An environmental scan of mental health services for indigenous youth in Canada.

Background: There is an urgent need for culturally and contextually relevant mental health support for First Nations, Inuit and Métis youth. Objective: Our aim was to identify mental health and wellness services that are currently available to Indigenous youth across Canada. Methodology: As a first step, we conducted a web-based environmental scan of services tailored to Indigenous youth. Specific factors were examined for each program, including organization type and mission, types of services, and who provides services. Results: One hundred and seventeen programs were found, with 54% being non-profits and 34% being on-reserve. Four core features were identified. The first was a strengths-based focus, rather than a pathology/deficit-focus, in programs' vision and mission statements, reflected in words like wellness and resilience. The second (87% of included programs) was the integration of mental health services with a range of other services and supports (e.g., health, employment, housing). The third was the provision of land-based programming (in 34% of programs) such as camps or hunting. Such programs were framed as promoting wellness and healing and strengthening identity. The fourth was the role of community members without formal mental health professional training (in 42% of programs), for example, as youth workers or knowledge keepers. This stems not only from the dearth of specialists in many Indigenous settings, but also a valuing of Indigenous knowledge. Conclusion: These core features in mental health services for Indigenous youth may be promising avenues for communities seeking to strengthen the services they offer to First Nations, Inuit and Métis youth.

Contexte: Il y a un besoin urgent de soutien en santé mentale adapté à la culture et au contexte pour les jeunes des Premières Nations, Inuits et Métis. Objectif: Nous cherchions à identifier les services de santé mentale et de bien-être actuellement disponibles pour les jeunes autochtones du Canada. Méthodologie: Dans un premier temps, nous avons mené une analyse environnementale en ligne des services adaptés aux jeunes autochtones. Des facteurs spécifiques ont été examinés pour chaque programme, notamment le type et la mission de l'organisation, les types de services offerts, et les prestataires de ces services. Résultats: Cent dix-sept programmes ont été recensés, dont 54 % étaient sans but lucratif et 34 % situés dans une réserve. Quatre caractéristiques principales ont été identifiées. La première était l'accent mis sur les forces plutôt que sur la pathologie ou le déficit, reflété dans les énoncés de vision et de mission des programmes, où des termes comme bien-être et résilience étaient utilisés. La deuxième caractéristique (présente dans 87 % des programmes) était l'intégration des services de santé mentale avec une gamme d'autres services et soutiens (p.ex., santé, emploi, logement). La troisième était l'offre de programmes liés au territoire (dans 34 % des programmes) comme des camps ou des activités de chasse, conçus pour promouvoir le bien-être, la guérison et le renforcement de l'identité. La quatrième caractéristique était le rôle des membres de la communauté sans formation professionnelle officielle en santé mentale (dans 42 % des programmes), par exemple en tant que travailleurs auprès des jeunes ou gardiens du savoir. Cela découle non seulement du manque de spécialistes dans de nombreux contextes autochtones, mais aussi de la valorisation des connaissances autochtones. Conclusion: Ces principales caractéristiques des services de santé mentale pour les jeunes autochtones peuvent constituer des avenues prometteuses pour les communautés cherchant à consolider les services qu'elles offrent aux jeunes des Premières Nations, Inuits et Métis.

Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP): study protocol for a multicenter, randomized, adaptive allocation clinical trial to identify the optimal duration of induced hypothermia for neuroprotection in comatose, adult survivors of after out-of-hospital cardiac arrest.

Background: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the United States. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. Methods: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 hours of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 hours will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient reported quality of life measures. Discussion: In-vitro and in-vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. Trial registration: ClinicalTrials.gov (NCT04217551, 2019-12-30).

Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP): study protocol for a multicenter, randomized, adaptive allocation clinical trial to identify the optimal duration of induced hypothermia for neuroprotection in comatose, adult survivors of after out-of-hospital cardiac arrest.

