Spider Bite Wound Care and Review of Traditional and Advanced Treatment Options.

Background: Approaches to chronic wound care are worlds apart: In developing nations, the care of chronic wounds often involves traditional management with local products (eg, honey, boiled potato peels, aloe vera gel, banana leaves); whereas in developed nations, more expensive and technologically advanced products are available (eg, wound vacuum, saline wound chamber, hyperbaric oxygen therapy, antibacterial foam). The cost for wound care plays a significant role in total health care costs, and that cost is expected to rise dramatically. Case Presentation: A healthy, 60-year-old man presented after being bitten by a spider 6 days earlier. He was treated and prescribed clindamycin 300 mg 4 times daily for 14 days. Despite treatment, the wound continued to enlarge, and the patient showed symptoms of septicemia. The patient was admitted to the hospital and remained for 3 days. On discharge the patient was given a prescription for doxycycline 100 mg twice a day for 10 days and instructed to use iodoform gauze to pack the wound during daily dressing changes. However, the gauze was ineffective. The patient's dressing was switched to an antibacterial foam dressing impregnated with gentian violet and methylene blue. Conclusions: There is a disparity in available wound care product availability. Modern products may yield faster healing times with fewer adverse effects than traditional products. Products used by local healers can produce satisfactory results when more modern products are unavailable and at a fraction of the cost.

Strategies to Increase Racial and Ethnic Diversity in the Surgical Workforce: A State of the Art Review.

OBJECTIVE: To evaluate strategies to increase racial and ethnic diversity in the surgical workforce among trainees and faculty across surgical specialties. DATA SOURCES: Embase, OVID/Medline, and Web of Science Core Collection. REVIEW METHODS: A review of US-based, peer-reviewed articles examining the effect of targeted strategies on racial and ethnic diversity in the surgical workforce was conducted from 2000 to 2020 with the PRISMA checklist and STROBE tool. Studies without an outlined strategy and associated outcomes were excluded. Eleven studies met inclusion criteria and were completed in general surgery, orthopaedic surgery, and otolaryngology-head and neck surgery. CONCLUSIONS: Efforts to increase exposure to surgery through internship programs and required clerkships with efforts to improve mentorship were common (6 of 11 [54.5%] and 3 of 11 [27.3%] studies, respectively). Three (27.3%) studies aimed to diversify the recruitment and selection process for the residency match and faculty hiring, and 2 (18.2%) aimed to increase representation among trainees, faculty, and leadership through holistic review processes paired with departmental commitment. Outcome metrics included surgical residency applications for individuals underrepresented in medicine, interview and match rates, faculty hiring, measures of a successful academic surgical career, and leadership representation. All strategies were successful in increasing diversity in the surgical workforce. IMPLICATIONS FOR PRACTICE: A convincing yet limited body of literature exists to describe strategies and outcomes that address racial and ethnic diversity in the surgical workforce. While future inquiry is needed to move this field of interest forward, the evidence presented provides a framework for surgical residency programs/departments to develop approaches to increase racial and ethnic diversity.

Researching, co-creating and testing innovations in paper-based health information systems (PHISICC) to support health workers' decision-making: protocol of a multi-country, transdisciplinary, mixed-methods research programme in three sub-Saharan countries.

