Fostering Inclusivity in Research Engagement for Underrepresented Populations in Parkinson's Disease: The FIRE-UP PD study.

BACKGROUND: Members of vulnerable populations are underrepresented in Parkinson's disease (PD) research. A complex web of research barriers perpetuates this gap. Community-based research methods are one approach to addressing this issue. The present PD study was designed to examine the effectiveness of community-based interventions to overcome barriers and increase research participation among underrepresented groups (URGs). METHODS: Eight study sites across the US were selected and paired based on proposed interventions with specific URGs. Surveys assessed knowledge and attitudes toward PD research. Finally, researchers examined whether the present study affected recruitment to Fox Insight, an online PD research study also recruiting at each site. RESULTS: In total, 474 participants were recruited. At post-intervention for the FIRE-UP PD Study, recruitment increased significantly in intervention compared to control sites among Black and African American non-Hispanic/Latino populations (p = 0.003), White Hispanic/Latino (p = 0.003) populations, and Not Listed Hispanic/Latino populations (p < 0.001) as well as those with an educational attainment of a high school diploma/General Education Diploma (GED) (p = 0.009), and an income <$20,000 (p = 0.005) or between $20,000-$34,999 (p < 0.001). Study surveys measuring changes in awareness and attitudes toward PD research had mixed results. In Fox Insight, 181 participants were passively recruited with a shift toward more diverse participant demographics. CONCLUSION: Research participation demographics reflective of the general population are critical to PD investigation and treatment. The FIRE-UP PD Study showed the effectiveness of localized community engagement strategies in increasing URG recruitment to PD research. Therefore, further PD research employing community-based methods to improve diverse participant recruitment is needed.

Do Surgical Smoke Evacuators Increase the Risk of Hearing Loss for Operative Personnel During Routine Adenotonsillectomy Surgery?

INTRODUCTION: Aerosol mitigation equipment implemented due to COVID-19 has increased noise levels in the operating room (OR) during otolaryngological procedures. Intraoperative sound levels may potentially place personnel at risk for occupational hearing loss. This study hypothesized that cumulative intraoperative noise exposures with aerosol mitigation equipment exceed recommended occupational noise exposure levels. METHODS: Sound levels generated by the surgical smoke evacuator (SSE) during adenotonsillectomy were measured using a sound level meter and compared to surgery without SSE. RESULTS: Thirteen adenotonsillectomy surgeries were recorded. Mean sound levels with the SSE were greater than the control (72 ± 3 A-weighted decibels (dBA) vs. 68 ± 2 dBA; p=0.015). Maximum noise levels during surgery with SSE reached 82 ± 3 dBA. CONCLUSION: Surgeons performing adenotonsillectomy with aerosol mitigation equipment are exposed to significant noise levels. Intraoperative sound levels exceeded international standards for work requiring concentration. Innovation is needed to reduce cumulative OR noise exposures.

Sensory nerve release of CGRP increases tumor growth in HNSCC by suppressing TILs.

BACKGROUND: Perineural invasion (PNI) and nerve density within the tumor microenvironment (TME) have long been associated with worse outcomes in head and neck squamous cell carcinoma (HNSCC). This prompted an investigation into how nerves within the tumor microenvironment affect the adaptive immune system and tumor growth. METHODS: We used RNA sequencing analysis of human tumor tissue from a recent HNSCC clinical trial, proteomics of human nerves from HNSCC patients, and syngeneic orthotopic murine models of HPV-unrelated HNSCC to investigate how sensory nerves modulate the adaptive immune system. FINDINGS: Calcitonin gene-related peptide (CGRP) directly inhibited CD8 T cell activity in vitro, and blocking sensory nerve function surgically, pharmacologically, or genetically increased CD8 and CD4 T cell activity in vivo. CONCLUSIONS: Our data support sensory nerves playing a role in accelerating tumor growth by directly acting on the adaptive immune system to decrease Th1 CD4 T cells and activated CD8 T cells in the TME. These data support further investigation into the role of sensory nerves in the TME of HNSCC and points toward the possible treatment efficacy of blocking sensory nerve function or specifically inhibiting CGRP release or activity within the TME to improve outcomes. FUNDING: 1R01DE028282-01, 1R01DE028529-01, 1P50CA261605-01 (to S.D.K.), 1R01CA284651-01 (to S.D.K.), and F31 DE029997 (to L.B.D.).

