Large language models and bariatric surgery patient education: a comparative readability analysis of GPT-3.5, GPT-4, Bard, and online institutional resources.

BACKGROUND: The readability of online bariatric surgery patient education materials (PEMs) often surpasses the recommended 6th grade level. Large language models (LLMs), like ChatGPT and Bard, have the potential to revolutionize PEM delivery. We aimed to evaluate the readability of PEMs produced by U.S. medical institutions compared to LLMs, as well as the ability of LLMs to simplify their responses. METHODS: Responses to frequently asked questions (FAQs) related to bariatric surgery were gathered from top-ranked health institutions. FAQ responses were also generated from GPT-3.5, GPT-4, and Bard. LLMs were then prompted to improve the readability of their initial responses. The readability of institutional responses, initial LLM responses, and simplified LLM responses were graded using validated readability formulas. Accuracy and comprehensiveness of initial and simplified LLM responses were also compared. RESULTS: Responses to 66 FAQs were included. All institutional and initial LLM responses had poor readability, with average reading levels ranging from 9th grade to college graduate. Simplified responses from LLMs had significantly improved readability, with reading levels ranging from 6th grade to college freshman. When comparing simplified LLM responses, GPT-4 responses demonstrated the highest readability, with reading levels ranging from 6th to 9th grade. Accuracy was similar between initial and simplified responses from all LLMs. Comprehensiveness was similar between initial and simplified responses from GPT-3.5 and GPT-4. However, 34.8% of Bard's simplified responses were graded as less comprehensive compared to initial. CONCLUSION: Our study highlights the efficacy of LLMs in enhancing the readability of bariatric surgery PEMs. GPT-4 outperformed other models, generating simplified PEMs from 6th to 9th grade reading levels. Unlike GPT-3.5 and GPT-4, Bard's simplified responses were graded as less comprehensive. We advocate for future studies examining the potential role of LLMs as dynamic and personalized sources of PEMs for diverse patient populations of all literacy levels.

Perceptions and Expectations Regarding the Step 1 Score Change Among Surgical and Non-Surgical Program Directors: A Systematic Review and Meta-Analysis.

There are currently no studies examining differences in perceptions and expected impact of the Step 1 score change to pass/fail between surgical and non-surgical program directors (PDs). We conducted a systematic review in May 2023 of PubMed, Scopus, Web of Science, and PSYCInfo to evaluate studies examining PDs' perspectives regarding the Step 1 score change. We performed random-effects meta-analyses to determine differences in perspectives among surgical and non-surgical PDs. Surgical PDs (76.8% [95% CI, 72.1%-82.0%], I2 = 52%) reported significantly greater rates of disagreement with the score change compared to non-surgical (65.1% [95% CI, 57.9%-73.1%], I2 = 69.7%) (P = .01). Surgical PDs also reported significantly greater rates of agreement that the score change will increase the difficulty in objectively comparing applicants (88.1% [95% CI, 84.6%-91.7%], I2 = 16.4%), compared to non-surgical (81.0% [95% CI, 75.6%-86.8%], I2 = 72.6%) (P = .04). There was less heterogeneity among non-surgical PDs (88.7% [95% CI, 86.2%-91.2%], I2 = 0%), compared to surgical (84.7% [95% CI, 79.0%-90.8%], I2 = 67.3%), regarding expected increases in emphasis on Step 2, although the difference in rates of agreement was not statistically significant. Overall, there is significant heterogeneity in the literature regarding expected changes in the residency application review process. Most PDs reported significant disagreement with the score change, greater expected difficulty in objectively evaluating applicants, and greater emphasis on Step 2, with surgical PDs reporting greater rates of disagreement, greater expected difficulty, and heterogeneity regarding expected increases in emphasis on Step 2, compared to non-surgical. Additionally, there is significant heterogeneity in the overall literature regarding expected changes in the residency application review process. Further research is needed to establish evidence-based guidelines that improve the overall residency application process for all stakeholders.

