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This study demonstrates the development of a unique hybrid thermoplastic composite using reduced Graphene oxide (rGO) content and Zirconia (ZrO2) nanoparticles into the Ultra-High Molecular Weight Polyethylene (UHMWPE) biomaterials for continuous loading conditions. Specimens with different loadings of rGO (0 to 1.5 wt.%) and ZrO2 (5 to 10 wt.%) were fabricated using liquid phase ultrasonication followed by the hot press moulding method. The samples were analyzed using Thermogravimetric Analysis (TGA), Impact (Izod) testing, and Dynamic Mechanical Analysis (DMA). The developed material feasibility was assessed using Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray (EDX) analyses. The findings revealed that the 1 wt.% rGO/5 wt.% ZrO2/UHMWPE sample improved the storage modulus by 66.15%, and the Impact absorbed energy by 11.33% compared to the pristine UHMWPE. The proposed nanocomposite could be endorsed for artificial joints, prostheses, and other Artificial Bio-Bearing (ABB) applications.

Inclusion of a decoy alternative dominated by a target option, but not its competitor, typically leads to increased choice for the target over the competitor, known as the attraction effect. However, the reverse sometimes occurs, known as the repulsion effect. This research tested factors that moderate the repulsion effect in preferential choice scenarios with numerical attributes. Experiment 1 used a between-subjects design with a small set of consumer products and demonstrated robust repulsion effects that did not depend on the relative similarity of the decoy and target. Experiments 2 and 4 used a more powerful within-subjects design along with an expanded set of products and showed that repulsion effects were generally enhanced when the decoy and target had more similar attributes; however, the moderating effect of decoy–target similarity appeared to be fragile and sensitive to stimulus presentation factors. These findings provided mixed support for the hypothesis that the target is tainted by its proximity to the decoy. Experiments 3 and 5 tested whether the extremity of values on the attribute favoring the target moderates the repulsion effect. The results demonstrated that repulsion is more likely when all the alternatives have extremely high values on the target’s better attribute. Extremity of attribute values on the dimension favoring the target may result in a categorical assessment along that dimension and shift focus to the attribute favoring the competitor as one way to foster the repulsion effect.

Small‐cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with poor patient prognosis. However, the mechanisms that regulate SCLC progression and metastasis remain undefined. Here, we show that the expression of the slit guidance ligand 2 (SLIT2) tumor suppressor gene is reduced in SCLC tumors relative to adjacent normal tissue. In addition, the expression of the SLIT2 receptor, roundabout guidance receptor 1 (ROBO1), is upregulated. We find a positive association between SLIT2 expression and the Yes1 associated transcriptional regulator (YAP1)‐expressing SCLC subtype (SCLC‐Y), which shows a better prognosis. Using genetically engineered SCLC cells, adenovirus gene therapy, and preclinical xenograft models, we show that SLIT2 overexpression or the deletion of ROBO1 restricts tumor growth in vitro and in vivo. Mechanistic studies revealed significant inhibition of myeloid‐derived suppressor cells (MDSCs) and M2‐like tumor‐associated macrophages (TAMs) in the SCLC tumors. In addition, SLIT2 enhances M1‐like and phagocytic macrophages. Molecular analysis showed that ROBO1 knockout or SLIT2 overexpression suppresses the transforming growth factor beta 1 (TGF‐β1)/β‐catenin signaling pathway in both tumor cells and macrophages. Overall, we find that SLIT2 and ROBO1 have contrasting effects on SCLC tumors. SLIT2 suppresses, whereas ROBO1 promotes, SCLC growth by regulating the Tgf‐β1/glycogen synthase kinase‐3 beta (GSK3)/β‐catenin signaling pathway in tumor cells and TAMs. These studies indicate that SLIT2 could be used as a novel therapeutic agent against aggressive SCLC.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32–1.67]); Black patients (aOR 1.74; 95 CI 1.24–2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70–6.79) and Other (aOR 2.97; 95 CI 1.71–5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83–12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63–3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20–2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66–3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89–22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. Clinical trial number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701.