High Prevalence of Obstructive Sleep-Disordered Breathing in Pediatric Patients With Turner Syndrome.

OBJECTIVE: Girls with Turner syndrome (TS) often have features that have been associated with obstructive sleep-disordered breathing (oSDB). However, little is known about oSDB in TS. Herein, we aimed to characterize oSDB in young patients with TS and identify associated risk factors. STUDY DESIGN: Retrospective cross-sectional study. SETTING: Tertiary care pediatric hospital. METHODS: We reviewed medical records for patients diagnosed with TS seen at our institution between October 1, 2007 and December 31, 2019 with the first outpatient visit before age 6 years. The prevalence of oSDB was compared to the general pediatric population with 1-sample binomial proportion tests. Clinical characteristics were compared between those diagnosed with oSDB and those without oSDB, and risk factors for oSDB were identified. RESULTS: Of 151 patients with TS, 73 (48%) were diagnosed with oSDB which is 4-fold higher than the general pediatric population (12%, P < 0.0001). In the multivariable model, adenoid, tonsillar, and inferior turbinate hypertrophy, birthweight, failure to thrive, and older age at the last clinic visit were all associated with increased odds for oSDB. CONCLUSION: Young children with TS have a high prevalence of oSDB and thus should be screened for oSDB. Polysomnography should be performed in those with associated risk factors and symptoms oSDB. Treatment of oSDB is imperative as individuals with TS are already at increased risk of behavioral problems, neurocognitive deficits, and growth impairment that may be worsened with oSDB.

Electrochemical Lipolysis Induces Adipocyte Death and Fat Necrosis: In Vivo Pilot Study in Pigs.

BACKGROUND: Current minimally invasive fat reduction modalities use equipment that can cost thousands of U.S. dollars. Electrochemical lipolysis (ECLL), using low-cost battery and electrodes (approximately $10), creates acid/base within fat (width, approximately 3 mm), damaging adipocytes. Longitudinal effects of ECLL have not been studied. In this pilot study, the authors hypothesize that in vivo ECLL induces fat necrosis, decreases adipocyte number/viability, and forms lipid droplets. METHODS: Two female Yorkshire pigs (50 to 60 kg) received ECLL. In pig 1, 10 sites received ECLL, and 10 sites were untreated. In pig 2, 12 sites received ECLL and 12 sites were untreated. For ECLL, two electrodes were inserted into dorsal subcutaneous fat and direct current was applied for 5 minutes. Adverse effects of excessive pain, bleeding, infection, and agitation were monitored. Histology, live-dead (calcein, Hoechst, ethidium homodimer-1), and morphology (Bodipy and Hoechst) assays were performed on day 0 and postprocedure days 1, 2, 7, 14 (pig 1 and pig 2), and 28 (pig 2). Average particle area, fluorescence signal areas, and adipocytes and lipid droplet numbers were compared. RESULTS: No adverse effects occurred. Live-dead assays showed adipocyte death on the anode on days 0 to 7 and the cathode on days 1 to 2 (not significant). Bodipy showed significant adipocyte loss at all sites ( P < 0.001) and lipid droplet formation at the cathode site on day 2 ( P = 0.0046). Histology revealed fat necrosis with significant increases in average particle area at the anode and cathode sites by day 14 (+277.3% change compared with untreated, P < 0.0001; +143.4%, P < 0.0001) and day 28 (+498.6%, P < 0.0001; +354.5%, P < 0.0001). CONCLUSIONS: In vivo ECLL induces fat necrosis in pigs. Further studies are needed to evaluate volumetric fat reduction. CLINICAL RELEVANCE STATEMENT: In vivo ECLL induces adipocyte death and fat necrosis. ECLL has the potential to be utilized in body fat contouring.

Effect of Perioperative Antithrombotics on Postoperative Transfusion and Hematoma in Head and Neck Free Flaps.

