A Narrative Review on the Viability of Osteopathic Manipulative Medicine in Treating Irritable Bowel Syndrome With Constipation (IBS-C).

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by chronic abdominal pain and alterations in bowel habits, with global prevalence. The etiology of the disease is likely multifactorial; however, autonomic nervous system (ANS) dysfunction and immune-mediated inflammation may contribute the most to the hallmark symptoms of abdominal pain and altered motility of the gut. Current pharmacological therapies operate to modulate intestinal transit, alter the composition of the gut flora and control pain. Non-pharmacological approaches include dietary changes, increased physical activity, or fecal microbiota transplants. None of these therapies can modulate ANS dysfunction or impact the underlying inflammation that is likely perpetuating the symptoms of IBS. Osteopathic Manipulative Medicine (OMM) is a clinical approach focused on physical manipulation of the body's soft tissues to correct somatic dysfunctions. OMM can directly target the pathophysiology of IBS through many approaches such as ANS modulation and lymphatic techniques to modify the inflammatory mechanisms within the body. Particular OMM techniques of use are lymphatic manipulation, myofascial release, sympathetic ganglia treatment, sacral rocking, counterstrain, and viscerosomatic treatment. The aim of this study is to identify OMM treatments that can be used to potentially reduce the inflammation and ANS dysfunction associated with IBS symptoms, thereby providing a new non-pharmacological targeted approach for treating the disease.

Efficacy and safety of early-start deferiprone in infants and young children with transfusion-dependent beta thalassemia: Evidence for iron shuttling to transferrin in a randomized, double-blind, placebo-controlled, clinical trial (START).

Children with transfusion-dependent thalassemia (TDT) require regular blood transfusions that, without iron-chelation therapy, lead to iron-overload toxicities. Current practice delays chelation therapy (late-start) until reaching iron overload (serum ferritin ≥1000 µg/L) to minimize risks of iron-depletion. Deferiprone's distinct pharmacological properties, including iron-shuttling to transferrin, may reduce risks of iron depletion during mild-to-moderate iron loads and iron overload/toxicity in children with TDT. The early-start deferiprone (START) study evaluated the efficacy/safety of early-start deferiprone in infants/young children with TDT. Sixty-four infants/children recently diagnosed with beta-thalassemia and serum ferritin (SF) between 200 and 600 µg/L were randomly assigned 1:1 to receive deferiprone or placebo for 12 months or until reaching SF-threshold (≥1000 µg/L at two consecutive visits). Deferiprone was initiated at 25 mg/kg/day and increased to 50 mg/kg/day; some recipients' dosages increased to 75 mg/kg/day based on iron levels. The primary endpoint was the proportion of patients ≥SF-threshold by month 12. Monthly transferrin saturation (TSAT) assessment evaluated iron-shuttling. At baseline, there was no significant difference in mean age (deferiprone: 3.03 years, placebo: 2.63 years), SF (deferiprone: 513.8 µg/L, placebo: 451.7 µg/L), or TSAT (deferiprone: 47.98%, placebo: 43.43%) between groups. At month 12, there was no significant difference in growth or adverse event (AE) rates between groups. No deferiprone-treated patients were iron-depleted. At month 12, 66% of patients receiving deferiprone remained below SF threshold versus 39% of placebo (p = .045). Deferiprone-treated patients showed higher TSAT levels and reached ≥60% TSAT threshold faster. Early-start deferiprone was well-tolerated, not associated with iron depletion, and efficacious in reducing iron overload in infants/children with TDT. TSAT results provide the first clinical evidence of deferiprone shuttling iron to transferrin.

Can Essential Oils Provide an Alternative Adjuvant Therapy for COVID-19 Infections and Pain Management at the Same Time?

