Impact of Stimulation Frequency on Verbal Fluency Following Bilateral Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease.

OBJECTIVE: The effects of stimulation frequency on verbal fluency (VF) following subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) are not well understood. The present study examines the impact stimulation frequency has on VF following bilateral STN-DBS in PD. METHODS: Prospective study of 38 consecutive patients with PD with low frequency STN-DBS (LFS) (n = 10) and high frequency STN-DBS (HFS) (n = 14), and a non-operated PD control group consisting of patients with fluctuating response to dopaminergic medication (n = 14) homogeneous in age, education, disease duration, and global cognitive function. Patients were evaluated on VF tasks (letter, semantic, action verbs, alternating). A one-way analysis of variance (ANOVA) was conducted to assess distinctions between groups. Pre- and post-surgical comparisons of fluencies were performed for operated groups. A mixed ANOVA was applied to the data to evaluate the interaction between treatment (HFS vs. LFS) and time (pre- vs. post-surgery). Strategy use (clustering and switching) was evaluated. RESULTS: Semantic and letter fluency performance revealed significant differences between HFS and LFS groups. Pre- and post-surgical comparisons revealed HFS negatively affected letter, semantic, and action fluencies, but LFS had no effect on VF. No interaction effect or main effect of treatment was found. Main effect of time was significant for semantic and action fluencies indicating a decrease in postoperative fluency performance. Patients with LFS produced larger average cluster sizes than patients with HFS. CONCLUSION: LFS may be less detrimental to VF, but these findings suggest that VF decline following STN-DBS is not caused by stimulation frequency alone.

Epigenome-wide association study of prostate cancer in African American men identified differentially methylated genes.

INTRODUCTION: Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide. METHODS: This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs. indolent PCa in 121 African American patients. Epigenome-wide DNA methylation patterns in tumor DNA were assessed using the human Illumina Methylation EPIC V1 array. RESULTS: Around 5,139 differentially methylated CpG-sites (q < 0.01, lΔßl > 0.2) were identified when comparing normal vs. tumor, with an overall trend of hypermethylation in prostate tumors.  Multiple representative differentially methylated regions (DMRs), including immune-related genes, such as CD40, Galectin3, OX40L, and STING, were detected in prostate tumors when compared to adjacent normal tissues. Based on an epigenetic clock model, we observed that tumors' total number of stem cell divisions and the stem cell division rate were significantly higher than adjacent normal tissues. Regarding PCa aggressiveness, 2,061 differentially methylated CpG-sites (q < 0.05, lΔßl > .05) were identified when the grade group (GG)1 was compared with GG4/5. Among these 2,061 CpG sites, 155 probes were consistently significant in more than one comparison. Among these genes, several immune system genes, such as COL18A1, S100A2, ITGA4, HLA-C, and ADCYAP1, have previously been linked to tumor progression in PCa. CONCLUSION: Several differentially methylated genes involved in immune-oncologic pathways associated with disease risk or aggressiveness were identified. In addition, 261 African American-specific differentially methylated genes related to the risk of PCa were identified. These results can shedlight on potential mechanisms contributing to PCa disparities in the African American Population.

Mangosteen extracts: Effects on intestinal bacteria, and application to functional fermented milk products.

Mangosteen (Garcinia mangostana L.) is a tasty, polyphenol-rich tropical fruit. The edible part is highly appreciated by its aroma, taste and texture. The non-edible part, rich in polyphenols, has been traditionally used in Thai medicine. In this work, flavonoids and phenolic acid/derivatives were identified in mangosteen extracts (ME) from edible and non-edible portions. We first studied the effects of MEs on the growth, metabolism, antioxidant capacity, biofilm formation and antimicrobial capacity of eight bifidobacteria and lactobacilli strains from intestinal origin and two commercial probiotic strains (BB536 and GG). ME concentrations higher than 10-20 % were inhibitory for all strains. However, ME concentrations of 5 % significantly (P < 0.01) increased all strains antioxidant capacity, reduced biofilm-formation, and enhanced inhibition against Gram-positive pathogens. To apply these knowledge, bifunctional fermented milk products were elaborated with 5 % ME and individual strains, which were selected taking into account their growth with ME, and the widest range of values on antioxidant capacity, biofilm formation and antimicrobial activity (bifidobacteria INIA P2 and INIA P467, lactobacilli INIA P459 and INIA P708, and reference strain GG). Most strains survived well manufacture, refrigerated storage and an in vitro simulation of major conditions encountered in the gastrointestinal tract. As expected, products supplemented with ME showed higher polyphenol content and antioxidant capacity levels than control. After sensory evaluation, products containing strains INIA P2, INIA P708 and GG outstood as best.