Abstract Background We aimed to evaluate the role of plasma fibrinogen and D-dimer as prognostic biomarkers in patients with non-muscle invasive bladder cancer (NMIBC). Methods The prospective study included 35 patients (30 males) with newly diagnosed NMIBC with no history of thromboembolic event or anti-coagulant intake or active infection and underwent complete trans-urethral resection between September 2020 and December 2021. Patients with deranged hepato-renal functions, refractory hypertension or diagnosed with COVID-19 infection with in one-month before surgery or routine follow-up were excluded. Follow-up was done as per NCCN guidelines. Fibrinogen and D-dimer levels were measured with in seven days of surgery or follow-up and analyzed for recurrence-free survival (RFS) and progression-free survival (PFS). Cox regression analyses were adopted to assess the influence of these two parameters on RFS and PFS. Results The mean age was 53.9 years with a median follow-up of 9-months. Nine had recurrence of which six had progression. The cut-off values of fibrinogen and D-dimer were 402.5 mg/dl and 0.55 µg/ml, respectively. Kaplan–Meier analysis demonstrated that high fibrinogen and D-dimer levels were significantly related to poor RFS and PFS (p

Abstract Introduction COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy. Methods Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors. Results Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3 months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 – 1.39; targeted therapy OR 1.89, 95% CI 0.64 – 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 – 2.35). Conclusions Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors.

The role of commensal bacterial microbiota in the pathogenesis of human malignancies has been a research field of incomparable progress in recent years. Although breast tissue is commonly assumed to be sterile, recent studies suggest that human breast tissue may contain a bacterial microbiota. In this study, we used an immune‐competent orthotopic breast cancer mouse model to explore the existence of a unique and independent bacterial microbiota in breast tumors. We observed some similarities in breast cancer microbiota with skin; however, breast tumor microbiota was mainly enriched with Gram‐negative bacteria, serving as a primary source of lipopolysaccharide (LPS). In addition, dextran sulfate sodium (DSS) treatment in late‐stage tumor lesions increased LPS levels in the breast tissue environment. We also discovered an increased expression of S100A7 and low level of TLR4 in late‐stage tumors with or without DSS as compared to early‐stage tumor lesions. The treatment of breast cancer cells with LPS increased the expression of S100A7 in breast cancer cells in vitro. Furthermore, S100A7 overexpression downregulated TLR4 and upregulated RAGE expression in breast cancer cells. Analysis of human breast cancer samples also highlighted the inverse correlation between S100A7 and TLR4 expression. Overall, these findings suggest that the commensal microbiota of breast tissue may enhance breast tumor burden through a novel LPS/S100A7/TLR4/RAGE signaling axis.

Summary: Background: Breakthrough SARS-CoV-2 infections following vaccination against COVID-19 are of international concern. Patients with cancer have been observed to have worse outcomes associated with COVID-19 during the pandemic. We sought to evaluate the clinical characteristics and outcomes of patients with cancer who developed breakthrough SARS-CoV-2 infections after 2 or 3 doses of mRNA vaccines. Methods: We evaluated the clinical characteristics of patients with cancer who developed breakthrough infections using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19; NCT04354701). Analysis was restricted to patients with laboratory-confirmed SARS-CoV-2 diagnosed in 2021 or 2022, to allow for a contemporary unvaccinated control population; potential differences were evaluated using a multivariable logistic regression model after inverse probability of treatment weighting to adjust for potential baseline confounding variables. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported. The primary endpoint was 30-day mortality, with key secondary endpoints of hospitalization and ICU and/or mechanical ventilation (ICU/MV). Findings: The analysis included 2486 patients, of which 564 and 385 had received 2 or 3 doses of an mRNA vaccine prior to infection, respectively. Hematologic malignancies and recent receipt of systemic anti-neoplastic therapy were more frequent among vaccinated patients. Vaccination was associated with improved outcomes: in the primary analysis, 2 doses (aOR: 0.62, 95% CI: 0.44–0.88) and 3 doses (aOR: 0.20, 95% CI: 0.11–0.36) were associated with decreased 30-day mortality. There were similar findings for the key secondary endpoints of ICU/MV (aOR: 0.60, 95% CI: 0.45–0.82 and 0.37, 95% CI: 0.24–0.58) and hospitalization (aOR: 0.60, 95% CI: 0.48–0.75 and 0.35, 95% CI: 0.26–0.46) for 2 and 3 doses, respectively. Importantly, Black patients had higher rates of hospitalization (aOR: 1.47, 95% CI: 1.12–1.92), and Hispanic patients presented with higher rates of ICU/MV (aOR: 1.61, 95% CI: 1.06–2.44). Interpretation: Vaccination against COVID-19, especially with additional doses, is a fundamental strategy in the prevention of adverse outcomes including death, among patients with cancer. Funding: This study was partly supported by grants from the National Cancer Institute grant number P30 CA068485 to C-YH, YS, SM, JLW; T32-CA236621 and P30-CA046592 to C.R.F; CTSA 2UL1TR001425-05A1 to TMW-D; ACS/FHI Real-World Data Impact Award, P50 MD017341-01, R21 CA242044-01A1, Susan G. Komen Leadership Grant Hunt to MKA. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH).