The active compounds from essential oils have been an important asset in treating different diseases for many centuries. Nowadays, there are various available formulations used as food supplements to stimulate the immune system. In light of the current pandemic and the large amount of fake news circulating the internet, it is important to analyze which of the active compounds from essential oils can be successfully used in the treatment of COVID-19 infections. We analyzed the current literature on the effects of essential oils against the new SARS-CoV-2 virus to gain a better understanding of the underlying mechanisms of these compounds and establish their possible antiviral efficacy. The available studies have highlighted the antiviral potential of active compounds from essential oils, indicating that they could be used as adjuvants in treating various viral infections, including COVID-19, leading to a milder course of the disease, and improving patients' outcomes. At the same time, these compounds relieve pain and lift the mood in comorbid patients suffering from opioid addiction. Essential oils might be useful as adjuvant tools, not only against SARS-CoV-2 but also for a subset of especially vulnerable patients affected with both COVID-19 and opioid addiction. However, randomized clinical trials are needed to determine their efficacy and develop standardized high-quality preparations that can be safely administered to the general population.

Non-essential heavy metals and protective effects of selenium against mercury toxicity in endangered Australian sea lion (Neophoca cinerea) pups with hookworm disease.

The endangered Australian sea lion, Neophoca cinerea, faces ongoing population decline. Identification of key threats to N. cinerea population recovery, including disease and pollutants, is an objective of the species' recovery plan. Previous studies have identified Uncinaria sanguinis, an intestinal nematode, as a significant cause of disease and mortality in N. cinerea pups. Given the impact of heavy metals on the immune response, investigation of these pollutants is critical. To this end, the concentrations of arsenic (As), total mercury (Hg), cadmium (Cd), chromium (Cr), lead (Pb) and selenium (Se) were determined in blood collected from N. cinerea pups sampled during the 2017/18, 2019 and 2020/21 breeding seasons at Seal Bay Conservation Park, South Australia. Significant differences (p < 0.05) in Hg, As, Cr, and Se concentrations and molar ratio of Se:Hg were seen between breeding seasons. Pup age, maternal parity and inter-individual foraging behaviour were considered factors driving these differences. The concentrations of Hg (357, 198 and 241 µg/L) and As (225, 834 and 608 µg/L) were high in 2017/18, 2019 and 2020/21 respectively with Hg concentrations in the blood of N. cinerea pups above toxicological thresholds reported for marine mammals. The concentration of Se (1332, 647, 763 µg/L) and molar ratio of Se:Hg (9.47, 7.98 and 6.82) were low compared to other pinniped pups, indicating potential vulnerability of pups to the toxic effects of Hg. Significant (p < 0.05) negative associations for Pb and Cd with several red blood cell parameters suggest they could be exacerbating the anaemia caused by hookworm disease. Temporal (age-related) changes in element concentrations were also seen, such that pup age needs to be considered when interpreting bioaccumulation patterns. Further investigation of the role of elevated heavy metal concentrations on N. cinerea pup health, disease and development is recommended, particularly with respect to immunological impacts.

HIV patients' perceptions of a potential multi-component mindfulness-based smoking cessation smartphone application intervention.

OBJECTIVES: Cigarette smoking rates among people living with HIV (PLWH) in the US is triple that of the general population. PLWH smokers are a high-risk group for smoking-related health disparities and should be a prime focus for smoking cessation efforts. Our team has developed a novel evidence-based Mindfulness Training (MT) smoking cessation smartphone application (app), "Craving-to-Quit." Using qualitative focus groups among PLWH smokers, this study aims to tailor and optimize the app's content and design to PLWH's unique psychosocial profile and needs. METHODS: We conducted 8 focus groups among PLWH smokers (n = 59; 47.5% females; ≥18 years) to gain insight into participants' perceptions about the app, MT, and the feasibility and acceptability of adding two additional strategies (CM: Contingency Management; self-monitoring of anti-retroviral therapies intake [ART]) to further optimize the app. Participants were asked to practice MTs and watch videos from the app presented on a screen in the conference room to discuss their experience. Sessions were audio-taped, transcribed verbatim, and analyzed thematically using NVivo. RESULTS: Most participants were non-Hispanic black (67.8%), on a federal health insurance program (61.0%). Participants considered it easy to learn the app and thought that MT is helpful in reducing stress and motivating quit attempts and were supportive of adding CM and recommended providing $20-$50 weekly cash incentives to help in quitting. Participants felt that adding self-monitoring of ART is helpful but were concerned about confidentiality in case they lost their phone. Participants recommended making the app cost-free and adding information about smoking cessation medications and the negative effects of smoking among PLWH. CONCLUSIONS: Findings will guide the development of a novel multi-component smoking cessation intervention app integrating MT, CM, and ART self-monitoring strategies. This intervention has the potential to address several barriers to quitting in PLWH. Further clinical research is needed to test this intervention.

