Design and Modification of COVID-19 Case Investigation and Contact Tracing Interview Scripts Used by Health Departments Throughout the COVID-19 Pandemic.

OBJECTIVES: We sought to (1) document how health departments (HDs) developed COVID-19 case investigation and contact tracing (CI/CT) interview scripts and the topics covered, and (2) understand how and why HDs modified those scripts. DESIGN: Qualitative analysis of CI/CT interview scripts and in-depth key informant interviews with public health officials in 14 HDs. Collected scripts represent 3 distinct points (initial, the majority of which were time stamped May 2020; interim, spanning from September 2020 to August 2021; and current, as of April 2022). SETTING: Fourteen state, local, and tribal health jurisdictions and Centers for Disease Control and Prevention (CDC). PARTICIPANTS: Thirty-six public health officials involved in leading CI/CT from 14 state, local, and tribal health jurisdictions (6 states, 3 cities, 4 counties, and 1 tribal area). MAIN OUTCOME MEASURE: Interview script elements included in CI/CT interview scripts over time. RESULTS: Many COVID-19 CI/CT scripts were developed by modifying questions from scripts used for other communicable diseases. Early in the pandemic, scripts included guidance on isolation/quarantine and discussed symptoms of COVID-19. As the pandemic evolved, the length of scripts increased substantially, with significant additions on contact elicitation, vaccinations, isolation/quarantine recommendations, and testing. Drivers of script changes included changes in our understanding of how the virus spreads, risk factors and symptoms, new treatments, new variants, vaccine development, and adjustments to CDC's official isolation and quarantine guidance. CONCLUSIONS: Our findings offer suggestions about components to include in future CI/CT efforts, including educating members of the public about the disease and its symptoms, offering mitigation guidance, and providing sufficient support and resources to help people act on that guidance. Assessing the correlation between script length and number of completed interviews or other quality and performance measures could be an area for future study.

Initial Safety and Feasibility Results From a Phase 1, Diagnose-and-Treat Trial of Neoadjuvant Intratumoral Cisplatin for Stage IV NSCLC.

Neoadjuvant intratumoral cisplatin has the potential to generate substantial cytotoxicity and immune priming within the tumor environment, while minimizing systemic, off-target, adverse events. We initiated a phase 1A, 3+3 dose-ranging study of neoadjuvant, intratumoral cisplatin, delivered through endobronchial ultrasound bronchoscopy, in the same procedure as the initial diagnosis. There were no dose-limiting toxicity identified at the 20mg level.

Changes in physical activity and sedentary behavior during the first COVID-19 pandemic- restrictions in Germany: a nationwide survey : Running head: physical activity during the COVID-19 restrictions.

BACKGROUND: The COVID-19 pandemic restrictions posed challenges to maintaining healthy lifestyles and physical well-being. During the first mobility restrictions from March to mid-July 2020, the German population was advised to stay home, except for work, exercise, and essential shopping. Our objective was to comprehensively assess the impact of these restrictions on changes in physical activity and sedentary behavior to identify the most affected groups. METHODS: Between April 30, 2020, and May 12, 2020, we distributed a COVID-19-specific questionnaire to participants of the German National Cohort (NAKO). This questionnaire gathered information about participants' physical activity and sedentary behavior currently compared to the time before the restrictions. We integrated this new data with existing information on anxiety, depressive symptoms, and physical activity. The analyses focused on sociodemographic factors, social relationships, physical health, and working conditions. RESULTS: Out of 152,421 respondents, a significant proportion reported altered physical activity and sedentary behavioral patterns due to COVID-19 restrictions. Over a third of the participants initially meeting the WHO's physical activity recommendation could no longer meet the guidelines during the restrictions. Participants reported substantial declines in sports activities (mean change (M) = -0.38; 95% CI: -.390; -.378; range from -2 to + 2) and reduced active transportation (M = -0.12; 95% CI: -.126; -.117). However, they also increased recreational physical activities (M = 0.12; 95% CI: .117; .126) while engaging in more sedentary behavior (M = 0.24; 95% CI: .240; .247) compared to pre-restriction levels. Multivariable linear and log-binomial regression models indicated that younger adults were more affected by the restrictions than older adults. The shift to remote work, self-rated health, and depressive symptoms were the factors most strongly associated with changes in all physical activity domains, including sedentary behavior, and the likelihood to continue following the physical activity guidelines. CONCLUSIONS: Mobility patterns shifted towards inactivity or low-intensity activities during the nationwide restrictions in the spring of 2020, potentially leading to considerable and lasting health risks.