Providers' Knowledge and Perceptions of Bariatric Surgery: a Systematic Review.

Bariatric surgery remains underutilized despite its proven efficacy in the management of obesity. Provider perceptions of bariatric surgery are important to consider when discussing utilization rates. PubMed, SCOPUS, and OVID databases were searched in April 2023, and 40 published studies discussing providers' knowledge and perceptions of bariatric surgery were included. There were generally positive perceptions of the efficacy of bariatric surgery, although overestimations of surgical risks and postoperative complications were common. Providers' previous training was associated with knowledge and perceptions of bariatric surgery and familiarity with perioperative management across studies. These perceptions were also associated with referral rates, suggesting that inadequate provider knowledge may contribute to bariatric surgery underutilization. We advocate for increased bariatric surgery-related education throughout all stages of medical training and across specialties.

Patient and the Public's Perceptions of Bariatric Surgery: A Systematic Review.

INTRODUCTION: Bariatric surgery is an effective therapeutic modality for obesity and related comorbidities, yet it remains significantly underutilized. Patient perceptions and expectations may influence the decisions of eligible patients in pursuing surgery. METHODS: PubMed, SCOPUS, and OVID databases were searched in July 2022 to identify published studies discussing patient and the public's perceptions of bariatric surgery. RESULTS: The literature shows participants often reported bariatric surgery to be a life-changing intervention known to induce weight loss, improve obesity-related comorbidities, and improve quality of life. However, a significant proportion of survey respondents perceived bariatric surgery as unsafe or risky. Patients belonging to racial minority groups cited higher concern with mortality risk, lower weight loss expectations, and different motivations to pursue bariatric surgery. Female patients were significantly more likely to have more positive perceptions of, and higher expectations of weight loss from, bariatric surgery. CONCLUSIONS: The literature highlighted discordance between patient perceptions and the demonstrated clinical safety and efficacy profile of bariatric surgery. Overestimations of the risks, unrealistic expectations, and unfamiliarity with bariatric surgery outcomes were common findings. These perceptions of bariatric surgery may contribute to its underutilization among eligible patients. Perceptions and motivations often varied by race, region, sex, and age, which demonstrates the necessity of patient-centered education in the prereferral stage. The literature also demonstrated misconceptions of bariatric surgery among the public. Further research should explore the impact of education on the perceptions of patients and the public.

Exploratory study of the provision of academic and health-related accommodations to transition-age adolescents and emerging adults with spina bifida.

PURPOSE: The purpose of this exploratory study was to investigate the types of academic and health-related accommodations provided to adolescents and emerging adults with spina bifida aged 9-20 years. METHODS: Data were extracted from the paper and electronic records of transition-age youth enrolled in the study. Four open ended items involved content analysis. RESULTS: The most frequently identified accommodation was enrollment in special education classes in 47.7% of the charts. Other academic accommodations that were most often reported were adaptive physical education (n = 71, 39.9%), tutoring (n = 28; 15.7%), and home schooling (n = 21; 11.8%). Clean intermittent catheterization was the most frequently identified health-related accommodation provided by the school nurse/aide (n = 57; 32%).The largest percentage of requests for additional accommodations were made during the middle school grades (15; 54.8%) followed by high school (10; 32.2%). CONCLUSION: Findings demonstrated that persistent issues were identified by parents/adolescents regarding the provision of school-related accommodations. This is a relevant area for clinical practice to ensure students with special health care needs and those with spina bifida receive the academic and health-related accommodations in their Individualized Education Program/504 plans.

Dialogue as a tool of nutrition literacy in an agricultural intervention programme in Odisha, India.