Hyperbaric oxygen for COVID-19 patients with severe hypoxia prior to vaccine availability.

Introduction: Few treatments have demonstrated mortality benefits among hospitalized hypoxic COVID-19 patients. We evaluated the use of hyperbaric oxygen (HBO2) therapy as a therapeutic intervention among hospitalized patients with a high oxygen requirement prior to vaccine approval. Methods: We extracted data on patients with COVID-19 hypoxia who required oxygen supplementation ranging from a 6L nasal cannula up to a high-flow nasal cannula at 100% FiO2 at 60L/minute with a 100% non-rebreather mask at 15 L/minute and were eligible for off-label HBO2 therapy from October 2020 to February 2021. We followed the Monitored Emergency use of Unregistered and Investigational Interventions or (MEURI) in conjunction with the consistent re-evaluation of the protocol using the Plan-Do-Study-Act (PDSA) tool [1]. We compared patient characteristics and used Fisher's exact test and a survival analysis to assess the primary endpoint of inpatient death. Results: HBO2 therapy was offered to 36 patients, of which 24 received treatment and 12 did not receive treatment. Patients who did not receive treatment were significantly older (p ≺ 0.01) and had worse baseline hypoxia (p = 0.06). Three of the 24 (13%) patients who received treatment died compared to six of 12 (50%) patients who did not receive treatment (RR ratio: 0.25, p = 0.04, 95% CI: 0.08 to 0.83). In the survival analysis, there was a statistically significant reduction in inpatient mortality in the treatment group (HR: 0.19, p = 0.02, 95% CI: 0.05-0.74). However, after adjusting for age and baseline hypoxia, there was no difference in inpatient mortality (hazard ratio: 0.48, p = 0.42, 95% CI: 0.08-2.86). Conclusion: The survival benefit of HBO2 therapy observed in our unadjusted analysis suggests that there may be therapeutic benefits of HBO2 in treating COVID-19 hypoxia as an adjunct to standard care.

Does the Broaden-and-Build Theory Explain Reduction in Social Disruption After a Brief Relaxation Intervention for Women With Breast Cancer Undergoing Treatment?

Women with breast cancer experience social disruption during and after treatment. Brief cognitive-behavioral (CBT) and relaxation (RT) interventions may improve social disruption by increasing positive affect. Using the Broaden-and-Build Theory as a framework, this study examined whether short-term CBT- and RT-related increases in positive affect mediate long-term reductions in social disruption in women with breast cancer undergoing treatment (N = 183). This secondary analysis used latent change score and growth models to test 6- and 12-month intervention effects on positive affect and social disruption, respectively; a parallel-process model assessed mediation. RT demonstrated larger reductions in social disruption across 12 months compared to CBT and a health education control. Six-month latent change in positive affect was significant but not driven by condition. There was a significant direct effect linking the latent slopes of positive affect and social disruption but meditation was not observed. These preliminary findings hint at the value of promoting positive affect and inform the development of brief behavioral interventions that aim to augment social functioning among women surviving breast cancer.

Natural medicine HLXL targets multiple pathways of amyloid-mediated neuroinflammation and immune response in treating alzheimer's disease.

