Evaluation of pulp tissue dissolution capacity through different sodium hypochlorite agitation protocols.

Aims: This ex vivo study aimed to assess the dissolving capacity of 2.5% sodium hypochlorite using eight agitation protocols within swine pulp tissue. Subjects and Methods: Twelve lower first premolars were prepared and split into the fragments with a groove housing porcine dental pulp. Groups were assigned based on agitation systems: manual, passive ultrasonic, Easy Clean and XP-Endo Finisher. Two agitation time protocols were applied: One min (3 s × 20 s cycles) and 2 min (6 s × 20 s cycles). Wilcoxon Mann-Whitney U test was used to compare the groups. Results: Both time frames demonstrated superior results compared to manual group (P > 0.5). However, in the two min groups, no significant differences were observed among the other protocols (P < 0.5). Intriguingly, increasing cycle numbers significantly improved results within each group (P > 0.5). Conclusion: Extending the chemical agitation time during final irrigation enhances tissue removal, regardless of the irrigation protocol employed.

Presynaptic regulators in memory formation.

The intricate molecular and structural sequences guiding the formation and consolidation of memories within neuronal circuits remain largely elusive. In this study, we investigate the roles of two pivotal presynaptic regulators, the small GTPase Rab3, enriched at synaptic vesicles, and the cell adhesion protein Neurexin-1, in the formation of distinct memory phases within the Drosophila mushroom body Kenyon cells. Our findings suggest that both proteins play crucial roles in memory-supporting processes within the presynaptic terminal, operating within distinct plasticity modules. These modules likely encompass remodeling and maturation of existing active zones (AZs), as well as the formation of new AZs.

Post-Treatment Displacement of Facial Soft Tissue Fillers-A Retrospective Ultrasound-based Investigation of 382 Zygomatic Regions.

BACKGROUND: Clinical and ultrasound experience has revealed that after soft tissue injections of the lateral cheek, the filler may displace from the zygoma to the caudal temporal area. OBJECTIVE: To obtain more data to provide insight into product distribution when soft tissue fillers are injected in the zygomatic region. METHODS: Two hundred patients were examined with facial ultrasound imaging of the zygomatic and temporal region. Inclusion criteria were simply a positive response on the screening questionnaire as to whether or not they had filler injections placed in their lateral cheek. Control injections were also performed to the zygomatic regions of a body donor and in 10 patients ultrasound-guided. RESULTS: A correlation was found between the layers in which filler was detected on the zygoma and where it was ultimately found in the temples. Four different redistribution patterns were observed: (1) migration of filler within the superficial muscular aponeurotic system (SMAS) on the zygoma into the superficial temporal fascia. Migration of filler from the lateral suborbicularis oculi fat to (2) the deep interfacial plane of the temple or (3) to the superficial temporal fat pad; (4) migration from the supraperiosteal layer of the zygoma to the superficial temporal fat pad. Body donor and patients: filler deposits injected on the zygoma were witnessed to shift during injection into the caudal part of the temple. CONCLUSION: Soft tissue filler aliquots may be redistributed into the temples after injections of the lateral side of the zygomatic arch. The displacement follows a distinct pattern depending on the initial layer of injection.

Ensuring microbial water quality for on-site water reuse: Importance of online sensors for reliable operation.

