Modulation of cannabinoid receptor 2 alters neuroinflammation and reduces formation of alpha-synuclein aggregates in a rat model of nigral synucleinopathy.

Research into the disequilibrium of microglial phenotypes has become an area of intense focus in neurodegenerative disease as a potential mechanism that contributes to chronic neuroinflammation and neuronal loss in Parkinson's disease (PD). There is growing evidence that neuroinflammation accompanies and may promote progression of alpha-synuclein (Asyn)-induced nigral dopaminergic (DA) degeneration. From a therapeutic perspective, development of immunomodulatory strategies that dampen overproduction of pro-inflammatory cytokines from chronically activated immune cells and induce a pro-phagocytic phenotype is expected to promote Asyn removal and protect vulnerable neurons. Cannabinoid receptor-2 (CB2) is highly expressed on activated microglia and peripheral immune cells, is upregulated in the substantia nigra of individuals with PD and in mouse models of nigral degeneration. Furthermore, modulation of CB2 protects against rotenone-induced nigral degeneration; however, CB2 has not been pharmacologically and selectively targeted in an Asyn model of PD. Here, we report that 7 weeks of peripheral administration of CB2 inverse agonist SMM-189 reduced phosphorylated (pSer129) alpha-synuclein in the substantia nigra compared to vehicle treatment. Additionally, SMM-189 delayed Asyn-induced immune cell infiltration into the brain as determined by flow cytometry, increased CD68 protein expression, and elevated wound-healing-immune-mediator gene expression. Additionally, peripheral immune cells increased wound-healing non-classical monocytes and decreased pro-inflammatory classical monocytes. In vitro analysis of RAW264.7 macrophages treated with lipopolysaccharide (LPS) and SMM-189 revealed increased phagocytosis as measured by the uptake of fluorescence of pHrodo E. coli bioparticles. Together, results suggest that targeting CB2 with SMM-189 skews immune cell function toward a phagocytic phenotype and reduces toxic aggregated species of Asyn. Our novel findings demonstrate that CB2 may be a target to modulate inflammatory and immune responses in proteinopathies.

Replacing the Scalpel With a Computer Mouse: An Evaluation of Time Spent on Electronic Health Record for Plastic Surgery Residents and Its Impact on Resident Training.

BACKGROUND: Following the integration of the electronic health record (EHR) into the healthcare system, concern has grown regarding EHR use on physician well-being. For surgical residents, time spent on the EHR increases the burden of a demanding, hourly restricted schedule and detracts from time spent honing surgical skills. To better characterize these burdens, we sought to describe EHR utilization patterns for plastic surgery residents. METHODS: Integrated plastic surgery resident EHR utilization from March 2019 to March 2020 was extracted via Cerner Analytics at a tertiary academic medical center. Time spent in the EHR on-duty (0600-1759) and off-duty (1800-0559) in the form of chart review, orders, documentation, and patient discovery was analyzed. Statistical analysis was performed in the form of independent t tests and Analysis of Variance (ANOVA). RESULTS: Twelve plastic surgery residents spent a daily average of 94 ± 84 minutes on the EHR, one-third of which was spent off-duty. Juniors (postgraduate years 1-3) spent 123 ± 99 minutes versus seniors (postgraduate years 4-6) who spent 61 ± 49 minutes (P < 0.01). Seniors spent 19% of time on the EHR off-duty, compared with 37% for juniors (P < 0.01). Chart review comprised the majority (42%) of EHR usage, followed by patient discovery (22%), orders (14%), documentation (12%), other (6%), and messaging (1%). Seniors spent more time on patient discovery (25% vs 21%, P < 0.001), while juniors spent more time performing chart review (48% vs 36%, P = 0.19). CONCLUSION: Integrated plastic surgery residents average 1.5 hours on the EHR daily. Junior residents spend 1 hour more per day on the EHR, including more time off-duty and more time performing chart review. These added hours may play a role in duty hour violations and detract from obtaining operative skill sets.

Aberrant neural computation of social controllability in nicotine-dependent humans.