BACKGROUND: Health information systems are crucial to provide data for decision-making and demand for data is constantly growing. However, the link between data and decisions is not always rational or linear and the management of data ends up overloading frontline health workers, which may compromise quality of healthcare delivery. Despite limited evidence, there is an increasing push for the digitalization of health information systems, which poses enormous challenges, particularly in remote, rural settings in low- and middle-income countries. Paper-based tools will continue to be used in combination with digital solutions and this calls for efforts to make them more responsive to local needs. Paper-based Health Information Systems in Comprehensive Care (PHISICC) is a transdisciplinary, multi-country research initiative to create and test innovative paper-based health information systems in three sub-Saharan African countries. METHODS/DESIGN: The PHISICC initiative is being carried out in remote, rural settings in Côte d'Ivoire, Mozambique and Nigeria through partnership with ministries of health and research institutions. We began with research syntheses to acquire the most up-to-date knowledge on health information systems. These were coupled with fieldwork in the three countries to understand the current design, patterns and contexts of use, and healthcare worker perspectives. Frontline health workers, with designers and researchers, used co-creation methods to produce the new PHISICC tools. This suite of tools is being tested in the three countries in three cluster-randomized controlled trials. Throughout the project, we have engaged with a wide range of stakeholders and have maintained the highest scientific standards to ensure that results are relevant to the realities in the three countries. DISCUSSION: We have deployed a comprehensive research approach to ensure the robustness and future policy uptake of findings. Besides the innovative PHISICC paper-based tools, our process is in itself innovative. Rather than emphasizing the technical dimensions of data management, we focused instead on frontline health workers' data use and decision-making. By tackling the whole scope of primary healthcare areas rather than a subset of them, we have developed an entirely new design and visual language for a suite of tools across healthcare areas. The initiative is being tested in remote, rural areas where the most vulnerable live.

Does an innovative paper-based health information system (PHISICC) improve data quality and use in primary healthcare? Protocol of a multicountry, cluster randomised controlled trial in sub-Saharan African rural settings.

INTRODUCTION: Front-line health workers in remote health facilities are the first contact of the formal health sector and are confronted with life-saving decisions. Health information systems (HIS) support the collection and use of health related data. However, HIS focus on reporting and are unfit to support decisions. Since data tools are paper-based in most primary healthcare settings, we have produced an innovative Paper-based Health Information System in Comprehensive Care (PHISICC) using a human-centred design approach. We are carrying out a cluster randomised controlled trial in three African countries to assess the effects of PHISICC compared with the current systems. METHODS AND ANALYSIS: Study areas are in rural zones of Côte d'Ivoire, Mozambique and Nigeria. Seventy health facilities in each country have been randomly allocated to using PHISICC tools or to continuing to use the regular HIS tools. We have randomly selected households in the catchment areas of each health facility to collect outcomes' data (household surveys have been carried out in two of the three countries and the end-line data collection is planned for mid-2021). Primary outcomes include data quality and use, coverage of health services and health workers satisfaction; secondary outcomes are additional data quality and use parameters, childhood mortality and additional health workers and clients experience with the system. Just prior to the implementation of the trial, we had to relocate the study site in Mozambique due to unforeseen logistical issues. The effects of the intervention will be estimated using regression models and accounting for clustering using random effects. ETHICS AND DISSEMINATION: Ethics committees in Côte d'Ivoire, Mozambique and Nigeria approved the trials. We plan to disseminate our findings, data and research materials among researchers and policy-makers. We aim at having our findings included in systematic reviews on health systems interventions and future guidance development on HIS. TRIAL REGISTRATION NUMBER: PACTR201904664660639; Pre-results.

Diarrhoea Management using Over-the-counter Nutraceuticals in Daily practice (DIAMOND): a feasibility RCT on alternative therapy to reduce antibiotic use.

BACKGROUND: Although rarely indicated, antibiotics are commonly used for acute diarrhoea in China. We conducted a randomised, double blind exploratory clinical trial of loperamide, berberine and turmeric for treatment of acute diarrhoea. METHODS: Adults with acute uncomplicated diarrhoea aged 18 to 70 were randomised to 4 groups: (A) loperamide; (B) loperamide and berberine; (C) loperamide and turmeric; (D) loperamide, berberine and turmeric. All participants were given rescue ciprofloxacin for use after 48 h if symptoms worsened or were unimproved. Primary endpoints were feasibility and ciprofloxacin use during the 2-week follow-up period. Semi-structured interviews were conducted following recruitment and were analysed thematically. Recruiting doctors, delivery pharmacists and research assistants were blinded to treatment allocation. RESULTS: Only 21.5% (278/1295) of patients screened were deemed eligible, and 49% (136/278) of these consented and were entered into the final analysis. Most participants had mild symptoms, because most patients with moderate or severe symptoms wanted to be given antibiotics. Follow-up was good (94% at 2 weeks). Only three participants used rescue antibiotics compared to 67% of acute diarrhoea patients in the hospital during the recruitment period. The median symptom duration was 14 h in group B (interquartile range (IQR) 10-22), 16 h in group D (IQR 10-22), 18 h in group A (IQR 10-33) and 20 h in group C (IQR 16-54). Re-consultation rates were low. There were no serious treatment-related adverse events. Most interviewed participants said that although they had believed antibiotics to be effective for diarrhoea, they were surprised by their quick recovery without antibiotics in this trial. CONCLUSION: Although recruitment was challenging because of widespread expectations for antibiotics, patients with mild diarrhoea accepted trying an alternative. The three nutraceuticals therapy require further evaluation in a fully powered, randomised controlled trial among a broader sample. TRIAL REGISTRATION: ChiCTR-IPR-17014107.