Bridge to M4 (B2M4): An innovative residency application preparation curriculum.

BACKGROUND: The medical residency application process is daunting, time-consuming, and variable, making mentorship in preparation for this process important. In light of changes to the residency application process due to the COVID-19 pandemic, medical students identified a need to create a formal residency application preparation curriculum. The curriculum focused on reflection, while also furthering professional development and preparing for the nuances of the residency application cycle through structured advising. APPROACH: Bridge to M4 (B2M4) included reflective activities to help guide curriculum vitae (CV) refinement, personal and professional values clarification, residency program exploration, elevator pitch formation, personal statement development, mentor identification, guidance on requesting letters of recommendation, and virtual residency interview preparation. EVALUATION: The B2M4 elective first took place in June 2020 with 36 rising fourth year students enrolled. Perceived effectiveness of the curriculum was assessed by having student cohorts evaluate the importance of the CV, personal statement, general preparation, and residency program selection before and after the course. Student feedback was reviewed with content analysis, which highlighted the usefulness of a structured residency preparation course that was rooted in reflection and incorporated faculty mentorship and feedback. IMPLICATIONS: This student-driven, innovative curricular design provided students the opportunity to prepare for the residency application process through reflective activities including values clarification, strengths identification, and goal setting. B2M4 demonstrates a process that can be used not only during the Residency Match process, but also throughout graduate medical education and future career decisions.

Ready Day One: What Residents and Program Directors Think is Needed for a Successful Transition to Residency.

OBJECTIVE: To evaluate perceived gaps in preparedness, current on-boarding practices, and need for specialty wide resources in the transition to residency training in obstetrics and gynecology (OB/GYN) DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional survey of current U.S. OB/GYN residents and program directors (PDs) at the time of the resident in-training exam was conducted in 2022. Both groups provide demographic information and identified specific knowledge, skills, and abilities in need of more preparation at the start of residency. PDs were queried on perceptions of readiness for their current first year class, educational on-boarding practices, and their preference for standardized curricular materials and assessment tools. Chi-squared and Kruskal-Wallis tests were used to compare perceptions of skills deficits between PDs and residents, and the relationship of preparedness to program type and resident year in training. RESULTS: Response rates for residents and program directors were 64.9% and 72.6% respectively. A majority (115/200, 57.5%) of program directors agreed or strongly agreed with the statement, "In general, I feel that my new interns are well prepared for residency when they arrive at my program." Both groups agreed that basic suturing and ultrasound skills were deficits. Residents identified a need for better preparation in management of inpatient issues while PDs identified time management skills as lacking. There was considerable heterogeneity of program on-boarding practices across the specialty. Most PDs agreed or strongly agreed that a standardized curriculum (80.5%, 161/200) and assessment tools (75.3%, 150/199) would be helpful. CONCLUSION: OBGYN PDs feel that not all residents arrive prepared for residency and overwhelmingly support the development of standardized transition curricular and assessment tools, similar to the curriculum developed in general surgery. Based on input from PDs and residents, early curricular efforts should focus on basic surgical, ultrasound, and time management skills and on management of inpatient issues.

A new tissue-agnostic microfluidic device to model physiology and disease: the lattice platform.

To accurately phenocopy human biology in vitro, researchers have been reducing their dependence on standard, static two-dimensional (2D) cultures and instead are moving towards three-dimensional (3D) and/or multicellular culture techniques. While these culture innovations are becoming more commonplace, there is a growing body of research that illustrates the benefits and even necessity of recapitulating the dynamic flow of nutrients, gas, waste exchange and tissue interactions that occur in vivo. However, cost and engineering complexity are two main factors that hinder the adoption of these technologies and incorporation into standard laboratory workflows. We developed LATTICE, a plug-and-play microfluidic platform able to house up to eight large tissue or organ models that can be cultured individually or in an interconnected fashion. The functionality of the platform to model both healthy and diseased tissue states was demonstrated using 3D cultures of reproductive tissues including murine ovarian tissues and human fallopian tube explants (hFTE). When exogenously exposed to pathological doses of gonadotropins and androgens to mimic the endocrinology of polycystic ovarian syndrome (PCOS), subsequent ovarian follicle development, hormone production and ovulation copied key features of this endocrinopathy. Further, hFTE cilia beating decreased significantly only when experiencing continuous media exchanges. We were then able to endogenously recreate this phenotype on the platform by dynamically co-culturing the PCOS ovary and hFTE. LATTICE was designed to be customizable with flexibility in 3D culture formats and can serve as a powerful automated tool to enable the study of tissue and cellular dynamics in health and disease in all fields of research.

