Early life adversity promotes resilience to opioid addiction-related phenotypes in male rats and sex-specific transcriptional changes.

Experiencing some early life adversity can have an "inoculating" effect that promotes resilience in adulthood. However, the mechanisms underlying stress inoculation are unknown, and animal models are lacking. Here we used the limited bedding and nesting (LBN) model of adversity to evaluate stress inoculation of addiction-related phenotypes. In LBN, pups from postnatal days 2 to 9 and their dams were exposed to a low-resource environment. In adulthood, they were tested for addiction-like phenotypes and compared to rats raised in standard housing conditions. High levels of impulsivity are associated with substance abuse, but in males, LBN reduced impulsive choice compared to controls. LBN males also self-administered less morphine and had a lower breakpoint on a progressive ratio reinforcement schedule than controls. These effects of LBN on addiction-related behaviors were not found in females. Because the nucleus accumbens (NAc) mediates these behaviors, we tested whether LBN altered NAc physiology in drug-naïve and morphine-exposed rats. LBN reduced the frequency of spontaneous excitatory postsynaptic currents in males, but a similar effect was not observed in females. Only in males did LBN prevent a morphine-induced increase in the AMPA/NMDA ratio. RNA sequencing was performed to delineate the molecular signature in the NAc associated with LBN-derived phenotypes. LBN produced sex-specific changes in transcription, including in genes related to glutamate transmission. Collectively, these studies reveal that LBN causes a male-specific stress inoculation effect against addiction-related phenotypes. Identifying factors that promote resilience to addiction may reveal novel treatment options for patients.

Integration of palliative care consultation into the management of patients with chronic limb-threatening ischemia.

OBJECTIVE: We assessed the feasibility of integrating palliative care consultation into the routine management of patients with chronic limb-threatening ischemia (CLTI). Additionally, we sought to describe patient-reported outcomes from the palliative care and vascular literature in patients with CLTI receiving a palliative care consultation at our institution. METHODS: This was a single-institution, prospective, observational study that aimed to assess feasibility of incorporating palliative care consultation into the management of patients admitted to our tertiary academic medical center with CLTI by looking at utilization of palliative care before and after implementation of a protocol-based palliative care referral system. A survey comprised of patient-reported outcomes from the palliative care literature was administered to patients before and after palliative consultation. Length of stay and mortality were compared between our study cohort and a historic cohort of patients admitted with CLTI. RESULTS: Over a 14-month enrollment period, 44% of patients (n = 39) with CLTI (rest pain, 36%; tissue loss, 64%) admitted to the vascular service received palliative care consultation, compared with 5% of patients (n = 4) who would have met criteria over the preceding 14 months before our protocol was instituted. The mean age was 69 years, 23% were female, 92% were white, and 49% were able to ambulate independently. Revascularization included bypass (46%), peripheral vascular intervention (23%), and femoral endarterectomy (21%). Additional procedures included minor amputation or wound debridement (26%) and major amputation (15%). No patients received medical management alone. After receiving palliative care consultation, patients reported experiencing less emotional distress than before consultation (P = .03). They also reported being less bothered by uncertainty regarding what to expect from the course of their illness (P = .002). Fewer patients reported being unsure of the purpose of their medical care after palliative care consultation (8%) vs before (18%), although this was not statistically significant (P = .10). Median length of stay was longer in the study group compared with the historic cohort (8 vs 7 days; P = .02). There was no difference in 30-day mortality (3% vs 8%; P = .42) between the study group and the historic cohort (n = 77). CONCLUSIONS: Integrating inpatient palliative care consultation into the routine management of patients with CLTI is feasible and may improve emotional domains of health-related quality of life. This study laid the foundation for future studies on longer term outcomes of patients with CLTI undergoing palliative care consultation as well as the benefit of outpatient palliative care consultation in patients with CLTI.