BACKGROUND: Based on the complex pathology of AD, a single chemical approach may not be sufficient to deal simultaneously with multiple pathways of amyloid-tau neuroinflammation. A polydrug approach which contains multiple bioactive components targeting multiple pathways in AD would be more appropriate. Here we focused on a Chinese medicine (HLXL), which contains 56 bioactive natural products identified in 11 medicinal plants and displays potent anti-inflammatory and immuno-modulatory activity. HYPOTHESIS/PURPOSE: We investigated the neuroimmune and neuroinflammation mechanisms by which HLXL may attenuate AD neuropathology. Specifically, we investigated the effects of HLXL on the neuropathology of AD using both transgenic mouse models as well as microglial cell-based models. STUDY DESIGN: The 5XFAD transgenic animals and microglial cell models were respectively treated with HLXL and Aß42, and/or lipopolysaccharide (LPS), and then analyzed focusing on microglia mediated Aß uptake and clearance, as well as pathway changes. METHODS: We showed that HLXL significantly reduced amyloid neuropathology by upregulation of microglia-mediated phagocytosis of Aß both in vivo and in vitro. HLXL displayed multi-modal mechanisms regulating pathways of phagocytosis and energy metabolism. RESULTS: Our results may not only open a new avenue to support pharmacologic modulation of neuroinflammation and the neuroimmune system for AD intervention, but also identify HLXL as a promising natural medicine for AD. CONCLUSION: It is conceivable that the traditional wisdom of natural medicine in combination with modern science and technology would be the best strategy in developing effective therapeutics for AD.

Cisplatin exposure acutely disrupts mitochondrial bioenergetics in the zebrafish lateral-line organ.

Cisplatin is a commonly used chemotherapeutic agent that causes debilitating high-frequency hearing loss. No targeted therapies currently exist to treat cisplatin ototoxicity, partly because the underlying mechanisms of cisplatin-induced hair cell damage are not completely defined. Zebrafish may offer key insights to cisplatin ototoxicity because their lateral-line organ contains hair cells that are remarkably similar to those within the cochlea but are optically accessible, permitting observation of cisplatin injury in live intact hair cells. In this study, we used a combination of genetically encoded biosensors in zebrafish larvae and fluorescent indicators to characterize changes in mitochondrial bioenergetics in response to cisplatin. Following exposure to cisplatin, confocal imaging of live intact neuromasts demonstrated increased mitochondrial activity. Staining with fixable fluorescent dyes that accumulate in active mitochondria similarly showed hyperpolarized mitochondrial membrane potential. Zebrafish expressing a calcium indicator within their hair cells revealed elevated levels of mitochondrial calcium immediately following completion of cisplatin treatment. A fluorescent ROS indicator demonstrated that these changes in mitochondrial function were associated with increased oxidative stress. After a period of recovery, cisplatin-exposed zebrafish demonstrated caspase-3-mediated apoptosis. Altogether, these findings suggest that cisplatin acutely disrupts mitochondrial bioenergetics and may play a key role in initiating cisplatin ototoxicity.

Profiles and predictors of healthcare utilization: using a cluster-analytic approach to identify typical users across conventional, allied and complementary medicine, and self-care.

INTRODUCTION: The identification of typologies of health care users and their specific characteristics can be performed using cluster analysis. This statistical approach aggregates similar users based on their common health-related behavior. This study aims to examine health care utilization patterns using cluster analysis; and the associations of health care user types with sociodemographic, health-related and health-system related factors. METHODS: Cross-sectional data from the 2012 National Health Interview Survey were used. Health care utilization was measured by consultations with a variety of medical, allied and complementary health practitioners or the use of several interventions (exercise, diet, supplementation etc.) within the past 12 months (used vs. not used). A model-based clustering approach based on finite normal mixture modelling, and several indices of cluster fit were determined. Health care utilization within the cluster was analyzed descriptively, and independent predictors of belonging to the respective clusters were analyzed using logistic regression models including sociodemographic, health- and health insurance-related factors. RESULTS: Nine distinct health care user types were identified, ranging from nearly non-use of health care modalities to over-utilization of medical, allied and complementary health care. Several sociodemographic and health-related characteristics were predictive of belonging to the respective health care user types, including age, gender, health status, education, income, ethnicity, and health care coverage. CONCLUSIONS: Cluster analysis can be used to identify typical health care utilization patterns based on empirical data; and those typologies are related to a variety of sociodemographic and health-related characteristics. These findings on individual differences regarding health care access and utilization can inform future health care research and policy regarding how to improve accessibility of different medical approaches.