From the Operating Room to the Cave: Ultrasound-Guided Locoregional Anesthesia in the Setting of Cave Rescue-A Description of 2 Cases.

Caving accidents are rare, but when they occur, they represent a unique logistical and medical challenge. Retrieving the patient to the surface often means navigating stretchers through narrow corridors with limited options for monitoring and interventions. Because the patient is usually not fasting, opioids and sedatives should be used with extreme caution. Therefore, alternative analgesic techniques such as locoregional nerve blocks are a promising strategy to improve patient comfort and safety during cave rescues. In this article, we describe 2 cases in which portable point-of-care ultrasound equipment was used to supplement clinical assessment and provide locoregional anesthesia to facilitate patient evacuation and transport. In this context, we discuss the role of portable ultrasound-guided locoregional anesthesia in cave rescue and in the global preclinical context. In summary, our cases demonstrated that the administration of ultrasound-guided prehospital locoregional anesthesia is a safe, rapid, and effective procedure even in extreme situations such as cave rescues. The advent of portable, high-quality ultrasound equipment may open the door for more widespread application of this technique in the global preclinical setting.

Endobronchial ultrasound-guided transbronchial needle injection of cisplatin results in dynamic changes in the tumor immune microenvironment.

RATIONALE: Direct intratumoral delivery of cisplatin via endobronchial ultrasound guided-transbronchial needle injections (EBUS-TBNI) is a novel approach for salvage treatment of advanced stage non-small cell lung cancer (NSCLC). The goal of this study was to evaluate changes in the tumor immune microenvironment during the course of EBUS-TBNI cisplatin therapy. METHODS: Under an IRB approved protocol, patients with recurrence after radiation therapy who were not receiving other cytotoxic therapy, were prospectively enrolled, and underwent weekly treatments with EBUS-TBNI with additional biopsies obtained for research. Needle aspiration was performed prior to cisplatin delivery at each procedure. Samples were evaluated by flow cytometry for the presence of immune cell types. RESULTS: Three of the six patients responded to the therapy based on RECIST criteria. Compared to the pre-treatment baseline, intratumoral neutrophils increased in 5 of the 6 patients (p = 0.041), with an average increase of 27.1%, but was not associated with response. A lower pre-treatment CD8+/CD4+ ratio at baseline was associated with response (P = 0.01). Responders demonstrated a lower final proportion of PD-1+ CD8+ T cells compared to non-responders (8.6% vs. 62.3%, respectively, P<0.001. Lower doses of intratumoral cisplatin were associated with subsequent increases in CD8+ T cells within the tumor microenvironment (P = 0.008). CONCLUSIONS: EBUS-TBNI cisplatin resulted in significant alterations in the tumor immune microenvironment. Further studies are needed to determine if the changes seen here generalize to larger cohorts.

The relationship between blood-brain barrier dysfunction and neurocognitive impairments in first-episode psychosis: findings from a retrospective chart analysis.

BACKGROUND: Even before the onset of psychotic symptoms, individuals with schizophrenia display cognitive impairments. Simultaneously, increasing amounts of individuals exhibit dysfunction of the blood-brain barrier (BBB). However, the impact of BBB dysfunction on neurocognitive impairment in people with first-episode psychosis has not yet been investigated. AIMS: To advance understanding of said relationship, we considered one of the largest first-episode psychosis cohorts with cerebrospinal fluid parameters available, and investigated whether BBB dysfunction is related to working memory, working speed and attention. METHOD: We conducted a retrospective chart review of 121 in-patients diagnosed with a first episode of a schizophrenia spectrum disorder. Patients underwent neurocognitive testing and a lumbar puncture within routine clinical care. To define BBB dysfunction, albumin cerebrospinal fluid/serum quotients, immunoglobulin G ratios and oligoclonal band types were evaluated, and gender-specific differences investigated. Neurocognitive functioning was assessed by the Wechsler Adult Intelligence Scale, Test of Attentional Performance and Repeatable Battery for the Assessment of Neuropsychological Status. We performed simple and multiple linear regression analyses to interpret associations of interest. RESULTS: Of those tested, 16% showed an alteration in albumin quotients and 12% had an oligoclonal band type indicating BBB dysfunction. Notably, male patients were more likely to have an increased albumin quotient and a higher immunoglobulin G ratio than female patients. We found no significant association between BBB dysfunction and neurocognitive assessments. CONCLUSIONS: The hypothesised relationship between BBB and neurocognitive impairments was not detectable in our retrospective cohort. Further cerebrospinal fluid-based studies with a longitudinal assessment of cognitive functioning and disease trajectory are urgently needed.