BACKGROUND: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the USA. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. METHODS: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 h of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 h will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient-reported quality of life measures. DISCUSSION: In vitro and in vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. TRIAL REGISTRATION: ClinicalTrials.gov NCT04217551. Registered on 30 December 2019.

From diagnosis to intervention: a review of telemedicine's role in skin cancer care.

Skin cancer treatment is a core aspect of dermatology that relies on accurate diagnosis and timely interventions. Teledermatology has emerged as a valuable asset across various stages of skin cancer care including triage, diagnosis, management, and surgical consultation. With the integration of traditional dermoscopy and store-and-forward technology, teledermatology facilitates the swift sharing of high-resolution images of suspicious skin lesions with consulting dermatologists all-over. Both live video conference and store-and-forward formats have played a pivotal role in bridging the care access gap between geographically isolated patients and dermatology providers. Notably, teledermatology demonstrates diagnostic accuracy rates that are often comparable to those achieved through traditional face-to-face consultations, underscoring its robust clinical utility. Technological advancements like artificial intelligence and reflectance confocal microscopy continue to enhance image quality and hold potential for increasing the diagnostic accuracy of virtual dermatologic care. While teledermatology serves as a valuable clinical tool for all patient populations including pediatric patients, it is not intended to fully replace in-person procedures like Mohs surgery and other necessary interventions. Nevertheless, its role in facilitating the evaluation of skin malignancies is gaining recognition within the dermatologic community and fostering high approval rates from patients due to its practicality and ability to provide timely access to specialized care.

Numerical Simulations of the Epley Maneuver With Clinical Implications.

OBJECTIVES: Canalith repositioning procedures to treat benign paroxysmal positional vertigo are often applied following standardized criteria, without considering the possible anatomical singularities of the membranous labyrinth for each individual. As a result, certain patients may become refractory to the treatment due to significant deviations from the ideal membranous labyrinth, that was considered when the maneuvers were designed. This study aims to understand the dynamics of the endolymphatic fluid and otoconia, within the membranous labyrinth geometry, which may contribute to the ineffectiveness of the Epley maneuver. Simultaneously, the study seeks to explore methods to avoid or reduce treatment failure. DESIGN: We conducted a study on the Epley maneuver using numerical simulations based on a three-dimensional medical image reconstruction of the human left membranous labyrinth. A high-quality micro-computed tomography of a human temporal bone specimen was utilized for the image reconstruction, and a mathematical model for the endolymphatic fluid was developed and coupled with a spherical particle model representing otoconia inside the fluid. This allowed us to measure the position and time of each particle throughout all the steps of the maneuver, using equations that describe the physics behind benign paroxysmal positional vertigo. RESULTS: Numerical simulations of the standard Epley maneuver applied to this membranous labyrinth model yielded unsatisfactory results, as otoconia do not reach the frontside of the utricle, which in this study is used as the measure of success. The resting times between subsequent steps indicated that longer intervals are required for smaller otoconia. Using different angles of rotation can prevent otoconia from entering the superior semicircular canal or the posterior ampulla. Steps 3, 4, and 5 exhibited a heightened susceptibility to failure, as otoconia could be accidentally displaced into these regions. CONCLUSIONS: We demonstrate that modifying the Epley maneuver based on the numerical results obtained in the membranous labyrinth of the human specimen under study can have a significant effect on the success or failure of the treatment. The use of numerical simulations appears to be a useful tool for future canalith repositioning procedures that aim to personalize the treatment by modifying the rotation planes currently defined as the standard criteria.

The Use of Anemia Control Model Is Associated with Improved Hemoglobin Target Achievement, Lower Rates of Inappropriate Erythropoietin Stimulating Agents, and Severe Anemia among Dialysis Patients.

