Efficacy and feasibility of SMS m-Health for the detection of adverse events following immunisation (AEFIs) in resource-limited setting-The Zimbabwe stimulated telephone assisted rapid safety surveillance (Zm-STARSS) randomised control trial.

INTRODUCTION: The mHealth active participant centred (MAPC) adverse events following immunisation (AEFI) surveillance is a promising area for early AEFI detection resulting in risk minimisation. Passive (spontaneous) AEFI surveillance is the backbone for vaccine pharmacovigilance, but has inherent drawbacks of under reporting, and requires strengthening with active surveillance methods. AIM: The Zimbabwe stimulated telephone assisted rapid safety surveillance (Zm-STARSS) randomised controlled trial (RCT) sought to evaluate the efficacy and feasibility of AEFI detection using a short message service (SMS) and computer assisted telephone interview (CATI) approach. METHOD: A multicentre Zm-STARSS RCT enrolled consented adult vaccinees or parents or guardians of children receiving vaccines, including COVID-19 vaccines, at study vaccination clinics. At enrolment study participants were randomised to either SMS-CATI group or control group. SMS prompts were sent on days 0-2 and 14 post-vaccination to SMS-CATI group to ascertain if a medically attendance or attention due to an Adverse event following immunisation (AEFI) had occurred. However, no SMSs were sent to the control group. SMS-CATI group who responded "Yes" to SMS prompts were interviewed by research healthcare workers (RHCWs) who completed a CATI to determine if an AEFI had occurred whilst an AEFI in control group was determined from passive AEFI reporting channels. The primary study outcome was the AEFI detection rate in the SMS-CATI group compared to the control group. RESULTS: A total of 4560 participants were enrolled after signed informed consent, all were encouraged to report AEFIs and randomised automatically on 1:1 basis into two arms SMS CATI intervention group (n = 2280) and a control passive AEFI surveillance group (n = 2280) on day 0. A total of 704 (31 %) participants responded to the SMS prompts, with 75 % (528/704) indicating "No" and 25 % (176/704) reporting "Yes" to seeking medical attention or attendance post-immunisation. 69 % (121/176) completed a CATI survey but in only 36 % (44/121) was the AEFI confirmed. There were no AEFIs reported in control group participants. The detection rate of a AEFI associated with medically attendance or attention using the SMS-CATI methodology was 2 % (44/2280) on an intention to treat cohort. CONCLUSION: Despite the low SMS response and CATI completion rate, we demonstrated that Zm-STARSS SMS system improves AEFI detection compared to passive AEFI surveillance. We recommend that this and similar approaches are explored further using cost-effective multi-channel digital approaches for holistic pharmacovigilance to improve AEFI detection in Low Middle-Income Countries (LMICs) for all vaccines.

Survival in borderline resectable and locally advanced pancreatic cancer is determined by the duration and response of neoadjuvant therapy.

BACKGROUND: Pancreatic cancer is the 8th commonest cancer and the 5th commonest cause of cancer-related death in Australia, with a 9% average 5-year survival. This study aims to investigate the effects of neoadjuvant treatment on overall survival (OS) and recurrence-free survival (RFS) in borderline resectable (BRPC) and locally advanced (LAPC) pancreatic adenocarcinoma followed by curative resection. MATERIALS AND METHODS: Prospectively-collected demographic, medical, surgical and pathological data of patients with BRPC and LAPC treated with both neoadjuvant therapy (NAT) and surgery at a single tertiary referral centre in Australia were reviewed and analysed. RESULTS: Between 2012 and 2018, 60 patients, 34 with BRPC and 26 with LAPC, were treated with NAT followed by curative resection. The commonest neoadjuvant chemotherapy regimens were Gemcitabine + Abraxane (51.7%) and FOLFIRINOX (35.0%), with 48.3% of patients additionally receiving neoadjuvant radiotherapy. Median RFS was 30 months and median OS was 35 months. On multivariable analysis, inferior OS was predicted by enlarged loco-regional lymph nodes on initial computed tomography (p = 0.032), larger tumour size post-NAT (p = 0.006) and Common Terminology Criteria for Adverse Events post-NAT toxicity greater than grade 2 (p = 0.015). LAPC patients received more neoadjuvant chemotherapy (p = 0.008) and radiotherapy (p = 0.021) than BRPC and achieved a superior pathological response (p = 0.010). CONCLUSION: Patients who respond to NAT likely have a favourable disease biology and will progress well following resection. It is these patients who should be selected for more aggressive upfront management, and those with resistant disease should be spared from high-risk surgery.

Emerging biological therapies for the treatment of malignant pleural mesothelioma.