Background: An ongoing action research nutrition literacy programme based on Freire's approach of raising critical consciousness through the use of dialogue as a pedagogic tool is being implemented as part of a nutrition sensitive agricultural intervention in tribal Odisha. One hundred and eight adults, referred to as Community Hunger Fighters (CHFs) underwent two modules of a residential training programme of two and a half days each, spread over two months. Through discussion they explored the reasons behind the lack of diversity in their daily diets and identified the social, economic and cultural barriers to food intake in the context of their own poverty. They undertook collective exercises in nutrition sensitive agricultural planning. The transformative behaviour of the CHFs was captured through observation, interviews and focus group discussion with a set of qualitative indicators. Results: The methodology of dialogue as a pedagogic tool generated a discussion about food security among the community. CHFs identified key messages and shared them with fellow villagers in imaginative ways. The process of critical reflection and analysis helped understand gender disparities, the bottlenecks in food production, brought in life style changes to improve food intake and created a demand for technical training for improving agricultural productivity. Thirty eight had started a nutri-garden and several took on leadership roles on other issues of importance besides food security. Conclusion: Dialogue as a pedagogic tool for nutrition literacy in an agricultural intervention programme has the potential to facilitate a process of critical reflection on the socio cultural and economic barriers to food production and consumption thereby leading to transformative action. Supplementary Information: The online version contains supplementary material available at 10.1186/s43170-022-00090-x.

Polypharmacy leads to increased prevalence of potentially inappropriate medication in the Indonesian geriatric population visiting primary care facilities.

BACKGROUND: The geriatric population is particularly vulnerable to being prescribed potentially inappropriate medication (PIM); however, the prevalence of this occurrence remains poorly investigated in Indonesia. Thus in this research, we focused on investigating the prevalence and predictors of PIM among the Indonesian geriatric population in a primary health care setting. METHODS: A retrospective observational study was conducted in 25 primary health care facilities in Karawang District, Indonesia. The medical prescriptions of patients aged ≥60 years during January-December 2014 were documented, and the PIM was assessed based on Beers and McLeod criteria. The influence of age, sex, number of diseases, and polypharmacy toward PIM was assessed using a logistic regression model. A P-value of <0.05 defined statistical significance. RESULTS: A total of 3,819 subjects were included in the study. PIM was highly prevalent (52.2%) among the Indonesian elderly. Chlorpheniramine, mefenamic acid, ibuprofen, and nifedipine were the most commonly prescribed PIM. Polypharmacy (odds ratio: 1.2 [0.6, 2.1]) was the only factor associated with the use of PIM, while sex, age, and multiple diseases did not show significant association. CONCLUSION: PIM is a concern in the Indonesian geriatric population. Health care professionals are encouraged to review the medications of their geriatric patients using updated safety guidelines to prevent risks associated with PIM.

DIETARY DIVERSITY AND ITS RELATIONSHIP WITH NUTRITIONAL STATUS AMONG ADOLESCENTS AND ADULTS IN RURAL INDIA.

Dietary diversity is associated with household or individual food availability and intake of nutrients from different food groups and is an important component of nutritional outcome. This study examined the Nutrient Adequacy Ratio (NAR) and the Mean Adequacy Ratio (MAR) of three dietary diversity indices and their relationship with the nutritional status of adolescents and adults in rural regions of two states in India, Wardha district in Maharashtra and Koraput district in Odisha, in 2014. Individual dietary diversity was calculated using 24-hour diet recall (FS24hr) data and household dietary diversity was measured with food frequency data using Berry's index (DDI) and food scores (FSFFQ). The nutritional status of individuals was assessed using anthropometric indices. The diets in both locations were cereal dominated. It was observed that 51% of adolescent boys and 27% of adolescent girls had 'thinness' and stunting. The prevalence of undernutrition was higher among adult women (48%) than adult men (36%). The mean diversity indices were FS24hr of 8, DDI of 89-90 and FSFFQ of 64-66 in the two locations. The FS24hr was found to be positively correlated with the NAR of all nutrients while DDI and FSFFQ were correlated with seven and six nutrients, respectively. The DDI and FS24hr showed an association with MAR if the two locations were combined together. Sensitivity and specificity analysis showed that FS24hr gave more true positives than false positives and the area under the Receiver Operating Characteristic curve was 0.68, implying that this measure truly differentiates individuals having low dietary diversity with low MAR from those with low dietary diversity and a high MAR. All three measures of dietary diversity showed a linear association with the nutritional outcomes of adults, while in the adolescent group only DDI showed a relationship. It is concluded that 24-hour diet recall is a good measure for studying the relationship between dietary diversity and nutritional status in adults.