Visualizing intratumoral injections in lung tumors by endobronchial ultrasound.

Real-time endobronchial ultrasound images are crucial for the accurate placement of the needle in peribronchial lung tumors and lymph nodes for diagnostic sampling. Beyond its role as a diagnostic tool, ultrasound-guided bronchoscopy can also aid the delivery of anti-cancer agents intratumorally, enabling diagnosis, staging, and treatment to occur within the same anesthesia, reducing the patient's burden. However, determining drug retention and distribution in situ remains challenging, albeit pivotal in assessing the success or failure of the therapeutic intervention. We hypothesized that ultrasound images acquired by the bronchoscope during the injection can provide qualitative and quantitative real-time information about drug transport. As a proof-of-concept, we retrospectively analyzed 13 videos of intratumoral cisplatin injections in advanced non-small cell lung cancers. We identified the injection and performed quantitative analysis through image processing and segmentation algorithms and mathematical models in 5 of them. We were able to infer the unlikeliness of a laminar flow through interstitial pores in favor of the emergence of tissue fractures. These data imply that the structural integrity of the tumor is a critical determinant of the ultimate distribution of an intratumorally delivered agent.

Seeing Yourself Through the Learner's Eyes: Incorporating Smart Glasses Into Objective Structured Teaching Exercises for Faculty Development.

INTRODUCTION: Although physicians gain clinical knowledge in their specialty, it does not mean they receive adequate instruction to teach and provide feedback. Using smart glasses (SG) to provide educators with a first-person learner perspective has not been explored in faculty development such as Objective Structured Teaching Exercises (OSTEs). METHODS: Integrated within a 6-session continuing medical education-bearing certificate course, this descriptive study involved one session where participants provided feedback to a standardized student in an OSTE. Participants were recorded by mounted wall cameras (MWCs) and SG. They received verbal feedback on their performance based on a self-designed assessment tool. Participants reviewed the recorded content and identified areas for improvement, completed a survey about their experience with SG, and wrote a narrative reflection. RESULTS: Seventeen physicians at the assistant professor level participated in the session; data were analyzed on the 14 who had both MWC and SG recordings and who also completed the survey and reflection. All were comfortable with the standardized student wearing SG and indicated it did not affect communication. Eighty-five percent of the participants felt the SG provided additional feedback not available with the MWC, with majority noting additional feedback was related to eye contact, body language, voice inflection, and tone. Eighty-six percent see value in using SG for faculty development, and 79% felt that periodically using SG in their teaching would improve quality. CONCLUSION: Use of SG during an OSTE on giving feedback was a nondistracting and positive experience. SG provided affective feedback otherwise not perceived from a standard MWC.

Facilitating an Optimal Transition to Residency in Obstetrics and Gynecology.

The transition to residency in obstetrics and gynecology is difficult, threatening the well-being of residents as well as their preparedness to care for patients. In addition to essential foundational knowledge and skills, obstetrics and gynecology interns must develop professional identity and a growth mindset toward learning to acquire the self-directed learning skills required of physicians throughout their careers. The transition to residency is a critical opportunity for learning and development. A group of educators and learners from around the country created a preparedness program building on available resources. The result is a national curriculum for improving the transition to obstetrics and gynecology residency on three levels: self-directed learning, facilitated small-group workshops, and coaching. Sharing tools for preparing matched applicants for residency in obstetrics and gynecology ensures adequate residency preparation for all interns, independent of medical school attended. This program aims to address potential threats to equity in the training of our future workforce and to ensure that all obstetrics and gynecology interns are prepared to thrive in residency training.

Synthesis of Four Steroidal Carbamates with Antitumor Activity against Mouse Colon Carcinoma CT26WT Cells: In Vitro and In Silico Evidence.

