Optogenetic behavioral studies in depression research: A systematic review.

Optogenetics has made substantial contributions to our understanding of the mechanistic underpinnings of depression. This systematic review employs quantitative analysis to investigate the impact of optogenetic stimulation in mice and rats on behavioral alterations in social interaction, sucrose consumption, and mobility. The review analyses optogenetic behavioral studies using standardized behavioral tests to detect behavioral changes induced via optogenetic stimulation in stressed or stress-naive mice and rats. Behavioral changes were evaluated as either positive, negative, or not effective. The analysis comprises the outcomes of 248 behavioral tests of 168 studies described in 37 articles, including negative and null results. Test outcomes were compared for each behavior, depending on the animal cohort, applied type of stimulation and the stimulated neuronal circuit and cell type. The presented synthesis contributes toward a comprehensive picture of optogenetic behavioral research in the context of depression.

Fibrotic pathways and fibroblast-like synoviocyte phenotypes in osteoarthritis.

Osteoarthritis (OA) is the most common form of arthritis, characterized by osteophyte formation, cartilage degradation, and structural and cellular alterations of the synovial membrane. Activated fibroblast-like synoviocytes (FLS) of the synovial membrane have been identified as key drivers, secreting humoral mediators that maintain inflammatory processes, proteases that cause cartilage and bone destruction, and factors that drive fibrotic processes. In normal tissue repair, fibrotic processes are terminated after the damage has been repaired. In fibrosis, tissue remodeling and wound healing are exaggerated and prolonged. Various stressors, including aging, joint instability, and inflammation, lead to structural damage of the joint and micro lesions within the synovial tissue. One result is the reduced production of synovial fluid (lubricants), which reduces the lubricity of the cartilage areas, leading to cartilage damage. In the synovial tissue, a wound-healing cascade is initiated by activating macrophages, Th2 cells, and FLS. The latter can be divided into two major populations. The destructive thymocyte differentiation antigen (THY)1─ phenotype is restricted to the synovial lining layer. In contrast, the THY1+ phenotype of the sublining layer is classified as an invasive one with immune effector function driving synovitis. The exact mechanisms involved in the transition of fibroblasts into a myofibroblast-like phenotype that drives fibrosis remain unclear. The review provides an overview of the phenotypes and spatial distribution of FLS in the synovial membrane of OA, describes the mechanisms of fibroblast into myofibroblast activation, and the metabolic alterations of myofibroblast-like cells.

Do Transtibial Amputations Outperform Amputations of the Hind- and Midfoot Following Severe Limb Trauma?: A Secondary Analysis of the OUTLET Study.

BACKGROUND: The purpose of this study was to compare 18-month clinical and patient-reported outcomes between patients with severe lower-limb injuries treated with a transtibial amputation or a hind- or midfoot amputation. Despite the theoretical benefits of hind- and midfoot-level amputation, we hypothesized that patients with transtibial amputations would report better function and have fewer complications. METHODS: The study included patients 18 to 60 years of age who were treated with a transtibial amputation (n = 77) or a distal amputation (n = 17) and who were enrolled in the prospective, multicenter Outcomes Following Severe Distal Tibial, Ankle, and/or Foot Trauma (OUTLET) study. The primary outcome was the difference in Short Musculoskeletal Function Assessment (SMFA) scores, and secondary outcomes included pain, complications, amputation revision, and amputation healing. RESULTS: There were no significant differences between patients with distal versus transtibial amputation in any of the domains of the SMFA: dysfunction index [distal versus transtibial], 31.2 versus 22.3 (p = 0.13); daily activities, 37.3 versus 26.0 (p = 0.17); emotional status, 41.4 versus 29.3 (p = 0.07); mobility, 36.5 versus 27.8 (p = 0.20); and bother index, 34.4 versus 23.6 (p = 0.14). Rates of complications requiring revision were higher for distal amputations but not significantly so (23.5% versus 13.3%; p = 0.28). One distal and no transtibial amputees required revision to a higher level (p = 0.18). A higher proportion of patients with distal compared with transtibial amputation required local surgical revision (17.7% versus 13.3%; p = 0.69). There was no significant difference between the distal and transtibial groups in scores on the Brief Pain Index at 18 months post-injury. CONCLUSIONS: Surgical complication rates did not differ significantly between patients who underwent transtibial versus hind- or midfoot amputation for severe lower-extremity injury. The average SMFA scores were higher (worse), although not significantly different, for patients undergoing distal compared with transtibial amputation, and more patients with distal amputation had a complication requiring surgical revision. Of note, more patients with distal amputation required closure with an atypical flap, which likely contributed to less favorable outcomes. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Defining Incidence of Acute Compartment Syndrome in the Research Setting: A Proposed Method From the PACS Study.