Abstract Background Molecular mechanisms underlying inflammation-associated breast tumor growth are poorly studied. S100A7, a pro-inflammatory molecule has been shown to enhance breast cancer growth and metastasis. However, the S100A7-mediated molecular mechanisms in enhancing tumor growth and metastasis are unclear. Methods Human breast cancer tissue and plasma samples were used to analyze the expression of S100A7, cPLA2, and PGE2. S100A7-overexpressing or downregulated human metastatic breast cancer cells were used to evaluate the S100A7-mediated downstream signaling mechanisms. Bi-transgenic mS100a7a15 overexpression, TNBC C3 (1)/Tag transgenic, and humanized patient-derived xenograft mouse models and cPLA2 inhibitor (AACOCF3) were used to investigate the role of S100A7/cPLA2/PGE2 signaling in tumor growth and metastasis. Additionally, CODEX, a highly advanced multiplexed imaging was employed to delineate the effects of S100A7/cPLA2 inhibition on the recruitment of various immune cells. Results In this study, we found that S100A7 and cPLA2 are highly expressed and correlate with decreased overall survival in breast cancer patients. Further mechanistic studies revealed that S100A7/RAGE signaling promotes the expression of cPLA2 to mediate its oncogenic effects. Pharmacological inhibition of cPLA2 suppressed S100A7-mediated tumor growth and metastasis in multiple pre-clinical models including transgenic and humanized patient-derived xenograft (PDX) mouse models. The attenuation of cPLA2 signaling reduced S100A7-mediated recruitment of immune-suppressive myeloid cells in the tumor microenvironment (TME). Interestingly, we discovered that the S100A7/cPLA2 axis enhances the immunosuppressive microenvironment by increasing prostaglandin E2 (PGE2). Furthermore, CO-Detection by indEXing (CODEX) imaging-based analyses revealed that cPLA2 inhibition increased the infiltration of activated and proliferating CD4+ and CD8+ T cells in the TME. In addition, CD163+ tumor associated-macrophages were positively associated with S100A7 and cPLA2 expression in malignant breast cancer patients. Conclusions Our study provides new mechanistic insights on the cross-talk between S100A7/cPLA2 in enhancing breast tumor growth and metastasis by generating an immunosuppressive TME that inhibits the infiltration of cytotoxic T cells. Furthermore, our studies indicate that S100A7/cPLA2 could be used as novel prognostic marker and cPLA2 inhibitors as promising drugs against S100A7-overexpressing aggressive breast cancer.

