Immune-Inhibitory Gene Expression is Positively Correlated with Overall Immune Activity and Predicts Increased Survival Probability of Cervical and Head and Neck Cancer Patients

Background: Limited immunotherapy options are approved for the treatment of cervical cancer and only 10–25% of patients respond effectively to checkpoint inhibition monotherapy. To aid the development of novel therapeutic immune targets, we aimed to explore survival-associated immune biomarkers and co-expressed immune networks in cervical cancer. Methods: Using The Cancer Genome Atlas (TCGA) Cervical Squamous Cell Carcinoma (CESC) data (n = 304), we performed weighted gene co-expression network analysis (WGCNA), and determined which co-expressed immune-related genes and networks are associated with survival probability in CESC patients under conventional therapy. A “Pan-Immune Score” and “Immune Suppression Score” was generated based on expression of survival-associated co-expressed immune networks and immune suppressive genes, which were subsequently tested for association with survival probablity using the TCGA Head Neck Squamous Cell Carcinoma (HNSCC) data (n = 528), representing a second SCC cancer type. Results: In CESC, WGCNA identified a co-expression module enriched in immune response related genes, including 462 genes where high expression was associated with increased survival probability, and enriched for genes associated with T cell receptor, cytokine and chemokine signaling. However, a high level of expression of 43 of the genes in this module was associated with decreased survival probability but were not enriched in particular pathways. Separately, we identified 20 genes associated with immune suppression including inhibitory immune checkpoint and regulatory T cell-related genes, where high expression was associated with increased survival probability. Expression of these 20 immune suppressive genes (represented as “Immune Suppression Score”) was highly correlated with expression of overall survival-associated immune genes (represented as “Pan-Immune Score”). However, high expression of seven immune suppression genes, including TWEAK-R, CD73, IL1 family and TGFb family genes, was significantly associated with decreased survival probability. Both scores also significantly associated with survival probability in HNSCC, and correlated with the previously established “Immunophenoscore.” Conclusion: CESC and HNSCC tumors expressing genes predictive of T cell infiltrates (hot tumors) have a better prognosis, despite simultaneous expression of many immune inhibitory genes, than tumors lacking expression of genes associated with T cell infiltrates (cold tumors) whether or not these tumor express immune inhibitory genes.</p

Lack of awareness of erectile dysfunction in many men with risk factors for erectile dysfunction

<p>Abstract</p> <p>Background</p> <p>Men with erectile dysfunction often have concurrent medical conditions. Conversely, men with these conditions may also have underlying erectile dysfunction. The prevalence of unrecognized erectile dysfunction in men with comorbidities commonly associated with erectile dysfunction was determined in men invited to participate in a double-blind, randomized, placebo-controlled trial of sildenafil citrate.</p> <p>Methods</p> <p>Men ≥30 years old presenting with ≥1 erectile dysfunction risk factor (controlled hypertension, hypercholesterolemia, smoking, metabolic syndrome, stable coronary artery disease, diabetes, depression, lower urinary tract symptoms, obesity [body mass index ≥30 kg/m²] or waist circumference ≥40 inches), and not previously diagnosed with erectile dysfunction were evaluated. The screening question, "Do you have erectile dysfunction?," with responses of "no," "yes," and "unsure," and the Erectile Function domain of the International Index of Erectile Function (IIEF-EF) were administered.</p> <p>Results</p> <p>Of 1084 men screened, 1053 answered the screening question and also had IIEF-EF scores. IIEF-EF scores indicating erectile dysfunction occurred in 71% (744/1053), of whom 54% (399/744) had moderate or severe erectile dysfunction. Of 139 answering "yes," 526 answering "unsure," and 388 answering "no," 96%, 90%, and 36%, respectively, had some degree of erectile dysfunction. The mean±SD (range) number of risk factors was 2.9 ± 1.7 (3-8) in the "yes" group, 3.2 ± 1.7 (3-9) in the "unsure" group, and 2.6 ± 1.5 (2-8) in the "no" group.</p> <p>Conclusion</p> <p>Although awareness of having erectile dysfunction was low, most men with risk factors had IIEF-EF scores indicating erectile dysfunction. Erectile dysfunction should be suspected and assessed in men with risk factors, regardless of their apparent level of awareness of erectile dysfunction.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier NCT00343200.</p

Examining the Relationships between Experienced and Anticipated Stigma in Health Care Settings, Patient-Provider Race Concordance, and Trust in Providers among Women Living with HIV

