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Ayurveda being a most ancient system of medicine has given a proper deserving position to women that is Stree, defining her as Apathyanam Moolam (the root cause of progeny). In Synch with this Kamashastra has portrayed women with esteem. Thus, stating the importance of female’s reproductive role in procreating and sustenance of human rays. Female sexual identity and conduct, as well as the physiological, psychological, social, cultural, political, and spiritual or religious components of sexual activity, all fall under the umbrella of human female sexuality, which covers a wide range of behavior activities. This sexuality is encountered and revealed through thoughts, desire, belief, fantasy, and relationship. The pursuit of sexual pleasure is a key motivating factor in sexual activity. Classical texts of Kamashastra have captured this sexual pleasure and portrayed them with impeccable accuracy in both genders providing an ample sexual motivation for sexual activity. This sexual activity is considered to attain fruition when the partner reaches the epitome of orgasm, among these partners we have given more importance to the female as she is a being of multiple sexual orgasms. Hence the main aim of this article is to understand and analyze the female sexual orgasm, and different approaches to attain it. Thus, an attempt is made to decode the mystery of female sexuality in the heritage of Kamasutra through Ayurveda.

Cancer immunotherapies, such as immune checkpoint blockade or adoptive T-cell transfer, can lead to durable responses in the clinic, but response rates remain low due to undefined suppression mechanisms. Solid tumors are characterized by a highly acidic microenvironment that might blunt the effectiveness of antitumor immunity. In this study, we directly investigated the effects of tumor acidity on the efficacy of immunotherapy. An acidic pH environment blocked T-cell activation and limited glycolysis in vitro. IFNγ release blocked by acidic pH did not occur at the level of steady-state mRNA, implying that the effect of acidity was posttranslational. Acidification did not affect cytoplasmic pH, suggesting that signals transduced by external acidity were likely mediated by specific acid-sensing receptors, four of which are expressed by T cells. Notably, neutralizing tumor acidity with bicarbonate monotherapy impaired the growth of some cancer types in mice where it was associated with increased T-cell infiltration. Furthermore, combining bicarbonate therapy with anti-CTLA-4, anti-PD1, or adoptive T-cell transfer improved antitumor responses in multiple models, including cures in some subjects. Overall, our findings show how raising intratumoral pH through oral buffers therapy can improve responses to immunotherapy, with the potential for immediate clinical translation. Cancer Res; 76(6); 1381–90. ©2015 AACR.

Supplemental Figure S1: Inhibition of PI3 kinase signaling leads to loss of T cell function. Activated T cells were cultured at pH 6.6 or 7.4 for 24h in presence or absence of the PI3K Supplemental Figure S2: OT-1 T cell metabolism. OT-1 T cells were cultured with OVASIINFEKL peptide for 48 hours at either pH 6.6 or 7.4. Cells were subsequently metabolically profiled using a Seahorse XF-96 analyzer. Supplemental Figure S3: Knocking out the acid sensor, TDAG8, does not rescue IFN-gamma production by T cells. T cells were isolated from TDAG8 k/o or wild-type (WT) mice and stimulated in the presence of 10 ug/ml plate-bound anti-CD3 antibodies for 48 hours at pH 6.6 or 7.4. Supernatants were collected and IFN-gamma was measured by ELISA. Supplemental Figure S4: Representative B16 tumors in mice treated with anti-CTLA4 antibodies with or without buffer therapy. Supplemental Figure S5: Buffer therapy has little effect on systemic T cell activity in B16- bearing mice treated with anti-PD-1 antibody. inhibitor BEZ-235.