BACKGROUND: Astigmatism is a refractive error that accounts for 70% of refractive errors in the elderly population. It is important to be aware of the distribution, extent, and type of astigmatism in patients undergoing cataract surgery to guide in reducing postoperative spectacle dependency. AIM: To study the demography, amount, and pattern of astigmatism using partial coherence interferometry in patients of different age groups undergoing cataract surgery. MATERIALS AND METHODS: A cross-sectional observational study. Keratometry and demography data were collected for patients planned for cataract surgery at a tertiary care center between January 2018 and December 2019. It was done with noncontact partial coherence interferometry in patients above 50 years undergoing cataract surgery. RESULTS: Out of 385 patients, 216 (56%) were males and 169 (44%) were females. Astigmatism was more common in males than females (P = 0.00). Against-the-rule (ATR) astigmatism was found in 262 cases (68%), while with-the-rule (WTR) astigmatism was seen in 87 cases (23%). ATR was more common than WTR (P = 0.00). The number of patients with ATR seems to be increased with aging eyes and was more common between 61 and 70 years of age group (P = 0.00). The total amount of astigmatism increased with increasing age (P = 0.00029) which was found to be significant. Frthermore, there was a gradual change of WTR to ATR astigmatism with aging eyes. CONCLUSION: Two hundred and sixty-two cases (68%) had ATR astigmatism mainly seen in the age group of 61–70 years. Majority had astigmatism up to 1.0 D that can be easily managed by simple cost-effective keratorefractive procedures like on-axis incision, opposite clear corneal incision, and limbal relaxing incisions.

Background: Free radicals lead to inflammation, which in turn could intervene several chronic diseases including cancer. The promising scientific finding for anti-cancer properties of honey is an area of great interest. Objective: The present study was designed to investigate the in vitro biological effects (cytotoxic, and anti-inflammatory through differential inhibition of metalloproteinases and antioxidant) of unifloral Ajwain honey along with its physicochemical properties (pH, moisture, ash content, electrical conductivity, color, protein). Materials and methods: Three Ajwain honey samples (AJ-1, AJ-2, and AJ-3) were collected from different geographical origins of Western Ghats of India. Melissopalynological analysis was carried out to confirm uniflorality. Physicochemical analysis for ash, moisture content, pH, electrical conductivity, color, and total protein was estimated. Total polyphenol, total flavonoid content, and ferric reducing ability of plasma assay were determined using appropriate methods. The cytotoxic effect was assessed against breast cancer cells (MDA-MB-231) by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the anti-inflammatory activity was evaluated by gelatin zymography of matrix metalloproteinases MMP-2 and MMP-9 proteins. Results: Melissopalynological analysis confirmed pollens from Ajwain plant's and so-called Ajwain honey. MTT assay depicted inhibitory trend for all honey samples across the concentrations (6.25–100 mg/ml) as compared to untreated cells. Gelatin zymography of metalloproteinases (MMP-2 and MMP-9) showed inhibitory tendency in all Ajwain honey samples. The AJ-3 honey sample had the highest inhibition at 0.625%. A significant correlation between honey color, pH, and protein content was perceived throughout the study. Conclusion: This study highlights the in vitro biological evidence for possible therapeutic application of Ajwain honey samples in cytotoxic, anti-inflammatory, and antioxidant management as well as can be considered a potent source of supplements in human nutrition.

Retinal hemorrhage is common in Plasmodium falciparum and has been seldom reported with Plasmodium vivax. A 13-year-old girl presented with vision loss in both eyes after 1 week of intravenous artemisinin-based combination treatment for P. vivax. The patient had bilateral vision of 1/60 with retinal hemorrhage and internal limiting membrane (ILM) detachment. In view of heme-toxicity, the patient underwent an intravitreal tissue plasminogen activator along with 100% sulfur hexafluoride. Following this, hemorrhage resolved and vision improved to 6/9. Thus, although rare, retinal hemorrhage and ILM detachment can also be seen with P. vivax, albeit more common in P. falciparum.

With the advent of several new means of communication, safeguarding the confidentiality of messages has become more crucial. Financial institutions, virtual currencies, and government organizations are all examples of high-risk contexts where information exchanges need particular care. The importance of data security in preventing unauthorized access to data is emphasized. Several cryptographic methods for protecting the secrecy and integrity of data were compared. In this research, the proposed work includes a new Turbo Code-based encryption algorithm. The Turbo encoder’s puncturing process is controlled by a secret key, and a typical random sequence is generated to encrypt the data and fix any mistakes. Key generation utilizing pre-existing data eliminates the requirement for sending keys over a secure channel. Using recurrence relations and the Lower–Upper (LU) decomposition method, the presented study suggests a novel approach to message encryption and decryption. The resulting encrypted grayscale image has a very high level of security, with an entropy of 7.999, a variation from perfection of 0.0245, and a correlation of 0.0092 along the diagonal, 0.0009 along the horizontal, and −0.0015 along the vertical. Directly decrypted pictures have a Peak Signal-to-Noise Ratio (PSNR) of 56.22 dB, but the suggested approach only manages an embedding capacity of 0.5 bpp (bits per pixel). This may be achieved by decreasing the size of the location map by only 0.02 bpp.