Intraoperative frozen section analysis for the diagnosis of early stage ovarian cancer in suspicious pelvic masses.

BACKGROUND: Women with suspected early-stage ovarian cancer need surgical staging which involves taking samples from areas within the abdominal cavity and retroperitoneal lymph nodes in order to inform further treatment. One potential strategy is to surgically stage all women with suspicious ovarian masses, without any histological information during surgery. This avoids incomplete staging, but puts more women at risk of potential surgical over-treatment.A second strategy is to perform a two-stage procedure to remove the pelvic mass and subject it to paraffin sectioning, which involves formal tissue fixing with formalin and paraffin embedding, prior to ultrathin sectioning and multiple site sampling of the tumour. Surgeons may then base further surgical staging on this histology, reducing the rate of over-treatment, but conferring additional surgical and anaesthetic morbidity.A third strategy is to perform a rapid histological analysis on the ovarian mass during surgery, known as 'frozen section'. Tissues are snap frozen to allow fine tissue sections to be cut and basic histochemical staining to be performed. Surgeons can perform or avoid the full surgical staging procedure depending on the results. However, this is a relatively crude test compared to paraffin sections, which take many hours to perform. With frozen section there is therefore a risk of misdiagnosing malignancy and understaging women subsequently found to have a presumed early-stage malignancy (false negative), or overstaging women without a malignancy (false positive). Therefore it is important to evaluate the accuracy and usefulness of adding frozen section to the clinical decision-making process. OBJECTIVES: To assess the diagnostic test accuracy of frozen section (index test) to diagnose histopathological ovarian cancer in women with suspicious pelvic masses as verified by paraffin section (reference standard). SEARCH METHODS: We searched MEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015) and relevant Cochrane registers. SELECTION CRITERIA: Studies that used frozen section for intraoperative diagnosis of ovarian masses suspicious of malignancy, provided there was sufficient data to construct 2 x 2 tables. We excluded articles without an available English translation. DATA COLLECTION AND ANALYSIS: Authors independently assessed the methodological quality of included studies using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) domains: patient selection, index test, reference standard, flow and timing. Data extraction converted 3 x 3 tables of per patient results presented in articles into 2 x 2 tables, for two index test thresholds. MAIN RESULTS: All studies were retrospective, and the majority reported consecutive sampling of cases. Sensitivity and specificity results were available from 38 studies involving 11,181 participants (3200 with invasive cancer, 1055 with borderline tumours and 6926 with benign tumours, determined by paraffin section as the reference standard). The median prevalence of malignancy was 29% (interquartile range (IQR) 23% to 36%, range 11% to 63%). We assessed test performance using two thresholds for the frozen section test. Firstly, we used a test threshold for frozen sections, defining positive test results as invasive cancer and negative test results as borderline and benign tumours. The average sensitivity was 90.0% (95% confidence interval (CI) 87.6% to 92.0%; with most studies typically reporting range of 71% to 100%), and average specificity was 99.5% (95% CI 99.2% to 99.7%; range 96% to 100%).Similarly, we analysed sensitivity and specificity using a second threshold for frozen section, where both invasive cancer and borderline tumours were considered test positive and benign cases were classified as negative. Average sensitivity was 96.5% (95% CI 95.5% to 97.3%; typical range 83% to 100%), and average specificity was 89.5% (95% CI 86.6% to 91.9%; typical range 58% to 99%).Results were available from the same 38 studies, including the subset of 3953 participants with a frozen section result of either borderline or invasive cancer, based on final diagnosis of malignancy. Studies with small numbers of disease-negative cases (borderline cases) had more variation in estimates of specificity. Average sensitivity was 94.0% (95% CI 92.0% to 95.5%; range 73% to 100%), and average specificity was 95.8% (95% CI 92.4% to 97.8%; typical range 81% to 100%).Our additional analyses showed that, if the frozen section showed a benign or invasive cancer, the final diagnosis would remain the same in, on average, 94% and 99% of cases, respectively.In cases where the frozen section diagnosis was a borderline tumour, on average 21% of the final diagnoses would turn out to be invasive cancer.In three studies, the same pathologist interpreted the index and reference standard tests, potentially causing bias. No studies reported blinding pathologists to index test results when reporting paraffin sections.In heterogeneity analyses, there were no statistically significant differences between studies with pathologists of different levels of expertise. AUTHORS' CONCLUSIONS: In a hypothetical population of 1000 patients (290 with cancer and 80 with a borderline tumour), if a frozen section positive test result for invasive cancer alone was used to diagnose cancer, on average 261 women would have a correct diagnosis of a cancer, and 706 women would be correctly diagnosed without a cancer. However, 4 women would be incorrectly diagnosed with a cancer (false positive), and 29 with a cancer would be missed (false negative).If a frozen section result of either an invasive cancer or a borderline tumour was used as a positive test to diagnose cancer, on average 280 women would be correctly diagnosed with a cancer and 635 would be correctly diagnosed without. However, 75 women would be incorrectly diagnosed with a cancer and 10 women with a cancer would be missed.The largest discordance is within the reporting of frozen section borderline tumours. Investigation into factors leading to discordance within centres and standardisation of criteria for reporting borderline tumours may help improve accuracy. Some centres may choose to perform surgical staging in women with frozen section diagnosis of a borderline ovarian tumour to reduce the number of false positives. In their interpretation of this review, readers should evaluate results from studies most typical of their population of patients.