Deferiprone vs deferoxamine for transfusional iron overload in SCD and other anemias: a randomized, open-label noninferiority study.

Many people with sickle cell disease (SCD) or other anemias require chronic blood transfusions, which often causes iron overload that requires chelation therapy. The iron chelator deferiprone is frequently used in individuals with thalassemia syndromes, but data in patients with SCD are limited. This open-label study assessed the efficacy and safety of deferiprone in patients with SCD or other anemias receiving chronic transfusion therapy. A total of 228 patients (mean age: 16.9 [range, 3-59] years; 46.9% female) were randomized to receive either oral deferiprone (n = 152) or subcutaneous deferoxamine (n = 76). The primary endpoint was change from baseline at 12 months in liver iron concentration (LIC), assessed by R2* magnetic resonance imaging (MRI). The least squares mean (standard error) change in LIC was -4.04 (0.48) mg/g dry weight for deferiprone vs -4.45 (0.57) mg/g dry weight for deferoxamine, with noninferiority of deferiprone to deferoxamine demonstrated by analysis of covariance (least squares mean difference 0.40 [0.56]; 96.01% confidence interval, -0.76 to 1.57). Noninferiority of deferiprone was also shown for both cardiac T2* MRI and serum ferritin. Rates of overall adverse events (AEs), treatment-related AEs, serious AEs, and AEs leading to withdrawal did not differ significantly between the groups. AEs related to deferiprone treatment included abdominal pain (17.1% of patients), vomiting (14.5%), pyrexia (9.2%), increased alanine transferase (9.2%) and aspartate transferase levels (9.2%), neutropenia (2.6%), and agranulocytosis (0.7%). The efficacy and safety profiles of deferiprone were acceptable and consistent with those seen in patients with transfusion-dependent thalassemia. This trial study was registered at www://clinicaltrials.gov as #NCT02041299.

The bioactive alkaloids identified from Cortex Phellodendri ameliorate benign prostatic hyperplasia via LOX-5/COX-2 pathways.

BACKGROUND: The bioactive alkaloids identified from Cortex Phellodendri (CP) were highly effective in treating rats with benign prostatic hyperplasia (BPH). Specifically, lipoxygenase-5 (LOX-5) and cyclooxygenase-2 (COX-2) were identified as two primary targets for alleviating inflammation in BPH rats. However, it remains unknown whether the alkaloid components in CP can interact with the two target proteins. PURPOSE: To further identify bioactive alkaloids targeting LOX/COX pathways. METHODS: An affinity-ultrafiltration mass spectrometry approach was employed to screen dual-target LOX-5/COX-2 ligands from alkaloid extract. The structures of bioactive alkaloids were characterized by high-resolution Fourier transform ion cyclotron resonance mass spectrometry. To understand the molecular mechanisms underlying the effects of bioactive alkaloids, the expression levels of LOX-5 and COX-2 in BPH model rats were investigated at both protein and mRNA levels. The LOX-5/COX-2 enzymes activity experiments and molecular docking analysis were performed to fully evaluate the interactions between bioactive alkaloids and LOX-5/COX-2. RESULTS: After comprehensive analysis, the results showed that bioactive alkaloids could suppress the expression of LOX-5 and COX-2 simultaneously to exert an anti-inflammatory effect on the progression of BPH. In addition, the screened protoberberine, demethyleneberberine was found to exhibit prominent inhibitory activities against both LOX-5 and COX-2 enzymes, palmatine and berberine with moderate inhibitory activities. Molecular docking analysis confirmed that demethyleneberberine could interact well with LOX-5/COX-2. CONCLUSION: This study is the first to explore the inhibitory effects of bioactive alkaloids from CP on LOX-5 and COX-2 activities in BPH rats. Our findings demonstrate that the bioactive alkaloids from CP can ameliorate BPH via dual LOX-5/COX-2 pathways, which serves as an efficient approach for the discovery of novel drug leads from natural products with reduced side effects.