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The valayan tribes of Somagiri hills, Eastern Ghats of Tamil Nadu, India were interviewed during January 2020 to November 2021 through a survey instrument to record the details of ethnomedicines currently used by them to cure and manage various human ailments. The informants who had cooperated with the researchers have also revealed the method of drug preparation and the application besides the places of collection in and around the Somagiri hills. The present study has revealed that a total of 107 medicinal plants belonging to 47 angiosperm families and one pteridophyte family are being traditionally used to cure 19 different human ailments. Fabaceae (with 18 plant species) is found topping the list of ethnomedicines of the valayan community. Of the 107 ethnomedicinal plants verified using IUCN Red List, Chlorophytum borivilianum, and Aegle marmelos gain greater conservation significance owing to their enlistment as Endangered and Near Threatened categories, respectively. Of the different plant parts, leaves were the most widely used plant part which accounted for 41 species, followed by whole plant (36 species) and bark (21 species). The majority of plants species were used for Dermatological diseases (25%), followed by Gastro-intestinal diseases (14%), Poisonous bites (10%), General debility (9%), and Skeleto-Muscular System Disorders (7%). The majority of the ethnomedicinal drug preparation type was in the form of juice from 50% plants. The results confirm that the valayan tribes depended heavily on the medicinal plants of the Somagiri hills inhabited by them for their health care and so, stressing the need for revival of interest in ethnomedicine. Documentation of ethnobotanical knowledge is a valuable effort as it may carry secret solution for cancer and emerging forms of dreadful diseases like COVID-19 and Omicron.

Purpose: To study the outcome of amniotic membrane graft versus conjunctival autograft after primary pterygium excision surgeries amongst various genders and age groups and to compare recurrences, complications and pre and post-operative astigmatism in various grades of nasal and temporal pterygium. Materials and Methods: A total of 90 eyes of 90 patients with previously unoperated primary pterygium were enrolled in a randomised control trial. The patients had a follow-up of 6 months during analysis and the results were compared retrospectively with patients who had pterygium excision surgeries with conjunctival autografts performed by the same surgeon. Results: A higher proportion of males underwent grafting with amniotic membrane while more females underwent conjunctival autografting. The p value =0.011 was significant. A higher proportion of patients were between the ages of 31-40 years and the p value=0.001 was significant. A majority of patients from both groups had nasal pterygium with p value=0.026 being significant. The overall astigmatism pre operatively from both groups=0.431 and 0.143 postoperatively. Conclusion: Amniotic membrane grafting in primary pterygium surgery led to fewer complications, recurrences and astigmatism postoperatively and was more useful in patients who may have lesser amounts of conjunctiva for future surgeries. Keywords: Pterygium excision, Amniotic membrane graft, Conjunctival autograft.

The HER3/ERBB3 receptor is an oncogenic receptor tyrosine kinase that forms heterodimers with EGFR family members and is overexpressed in numerous cancers. HER3 overexpression associates with reduced survival and acquired resistance to targeted therapies, making it a potential therapeutic target in multiple cancer types. Here, we report on immunogenic, promiscuous MHC class II-binding HER3 peptides, which can generate HER3-specific CD4