Influence of moisture, particle size and pulse flour composition on phase transition behavior of rice flour.

Study on the phase transition characteristics is an important parameter in extrusion processing. The influence of Moisture Content (MC), particle size and level of cereal-pulse blend on the glass transition (Tg) and melt (Tm) temperatures of a ready to eat cereal-pulse formulation was determined. All samples were moisture conditioned in a 9 to 27 % with 3 % interval. Tg and Tm were measured by phase transition analyser (PTA). A substantial decrease in Tg and Tm was observed as moisture content level increased from 9 to 27 %. However Tg and Tm values could not be clearly defined below 9 % moisture content and above 27 % moisture content. The Tg and Tm values of the cereal-pulse formulation were found to be increased with increasing pulse composition (5 to 30 % with 5 % interval). Increase in particle size (150, 180, 212, 300, 425 and 500 µ) exhibited significant increase effect on Tg while less significant effect on Tm. This may be due to crystalline regions which play a role in cross linking amorphous regions of the polymeric network and thus suppress the mobility of amorphous regions. The observed differences in Tg and Tm induced by the moisture content, concentration of Bengal gram and particle size will be useful in simulation and optimization of barrel temperature set during extrusion processing.

Sentinel node assessment for diagnosis of groin lymph node involvement in vulval cancer.