Use of diagnostic tests in elderly patients consulting the emergency department. Analysis of the emergency department and elder needs cohort (EDEN-8).

OBJECTIVE: Analyse the association between the use of diagnostic tests and the characteristics of older patients 65 years of age or more who consult the emergency department (ED). METHODS: We performed an analysis of the EDEN cohort that includes patients who consulted 52 Spanish EDs. The association of age, sex, and ageing characteristics with the use of diagnostic tests (blood tests, electrocardiogram (ECG), microbiological cultures, X-ray, computed tomography, ultrasound, invasive techniques) was studied. The association was analysed by calculating the adjusted odds ratios (aOR) and their 95 % confidence intervals (CI) using a logistic regression model. RESULTS: A total of 25,557 patients were analysed. There was an increase in the use of diagnostic tests based on age, with an aOR for blood test of 1.805 (95 %CI 1.671 - 1.950), ECG 1.793 (95 %CI 1.664 - 1.932) and X-ray 1.707 (95 %CI 1.583 - 1.840) in the group of 85 years or more. The use of diagnostic tests is lower in the female population. Most ageing characteristics (cognitive impairment, previous falls, polypharmacy, dependence, and comorbidity) were independently associated with increased use of diagnostic tests. CONCLUSIONS: Age, and the characteristics of ageing itself are generally associated with a greater use of diagnostic tests in the ED.

Clinical Features and Therapeutic Outcomes Comparing Primary Mediastinal Large B-cell Lymphoma to Mediastinal Hodgkin Disease.

Currently, there is limited data available comparing Primary Mediastinal Large B-cell Lymphoma (PMBL) and mediastinal Hodgkin disease, nodular sclerosis type (HDNS). This is a retrospective cohort study that compares the clinical features, histology through immunohistochemistry (IHC) and treatment outcomes of 19 cases of PMBL and 39 cases of HDNS diagnosed over 13 years at a single institution in San Juan, PR. Superior Vena Cava syndrome (SVCS) and elevated Lactate Dehydrogenase (LDH) levels were more frequently seen in the PMBL cohort. At the median follow-up visit, of 74 months, no significant difference was seen in overall survival or progression free survival between PMBL and HDNS. Almost all of the relapses in the PMBL group occurred within 12 months of diagnosis. Our data suggests that PMBL and HDNS differ in their clinical presentation and have a favorable prognosis.

Impact of the laparoscopic approach, early closure and preoperative stimulation on outcomes of ileostomy closure after rectal resection.

AIM: To evaluate the clinical outcome of early closure of a protective ileostomy and preoperative stimulation of the efferent limb in a cohort of patients with rectal cancer treated surgically, primarily using the laparoscopic approach. METHODS: We performed an observational retrospective cohort study in a prospectively recorded series of patients with rectal cancer who underwent laparoscopic surgery with a protective loop ileostomy between 2017 and 2022. Ileostomy closure was programmed for within 3 months after surgery. All patients underwent stimulation of the efferent limb. Primary outcomes were morbidity and mortality, length of stay (LOS), and re-admission. RESULTS: Between 2017 and 2022, 108 patients underwent resection for rectal cancer and protective ileostomy. The laparoscopic approach was performed in 84.3% of patients (n = 91). Permanent ileostomy was performed in 5 patients (4.6%). Ileostomy closure was thus performed in 95.4% of patients (n = 103). Median time to closure was 74.5 days (range 57-113). In 63.1% (n = 65) of patients, reconstructive surgery was performed within 90 days. Prior to closure, efferent limb stimulation was performed in 77.8% (n = 84) of patients. Global morbidity was 26.2% (n = 27) (85.19%, n = 23 Clavien-Dindo I and 7.41%, n = 2 Clavien-Dindo II). The main causes of morbidity were postoperative ileus (10.7%, n = 11) and rectal bleeding (8.7%, n = 9). Anastomosis leakage occurred in 2 patients. Median hospital stay was 6 days (5-7). Readmission was needed in 6.8% (n = 7) of patients. CONCLUSION: A previous laparoscopic approach, early closure and stimulation of the efferent limb could be a useful strategy to reduce the morbidity and mortality of temporary ileostomy closure.