Dose Fractionation of Moxifloxacin for Treatment of Tuberculosis: Impact of Dosing Interval and Elimination Half-Life on Microbial Kill and Resistance Suppression.

The repurposed agent moxifloxacin has become an important addition to the physician's armamentarium for the therapy of Mycobacterium tuberculosis When a drug is administered, we need to have metrics for success. As for most antimicrobial chemotherapy, we contend that for Mycobacterium tuberculosis therapy, these metrics should be a decline in the susceptible bacterial burden and the suppression of amplification of less-susceptible populations. To achieve optimal outcomes relative to these metrics, a dose and schedule of administration need to be chosen. For large populations of patients, there are true between-patient differences in important pharmacokinetic parameters. These distributions of parameter values may have an impact on these metrics, depending on what measure of drug exposure drives the metrics. To optimize dose and schedule choice of moxifloxacin, we performed a dose fractionation experiment in the hollow fiber infection model. We examined 12-, 24-, and 48-h dosing intervals with doses of 200, 400, and 800 mg for each interval, respectively. Within each interval, we had an arm where half-lives of 12, 8, and 4 h were simulated. We attempted to keep the average concentration (Cavg) or area under the concentration-time curve (AUC) constant across arms. We found that susceptible bacterial load decline was linked to Cavg, as we had indicated previously. Resistance suppression, a nonmonotonic function, had minimum concentration (Cmin) as the linked index. The 48-h interval with the 4-h half-life had the largest less-susceptible population. Balancing bacterial kill, resistance suppression, toxicity (linked to peak concentration [Cpeak]), and adherence, we conclude that the dose of 400 mg daily is optimal for moxifloxacin.

The Cost-Effectiveness of Platelet-Rich Plasma Compared With Hyaluronic Acid Injections for the Treatment of Knee Osteoarthritis.

PURPOSE: To examine the cost-effectiveness of a series (total of 3 injections) of intra-articular platelet-rich plasma (PRP) injections in comparison to that of hyaluronic acid (HA) viscosupplementation for the treatment of symptomatic knee osteoarthritis. METHODS: Outcome data regarding the use of PRP or HA injections for the treatment of symptomatic knee osteoarthritis were determined from the highest-quality data (Level I) available in the literature until 2015. Health utility values were then derived from these high-quality data. Costs were determined by examining typical charges for patients undergoing a series of either PRP or HA injections for the treatment of this condition at a large private orthopaedic practice. These health utility values and costs were used to create an expected-value decision analysis model. RESULTS: The results of the model revealed that the cost per quality-adjusted life-year (QALY) of a series of PRP injections was $8,635.23/QALY and that of a series of HA injections was $5,331.75/QALY. A series of PRP injections was associated with a higher initial cost than a series of HA injections (difference, $1,433.67); however, PRP was also more effective (higher utility value) than HA by 0.11 QALYs (0.69 vs 0.58, P = .0062) at 1 year. The incremental cost-effectiveness ratio of the use of PRP injections as opposed to HA was $12,628.15/QALY. CONCLUSIONS: Although a series of either PRP ($8,635.23/QALY) or HA ($5,331.75/QALY) injections for the treatment of symptomatic knee osteoarthritis would be considered cost-effective (cost per QALY < $50,000), PRP injections were not more cost-effective than HA injections. However, PRP was significantly more effective at 1 year, and being associated with an incremental cost-effectiveness ratio of $12,628.15/QALY when compared with HA, a series of PRP injections should be considered a reasonable and acceptable alternative to HA injections for the treatment of symptomatic knee osteoarthritis. LEVEL OF EVIDENCE: Level II, economic and decision analysis of Level I studies.

