Nutrition risk screening and implications for patients with gynaecological cancers undergoing pelvic radiotherapy and/or other treatment modalities: A retrospective observational study.

AIM: There is scarcity of research for the nutritional management of pelvic radiotherapy in gynaecological malignancies and delivery of specialised nutrition care is limited due to the current knowledge gap in guidelines. This study aimed to better understand the nutritional risk, weight changes and pattern of nutrition impact symptoms occurring at various treatment timepoints in this population, to inform an effective model of care. METHODS: This retrospective, observational study included women with gynaecological cancers receiving pelvic radiotherapy at a tertiary hospital from January 2017 to December 2018 (n = 104). Information was collected on: first day of radiotherapy; weekly during treatment; acute-phase post-treatment (0-6 weeks); and intermediate-phase post-treatment (6 weeks to 6 months). This study reported on incidence of clinically significant weight change (±5%), documented nutrition impact symptoms and the current nutrition care model (nutrition screening, referral, assessment and interventions). RESULTS: Clinically significant weight loss was experienced by 38% (n = 40/104) of patients prior to commencing treatment and 19% (n = 14/73) during treatment. Diarrhoea (n = 40/79), fatigue (n = 54/79), nausea (n = 38/79) and pain (n = 31/79) were frequently reported during treatment, and fatigue (n = 33/92) and pain (n = 25/92) continued acutely post-treatment. Despite high rates of weight loss and prevalence of nutrition impact symptoms, only 38% (n = 40/104) of patients were referred to a dietitian. CONCLUSIONS: A considerable proportion of patients with gynaecological cancers are at nutrition risk before and during treatment due to clinically significant weight loss and prevalence of nutrition impact symptoms experienced. This highlights the importance of nutrition-risk screening and access to specialised dietetic care as part of their model of care.

Telephone-Delivered Mindfulness Training to Promote Medication Adherence and Reduce Sexual Risk Behavior Among Persons Living with HIV: An Exploratory Clinical Trial.

This study explored whether telephone-delivered mindfulness training (MT) to promote medication adherence and reduce sexual risk behavior was feasible for and acceptable to people living with HIV. Participants (N = 42; 50% female; M age = 47.5 years) were randomized to MT or health coaching (HC). Pre- and post-intervention, and at 3-month follow-up, we assessed adherence to ART, sexual risk behavior, and hypothesized mediators; we also conducted individual interviews to obtain qualitative data. Results showed that 55% of patients assigned to MT completed ≥ 50% of the training calls compared with 86% of HC patients (p < .05). Most patients reported satisfaction with their intervention (MT = 88%, HC = 87%). Patients in MT and HC reported improvements in medication adherence, mindfulness, and sexual risk reduction as well as reductions in anxiety, depressive symptoms, perceived stress, and impulsivity over time; however, no between-groups differences were observed.

The interaction between irreversible electroporation therapy (IRE) and embolization material using a validated vegetal model: an experimental study.

PURPOSE: Irreversible electroporation (IRE) is a nonthermal tumor ablation technique that induces cell apoptosis while preserving extracellular architecture. Surgical clips and embolic agents may lie adjacent to, or within, the target lesion. It is unknown to date if IRE causes degradation to the embolic agents or surgical clips that may have adverse effects to patients. We aimed to examine the effects of the IRE on the morphology of various embolic agents and the effects of these agents to the ablation field using a previously validated vegetal model. METHODS: Metallic surgical clips and various metallic and nonmetallic embolic agents were inserted within the center of the tuber ablation field. Additionally, clips were inserted on the edge and outside the ablation field. One tuber was ablated as a control. Ablation settings were based on previous published experiments. Tubers were imaged with magnetic resonance imaging (MRI) 18-24 hours after ablation and the ablated field dimensions were measured. Nonmetallic embolic agents were examined microscopically by the pathologist. RESULTS: Nonmetallic agents did not affect the ablation pattern. Metallic implants, however, caused arcing of the ablation margins. There was no macroscopic or microscopic degradation to the agents after IRE. CONCLUSION: The ablation zone arced in the presence of surgical clips at the edge or outside the ablation margins; therefore, nearby critical structures may be susceptible to the effects of IRE. Furthermore, there was no physical degradation of the embolic agents or surgical clips, and this may have importance when considering IRE ablation of previously embolized lesions in vivo.

Prevalence and Correlates of Unhealthy Alcohol and Drug Use Among Men Who Have Sex with Men Prescribed HIV Pre-exposure Prophylaxis in Real-World Clinical Settings.

