Social Transmission of Fear in Rats: The Role of 22-kHz Ultrasonic Distress Vocalization

Background: Social alarm calls alert animals to potential danger and thereby promote group survival. Adult laboratory rats in distress emit 22-kHz ultrasonic vocalization (USV) calls, but the question of whether these USV calls directly elicit defensive behavior in conspecifics is unresolved. Methodology/Principal Findings: The present study investigated, in pair-housed male rats, whether and how the conditioned fear-induced 22-kHz USVs emitted by the ‘sender ’ animal affect the behavior of its partner, the ‘receiver ’ animal, when both are placed together in a novel chamber. The sender rats ’ conditioned fear responses evoked significant freezing (an overt evidence of fear) in receiver rats that had previously experienced an aversive event but not in naïve receiver rats. Permanent lesions and reversible inactivations of the medial geniculate nucleus (MGN) of the thalamus effectively blocked the receivers ’ freeezing response to the senders ’ conditioned fear responses, and this occurred in absence of lesions/ inactivations impeding the receiver animals ’ ability to freeze and emit 22-kHz USVs to the aversive event per se. Conclusions/Significance: These results—that prior experience of fear and intact auditory system are required for receiver rats to respond to their conspecifics ’ conditioned fear responses—indicate that the 22-kHz USV is the main factor for socia

The topology of connections between rat prefrontal, motor and sensory cortices

The connections of prefrontal cortex (PFC) were investigated in the rat brain to determine the order and location of input and output connections to motor and somatosensory cortex. Retrograde (100 nl Fluoro-Gold) and anterograde (100 nl Biotinylated Dextran Amines, BDA; Fluorescein and Texas Red) neuronanatomical tracers were injected into the subdivisions of the PFC (prelimbic, ventral orbital, ventrolateral orbital, dorsolateral orbital) and their projections studied. We found clear evidence for organized input projections from the motor and somatosensory cortices to the PFC, with distinct areas of motor and cingulate cortex projecting in an ordered arrangement to the subdivisions of PFC. As injection location of retrograde tracer was moved from medial to lateral in PFC, we observed an ordered arrangement of projections occurring in sensory-motor cortex. There was a significant effect of retrograde injection location on the position of labelled cells occurring in sensory-motor cortex (dorsoventral, anterior-posterior and mediolateral axes p < 0.001). The arrangement of output projections from PFC also displayed a significant ordered projection to sensory-motor cortex (dorsoventral p < 0.001, anterior-posterior p = 0.002 and mediolateral axes p < 0.001)

Value-based care in surgery : implications in crisis and beyond

Over the past 2 years, surgeons and surgical systems have demonstrated an ability to rapidly adopt value-driven care, triage patients and make evidence-based decisions in response to crisis. Building on these successes, this paper explores a framework to expand these advances in creating a value-based approach to patient care through clinician leadership and state-wide clinical networks

The PROVe study: US real-world experience with chlormethine/mechlorethamine gel in combination with other therapies for patients with mycosis fungoides cutaneous T-cell lymphoma

BACKGROUND: Chlormethine/mechlorethamine gel is a skin-directed therapy for patients with mycosis fungoides cutaneous T-cell lymphoma. Currently, real-world data on chlormethine gel are lacking. OBJECTIVE: Our objective was to analyze the effect of chlormethine gel in combination with other therapies on efficacy, safety, and health-related quality of life in a real-world setting. METHODS: This prospective, observational study enrolled adult patients actively using chlormethine gel. Patients were monitored for up to 2 years during standard-of-care clinic visits. No specific visit schedules or clinical assessments, with the exception of patient-completed questionnaires, were mandated because of the expected variability in practice patterns. The primary efficacy endpoint was the proportion of patients with stage IA-IB disease receiving chlormethine + topical corticosteroids + other with ≥ 50% decrease in body surface area from baseline to 12 months. Response was assessed at each visit using by-time analysis, which investigates the trend to treatment response and allows assessment of response over time. Health-related quality of life was assessed with the Skindex-29 questionnaire. RESULTS: In total, 298 patients were monitored. At 12 months post-treatment initiation, 44.4% (chlormethine + topical corticosteroids + other) and 45.1% (patients receiving chlormethine + other treatment) of efficacy-evaluable patients were responders. By-time analysis demonstrated that peak response occurred (chlormethine + other; 66.7%) at 18 months. There was a significant correlation between responder status and lower post-baseline Skindex-29 scores. CONCLUSIONS: This real-world study confirmed that chlormethine gel is an important therapeutic option for patients with mycosis fungoides and contributes to reducing the severity of skin lesions and improving health-related quality of life