Neighborhood-Level Predictors of Sexual Violence Across Intimate Partner and Non-Intimate Partner Relationships: A Case-Control Study.

Ample research explores individual factors associated with sexual violence, yet individual, dyadic, and environmental influences on intimate partner sexual violence (IPSV) occurring in the larger context of non-intimate partner violence (NIPSV) remain relatively unexplored. The current study aimed to determine the extent to which county-level indicators in combination with individual and dyadic factors are associated with sexual violence across relationship types. Reported IPSV and NIPSV cases were obtained from the Tennessee Bureau of Investigation's (TBI) online incident-based reporting system. County-level variables indicative of neighborhood physical disorder, violent crime, income inequality, firearm prevalence, and community alcohol use patterns were retrieved from the online resource County Health Rankings and Roadmaps. Using a nested case-control design, we determined significant sexual violence risk within younger cohorts and across relationship types, finding three significant county-level factors: 1) income inequality, 2) rate of firearm fatalities, and 3) percentage of female residents. Suggested prevention and intervention efforts include targeting younger age groups for IPSV and NIPSV education, developing resources for a range of relational partners, improving legal access and law enforcement training for reporting, and continued examination of the role of firearms.

Anesthetic efficacy of dexmedetomidine-ketamine in eastern box turtles (Terrapene carolina carolina) is enhanced with the addition of midazolam and when administered in the forelimb versus the hindlimb.

OBJECTIVE: To compare dexmedetomidine-ketamine (DK; 0.1 and 10 mg/kg, respectively) with midazolam (M; 1.0 mg/kg) or 0.9% sodium chloride (S; 0.2 mL/kg) administered IM in the forelimb (F) or hindlimb (H) in eastern box turtles (Terrapene carolina carolina). ANIMALS: 20 clinically healthy, captive adult eastern box turtles. METHODS: In a randomized, blinded, complete crossover study with 1-week washout periods, turtles were administered each of 3 treatments: F-DKS, F-DKM, or H-DKM. Palpebral reflex, muscle tone, and withdrawal responses were serially assessed and used to calculate cumulative sedation scores at each 5-minute time point. The ability to intubate was evaluated. At 60 minutes, atipamezole (1.0 mg/kg) and either flumazenil (F-DKM, H-DKM; 0.05 mg/kg) or 0.9% sodium chloride (F-DKS; 0.5 mL/kg) were administered IM. RESULTS: All treatments resulted in clinically relevant anesthetic effects. F-DKM produced significantly higher sedation scores than H-DKM or F-DKS at all time points between 10 and 60 minutes (P < .05). Sedation score variability was observed with all treatments with significantly higher variability for H-DKM (P < .05). Intubation was successful in 32, 89, and 11% of turtles in F-DKS, F-DKM, and H-DKM, respectively. Median (range) recovery time was 10 (5-22), 16 (7-45), and 12 (4-28) minutes for F-DKS, F-DKM, and H-DKM, respectively. CLINICAL RELEVANCE: In eastern box turtles, forelimb dexmedetomidine-ketamine resulted in clinically relevant anesthetic effects that were heightened with the addition of midazolam. Hindlimb administration of midazolam-dexmedetomidine-ketamine resulted in reduced and more variable anesthetic effects compared to forelimb administration, supporting a hepatic first-pass effect.

The Role of the Flexor Hallucis Longus in the Treatment of the Painful Hallux Metatarsophalangeal Joint.

