MiR-21 Regulates Growth and Migration of Cervical Cancer Cells by RECK Signaling Pathway.

Expression of miR-21 has been found to be altered in almost all types of cancers, and it has been classified as an oncogenic microRNA. In addition, the expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In the present study, we analyze the role of miR-21 in RECK gene regulation in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression using siRNAs. We analyzed the expression of miR-21 and RECK, as well as functional effects on cell proliferation and migration. We found that in cervical cancer cells, there was an inverse correlation between miR-21 expression and RECK mRNA and protein expression. SiRNAs to miR-21 increased luciferase reporter activity in construct plasmids containing the RECK-3'-UTR microRNA response elements MRE21-1, MRE21-2, and MRE21-3. The role of miR-21 in cell proliferation was also analyzed, and cancer cells transfected with siRNAs exhibited a markedly reduced cell proliferation and migration. Our findings indicate that miR-21 post-transcriptionally down-regulates the expression of RECK to promote cell proliferation and cell migration inhibition in cervical cancer cell survival. Therefore, miR-21 and RECK may be potential therapeutic targets in gene therapy for cervical cancer.

Visceral Adipose Tissue: The Hidden Culprit for Type 2 Diabetes.

Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by insulin resistance in various tissues. Though conventionally associated with obesity, current research indicates that visceral adipose tissue (VAT) is the leading determining factor, wielding more influence regardless of individual body mass. The heightened metabolic activity of VAT encourages the circulation of free fatty acid (FFA) molecules, which induce insulin resistance in surrounding tissues. Individuals most vulnerable to this preferential fat deposition are older males with ancestral ties to Asian countries because genetics and sex hormones are pivotal factors for VAT accumulation. However, interventions in one's diet and lifestyle have the potential to strategically discourage the growth of VAT. This illuminates the possibility that the expansion of VAT and, subsequently, the risk of T2D development are preventable. Therefore, by reducing the amount of VAT accumulated in an individual and preventing it from building up, one can effectively control and prevent the development of T2D.

Assessment and report of individual symptoms in studies of delirium in postoperative populations: a systematic review.

OBJECTIVES: Delirium is most often reported as present or absent. Patients with symptoms falling short of the diagnostic criteria for delirium fall into 'no delirium' or 'control' groups. This binary classification neglects individual symptoms and may be hindering identification of the pathophysiology underlying delirium. This systematic review investigates which individual symptoms of delirium are reported by studies of postoperative delirium in adults. METHODS: Medline, EMBASE and Web of Science databases were searched on 03 June 2021 and 06 April 2023. Two reviewers independently examined titles and abstracts. Each paper was screened in duplicate and conflicting decisions settled by consensus discussion. Data were extracted, qualitatively synthesised and narratively reported. All included studies were quality assessed. RESULTS: These searches yielded 4,367 results. After title and abstract screening, 694 full-text studies were reviewed, and 62 deemed eligible for inclusion. This review details 11,377 patients including 2,049 patients with delirium. In total, 78 differently described delirium symptoms were reported. The most reported symptoms were inattention (N = 29), disorientation (N = 27), psychomotor agitation/retardation (N = 22), hallucination (N = 22) and memory impairment (N = 18). Notably, psychomotor agitation and hallucinations are not listed in the current Diagnostic and Statistical Manual for Mental Disorders-5-Text Revision delirium definition. CONCLUSIONS: The 78 symptoms reported in this systematic review cover domains of attention, awareness, disorientation and other cognitive changes. There is a lack of standardisation of terms, and many recorded symptoms are synonyms of each other. This systematic review provides a library of individual delirium symptoms, which may be used to inform future reporting.

Use of Electronic Health Record-Based Measures to Assess Quality of Care for Pediatric Agitation.