Disruptions in reproductive health, sex hormonal profiles, and hypothalamic hormone receptors content in females of the C58/J mouse model of autism.

Autism Spectrum Disorder (ASD) is characterized by differences in social communication and interaction, as well as areas of focused interests and/or repetitive behaviors. Recent studies have highlighted a higher prevalence of endocrine and reproductive disturbances among females on the autism spectrum, hinting at potential disruptions within the hypothalamus-pituitary-ovary (HPO) axis. This research aims to explore the reproductive health disparities in ASD using an animal model of autism, the C58/J inbred mouse strain, with a focus on reproductive performance and hormonal profiles compared to the C57BL/6J control strain. Our findings revealed that the estrous cycle in C58/J females is disrupted, as evidenced by a lower frequency of complete cycles and a lack of cyclical release of estradiol and progesterone compared to control mice. C58/J females also exhibited poor performance in several reproductive parameters, including reproductive lifespan and fertility index. Furthermore, estrogen receptor alpha content showed a marked decrease in the hypothalamus of C58/J mice. These alterations in the estrous cycle, hormonal imbalances, and reduced reproductive function imply dysregulation in the HPO axis. Additionally, our in-silico study identified a group of genes involved in infertility carrying single-nucleotide polymorphisms (SNPs) in the C58/J strain, which also have human orthologs associated with autism. These findings could offer valuable insights into the molecular underpinnings of neuroendocrine axis disruption and reproductive issues observed in ASD.

Renal Cell Carcinoma With Tumor Thrombus: A Case Series in Puerto Rico.

INTRODUCTION:  Renal cell carcinoma (RCC) is one of the most common types of kidney cancer. While RCC tends to present as a localized tumor, a notable proportion may present with distant metastasis. In some instances, RCC may also present with intravascular tumor extension, often called tumor thrombus (TT). Its presence confers a worse prognosis and has important implications for the tumor's staging and treatment. Despite extensive documentation of RCC TT in the US, limited data exists regarding its presentation, management, and outcomes in Puerto Rico (PR). This study aims to broaden the available information on RCC TT, emphasizing surgical management and outcomes. We also provide descriptive data on patient demographics and clinical presentation to improve decision-making among clinicians caring for Puerto Rican men and women. METHODS:  In this single-center, retrospective study, we evaluated patients who underwent partial or total nephrectomy at Saint Luke's Episcopal Medical Center between 2018 and 2022. Data was abstracted from electronic health records (EHR). Patients without documented evidence of TT during the peri-operative period were excluded from the study. A total of 220 patient records were evaluated, of which 12 met the inclusion criteria for the study. Cases were categorized using the latest RCC TT guidelines. Central tendency measurements were used to describe the sample distribution. The mean was considered to make assumptions regarding the prevalent observations, and the median was considered to rule out possible outliers. Categorical data were evaluated using proportion analyses, including TT extension level and BMI variables. Fisher's exact test evaluated the association between the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade and TT extension level. RESULTS:  Most patients lacked TT-related symptoms. The most severe presenting symptom was a pulmonary embolism (8.3%). Hypertension (83.3%), BMI greater than 25 at the time of diagnosis (75%), and type 2 diabetes mellitus (66.7%) were the most common comorbid conditions within our cohort. Nearly 75% of patients underwent laparoscopic radical nephrectomy with TT resection. One left-sided level III case was managed by laparoscopic-assisted open radical nephrectomy with a right subcostal incision. There were zero intraoperative complications and two postoperative complications. The histopathological reports of all cases were consistent with clear cell carcinoma, and half of the cases (n=6) were WHO/ISUP G4. All patients are alive and free of disease. CONCLUSION:  RCC is a common renal neoplasm in PR that can present with intravascular tumor extension. Our findings do not establish a definitive association between BMI, tumor size, WHO/ISUP grading, and TT extension level. Our study shows that laparoscopic removal of RCC TT is a safe and effective approach. However, the generalizability of our findings is limited by the study's design and sample size. Future research should focus on identifying predictive markers, establishing effective screening protocols, and determining if our hybrid approach has comparable outcomes to the standard open approach.