Neural Responses to Fluoxetine in Youths with Disruptive Behavior and Trauma Exposure: A Pilot Study

Objective: A preliminary investigation of the impact of a serotonergic agent (fluoxetine) on symptom profile and neural response in youths with disruptive behavior disorders (DBDs) and a history of trauma exposure. Methods: There were three participant groups: (i) Youths with DBDs and trauma exposure who received fluoxetine treatment for 8 weeks (n = 11); (ii) A matched group of youths with DBDs and trauma exposure who received routine regular follow-up in an outpatient clinic (n = 10); and (iii) Typically developing youths (n = 18). All participants conducted an expression processing functional magnetic resonance imaging task twice, 8 weeks apart: (pretreatment and post-treatment for youths with DBDs). Results: Youths with DBDs and trauma exposure who received fluoxetine treatment compared to the other two groups showed: (i) significant improvement in externalizing, oppositional defiant disorder, irritability, anxiety-depression, and trauma-related symptoms; (ii) as a function of fearful expression intensity, significantly decreased amygdala response and increased recruitment of regions implicated in top-down attention control (insula cortex, inferior parietal lobule, and postcentral gyrus) and emotional regulation (ventromedial prefrontal cortex [vmPFC]); and (iii) correlation between DBD/irritability symptom improvement and increased activation of top-down attention control areas (inferior parietal lobule, insula cortex, and postcentral gyrus) and an emotion regulation area (vmPFC). Conclusions: This study provides preliminary evidence that a serotonergic agent (fluoxetine) can reduce disruptive behavior and mood symptoms in youths with DBDs and trauma exposure and that this may be mediated by enhanced activation of top-down attention control and emotion regulation areas (inferior parietal lobule, insula cortex, and vmPFC)

What Does Weight Have to Do with It? Parent Perceptions of Weight and Pain in a Pediatric Chronic Pain Population

Tailored pain management strategies are urgently needed for youth with co-occurring chronic pain and obesity; however, prior to developing such strategies, we need to understand parent perspectives on weight in the context of pediatric chronic pain. Participants in this study included 233 parents of patients presenting to a multidisciplinary pediatric chronic pain clinic. Parents completed a brief survey prior to their child\u27s initial appointment; questions addressed parents\u27 perceptions of their child\u27s weight, and their perceptions of multiple aspects of the relationship between their child\u27s weight and chronic pain. The majority (64%) of parents of youth with obesity accurately rated their child\u27s weight; this group of parents was also more concerned (p \u3c 0.05) about their child\u27s weight than parents of youth with a healthy weight. However, the majority of parents of youth with obesity did not think their child\u27s weight contributed to his/her pain, or that weight was relevant to their child\u27s pain or pain treatment. Overall, only half of all parents saw discussions of weight, nutrition, and physical activity as important to treating their child\u27s pain. Results support the need for addressing parents\u27 perceptions of their child\u27s weight status, and educating parents about the relationship between excessive weight and chronic pain

Interventions that support novice nurses' transition into practice:A realist review

Background: Many transition-to-practice programs have been developed to support novice nurses during their first years into practice. These programs report improvements in retention, wellbeing and clinical competence, but the driving mechanisms of these interventions remain largely unclear. Objective: To identify how transition-to-practice programs for novice nurses work and in what contexts they work successfully. Methods: A realist review was conducted. Eligibility criteria included intervention studies aimed at novice nurses in their first two years of practice that reported outcomes on organizational or individual nurse level. The underlying theory of included transition-to-practice programs was extracted, and relevant contextual factors, mechanisms and outcomes were explored and synthesized into context-mechanism-outcome (CMO) configurations. The search was limited to studies between 2000 and 2023. Results: A total of 32 studies were included, evaluating 30 different transition-to-practice programs with a wide range of intervention components including stress management, clinical education, professional and peer support, and ward rotations. Transition-to-practice programs were often designed without a theoretical foundation. Driving mechanisms behind the programs pertained to psychological, professional, and social development. Contextual factors that activated the mechanisms were enabling conditions for mentors and novice nurses, selection and motivation of novice nurses and organizational culture. Conclusions: Current transition-to-practice programs primarily focus on the individual and professional development of nurses. However, transition to practice can benefit from a systemic approach that includes development initiatives on the organizational level. Registration: PROSPERO ID CRD42021268080, August 15, 2021. Tweetable abstract: Context and mechanisms determine successful implementation of transition to practice programs for novice nurses. @transitiontopractice @nurseworkforce.</p