INTRODUCTION: The Anemia Control Model (ACM) is a certified medical device suggesting the optimal ESA and iron dosage for patients on hemodialysis. We sought to assess the effectiveness and safety of ACM in a large cohort of hemodialysis patients. METHODS: This is a retrospective study of dialysis patients treated in NephroCare centers between June 1, 2013 and December 31, 2019. We compared patients treated according to ACM suggestions and patients treated in clinics where ACM was not activated. We stratified patients belonging to the reference group by historical target achievement rates in their referral centers (tier 1: <70%; tier 2: 70-80%; tier 3: >80%). Groups were matched by propensity score. RESULTS: After matching, we obtained four groups with 85,512 patient-months each. ACM had 18% higher target achievement rate, 63% smaller inappropriate ESA administration rate, and 59% smaller severe anemia risk compared to Tier 1 centers (all p < 0.01). The corresponding risk ratios for ACM compared to Tier 2 centers were 1.08 (95% CI: 1.08-1.09), 0.49 (95% CI: 0.47-0.51), and 0.64 (95% CI: 0.61-0.68); for ACM compared to Tier 3 centers, 1.01 (95% CI: 1.01-1.02), 0.66 (95% CI: 0.63-0.69), and 0.94 (95% CI: 0.88-1.00), respectively. ACM was associated with statistically significant reductions in ESA dose administration. CONCLUSION: ACM was associated with increased hemoglobin target achievement rate, decreased inappropriate ESA usage and a decreased incidence of severe anemia among patients treated according to ACM suggestion.

Household food insecurity is associated with greater autonomic dysfunction testing score in Latinos with type 2 diabetes.

AIM: We examined household food insecurity (HFI) and autonomic nervous system (ANS) function in a subset of low-income Latinos with type 2 diabetes with data from a stress management trial. METHODS: InclusionLatino or Hispanic, Spanish speaking, age less than 18 years, ambulatory status, type 2 diabetes more than 6 months, A1c less than 7.0%. ExclusionPain or dysfunction in hands (e.g., arthritis) precluding handgrip testing; medical or psychiatric instability. HFI was assessed with the 6-item U.S. household food security survey module; with responses to > = 1 question considered HFI. An ANS dysfunction index was calculated from xix autonomic function tests which were scored 0 = normal or 1 = abnormal based on normative cutoffs and then summed. Autonomic function tests were: 1) 24-hour heart rate variability as reflected in standard deviation of the normal-to-normal (SDNN) heart rate acquired with 3-channel, 7-lead ambulatory electrocardiogram (Holter) monitors; 2) difference between the highest diastolic blood pressure (DBP) during sustained handgrip and the average DBP at rest; 3) difference between baseline supine and the minimal BP after standing up; and, from 24-hour urine specimens 4) cortisol, 5) normetanephrine, and, 6) metanephrine. RESULTS: Thirty-five individuals participated, 23 (65.7%) of them were women, age mean = 61.6 (standard deviation = 11.2) years, HbA1c mean = 8.5% (standard deviation = 1.6) and 20 participants (57.1%) used insulin. Twenty-two participants (62.9%) reported HFI and 25 (71.4%) had one or more abnormal ANS measure. Independent t-tests showed that participants with HFI had a higher ANS dysfunction index (mean = 1.5, standard deviation = 0.9) than patients who were food secure (mean = 0.7, standard deviation = 0.8), p = 0.02. Controlling for financial strain did not change significance. Total ANS index was not related to glycemia, insulin use or other socioeconomic indicators. In this sample, HFI was associated with ANS dysfunction. Policies to improve food access and affordability may benefit health outcomes for Latinos with diabetes.

Lay health worker research personnel for home-based data collection in clinical and translational research: Qualitative and quantitative findings from two trials in hard-to-reach populations.