A Comparative Analysis of Cognitive Deficits in Rheumatoid Arthritis and Fibromyalgia: Impact of Symptoms Severity and Its Clinical Implications.

Purpose: Fibromyalgia syndrome (FMS) and rheumatoid arthritis (RA) are chronic pain disorders, with clearly distinct pathogenetic mechanisms, frequently accompanied by symptoms like depression, fatigue, insomnia and cognitive problems. This study compared performance in various cognitive domains between patients with FMS and RA. The role of clinical symptoms severity in determine the differences in cognitive performance was also investigated. Patients and Methods: A cross-sectional study was conducted according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement. In total, 64 FMS patients, 34 RA patients and 32 healthy controls participated, all women. Using factor analysis, questionnaire scores were combined to yield a symptom severity factor, which was used as a control variable in the group comparisons. Results: Without controlling for symptom severity, both patient groups performed worse than controls in all the cognitive domains assessed (visuospatial memory; verbal memory; strategic planning and self-regulation; processing speed, attention and cognitive flexibility; and planning and organizational abilities); overall deficits were greater in FMS than in RA patients. FMS patients reported more severe clinical symptoms (current pain intensity, total pain, state anxiety, depression, fatigue and insomnia) than RA patients. After controlling for symptom severity, a large proportion of the cognitive test parameters no longer differed between FMS and RA patients. Conclusion: The study confirmed significant impairments in attention, memory, and higher cognitive functions in both FMS and RA. The greater deficits seen in FMS patients may at least partly be explained by more severe pain and secondary symptoms. Cognitive screening may facilitate the development of personalized treatment plans to optimize the quality of life of FMS and RA patients.

The investigation substantiated noteworthy impairments in attention, memory, and executive functions among individuals diagnosed with Fibromyalgia Syndrome (FMS) and Rheumatoid Arthritis (RA).The heightened cognitive deficits observed in FMS patients compared to those with RA could be attributed in part to the heightened severity of pain and secondary symptoms characteristic of FMS.Semantic clustering, by leveraging cognitive resources optimally, may serve as a compensatory mechanism for memory deficits and thus warrants inclusion in interventions aimed at assisting patients in coping with cognitive impairments.Incorporating cognitive deficit screenings into routine diagnostic protocols for FMS and RA is recommended, as it may facilitate the development of personalized treatment strategies aimed at enhancing the overall quality of life for affected individuals.

Long-Term Results of Cortical Motor Stimulation for Neuropathic Peripheral and Central Pain: Real-World Evidence From Two Independent Centers.