In this manuscript, we introduce the concept of modified α-admissible contraction with the help of a simulation function and use this concept to establish some coincidence and common fixed-point theorems in metric space. An illustrative example that yields the main result is given. Also, several existing results within the frame of metric space are established. The main theorem was applied to derive the coincidence and common fixed-point results for α-admissible 𝒵-contraction.

The COVID-19 pandemic has caused disruption in everyone's lives globally. Optometrists, being primary health care professionals are at a higher risk of infection in their practices during these testing times. Optometrists and optical store owners need practically implementable guidelines as lockdown gets lifted in various parts of our country. As these practices gear up to provide eye examination and vision correction to people, they need to take necessary precautions to avoid any cross contaminations. Optometry Council of India guidelines were circulated among optometry and optical associations and among experts in various optometry specialty. A consensus among various bodies were arrived. These guidelines provide recommendation for optical and optometry practices.

Slit2 exerts antitumor effects in various cancers; however, the underlying mechanism, especially its role in regulating the immune, especially in the bone marrow niche, system is still unknown. Elucidating the behavior of macrophages in tumor progression can potentially improve immunotherapy. Using a spontaneous mammary tumor virus promoter-polyoma middle T antigen (PyMT) breast cancer mouse model, we observed that Slit2 increased the abundance of antitumor M1 macrophage in the bone marrow upon differentiation in vitro. Moreover, myeloablated PyMT mice injected with Slit2-treated bone marrow allografts showed a marked reduction in tumor growth, with enhanced recruitment of M1 macrophage in their tumor stroma. Mechanistic studies revealed that Slit2 significantly enhanced glycolysis and reduced fatty acid oxidation in bone marrow-derived macrophages (BMDMs). Slit2 treatment also altered mitochondrial respiration metabolites in macrophages isolated from healthy human blood that were treated with plasma from breast cancer patients. Overall, this study, for the first time, shows that Slit2 increases BMDM polarization toward antitumor phenotype by modulating immune-metabolism. Furthermore, this study provides evidence that soluble Slit2 could be developed as novel therapeutic strategy to enhance antitumor immune response.

Major challenges facing clinicians treating burn wounds are the lack of integration of treatment to wound, inadequate mechanical properties of treatments, and high infection rates which ultimately lead to poor wound resolution. Electrospun chitosan membranes (ESCM) are gaining popularity for use in tissue engineering applications due to their drug loading ability, biocompatibility, biomimetic fibrous structure, and antimicrobial characteristics. This work aims to modify ESCMs for improved performance in burn wound applications by incorporating elastin and magnesium-phosphate particles (MgP) to improve mechanical and bioactive properties. The following ESCMs were made to evaluate the individual components’ effects; (C: chitosan, CE: chitosan-elastin, CMg: chitosan-MgP, and CEMg: chitosan-elastin-MgP). Membrane properties analyzed were fiber size and structure, hydrophilic properties, elastin incorporation, MgP incorporation and in vitro release, mechanical properties, degradation profiles, and in vitro cytocompatibility with NIH3T3 fibroblasts. The addition of both elastin and MgP increased the average fiber diameter of CE (~400 nm), CMg (~360 nm), and CEMg (565 nm) compared to C (255 nm). Water contact angle analysis showed elastin incorporated membranes (CE and CEMg) had increased hydrophilicity (~50°) compared to the other groups (C and CMg, ~110°). The results from the degradation study showed mass retention of ~50% for C and CMg groups, compared to ~ 30% seen in CE and CEMg after 4 weeks in a lysozyme/PBS solution. CMg and CEMg exhibited burst-release behavior of ~6 µg/ml or 0.25 mM magnesium within 72 h. In vitro analysis with NIH3T3 fibroblasts showed CE and CEMg groups had superior cytocompatibility compared to C and CMg. This work has demonstrated the successful incorporation of elastin and MgP into ESCMs and allows for future studies on burn wound applications.