Aims: The role of lay health workers in data collection for clinical and translational research studies is not well described. We explored lay health workers as data collectors in clinical and translational research studies. We also present several methods for examining their work, i.e., qualitative interviews, fidelity checklists, and rates of unusable/missing data. Methods: We conducted 2 randomized, controlled trials that employed lay health research personnel (LHR) who were employed by community-based organizations. In one study, n = 3 Latina LHRs worked with n = 107 Latino diabetic participants. In another study, n = 6 LHR worked with n = 188 Cambodian American refugees with depression. We investigated proficiency in biological, behavioral, and psychosocial home-based data collection conducted by LHR. We also conducted in-depth interviews with lay LHR to explore their experience in this research role. Finally, we described the training, supervision, and collaboration for LHR to be successful in their research role. Results: Independent observers reported a very high degree of fidelity to technical data collection protocols (>95%) and low rates of missing/unusable data (1.5%-11%). Qualitative results show that trust, training, communication, and supervision are key and that LHR report feeling empowered by their role. LHR training included various content areas over several weeks with special attention to LHR and participant safety. Training and supervision from both the academic researchers and the staff at the community-based organizations were necessary and had to be well-coordinated. Conclusions: Carefully selected, trained, and supervised LHRs can collect sophisticated data for community-based clinical and translational research.

Thymoquinone Potentially Modulates the Expression of Key Onco- and Tumor Suppressor miRNAs in Prostate and Colon Cancer Cell Lines: Insights from PC3 and HCT-15 Cells.

Prostate cancer (PC) and colon cancer significantly contribute to global cancer-related morbidity and mortality. Thymoquinone (TQ), a naturally occurring phytochemical found in black cumin, has shown potential as an anticancer compound. This study aimed to investigate the effects of TQ on the expression profile of key tumor suppressor and onco-suppressor miRNAs in PC3 prostate cancer cells and HCT-15 colon cancer cells. Cell viability assays revealed that TQ inhibited the growth of both cell lines in a dose-dependent manner, with IC50 values of approximately 82.59 µM for HCT-15 and 55.83 µM for PC3 cells. Following TQ treatment at the IC50 concentrations, miRNA expression analysis demonstrated that TQ significantly downregulated miR-21-5p expression in HCT-15 cells and upregulated miR-34a-5p, miR-221-5p, miR-17-5p, and miR-21-5p expression in PC3 cells. However, no significant changes were observed in the expression levels of miR-34a-5p and miR-200a-5p in HCT-15 cells. The current findings suggest that TQ might exert its antiproliferative effects by modulating specific tumor suppressor and onco-suppressor miRNAs in prostate and colon cancer cells. Further investigations are warranted to elucidate the precise underlying mechanisms and to explore the therapeutic potential of TQ in cancer treatment. To the best of our knowledge, this is the first report regarding the effect of TQ on the miRNA expression profile in colon and prostate cancer cell lines.

Fgf signalling triggers an intrinsic mesodermal timer that determines the duration of limb patterning.

Complex signalling between the apical ectodermal ridge (AER - a thickening of the distal epithelium) and the mesoderm controls limb patterning along the proximo-distal axis (humerus to digits). However, the essential in vivo requirement for AER-Fgf signalling makes it difficult to understand the exact roles that it fulfils. To overcome this barrier, we developed an amenable ex vivo chick wing tissue explant system that faithfully replicates in vivo parameters. Using inhibition experiments and RNA-sequencing, we identify a transient role for Fgfs in triggering the distal patterning phase. Fgfs are then dispensable for the maintenance of an intrinsic mesodermal transcriptome, which controls proliferation/differentiation timing and the duration of patterning. We also uncover additional roles for Fgf signalling in maintaining AER-related gene expression and in suppressing myogenesis. We describe a simple logic for limb patterning duration, which is potentially applicable to other systems, including the main body axis.

Botulinum Toxin for Scalp Conditions: A Systematic Review.

BACKGROUND: Many reports have described the use of botulinum toxin (BTX) in the treatment of scalp conditions, but no studies have synthesized these collective findings. OBJECTIVE: We conducted a systematic review to summarize the scalp conditions for which treatment with BTX has been described. METHODS: We searched PubMed/MEDLINE and Scopus for articles in English published before November 1, 2022, using the keywords "hair" or "scalp" and BTX-related search terms. Articles that described patients who received injections of BTX for the management of scalp conditions were included. RESULTS: Twenty-four original articles (12 case reports, 9 clinical trials, and 3 case series) were identified that described 309 patients with a scalp condition treated with BTX. Androgenetic alopecia, craniofacial hyperhidrosis, and scalp hyperseborrhea had the most robust data supporting the clinical efficacy of BTX. CONCLUSION: The current quality of evidence is highly variable and, for many conditions, limited to small observational studies. Botulinum toxin may be a promising therapeutic option for patients with various scalp conditions, but future studies are needed to better understand its efficacy and safety.