A growing number of cities and regions are promoting or mandating on-site treatment and reuse of wastewater, which has resulted in the implementation of several thousand on-site water reuse systems on a global scale. However, there is only limited information on the (microbial) water quality from implemented systems. The focus of this study was on two best-in-class on-site water reuse systems in Bengaluru, India, which typically met the local water quality requirements during monthly compliance testing. This study aimed to (i) assess the microbial quality of the reclaimed water at a high temporal resolution (daily or every 15 min), and (ii) explore whether measurements from commercially available sensors can be used to improve the operation of such systems. The monitoring campaign revealed high variations in microbial water quality, even in these best-in-class systems, rendering the water inadequate for the intended reuse applications (toilet flushing and landscape irrigation). These variations were attributed to two key factors: (1) the low frequency of chlorination, and (2) fluctuations of the chlorine demand of the water, in particular of ammonium concentrations. Such fluctuations are likely inherent to on-site systems, which rely on a low level of process control. The monitoring campaign showed that the microbial water quality was most closely related to oxidation-reduction potential (ORP) and free chlorine sensors. Due to its relatively low cost and low need for maintenance, the ORP emerges as a compelling candidate for automating the chlorination to effectively manage variations in chlorine demand and ensure safe water reuse. Overall, this study underscores the necessity of integrating treatment trains, operation, and monitoring for safe on-site water reuse.

Sleep restriction reduces voluntary isometric quadriceps strength through reduced neuromuscular efficiency, not impaired contractile performance.

Acute sleep restriction (SR) reduces strength through an unknown mechanism. PURPOSE: To determine how SR affects quadriceps contractile function and recruitment. METHODS: Eighteen healthy subjects (9 M, 9F, age 23.8 ± 2.8y) underwent isometric (maximal and submaximal), isokinetic (300-60°·s-1), and interpolated twitch (ITT) assessment of knee extensors following 3d of adequate sleep (SA; 7-9 h·night-1), 3d of SR (5 h·night-1), and 7d of washout (WO; 7-9 h·night-1). RESULTS: Compared to SA (227.9 ± 76.6Nm) and WO (228.19 ± 62.9Nm), MVIC was lesser following SR (209.9 ± 73.9Nm; p = 0.006) and this effect was greater for males (- 9.8 v. - 4.8%). There was no significant effect of sleep or sleep x speed interaction on peak isokinetic torque. Peak twitch torque was greater in the potentiated state, but no significant effect of sleep was noted. Males displayed greater potentiation of peak twitch torque (12 v. 7.5%) and rate of torque development (16.7 v. 8.2%) than females but this was not affected by sleep condition. ITT-assessed voluntary activation did not vary among sleep conditions (SA: 81.8 ± 13.1% v. SR: 84.4 ± 12.6% v. WO 84.9 ± 12.6%; p = 0.093). SR induced a leftward shift in Torque-EMG relationship at high torque output in both sexes. Compared to SA, females displayed greater y-intercept and lesser slope with SR and WO and males displayed lesser y-intercept and greater slope with SR and WO. CONCLUSIONS: Three nights of SR decreases voluntary isometric knee extensor strength, but not twitch contractile properties. Sex-specific differences in neuromuscular efficiency may explain the greater MVIC reduction in males following SR.

Subclinical patterns of disordered eating behaviors in the daily life of adolescents and young adults from the general population.

BACKGROUND: Disordered eating behaviors (DEBs), a risk factor for the development of eating disorders (EDs), are prevalent in young people and different DEBs frequently co-occur. Previous studies on DEB-patterns have largely used traditional retrospective questionnaires to assess DEBs. In addition, most previous studies did not specifically exclude individuals with clinical EDs, which limits current knowledge concerning purely subclinical patterns of DEBs. In the present study, we aimed to explore phenotypes and group sizes of subclinical patterns of DEBs reported in everyday life via smartphone-based ecological momentary assessment (EMA) in adolescents and young adults from the general population without lifetime EDs. In secondary analyses, we further aimed to investigate whether DEB-patterns would be associated with additional previously identified risk factors for ED-development. METHODS: EMA was conducted in a community sample of 14-21-year-olds from Dresden, Germany, over four days for up to eight times a day and covered engagement in four DEBs: skipping eating, restrained eating, eating large amounts of food, and loss-of-control eating. Data were analyzed from N = 966 individuals without lifetime EDs with an EMA compliance rate of at least 50% (81.9% of the total sample; average compliance: 84.6%). Latent profile analyses were performed to identify subclinical patterns of DEBs, stratified by sex. Associations between symptomatic profiles and ED-risk factors were tested via regression analyses. RESULTS: Based on theoretical deliberations, statistical indices, interpretability, and parsimony, a three-profile solution, namely no DEBs, high-mixed DEBs, and low-mixed DEBs, was selected for both sexes. Both symptomatic profiles in both sexes were associated with more unfavorable manifestations in additional ED risk factors compared to the no DEBs profile, with the highest number of associations being observed in the female high-mixed profile. CONCLUSIONS: The present findings suggest that problematic manifestations of DEBs in young people may occur even in the absence of an ED diagnosis and that they are associated with additional risk factors for EDs, warranting increased efforts in targeted prevention, early identification and intervention in order to counteract symptom progression.