Recent studies revealed that ethnic differences in mechanistic target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK-1/2) signaling pathways might be associated with the development and progression of different human malignancies. The African American (AA) population has an increased rate of cancer incidence and mortality compared to the Caucasian American (CA) population. Although the socioeconomic differences across different ethnic groups contribute to the disparity in developing different cancers, recent scientific evidence indicates the association of molecular and genetic variations in racial disparities of different human malignancies. The mTOR and ERK-1/2 signaling pathways are one of the well-known oncogenic signaling mechanisms that regulate diverse molecular and phenotypic aspects of normal as well as cancer cells in response to different external or internal stimuli. To date, very few studies have been carried out to explore the significance of racial disparity with abnormal mTOR and ERK-1/2 kinase signaling pathways, which may contribute to the development of aggressive human cancers. In this review, we discuss the differential regulation of mTOR and ERK-1/2 kinase signaling pathways across different ethnic groups, especially between AA and CA populations. Notably, we observed that key signaling proteins associated with mTOR and ERK-1/2 pathway including transforming growth factor-beta (TGF-β), Akt, and VEGFR showed racially disparate expression in cancer patients. Overall, this review article encompasses the significance of racially disparate signaling molecules related to mTOR/ERK1/2 and their potential in developing tailor-made anti-cancer therapies.

Background: Fruits and vegetables are important components of the human diet since they provide essential nutrients that are required for most of the reactions occurring in the body. However, indiscriminate and overuse of pesticides damage agriculture and environment, but the pesticide residues on food products affect the health. Aim and Objective: The present study aimed to assess the Knowledge, Attitude and Practices (KAP) among the farmers of Belagavi taluka, regarding the pesticide use and to determine pesticide residues in commonly used vegetables. Materials and Methods: The present cross-sectional study included a total of 200 farmers selected randomly from 4 divisions of Belagavi taluka. Questionnaire was developed to assess the KAP. Fresh tomatoes and chilies were used as samples, fine homogenized sample (200 g) was extracted with ethyl acetate and analyzed using gas chromatography-mass spectrometry. Results: Most of them were aware of the precautions to be taken during pesticide use. However, not all farmers followed the measures. Maximum of them used pesticides (n=150), followed recommended method (n=130) and concentration (n=152). Pesticide residues found in chili and tomato samples exceeded the maximum residue limit. Conclusion: Chlorpyrifos and ethion in tomato sample, and chlorpyrifos and cypermethrin in chillies sample were the pesticide residues. Protective measures followed by the farmers was poor. Therefore, the knowledge of the farmers should be upgraded and, camps should be conducted periodically to monitor pesticide residues and health of the farmers.

Grosourdya muriculata (Rchb.f.) R. Rice (Orchidaceae) is a little known epiphytic, endemic orchid from the Andaman & Nicobar Islands in India. The present article provides the detailed taxonomy, ecology, distribution, conservation status, and photographic account of the species. The data collected from field surveys indicates that the status of the species needs to be downgraded to Near Threatened as per the criteria of IUCN (2018).

Chemotherapy forms the backbone of current treatments for many patients with advanced non-small-cell lung cancer (NSCLC). However, the survival rate is low in these patients due to the development of drug resistance, including cisplatin resistance. In this study, we developed a novel strategy to combat the growth of cisplatin-resistant (CR) NSCLC cells. We have shown that treatment with the plant-derived, non-psychotropic small molecular weight molecule, cannabidiol (CBD), significantly induced apoptosis of CR NSCLC cells. In addition, CBD treatment significantly reduced tumor progression and metastasis in a mouse xenograft model and suppressed cancer stem cell properties. Further mechanistic studies demonstrated the ability of CBD to inhibit the growth of CR cell lines by reducing NRF-2 and enhancing the generation of reactive oxygen species (ROS). Moreover, we show that CBD acts through Transient Receptor Potential Vanilloid-2 (TRPV2) to induce apoptosis, where TRPV2 is expressed on human lung adenocarcinoma tumors. High expression of TRPV2 correlates with better overall survival of lung cancer patients. Our findings identify CBD as a novel therapeutic agent targeting TRPV2 to inhibit the growth and metastasis of this aggressive cisplatin-resistant phenotype in NSCLC.