Introduction: Malignant pleural mesothelioma (MPM) has limited treatment options with minimal new therapy approvals for unresectable disease in the past 15 years. However, considerable work has occurred to develop immunotherapies and biomarker driven therapy to improve patient outcomes over this period.Areas covered: This review examines current standard of care systemic therapy in the first- and second line setting. The last 12 months has seen 2 significant trials (Checkmate 743 and CONFIRM) which provide evidence supporting the role of immunotherapy in the management of MPM. Further trials are underway to assess the role of combination chemoimmunotherapy and personalized therapy. Additionally, a large number of clinical trials are ongoing to assess the efficacy of oncoviral, dendritic cell, anti-mesothelin and chimeric antigen receptor T cell therapy in the treatment of MPM.Expert opinion: Recent Phase III trial results have established a role for immunotherapy in the management of MPM. The optimal sequencing and combination of chemotherapy and immunotherapy remains to be determined. Novel therapies for MPM are promising however efficacy remains to be determined and issues remain regarding access to and delivery of these therapies.

Deficiency of ß-carotene oxygenase 2 induces mitochondrial fragmentation and activates the STING-IRF3 pathway in the mouse hypothalamus.

Hypothalamic inflammation has been linked to various aspects of central metabolic dysfunction and diseases in humans, including hyperphagia, altered energy expenditure, and obesity. We previously reported that loss of ß-carotene oxygenase 2 (BCO2), a mitochondrial inner membrane protein, causes the alteration of the hypothalamic metabolome, low-grade inflammation, and an increase in food intake in mice at an early age, e.g., 3-6 weeks. Here, we determined the extent to which the deficiency of BCO2 induces hypothalamic inflammation in BCO2 knockout mice. Mitochondrial proteomics, electron microscopy, and immunoblotting were used to assess the changes in hypothalamic mitochondrial dynamics and mitochondrial DNA sensing and signaling. The results showed that deficiency of BCO2 altered hypothalamic mitochondrial proteome and respiratory supercomplex assembly by enhancing the expression of NADH:ubiquinone oxidoreductase subunit A11 protein and improved cardiolipin synthesis. BCO2 deficiency potentiated mitochondrial fission but suppressed mitophagy and mitochondrial biogenesis. Furthermore, deficiency of BCO2 resulted in inactivation of mitochondrial MnSOD enzyme, excessive production of reactive oxygen species, and elevation of protein levels of stimulator of interferon genes (STING) and interferon regulatory factor 3 (IRF3) in the hypothalamus. The data suggest that BCO2 is essential for hypothalamic mitochondrial dynamics. BCO2 deficiency induces mitochondrial fragmentation and mitochondrial oxidative stress, which may lead to mitochondrial DNA release into the cytosol and subsequently sensing by activation of the STING-IRF3 signaling pathway in the mouse hypothalamus.

Pinto beans modulate the gut microbiome, augment MHC II protein, and antimicrobial peptide gene expression in mice fed a normal or western-style diet.

The onset of type 2 diabetes in obesity is associated with gut dysbiosis and a failure to confine commensal bacteria and toxins to the gut lumen while prebiotics may prevent these effects. This study evaluated the effects of pinto beans (PB) supplementation on cecal bacteria, short-chain fatty acids (SCFAs), distal ileal antigen presentation marker (major histocompatibility complex [MHC] II) and antimicrobial peptide genes during short-term high-fat, high sucrose (HFS) feeding. Six-week-old, male C57BL/6J mice were randomly assigned to four groups (n=12/group), and fed a control (C) or HFS diet with or without cooked PB (10%, wt/wt) for 30 days. Supplemental PB in both the C and HFS diets decreased the abundance of Tenericutes and the sulfate-reducing bacteria Bilophila. In contrast, PB raised the abundance of taxa within the SCFAs-producing family, Lachnospiraceae, compared to groups without PB. Consequently, fecal butyric acid was significantly higher in PB-supplemented groups compared to C and HFS groups. PB reversed the HFS-induced ablation of the distal ileal STAT3 phosphorylation, and up-regulated antimicrobial peptide genes (Reg3γ and Reg3ß). Furthermore, the expression of MHC II protein was elevated in the PB supplemented groups compared to C and HFS. Tenericutes and Bilophilia negatively correlated with activated STAT3 and MHC II proteins. Finally, supplemental PB improved fasting blood glucose, glucose tolerance and suppressed TNFα and inducible nitric oxide synthase mRNA in the visceral adipose tissue. Put together, the beneficial impact of PB supplementation on the gut may be central to its potential to protect against diet-induced inflammation and impaired glucose tolerance.

The Effects of Acupuncture on Cancer-Related Fatigue: Updated Systematic Review and Meta-Analysis.