Objective: To explore if antiplatelet or anticoagulant therapy increases the risk of transfusion requirement or postoperative hematoma formation in patients undergoing microvascular reconstruction for head and neck defects. Study Design: Retrospective cohort study. Setting: Departments of Otolaryngology-Head and Neck Surgery at the University of Alabama at Birmingham, the University of Colorado, and the University of California Irvine. Methods: A multi-institutional, retrospective review on microvascular reconstruction of the head and neck between August 2013 to July 2021. Perioperative antithrombotic data were collected to examine predictors of postoperative transfusion and hematoma. Results: A total of 843 free flaps were performed. Preoperative hemoglobin, hematocrit, operative time, and flap type were positive predictors of postoperative transfusion in both bivariate (P < .0001) and multivariate analyses (P < .0001). However, neither anticoagulation nor antiplatelet therapy were predictive of postoperative transfusion rates and hematoma formation. Conclusion: Antithrombotic regimens do not increase the risk of postoperative transfusion or hematoma in head and neck microvascular reconstruction. Based on this limited data, perioperative antithrombotic regimens can be considered in patients who may otherwise be at risk for these postoperative complications.

Selective targeting of IL2Rßγ combined with radiotherapy triggers CD8- and NK-mediated immunity, abrogating metastasis in HNSCC.

The implementation of cancer immunotherapies has seen limited clinical success in head and neck squamous cell carcinoma (HNSCC). Interleukin-2 (IL-2), which modulates the survival and functionality of lymphocytes, is an attractive target for new immunotherapies but one that is limited by presence of regulatory T cells (Tregs) expressing the high-affinity IL-2Rα. The bispecific immunocytokine PD1-IL2v preferentially delivers IL-2 signaling through IL-2Rßγ on PD-1-expressing cells. Selectively targeting the intermediate-affinity IL-2Rßγ can be leveraged to induce anti-tumor immune responses in effector T cells and natural killer (NK) cells while limiting the negative regulation of IL-2Rα activation on Tregs. Using radiation therapy (RT) in combination with PD1-IL2v improves local tumor control and survival, and controls metastatic spread in orthotopic HNSCC tumor models. PD1-IL2v drives systemic activation and expansion of circulating and tumor-infiltrating cytotoxic T cells and NK cells while limiting Treg-mediated immunosuppression. These data show that PD1-L2v induces durable systemic tumor control in HNSCC.

Discovery of Antimicrobial Phosphonopeptide Natural Products from Bacillus velezensis by Genome Mining.

Phosphonate natural products are renowned for inhibitory activities which underly their development as antibiotics and pesticides. Although most phosphonate natural products have been isolated from Streptomyces, bioinformatic surveys suggest that many other bacterial genera are replete with similar biosynthetic potential. While mining actinobacterial genomes, we encountered a contaminated Mycobacteroides data set which included a biosynthetic gene cluster predicted to produce novel phosphonate compounds. Sequence deconvolution revealed that the contig containing this cluster, as well as many others, belonged to a contaminating Bacillus and is broadly conserved among multiple species, including the epiphyte Bacillus velezensis. Isolation and structure elucidation revealed a new di- and tripeptide composed of l-alanine and a C-terminal l-phosphonoalanine which we name phosphonoalamides E and F. These compounds exhibit broad-spectrum antibacterial activity, including strong inhibition against the agricultural pests responsible for vegetable soft rot (Erwinia rhapontici), onion rot (Pantoea ananatis), and American foulbrood (Paenibacillus larvae). This work expands our knowledge of phosphonate metabolism and underscores the importance of including underexplored microbial taxa in natural product discovery. IMPORTANCE Phosphonate natural products produced by bacteria have been a rich source of clinical antibiotics and commercial pesticides. Here, we describe the discovery of two new phosphonopeptides produced by B. velezensis with antibacterial activity against human and plant pathogens, including those responsible for widespread soft rot in crops and American foulbrood. Our results provide new insight on the natural chemical diversity of phosphonates and suggest that these compounds could be developed as effective antibiotics for use in medicine or agriculture.

Simultaneous targeting of PD-1 and IL-2Rßγ with radiation therapy inhibits pancreatic cancer growth and metastasis.