Is the Arrhenius-correction of biodegradation rates, as recommended through REACH guidance, fit for environmentally relevant conditions? An example from petroleum biodegradation in environmental systems.

Biodegradation is a major determinant of chemical persistence in the environment and an important consideration for PBT and environmental risk assessments. It is influenced by several environmental factors including temperature and microbial community structure. According to REACH guidance, a temperature correction based on the Arrhenius equation is recommended for chemical persistence data not performed at the recommended EU mean surface water temperature. Such corrections, however, can lead to overly conservative P/vP assessments. In this paper, the relevance of this temperature correction is assessed for petroleum hydrocarbons, using measured surface water (marine and freshwater) degradation half-time (DT50) and degradation half-life (HL) data compiled from relevant literature. Stringent screening criteria were used to specifically select data from biodegradation tests containing indigenous microbes and conducted at temperatures close to their ambient sampling temperature. As a result, ten independent studies were identified, with 993 data points covering 326 hydrocarbon constituents. These data were derived from tests conducted with natural seawater, or freshwater, at temperatures ranging from 5 to 21 °C. Regressions were performed on the full hydrocarbon dataset and on several individual hydrocarbons. The results were compared to the trend as predicted by the Arrhenius equation and using the activation energy (Ea) as recommend in the REACH Guidance. The comparison shows that the correction recommended in REACH Guidance over predicts the effect of temperature on hydrocarbon biodegradation. These results contrast with temperature manipulated inocula where the test temperature is different from the ambient sampling temperature. In these manipulated systems, the effect of temperature follows the Arrhenius equation more closely. In addition, a more striking effect of temperature on the lag phase was observed with longer lag phases more apparent at lower temperatures. This indicates that the effect of temperature may indeed be even lower when considering hydrocarbon biodegradation without the initial lag phase.

Biodegradability assessment of complex, hydrophobic substances: Insights from gas-to-liquid (GTL) fuel and solvent testing.

The assessment of substances of Unknown or Variable composition, Complex reaction products or Biological materials (UVCBs) presents significant challenges when determining biodegradation potential and environmental persistence for regulatory purposes. An example of UVCBs is the gas-to-liquid (GTL) products, which are synthetic hydrocarbons produced from natural gas using a catalytic process known as the Fischer-Tropsch process. These synthetic hydrocarbons are fractionated into a wide array of products equivalent in function to their petroleum-derived analogues. Here we summarise the results of an extensive testing program to assess the biodegradability of several GTL products. This program highlights the challenges associated with UVCBs and provides a case study for the assessment of such substances that are also poorly soluble and volatile. When tested with the appropriate methods, all the GTL products assessed in this study were found to be readily biodegradable indicating they are not likely to be persistent in the environment.

In-Office Tympanostomy Tube Placement in Children Using Iontophoresis and Automated Tube Delivery.

OBJECTIVES/HYPOTHESIS: Evaluate technical success, tolerability, and safety of lidocaine iontophoresis and tympanostomy tube placement for children in an office setting. STUDY DESIGN: Prospective individual cohort study. METHODS: This prospective multicenter study evaluated in-office tube placement in children ages 6 months through 12 years of age. Anesthesia was achieved via lidocaine/epinephrine iontophoresis. Tube placement was conducted using an integrated and automated myringotomy and tube delivery system. Anxiolytics, sedation, and papoose board were not used. Technical success and safety were evaluated. Patients 5 to 12 years old self-reported tube placement pain using the Faces Pain Scale-Revised (FPS-R) instrument, which ranges from 0 (no pain) to 10 (very much pain). RESULTS: Children were enrolled into three cohorts with 68, 47, and 222 children in the Operating Room (OR) Lead-In, Office Lead-In, and Pivotal cohorts, respectively. In the Pivotal cohort, there were 120 and 102 children in the <5 and 5- to 12-year-old age groups, respectively, with a mean age of 2.3 and 7.6 years, respectively. Bilateral tube placement was indicated for 94.2% of children <5 and 88.2% of children 5 to 12 years old. Tubes were successfully placed in all indicated ears in 85.8% (103/120) of children <5 and 89.2% (91/102) of children 5 to 12 years old. Mean FPS-R score was 3.30 (standard deviation [SD] = 3.39) for tube placement and 1.69 (SD = 2.43) at 5 minutes postprocedure. There were no serious adverse events. Nonserious adverse events occurred at rates similar to standard tympanostomy procedures. CONCLUSIONS: In-office tube placement in selected patients can be successfully achieved without requiring sedatives, anxiolytics, or papoose restraints via lidocaine iontophoresis local anesthesia and an automated myringotomy and tube delivery system. LEVEL OF EVIDENCE: 2b Laryngoscope, 130:S1-S9, 2020.