Pre-exposure prophylaxis (PrEP) is effective in preventing HIV acquisition among men who have sex with men (MSM). However, little is known about unhealthy substance use among MSM initiating PrEP in real-world settings. Unhealthy substance use is a risk factor for HIV acquisition and non-adherence to treatment, and may also impact PrEP use. MSM who were prescribed PrEP from 2015 to 2017 at clinics in Providence, Rhode Island and New Haven, Connecticut were recruited to participate in a prospective observational study. Structured clinical assessments were used to assess demographics, HIV risk behaviors, and unhealthy alcohol (alcohol use disorders identification test [AUDIT]-C scores ≥ 4) and drug use (use of any drugs in the past 3 months). Bivariate and multivariate analyses were performed to determine demographics and behaviors associated with unhealthy alcohol and drug use. Among 172 MSM initiating PrEP, 64% were white and 40% were 25-34 years old. Participants reported a median of 3 (IQR 2-7) sexual partners in the last 3 months; 20% reported an HIV positive partner. Unhealthy alcohol and any drug use were reported by 54 and 57%, respectively, and 76% reported at least one of the two. The majority of drug use reported was marijuana and poppers (41 and 26% of participants, respectively). Relative to those without unhealthy alcohol use, unhealthy alcohol use was independently associated with any drug use (adjusted odds ratio [AOR] = 2.57, 95% CI 1.32-5.01). Frequent drug use was associated with younger age (< 25 years, AOR 4.27, 95% CI 1.51-12.09). Unhealthy alcohol use is common among MSM taking PrEP. Drug use other than marijuana and poppers was uncommon among our cohort. Further efforts may be needed to understand the influence of unhealthy alcohol and other substance use on PrEP outcomes and to engage MSM who use drugs for PrEP.

Association of Spirituality With Mental Health Conditions in Ohio National Guard Soldiers.

Research exploring spirituality in military populations is a relatively new field with limited published reports. This study used the Spiritual Well-Being Scale to examine the association of spiritual well-being with suicidal ideation/behavior, posttraumatic stress disorder (PTSD), and depression and alcohol use disorders in a randomized sample of Ohio Army National Guard soldiers. The participants were 418 soldiers, mostly white and male, with nearly three-quarters indicating that they had been deployed at least once during their careers. Higher spirituality, especially in the existential well-being subscale, was associated with significantly less lifetime PTSD, depression, and alcohol use disorders and with less suicidal ideation over the past year. Future research in this area may benefit from a longitudinal design that can assess spirituality and mental health behaviors in addition to diagnoses at different time points, to begin to explore spirituality in a larger context.

Selenium Attenuates HPV-18 Associated Apoptosis in Embryo-Derived Trophoblastic Cells but Not Inner Cell Mass In Vitro.

Objectives. Human papillomaviruses (HPV) are associated with cell cycle arrest. This study focused on antioxidant selenomethionine (SeMet) inhibition of HPV-mediated necrosis. The objectives were to determine HPV-18 effects on embryonic cells and to evaluate SeMet in blocking HPV-18 effects. Methods. Fertilized mouse embryos were cultured for 5 days to implanted trophoblasts and exposed to either control medium (group 1), HPV-18 (group 2), combined HPV-18 and 0.5 µM SeMet (group 3), or combined HPV-18 and 5.0 µM SeMet (group 4). After 48 hrs, trophoblast integrity and, apoptosis/necrosis were assessed using morphometric and dual-stain fluorescence assays, respectively. Results. HPV-18 exposed trophoblasts nuclei (253.8 ± 28.5 sq·µ) were 29% smaller than controls (355.6 ± 35.9 sq·µ). Supplementation with 0.5 and 5.0 µM SeMet prevented nuclear shrinkage after HPV-18 exposure. HPV-18 infected trophoblasts remained larger with SeMet supplementation. HPV-18 decreased cell viability by 44% but SeMet supplementation sustained cell viability. Apoptosis was lower when SeMet was present. HPV-18 decreased inner cell mass (ICM) viability by over 60%. Conclusions. HPV-18 decreased nuclear size and trophoblast viability but these effects were attenuated by the antioxidant SeMet. SeMet blocked HPV-18 associated apoptosis process in trophoblasts but not ICM cells suggesting involvement of different oxidative stress pathways.

Combined ultrasound-curcumin treatment of human cervical cancer cells.

OBJECTIVES: Human papillomavirus (HPV) is associated with cervical cancer. Studies showed curcumin inhibits HPV oncogenes expression but curcumin has low bioavailability. The objectives were: (1) to study ultrasound enhancement of curcumin effects on HeLa, SiHa and C33A, (2) to compare two frequencies for sonoporation and (3) to detect cell-free DNA released by the treatment. STUDY DESIGN: HeLa, SiHa and C33A cells (non-HPV control) were processed and exposed to either: (1) 10µM curcumin only, (2) 10µM curcumin with 8s of 7.5MHz ultrasound, (3) 10µM curcumin with 8s of 5.0MHz ultrasound, (4) control medium, or (5) 8s of 7.5MHz ultrasound. The five treated groups were incubated (48h) and analyzed by dual fluorescence apoptosis/necrosis assay. DNA in spent media was analyzed by capillary analysis. RESULTS: Combined curcumin ultrasound resulted in 9-, 12- and 16-fold higher necrosis in HeLa, SiHa and C33A cells respectively. Increased necrosis correlated with higher ultrasound frequencies. There was increased apoptosis in HeLa or SiHa cells with the combined treatment. Curcumin alone resulted in a lesser 2-4-fold increase in necrosis in the groups. Cell-free DNA was detected in the spent media of HeLa and SiHa but not C33A cultures. CONCLUSIONS: The results showed enhanced necrosis in cervical carcinoma cell lines after combined treatment and confirmed the ultrasound capacity to increase effectiveness of curcumin. Cancer cells were smaller post-treatment suggesting microtubule structural disruption. Cell-free DNA was low molecular weight consistent with lysed host cell.