Effect of Autoclave Sterilization on the Number of Uses and Resistance to Cyclic Fatigue of WaveOne Gold and Four Replica-Like Endodontic Instruments.

This study aimed to evaluate the effect of autoclave sterilization on the integrity and instruments' fracture number after multiple uses and cyclic fatigue of the original WaveOne Gold (Dentsply Sirona Endodontics) compared to four replica-like instruments (TF4-Gold, Roll-Wave-Gold, W-File, and Micro-Gold). The instruments were analyzed by scanning electron microscope (SEM) before being used in root canal instrumentation (baseline). One hundred and fifty human molars, freshly extracted for orthodontic reasons or periodontal disease and with severe curvature (between 30° and 60°), were used. Fifty teeth were instrumented with 10 instruments from each group and were evaluated for integrity. After sterilization in an autoclave, the instruments were analyzed by SEM. This procedure was repeated twice more, totaling three rounds of instrumentation, sterilization, and SEM analysis. Ten unused instruments from each group were evaluated for resistance to cyclic fatigue in a static test using a motor and a device simulating a canal with a 60° curvature angle. The instruments were driven by the motor until separation, visually verified, and the time measured in seconds. Data were analyzed by Chi-square, one-way ANOVA, and Tukey analysis, considering a significance level of 5%. It was found that there was no statistically significant difference between the groups tested in the effect of sterilization on the number of uses. The SEM analysis showed distortions in the instruments after the 3rd use. There was a statistically significant difference in the cyclic fatigue test between the results of WaveOne Gold, TF4 Gold, and Roll Wave Gold compared to W File and Micro Gold (P < 0.0001) and a statistically significant difference between the W File and Micro Gold groups (P < 0.0001). In conclusion, this study affirmed that WaveOne Gold, TF4-Gold, and Roll-Wave-Gold instruments exhibit comparable cyclic fatigue resistance. Besides, all examined instruments can be reliably employed for up to two cases.

Effectiveness of home treatment in children and adolescents with psychiatric disorders-systematic review and meta-analysis.

BACKGROUND: Home treatment in child and adolescent psychiatry offers an alternative to conventional inpatient treatment by involving the patient's family, school, and peers more directly in therapy. Although several reviews have summarised existing home treatment programmes, evidence of their effectiveness remains limited and data synthesis is lacking. METHODS: We conducted a meta-analysis on the effectiveness of home treatment compared with inpatient treatment in child and adolescent psychiatry, based on a systematic search of four databases (PubMed, CINAHL, PsychINFO, Embase). Primary outcomes were psychosocial functioning and psychopathology. Additional outcomes included treatment satisfaction, duration, costs, and readmission rates. Group differences were expressed as standardised mean differences (SMD) in change scores. We used three-level random-effects meta-analysis and meta-regression and conducted both superiority and non-inferiority testing. RESULTS: We included 30 studies from 13 non-overlapping samples, providing data from 1795 individuals (mean age: 11.95 ± 2.33 years; 42.5% female). We found no significant differences between home and inpatient treatment for postline psychosocial functioning (SMD = 0.05 [- 0.18; 0.30], p = 0.68, I2 = 98.0%) and psychopathology (SMD = 0.10 [- 0.17; 0.37], p = 0.44, I2 = 98.3%). Similar results were observed from follow-up data and non-inferiority testing. Meta-regression showed better outcomes for patient groups with higher levels of psychopathology at baseline and favoured home treatment over inpatient treatment when only randomised controlled trials were considered. CONCLUSIONS: This meta-analysis found no evidence that home treatment is less effective than conventional inpatient treatment, highlighting its potential as an effective alternative in child and adolescent psychiatry. The generalisability of these findings is reduced by limitations in the existing literature, and further research is needed to better understand which patients benefit most from home treatment. TRIAL REGISTRATION: Registered at PROSPERO (CRD42020177558), July 5, 2020.