OBJECTIVES: Acute agitation during pediatric mental health emergency department (ED) visits presents safety risks to patients and staff. We previously convened multidisciplinary stakeholders who prioritized 20 proposed quality measures for pediatric acute agitation management. Our objectives were to assess feasibility of evaluating performance on these quality measures using electronic health record (EHR) data and to examine performance variation across 3 EDs. METHODS: At a children's hospital and 2 nonchildren's hospitals, we assessed feasibility of evaluating quality measures for pediatric acute agitation management using structured EHR data elements. We retrospectively evaluated measure performance during ED visits by children 5 to 17 years old who presented for a mental health condition, received medication for agitation, or received physical restraints from July 2020 to June 2021. Bivariate and multivariable regression were used to examine measure performance by patient characteristics and hospital. RESULTS: We identified 2785 mental health ED visits, 275 visits with medication given for agitation, and 35 visits with physical restraints. Performance was feasible to measure using EHR data for 10 measures. Nine measures varied by patient characteristics, including 4.87 times higher adjusted odds (95% confidence interval 1.28-18.54) of physical restraint use among children with versus without autism spectrum disorder. Four measures varied by hospital, with physical restraint use varying from 0.5% to 3.3% of mental health ED visits across hospitals. CONCLUSIONS: Quality of care for pediatric acute agitation management was feasible to evaluate using EHR-derived quality measures. Variation in performance across patient characteristics and hospitals highlights opportunities to improve care quality.

Wrist-worn actigraphy in agitated late-stage dementia patients: A feasibility study on digital inclusion.

BACKGROUND: Wrist-worn actigraphy can be an objective tool to assess sleep and other behavioral and psychological symptoms in dementia (BPSD). We investigated the feasibility of using wearable actigraphy in agitated late-stage dementia patients. METHODS: Agitated, late-stage Alzheimer's dementia care home residents in Greater London area (n = 29; 14 females, mean age ± SD: 80.8 ± 8.2; 93.1% White) were recruited to wear an actigraphy watch for 4 weeks. Wearing time was extracted to evaluate compliance, and factors influencing compliance were explored. RESULTS: A high watch-acceptance (96.6%) and compliance rate (88.0%) was noted. Non-compliance was not associated with age or BPSD symptomatology. However, participants with "better" cognitive function (R = 0.42, p = 0.022) and during nightshift (F1.240, 33.475 = 8.075, p = 0.005) were less compliant. Female participants were also marginally less compliant (F1, 26 = 3.790, p = 0.062). DISCUSSIONS: Wrist-worn actigraphy appears acceptable and feasible in late-stage agitated dementia patients. Accommodating the needs of both the patients and their carers may further improve compliance.

Neuropsychiatric Side Effects After Lumbosacral Epidural Steroid Injections: A Prospective Cohort Study.

BACKGROUND: The central nervous system contains steroid receptors, particularly in the hypothalamic and limbic systems. These systems are responsible for driving certain emotions in humans, especially stress, anxiety, motivation, energy levels, and mood. Thus, corticosteroids may precipitate patients to experience these emotions. Most existing studies report neuropsychiatric side effects after oral or intravenous corticosteroids rather than epidural. OBJECTIVES: This study examines the neuropsychiatric side effects after epidural steroid injections (ESIs), with a focus on whether certain factors in patients' histories further exacerbate symptomatology. STUDY DESIGN: Prospective observational cohort study. SETTING: Fluoroscopy suite at an urban academic teaching hospital. METHODS: Patients were called 24 hours and one week after their ESIs and asked if they experienced certain neuropsychiatric symptoms more than usual compared to baseline. PATIENTS: Seventy-four patients undergoing a lumbosacral ESI (interlaminar (ILESI), caudal or transforaminal (TFESI)) were invited to take part in the study the day of his or her procedure. INTERVENTION/MEASUREMENT: Assessed whether psychiatric history, gender, race, type of ESI, or the number of levels injected affected frequency and duration of neuropsychiatric symptoms at one day and one week after an ESI. RESULTS: Significantly (P < 0.05) more patients with a psychiatric history experienced restlessness and irritability at day one than those without a psychiatric history. At week one, male gender (IRR 2.29, 95% CI 1.37, 3.83, P = 0.002), ILESI (IRR 7.75, 95% CI 1.03, 58.6, P = 0.047), and 2-level injections (IRR 2.14, 95% CI 1.13, 4.06, P = 0.019) were significantly associated to more total symptoms. LIMITATIONS: Single center study, reliance on subjective responses from patients, lack of follow-up after one week post-ESI. CONCLUSION(S): This study demonstrates that neuropsychiatric symptoms are rare overall after an ESI, though certain factors may influence patients experiencing these symptoms. Restlessness and irritability were more likely to occur one day after an ESI in those with a psychiatric history. Those who had a 2-level injection were more likely to keep experiencing most symptoms by week one, suggesting a possible correlation between corticosteroid dose and neuropsychiatric symptoms.