Social controllability, defined as the ability to exert influence when interacting with others, is crucial for optimal decision-making. Inability to do so might contribute to maladaptive behaviors such as drug use, which often takes place in social settings. Here, we examined nicotine-dependent humans using fMRI, as they made choices that could influence the proposals from simulated partners. Computational modeling revealed that smokers under-estimated the influence of their actions and self-reported a reduced sense of control, compared to non-smokers. These findings were replicated in a large independent sample of participants recruited online. Neurally, smokers showed reduced tracking of forward projected choice values in the ventromedial prefrontal cortex, and impaired computation of social prediction errors in the midbrain. These results demonstrate that smokers were less accurate in estimating their personal influence when the social environment calls for control, providing a neurocomputational account for the social cognitive deficits in this population.

The Cost Does Not Outweigh the Benefit: Pathologic Evaluation of Wrist Ganglion Cysts Should Not Be Routine.

BACKGROUND: As health care costs in the United States continue to rise, there is increasing attention on cost-saving measures. One area of investigation is the utility of pathologic examination of specimens from routine procedures with a suspected benign pathology. We assessed the utility and cost of routine pathologic analysis for wrist ganglion cyst excision. METHODS: A retrospective cohort study of all wrist ganglion cyst excisions performed by seven hand surgeons was conducted from 2015 to 2019 at Penn State Hershey Medical Center. Preoperative and intraoperative diagnoses, pathologic diagnosis, and pathology cost were assessed. RESULTS: A total of 407 patients underwent ganglion cyst excision, with 318 (78.1%) specimens sent for pathologic review. Of the 318, 317 (99.6%) specimens were concordant with the preoperative or intraoperative diagnosis of ganglion cyst. One specimen (0.3%) resulted as a benign cystic vascular malformation. The charge per specimen was $258, totaling $81,786 spent confirming benign pathology that was clinically correctly diagnosed by the operating surgeon in 99.6% of cases. CONCLUSIONS: Routine pathologic analysis is not indicated in cases in which surgeons have a high clinical suspicion for ganglion cyst based on preoperative and intraoperative findings. Pathologic review should be reserved for cases with atypical presentations or intraoperative findings.

A natural language processing approach reveals first-person pronoun usage and non-fluency as markers of therapeutic alliance in psychotherapy.

It remains elusive what language markers derived from psychotherapy sessions are indicative of therapeutic alliance, limiting our capacity to assess and provide feedback on the trusting quality of the patient-clinician relationship. To address this critical knowledge gap, we leveraged feature extraction methods from natural language processing (NLP), a subfield of artificial intelligence, to quantify pronoun and non-fluency language markers that are relevant for communicative and emotional aspects of therapeutic relationships. From twenty-eight transcripts of non-manualized psychotherapy sessions recorded in outpatient clinics, we identified therapists' first-person pronoun usage frequency and patients' speech transition marking relaxed interaction style as potential metrics of alliance. Behavioral data from patients who played an economic game that measures social exchange (i.e. trust game) suggested that therapists' first-person pronoun usage may influence alliance ratings through their diminished trusting behavior toward therapists. Together, this work supports that communicative language features in patient-therapist dialogues could be markers of alliance.

Comparison of Tumescent Anesthesia Versus Pectoral Nerve Block in Bilateral Reduction Mammaplasty.