Complications of collagen biostimulators in Brazil: Description of products, treatments, and evolution of 55 cases.

BACKGROUND: Complications of temporary and permanent fillers have been extensively studied. However, there is a lack of comparative data regarding poly-L-lactic acid (PLLA), calcium hydroxyapatite (CaHA), and polycaprolactone (PCL) known as collagen biostimulators. AIMS: This study addressed the complications of collagen biostimulators concerning their diagnosis, type of product, treatment, and monitoring. PATIENTS/METHODS: An electronic questionnaire was sent to Brazilian dermatologic ultrasound experts to identify complications related to biostimulators. The type of biostimulator, location of application, number of vials injected, application plan, time between injection treatment and complication, injector profile, treatment, and prognosis were assessed. RESULTS: Fifty-five cases were identified, of which 49.1% were caused by PLLA-Elleva®, 23.6% by CaHA (alone or combined with hyaluronic acid), 20.0% by PLLA-Sculptra®, and 7.3% by PCL. The most affected area was the face (72.7%), with nodules being the most common clinical form (89.1%), generally occurring late (60.0%) (>1 month). Only one case was injected at an incorrect depth (musculoaponeurotic system-SMAS). Despite several treatments, including saline (45.5%), hyaluronidase (25.5%), diluted corticosteroids (23.6%), and energy-based devices (10.9%), only five cases showed complete resolution. Hyaluronidase was beneficial in complications related to fillers when there was an association of calcium hydroxyapatite with hyaluronic acid (p < 0.01). CONCLUSIONS: Complications from collagen biostimulators were more common on the face, typically manifesting about 1 month after treatment. These issues seemed to be related more to the properties of the products rather than inadequate technique. Furthermore, hyaluronidase demonstrated efficacy only in cases where there was an association with HA.

In vitro study of structural and chemical changes in two reciprocating files after multiple reuses and sterilisation.

To use scanning electron microscopy and energy dispersive X-ray spectroscopy to evaluate the metallurgical-chemical changes of WaveOne Gold (WOG) and R-Motion (RM), after multiple uses. The instruments were divided into groups (n = 8): WOG and RM-control groups, new instruments; WOG1 and RM1; WOG2 and RM2; WOG3 and RM3 after instrumentation of 1, 2 or 3 molars, respectively. Burrs occurred mainly in the control group and after the first use. The RM files were found to have a higher nickel content, which increased during reuse, and a decrease in oxygen content with increasing reuse, in addition to calcium impregnation, which occurred in greater amounts in the corrosion areas in the WOG files. The presence of topographic and chemical changes was demonstrated, indicating that caution should be taken when reusing endodontic instruments to avoid fractures.

Maramycin, a Cytotoxic Isoquinolinequinone Terpenoid Produced through Heterologous Expression of a Bifunctional Indole Prenyltransferase/Tryptophan Indole-Lyase in S. albidoflavus.