Colorectal cancer (CRC) is one of the most lethal cancers worldwide. If detected on time, surgery can expand life expectations of patients up to five more years. However, if metastasis has grown deliberately, the use of chemotherapy can play a crucial role in CRC control. Moreover, the lack of selectivity of current anticancer drugs, plus mutations that occur in cancerous cells, demands the development of new chemotherapeutic agents. Several steroids have shown their potentiality as anticancer agents, while some other compounds, such as Taxol and its derivatives bearing a carbamate functionality, have reached the market. In this article, the synthesis, characterization, and antiproliferative activity of four steroidal carbamates on mouse colon carcinoma CT26WT cells are described. Carbamate synthesis occurred via direct reaction between diosgenin, its B-ring modified derivative, and testosterone with phenyl isocyanate under a Brønsted acid catalysis. All obtained compounds were characterized by 1H and 13C Nuclear Magnetic Resonance (NMR), High Resolution Mass Spectroscopy (HRMS); their melting points are also reported. Results obtained from antiproliferative activity assays indicated that carbamates compounds have inhibitory effects on the growth of this colon cancer cell line. A molecular docking study carried out on Human Prostaglandin E Receptor (EP4) showed a high affinity between carbamates and protein, thus providing a valuable theoretical explanation of the in vitro results.

Preventing caesarean section wound complications: use of a silver-impregnated antimicrobial occlusive dressing.

OBJECTIVE: To investigate the role of an adherent soft silicone antimicrobial occlusive foam silver-impregnated dressing for reduction of surgical site infections (SSI) in primary low-transverse caesarean section (1°LTCS) delivery. METHOD: Women aged 18-45 years admitted to the labour and delivery or the antepartum unit undergoing a 1°LTCS were recruited. Exclusion criteria included repeat caesarean, vertical skin incision, intrapartum fever and closure with staples. Consented participants delivered by scheduled or unscheduled 1°LTCS received the silver-impregnated dressing. Those who declined to participate and were delivered by scheduled or unscheduled caesarean received a standard gauze with tape dressing (controls). Surgical preparation and preoperative antibiotics were administered as per hospital policy. RESULTS: A total of 362 participants were consented for use of the silver-impregnated dressing, with 190 participants undergoing 1°LTCS, of whom 185 were included in the final analysis. Of those who declined to participate, 190 ultimately underwent 1°LTCS during the same time period. Cases and controls were similar in demographics, body mass index, diabetes status, labour and procedure length, and tobacco use. The overall incidence of SSI was 3.7%. A 50% reduction in incidence of SSI was observed in the silver-impregnated dressing group compared with control group (2.7% versus 4.7%, respectively), but this was not statistically significant (p=0.08; odds ratio 0.55; 95% confidence interval: 0.18-1.67). CONCLUSION: Among women undergoing 1°LTCS with subcuticular closure of a transverse incision, use of a silver-impregnated dressing reduced the rate of SSI by >50% but was not statistically significant.

Analysis of cervical HPV infections among unvaccinated young adult women to inform vaccine strategies in this age group: the Costa Rica HPV Vaccine Trial.

INTRODUCTION: Human papillomavirus (HPV) vaccines protect against incident HPV infections, which cause cervical cancer. OBJECTIVES: We estimated the prevalence and incidence of HPV infections in young adult women to understand the impact of an HPV vaccination programme in this population. METHODS: We collected cervical specimens from 6322 unvaccinated women, aged 18-37 years, who participated in the Costa Rica Vaccine Trial and its long-term follow-up. Women were followed for (median) 4.8 years and had (median) 4.0 study visits. Cervical specimens were tested for the presence/absence of 25 HPV genotypes. For each age band, we estimated the percentage of women with 1+ prevalent or 1+ incident HPV infections using generalised estimating equations. We also estimated the prevalence and incidence of HPV as a function of time since first sexual intercourse (FSI). RESULTS: The model estimated HPV incident infections peaked at 28.0% (95% CI 25.3% to 30.9%) at age 20 years then steadily declined to 11.8% (95% CI 7.6% to 17.8%) at age 37 years. Incident oncogenic HPV infections (HPV16/18/31/33/35/39/45/51/52/56/58/59) peaked and then declined from 20.3% (95% CI 17.9% to 22.9%) to 7.7% (95% CI 4.4% to 13.1%); HPV16/18 declined from 6.4% (95% CI 5.1% to 8.1%) to 1.1% (95% CI 0.33% to 3.6%) and HPV31/33/45/52/58 declined from 11.0% (95% CI 9.3% to 13.1%) to 4.5% (95% CI 2.2% to 8.9%) over the same ages. The percentage of women with 1+ incident HPV of any, oncogenic, non-oncogenic and vaccine-preventable (HPV16/18, HPV31/33/45, HPV31/33/45/52/58, and HPV6/11) types peaked <1 year after FSI and steadily declined with increasing time since FSI (p for trends <0.001). We observed similar patterns for model estimated HPV prevalences. CONCLUSION: Young adult women may benefit from HPV vaccination if newly acquired vaccine-preventable oncogenic infections lead to cervical precancer and cancer. HPV vaccination targeting this population may provide additional opportunities for primary prevention. TRIAL REGISTRATION NUMBER: NCT00128661.