Background: The receptor tyrosine kinase inhibitor (TKI) Sunitinib has proven useful in the treatment of a variety of tumors. Sunitinib has shown therapeutic activity in patients with metastatic renal cell carcinoma and currently represents a frontline therapy for this disease. The immune modulatory effect of Sunitinib on immune cells within the tumor microenvironment has been well documented. Here, we developed a novel 3D ex-vivo platform (3D-EXplore) using fresh patient tumor samples with intact stromal components and tumor immune microenvironment to assess the therapeutic efficacy of Sunitinib. Methods: All tumor samples were obtained with patient consent and relevant IRB approval. Unpropagated 3D tumoroids with intact TME measuring 150 µm in size were prepared from fresh tumor samples of renal cell carcinoma using a proprietary technology developed at Nilogen Oncosystems. Tumoroids prepared from each patient’s tumor sample were pooled to represent the tumor heterogeneity and treated ex vivo with Sunitinib for 48h to detect treatment-mediated changes in tumor immune cell composition including CD4 and CD8 T-cells, NK cells, and macrophages. Additionally, we analyzed treatment-mediated changes in T-cell activation and phagocytic activity of myeloid cells. Results: Multiparameter flow analysis revealed that Sunitinib treatment led to an increase in CD8+CD25+ central memory-like phenotype and increased granzyme B expression in CD4 and CD8+ T cells indicating T cell activation. Furthermore, multiparameter flow cytometry analysis showed increased EdU uptake by CD8 and NK cells with sunitinib treatment, while cytokine release assays demonstrated increased IFN-γ and IL-2 production accompanied by downregulation of IL-10 and IL-6 cytokines. We observed Sunitinib mediated phagocytotic activity by tumor resident myeloid macrophages, monocytes, and dendritic cells using a quantitative phagocytosis assay. Conclusions: These results demonstrate that 3D-EXplore using fresh tumor samples provides a clinically relevant platform to assess drug response and serves as a critical tool for reflecting the true intact tumor microenvironment for novel immune-oncology drug development. Citation Format: Brittany Bunch, Krithika N. Kodumudi, Jared Ehrhart, Matt Weitzman, Olivia MacIntosh, Kelly Sussman, Soner Altiok. Application of the 3d fresh patient tumoroid platform 3d-explore to assess the immunomodulatory and phagocytic activity of the receptor tyrosine kinase inhibitor, Sunitinib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 246.

OBJECTIVE: The aging HIV population has increased comorbidity burden and consequently non-antiretroviral (ARV) medication utilization. Many non-ARV medications have known neurocognitive-adverse effects (“NC-AE medications”). We assessed the cognitive effects of NC-AE medications in HIV+ and HIV− women. METHODS: 1558 participants (1037 HIV+; mean age 46) from the Women’s Interagency HIV Study completed a neuropsychological test battery between 2009 and 2011. The total number of NC-AE medications and subgroups (e.g., anticholinergics) were calculated based on self-report. Generalized linear models for non-normal data were used to examine the cognitive burden of medications and factors which exacerbate these effects. RESULTS: HIV+ women reported taking more NC-AE medications versus HIV− women (p1 anticholinergic medications. HIV-serostatus differences in performance on learning and psychomotor speed were also greatest among women taking 1 or more anxiolytics/anticonvulsants and 1 or more opioids, respectively. CONCLUSIONS: HIV+ women have increased cognitive vulnerabilities to anticholinergic, anxiolytic/anticonvulsant, and opioid medications. Potential synergy between these medications and HIV may explain some HIV-related cognitive impairments. It may be important clinically to consider these specific types of medications as a contributor to impaired cognitive performance in HIV+ women and assess the cost/benefit of treatment dosage for underlying conditions.

Despite the availability of effective antiretroviral therapies, cognitive impairment (CI) remains prevalent in HIV-infected (HIV+) individuals. Evidence from primarily cross-sectional studies, in predominantly male samples, implicates monocyte- and macrophage-driven inflammatory processes linked to HIV-associated CI. Thus, peripheral systemic inflammatory markers may be clinically useful biomarkers in tracking HIV-associated CI. Given sex differences in immune function, we focused here on whether mean and intra-individual variability in inflammatory marker-predicted CI in HIV+ and HIV- women. Seventy-two HIV+ (36 with CI) and 58 HIV- (29 with CI) propensity-matched women participating in the Women's Interagency HIV Study completed a neuropsychological battery once between 2009 and 2011, and performance was used to determine CI status. Analysis of 13 peripheral immune markers was conducted on stored biospecimens at three time points (7 and 3.5years before neuropsychological data collection and concurrent with data collection). HIV+ women showed alterations in 8 immune markers compared to HIV- women. The strongest predictors of CI across HIV+ and HIV- women were lower mean soluble tumor necrosis factor receptor I (sTNFRI) levels, higher mean interleukin (IL)-6 levels, and greater variability in C-reactive protein (CRP) and matrix metalloproteinase (MMP)-9 (p values