OBJECTIVE: Folate and Vitamin B12 (B12) are crucial for normal growth, development, and cellular functions. The aim of this study was to determine the effect of required and excess folic acid (FA) concentration and imbalance of FA and B12 caused due to folate fortification on hepatocytes health and function in vitro. MATERIALS AND METHODS: Human hepatocellular carcinoma (HepG2) cells were cultured in FA and B12 deficient media for 15 days and further were supplemented with required FA: (6 μM) and excess FA: (60 μM) individually and in combination with B12: (500 nM). We assessed HepG2 proliferation, viability, tumor necrosis factor-alpha (TNFα) and methylenetetrahydrofolate reductase (MTHFR) mRNA expression, homocysteine, and malondialdehyde levels. RESULTS: Supplementation of B12 with FA increased proliferation as compared to only FA supplemented group. FA and B12 deficient cells and excess FA supplementation resulted in decreased viability. Supplementation of B12 at both FA concentrations increased (P < 0.05) cell viability. In the presence of B12 oxidative stress, TNFα mRNA and TNFα levels in cell lysate significantly decreased (P < 0.05) in both FA supplemented cells as compared to excess FA cells. Homocysteine levels significantly decreased (P < 0.05) in cells supplemented with normal FA + B12 as compared to excess FA supplemented cells and FA and B12 deficient cells. Supplementation of excess FA significantly downregulated (P < 0.05) MTHFR mRNA levels as compared to required FA cells. Combination of FA + B12 significantly upregulated (P < 0.01) MTHFR mRNA levels as compared to excess FA. CONCLUSION: These results accord the promoting effect of B12 with FA in developing nations like India where B12 deficiency is common while the concentration of folate is adequate.

Background: Arjunarishta (AA), a formulation used as cardiotonic is a hydroalcoholic formulation of Terminalia arjuna (Roxb.) Wight and Arn. (TA) belonging to family Combretaceae. Objective: To evaluate the anti-hyperglycemic and anti-hyperlipidemic effect of Arjunarishta on high-fat diet fed animals. Materials and methods: High-fat diet fed (HFD) Wistar rats were randomly divided into three groups and treated with phytochemically standardized Arjunarishta (1.8 ml/kg), and hydroalcoholic extract of T. arjuna (TAHA) (250 mg/kg) and rosuvastatin (10 mg/kg), for 3 months. Intraperitoneal glucose tolerance test, blood biochemistry, liver triglyceride and systolic blood pressure were performed in all the groups. Effect of these drugs on the expression of tumor necrosis factor-α (TNF-α) and insulin receptor substrate-1 (IRS-1) and peroxisome proliferators activated receptor γ coactivator 1-α (PGC-1α) were studied in liver tissue using Quantitative Real-time PCR. Results: HFD increased fasting blood glucose, liver triglyceride, systolic blood pressure and gene expression of TNF-α, IRS-1 and PGC-1α. Treatment of AA and TAHA significantly reduced fasting blood glucose, systolic blood pressure, total cholesterol and triglyceride levels. These treatments significantly decreased gene expression of TNF-α (2.4, 2.2 and 2.6 fold change); increased IRS-1 (2.8, 2.9 and 2.8 fold change) and PGC-1α (2.9, 3.7 and 3.3 fold change) as compared to untreated HFD. Conclusion: Anti-hyperglycemic, anti-hyperlipidemic effect of Arjunarishta may be mediated by decreased TNF-α and increased PGC-1α and IRS-1. Keywords: Rosuvastatin, Type 2 diabetes, Insulin sensitizer genes, Arjunarishta

Dapsone (4,4′- diaminodiphenylsulfone) is the parent compound of the sulfones, and it has potent antiparasitic, anti-inflammatory, and immunomodulatory effects. It is used in the treatment of leprosy, dermatitis herpetiformis, and prophylactically to prevent Pneumocystis pneumonia and toxoplasmosis in patients unable to tolerate trimethoprim with sulfamethoxazole. We hereby report a case of dapsone toxicity who developed pure red cell aplasia and cholestatic jaundice in a suspected case of dermatitis herpetiformis. Patient had an excellent response to corticosteroids after withdrawal of dapsone.

