+CD3- NK cells. As some AML blasts and monocytes also express CD56, we performed multichannel flow cytometry and carefully gated out other cell components when assessing TIGIT expression. To our surprise, we observed a significantly lower frequency of TIGIT-expressing NK cells in AML compared with that of healthy controls (36.82 ±4.543% vs. 48.9±3.818%, P=0.0463). This data indicated that low-TIGIT expression associates with impaired NK cell function and AML progression. We further examined the phenotype and functional status of TIGIT+ NK cells. Expression of activating receptors (CD16 and CD160) and inhibiting receptors (KIR and NKG2A) on TIGIT+ vs. TIGIT- NK cells were analyzed. We observed a significant higher expression of CD16 (51.27±9.009% vs. 20.63±5.334%, P=0.0001) and CD160 (39.84±6.447% vs. 21.24±4.287%, P=0.0103) on TIGIT+ NK cells compared with that of TIGIT- NK cells. By contrast, TIGIT+ NK cells expressed lower KIR (24.06±3.796% vs. 43.59±6.96%, P=0.0046) and NKG2A (7.658±1.717% vs. 18.68±4.256%, P=0.0167) than TIGIT- NK cells. Importantly, functional studies demonstrated an elevated expression of Granzyme B and increased cytokine (IFN-γ and TNF-α) production by TIGIT+ NK cells compared with TIGIT- NK cells (IFN-γ, P=0.0283; TNF-α P=0.0347; Granzyme B, P=0.0493). These data suggest that TIGIT expression on NK cells associated with activated and high functional status. Collectively, our study demonstrates that 1) in line with lower capacity to produce IFN-γ, NK cells from AML patients express less frequency of TIGIT compared with healthy individuals; 2) TIGIT+ NK cells from AML patients express high levels of activating receptors and are highly functional manifested by more cytokine production and enhanced expression of Granzyme B compared with TIGIT- NK cells. These results indicate that in AML patient, TIGIT may contribute to the upregulation of NK cell function. This is in contrast to the observations of CD8 T cells in which TIGIT plays a suppressive role. Targeting TIGIT for cancer treatment is currently under active development. Our findings bring a call for caution on the TIGIT-targeted therapeutic strategy in AML as TIGIT might be a double-edged sword in anti-leukemia immune regulation. Disclosures No relevant conflicts of interest to declare.

Our sample demonstrates an inadequate knowledge regarding the presentations, risk factors, and screening of cancers. Efforts aiming to correct these deficiencies might result in a successful and cost-effective model for primary and secondary prevention of major cancers in Pakistan.