Alternative Options for Complex, Recurrent Pain States Using Cannabinoids, Psilocybin, and Ketamine: A Narrative Review of Clinical Evidence.

With emerging information about the potential for morbidity and reduced life expectancy with long-term use of opioids, it is logical to evaluate nonopioid analgesic treatments to manage pain states. Combinations of drugs can provide additive and/or synergistic effects that can benefit the management of pain states. In this regard, tetrahydrocannabinol (THC) and cannabidiol (CBD) modulate nociceptive signals and have been studied for chronic pain treatment. Psilocybin, commonly known as "magic mushrooms", works at the serotonin receptor, 5-HT2A. Psilocybin has been found in current studies to help with migraines since it has a tryptamine structure and works similarly to triptans. Psilocybin also has the potential for use in chronic pain treatment. However, the studies that have looked at alternative plant-based medications such as THC, CBD, and psilocybin have been small in terms of their sample size and may not consider the demographic or genetic differences in the population because of their small sample sizes. At present, it is unclear whether the effects reported in these studies translate to the general population or even are significant. In summary, additional studies are warranted to evaluate chronic pain management with alternative and combinations of medications in the treatment of chronic pain.

Storing and analyzing a genome on a blockchain.

There are major efforts underway to make genome sequencing a routine part of clinical practice. A critical barrier to these is achieving practical solutions for data ownership and integrity. Blockchain provides solutions to these challenges in other realms, such as finance. However, its use in genomics is stymied due to the difficulty in storing large-scale data on-chain, slow transaction speeds, and limitations on querying. To overcome these roadblocks, we developed a private blockchain network to store genomic variants and reference-aligned reads on-chain. It uses nested database indexing with an accompanying tool suite to rapidly access and analyze the data.

Pharmacokinetics of a single dose of oclacitinib maleate as a top dress in adult horses.

The objective of this study was to determine the pharmacokinetic parameters of oclacitinib maleate as a top dress given to adult horses. Six adult horses with a mean weight of 528 kg were administered a single dose of 0.5 mg/kg oclacitinib maleate. Blood was collected prior to drug administration and at 15 min, 30 min, 45 min, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h after treatment. Oclacitinib maleate plasma concentrations were measured by liquid chromatography/mass spectrometry. Pharmacokinetic parameters were found best to fit a one-compartment model. Mean Cmax was 486 ng/ml (range 423-549 ng/ml), and Tmax was estimated to be 1.7 h (range 0.3-3.1 h). The estimated T1/2 was 7.5-8 h.

MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer.

BACKGROUND: The long non-coding RNA (lncRNA), MALAT1, plays a key role in the development of different cancers, and its expression is associated with worse prognosis in patients. However, its mechanism of action and its regulation are not well known in prostate cancer (PCa). A general mechanism of action of lncRNAs is their interaction with other epigenetic regulators including microRNAs (miRNAs). METHODS: Using lentiviral stable miRNA transfection together with cell biology functional assays and gene expression/target analysis, we investigated the interaction between MALAT1 and miR-423-5p, defined as a target with in silico prediction analysis, in PCa. RESULTS: Through bioinformatic analysis of data available from TCGA, we have found that MALAT1 expression correlates with high Gleason grade, metastasis occurrence, and reduced survival in PCa patients. These findings were validated on a TMA of PCa showing a significant correlation between MALAT1 expression with both stage and grading. We report that, in PCa cells, MALAT1 expression and activity is regulated by miR-423-5p that binds MALAT1, downregulates its expression and inhibits its activity in promoting proliferation, migration, and invasion. Using NanoString analysis, we unraveled downstream cell pathways that were affected by miR-423-5p expression and MALAT1 downregulation and identified several alterations in genes that are involved in metastatic response and angiogenic pathways. In addition, we showed that the overexpression of miR-423-5p increases survival and decreases metastases formation in a xenograft mouse model. CONCLUSIONS: We provide evidence on the role of MALAT1 in PCa tumorigenesis and progression. Also, we identify a direct interaction between miR-423-5p and MALAT1, which results in the suppression of MALAT1 action in PCa.