Aluminum Effects in Infants and Children

Aluminum has no known biological function; however, it is a contaminant present in most foods and medications. Aluminum is excreted by the renal system, and patients with renal diseases should avoid aluminum-containing medications. Studies demonstrating long-term toxicity from the aluminum content in parenteral nutrition components led the US Food and Drug Administration to implement rules for these solutions. Large-volume ingredients were required to reduce the aluminum concentration, and small-volume components were required to be labeled with the aluminum concentration. Despite these rules, the total aluminum concentration from some components continues to be above the recommended final concentration. The concerns about toxicity from the aluminum present in infant formulas and antiperspirants have not been substantiated but require more research. Aluminum is one of the most effective adjuvants used in vaccines, and a large number of studies have documented minimal adverse effects from this use. Long-term, high-concentration exposure to aluminum has been linked in meta-analyses with the development of Alzheimer disease

Antecedents and outcomes of consumer environmentally friendly attitudes and behaviour

With the intensification of problems relating to the environment, a growing number of consumers are becoming more ecologically conscious in their preferences and purchases of goods. This paper presents the results of a study conducted among 500 Cypriot consumers, focusing on the factors that shape consumer environmental attitudes and behaviour, as well as on the resulting outcomes. The findings confirmed that both the inward and outward environmental attitudes of a consumer are positively influenced by his/her degree of collectivism, long-term orientation, political involvement, deontology, and law obedience, but have no connection with liberalism. The adoption of an inward environmental attitude was also found to be conducive to green purchasing behaviour that ultimately leads to high product satisfaction. On the other hand, an outward environmental attitude facilitates the adoption of a general environmental behaviour, which is responsible for greater satisfaction with life. The findings of the study have important implications for shaping effective company offerings to consumers in target markets, as well as formulating appropriate policies at the governmental level to enhance environmental sensitivity among citizens

A Synthetic HIV-1 Subtype C Backbone Generates Comparable PR and RT Resistance Profiles to a Subtype B Backbone in a Recombinant Virus Assay

In order to determine phenotypic protease and reverse transcriptase inhibitor-associated resistance in HIV subtype C virus, we have synthetically constructed an HIV-1 subtype C (HIV-1-C) viral backbone for use in a recombinant virus assay. The in silico designed viral genome was divided into 4 fragments, which were chemically synthesized and joined together by conventional subcloning. Subsequently, gag-protease-reverse-transcriptase (GPRT) fragments from 8 HIV-1 subtype C-infected patient samples were RT-PCR-amplified and cloned into the HIV-1-C backbone (deleted for GPRT) using In-Fusion reagents. Recombinant viruses (1 to 5 per patient sample) were produced in MT4-eGFP cells where cyto-pathogenic effect (CPE), p24 and Viral Load (VL) were monitored. The resulting HIV-1-C recombinant virus stocks (RVS) were added to MT4-eGFP cells in the presence of serial dilutions of antiretroviral drugs (PI, NNRTI, NRTI) to determine the fold-change in IC50 compared to the IC50 of wild-type HIV-1 virus. Additionally, viral RNA was extracted from the HIV-1-C RVS and the amplified GPRT products were used to generate recombinant virus in a subtype B backbone. Phenotypic resistance profiles in a subtype B and subtype C backbone were compared. The following observations were made: i) functional, infectious HIV-1 subtype C viruses were generated, confirmed by VL and p24 measurements; ii) their rate of infection was slower than viruses generated in the subtype B backbone; iii) they did not produce clear CPE in MT4 cells; and iv) drug resistance profiles generated in both backbones were very similar, including re-sensitizing effects like M184V on AZT