In pancreatic ductal adenocarcinoma (PDAC) patients, we show that response to radiation therapy (RT) is characterized by increased IL-2Rß and IL-2Rγ along with decreased IL-2Rα expression. The bispecific PD1-IL2v is a PD-1-targeted IL-2 variant (IL-2v) immunocytokine with engineered IL-2 cis targeted to PD-1 and abolished IL-2Rα binding, which enhances tumor-antigen-specific T cell activation while reducing regulatory T cell (Treg) suppression. Using PD1-IL2v in orthotopic PDAC KPC-driven tumor models, we show marked improvement in local and metastatic survival, along with a profound increase in tumor-infiltrating CD8+ T cell subsets with a transcriptionally and metabolically active phenotype and preferential activation of antigen-specific CD8+ T cells. In combination with single-dose RT, PD1-IL2v treatment results in a robust, durable expansion of polyfunctional CD8+ T cells, T cell stemness, tumor-specific memory immune response, natural killer (NK) cell activation, and decreased Tregs. These data show that PD1-IL2v leads to profound local and distant response in PDAC.

Effect of Perioperative Antithrombotics on Head and Neck Microvascular Free Flap Survival After Anastomotic Revision.

OBJECTIVE: To determine if antithrombotic therapy improves head and neck microvascular free flap survival following anastomotic revision. STUDY DESIGN: A retrospective review of all patients with microvascular free tissue transfer to the head and neck between August 2013 and July 2021. SETTING: Otolaryngology-Head and Neck Surgery Departments at University of Alabama at Birmingham, University of Colorado, and University of California Irvine. METHODS: Perioperative use of anticoagulation, antiplatelets, intraoperative heparin bolus, tissue plasminogen activator (tPA) and vasopressor use, and leech therapy were collected plus microvascular free flap outcomes. The primary endpoint was free flap failure. Analyses of free flaps that underwent anastomotic revision with or without thrombectomy were performed. RESULTS: A total of 843 microvascular free flaps were included. The overall rate of flap failure was 4.0% (n = 34). The overall rate of pedicle anastomosis revision (artery, vein, or both) was 5.0% (n = 42) with a failure rate of 47.6% (n = 20) after revision. Anastomotic revision significantly increased the risk of flap failure (odds ratio [OR] 52.68, 95% confidence interval [CI] [23.90, 121.1], p < .0001) especially when both the artery and vein were revised (OR 9.425, 95% CI [2.117, 52.33], p = .005). Free flap failure after the anastomotic revision was not affected by postoperative antiplatelet therapy, postoperative prophylactic anticoagulation, intraoperative heparin bolus, tPA, and therapeutic anticoagulation regardless of which vessels were revised and if a thrombus was identified. CONCLUSION: In cases of microvascular free tissue transfer pedicle anastomotic revision, the use of antithrombotic therapy does not appear to significantly change free flap survival outcomes.

Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors.

In the setting of conventional radiation therapy, even when combined with immunotherapy, head and neck cancer often recurs locally and regionally. Elective nodal irradiation (ENI) is commonly employed to decrease regional recurrence. Given our developing understanding that immune cells are radio-sensitive, and that T cell priming occurs in the draining lymph nodes (DLNs), we hypothesize that radiation therapy directed at the primary tumor only will increase the effectiveness of immunotherapies. We find that ENI increases local, distant, and metastatic tumor growth. Multi-compartmental analysis of the primary/distant tumor, the DLNs, and the blood shows that ENI decreases the immune response systemically. Additionally, we find that ENI decreases antigen-specific T cells and epitope spreading. Treating the primary tumor with radiation and immunotherapy, however, fails to reduce regional recurrence, but this is reversed by either concurrent sentinel lymph node resection or irradiation. Our data support using lymphatic sparing radiation therapy for head and neck cancer.

Promising Implants in Rhinoplasty.

Many dilemmas in rhinoplasty tempt surgeons to use exogenous materials. We have long looked toward implants to decrease operative time, to achieve a more reliable result, or when there is a paucity of autologous material. More than ever, the innovative and highly lucrative field of nasal implantology is developing technologically advanced products. This article looks at some popular nasal implant choices with a look toward what might be on the horizon.

Incidental Meckel's Diverticulum With Neuroendocrine Tumor.