BACKGROUND AND OBJECTIVES: Cortical motor stimulation (CMS) is used to modulate neuropathic pain. The literature supports its use; however, short follow-up studies might overestimate its real effect. This study brings real-world evidence from two independent centers about CMS methodology and its long-term outcomes. METHODS: Patients with chronic refractory neuropathic pain were implanted with CMS. The International Classification of Headache Disorders 3rd Edition was used to classify craniofacial pain and the Douleur Neuropathique en 4 Questions Scale score to explore its neuropathic nature. Demographics and clinical and surgical data were collected. Pain intensity at 6, 12, and 24 months and last follow-up was registered. Numeric rating scale reduction of ≥50% was considered a good response. The Clinical Global Impression of Change scale was used to report patient satisfaction. RESULTS: Twelve males (38.7%) and 19 females (61.3%) with a mean age of 55.8 years (±11.9) were analyzed. Nineteen (61.5%) were diagnosed from painful trigeminal neuropathy (PTN), and seven (22.5%) from central poststroke pain. The mean follow-up was 51 months (±23). At 6 months, 42% (13/31) of the patients were responders, all of them being PTN (13/19; 68.4%). At last follow-up, only 35% (11/31) remained responders (11/19 PTN; 58%). At last follow-up, the global Numeric rating scale reduction was 34% ( P = .0001). The Clinical Global Impression of Change scale punctuated 2.39 (±0.94) after 3 months from the surgery and 2.95 (±1.32) at last follow-up ( P = .0079). Signs of suspicious placebo effect were appreciated in around 40% of the nonresponders. CONCLUSION: CMS might show long-term efficacy for neuropathic pain syndromes, with the effect on PTN being more robust in the long term. Multicentric clinical trials are needed to confirm the efficacy of this therapy for this and other conditions.

Timely Assessment of Breathing-Related Distress in Community Palliative Care: A Multidisciplinary Collaborative Quality Improvement Project.

Background: Breathlessness is a common symptom for palliative patients that can cause distress and decrease function and quality of life. Palliative care services in Australia aim to routinely assess patients for breathing-related distress, but timely reassessment is not always achieved. Objective: To improve the timeliness of breathlessness reassessment in a home-based community palliative care service in New South Wales for people with moderate-to-severe breathing-related distress. Breathing-related distress was defined as a Symptom Assessment Score for "breathing problems" of four or more. Methods: This collaborative quality improvement (QI) project between SPHERE Palliative Care CAG, Stanford University mentors, and a Sydney metropolitan specialist palliative care service included a: (1) retrospective chart audit; (2) cause and effect analyses using a fishbone diagram; (3) development and implementation of key drivers and interventions; and (4) a pre-and-post evaluation of the timeliness of reassessment of breathing-related distress and changes in Symptom Assessment Scale scores for "breathing problems." Results: Key interventions included multidisciplinary education sessions to facilitate buy-in, with nurses as case managers responsible for breathlessness reassessment and documentation of scores, access and training in electronic palliative care data entry software, fortnightly monitoring and reporting of breathing-related distress scores, and development of an educational flowchart. The proportion of patients reassessed within seven days of an initial nursing assessment of moderate-to-severe breathing-related distress increased from 34% at baseline to 92% at six months. Conclusion: A local QI project increased the proportion of patients with a timely reassessment of their breathing-related distress in a community palliative care service.

Immunosuppressants alter the immune response associated with Glucantime® treatment for Leishmania infantum infection in a mouse model.

Background: Immunosuppression is a major risk factor for the development of visceral leishmaniasis (VL). The number of patients receiving immunosuppressant drugs such as TNF antagonist (anti-TNF) and methotrexate (MTX) is increasing. In these patients, VL is more severe, their response to treatment poorer, and they are at higher risk of relapse, a consequence (largely) of the poor and inappropriate immune response they develop. Objectives: To examine the effect of immunosuppressive treatment on the host immune response and thus gain insight into the reduced efficacy of pentavalent antimonials in these patients. Experiments were performed using BALB/c mice immunosuppressed with anti-TNF or MTX, infected with Leishmania infantum promastigotes, and then treated with Glucantime® at clinical doses. Results: Immunosuppression with both agents impeded parasite elimination from the spleen and bone marrow. Low pro-inflammatory cytokine production by CD4+ and CD8+ T cells was detected, along with an increase in PD-1 and IL-10 expression by B and T cells in the immunosuppressed groups after treatment. Conclusion: The immunosuppressed mice were unable to develop specific cellular immunity to the parasite, perhaps explaining the greater risk of VL relapse seen in pharmacologically immunosuppressed human patients.

Impact of the ABO and RhD Blood Groups on the Evaluation of the Erythroprotective Potential of Fucoxanthin, ß-Carotene, Gallic Acid, Quercetin and Ascorbic Acid as Therapeutic Agents against Oxidative Stress.

