A comparative study of the effectiveness of self-management and group management on the amount of weight loss of nurses under low-calorie diet treatment: A simultaneous mixed-methods study.

BACKGROUND: Nursing is a profession that is associated with a lot of stress and a risk of being overweight or obese. The purpose of this research was to determine the comparative effectiveness of self-management (self-M) and group management (group-M) on nurses who were following a diet with the aim of proposing a proper planning and a healthy lifestyle for them. MATERIALS AND METHODS: This study was a simultaneous mixed-methods design (interventional and qualitative). The participants were all overweight or obese nurses working in teaching hospitals at Guilan University of Medical Sciences in 2019 (n = 96). In the qualitative part, data were extracted from semi-structured interviews. For quantitative data analysis, relevant statistical methods such as Kolmogorov-Smirnov test, analysis of variance (ANOVA), and analysis of covariance (ANCOVA) were used. For qualitative data analysis, the conventional content analysis approach was used and Lincoln and Guba's criteria were applied to ensure the accuracy of the data. RESULTS: In both quantitative and qualitative sections, the results showed that following a diet treatment with group-M is more effective than self-M. CONCLUSION: The results showed that a healthy lifestyle can be achieved for nurses if they participate in training classes and group programs, which are proven to be effective based on this article and some other studies. Also, since weight gain and obesity, as one of the most important problems of health systems, continue to increase and can impose a heavy economic and social burden on human societies, various general policies should be used and these solutions can range from home to society to prevent and control them.

Reactions to Misoprostol: A Case Report.

Background: Most of abortions occur before the 13th week of pregnancy. Nowadays, non-surgical approaches for evacuation of uterine have been replaced with surgical ones due to the reduction in bleeding, fewer complications, ease of management, and cost-effectiveness. Misoprostol is a prostaglandin E1 analog that is used for labor induction. It is known as a safe drug with very few side effects. Case Presentation: A 29-year-old woman with the gestational age of 11 weeks and 6 days with a diagnosis of cystic hygroma introduced herself to the labor ward. At the time of hospitalization, the patient was conscious. The heart sounds were normal. A vaginal exam indicated no pathological findings. Totally, she received 1000 mg of Misoprostol. Approximately, 2 hours after the last placement of Misoprostol, the patient developed bending and mild cyanosis of fingers and showed tachycardia with a pulse rate of 140 beats/min. Her O2 saturation decreased to 78%. At this time, the patient had a successful miscarriage. Echocardiography showed an ejection fraction of 55% and normal right ventricular size. The electrocardiogram showed sinus tachycardia. Therefore, she was sent to CCU with a possible diagnosis of embolism. The cardiologist administered a heparin drip of 5000-unit IV stat, and 1000 unit/h heparin and asked for a D-Dimer test. However, the laboratory reported that the patient's blood sample was hemolyzed and they could only check her hemoglobin which was 4 g/dl. Immediately, the heparin drip was held and the patient received 3 packed cells. Her Hb was 6.5 g/dl. 12 hours later she showed tachycardia, and her O2 saturation reduced to 70%. She lost her consciousness. Nearly 40 minutes later, she had cardiorespiratory arrest and CPR wasn't successful and she died. Conclusions: In Conclusion, even a frequently used drug such as Misoprostol can cause life-threatening side effects, leading to emergent situations.

Psychometric evaluation of the heart failure somatic perception scale in Iranian heart failure patients: a cross-sectional study.