Isoquinolinequinones represent an important family of natural alkaloids with profound biological activities. Heterologous expression of a rare bifunctional indole prenyltransferase/tryptophan indole-lyase enzyme from Streptomyces mirabilis P8-A2 in S. albidoflavus J1074 led to the activation of a putative isoquinolinequinone biosynthetic gene cluster and production of a novel isoquinolinequinone alkaloid, named maramycin (1). The structure of maramycin was determined by analysis of spectroscopic (1D/2D NMR) and MS spectrometric data. The prevalence of this bifunctional biosynthetic enzyme was explored and found to be a recent evolutionary event with only a few representatives in nature. Maramycin exhibited moderate cytotoxicity against human prostate cancer cell lines, LNCaP and C4-2B. The discovery of maramycin (1) enriched the chemical diversity of natural isoquinolinequinones and also provided new insights into crosstalk between the host biosynthetic genes and the heterologous biosynthetic genes in generating new chemical scaffolds.

Discovery and preclinical development of a therapeutically active nanobody-based chimeric antigen receptor targeting human CD22.

Chimeric antigen receptor (CAR) T cell therapies targeting B cell-restricted antigens CD19, CD20, or CD22 can produce potent clinical responses for some B cell malignancies, but relapse remains common. Camelid single-domain antibodies (sdAbs or nanobodies) are smaller, simpler, and easier to recombine than single-chain variable fragments (scFvs) used in most CARs, but fewer sdAb-CARs have been reported. Thus, we sought to identify a therapeutically active sdAb-CAR targeting human CD22. Immunization of an adult Llama glama with CD22 protein, sdAb-cDNA library construction, and phage panning yielded >20 sdAbs with diverse epitope and binding properties. Expressing CD22-sdAb-CAR in Jurkat cells drove varying CD22-specific reactivity not correlated with antibody affinity. Changing CD28- to CD8-transmembrane design increased CAR persistence and expression in vitro. CD22-sdAb-CAR candidates showed similar CD22-dependent CAR-T expansion in vitro, although only membrane-proximal epitope targeting CD22-sdAb-CARs activated direct cytolytic killing and extended survival in a lymphoma xenograft model. Based on enhanced survival in blinded xenograft studies, a lead CD22sdCAR-T was selected, achieving comparable complete responses to a benchmark short linker m971-scFv CAR-T in high-dose experiments. Finally, immunohistochemistry and flow cytometry confirm tissue and cellular-level specificity of the lead CD22-sdAb. This presents a complete report on preclinical development of a novel CD22sdCAR therapeutic.

Potentially toxic trace elements in the muscle of coastal South American fish: Implications for human consumption and health risk assessment.

Micropogonias furnieri and Urophycis brasiliensis are two coastal demersal fish species distributed in the southwestern Atlantic Ocean. Considering that many coastal areas in the southwestern Atlantic Ocean suffer from anthropogenic pressure, the aim of this study was to assess the level of potentially toxic trace elements (Ag, Al, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Se, Sr, V and Zn) in the muscle of coastal species, and evaluated the human health risk related to the consumption of muscle. Mercury, inorganic As (Asi), V, and Se showed a higher contribution to the total THQ. Considering two possible scenarios, Asi represents 1 % or 5 % of the total As, the total THQ was <1 for general population and of some health concerns for fishermen population (Total THQ > 1; 5 % Asi). Consequently these results show the importance of quantifying As species in muscle to generate more reliable risk estimates for human health.

Influence of Passive Ultrasonic Irrigation of the Photosensitizer Used in Photodynamic Therapy on Microbial Reduction in the Root Canal System: An in Vitro Study.