Stigma in health care settings can have negative consequences on women living with HIV, such as increasing the likelihood of missed visits and reducing trust in their clinical providers. Informed by prior stigma research and considering knowledge gaps related to the effect of patient-provider race concordance, we conducted this study to assess if patient-provider race concordance moderates the expected association between HIV-related stigma in health care settings and patients' trust in their providers. Moderation analyses were conducted using Women's Interagency HIV Study data (N = 931). We found significant main effects for patient-provider race concordance. Higher experienced stigma was associated with lower trust in providers in all patient-provider race combinations [White-White: B =-0.89, standard error (SE) = 0.14, p = 0.000, 95% confidence interval, CI (-1.161 to-0.624); Black patient-White provider: B =-0.19, SE = 0.06, p = 0.003, 95% CI (-0.309 to-0.062); and Black-Black: B =-0.30, SE = 0.14, p = 0.037, 95% CI (-0.575 to-0.017)]. Higher anticipated stigma was also associated with lower trust in providers [White-White: B =-0.42, SE = 0.07, p = 0.000, 95% CI (-0.552 to-0.289); Black patient-White provider: B =-0.17, SE = 0.03, p = 0.000, 95% CI (-0.232 to-0.106); and Black-Black: B =-0.18, SE = 0.06, p = 0.002, 95% CI (-0.293 to-0.066)]. Significant interaction effects indicated that the negative associations between experienced and anticipated HIV-related stigma and trust in providers were stronger for the White-White combination compared with the others. Thus, we found that significant relationships between HIV-related experienced and anticipated stigma in health care settings and trust in providers exist and that these associations vary across different patient-provider race combinations. Given that reduced trust in providers is associated with antiretroviral medication nonadherence and higher rates of missed clinical visits, interventions to address HIV-related stigma in health care settings may improve continuum of care outcomes

Resilience and Optimism as Moderators of the Negative Effects of Stigma on Women Living with HIV

Resilience and optimism may not only have main effects on health outcomes, but may also moderate and buffer negative effects of stressors. We examined whether dispositional resilience and optimism moderate the associations between HIV-related stigma in health care settings and health-related outcomes (trust in HIV health care providers and depression symptoms) among women living with HIV (WLHIV). One thousand four hundred five WLHIV in nine US cities completed validated questionnaires for cross-sectional analyses. Higher self-reported experienced and anticipated stigma and lower resilience and optimism were associated with higher depression symptoms and with lower trust in HIV providers. Importantly, resilience moderated the effects of experienced stigma (but not of anticipated stigma): When resilience was high, the association of experienced stigma with higher depression symptoms and lower trust in HIV providers was weaker compared with when resilience was low. Further, significant moderation effects suggested that when optimism was high, experienced and anticipated stigma was both less strongly associated with depression symptoms and with lower trust in one's HIV care providers compared with when optimism was low. Thus, the effects of experienced stigma on depression symptoms and provider trust were moderated by both resilience and optimism, but the effects of anticipated stigma were moderated only by optimism. Our findings suggest that in addition to their main effects, resilience and optimism may function as buffers against the harmful effects of stigma in health care settings. Therefore, optimism and resilience may be valuable intervention targets to reduce depression symptoms or improve trust in providers among populations that experience or anticipate stigma, such as WLHIV

Patient Health Literacy and Communication with Providers Among Women Living with HIV: A Mixed Methods Study

In this mixed-methods study, we examine the relationship between provider communication and patient health literacy on HIV continuum of care outcomes among women living with HIV in the United States. We thematically coded qualitative data from focus groups and interviews (N = 92) and conducted mediation analyses with quantitative survey data (N = 1455) collected from Women’s Interagency HIV Study participants. Four qualitative themes related to provider communication emerged: importance of respect and non-verbal cues; providers’ expressions of condescension and judgement; patient health literacy; and unclear, insufficient provider communication resulting in diminished trust. Quantitative mediation analyses suggest that higher health literacy is associated with higher perceived patient–provider interaction quality, which in turn is associated with higher levels of trust in HIV providers, improved antiretroviral medication adherence, and reduced missed clinical visits. Findings indicate that enhancing provider communication and bolstering patient health literacy could have a positive impact on the HIV continuum of care

Measuring Surface and Interfacial Tension In Situ in Microdripping Mode for Electrohydrodynamic Applications