An automated ICU agitation monitoring system for video streaming using deep learning classification.

OBJECTIVE: To address the challenge of assessing sedation status in critically ill patients in the intensive care unit (ICU), we aimed to develop a non-contact automatic classifier of agitation using artificial intelligence and deep learning. METHODS: We collected the video recordings of ICU patients and cut them into 30-second (30-s) and 2-second (2-s) segments. All of the segments were annotated with the status of agitation as "Attention" and "Non-attention". After transforming the video segments into movement quantification, we constructed the models of agitation classifiers with Threshold, Random Forest, and LSTM and evaluated their performances. RESULTS: The video recording segmentation yielded 427 30-s and 6405 2-s segments from 61 patients for model construction. The LSTM model achieved remarkable accuracy (ACC 0.92, AUC 0.91), outperforming other methods. CONCLUSION: Our study proposes an advanced monitoring system combining LSTM and image processing to ensure mild patient sedation in ICU care. LSTM proves to be the optimal choice for accurate monitoring. Future efforts should prioritize expanding data collection and enhancing system integration for practical application.

An Evidence-Based Update on Anticholinergic Use for Drug-Induced Movement Disorders.

Drug-induced movement disorders (DIMDs) are associated with use of dopamine receptor blocking agents (DRBAs), including antipsychotics. The most common forms are drug-induced parkinsonism (DIP), dystonia, akathisia, and tardive dyskinesia (TD). Although rare, neuroleptic malignant syndrome (NMS) is a potentially life-threatening consequence of DRBA exposure. Recommendations for anticholinergic use in patients with DIMDs were developed on the basis of a roundtable discussion with healthcare professionals with extensive expertise in DIMD management, along with a comprehensive literature review. The roundtable agreed that "extrapyramidal symptoms" is a non-specific term that encompasses a range of abnormal movements. As such, it contributes to a misconception that all DIMDs can be treated in the same way, potentially leading to the misuse and overprescribing of anticholinergics. DIMDs are neurobiologically and clinically distinct, with different treatment paradigms and varying levels of evidence for anticholinergic use. Whereas evidence indicates anticholinergics can be effective for DIP and dystonia, they are not recommended for TD, akathisia, or NMS; nor are they supported for preventing DIMDs except in individuals at high risk for acute dystonia. Anticholinergics may induce serious peripheral adverse effects (e.g., urinary retention) and central effects (e.g., impaired cognition), all of which can be highly concerning especially in older adults. Appropriate use of anticholinergics therefore requires careful consideration of the evidence for efficacy (e.g., supportive for DIP but not TD) and the risks for serious adverse events. If used, anticholinergic medications should be prescribed at the lowest effective dose and for limited periods of time. When discontinued, they should be tapered gradually.

Preoperative Intrathecal Morphine is Associated With Reduced Postoperative Pain, Agitation, and Delirium In Living Donor Kidney Transplantation Recipients.