Meckel's diverticulum (MD), the most common congenital disease of the small bowel, commonly presents with symptoms of painless rectal bleeding and intestinal obstruction. The treatment of symptomatic MD involves resection of the lesion regardless of patient age; however, the excision of asymptomatic and incidentally identified MDs in adults remain controversial. On one hand, the complications arising from MDs decrease with age, leading to a lower benefit than risk ratio with prophylactic resection. On the other hand, malignancies, such as neuroendocrine tumors, may arise over time from untreated MDs. This can lead to poor prognostic complications, such as liver or lymph node metastases. In this case report, we describe an incidental Meckel's diverticulum discovered during an exploratory laparotomy for acute sigmoid diverticulitis in an adult male. Later biopsy findings discovered the lesion to contain a grade 1 neuroendocrine tumor. Based on our literature review findings, resection of the incidental Meckel's diverticulum was a reasonable approach given the low complication risks of the procedure and the possibility of malignant transformation and progression.

Visualization of ex vivo rabbit olfactory mucosa and foramina with three-dimensional optical coherence tomography.

There is increasing interest in developing a minimally invasive imaging modality to safely evaluate dynamic microscopic changes of the olfactory mucosa and cribriform foramina. Herein, we utilized three-dimensional (3D) optical coherence tomography (OCT) to characterize the ex vivo stratified substructure of olfactory mucosa in rabbits and create 3D reconstructed images of olfactory foramina. Olfactory mucosa and cribriform plates from four New Zealand White rabbits were dissected and imaged using two swept-source OCT systems: (1) 1.3-µm (µm) center wavelength, 100-nm bandwidth, 200-kHz sweep rate, and (2) 1.7-µm center wavelength, 120-nm bandwidth, 90-kHz sweep rate. Volumetric OCT images were compiled to create a 3D reconstruction of the cribriform plate. The ability of OCT to distinguish the olfactory mucosa substructure and foramina was compared to histology. To estimate imaging penetration depth of each system, the first-order exponential decays of depth-resolved intensity were calculated and compared using a paired t-test. Three-dimensional OCT depicted the stratified layered structures within the olfactory mucosa correlating with histology. The epithelium and lamina propria were measured to be 32 µm and 107 µm in 1.3-µm OCT compared to 30 µm and 105 µm in histology. Olfactory foramina were visualized via 3D reconstruction. The 1.7-µm system provided greater depth penetration compared to the 1.3-µm system, allowing for improved foramina visualization. We have shown that OCT can be used to image non-pathologic olfactory mucosa and foramina. Implications for this work include diagnostic and therapeutic potentials for neurorhinological and neurodegenerative diseases.

Biosynthesis of Argolaphos Illuminates the Unusual Biochemical Origins of Aminomethylphosphonate and Nε-Hydroxyarginine Containing Natural Products.

Phosphonate natural products have a history of successful application in medicine and biotechnology due to their ability to inhibit essential cellular pathways. This has inspired efforts to discover phosphonate natural products by prioritizing microbial strains whose genomes encode uncharacterized biosynthetic gene clusters (BGCs). Thus, success in genome mining is dependent on establishing the fundamental principles underlying the biosynthesis of inhibitory chemical moieties to facilitate accurate prediction of BGCs and the bioactivities of their products. Here, we report the complete biosynthetic pathway for the argolaphos phosphonopeptides. We uncovered the biochemical origins of aminomethylphosphonate (AMPn) and Nε-hydroxyarginine, two noncanonical amino acids integral to the antimicrobial function of argolaphos. Critical to this pathway were dehydrogenase and transaminase enzymes dedicated to the conversion of hydroxymethylphosphonate to AMPn. The interconnected activities of both enzymes provided a solution to overcome unfavorable energetics, empower cofactor regeneration, and mediate intermediate toxicity during these transformations. Sequential ligation of l-arginine and l-valine was afforded by two GCN5-related N-acetyltransferases in a tRNA-dependent manner. AglA was revealed to be an unusual heme-dependent monooxygenase that hydroxylated the Nε position of AMPn-Arg. As the first biochemically characterized member of the YqcI/YcgG protein family, AglA enlightens the potential functions of this elusive group, which remains biochemically distinct from the well-established P450 monooxygenases. The widespread distribution of AMPn and YqcI/YcgG genes among actinobacterial genomes suggests their involvement in diverse metabolic pathways and cellular functions. Our findings illuminate new paradigms in natural product biosynthesis and realize a significant trove of AmPn and Nε-hydroxyarginine natural products that await discovery.