Visual-to-auditory sensory substitution alters language asymmetry in both sighted novices and experienced visually impaired users.

Visual-to-auditory sensory substitution devices (SSDs) provide improved access to the visual environment for the visually impaired by converting images into auditory information. Research is lacking on the mechanisms involved in processing data that is perceived through one sensory modality, but directly associated with a source in a different sensory modality. This is important because SSDs that use auditory displays could involve binaural presentation requiring both ear canals, or monaural presentation requiring only one - but which ear would be ideal? SSDs may be similar to reading, as an image (printed word) is converted into sound (when read aloud). Reading, and language more generally, are typically lateralised to the left cerebral hemisphere. Yet, unlike symbolic written language, SSDs convert images to sound based on visuospatial properties, with the right cerebral hemisphere potentially having a role in processing such visuospatial data. Here we investigated whether there is a hemispheric bias in the processing of visual-to-auditory sensory substitution information and whether that varies as a function of experience and visual ability. We assessed the lateralization of auditory processing with two tests: a standard dichotic listening test and a novel dichotic listening test created using the auditory information produced by an SSD, The vOICe. Participants were tested either in the lab or online with the same stimuli. We did not find a hemispheric bias in the processing of visual-to-auditory information in visually impaired, experienced vOICe users. Further, we did not find any difference between visually impaired, experienced vOICe users and sighted novices in the hemispheric lateralization of visual-to-auditory information processing. Although standard dichotic listening is lateralised to the left hemisphere, the auditory processing of images in SSDs is bilateral, possibly due to the increased influence of right hemisphere processing. Auditory SSDs might therefore be equally effective with presentation to either ear if a monaural, rather than binaural, presentation were necessary.

Impact of Urgent Care Openings on Emergency Department Visits to Two Academic Medical Centers Within an Integrated Health Care System.

STUDY OBJECTIVE: The effect of urgent cares on local emergency department (ED) patient volumes is presently unknown. In this paper, we aimed to assess the change in low-acuity ED utilization at 2 academic medical centers in relation to patient proximity to an affiliated urgent care. METHODS: We created a geospatial database of ED visits occurring between April 2016 and March 2018 to 2 academic medical centers in an integrated health care system, geocoded by patient home address. We used logistic regression to characterize the relationship between the likelihood of patients visiting the ED for a low-acuity condition, based on ED discharge diagnosis, and urgent care center proximity, defined as living within 1 mile of an open urgent care center, for each of the academic medical centers in the system, adjusting for spatial, temporal, and patient factors. RESULTS: We identified a statistically significant reduction in the likelihood of ED visits for low-acuity conditions by patients living within 1 mile of an urgent care center at 1 of the 2 academic medical centers, with an adjusted odds ratio of 0.87 (95% confidence interval 0.78 to 0.98). There was, however, no statistically significant reduction at the other affiliated academic medical center. Further analysis showed a statistically significant temporal relationship between time since urgent care center opening and likelihood of a low-acuity ED visit, with approximately a 1% decrease in the odds of a low-acuity visit for every month that the proximal urgent care center was open (odds ratio 0.99; 95% confidence interval 0.985 to 0.997). CONCLUSION: Although further research is needed to assess the factors driving urgent care centers' variable influence on low-acuity ED use, these findings suggest that in similar settings urgent care center development may be an effective strategy for health systems hoping to decrease ED utilization for low-acuity conditions at academic medical centers.