BACKGROUND: Postoperative delirium after organ transplantation can lead to increased length of hospital stay and mortality. Because pain is an important risk factor for delirium, perioperative analgesia with intrathecal morphine (ITM) may mitigate postoperative delirium development. We evaluated if ITM reduces postoperative delirium incidence in living donor kidney transplant (LDKT) recipients. METHODS: Two hundred ninety-six patients who received LDKT between 2014 and 2018 at our hospital were retrospectively analyzed. Recipients who received preoperative ITM (ITM group) were compared with those who did not (control group). The primary outcome was postoperative delirium based on the Confusion Assessment Method for Intensive Care Unit results during the first 4 postoperative days. RESULTS: Delirium occurred in 2.6% (4/154) and 7.0% (10/142) of the ITM and control groups, respectively. Multivariable analysis showed age (odds ratio [OR]: 1.07, 95% CI: 1.01-1.14; P = .031), recent smoking (OR: 7.87, 95% CI: 1.43-43.31; P = .018), preoperative psychotropics (OR: 23.01, 95% CI: 3.22-164.66; P = .002) were risk factors, whereas ITM was a protective factor (OR: 0.23, 95% CI: 0.06-0.89; P = .033). CONCLUSIONS: Preoperative ITM showed an independent association with reduced post-LDKT delirium. Further studies and the development of regional analgesia for delirium prevention may enhance the postoperative recovery of transplant recipients.

Real-World Evidence of Antipsychotic Monotherapy Versus Polypharmacy in the Treatment of Schizophrenia Spectrum Disorders.

PURPOSE/BACKGROUND: It is still not well known whether antipsychotic monotherapy versus polypharmacy differs in terms of efficacy in the emergency department (ED) utilization, presentation with agitation/aggression, and rehospitalization in schizophrenia spectrum disorders (SSD) patients. This study aimed to determine the effectiveness of antipsychotic monotherapy and polypharmacy for these outcomes in the real world. METHODS/PROCEDURES: The study was conducted with electronic health records of 669 SSD patients admitted to the ED. Patients were evaluated in 4 groups according to antipsychotic use at the first admission to ED: antipsychotic noncompliance for more than 90 days, antipsychotic noncompliance for 15 to 90 days, antipsychotic monotherapy, and polypharmacy. All patients followed up for at least 1 year after index admission. The primary outcomes determined an association between antipsychotic monotherapy versus polypharmacy and all-cause psychiatric hospitalization between the groups after index admission in the SSD. FINDINGS/RESULTS: The groups, including patients with antipsychotic noncompliance, had higher ED visits, more hospitalizations, and more admissions with agitation/aggression compared with antipsychotic monotherapy or polypharmacy. However, no differences were found between monotherapy and polypharmacy groups regarding these outcomes. In addition, there was no difference in the risk of hospitalization in monotherapy antipsychotic users compared with polypharmacy users. Patients discharged with monotherapy or polypharmacy also had similar rehospitalization rates at follow-up. IMPLICATIONS/CONCLUSIONS: There is no positive evidence that recommending polypharmacy over antipsychotic monotherapy is superior with regard to the resulting frequency of ED visits, ED admissions with agitation/aggression, hospitalization, and rehospitalization. In this context, antipsychotic monotherapy may be preferred over polypharmacy in patients who are not resistant to treatment.

Vitamin D and behavioral disorders in older adults: results from the CLIP study.

OBJECTIVES: Vitamin D is involved in brain health and function. Our objective was to determine whether vitamin D deficiency was associated with behavioral disorders in geriatric patients. DESIGN: The observational cross-sectional CLIP (Cognition and LIPophilic vitamins) study. The report followed the STROBE statement. SETTING: Geriatric acute care unit in a tertiary university hospital in France for 3 months at the end of winter and beginning of spring. PARTICIPANTS: 272 patients ≥65 years consecutively hospitalized or seen in consultation. MEASUREMENTS: Participants were separated into two groups according to vitamin D deficiency (i.e., serum 25-hydroxyvitamin D ≤25 nmol/L). Behavior was assessed using the reduced version of the Neuropsychiatric Inventory Scale (NPI-R) score and subscores. Age, sex, BMI, education level, comorbidities, MMSE and GDS scores, use psychoactive drugs and vitamin D supplements, and serum concentrations of calcium, parathyroid hormone, TSH and estimated glomerular filtration rate (eGFR) were used as potential confounders. RESULTS: Participants with vitamin D deficiency (n = 78) had similar NPI-R score (17.4 ± 20.3 versus 17.2 ± 16.1, p = 0.92) but higher (i.e., worse) subscore of agitation and aggressiveness (2.0 ± 3.3 versus 1.2 ± 2.4, p = 0.02) and higher (i.e., worse) subscore of disinhibition (0.99 ± 2.98 versus 0.38 ± 1.42, p = 0.02) than those without vitamin D deficiency (n = 194). In multiple linear regressions, vitamin D deficiency was inversely associated with the subscore of agitation and aggressiveness (ß = 1.37, p = 0.005) and with the subscore of disinhibition (ß = 0.96, p = 0.008). CONCLUSION: Vitamin D deficiency was associated with more severe subscores of agitation and aggressiveness and of disinhibition among older adults. This provides a scientific basis to test the efficacy of vitamin D supplementation on behavioral disorders in older patients with vitamin D deficiency.