Previous studies detail that different blood groups are associated with incidence of oxidative stress-related diseases such as certain carcinomas. Bioactive compounds represent an alternative for preventing this oxidative stress. The aim of this study was to elucidate the impact of blood groups on the erythroprotective potential of fucoxanthin, ß-Carotene, gallic acid, quercetin and ascorbic acid as therapeutic agents against oxidative stress. The impact of ABO blood groups on the erythroprotective potential was evaluated via the antioxidant capacity, blood biocompatibility, blood susceptibility and erythroprotective potential (membrane stabilization, in vitro photostability and antihemolytic activity). All tested antioxidants exhibited a high antioxidant capacity and presented the ability to inhibit ROO•-induced oxidative stress without compromising the cell membrane, providing erythroprotective effects dependent on the blood group, effects that increased in the presence of antigen A. These results are very important, since it has been documented that antigen A is associated with breast and skin cancer. These results revealed a probable relationship between different erythrocyte antigens with erythroprotective potential, highlighting the importance of bio-targeted drugs for groups most susceptible to certain chronic-degenerative pathologies. These compounds could be applied as additive, nutraceutical or encapsulated to improve their bioaccessibility.

Evaluating smoking cessation interventions in China's primary care facility networks for hypertensive patients aged 45 years and older: A retrospective cohort study.

INTRODUCTION: In China's aging population, hypertension, aggravated by smoking, constitutes a substantial health concern. However, the effectiveness of the national public health interventions for smoking cessation under the Essential Public Health Services remains unverified. Our aim was to examine smoking prevalence, the proportion of individuals receiving smoking cessation advice, its impact on successful cessation among Chinese hypertensive patients aged ≥45 years, and to discern disparities in the coverage and efficacy of smoking cessation interventions between primary care facilities and hospitals. METHODS: Employing a longitudinal cohort approach, we examined four waves (2011-2018) of the China Health and Retirement Longitudinal Study (CHARLS). We surveyed a nationally representative cohort of hypertensive individuals, accounting for smoking status, cessation advice, healthcare preferences, and 11 pertinent covariates. RESULTS: Among the 4269 hypertensive patients, smokers were predominantly male, aged <65 years, with lower education and lower wealth. Smoking prevalence decreased from 25.2% in 2011 to 21.1% in 2018. The incidence of physician-provided smoking cessation advice reached a peak of 60.3% in 2015, decreasing to 54.8% in 2018. Visitors to primary care facilities reported the highest rate of advice reception. While patients receiving advice exhibited a higher smoking prevalence, instrumental variable regression and subgroup analyses found no significant correlation between advice receipt and successful cessation. CONCLUSIONS: We observed a substantial smoking prevalence among older hypertensive Chinese individuals and limited effectiveness of existing cessation programs. This underscores the necessity for augmenting primary care and devising a comprehensive health policy for more successful smoking cessation interventions, particularly considering China's rapidly aging population.

"Long-term oncologic outcomes and risk factors for distant recurrence after pathologic complete response following neoadjuvant treatment for locally advanced rectal cancer. A nationwide, multicentre study".

BACKGROUND: Pathologic complete response (pCR) after multimodal treatment for locally advanced rectal cancer (LARC) is used as surrogate marker of success as it is assumed to correlate with improved oncologic outcome. However, long-term oncologic data are scarce. METHODS: This retrospective, multicentre study updated the oncologic follow-up of prospectively collected data from the Spanish Rectal Cancer Project database. pCR was described as no evidence of tumour cells in the specimen. Endpoints were distant metastases-free survival (DMFS) and overall survival (OS). Multivariate regression analyses were run to identify factors associated with survival. RESULTS: Overall, 32 different hospitals were involved, providing data on 815 patients with pCR. At a median follow-up of 73.4 (IQR 57.7-99.5) months, distant metastases occurred in 6.4% of patients. Abdominoperineal excision (APE) (HR 2.2, 95%CI 1.2-4.1, p = 0.008) and elevated CEA levels (HR = 1.9, 95% CI 1.0-3.7, p = 0.049) were independent risk factors for distant recurrence. Age (years) (HR 1.1; 95%-CI 1.05-41.09; p < 0.001) and ASA III-IV (HR = 2.0; 95%-CI 1.4-2.9; p < 0.001), were the only factors associated with OS. The estimated 12, 36 and 60-months DMFS rates were 96.9%, 91.3%, and 86.8%. The estimated 12, 36 and 60-months OS rates were 99.1%, 94.9% and 89.3%. CONCLUSIONS: The incidence of metachronous distant metastases is low after pCR, with high rates of both DMFS and OS. The oncologic prognosis in LARC patients that achieve pCR after neoadjuvant chemo-radiotherapy is excellent in the long term.