Background: This study aimed to evaluate the psychometric evaluation of heart failure somatic perception scale (HFSPS) in Iranian heart failure patients. Materials and methods: A total of 220 heart failure (HF) patients were enroled in the study. Data gathering was conducted via consecutive sampling from August 2022 to April 2023. Face validity, content validity, construct validity, and internal consistency were used to evaluate the validity and reliability of the Persian version of the HFSPS. Construct validity was done through confirmatory factor analysis and convergent validity. Convergent validity between HFSPS and symptom status questionnaire-heart failure was measured using Pearson's correlation coefficient. Cronbach's alpha and Macdonald's omega coefficient were used to evaluate the reliability of instruments. Results: A total of 220 HF patients participated in this study. Their mean age was 66.46 (SD=11.40). Among the participants, 70% were men. The results of the confirmatory factor analysis evaluation showed the goodness of fit indices of the final HFSPS model after modification was within an acceptable range (χ2=306.18 P<0.001, Minimum Discrepancy Function Divided by Degrees of Freedom=2.47, Comparative of Fit Index=0.91, Tucker-Lewis index=0.90, Adjusted goodness of fit index=0.81, Parsimonious norm fit index=0.70, root mean square error of approximation=0.082). Convergent validity between HFSPS and symptom status questionnaire-heart failure indicated a positive and significant correlation. Cronbach's alpha coefficient in the HFSPS was 0.868, and McDonald's omega coefficient in the HFSPS was 0.832. Conclusion: Overall, the Persian version of the HFSPS was determined to be a reliable and valid scale among Iranians with HF.

Exosc9 Initiates SUMO-Dependent lncRNA TERRA Degradation to Impact Telomeric Integrity in Endocrine Therapy Insensitive Hormone Receptor-Positive Breast Cancer.

Long, noncoding RNAs (lncRNAs) are indispensable for normal cell physiology and, consequently, are tightly regulated in human cells. Yet, unlike mRNA, substantially less is known about the mechanisms for lncRNA degradation. It is important to delineate the regulatory control of lncRNA degradation, particularly for lncRNA telomeric repeat-containing RNA (TERRA), as the TERRA-telomere R-loops dictate cell cycle progression and genomic stability. We now report that the exosome complex component Exosc9 degrades lncRNA TERRA in human mammary epithelial cells. Heterochromatin protein 1 alpha (HP1α) recruits Exosc9 to the telomeres; specifically, the SUMO-modified form of HP1α supports interaction with Exosc9 and, as previously reported, lncRNA TERRA. The telomeric enrichment of Exosc9 is cell cycle-dependent and consistent with the loss of telomeric TERRA in the S/G2 phase. Elevated Exosc9 is frequently observed and drives the growth of endocrine therapy-resistant (ET-R) HR+ breast cancer (BCa) cells. Specifically, the knockdown of Exosc9 inversely impacts telomeric R-loops and the integrity of the chromosome ends of ET-R cells. Consistently, Exosc9 levels dictate DNA damage and the sensitivity of ET-R BCa cells to PARP inhibitors. In this regard, Exosc9 may serve as a promising biomarker for predicting the response to PARP inhibitors as a targeted monotherapy for ET-R HR+ BCa.

Androgen Receptor in Hormone Receptor-Positive Breast Cancer.

Breast cancer subtypes expressing hormone receptors (HR+ BCa) have a good prognosis and respond to first-line endocrine therapy (ET). However, the majority of HR+ BCa patients exhibit intrinsic or acquired ET resistance (ET-R) and rapid onset of incurable metastatic BCa. With the failure of conventional ET, limited targeted therapy exists for ET-R HR+ BCa patients. The androgen receptor (AR) in HR-negative BCa subtypes is emerging as an attractive alternative target for therapy. The AR drives Luminal AR (LAR) triple-negative breast cancer progression, and LAR patients consistently exhibit positive clinical benefits with AR antagonists in clinical trials. In contrast, the function of the AR in HR+ BCa is more conflicting. AR in HR+ BCa correlates with a favorable prognosis, and yet, the AR supports the development of ET-R BCa. While AR antagonists were ineffective, ongoing clinical trials with a selective AR modulator have shown promise for HR+ BCa patients. To understand the incongruent actions of ARs in HR+ BCa, the current review discusses how the structure and post-translational modification impact AR function. Additionally, completed and ongoing clinical trials with FDA-approved AR-targeting agents for BCa are presented. Finally, we identify promising investigational small molecules and chimera drugs for future HR+ BCa therapy.