The Feasibility of Group Therapeutic Singing Telehealth for Persons with Parkinson's Disease in Rural Iowa.

Introduction: Group therapeutic singing (GTS) may be an effective treatment for voice and respiratory impairments in persons with Parkinson's disease (PD). However, it remains unknown if GTS can be effectively delivered through telemedicine. Methods: Participants with PD from rural areas were recruited to complete a prerecorded GTS program, once a week for 8 weeks. Voice and respiratory outcome measures were collected 1 week before and 1 week after intervention. Results: Ten participants were enrolled in the study. One participant dropped at week 3. Five participants attended all eight sessions, two participants completed seven sessions, and one participant completed six sessions for 93.75% compliance. Statistical analysis for the data collected from the eight participants enrolled in the study revealed that voice outcome measures improved but did not reach significance. However, respiratory outcome measures significantly improved. Discussion: Results suggest that prerecorded GTS is feasible. Moreover, results are in keeping with results from a previous study using the exact same intervention with an in person therapist. Thus, this pilot work suggests that the use of prerecorded GTS may be a viable treatment option for those with limited access to care.

Bioenergetics underlying single-cell migration on aligned nanofiber scaffolds.

Cell migration is centrally involved in a myriad of physiological processes, including morphogenesis, wound healing, tissue repair, and metastatic growth. The bioenergetics that underlie migratory behavior are not fully understood, in part because of variations in cell culture media and utilization of experimental cell culture systems that do not model physiological connective extracellular fibrous networks. In this study, we evaluated the bioenergetics of C2C12 myoblast migration and force production on fibronectin-coated nanofiber scaffolds of controlled diameter and alignment, fabricated using a nonelectrospinning spinneret-based tunable engineered parameters (STEP) platform. The contribution of various metabolic pathways to cellular migration was determined using inhibitors of cellular respiration, ATP synthesis, glycolysis, or glucose uptake. Despite immediate effects on oxygen consumption, mitochondrial inhibition only modestly reduced cell migration velocity, whereas inhibitors of glycolysis and cellular glucose uptake led to striking decreases in migration. The migratory metabolic sensitivity was modifiable based on the substrates present in cell culture media. Cells cultured in galactose (instead of glucose) showed substantial migratory sensitivity to mitochondrial inhibition. We used nanonet force microscopy to determine the bioenergetic factors responsible for single-cell force production and observed that neither mitochondrial nor glycolytic inhibition altered single-cell force production. These data suggest that myoblast migration is heavily reliant on glycolysis in cells grown in conventional media. These studies have wide-ranging implications for the causes, consequences, and putative therapeutic treatments aimed at cellular migration.

Impact of a Multidisciplinary Treatment Pathway for Atrial Fibrillation in the Emergency Department on Hospital Admissions and Length of Stay: Results of a Multi-Center Study.

Background Variability in the management of atrial fibrillation (AF) in the emergency department (ED) leads to avoidable hospital admissions and prolonged length of stay (LOS). In a retrospective single-center study, a multidisciplinary AF treatment pathway was associated with a reduced hospital admission rate and reduced LOS. To assess the applicability of the AF pathway across institutions, we conducted a 2-center study. Methods and Results We performed a prospective, 2-stage study at 2 tertiary care hospitals. During the first stage, AF patients in the ED received routine care. During the second stage, AF patients received care according to the AF pathway. The primary study outcome was hospital admission rate. Secondary outcomes included ED LOS and inpatient LOS. We enrolled 104 consecutive patients in each stage. Patients treated using the AF pathway were admitted to the hospital less frequently than patients who received routine care (15% versus 55%; P<0.001). For admitted patients, average hospital LOS was shorter in the AF pathway cohort than in the routine care cohort (64 versus 105 hours, respectively; P=0.01). There was no significant difference in the average ED LOS between AF pathway and routine care cohorts (14 versus 12 hours, respectively; P=0.32). Conclusions In this prospective 2-stage, 2-center study, utilization of a multidisciplinary AF treatment pathway resulted in a 3.7-fold reduction in admission rate and a 1.6-fold reduction in average hospital LOS for admitted patients. Utilization of the AF pathway was not associated with a significant change in ED LOS.