Trends, survival outcomes, and predictors of nonadherence to mastectomy guidelines for nonmetastatic inflammatory breast cancer.

BACKGROUND: The Current National Comprehensive Cancer Network guidelines recommend modified radical mastectomy (MRM) as the surgical treatment of choice for nonmetastatic inflammatory breast cancer (IBC). Limited studies have looked into the outcomes of breast conserving surgery (BCS) vs. MRM for IBC. METHODS: National Cancer Database (NCDB) data from 2004 to 2014 were retrospectively analyzed. Patients' demographics, tumor characteristics, and overall survival (OS) trends were compared for BCS and MRM cases of nonmetastatic IBC. Univariate and multivariate analyses were performed. RESULTS: A total of 413 (3.89%) BCS and 10,197 (96.11%) MRM cases were identified. Median follow-up was 58.45 months. Compared to MRM, BCS patients were more likely to be older, be African American, have Medicare/Medicaid or be uninsured, live in lower education ZIP codes, and live in a metropolitan area (all p < 0.05). BCS rates significantly decreased from 5.84% in 2004 to 3.19% in 2014 (p < 0.001). BCS patients also were more likely to have less than 50% of the breast involved (51.57% vs. 43.88%; p = 0.0081) and were less likely to receive trimodal therapy (50.85% vs. 74.62%; p = <0.0001). The OS was significantly higher in the mastectomy group over 9 years at 62.02% vs. 54.47% in the BCS group. Additionally, in the adjusted multivariate model, BCS cases were associated with 23% higher hazards of overall mortality (p = 0.0091). CONCLUSION: BCS was performed in a limited number of cases, which decreased over the study period. The analysis identified both demographic predictors of receiving BCS and significantly lower OS for IBC patients undergoing a BCS.

Reach versus effectiveness: The design and protocol of randomized clinical trial testing a smartphone application versus in-person mindfulness-based smoking cessation intervention among young cancer survivors.

Approximately 45% of young cancer survivors (18-40 years) are cigarette smokers. Continued smoking after cancer diagnosis leads to lower survival rates. A major logistical problem with smoking cessation efforts in this group is their geographic dispersion which makes them hard to reach. In addition, depression is a major predictor of smoking relapse and its rates are roughly twice as high in cancer survivors as the general population. Smartphone applications (apps) show promise in terms of efficacy, dissemination, and improving access to treatment. Mindfulness training (defined as maintaining attention on one's immediate experience and cultivating an attitude of acceptance toward this experience) is effective in improving smoking cessation outcomes by reducing psychological stress and controlling craving. Given that smartphone apps can address the issues of mobility and remote access, and mindfulness can address the high depression rate among cancer survivors, validating the feasibility and efficacy of a mindfulness-based smoking cessation intervention app in young cancer survivors is a high priority. Thus, the aims of the current study are: (1) test the feasibility, acceptability, and potential efficacy of the mindfulness-based smoking cessation app versus in-person mindfulness or usual care in a 3-arm pilot randomized clinical trial among young cancer survivors (n = 60; 18-40 years); and 2) conduct semi-structured exit interviews with participants in the two mindfulness groups to fine-tune the two active interventions based on feedback from participants. Findings will have implications for the development and dissemination of innovative and highly scalable tobacco cessation interventions designed for young cancer survivors.

Role of Levo-tetrahydropalmatine and its metabolites for management of chronic pain and opioid use disorders.

