Diabetic retinal disease (DRD) is the leading cause of blindness among working-aged individuals with diabetes. In the United States, underserved and minority populations are disproportionately affected by diabetic retinopathy and other diabetes-related health outcomes. In this narrative review, we describe racial disparities in the prevalence and screening of diabetic retinopathy, as well as the wide-range of disparities associated with social determinants of health (SDOH), which include socioeconomic status, geography, health-care access, and education.

Objectives. Tobacco use is one of the most critical risk factors for different oral diseases. The aim of this study is to demonstrate the effect of tobacco on oral mucosa by cytomorphometric analysis of cells with the help of exfoliative cytology and to find out the improvement in diagnostic sensitivity of exfoliative cytology in the detection of dysplastic changes and early oral malignancy. Methods. The nuclear area (NA) and cytoplasmic area (CA) of cells were measured within cytological smear obtained from leukoplakia lesions of buccal mucosa of 90 tobacco users, 30 smokers (TS), 30 chewers (TC) and 30 with combined habit of smoking and chewing (TSC)] and from normal buccal mucosa of 30 non users (NU) of tobacco. Each habit group consisted of 30 tobacco users with oral leukoplakia lesion with mild epithelial dysplasia only. The 30 non-users of tobacco served as controls. The mean values of the CA and NA were obtained for each case, and the nuclear/cytoplasmic area (NA/CA) ratio was calculated. Results. The results showed a statistically significant increase (P<0.001) in mean NA and a statistically significant decrease (P<0.001) in mean CA values of tobacco users with leukoplakia as compared to non-users, hence NA/CA ratio value was significantly higher in tobacco users with the lesion. Conclusion. The changes in cellular morphology caused by tobacco use can be visualized by use of exfoliative cytology with the help of cytomorphometric analysis. The evaluation of parameters (NA, CA and NA/CA ratio) may increase the sensitivity of exfoliative cytology for the early diagnosis of oral premalignant and malignant lesions.

Mobile Ad-hoc Network (MANETs) is a temporary wireless network, which is self-configuring in which nodes moves freely and continuously. It consists of a collection of wireless mobile nodes which dynamically exchange data among themselves without the reliance on a fixed base station or a wired resolution network. Due to its mobility and self-routing effective nature, there are many deficiencies in its security. Various security threats show their impact at different layer. Wormhole attack is a network layer attack observed in MANET, which completely disrupts the communication channel. Among all of security thread worm hole is consider to be a very serious security thread over MANET. In wormhole two selfish node which is geographically very far away to each other, makes tunnel between each other to cover their actual location and try to believe that they are true neighbours and makes conversation through the wormhole tunnel. The goal of this paper to study wormhole attack, some detection methods and different techniques to prevent network from these attacks.