OBJECTIVE: To compare the retrospective decision of an expert panel who assessed likelihood of acute compartment syndrome (ACS) in a patient with a high-risk tibia fracture with decision to perform fasciotomy. DESIGN: Prospective observational study. SETTING: Seven Level 1 trauma centers. PATIENTS/PARTICIPANTS: One hundred eighty-two adults with severe tibia fractures. MAIN OUTCOME MEASUREMENTS: Diagnostic performance (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver-operator curve) of an expert panel's assessment of likelihood ACS compared with fasciotomy as the reference diagnostic standard. SECONDARY OUTCOMES: The interrater reliability of the expert panel as measured by the Krippendorff alpha. Expert panel consensus was determined using the percent of panelists in the majority group of low (expert panel likelihood of ≤0.3), uncertain (0.3-0.7), or high (>0.7) likelihood of ACS. RESULTS: Comparing fasciotomy (the diagnostic standard) and the expert panel's assessment as the diagnostic classification (test), the expert panel's determination of uncertain or high likelihood of ACS (threshold >0.3) had a sensitivity of 0.90 (0.70, 0.99), specificity of 0.95 (0.90, 0.98), PPV of 0.70 (0.50, 0.86), and NPV of 0.99 (0.95, 1.00). When a threshold of >0.7 was set as a positive diagnosis, the expert panel assessment had a sensitivity of 0.67 (0.43, 0.85), specificity of 0.98 (0.95, 1.00), PPV of 0.82 (0.57, 0.96), and NPV of 0.96 (0.91, 0.98). CONCLUSION: In our study, the retrospective assessment of an expert panel of the likelihood of ACS has good specificity and excellent NPV for fasciotomy, but only low-to-moderate sensitivity and PPV. The discordance between the expert panel-assessed likelihood of ACS and the decision to perform fasciotomy suggests that concern regarding potential diagnostic bias in studies of ACS is warranted. LEVEL OF EVIDENCE: Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.

Cognitive-Behavioral-Based Physical Therapy for Improving Recovery After Traumatic Orthopaedic Lower Extremity Injury (CBPT-Trauma).

SUMMARY: Physical and psychological impairment resulting from traumatic injuries is often significant and affects employment and functional independence. Extremity trauma has been shown to negatively affect long-term self-reported physical function, the ability to work, and participation in recreational activities and contributes to increased rates of anxiety and/or depression. High pain levels early in the recovery process and psychosocial factors play a prominent role in recovery after traumatic lower extremity injury. Cognitive-behavioral therapy pain programs have been shown to mitigate these effects. However, patient access issues related to financial and transportation constraints and the competing demands of treatment focused on the physical sequelae of traumatic injury limit patient participation in this treatment modality. This article describes a telephone-delivered cognitive-behavioral-based physical therapy (CBPT-Trauma) program and design of a multicenter trial to determine its effectiveness after lower extremity trauma. Three hundred twenty-five patients from 7 Level 1 trauma centers were randomized to CBPT-Trauma or an education program after hospital discharge. The primary hypothesis is that compared with patients who receive an education program, patients who receive the CBPT-Trauma program will have improved physical function, pain, and physical and mental health at 12 months after hospital discharge.

Can financial payments incentivize short-term smoking cessation in orthopaedic trauma patients? Evidence from a discrete choice experiment.

BACKGROUND: Smoking increases the risk of complications and related costs after an orthopaedic fracture. Research in other populations suggests that a one-time payment may incentivize smoking cessation. However, little is known on fracture patients' willingness to accept financial incentives to stop smoking; and the level of incentive required to motivate smoking cessation in this population. This study aimed to estimate the financial threshold required to motivate fracture patients to stop smoking after injury. METHODS: This cross-sectional study utilized a discrete choice experiment (DCE) to elicit patient preferences towards financial incentives and reduced complications associated with smoking cessation. We presented participants with 12 hypothetical options with several attributes with varying levels. The respondents' data was used to determine the utility of each attribute level and the relative importance associated with each attribute. RESULTS: Of the 130 enrolled patients, 79% reported an interest in quitting smoking. We estimated the financial incentive to be of greater relative importance (ri) (45%) than any of the included clinical benefits of smoking cessations (deep infection (ri: 24%), bone healing complications (ri: 19%), and superficial infections (ri: 12%)). A one-time payment of $800 provided the greatest utility to the respondents (0.64, 95% CI: 0.36 to 0.93), surpassing the utility associated with a single $1000 financial incentive (0.36, 95% CI: 0.18 to 0.55). CONCLUSIONS: Financial incentives may be an effective tool to promote smoking cessation in the orthopaedic trauma population. The findings of this study define optimal payment thresholds for smoking cessation programs.