Valinophos Reveals a New Route in Microbial Phosphonate Biosynthesis That Is Broadly Conserved in Nature.

Phosphonate natural products are potent inhibitors of cellular metabolism with an established record of commercialization in medicine and biotechnology. Although genome mining has emerged as an accelerated method for the discovery of new phosphonates, a robust framework of their metabolism is needed to identify the pathways most likely to yield compounds with desired activities. Here we expand our understanding of these natural products by reporting the complete biosynthetic pathway for valinophos, a phosphonopeptide natural product containing the unusual (R)-2,3-dihydroxypropylphosphonate (DHPPA) scaffold. The pathway was defined by several enzymatic transformations and intermediates previously unknown to phosphonate natural products. A dedicated dehydrogenase served as a new phosphoenolpyruvate mutase coupling enzyme. Notably, its reduction of phosphonopyruvate to phosphonolactate defined a new early branchpoint in phosphonate biosynthesis. Functionally interconnected kinase and reductase enzymes catalyzed reactions reminiscent of glycolysis and arginine biosynthesis to produce a transient, but essential, phosphonolactaldehyde intermediate. We demonstrate esterification of l-valine onto DHPPA as a new biochemical activity for ATP-Grasp ligase enzymes. Unexpectedly, a second amino acid ligase then adjoined additional amino acids at the valinyl moiety to produce a suite of DHPPA-dipeptides. The genes for DHPPA biosynthesis were discovered among genomes of bacteria from wide-ranging habitats, suggesting a wealth of unknown compounds that may originate from this core pathway. Our findings establish new biosynthetic principles for natural products and provide definition to unexplored avenues for bioactive phosphonate genome mining.

Dichotomous effects of cellular expression of STAT3 on tumor growth of HNSCC.

STAT3 signaling has been shown to regulate cellular function and cytokine production in the tumor microenvironment (TME). Within the head and neck squamous cell carcinoma (HNSCC) TME, we previously showed that therapeutic targeting of STAT3 in combination with radiation resulted in improved tumor growth delay. However, given the independent regulatory effects STAT3 has on anti-tumor immunity, we aimed to decipher the effects of individually targeting STAT3 in the cancer cell, regulatory T cells (Tregs), and natural killer (NK) cell compartments in driving tumor growth and resistance to therapy in HNSCCs. We utilized a CRISPR knockout system for genetic deletion of STAT3 within the cancer cell as well as two genetic knockout mouse models, FoxP3-Cre/STAT3 fl and NKp46-Cre/STAT3 fl, for Tregs and NK cell targeting, respectively. Our data revealed differences in development of resistance to treatment with STAT3 CRISPR knockout in the cancer cell, driven by differential recruitment of immune cells. Knockout of STAT3 in Tregs overcomes this resistance and results in Treg reprogramming and recruitment and activation of antigen-presenting cells. In contrast, knockout of STAT3 in the NK cell compartment results in NK cell inactivation and acceleration of tumor growth. These data underscore the complex interplay between the cancer cell and the immune TME and carry significant implications for drug targeting and design of combination approaches in HNSCCs.

Exploring feedback-controlled versus open-circuit electrochemical lipolysis in ex vivo and in vivo porcine fat: A feasibility study.