BACKGROUND: Opioids have been prescribed to reduce suffering from pain and to enhance quality of life. Due to the addictive potential and the lack of other effective alternatives to treat severe acute and chronic pains, opioids remain a serious public health issue. While, opioids directly influence the drug-seeking behavior, tolerance and withdrawal processes, through neuroadaptation, the brain's endogenous opioid system also adapts in the presence of chronic pain and could contribute to the difficulty of treatment. Despite the seemingly obvious interaction between the presence of pain and opioid-abuse, little is known about the underlying mechanisms in the brain. PURPOSE: To review the current understanding of the interaction mechanisms of neurotransmitter circuitries in pain modulation and reward in the brain and the effects of L-tetrahydropalmatine (L-THP) and its metabolites in pain management and opioid use disorder and gain a better insight on the pharmacological profile and in vivo effects of L-THP and its metabolites. METHOD: A detailed literature search on available (preclinical and clinical) studies about the effects of L-THP and its metabolites against drug addiction and chronic pain has been performed. The data was collected using various search engines such as PubMed, ScienceDirect, Google scholar and articles in English up to December 2020 were included in this review. RESULTS: L-THP and its metabolites demonstrated analgesic and anti-addiction effects. Due to their dual pharmacological properties (D1 partial agonist and D2 antagonist) these compounds could be used as molecular tools to provide a better understanding of the interactions between pain and addiction. CONCLUSION: The available data confirms the potential of L-THP and its metabolites to treat both chronic pain and drug addiction. However, further clinical trials are needed to establish safety and efficacy.

Review of Current Evidence for Minimally Invasive Posterior Sacroiliac Joint Fusion.

The sacroiliac joint (SIJ) is a large, irregularly shaped, serpentine joint structure bordered anteriorly and posteriorly by the sacroiliac ligaments. With increased recognition of the SIJ as a pain source, treatments have been historically nonsurgical in nature. Common treatments include bracing, medications, activity modification, manual therapy, chiropractic manipulation, physical therapy, and intra-articular SIJ injections. Surgical stabilization and/or fusion of the SIJ may be considered when a patient has persistent moderate to severe pain, functional impairment, and failed conservative management. Surgical stabilization and fusion has traditionally been by way of the transiliac approach. More recent SIJ fusion systems have proposed not only a posterior approach but one that stabilizes the joint space by placing an allograft within the SIJ. Anatomically, a posterior approach is able to avoid neurovascular structures that otherwise are encountered with the transiliac approach and may be performed percutaneously. Preliminary evidence reports consistent pain reduction with minimal complications. This paper is purposed to detail the present evidence of minimally invasive posterior SIJ fusion, as well as highlight the need for further research moving forward.

Can eastern wisdom resolve western epidemics? Traditional Chinese medicine therapies and the opioid crisis.

The widespread use of opioids to treat chronic pain led to a nation-wide crisis in the United States. Tens of thousands of deaths annually occur mainly due to respiratory depression, the most dangerous side effect of opioids. Non-opioid drugs and non-pharmacological treatments without addictive potential are urgently required. Traditional Chinese medicine (TCM) is based on a completely different medical theory than academic Western medicine. The scientific basis of acupuncture and herbal treatments as main TCM practices has been considerably improved during the past two decades, and large meta-analyses with thousands of patients provide evidence for their efficacy. Furthermore, opinion leaders in the United States favor non-pharmacological techniques including TCM for pain management to fight the opioid crisis. We advocate TCM as therapeutic option without addictive potential and without life-threatening side effects (e.g., respiratory depression) to treat chronic pain patients suffering from opioid misuse. The evidence suggests that: (1) opioid misuse cannot be satisfactorily managed with standard medication; (2) opinion leaders in the United States favor to consider non-opioid and non-pharmacological treatment strategies including those from TCM to treat acute and chronic pain conditions; (3) large meta-analyses provide scientific evidence for the clinical activity of acupuncture and herbal TCM remedies in the treatment of chronic pain. Future clinical trials should demonstrate the safety of TCM treatments if combined with Western medical practices to exclude negative interactions between both modalities.

The Growth Response to Beta-Hydroxybutyrate in SH-SY5Y Neuroblastoma Cells is Suppressed by Glucose and Pyruvate Supplementation.