Preliminary examination of ADHD inattentive and cognitive disengagement syndrome symptoms in relation to probe-caught mind-wandering during a sustained attention to response task.

OBJECTIVE: The role of mind-wandering- periods of internally-directed distractibility - among patients with attention-deficit/hyperactivity disorder (ADHD) has recently garnered attention, though few studies have assessed mind-wandering using thought probes during a sustained attention to response task (SART) or examined the possible role of cognitive disengagement syndrome (CDS) symptoms. We examined whether parent- and/or teacher-reported ADHD-inattentive (ADHD-IN) or CDS symptoms were independently associated with probe-caught mind-wandering. METHODS: Fifty-four children (ages 9-12; 35.2% female) completed a SART with thought probes inquiring about various on- and off-task thoughts, including mind-wandering and distraction. Questionnaires provided information on demographics, medication treatment, and parent- and teacher-reported ADHD-IN and CDS symptoms. Regression models were estimated separately by informant to examine whether ADHD-IN or CDS symptoms were uniquely associated with mind-wandering or distraction frequency during the SART. RESULTS: Higher teacher-reported CDS ratings, but not ADHD-IN ratings, were uniquely associated with more probe-caught mind-wandering. No significant findings related to parent-reported symptoms or probe-caught distraction were observed. CONCLUSIONS: These preliminary findings add to an emerging body of work pointing to CDS as more consistently or strongly associated than ADHD-IN with mind-wandering. Theoretical and clinical implications are discussed.

Restless nights when sick: ectoparasite infections alter rest-activity cycles of diurnal fish hosts.

Circadian rhythms are timekeeping mechanisms responsible for an array of biological processes. Disruption of such cycles can detrimentally affect animal health. Circadian rhythms are critical in the co-evolution of host­parasite systems, as synchronization of parasite rhythms to the host can influence infection dynamics and transmission potential. This study examines the circadian rhythms in behaviour and activity of a model fish species (Poecilia reticulata) in isolation and in shoals, both when uninfected and infected with an ectoparasite (Gyrodactylus turnbulli). Additionally, the rhythmical variance of parasite activity under different light conditions as well as rhythmical variance in parasite transmissibility was explored. Overall, infection alters the circadian rhythm of fish, causing nocturnal restlessness. Increased activity of gyrodactylids on the host's skin at night could potentially contribute to this elevated host activity. Whilst migration of gyrodactylids across the host's skin may have caused irritation to the host resulting in nocturnal restlessness, the disruption in guppy activity rhythm caused by the expression of host innate immunity cannot be excluded. We discuss the wider repercussions such behavioural responses to infection have for host health, the implications for animal behaviour studies of diurnal species as well as the application of chronotherapeutic approaches to aquaculture.

Approach to acute agitation in the pediatric emergency department.