Recent studies have demonstrated that racial differences can influence breast cancer incidence and survival rate. African American (AA) women are at two to three fold higher risk for breast cancer than other ethnic groups. AA women with aggressive breast cancers show worse prognoses and higher mortality rates relative to Caucasian (CA) women. Over the last few years, effective treatment strategies have reduced mortality from breast cancer. Unfortunately, the breast cancer mortality rate among AA women remains higher compared to their CA counterparts. The focus of this review is to underscore the racial differences and differential regulation/expression of genetic signatures in CA and AA women with breast cancer. Moreover, immune cell infiltration significantly affects the clinical outcome of breast cancer. Here, we have reviewed recent findings on immune cell recruitment in the tumor microenvironment (TME) and documented its association with breast cancer racial disparity. In addition, we have extensively discussed the role of cytokines, chemokines, and other cell signaling molecules among AA and CA breast cancer patients. Furthermore, we have also reviewed the distinct genetic and epigenetic changes in AA and CA patients. Overall, this review article encompasses various molecular and cellular factors associated with breast cancer disparity that affects mortality and clinical outcome.

Mutations in the small heat shock proteins α-crystallins have been linked to autosomal dominant cataracts in humans. Extensive studies in vitro have revealed a spectrum of alterations to the structure and function of these proteins including shifts in the size of the oligomer, modulation of subunit exchange and modification of their affinity to client proteins. Although mouse models of these mutants were instrumental in identifying changes in cellular proliferation and lens development, a direct comparative analysis of their effects on lens proteostasis has not been performed. Here, we have transgenically expressed cataract-linked mutants of αA- and αB-crystallin in the zebrafish lens to dissect the underlying molecular changes that contribute to the loss of lens optical properties. Zebrafish lines expressing these mutants displayed a range of morphological lens defects. Phenotype penetrance and severity were dependent on the mutation even in fish lines lacking endogenous α-crystallin. The mechanistic origins of these differences were investigated by the transgenic co-expression of a destabilized human γD-crystallin mutant. We found that the R49C but not the R116C mutant of αA-crystallin drove aggregation of γD-crystallin, although both mutants have similar affinity to client proteins in vitro. Our working model attributes these differences to the propensity of R49C, located in the buried N-terminal domain of αA-crystallin, to disulfide crosslinking as previously demonstrated in vitro. Our findings complement and extend previous work in mouse models and emphasize the need of investigating chaperone/client protein interactions in appropriate cellular context.

The aims of this paper is to introduce new approach of separate sets, disconnected sets and connected sets called α- τ-separate sets, α- τ-disconnected sets and α- τ-connected sets of topological spaces with the help of α-open and α-closed sets. On the basis of new introduce approach, some relationship of α- τ-disconnected and α- τ-connected set with α- τ-separate sets have been investigated thoroughly.

Purpose. To conduct an in vitro strength test for the Joshi External Stabilising System (JESS) for stabilisation of tibial fractures using a cadaveric tibia and steel rods. Methods. The configuration of the JESS specimens was based on a 62-year-old man with a metaphyseal tibial fracture. Two types of JESS specimens were prepared, using either the tibia of an average male adult cadaver (n=1) or stainless steel cylindrical rods (n=3). The strength of the JESS rather than that of the rods was measured using a universal testing machine. The axial compressive load was gradually increased at 1 mm/min to 35 N. Axial deformation of the fracture fragment was recorded. Each experiment was repeated 3 times in identical manner. A finite element analysis of the JESS was developed. The axial compressive loads and corresponding interfragmentary displacement in the experimental specimens and in the finite element analysis were compared. Results. The mean strength of the JESS was 32.5 N/mm in experiments and 35.3 N/mm in finite element analysis; the difference was 8.4%. The interfragmentary displacement was directly proportional to the axial compressive load. Conclusion. The strength of the JESS is one fourth of that of the Ilizarov fixator, and therefore not suitable for full load bearing activities.