Constitutively active androgen receptor supports the metastatic phenotype of endocrine-resistant hormone receptor-positive breast cancer.

BACKGROUND: Hormone receptor positive (HR+) breast cancer (BCa) is the most frequently diagnosed subtype. Acquired and intrinsic resistance to conventional endocrine therapy (ET) commonly occurs and prompts incurable metastatic disease. Hence, ET-resistant (ET-R) HR+ BCa presents a therapeutic challenge. Previous studies show elevated androgen receptor (AR) that supports resistance to ET tamoxifen and correlates with HR+ BCa metastasis. Yet surprisingly, studies with AR-blocker enzalutamide (Enz) in ET-R HR+ BCa present conflicting results. We now report that a constitutively active, unique from canonical Enz-targeted, AR accumulates in endocrine resistant HR+ BCa cells. METHODS: AR protein profiles in acquired and intrinsic ET-R HR + -BCa were defined with cell-free modification tests, in-house in-vivo SUMOylation assays, and PLA imaging. Genomic activity of native AR and modified-AR mimetic was tested with reporter assays and limited transcriptome analysis. Spheroid growth and migration studies were used to evaluate inhibitory actions of Enz and combinatorial therapy. RESULTS: Sustained higher molecular weight SUMO-modified AR (SUMO-AR) persists in acquired and intrinsic ET-R BCa cell lines. Concurrently, SUMO isoforms and global SUMO-modified proteome also accumulates in the same cell lines. We identified AR as a novel substrate for the SUMO-E3 ligase HSPB1/Hsp27. Independent of ligand, SUMO-AR is resilient to ubiquitin-mediated proteasomal degradation, enriched in the nucleus, readily chromatin-bound, and transcriptionally active. Constitutive SUMO-AR initiates a gene-expression profile that favors epithelial-mesenchymal transition. Enz combined with a SUMO inhibitor attenuates migration and metastatic phenotype of ET-R HR+ BCa. CONCLUSION: Targeting both unmodified and SUMO-modified AR prevents the metastatic progression of HR+ BCa with ET-R. Video abstract.

The ERß4 variant induces transformation of the normal breast mammary epithelial cell line MCF-10A; the ERß variants ERß2 and ERß5 increase aggressiveness of TNBC by regulation of hypoxic signaling.

Triple negative breast cancer (TNBC) still remains a challenge to treat in the clinic due to a lack of good targets for treatment. Although TNBC lacks expression of ERα, the expression of ERß and its variants are detected quite frequently in this cancer type and can represent an avenue for treatment. We show that two of the variants of ERß, namely ERß2 and ERß5, control aggressiveness of TNBC by regulating hypoxic signaling through stabilization of HIF-1α. RNA-seq of patient derived xenografts (PDX) from TNBC shows expression of ERß2, ERß4 and ERß5 variants in more than half of the samples. Furthermore, expression of ERß4 in the immortalized, normal mammary epithelial cell line MCF-10A that is resistant to tumorsphere formation caused transformation and development of tumorspheres. By contrast, ERß1, ERß2 or ERß5 were unable to support tumorsphere formation. We have previously shown that all variants except ERß1 stabilize HIF-1α but only ERß4 appears to have the ability to transform normal mammary epithelial cells, pointing towards a unique property of ERß4. We propose that ERß variants may be good diagnostic tools and also serve as novel targets for treatment of breast cancer.

Novel SUMO-Protease SENP7S Regulates ß-catenin Signaling and Mammary Epithelial Cell Transformation.