OBJECTIVES: Minimally invasive fat sculpting techniques are becoming more widespread with the development of office-based devices and therapies. Electrochemical lipolysis (ECLL) is a needle-based technology that uses direct current (DC) to electrolyze tissue water creating acid and base in situ. In turn, fat is saponified and adipocyte cell membrane lysis occurs. The electrolysis of water can be accomplished using a simple open-loop circuit (V-ECLL) or by incorporating a feedback control circuit using a potentiostat (P-ECLL). A potentiostat utilizes an operational amplifier with negative feedback to allow users to precisely control voltage at specific electrodes. To date, the variation between the two approaches has not been studied. The aim of this study was to assess current and charge transfer variation and lipolytic effect created by the two approaches in an in vivo porcine model. METHODS: Charge transfer measurements from ex vivo V-ECLL and P-ECLL treated porcine skin and fat were recorded at -1 V P-ECLL, -2 V P-ECLL, -3 V P-ECLL, and -5 V V-ECLL each for 5 min to guide dosimetry parameters for in vivo studies. In follow-up in vivo studies, a sedated female Yorkshire pig was treated with both V-ECLL and P-ECLL across the dorsal surface over a range of dosimetry parameters, including -1.5 V P-ECLL, -2.5 V P-ECLL, -3.5 V P-ECLL, and 5 V V-ECLL each treated for 5 min. Serial biopsies were performed at baseline before treatment, 1, 2, 7, 14, and 28 days after treatment. Tissue was examined using fluorescence microscopy and histology to compare the effects of the two ECLL approaches. RESULTS: Both V-ECLL and P-ECLL treatments induced in-vivo fat necrosis evident by adipocyte membrane lysis, adipocyte denuclearization, and an acute inflammatory response across a 28-day longitudinal study. However, -1.5 V P-ECLL produced a smaller spatial necrotic effect compared to 5 V V-ECLL. In addition, 5 V V-ECLL produced a comparable necrotic effect to that of -2.5 V and -3.5 V P-ECLL. CONCLUSIONS: V-ECLL and P-ECLL at the aforementioned dosimetry parameters both achieved fat necrosis by adipocyte membrane lysis and denuclearization. The -2.5 V and -3.5 V P-ECLL treatments created spatially similar fat necrotic effects when compared to the 5 V V-ECLL treatment. Quantitatively, total charge transfer between dosimetry parameters suggests that -2.5 V P-ECLL and 5 V V-ECLL produce comparable electrochemical reactions. Such findings suggest that a low-voltage closed-loop potentiostat-based system is capable of inducing fat necrosis to a similar extent compared to that of a higher voltage direct current system.

Multimodality Management of EBV-Associated Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is a rare cancer of the nasopharyngeal mucosa with a specific geographic predisposition. NPC is often associated with Epstein-Barr Virus (EBV) infection and as a result contains many characteristic biomarkers. Treatment of locally-contained NPC is generally achieved through use of radiotherapy (RT), as part of a multimodality treatment regimen. Induction chemotherapy followed by concurrent RT and platinum-based chemotherapy regimen has emerged as the definitive treatment of choice for locoregionally-advanced NPC. Recently, immunotherapy is finding a role in the treatment of recurrent or metastatic NPC. Immune checkpoint blockade therapies targeted against the programmed death-1 (PD-1) receptor have demonstrated efficacy in early phase clinical trials, with ongoing phase III trials in effect. Biomarkers for treatment efficacy remain an ongoing area of investigation, with important prognostic implications on the horizon.

Mind-Body Therapies for Cancer Patients Living with Depression, Anxiety or Insomnia (MIRACLE): A Systematic Review with Individual Participant Data Network Meta-Analysis.

Depression, anxiety, and insomnia are common in cancer patients. Mind-body therapies (MBTs) are promising forms of treatment for cancer patients living with depression, anxiety, and insomnia. The objective of this study is to assess the effectiveness and acceptability of MBTs in cancer patients living with depression, anxiety, or insomnia. EMBase, PubMed, Cinahl, PsychINFO, IndMED, CSI-NISCAIR, CNKI, Clinicaltrial.gov, ChiCTR, and CTRI will be searched until October 2020 for relevant studies. Randomized controlled studies in which MBTs were tested in a cancer population will be selected. The authors of the selected studies will be contacted to obtain individual participant data. The participants who reached a defined clinical threshold for depression, anxiety, or insomnia will be selected for the three sub-studies on depression, anxiety, and insomnia, respectively. Pairwise and network meta-analyses will be used to assess the changes in depression, anxiety, sleep quality, and completion rate. We will assess the effect of the treatment dose (number and frequency of interventions) on effectiveness. The results of this study will inform clinical decision-making for the treatment of psychological disturbances in cancer patients. If MBTs are found effective, they will potentially be recommended as treatments for cancer patients with psychological symptoms.