Discovery of a small-molecule inhibitor of STAT3 by ligand-based pharmacophore screening.

STAT3 modulates the transcription of a wide variety of regulatory genes involved in cell proliferation, differentiation, migration, apoptosis, and other critical cellular functions. Constitutive activation of STAT3 has been detected in a wide spectrum of human malignancies. A pharmacophore model constructed from a training set of STAT3 inhibitors binding to the SH2 domain was used to screen an in-house database of compounds, from which azepine 1 emerged as a top candidate. Compound 1 inhibited STAT3 DNA-binding activity in vitro and attenuated STAT3-directed transcription in cellulo with comparable potency to the well-known STAT3 inhibitor S3I-201. A fluorescence polarization assay revealed that compound 1 targeted the SH2 domain of STAT3. Furthermore, compound 1 inhibited STAT3 phosphorylation in cells without affecting the total expression of STAT3. This study also validates the use of pharmacophore modeling to identify inhibitors of protein-protein interactions.

Discovery of a natural product-like iNOS inhibitor by molecular docking with potential neuroprotective effects in vivo.

In this study, we applied structure-based virtual screening techniques to identify natural product or natural product-like inhibitors of iNOS. The iNOS inhibitory activity of the hit compounds was characterized using cellular assays and an in vivo zebrafish larvae model. The natural product-like compound 1 inhibited NO production in LPS-stimulated Raw264.7 macrophages, without exerting cytotoxic effects on the cells. Significantly, compound 1 was able to reverse MPTP-induced locomotion deficiency and neurotoxicity in an in vivo zebrafish larval model. Hence, compound 1 could be considered as a scaffold for the further development of iNOS inhibitors for potential anti-inflammatory or anti-neurodegenerative applications.

UVA-photoactivated riboflavin treatment of vaginal cells derived from pelvic organ prolapse cases.

BACKGROUND: The pathophysiology of pelvic organ prolapse (POP) involves vaginal collagen degradation. Strengthening collagen by UVA-photoactivated cross-linking has been demonstrated and suggested target applications include the vaginal wall. AIM: To identify UVA irradiation and riboflavin effects on vaginal cells. MATERIALS AND METHODS: Vaginal cells were incubated for 24 h (DMEM/F-12 Ham's media) and were exposed to riboflavin (0, 0.1 and 10%) for 30 min before UVA photoactivation. Percentages of live, apoptotic and necrotic cells were determined by propidium iodide/Hoechst 33342 stains. RESULTS: UVA decreased vaginal cell viability [mean ± standard error of the mean: 26.2 ± 0.5% vs. control (43.9 ± 3.8%)], but riboflavin blocked UVA-induced damage (57.9 ± 2.7 and 56.7 ± 2.1% at 0.1 and 10% riboflavin, respectively). Cells treated with low- and high-dose riboflavin had lower apoptosis (32.9 ± 1.0 and 35.5 ± 0.9%, respectively). Furthermore, riboflavin-treated cells had reduced necrosis (9.3 ± 1.7, 7.8 ± 3.0%) versus UVA-only (32.4 ± 5.5%) or control (17.1 ± 2.8%). Viability was similar for cells from the cervical and hymenal segments. CONCLUSION: The results demonstrated that riboflavin attenuated UVA damage in vaginal cells by inhibiting necrosis. Cervical and hymenal end vaginal cells were equally affected by UVA. UVA phototoxicity was reduced by the presence of riboflavin.

Cyclooxygenase (COX)-2 and granulosa cell apoptosis in vitro.

PURPOSE: C-myc was studied in cyclooxygenase (COX)-2 associated granulosa cell apoptosis, METHODS: Granulosa cells (N = 5 cases) were incubated for 24 h in either 1 or 50 microM COX-2 inhibitor, 1 or 50 microM COX-1/COX-2 inhibitor, negative or positive controls Single primer polymerase chain reaction of c-myc exon 1 were performed. Bisbenzimide-stained control single-stranded (ssDNA) were hybridized to SYBR Gold-stained ssDNA and fluorescent images analyzed. RESULTS: C-myc was disrupted by the high-dose COX-2 inhibitor. Cell viability decreased with COX-1 and COX-2 inhibition. However, cell viability was similar for the positive control and at low-dose COX-2 inhibition. CONCLUSIONS: Inhibition of both COX-1 and COX-2 initiated apoptosis without disrupting c-myc suggesting a protective effect on c-myc. The low dosage of the COX-2 inhibitor did not disrupt c-myc and cell viability. C-myc sensitization was not part of apoptosis.