Progesterone and its metabolite allopregnanolone promote invasion of human glioblastoma cells through metalloproteinase­9 and cSrc kinase.

Glioblastomas are the most aggressive and common primary brain tumors in adults. Glioblastoma cells have a great capacity to migrate and invade the brain parenchyma, often reaching the contralateral hemisphere. Progesterone (P4) and its metabolite, allopregnanolone (3α-THP), promote the migration and invasion of human glioblastoma-derived cells. P4 induces migration in glioblastoma cells by the activation of the proto-oncogene tyrosine-protein kinase Src (cSrc) and focal adhesion kinase (Fak). In breast cancer cells, cSrc and Fak promote invasion by increasing the expression and activation of extracellular matrix metalloproteinases (MMPs). However, the mechanism of action by which P4 and 3a-THP promote invasion in glioblastoma cells remains unclear. The effects of P4 and 3α-THP on the protein expression levels of MMP-2 and -9 and the participation of cSrc in progestin effects in U251 and U87 human glioblastoma-derived cells were evaluated. It was determined by western blotting that the P4 increased the protein expression level of MMP-9 in U251 and U87 cells, and 3α-THP increased the protein expression level of MMP-9 in U87 cells. None of these progestins modified MMP-2 protein expression levels. The increase in MMP-9 expression was reduced when the intracellular progesterone receptor and cSrc expression were blocked with small interfering RNAs. Cell invasion induced by P4 and 3α-THP was also blocked by inhibiting cSrc activity with PP2 or by cSrc gene silencing. These results suggest that P4 and its metabolite 3α-THP induce the invasion of glioblastoma cells by increasing MMP-9 expression through the cSrc kinase family. The results of this study provide information of interest in the context of targeted therapies against molecular pathways involved in glioblastoma invasion.

Experience of Pain and Unpleasantness during Mammography Screening: A Cross-Sectional Study on the Roles of Emotional, Cognitive, and Personality Factors.

BACKGROUND: Breast cancer is the most frequent cause of malignant tumors among women worldwide. Its successful prevention depends on the degree of participation in screening programs, which can be influenced by psychological factors, including fear. METHOD: A cross-sectional study was conducted according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement. Twenty-six healthy women aged 50-69 years took part in this study, all of whom were summoned for routine mammography screening and were randomly selected. Prior mammography screening, breast pain intensity, unpleasantness (visual analog scale), and psychological (catastrophizing, state anxiety, and fear of pain) and personality (neuroticism, psychoticism, and extraversion) variables were evaluated. Pain, unpleasantness, and state anxiety were further evaluated pre- and post-mammography screening. RESULTS: During the mammography screening, pain and unpleasantness levels were higher than those observed pre- and post-screening. Residual unpleasantness remained post-screening. State anxiety was positively associated with pain, and psychoticism with unpleasantness, as reported by participants during the mammography screening. CONCLUSIONS: Anxiety levels influence the pain experienced in association with the mammography procedure. Women subjected to mammography screenings might benefit from relaxation strategies aimed at reducing anxiety to pre-mammography levels and, by extension, pain and unpleasantness during mammography. The inclusion of these strategies in breast cancer prevention campaigns could improve the rates of mammography reattendance, and therefore, benefit cancer prevention efforts.

Psychoeducation for Fibromyalgia Syndrome: A Systematic Review of Emotional, Clinical and Functional Related-Outcomes.