SUMO post-translational modification of proteins or SUMOylation ensures normal cell function. Disruption of SUMO dynamics prompts various pathophysiological conditions, including cancer. The burden of deSUMOylating the large SUMO-proteome rests on 6 full-length mammalian SUMO-proteases or SENP. While multiple SENP isoforms exist, the function of these isoforms remains undefined. We now delineate the biological role of a novel SENP7 isoform SENP7S in mammary epithelial cells. SENP7S is the predominant SENP transcript in human mammary epithelia but is significantly reduced in precancerous ductal carcinoma in situ and all breast cancer subtypes. Like other SENP family members, SENP7S has SUMO isopeptidase activity but unlike full-length SENP7L, SENP7S is localized in the cytosol. In vivo, SUMOylated ß-catenin and Axin1 are both SENP7S-substrates. With knockdown of SENP7S in mammary epithelial cells, Axin1-ß-catenin interaction is lost and ß-catenin escapes ubiquitylation-dependent proteasomal degradation. SUMOylated ß-catenin accumulates at the chromatin and activates multiple oncogenes. Hence, non-tumorigenic MCF10-2A cells with reduced SENP7S exhibit greater cell proliferation and anchorage-dependent growth. SENP7S depletion directly potentiates tumorigenic properties of MCF10-2A cells with induction of anchorage-independent growth and self-renewal in 3D-spheroid conditions. Collectively, the results identify SENP7S as a novel mediator of ß-catenin signaling and normal mammary epithelial cell physiology.

SUMOylation of HP1α supports association with ncRNA to define responsiveness of breast cancer cells to chemotherapy.

Epigenetic reprogramming allows cancer cells to bypass normal checkpoints and potentiate aberrant proliferation. Several chromatin regulators are subject to reversible SUMO-modification but little is known about how SUMOylation of chromatin-remodelers modulates the cancer epigenome. Recently, we demonstrated that SUMO-protease SENP7L is upregulated in aggressive BCa and maintains hypoSUMOylated heterochromatin protein 1-α (HP1α). Canonical models define HP1α as a "reader" of repressive H3K9m3 marks that supports constitutive heterochromatin. It is unclear how SUMOylation affects HP1α function in BCa cells. This report shows HP1α SUMO-dynamics are closely regulated in a complex with SENP7L and SUMO-E3 Polycomb-2 (PC2/CBX4). This complex accumulates at H3K9m3 sites, hypoSUMOylates HP1α and PC2, and reduces PC2's SUMO-E3 activity. HyperSUMO conditions cause complex dissociation, SUMOylation of PC2 and HP1α, and recruitment of SUMOylated HP1α to multiple DNA-repair genes including Rad51C. SUMOylated HP1α's enrichment at euchromatin requires chromatin-bound non-coding RNA (ncRNA), reduces Rad51C protein, and increases DNA-breaks in BCa cells. Hence, HP1α SUMOylation and consistently low SENP7L increase efficacy of DNA-damaging chemotherapeutic agents. BCa patients on chemotherapy that express low SENP7L exhibit greater survival rates than patients with high SENP7L. Collectively, these studies suggest that SUMOylated HP1α is a critical epigenetic-regulator of DNA-repair in BCa that could define chemotherapy responsiveness.

A novel image analysis approach for evaluation of mixing uniformity in drug-filled silicone rubber matrix.

Nowadays, there is a lot of interest in developing long-acting drug delivery devices for human or veterinary applications including monolithic systems. Drug content uniformity of a monolithic device is highly dependent on the uniform distribution of drug particles within the polymeric matrix both in dispersion and distribution levels. Here, a range of formulations were prepared which consisted of progesterone (1%w/w) and estradiol benzoate (0.1%w/w) dispersed in a silicone rubber matrix. Blend uniformity of the compounds was analyzed by image analysis of SEM micrographs obtained from the cross-sections of the devices by a new image processing approach. Efficiency of mixing was investigated at the dispersion level by plotting the relative frequency of drug particles versus "projected area diameter" of their aggregates. Based on the particle size distribution results, a significant improvement was observed in the dispersion pattern of drug particles by adding silicone oil (9%w/w). Distribution pattern of the particles was investigated by transforming the micrographs into algebraic matrices. An "ideal matrix" was developed by assumption of uniform localization of the drug particles. Real matrices obtained for all of the formulations were compared with this ideal matrix as a reference. Closer similarity between the two matrices was observed for silicone oil-containing (9%w/w) samples showing the best dispersive and distributive mixing quality.