BACKGROUND: Pain in the hallux metatarsophalangeal joint (MTPJ) is very common, yet the underlying etiology remains unknown. Previous clinical research and biomechanical research has implicated stenosing flexor hallucis longus (FHL) tendonitis as a possible cause. The hypothesis of this study was that treatment solely focusing on alleviating restricted FHL excursion would be beneficial in patients with hallux MTPJ pain. METHODS: This is a retrospective study of those treated in the Foot & Ankle Division between January 2009, and December 2018, who were diagnosed with FHL tendonitis with associated pain in the hallux MTPJ. Demographics, comorbidities, examination findings, imaging results, pain scores, treatment instituted, and outcome was obtained from the electronic medical record. The primary outcome was the improvement in the pain score (visual analog scale [VAS]). The surgical patients were included if their procedure was solely related to the FHL (posteromedial ankle release ± os trigonum resection). The decision to have surgery was analyzed by univariate and multivariable statistics using demographics, comorbidities, and clinical findings as potential factors (P < .05). RESULTS: In 75% (59 of 79 feet), nonoperative treatment of FHL stenosis resulted in a decrease in pain scores that the patients felt was satisfactory. The operative group that had an FHL release showed decreased pain in 90% (18 of 20 feet). Multivariable analysis identified the need for immobilization (OR 9.8, 95% CI 1.8-55.2, P = .009), participating in athletics (OR 8.7, 95% CI 1.8-42.2, P = .007), and higher initial VAS (OR 1.7, 95% CI 1.3-2.3, P < .001) as being associated with the decision for surgery. CONCLUSION: Previous biomechanical studies have suggested that stenosing FHL synovitis can cause increased intraarticular loading in the hallux MTPJ. The current clinical study supports this hypothesis, demonstrating that treatment focused on relieving restricted FHL excursion can ameliorate pain in the hallux MTPJ in select cases.

Exploring Working Memory, Self-Criticism, and Rumination as Factors Related to Self-Harm.

The prevalence of self-harm and the relative emotional influences are well understood, but certain cognitive factors such as working memory, rumination, and self-criticism are not fully explored. The aim of the current study is to examine specific aspects of cognition to explore their influence on self-harming behaviors. Participants included 101 undergraduates from a British University. Factors were measured using the Center for Epidemiological Studies Depression Scale, the Depressive Experiences Questionnaire, Ruminative Response Scale, and the Automated Working Memory Assessment. Findings indicated a greater incidence of self-harming behaviors among those who demonstrated higher depressive symptoms, but depression scores were not significantly related to self-harm. Additionally, a binary logistic regression indicated that self-criticism was associated with the presence of self-harming behavior, and a Classification and Regression Trees found that the single strongest predictor of self-harming behavior was a belief that love needs to be continually earned from others. Incorporating treatments that reduce self-criticism, such as improving self-compassion with Compassionate Mind Training, may address underlying mechanisms that trigger self-harm behavior.

College student mental health, treatment utilization, and reduced enrollment: Findings across a state university system during the COVID-19 pandemic.

Objective: This study measured the rate of college student mental health concerns and mental health service utilization. The roles of mental health and seeking treatment regarding anticipated enrollment were explored. Methods: One thousand eight hundred thirty-one randomly selected students participated in this online survey. Results: Most students reported clinically significant symptoms (88.3%), and many sought treatment in the past year (28.8%). Most students had favorable attitudes toward telemental health. Barriers to seeking care included a preference for self-management of symptoms (68.8%) and limited time (43.3%). Mental health was the most commonly reported reason for anticipating reduced enrollment (ps < .001), and these individuals were more likely to seek treatment. Conclusions: Past and anticipated use of mental health treatment likely exceeds on-campus capacity. Student mental health and retention are linked, and treatment may support retention. Nontraditional services, including telemental health, could help address increasing symptom severity and demand for services.

Physical activity, sitting time, and thermal quantitative sensory testing responses in African Americans.