BACKGROUND: Vulval cancer is usually treated by wide local excision with removal of groin lymph nodes (inguinofemoral lymphadenectomy) from one or both sides, depending on the tumour location. However, this procedure is associated with significant morbidity. As lymph node metastasis occurs in about 30% of women with early vulval cancer, accurate prediction of lymph node metastases could reduce the extent of surgery in many women, thereby reducing morbidity. Sentinel node assessment is a diagnostic technique that uses traceable agents to identify the spread of cancer cells to the lymph nodes draining affected tissue. Once the sentinel nodes are identified, they are removed and submitted to histological examination. This technique has been found to be useful in diagnosing the nodal involvement of other types of tumours. Sentinel node assessment in vulval cancer has been evaluated with various tracing agents. It is unclear which tracing agent or combination of agents is most accurate. OBJECTIVES: To assess the diagnostic test accuracy of various techniques using traceable agents for sentinel lymph node assessment to diagnose groin lymph node metastasis in women with FIGO stage IB or higher vulval cancer and to investigate sources of heterogeneity. SEARCH METHODS: We searched MEDLINE (1946 to February 2013), EMBASE (1974 to March 2013) and the relevant Cochrane trial registers. SELECTION CRITERIA: Studies that evaluated the diagnostic accuracy of traceable agents for sentinel node assessment (involving the identification of a sentinel node plus histological examination) compared with histological examination of removed groin lymph nodes following complete inguinofemoral lymphadenectomy (IFL) in women with vulval cancer, provided there were sufficient data for the construction of two-by-two tables. DATA COLLECTION AND ANALYSIS: Two authors (TAL, AP) independently screened titles and abstracts for relevance, classified studies for inclusion/exclusion and extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We used univariate meta-analytical methods to estimate pooled sensitivity estimates. MAIN RESULTS: We included 34 studies evaluating 1614 women and approximately 2396 groins. The overall methodological quality of included studies was moderate. The studies included in this review used the following traceable techniques to identify sentinel nodes in their participants: blue dye only (three studies), technetium only (eight studies), blue dye plus technetium combined (combined tests; 13 studies) and various inconsistent combinations of these three techniques (mixed tests; 10 studies). For studies of mixed tests, we obtained separate test data where possible.Most studies used haematoxylin and eosin (H&E) stains for the histological examination. Additionally an immunohistochemical (IHC) stain with and without ultrastaging was employed by 14 and eight studies, respectively. One study used reverse transcriptase polymerase chain reaction analysis (CA9 RT-PCR), whilst three studies did not describe the histological methods used.The pooled sensitivity estimate for studies using blue dye only was 0.94 (68 women; 95% confidence interval (CI) 0.69 to 0.99), for mixed tests was 0.91 (679 women; 95% CI 0.71 to 0.98), for technetium only was 0.93 (149 women; 95% CI 0.89 to 0.96) and for combined tests was 0.95 (390 women; 95% CI 0.89 to 0.97). Negative predictive values (NPVs) for all index tests were > 95%. Most studies also reported sentinel node detection rates (the ability of the test to identify a sentinel node) of the index test. The mean detection rate for blue dye alone was 82%, compared with 95%, 96% and 98% for mixed tests, technetium only and combined tests, respectively. We estimated the clinical consequences of the various tests for 100 women undergoing the sentinel node procedure, assuming the prevalence of groin metastases to be 30%. For the combined or technetium only tests, one and two women with groin metastases might be 'missed', respectively (95% CI 1 to 3); and for mixed tests, three women with groin metastases might be 'missed' (95% CI 1 to 9). The wide CIs associated with the pooled sensitivity estimates for blue dye and mixed tests increased the potential for these tests to 'miss' women with groin metastases. AUTHORS' CONCLUSIONS: There is little difference in diagnostic test accuracy between the technetium and combined tests. The combined test may reduce the number of women with 'missed' groin node metastases compared with technetium only. Blue dye alone may be associated with more 'missed' cases compared with tests using technetium. Sentinel node assessment with technetium-based tests will reduce the need for IFL by 70% in women with early vulval cancer. It is not yet clear how the survival of women with negative sentinel nodes compares to those undergoing standard surgery (IFL). A randomised controlled trial of sentinel node dissection and IFL has methodological and ethical issues, therefore more observational data on the survival of women with early vulval cancer are needed.

RBx10080307, a dual EGFR/IGF-1R inhibitor for anticancer therapy.