Walking on water is made possible, at least for tiny insects, by molecular interaction at the interfaces of dissimilar materials. Impact of these interactions&mdash;surface tension (SFT) and, more broadly, interfacial tension (IFT)&mdash;is particularly evident at micro and nano sizescales. Thus, implications of walking on water can be significant for SFT or IFT (S/IFT)-driven nanofabrication technologies, such as electrohydrodynamic atomization (EHDA), in developing next generation biomimetic microphysiological systems (MPS) and drug delivery systems (DDS). However, current methods for estimating S/IFT, based on sessile drops or new surface formation on a ring or plate, are unsuitable for integration with EHDA assemblies used in electrospinning and electrospraying. Here, we show an in situ method for estimating S/IFT specifically devised for EHDA applications using signal processing algorithms that correlate the frequency and periodicity of liquid dispensed in EHDA microdripping mode with numerical solutions from computational fluid dynamics (CFD). Estimated S/IFT was generally in agreement with published ranges for water&ndash;air, 70% ethanol&ndash;air, chloroform&ndash;air, and chloroform&ndash;water. SFT for solutions with surfactants decreased with increasing concentrations of surfactant, but at relatively higher than published values. This was anticipated, considering that established methods measure SFT at boundaries with asymmetrically high concentrations of surfactants which lower SFT

A Singhal.pmd

Free radicals had been implicated in several human diseases e.g. atherosclerosis, arthritis, ischemia and reperfusion injury of many tissues, central nervous system injury, gastritis, ageing, inflammatory response syndrome, respiratory diseases, liver diseases, cancer and AIDS 1,2 . Many herbal plants contain antioxidant compounds and these compounds protect cells against the damaging effects of reactive oxygen species (ROS), such as singlet oxygen, superoxide, peroxyl radicals, hydroxyl radicals and peroxynitrite 3 . Moreover, these synthetic antioxidants also show low solubility and moderate antioxidant activity 4 . Therefore, many researchers are in search for antioxidants of natural origin. ABSTRACT In the present investigation we had attempted to investigate the in vitro antioxidant potential of aqueous extract of Terminalia Billerica bark (TBB). The 1, 1-Diphenyl, 2-picryl hydrazyl assay method had been performed at different doses (100-500 mg). The total phenolic and total flavonoids contents had also been determined. The results of the present study shows that the aqueous extract of TBB possess antioxidant activity through the DPPH free radical scavenging activity. The preliminary phytochemical investigations indicates the presence of flavonoids and polyphones. The results are found to be significant then compared with the standard Ascorbic acid. Further studies are required to determine the mechanism and isolation of active constituents involved in the antioxidant activity

A Review of Nursing Position Statements on Racism Following the Murder of George Floyd and Other Black Americans

National outrage over the killings of George Floyd and other Black Americans in the United States prompted public outcry against police brutality and racism in law enforcement and drew national attention to systemic racism as a public health crisis. In response, during the summer of 2020 many health organizations issued position statements in response to the murders. This article examines such statements issued by 3 prominent nursing organizations and 18 schools of nursing. Thematic analysis revealed six themes in the statements of the professional organizations, and a content analysis revealed that the statements of the schools of nursing were generally aligned with these themes. Such position statements can provide a viable approach to the public commitment to anti-racist reforms, but it is unclear if such statements can promote meaningful and measurable change

Experience with 40 cases of congenital pouch colon

Aim : The aim of this study was to analyze the clinical and management aspect of congenital pouch colon. Materials and Methods : This retrospective study was carried out on 40 cases of congenital pouch colon managed in the department of paediatric surgery from 01, January 2000 to 31, December 2005. Results : The incidence of congenital pouch colon (CPC) in the present study was 11.290 &#x0025; (40 of 354) of all anorectal malformations (ARM) and 19.60&#x0025; (40 of 204) of high ARM. Of these 40 cases of CPC included in the study, 82.5&#x0025; were male and 17.5&#x0025; were female. The average age of presentation to hospital was 3.36 days with a range of 1-11 days; of these 25&#x0025; patients were admitted with poor general condition. Preoperative diagnosis of CPC was possible in 75&#x0025; of cases in our study. 60&#x0025; ( n =24) of cases had incomplete pouch colon (Type III and IV) while 40&#x0025; ( n =16) had complete pouch colon (Type I and II). Right transverse colostomy was done in 16 patients and colostomy at descending colon just proximal to pouch in two patients for incomplete (Type III and IV) CPC as a primary initial procedure. Ileostomy was done in 14 patients and window colostomy in three patients for complete (Type I and II) CPC. As definitive procedures, pouch excision and abdomino-perineal pull-through of colon was done in 17 patients, coloplasty and abdomino-perineal pull-through of coloplasty colon was done in four patients and pouch excision and abdomino-perineal pull-through of terminal ileum in four patients in our series. None of our patients underwent primary single stage procedure. Conclusion: (1) CPC comprises 11.290 &#x0025; of all ARM and 19.60&#x0025; of high ARM. (2) Right transverse colostomy was opted for incomplete pouch colon, while Ileostomy and window colostomy were opted for complete pouch colon as initial surgical procedures. (3) Staged surgical procedures for management of CPC were well tolerated in our series