PURPOSE OF REVIEW: The complexity of pediatric mental and behavioral health (MBH) complaints presenting to emergency departments (EDs) is increasing at an alarming rate. Children may present with agitation or develop agitation during the ED visit. This causes significant distress and may lead to injury of the child, caregivers, or medical staff. This review will focus on providing safe, patient-centered care to children with acute agitation in the ED. RECENT FINDINGS: Approaching a child with acute agitation in the ED requires elucidation on the cause and potential triggers of agitation for optimal management. The first step in a patient-centered approach is to use the least restrictive means with behavioral and environmental strategies. Restraint use (pharmacologic or physical restraint) should be reserved where these modifications do not result in adequate de-escalation. The provider should proceed with medications first, using the child's medication history as a guide. The use of physical restraint is a last resort to assure the safety concerns of the child, family, or staff, with a goal of minimizing restraint time. SUMMARY: Children are increasingly presenting to EDs with acute agitation. By focusing primarily on behavioral de-escalation and medication strategies, clinicians can provide safe, patient-centered care around these events.

Acute and chronic alcohol modulation of extended amygdala calcium dynamics.

The central amygdala (CeA) and bed nucleus of the stria terminalis (BNST) are reciprocally connected nodes of the extended amygdala thought to play an important role in alcohol consumption. Studies of immediate-early genes indicate that BNST and CeA are acutely activated following alcohol drinking and may signal alcohol reward in nondependent drinkers, while stress signaling in the extended amygdala following chronic alcohol exposure drives increased drinking via negative reinforcement. However, the temporal dynamics of neuronal activation in these regions during drinking behavior are poorly understood. In this study, we used fiber photometry and the genetically encoded calcium sensor GCaMP6s to assess acute changes in neuronal activity during alcohol consumption in BNST and CeA before and after a chronic drinking paradigm. Activity was examined in the pan-neuronal population and separately in dynorphinergic neurons. BNST and CeA showed increased pan-neuronal activity during acute consumption of alcohol and other fluid tastants of positive and negative valence, as well as highly palatable chow. Responses were greatest during initial consummatory bouts and decreased in amplitude with repeated consumption of the same tastant, suggesting modulation by stimulus novelty. Dynorphin neurons showed similar consumption-associated calcium increases in both regions. Following three weeks of continuous alcohol access (CA), calcium increases in dynorphin neurons during drinking were maintained, but pan-neuronal activity and BNST-CeA coherence were altered in a sex-specific manner. These results indicate that BNST and CeA, and dynorphin neurons specifically, are engaged during drinking behavior, and activity dynamics are influenced by stimulus novelty and chronic alcohol.

Depression, anxiety and suicidality among Chinese mental health professionals immediately after China's dynamic zero-COVID policy: A network perspective.

BACKGROUND: Using network analysis, the interactions between mental health problems at the symptom level can be explored in depth. This study examined the network structure of depressive and anxiety symptoms and suicidality among mental health professionals after the end of China's Dynamic Zero-COVID Policy. METHODS: A total of 10,647 mental health professionals were recruited nationwide from January to February 2023. Depression and anxiety were assessed using the 9-item Patient Health Questionnaire (PHQ-9) and 7-item Generalized Anxiety Disorder Scale (GAD-7), respectively, while suicidality was defined by a 'yes' response to any of the standard questions regarding suicidal ideation (SI), suicide plan (SP) and suicide attempt (SA). Expected Influence (EI) and Bridge Expected Influence (bEI) were used as centrality indices in the symptom network to characterize the structure of the symptoms. RESULTS: The prevalence of depression, anxiety, and suicidality were 45.99 %, 28.40 %, and 7.71 %, respectively. The network analysis identified GAD5 ("Restlessness") as the most central symptom, followed by PHQ4 ("Fatigue") and GAD7 ("Feeling afraid"). Additionally, PHQ6 ("Guilt"), GAD5 ("Restlessness"), and PHQ8 ("Motor disturbance") were bridge nodes linking depressive and anxiety symptoms with suicidality. The flow network indicated that the strongest connections of S ("Suicidality") was with PHQ6 ("Guilt"), GAD7 ("Feeling afraid"), and PHQ2 ("Sad mood"). CONCLUSIONS: Depression, anxiety, and suicidality among mental health professionals were highly prevalent after China's Dynamic Zero-COVID Policy ended. Effective measures should target central and bridge symptoms identified in this network model to address the mental health problems in those at-risk.