Introduction: Prior research suggests that African Americans (AAs) have more frequent, intense, and debilitating pain and functional disability compared with non-Hispanic Whites (NHWs). Potential contributing factors to this disparity are physical activity and sedentary behavior, given that AAs are less physically active, and physical activity is associated with antinociception (whereas sedentary behavior is linked to pronociception). However, impact of these factors on pain processing has largely been unexplored in AAs, especially before chronic pain onset. Objective: This study examined relationships between physical activity, sedentary behavior (sitting time), and laboratory measures of pain and pain modulation in adult AAs. These included heat pain threshold and tolerance, temporal summation of pain (TSP, a marker of central sensitization), and conditioned pain modulation (CPM, a marker of descending pain inhibition). Methods: Multiple regressions were conducted to examine the effects of physical activity and sitting time on heat threshold and tolerance. Multilevel models were conducted to assess the relationship between physical activity, sitting time, and temporal summation of pain. Additional multilevel models were conducted to assess the relationship between physical activity, sitting time, and conditioned pain modulation. Results: Higher level of physical activity, but not sitting time, was associated with reduced TSP slopes. Neither physical activity nor sitting time was associated with CPM slopes. No significant relationships between physical activity or sitting time and heat pain threshold or tolerance were detected. Conclusions: These findings suggest that physical activity is associated with reduced TSP, an effect which may be driven by reduced spinal hyperexcitability in more active individuals. Thus, structural and individual interventions designed to increase physical activity in healthy, young AAs may be able to promote antinociceptive processes (ie, reduced TSP/reduced pain facilitation) potentially protective against chronic pain.

Time Perspective, Working Memory, and Depression in Non-Clinical Samples: Is There a Link?

Non-clinical depression is a major issue on college campuses, with some surveys estimating that 30% of college students have experienced a major depressive episode. One theoretical framework of depression is Zimbardo and Boyd (1999) time perspective model, which posits that our perspectives on time impact different aspects of life including our emotions, judgments, and decision making. The current study seeks to determine the role of this time perspectives model and a range of cognitive constructs including hope, rumination, and working memory on their influence in depression. Currently enrolled college students and participants not currently enrolled in college completed the Center for Epidemiologic Studies Depression Scale, the Zimbardo Time Perspective Inventory, the Adult Hope Scale, the Rumination Reflection Questionnaire, and the Automated Working Memory Assessment. Linear regression analysis revealed that, for the college students, Rumination and Past Negative scores predicted depressive symptoms. For the non-college students, Rumination, Present Fatalism, Hope Agency and Verbal Working Memory scores predicted depressive symptoms. The current results reiterate the importance of rumination in depression symptomology and that current cognitive depression models and treatments may benefit from including time perspective measures. Further implications of the results are discussed.

Hand size estimates of fibromyalgia patients are associated with clinical and experimental pain.

INTRODUCTION: Simply inspecting one's own body can reduce clinical pain and magnification of body parts can increase analgesia. Thus, body perceptions seem to play an important role for analgesia. Conversely, pain may also affect bodily perceptions. Therefore, we evaluated the effects of clinical and/or experimental pain on perceived hand size in fibromyalgia patients (FM) and healthy controls (HC). METHODS: To investigate the effects of chronic and/or acute pain on size perception we compared hand size estimates of 35 HC and 32 FM patients at baseline and during tonic mechanical pain stimuli applied to one ear lobe. Mechanical stimuli were adjusted for each individual pain sensitivity to achieve a rating of 4 ± 1 VAS (0-10) units. Photographs of each subject's hands were digitally manipulated to produce a monotonic series of 5 images larger and 6 smaller than actual size which were then presented to the participants in ascending and descending order (total number of images: 12). RESULTS: FM and HC participants' clinical pain ratings at baseline were 3.3 (3.1) and .3 (.8) VAS units, respectively. At baseline, FM participants selected significantly smaller hand images than HC as representative of their actual size (p < .02). During application of tonic experimental pain, the image size chosen to represent their actual hand size decreased significantly in FM participants and HC (p < .001) but this decrease was not different between groups (p > .05). Hand size estimates of FM participants correlated negatively with their clinical pain ratings (p < .04). CONCLUSION: The decreased hand size perception of FM patients and HC was associated with their clinical and/or experimental pain, supporting the hypothesis that pain can result in visual body distortions.