Neuroblastoma (NB) is a childhood malignancy of the sympathetic nervous system and is commonly studied using the SH-SY5Y cell line. Its neoplastic and neurodevelopmental manifestations are characterised by a high glucose demand which maintains its high proliferative capacity. This metabolic phenotype may be utilised in dietary therapies such as the ketone diet which alter substrate availability and thus starve NB cells of their preferred biosynthetic requirements. However, the effects of ketone metabolism on cancer growth remain poorly understood due to the involvement of other metabolic substrates in experimental paradigms and complexities underlying the Warburg effect. We investigated how the primary ketone body beta-hydroxybutyrate (ßOHB) affects the growth of SH-SY5Y NB cells in the presence or absence of culture metabolic substrates. We demonstrated that while glucose deprivation reduced the growth and viability of SH-SY5Y cells, they proliferated and were initially unaffected by the addition of ßOHB. However, a growth response to ßOHB was subsequently revealed in media containing low levels of glucose, as well as in glucose and pyruvate deprived conditions. These data shed light on the roles of metabolic substrate availability as key determinants of the responses of SH-SY5Y NB cells to ketone supplementation.

Frequency-specific Electrocochleography and Traveling Wave Time as a Clinical Test for Menière's Disease.

INTRODUCTION: Menière's disease is a clinical entity with no definitive objective testing. It has been hypothesized that underlying endolymphatic hydrops stiffens the basilar membrane leading to increased speed of the acoustic stimulus, therefore traveling wave velocity has been proposed as an objective test to aid in the diagnosis. The objective of this study is to compare electrocochleography frequency-specific action potential latency, basilar membrane traveling wave time, and summation to action potential (SP/AP) ratio in Menière's and non-Menière's patients. METHODS: Tympanic electrocochleography was performed with frequency-specific action potential latency time and SP/AP ratio recorded. Patient demographics, symptoms, audiogram data, AAO-HNS classification of Menière's disease, management interventions, and follow-up were recorded. Statistical analysis was performed to compare outcome measures across patient groups, demographics, and clinical data. RESULTS: Ninety-one patients (182 ears) were included. There was a significant difference between a "definite" Menière's diagnosis and an "unlikely" or "probable" diagnosis by an average of 13 dB HL for the pure-tone thresholds at 250 Hz on the affected side (p = 0.006). There was no significant difference in pure-tone thresholds at any other frequency, AP latency at any frequency, or AP/SP ratio between the different Menière's classification groups. CONCLUSIONS: Our study fails to show significance of the traveling wave velocity as an objective test for Menière's disease. A significant correlation was found with low-frequency hearing loss between AAO-HNS Menière's classification groups.

Traditional Chinese herbal medicine at the forefront battle against COVID-19: Clinical experience and scientific basis.

BACKGROUND: Throughout the 5000-year history of China, more than 300 epidemics were recorded. Traditional Chinese herbal medicine (TCM) has been used effectively to combat each of these epidemics' infections, and saved many lives. To date, there are hundreds of herbal TCM formulae developed for the purpose of prevention and treatment during epidemic infections. When COVID-19 ravaged the Wuhan district in China in early January 2020, without a deep understanding about the nature of COVID-19, patients admitted to the TCM Hospital in Wuhan were immediately treated with TCM and reported later with >90% efficacy. APPROACH: We conducted conduct a systematic survey of various TCM herbal preparations used in Wuhan and to review their efficacy, according to the published clinical data; and, secondly, to find the most popular herbs used in these preparations and look into the opportunity of future research in the isolation and identification of bioactive natural products for fighting COVID-19. RESULTS: Although bioactive natural products in these herbal preparations may have direct antiviral activities, TCM employed for fighting epidemic infections was primarily based on the TCM theory of restoring the balance of the human immune system, thereby defeating the viral infection indirectly. In addition, certain TCM teachings relevant to the meridian system deserve better attention. For instance, many TCM herbal preparations target the lung meridian, which connects the lung and large intestine. This interconnection between the lung, including the upper respiratory system, and the intestine, may explain why certain TCM formulae showed excellent relief of lung congestion and diarrhea, two characteristics of COVID-19 infection. CONCLUSION: There is good reason for us to learn from ancient wisdom and accumulated clinical experience, in combination with cutting edge science and technologies, to fight with the devastating COVID-19 pandemic now and emerging new coronaviruses in the future.