Introduction: The success of endodontic treatment is based on microbial reduction promoted by the interaction of chemical and mechanical procedures. Photodynamic therapy (PDT) is used as an adjunct to conventional treatment, with significant microbial reduction. This study aimed to evaluate the influence of passive ultrasonic irrigation (PUI) of the photosensitizer (PS) used in PDT on microbial reduction in the root canal system. Materials and Methods: Forty-five mesiobuccal root canals from extracted human mandibular molars that were inoculated with standard strains of Enterococcus faecalis, Candida albicans, and Streptococcus mutans for 21 days were selected. The root canals were prepared using the ProTaper Next system and randomly divided into 3 groups (n=15): 1) PDT: PDT alone; 2) PUI+PDT: PUI followed by PDT; and 3) PUI/PS+PDT: PUI of the PS followed by PDT. Microbiological samples were collected from the canals before and after using the protocols described above. The data were analyzed by analysis of variance (Tukey's test) at a significance level of 5%. Results: Microbial counts before PDT, PUI+PDT, and PUI/PS+PDT did not differ significantly (P>0.05), showing methodological standardization in the microbial contamination of the root canal system. There was a significant reduction in microbial counts after PDT (61.05%), PUI+PDT (65.04%), and PUI/PS+PDT (68.58%) (P<0.01), but with no statistically significant difference between the three groups (P>0.05). Conclusion: Based on the present findings, it was concluded that the combination of PUI with PDT or PS activation did not influence microbial reduction achieved by PDT alone.

A sex-specific pathway linking early life maltreatment, vagal activity, and depressive symptoms.

Background: Experiences of early life maltreatment (ELM) are alarmingly common and represent a risk factor for the development of psychopathology, particularly depression. Research has focused on alterations in autonomic nervous system (ANS) functioning as a mediator of negative mental health outcomes associated with ELM. Early alterations in autonomic vagal activity (vmHRV) may moderate the relationship between ELM and depression, particularly when considering forms of emotional maltreatment. Recent evidence suggests that the relationships of both ELM and vmHRV with depression may be non-linear, particularly considering females.Objective: Building on and extending theoretical considerations and previous work, the present work aims to further the current understanding of the complex relationships between ELM exposure, vmHRV, and depression.Methods: This study uses an adaptive modelling approach, combining exploratory network-based analyses with linear and quadratic moderation analyses, drawing on a large sample of males and females across adolescence (total N = 213; outpatient at-risk sample and healthy controls) and adulthood (total N = 85; community-based convenience sample).Results: Exploratory network-based analyses reveal that exposure to emotional abuse is particularly central within a network of ELM subtypes, depressive symptoms, and concurrent vmHRV in both adolescents and adults. In adults, emotional neglect shows strong associations with both emotional abuse and vmHRV and is highly central as a network node, which is not observed in adolescents. Moderator analyses reveal significant interactions between emotional maltreatment and vmHRV predicting depressive symptoms in adult females. Significant quadratic relationships of emotional maltreatment and vmHRV with depression are observed in both adolescent and adult females.Conclusions: The present findings contribute to the understanding of the psychological and physiological mechanisms by which ELM acts as a risk factor for the development of depression. Ultimately, this will contribute to the development of targeted and effective intervention strategies to mitigate the detrimental effects of early adversity.

Early exposure to chronic and severe adversity, which includes experiences of maltreatment, defined by the World Health Organization as physical, sexual, emotional abuse and/or neglect of children under the age of 18, is highly prevalent in the general population (estimated at 40­50 percent), and is a well-documented risk factor for depression.The present work combines network-based analyses with tests of different functions (i.e. linear, nonlinear quadratic) in moderator analyses to further explore the complex relationships among ELM exposure, vmHRV, and depression.The present findings contribute to the understanding of the psychological and physiological mechanisms by which early exposure to chronic and severe maltreatment acts as a risk factor for the development of depression.Ultimately, this will contribute to the development of targeted and effective intervention strategies to mitigate the detrimental effects of early adversity.

Effect of inulin on breath hydrogen, postprandial glycemia, gut hormone release, and appetite perception in RYGB patients: a prospective, randomized, cross-over pilot study.