Neuronal γ-secretase regulates lipid metabolism, linking cholesterol to synaptic dysfunction in Alzheimer's disease.

Presenilin mutations that alter γ-secretase activity cause familial Alzheimer's disease (AD), whereas ApoE4, an apolipoprotein for cholesterol transport, predisposes to sporadic AD. Both sporadic and familial AD feature synaptic dysfunction. Whether γ-secretase is involved in cholesterol metabolism and whether such involvement impacts synaptic function remains unknown. Here, we show that in human neurons, chronic pharmacological or genetic suppression of γ-secretase increases synapse numbers but decreases synaptic transmission by lowering the presynaptic release probability without altering dendritic or axonal arborizations. In search of a mechanism underlying these synaptic impairments, we discovered that chronic γ-secretase suppression robustly decreases cholesterol levels in neurons but not in glia, which in turn stimulates neuron-specific cholesterol-synthesis gene expression. Suppression of cholesterol levels by HMG-CoA reductase inhibitors (statins) impaired synaptic function similar to γ-secretase inhibition. Thus, γ-secretase enables synaptic function by maintaining cholesterol levels, whereas the chronic suppression of γ-secretase impairs synapses by lowering cholesterol levels.

Numerical simulations to determine the stimulation of the crista ampullaris during the Head Impulse Test.

The Head Impulse Test, the most widely accept test to assess the vestibular function, comprises rotations of the head based on idealized orientations of the semicircular canals, instead of their individual arrangement specific for each patient. In this study, we show how computational modelling can help personalize the diagnosis of vestibular diseases. Based on a micro-computed tomography reconstruction of the human membranous labyrinth and their simulation using Computational Fluid Dynamics and Fluid-Solid Interaction techniques, we evaluated the stimulus experienced by the six cristae ampullaris under different rotational conditions mimicking the Head Impulse Test. The results show that the maximum stimulation of the crista ampullaris occurs for directions of rotation that are more aligned with the orientation of the cupulae (average deviation from alignment of 4.7°, 9.8°, and 19.4° for the horizontal, posterior, and superior maxima, respectively) than with the planes of the semicircular canals (average deviation from alignment of 32.4°, 70.5°, and 67.8° for the horizontal, posterior, and superior maxima, respectively). A plausible explanation is that when rotations are applied with respect to the center of the head, the inertial forces acting directly over the cupula become dominant over the endolymphatic fluid forces generated in the semicircular canals. Our results indicate that it is necessary to consider cupulae orientation to ensure optimal conditions for testing the vestibular function.

Onychomycosis: Old and New.

Onychomycosis is a common chronic fungal infection of the nail that causes discoloration and/or thickening of the nail plate. Oral agents are generally preferred, except in the case of mild toenail infection limited to the distal nail plate. Terbinafine and itraconazole are the only approved oral therapies, and fluconazole is commonly utilized off-label. Cure rates with these therapies are limited, and resistance to terbinafine is starting to develop worldwide. In this review, we aim to review current oral treatment options for onychomycosis, as well as novel oral drugs that may have promising results in the treatment of onychomycosis.

Maternal emotional regulation strategy is associated with newborn feeding practices within 72 h after delivery: Cross sectional analyses of a multi-center study in China.