INTRODUCTION: With an increasing focus on multimodal pain control to reduce opioid requirements, regional and local anesthesia techniques have been investigated in bilateral reduction mammaplasty with variable results. The purpose of this study is to compare tumescent anesthesia with pectoral nerve block II (PECS II) in patients undergoing bilateral reduction mammaplasty with respect to postoperative pain and nausea, opioid consumption, length of stay, and cost. METHODS: A retrospective review of patients undergoing bilateral reduction mammaplasty for macromastia between November 2020 and December 2021 was performed. Demographic information, operative and anesthesia times, antiemetic and morphine equivalent requirements, postoperative numeric pain rating scales, and time until hospital discharge were compared between groups. χ2 and Fisher exact tests examined subgroup differences in categorical variables. Two-sample t test and Wilcoxon rank-sum test evaluated differences in continuous parametric and nonparametric variables, respectively. RESULTS: Fifty-three patients underwent bilateral reduction mammaplasty by 3 surgeons, 71.7% (n = 38) with tumescent anesthesia infiltrated by the operating surgeon before the start of the procedure and 28.3% (n = 15) with bilateral PECS II blocks performed by anesthesia before the start of the procedure. There was no difference in age, body mass index, weight resected, intraoperative medication, or immediate postoperative complications. Postoperative pain scores and opioid requirements were similar between the 2 groups. Twenty-one percent (n = 8) of tumescent patients compared with 66.7% (n = 10) of block patients required 1 or more doses of postoperative antiemetics ( P = 0.002). Patients who received blocks spent longer in the postoperative recovery area (5.3 vs 7.1 hours, P < 0.01). However, this did not translate to a significant increase in overnight stays. The block group had significantly higher hospitalization cost by an average of $4000, driven by pharmacy and procedural cost ( P < 0.01). CONCLUSION: In this cohort of multimodal perioperative pain-controlled reduction mammaplasty patients, tumescent anesthesia was associated with decreased antiemetic requirements, less time in recovery before discharge, and lower cost compared with PECS II blocks. Therefore, tumescent anesthesia may be favored over PECS II blocks when considering multimodal pain control strategies in reduction mammaplasty patients.

Mesenchymal Stem Cell-Derived Extracellular Vesicles for Therapeutic Use and in Bioengineering Applications.

Extracellular vesicles (EVs) are small lipid bilayer-delimited particles that are naturally released from cells into body fluids, and therefore can travel and convey regulatory functions in the distal parts of the body. EVs can transmit paracrine signaling by carrying over cytokines, chemokines, growth factors, interleukins (ILs), transcription factors, and nucleic acids such as DNA, mRNAs, microRNAs, piRNAs, lncRNAs, sn/snoRNAs, mtRNAs and circRNAs; these EVs travel to predecided destinations to perform their functions. While mesenchymal stem cells (MSCs) have been shown to improve healing and facilitate treatments of various diseases, the allogenic use of these cells is often accompanied by serious adverse effects after transplantation. MSC-produced EVs are less immunogenic and can serve as an alternative to cellular therapies by transmitting signaling or delivering biomaterials to diseased areas of the body. This review article is focused on understanding the properties of EVs derived from different types of MSCs and MSC-EV-based therapeutic options. The potential of modern technologies such as 3D bioprinting to advance EV-based therapies is also discussed.

Smooth Versus Textured Tissue Expander Breast Reconstruction: Complications and Efficacy.

INTRODUCTION: Ongoing recognition of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and its link with textured devices has brought a paradigm shift in prosthetic-based breast reconstruction. Many institutions no longer offer textured expansion devices for staged reconstruction. However, there is a paucity of data regarding the efficacy of smooth tissue expanders (TE). We hypothesized that the time to final reconstruction and complication profile between smooth and textured TEs would be similar in breast reconstruction patients. METHODS: A retrospective chart review was performed of all patients who underwent TE breast reconstruction during a 6-year period at the Penn State Hershey Medical Center. Rates of complications treated nonoperatively and those requiring reoperation were assessed. Mechanical complications, including expander malposition and rupture, were evaluated. Time to final breast reconstruction was quantified. Mixed-effects logistic regression and linear regression models, as appropriate, were used to compare textured to smooth TEs. Patient characteristics and anatomic plane placement were adjusted for in all analyses of outcomes. RESULTS: Data were collected on 389 patients, encompassing 140 smooth and 604 textured TEs. Textured devices had an increased incidence of complications treated nonsurgically (16.7% vs 10.7%; P = 0.14). However, smooth TEs had an increased incidence of reoperation (12.1% vs 7.6%; P = 0.06). Most noteworthy was that although smooth TEs had a 40-fold increase in malposition (13.6% vs 0.3%; P < 0.001), no reoperation for this complication was warranted. Further, the time to final reconstruction was comparable between the 2 devices (textured expanders: 221 days and smooth expanders: 234 days; P = 0.15). CONCLUSIONS: Staged, implant-based reconstruction is the most common surgical approach to recreate the breast mound following mastectomy. Textured TEs were the cornerstone to this approach. Unfortunately, the association between textured devices and BIA-ALCL now mandates an alternative. We postulated that smooth expanders would compare favorably for breast reconstruction. Although our study suggests that smooth TEs suffer more malposition, this has a negligible impact on the reconstructive timeline. Thus, smooth TEs may prove beneficial when considering the risk of BIA-ALCL associated with textured devices.