BACKGROUND AND OBJECTIVE: Large intestinal fermentation of dietary fiber may control meal-related glycemia and appetite via the production of short-chain fatty acids (SCFA) and the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). We investigated whether this mechanism contributes to the efficacy of the Roux-en-Y gastric bypass (RYGB) by assessing the effect of oligofructose-enriched inulin (inulin) vs. maltodextrin (MDX) on breath hydrogen (a marker of intestinal fermentation), plasma SCFAs, gut hormones, insulin and blood glucose concentrations as well as appetite in RYGB patients. METHOD: Eight RYGB patients were studied on two occasions before and ~8 months after surgery using a cross-over design. Each patient received 300 ml orange juice containing 25 g inulin or an equicaloric load of 15.5 g MDX after an overnight fast followed by a fixed portion snack served 3 h postprandially. Blood samples were collected over 5 h and breath hydrogen measured as well as appetite assessed using visual analog scales. RESULTS: Surgery increased postprandial secretion of GLP-1 and PYY (P ≤ 0.05); lowered blood glucose and plasma insulin increments (P ≤ 0.05) and reduced appetite ratings in response to both inulin and MDX. The effect of inulin on breath hydrogen was accelerated after surgery with an increase that was earlier in onset (2.5 h vs. 3 h, P ≤ 0.05), but less pronounced in magnitude. There was, however, no effect of inulin on plasma SCFAs or plasma GLP-1 and PYY after the snack at 3 h, neither before nor after surgery. Interestingly, inulin appeared to further potentiate the early-phase glucose-lowering and second-meal (3-5 h) appetite-suppressive effect of surgery with the latter showing a strong correlation with early-phase breath hydrogen concentrations. CONCLUSION: RYGB surgery accelerates large intestinal fermentation of inulin, however, without measurable effects on plasma SCFAs or plasma GLP-1 and PYY. The glucose-lowering and appetite-suppressive effects of surgery appear to be potentiated with inulin.

Mouse Model of Chronic Social Stress-Induced Excessive Pavlovian Aversion Learning-Memory.

Increased experience of aversive stimuli/events is a psychological-neurobiological state of major importance in psychiatry. It occurs commonly in generalized anxiety disorder, post-traumatic stress disorder, and major depression. A sustained period of exposure to threat (chronic stressor) is a common risk factor, and a major symptom is generalized excessive perception of, and reactivity to, aversive stimuli. In rodents, Pavlovian aversion learning and memory (PAL, PAM), quantified in terms of the conditioned defensive behavior freezing, is an extensively studied behavioral paradigm, and well understood in terms of underlying neural circuitry. In mice, chronic social stress (CSS) is a 15-day resident-intruder paradigm in which C57BL/6 adult males are exposed continuously and distally to dominant-aggressive CD-1 male mice (sustained threat) interspersed with a brief daily period of proximal attack (acute threat). To ensure that physical wounding is minimized, proximal attacks are limited to 30 to 60 s/day and lower incisor teeth of CD-1 mice are blunted. Control (comparison) mice are maintained in littermate pairs. The CSS and CD-1 mice are maintained in distal contact during subsequent behavioral testing. For PAL, CSS and control (CON) mice are placed in a conditioning chamber (context) and exposed to a tone [conditioned stimulus (CS)] and mild, brief foot shock [unconditioned stimulus (US)]. For PAM, mice are placed in the same context and presented with CS repetitions. The CSS mice acquire (learn) and express (memory) a higher level of freezing than CON mice, indicating that CSS leads to generalized hypersensitivity to aversion, i.e., chronic social aversion leads to increased aversion salience of foot shock. Distinctive features of the model include the following: high reproducibility; rare, mild wounding only; male specificity; absence of "susceptible" vs "resilient" subgroups; behavioral effects dependent on continued presence of CD-1 mice; and preclinical validation of novel compounds for normalizing aversion hypersensitivity with accurate feedforward prediction of efficacy in human patients. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Chronic social stress (CSS) Basic Protocol 2: Pavlovian aversion learning and memory (PALM).