Pharmacological intervention of epidermal growth factor receptor (EGFR) family members by antibodies or small molecule inhibitors has been one of the most successful approaches for anticancer therapy. However this therapy has its own limitations due to the development of resistance, over a period of time. One of the possible causes of the development of resistance to the therapy with EGFR inhibitors could be the simultaneous activation of parallel pathways. Both EGFR and insulin like growth factor-1 receptor (IGF-1R) pathways are reported to act reciprocal to each other and converge into the mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways. Inhibiting one pathway alone may therefore not be sufficient and could be a cause of development of resistance. The other cause could be mutations of EGFR which would be less sensitive to the inhibitors. We, therefore, suggest that co-targeting IGF-1R and EGFR kinases by dual inhibitors can lead to improved efficacy and address the problems of resistance. In the present manuscript, we report the identification of a novel, small molecule dual EGFR/IGF-1R inhibitor, RBx10080307 which displayed in vitro activity at the molecular level and oral efficacy in mouse xenograft model. The compound also showed in vitro activity in an EGFR mutant cell line and may thus have the potential to show activity in resistant conditions. Additional efficacy studies are needed in EGFR resistant mouse cancer model and if found efficacious, this can be a major advantage over standalone erlotinib and other existing therapies.

Dual epidermal growth factor receptor (EGFR)/insulin-like growth factor-1 receptor (IGF-1R) inhibitor: a novel approach for overcoming resistance in anticancer treatment.

Small molecule inhibitors of epidermal growth factor receptors (EGFR) have been found to show a good initial response in cancer patients but during the course of treatment, patients develop resistance after a few weeks of time. Development of secondary mutations or over-activation of insulin like growth factor (IGF-1R) pathway are a few of the several mechanisms proposed to explain the resistance. To study the effect of dual inhibition of EGFR and IGF-1R in overcoming the resistance, three strategies were envisaged and are reported in this manuscript: 1) a virtual predictive tumor model, 2) in vitro experimental data using a combination of EGFR and IGF-1R inhibitors and 3) in vitro experimental data using in house dual inhibitors. Findings reported in this manuscript suggest that simultaneous inhibition of IGF-1R and EGFR either by combination of two inhibitors or by dual kinase inhibitors is more efficacious compared to single agents. In vitro cell based experiments conducted using epidermoid cancer cell line, A431 and an EGFR mutant cell line, H1975 along with virtual predictions reported here suggests that dual inhibition of EGFR and IGF-1R is a viable approach to overcome EGFR resistance.

Wuchereria bancrofti: diminished platelet activation in filarial patients.

Blood platelets are the innate immune elements that have not been investigated in human filarial infections. Platelet activation status in the endemic normals (EN), microfilaria positive individuals (MF) and patients with chronic pathology (CP) was evaluated in whole blood, under unstimulated as well as antigen exposed (BmA, E. coli) conditions for PAC-1 expression by Flow cytometry. A diminished PAC-1 expression was observed in MF compared to CP and EN spontaneously as well as upon antigen exposure. Besides this, PAC-1 expression within the groups did not exhibit any significant difference under all the experimental conditions. However in CP patients, E. coli antigen exposure resulted in a significantly reduced PAC-1 expression compared to the spontaneous expression levels. NO release in platelet culture supernatants from EN was inversely proportional to platelet aggregation. Collagen stimulated platelets from EN, exposed to sera and immune complexes from CP and MF patients resulted in elevated Nitric Oxide (NO) release, compared to those exposed to autologous sera and fetal calf serum. In addition, under similar conditions, collagen stimulated platelets from EN, exposed to filarial antigen (BmA) exhibited increased NO compared to the E. coli antigen exposed ones and light microscopic observations of cultured platelets supported the above findings. Thus it appears from the results of the present study that filarial antigen may play a role in the loss of platelet aggregation, leading to platelet inactivation.