Regenerative Engineering: Current Applications and Future Perspectives.

Many pathologies, congenital defects, and traumatic injuries are untreatable by conventional pharmacologic or surgical interventions. Regenerative engineering represents an ever-growing interdisciplinary field aimed at creating biological replacements for injured tissues and dysfunctional organs. The need for bioengineered replacement parts is ubiquitous among all surgical disciplines. However, to date, clinical translation has been limited to thin, small, and/or acellular structures. Development of thicker tissues continues to be limited by vascularization and other impediments. Nevertheless, currently available materials, methods, and technologies serve as robust platforms for more complex tissue fabrication in the future. This review article highlights the current methodologies, clinical achievements, tenacious barriers, and future perspectives of regenerative engineering.

Osteoradionecrosis and microvascular free flap failure managed with negative pressure wound therapy: A case report.

A 56-year-old female with a history of meningioma status post subtotal resection (Simpson grade IV) and extensive radiation therapy presented with osteoradionecrosis (O.R.N.) managed previously with a microvascular free flap (MVFF). The evaluation revealed worsening O.R.N. and a scalp defect of 15 × 10 cm. The patient underwent MVFF reconstruction utilizing a free latissimus muscle flap covered by meshed split-thickness skin graft (STSG). Her surgery was complicated by delayed free flap failure and Serratia marcescens growth, which occurred sometime after discharge from the hospital. This was managed with removal of the free muscle flap and skin graft, serial debridement's, antibiotics, and replacements of a synthetic dural matrix and negative pressure wound therapy (NPWT). Once a clean wound bed was again obtained, the patient underwent fasciocutaneous anterolateral thigh (A.L.T.) MVFF reconstruction, which was complicated by left hypoglossal nerve injury, dehiscence of the flap inset, and dehiscence of the neck access incision requiring revision surgery. On the last follow-up 2 weeks after her surgery, the patient had 100% flap viability and a 2 × 1.5 cm on the left parietal aspect of the flap healing be secondary intent. We demonstrate that NPWT is successful in managing open calvarial wounds due to O.R.N.

Analysis of Cranial Base Suture Fusion Patterns.

PURPOSE: It is known from both anatomic and radiographic studies that the majority of cranial sutures begin fusing in early adulthood and are fused by late adulthood. However, most of the studies focus on the cranial vault rather than the cranial base. Most clinicians treating patients with craniosynostosis are interpreting the behavior of cranial sutures on CT imaging. Therefore, the purpose of this study was to further clarify the radiographic appearance of cranial base sutures over the natural human life span. METHODS: Thirty CT scans of the head and face were reviewed for each decade starting at 1 year of life up to age 90. Scans were evaluated for the appearance of the occipitomastoid, petrosoocciptial, sphenosquamous, sphenopetrosal, frontosphenoidal, sphenozygomatic, petrososquamosal, frontoethmoidal, sphenoethmoidal and sphenoccipital sutures. Sutures were categorized as obliterated, present with fusion, present without fusion and unable to visualize. RESULTS: The majority of cranial base sutures are visible up through the eighth decade, although evidence of ossification across the suture starts as early as the second decade. Some sutures such as the occipitomastoid appeared > 90% open even as late as the ninth decade. Other sutures such as the sphenosquamosal and frontozygomatic are mostly fused by that age. CONCLUSION: Cranial base sutures appear to behave radiographically similar, to the cranial vault sutures in that they largely remain visible throughout adulthood but show varying amounts of ossification. There are some cranial base sutures which appear to remain open throughout life although the significance of this has yet to be determined.

The red reflex.

Eliciting the red reflex is a useful clinical test that can be easily performed in the pediatric emergency room. A direct ophthalmoscope is the only tool needed to perform this test. The test is non-invasive, making it a quick screening tool for even the most apprehensive child. A normal red reflex can rule out intraocular pathology; an abnormal reflex can indicate need for urgent ophthalmologic referral. The differential diagnoses for an absent (or black) reflex; an abnormally sized, shaped or positioned reflex; leukocoria; as well as a non-homogenous reflex are listed.