BACKGROUND: Early feeding practices have a great impact on the growth and development of infants, and the health of mothers. Maternal emotional regulation (ER) is closely related to infant feeding practices. Exploring the relationship between ER strategy and feeding practice can inform early exclusive breastfeeding (EBF) interventions. METHODS: Using baseline survey of a longitudinal study, 965 mothers in Chongqing municipality, Guangzhou city, and Huizhou city were enrolled. At baseline, the study used self-administrated questionnaires to investigate the socio-demographic characteristics, maternal ER strategies and feeding practice within 72 h of delivery. Chi-square test and logistic regression were used to determine the associations of the mothers' ER and feeding practices within 72 h postpartum. RESULTS: Among 965 participants, 27.8 % of mothers practiced EBF, and 69.5 % of mothers reported getting breastfeeding education from health providers. The average scores on the cognitive reappraisal and the expressive suppression of the ERQ were 29.95 ± 7.24 and 14.47 ± 5.16 respectively. Multivariable analysis showed women with expressive suppression were less likely to practice EBF (aOR = 0.96, 95%CI: 0.93-0.98, p = 0.002), while receiving breastfeeding education was positively associated with EBF (aOR = 1.52, 95%CI: 1.09-2.12, p = 0.013). LIMITATIONS: Because the study started during the COVID-19 pandemic, the lock-down measures paused recruitments for quite some time reducing the enrollment of participation. The data we used was within 72 h postpartum, hence the period of time to study feeding practices was short. CONCLUSION: Mothers' ER strategy and breastfeeding education need to be addressed as part of interventions designed to improve EBF rates during the newborn period in China.

Fructose-1,6-bisphosphatase is a nonenzymatic safety valve that curtails AKT activation to prevent insulin hyperresponsiveness.

Insulin inhibits gluconeogenesis and stimulates glucose conversion to glycogen and lipids. How these activities are coordinated to prevent hypoglycemia and hepatosteatosis is unclear. Fructose-1,6-bisphosphatase (FBP1) is rate controlling for gluconeogenesis. However, inborn human FBP1 deficiency does not cause hypoglycemia unless accompanied by fasting or starvation, which also trigger paradoxical hepatomegaly, hepatosteatosis, and hyperlipidemia. Hepatocyte FBP1-ablated mice exhibit identical fasting-conditional pathologies along with AKT hyperactivation, whose inhibition reversed hepatomegaly, hepatosteatosis, and hyperlipidemia but not hypoglycemia. Surprisingly, fasting-mediated AKT hyperactivation is insulin dependent. Independently of its catalytic activity, FBP1 prevents insulin hyperresponsiveness by forming a stable complex with AKT, PP2A-C, and aldolase B (ALDOB), which specifically accelerates AKT dephosphorylation. Enhanced by fasting and weakened by elevated insulin, FBP1:PP2A-C:ALDOB:AKT complex formation, which is disrupted by human FBP1 deficiency mutations or a C-terminal FBP1 truncation, prevents insulin-triggered liver pathologies and maintains lipid and glucose homeostasis. Conversely, an FBP1-derived complex disrupting peptide reverses diet-induced insulin resistance.

MicroRNAs and long non-coding RNAs in pancreatic cancer: From epigenetics to potential clinical applications.

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two relevant classes of non-coding RNAs (ncRNAs) that play a pivotal role in a number of molecular processes through different epigenetic regulatory mechanisms of gene expression. As a matter of fact, the altered expression of these types of RNAs leads to the development and progression of a varied range of multifactorial human diseases. Several recent reports elucidated that miRNA and lncRNAs have been implicated in pancreatic cancer (PC). For instance, dysregulation of such ncRNAs has been found to be associated with chemoresistance, apoptosis, autophagy, cell differentiation, tumor suppression, tumor growth, cancer cell proliferation, migration, and invasion in PC. Moreover, several aberrantly expressed miRNAs and lncRNAs have the potential to be used as biomarkers for accurate PC diagnosis. Additionally, miRNAs and lncRNAs are considered as promising clinical targets for PC. Therefore, in this review, we discuss recent experimental evidence regarding the clinical implications of miRNAs and lncRNAs in the pathophysiology of PC, their future potential, as well as the challenges that have arisen in this field of study in order to drive forward the design of ncRNA-based diagnostics and therapeutics for PC.