Mechanisms by Which Dietary Fatty Acids Regulate Mitochondrial Structure-Function in Health and Disease.

Mitochondria are the energy-producing organelles within a cell. Furthermore, mitochondria have a role in maintaining cellular homeostasis and proper calcium concentrations, building critical components of hormones and other signaling molecules, and controlling apoptosis. Structurally, mitochondria are unique because they have 2 membranes that allow for compartmentalization. The composition and molecular organization of these membranes are crucial to the maintenance and function of mitochondria. In this review, we first present a general overview of mitochondrial membrane biochemistry and biophysics followed by the role of different dietary saturated and unsaturated fatty acids in modulating mitochondrial membrane structure-function. We focus extensively on long-chain n-3 (ω-3) polyunsaturated fatty acids and their underlying mechanisms of action. Finally, we discuss implications of understanding molecular mechanisms by which dietary n-3 fatty acids target mitochondrial structure-function in metabolic diseases such as obesity, cardiac-ischemia reperfusion injury, obesity, type 2 diabetes, nonalcoholic fatty liver disease, and select cancers.

Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome.

Cardiac mitochondrial phospholipid acyl chains regulate respiratory enzymatic activity. In several diseases, the rodent cardiac phospholipidome is extensively rearranged; however, whether specific acyl chains impair respiratory enzyme function is unknown. One unique remodeling event in the myocardium of obese and diabetic rodents is an increase in docosahexaenoic acid (DHA) levels. Here, we first confirmed that cardiac DHA levels are elevated in diabetic humans relative to controls. We then used dietary supplementation of a Western diet with DHA as a tool to promote cardiac acyl chain remodeling and to study its influence on respiratory enzyme function. DHA extensively remodeled the acyl chains of cardiolipin (CL), mono-lyso CL, phosphatidylcholine, and phosphatidylethanolamine. Moreover, DHA lowered enzyme activities of respiratory complexes I, IV, V, and I+III. Mechanistically, the reduction in enzymatic activities were not driven by a dramatic reduction in the abundance of supercomplexes. Instead, replacement of tetralinoleoyl-CL with tetradocosahexaenoyl-CL in biomimetic membranes prevented formation of phospholipid domains that regulate enzyme activity. Tetradocosahexaenoyl-CL inhibited domain organization due to favorable Gibbs free energy of phospholipid mixing. Furthermore, in vitro substitution of tetralinoleoyl-CL with tetradocosahexaenoyl-CL blocked complex-IV binding. Finally, reintroduction of linoleic acid, via fusion of phospholipid vesicles to mitochondria isolated from DHA-fed mice, rescued the major losses in the mitochondrial phospholipidome and complexes I, IV, and V activities. Altogether, our results show that replacing linoleic acid with DHA lowers select cardiac enzyme activities by potentially targeting domain organization and phospholipid-protein binding, which has implications for the ongoing debate about polyunsaturated fatty acids and cardiac health.

State-of-the-Art Techniques in Treating Peripheral Nerve Injury.

BACKGROUND: Peripheral nerve injuries remain a major clinical concern, as they often lead to chronic disability and significant health care expenditures. Despite advancements in microsurgical techniques to enhance nerve repair, biological approaches are needed to augment nerve regeneration and improve functional outcomes after injury. METHODS: Presented herein is a review of the current literature on state-of-the-art techniques to enhance functional recovery for patients with nerve injury. Four categories are considered: (1) electroceuticals, (2) nerve guidance conduits, (3) fat grafting, and (4) optogenetics. Significant study results are highlighted, focusing on histologic and functional outcome measures. RESULTS: This review documents the current state of the literature. Advancements in neuronal stimulation, tissue engineering, and cell-based therapies demonstrate promise with regard to augmenting nerve regeneration and appropriate rehabilitation. CONCLUSIONS: The future of treating peripheral nerve injury will include multimodality use of electroconductive conduits, fat grafting, neuronal stimulation, and optogenetics. Further clinical investigation is needed to confirm the efficacy of these technologies on peripheral nerve recovery in humans, and how best to implement this treatment for a diverse population of nerve-injured patients.