Lung tissue expression of epithelial injury markers is associated with acute lung injury severity but does not discriminate sepsis from ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients, and diffuse alveolar damage (DAD) is considered its histological hallmark. Sepsis is one of the most common aetiology of ARDS with the highest case-fatality rate. Identifying ARDS patients and differentiate them from other causes of acute respiratory failure remains a challenge. To address this, many studies have focused on identifying biomarkers that can help assess lung epithelial injury. However, there is scarce information available regarding the tissue expression of these markers. Evaluating the expression of elafin, RAGE, and SP-D in lung tissue offers a potential bridge between serological markers and the underlying histopathological changes. Therefore, we hypothesize that the expression of epithelial injury markers varies between sepsis and ARDS as well as according to its severity. METHODS: We compared the post-mortem lung tissue expression of the epithelial injury markers RAGE, SP-D, and elafin of patients that died of sepsis, ARDS, and controls that died from non-pulmonary causes. Lung tissue was collected during routine autopsy and protein expression was assessed by immunohistochemistry. We also assessed the lung injury by a semi-quantitative analysis. RESULTS: We observed that all features of DAD were milder in septic group compared to ARDS group. Elafin tissue expression was increased and SP-D was decreased in the sepsis and ARDS groups. Severe ARDS expressed higher levels of elafin and RAGE, and they were negatively correlated with PaO2/FiO2 ratio, and positively correlated with bronchopneumonia percentage and hyaline membrane score. RAGE tissue expression was negatively correlated with mechanical ventilation duration in both ARDS and septic groups. In septic patients, elafin was positively correlated with ICU admission length, SP-D was positively correlated with serum lactate and RAGE was correlated with C-reactive protein. CONCLUSIONS: Lung tissue expression of elafin and RAGE, but not SP-D, is associated with ARDS severity, but does not discriminate sepsis patients from ARDS patients.

Evidence-based recommendations for the rehabilitation and management of the ageing population with spinal cord injury: a systematic review of clinical practice guidelines.

INTRODUCTION: The intersection of ageing and spinal cord injury (SCI) is of global concern. Two scenarios have been described: 1) "SCI with ageing," an increase in the average age of SCI onset, and 2) "ageing with SCI," an increase in post-injury life expectancy. These scenarios entail complex health care and rehabilitation needs due to the accumulation of comorbidities, ageing-related and SCI-induced physiological changes, and post-SCI secondary health conditions. We systematically reviewed Clinical Practice Guidelines (CPGs) with the objective of identifying the extent to which SCI CPGs include recommendations for the rehabilitation and management of people who are "ageing with SCI" or who have acquired an "SCI with ageing". We termed these as "ageing-related recommendations". We also aimed to describe them and identify gaps. EVIDENCE ACQUISITION: We searched PubMed (NCBI), CINAHL Complete (EBSCOhost) and Embase (Elsevier) for relevant CPGs between 28 December 2022 and 5 January 2023. Included CPGs were evidence-based and had at least one ageing-related recommendation for SCI rehabilitation and management. We used the two core sets of the International Classification of Functioning, Disability and Health (ICF) to identify gaps. EVIDENCE SYNTHESIS: Only 16 (30%) of the 52 identified CPGs included ageing-related recommendations. Most were recent US or European publications and lacked specific chapters on ageing. These CPGs included 40 ageing-related recommendations, mostly "strong" but based on "low" to "very low" quality of evidence. The overall quality of the development process was low and did not consider the values and preferences of stakeholders and patients. Common topics included cardiovascular, bone, metabolic, bowel, bladder, and skin health. The recommendations could be linked to 30 ICF categories which represented only 18% of the ICF categories included in the comprehensive versions of two ICF Core Sets. Key gaps were found in mobility, interpersonal interactions, and relationships, neuromusculoskeletal and movement-related, mental, sensory and pain functions. CONCLUSIONS: There is a notable lack of high-quality ageing-related recommendations for SCI management and rehabilitation. Future research should prioritize the generation of high-quality evidence to develop age-sensitive CPGs. Future SCI CPGs need to address the complex challenges at the interface of ageing and SCI, considering patient and stakeholder preferences.