Fibromyalgia Syndrome (FMS) is a chronic condition of widespread pain accompanied by several symptoms such as stiffness, fatigue, sleep problems, depression, anxiety, and cognitive deficits. To date, there is no specific treatment for FMS. The European League Against Rheumatism, and the majority of the international recommendations for managing FMS, has claimed psychoeducational intervention as the first step in FMS treatment for adequate symptoms management. However, scientific studies in this regard are scarce, diverse, and with contradictory findings. Results integration from analogous studies could provide a clear presentation of the real clinical value of psychoeducation in FMS. Therefore, the current systematic review aims at exploring the effect of psychoeducation on emotional, clinical, and functional symptoms of FMS patients and encourages researchers towards psychoeducation's procedure optimization and systematization. The systematic review was conducted according to the guidelines of the Cochrane Collaboration and PRISMA statements. The selected articles were evaluated using the Cochrane risk of bias (ROB) assessment tool. The selected articles were extracted from PubMed, Scopus, and Web of Science databases. The literature search identified 11 studies eligible for the systematic review. The ROB evaluation revealed that 2 of the 11 studies showed a low quality, the other 2 had a moderate quality, and the remaining 7 studies exhibited a high quality. Results showed that psychoeducation is generally included as an important first therapeutic step in multicomponent treatments for FMS. Moreover, psychoeducation generally seems to be quite beneficial in reducing emotional (i.e., number of days feeling emotionally well, general anxiety, depression levels, etc.) and clinical symptoms (levels of fatigue, morning stiffness, pain intensity, etc.), as well as increasing functional status (i.e., general physical function, morning fatigue, stiffness, etc.). Despite that psychoeducation´s clinical benefits are highlighted, there is scarce amount of research on psychoeducation beyond its usefulness as part of multicomponent treatments.

Identification of Exo-miRNAs: A Summary of the Efforts in Translational Studies Involving Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) accounts for about 10-15% of all breast cancers (BC) in the US and its diagnosis is associated with poor survival outcomes. A better understanding of the disease etiology is crucial to identify target treatment options to improve patient outcomes. The role of exo-miRNAs in TNBC has been studied for more than two decades. Although some studies have identified exo-miR candidates in TNBC using clinical samples, consensus regarding exo-miR candidates has not been achieved. The purpose of this review is to gather information regarding exo-miR candidates reported in TNBC translational studies along with the techniques used to isolate and validate the potential targets. The techniques suggested in this review are based on the use of commercially available materials for research and clinical laboratories. We expect that the information included in this review can add additional value to the recent efforts in the development of a liquid biopsy to identify TNBC cases and further improve their survival outcomes.

Connecting the dots: Melanoma cell of origin, tumor cell plasticity, trans-differentiation, and drug resistance.

Melanoma, a lethal malignancy that arises from melanocytes, exhibits a multiplicity of clinico-pathologically distinct subtypes in sun-exposed and non-sun-exposed areas. Melanocytes are derived from multipotent neural crest cells and are present in diverse anatomical locations, including skin, eyes, and various mucosal membranes. Tissue-resident melanocyte stem cells and melanocyte precursors contribute to melanocyte renewal. Elegant studies using mouse genetic models have shown that melanoma can arise from either melanocyte stem cells or differentiated pigment-producing melanocytes depending on a combination of tissue and anatomical site of origin and activation of oncogenic mutations (or overexpression) and/or the repression in expression or inactivating mutations in tumor suppressors. This variation raises the possibility that different subtypes of human melanomas (even subsets within each subtype) may also be a manifestation of malignancies of distinct cells of origin. Melanoma is known to exhibit phenotypic plasticity and trans-differentiation (defined as a tendency to differentiate into cell lineages other than the original lineage from which the tumor arose) along vascular and neural lineages. Additionally, stem cell-like properties such as pseudo-epithelial-to-mesenchymal (EMT-like) transition and expression of stem cell-related genes have also been associated with the development of melanoma drug resistance. Recent studies that employed reprogramming melanoma cells to induced pluripotent stem cells have uncovered potential relationships between melanoma plasticity, trans-differentiation, and drug resistance and implications for cell or origin of human cutaneous melanoma. This review provides a comprehensive summary of the current state of knowledge on melanoma cell of origin and the relationship between tumor cell plasticity and drug resistance.