Background : Gilteritinib, an oral FMS-like tyrosine kinase 3 (FLT3) inhibitor, is approved for the treatment of adults with FLT3-mutated (FLT3mut+) relapsed or refractory (R/R) acute myeloid leukemia (AML) in the United States and many other countries/regions. However, not all respond to treatment and most patients eventually develop recurrent disease. Combining gilteritinib with other agents may improve response. Atezolizumab (840 mg intravenous [IV] every 2 weeks [Q2W]) + azacitidine demonstrated an overall response rate of 62% in hypomethylating agent-naive patients with higher-risk myelodysplastic syndrome (Gerds AT, et al. Blood. 2018;132[suppl 1]:466). Therefore, the safety and efficacy of combination therapy with gilteritinib and atezolizumab was investigated in an ongoing phase 1, open-label, single-arm, dose-escalation study (ClinicalTrials.gov identifier: NCT03730012) in adult patients with FLT3mut+ R/R AML. Methods : This phase 1 dose-escalation study enrolled adults with FLT3mut+ AML and Eastern Cooperative Oncology Group performance status of ≤2 who were refractory to ≥1 cycle of induction chemotherapy or relapsed after achieving remission with a prior therapy. Key exclusion criteria included AML secondary to prior chemotherapy for other neoplasms (except for myelodysplastic syndrome) and patients who have relapsed after allogeneic hematopoietic stem cell transplantation. Patients received gilteritinib 120 mg/day combined with atezolizumab 420 mg or 840 mg via IV infusion Q2W in 28-day cycles. Herein, we present safety and tolerability (dose-limiting toxicities [DLT] and treatment-emergent adverse events [TEAE]; primary end points). Decisions regarding DLTs and recommended phase 2 dose are determined by a dose evaluation committee. Composite complete remission (CRc) rate (primary end point), best response rate (secondary end point), and gilteritinib trough plasma concentrations (C trough; secondary end point) were also evaluated. Results : As of 13 June 2021, 3 patients received gilteritinib 120 mg/day + atezolizumab 420 mg Q2W (cohort 1) and 8 patients received gilteritinib 120 mg/day + atezolizumab 840 mg Q2W (cohort 2). Median (range) age was 82.0 (68-84) and 66.5 (20-87) years in cohorts 1 and 2, respectively. No patients received prior second-generation FLT3 inhibitor therapy. The median duration of gilteritinib exposure was 107.0 and 49.5 days in cohorts 1 and 2, respectively. Seven patients received ≥2 cycles of atezolizumab. No DLTs were reported in cohort 1; 2 patients (25%) reported DLTs in cohort 2 (1 occurrence each of increased alanine aminotransferase and encephalopathy). The most common TEAEs (≥30%) across both cohorts were febrile neutropenia (72.7%); fatigue (54.5%); dyspnea, muscular weakness, and decreased platelet count (45.5% each); and anemia, decreased appetite, diarrhea, dizziness, epistaxis, fall, and pyrexia (36.4% each; Table). Serious TEAEs were reported in 10 patients (91.0%). Treatment-related adverse events (TRAEs) were reported in 10 patients (90.9%), of which 9 patients (81.8%) reported serious TRAEs (only event reported in &gt;1 patient was febrile neutropenia [54.5%]). Study treatment was withdrawn for 8 patients (72.7%) due to TEAEs, of which TEAEs were considered TRAEs in 6 patients (54.5%). TEAEs lead to death in 3 patients (27.3%). Efficacy results will be provided at the time of presentation. Pharmacokinetic analyses suggested that C trough of gilteritinib in combination with atezolizumab (420 mg or 840 mg Q2W) was similar to single-agent gilteritinib in patients with R/R AML. Cohorts 1 and 2 showed similar gilteritinib C trough values. Conclusions: In this phase 1 dose-escalation study, the combination of gilteritinib and atezolizumab had an acceptable safety profile with no new safety signals identified for either agent. Owing to a strategic decision, the expansion phase of the study will not be conducted. The combinatorial prospect of gilteritinib observed in this study supports future studies of gilteritinib combination therapy. Figure 1 Figure 1. Disclosures Altman: Kuro Oncology: Consultancy; Syros: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; AbbVie: Consultancy; Glycomimetics: Membership on an entity's Board of Directors or advisory committees; BioSight: Consultancy, Other: Travel fees to attend an advisory meeting (I did not accept payment for the advisory board); Theradex: Consultancy. Bhatnagar: Sumitomo Dainippon Pharma: Research Funding; Novartis: Honoraria; Karyopharm Therapeutics Inc.: Honoraria, Research Funding; Astellas: Honoraria; Pfizer: Honoraria; Kite: Honoraria; Cell Therapeutics: Honoraria, Research Funding; Celgene: Honoraria. Abedin: Agios: Honoraria; AltruBio: Research Funding; Actinium: Research Funding; Amgen: Honoraria; Helsinn: Research Funding; Pfizer: Research Funding; Astellas Pharma Inc.: Research Funding. Przespolewski: Jazz: Research Funding. Schiller: Agios: Consultancy, Research Funding, Speakers Bureau; Kaiser Permanente: Consultancy; Leukemia & Lymphoma Society: Research Funding; Bio: Research Funding; Tolero: Research Funding; Forma: Research Funding; Takeda: Research Funding; Delta-Fly: Research Funding; Actuate: Research Funding; Jazz: Consultancy, Honoraria, Research Funding, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Elevate: Research Funding; Deciphera: Research Funding; Cyclacel: Research Funding; MedImmune: Research Funding; Johnson & Johnson: Current equity holder in publicly-traded company; Genentech-Roche: Research Funding; Gamida Cell Ltd.: Research Funding; Sanofi: Honoraria, Research Funding, Speakers Bureau; Eli Lilly: Research Funding; Actinium Pharmaceuticals, Inc: Research Funding; Abbvie: Research Funding; Arog: Research Funding; Biomed Valley Discoveries: Research Funding; Pharma: Consultancy; ASH foundation: Other: Chair-unpaid; Novartis: Consultancy, Research Funding; Sellas: Research Funding; Regimmune: Research Funding; PrECOG: Research Funding; Samus: Research Funding; Pfizer: Current equity holder in publicly-traded company, Research Funding; Onconova: Research Funding; Sangamo: Research Funding; Mateon: Research Funding; Karyopharm: Research Funding; Kite/Gilead: Honoraria, Research Funding, Speakers Bureau; FujiFilm: Research Funding; Ambit: Research Funding; Stemline Therapeutics, Inc.: Honoraria, Research Funding, Speakers Bureau; Geron: Research Funding; Amgen: Consultancy, Current equity holder in publicly-traded company, Honoraria, Research Funding, Speakers Bureau; Trovagene: Research Funding; Ono-UK: Consultancy, Research Funding; Ono: Consultancy; Incyte: Consultancy; Ariad: Research Funding; AstraZeneca: Consultancy; Daiichi-Sankyo: Research Funding; Constellation Pharmaceuticals: Research Funding; Celator: Research Funding; BMS/Celgene: Consultancy, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Astellas: Honoraria, Research Funding, Speakers Bureau; Bluebird Bio: Research Funding; Boehringer-Ingleheim: Research Funding; Cellerant: Research Funding; CTI Biopharma: Research Funding; Janssen: Research Funding; Kura Oncology: Research Funding; Pharmacyclics: Honoraria, Speakers Bureau; Millennium: Research Funding; National Marrow Donor Program: Research Funding; NIH: Research Funding; Onyx: Research Funding; Pharmamar: Research Funding; UC Davis: Research Funding; UCSD: Research Funding; Evidera: Consultancy; NCI: Consultancy; Novartis: Speakers Bureau. Gill: Astellas Pharma Global Development: Current Employment. Patel: Astellas Pharma Global Development: Current Employment. Fan: Astellas Pharma Global Development: Current Employment. Tiu: Astellas Pharma Global Development: Current Employment. Strickland: Sunesis: Research Funding; AbbVie: Other: Advisory Board; ArcherDx: Other: Advisory Board; Astellas: Other: Advisory Board; Genentech: Other: Advisory Board; Incyte: Other: Advisory Board; Jazz: Other: Advisory Board; Kite: Other: Advisory Board; Kura Oncology: Other: Advisory Board; Novartis: Other: Advisory Board; Pfizer: Other: Advisory Board; Syros: Other: Advisory Board. OffLabel Disclosure: New indication for atezolizumab