BACKGROUND: Several studies have identified fatigue as one of the major symptoms experienced during and after cancer treatment. However, there are limited options to manage cancer related fatigue (CRF) with pharmacological interventions. Several acupuncture studies suggested that acupuncture has a positive impact on CRF. This review aims to assess the evidence of acupuncture for the treatment of CRF. METHOD: Electronic database searches were conducted on 4 English databases (Medline, PubMed, Embase, and ScienceDirect). Search keywords were; "acupuncture" and "cancer," or "cancer related fatigue." Studies published as full text randomized controlled trials (RCTs) in English were included. Estimates of change in fatigue cores were pooled using a random effects meta-analysis where randomized comparisons were available for true acupuncture versus sham acupuncture and true acupuncture versus usual care. The quality of original papers were assessed using the Cochrane Collaboration's tool for assessing risk of bias (ROB). RESULTS: Nine RCTs were selected for review with a total of 809 participants and a range of 13 to 302 participants within the studies. Six RCTs reported significant improvement of CRF for the acupuncture intervention compared to the control groups. Pooled estimates suggest Brief Fatigue Inventory scores are 0.93 points lower 95% CI (-1.65, -0.20) in true acupuncture versus sham acupuncture and 2.12 points lower 95% C (-3.21, -1.04) in true acupuncture versus usual care. Six studies had low risk of bias (ROB) and 3 studies had a moderate ROB predominantly in blinding of participants, blinding of assessors and incomplete data outcomes. Among the 9 RCTs, 2 studies have reported the occurrence of minor adverse effects (spot bleeding and bruising) related to acupuncture treatment. No serious adverse reactions related to acupuncture were reported. CONCLUSION: The current literature review suggests that acupuncture has therapeutic potential in management of CRF for cancer survivors. Promotion of acupuncture in cancer care to manage CRF may improve the quality of life of cancer survivors.

Characterization hiPSC-derived neural progenitor cells and neurons to investigate the role of NOS1AP isoforms in human neuron dendritogenesis.

Abnormal dendritic arbor development has been implicated in a number of neurodevelopmental disorders, such as autism and Rett syndrome, and the neuropsychiatric disorder schizophrenia. Postmortem brain samples from subjects with schizophrenia show elevated levels of NOS1AP in the dorsolateral prefrontal cortex, a region of the brain associated with cognitive function. We previously reported that the long isoform of NOS1AP (NOS1AP-L), but not the short isoform (NOS1AP-S), negatively regulates dendrite branching in rat hippocampal neurons. To investigate the role that NOS1AP isoforms play in human dendritic arbor development, we adapted methods to generate human neural progenitor cells and neurons using induced pluripotent stem cell (iPSC) technology. We found that increased protein levels of either NOS1AP-L or NOS1AP-S decrease dendrite branching in human neurons at the developmental time point when primary and secondary branching actively occurs. Next, we tested whether pharmacological agents can decrease the expression of NOS1AP isoforms. Treatment of human iPSC-derived neurons with d-serine, but not clozapine, haloperidol, fluphenazine, or GLYX-13, results in a reduction in endogenous NOS1AP-L, but not NOS1AP-S, protein expression; however, d-serine treatment does not reverse decreases in dendrite number mediated by overexpression of NOS1AP isoforms. In summary, we demonstrate how an in vitro model of human neuronal development can help in understanding the etiology of schizophrenia and can also be used as a platform to screen drugs for patients.

Astaxanthin-Shifted Gut Microbiota Is Associated with Inflammation and Metabolic Homeostasis in Mice.

BACKGROUND: Astaxanthin is a red lipophilic carotenoid that is often undetectable in human plasma due to the limited supply in typical Western diets. Despite its presence at lower than detectable concentrations, previous clinical feeding studies have reported that astaxanthin exhibits potent antioxidant properties. OBJECTIVE: We examined astaxanthin accumulation and its effects on gut microbiota, inflammation, and whole-body metabolic homeostasis in wild-type C57BL/6 J (WT) and ß-carotene oxygenase 2 (BCO2) knockout (KO) mice. METHODS: Six-wk-old male and female BCO2 KO and WT mice were provided with either nonpurified AIN93M (e.g., control diet) or the control diet supplemented with 0.04% astaxanthin (wt/wt) ad libitum for 8 wk. Whole-body energy expenditure was measured by indirect calorimetry. Feces were collected from individual mice for short-chain fatty acid assessment. Hepatic astaxanthin concentrations and liver metabolic markers, cecal gut microbiota profiling, inflammation markers in colonic lamina propria, and plasma samples were assessed. Data were analyzed by 3-way ANOVA followed by Tukey's post hoc analysis. RESULTS: BCO2 KO but not WT mice fed astaxanthin had ∼10-fold more of this compound in liver than controls (P < 0.05). In terms of the microbiota composition, deletion of BCO2 was associated with a significantly increased abundance of Mucispirillum schaedleri in mice regardless of gender. In addition to more liver astaxanthin in male KO compared with WT mice fed astaxanthin, the abundance of gut Akkermansia muciniphila was 385% greater, plasma glucagon-like peptide 1 was 27% greater, plasma glucagon and IL-1ß were 53% and 30% lower, respectively, and colon NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation was 23% lower (all P < 0.05) in male KO mice than the WT mice. CONCLUSIONS: Astaxanthin affects the gut microbiota composition in both genders, but the association with reductions in local and systemic inflammation, oxidative stress, and improvement of metabolic homeostasis only occurs in male mice.

The Effects of Tai Chi and Qigong on Immune Responses: A Systematic Review and Meta-Analysis.

Background: Effective preventative health interventions are essential to maintain well-being among healthcare professionals and the public, especially during times of health crises. Several studies have suggested that Tai Chi and Qigong (TQ) have positive impacts on the immune system and its response to inflammation. The aim of this review is to evaluate the current evidence of the effects of TQ on these parameters. Methods: Electronic searches were conducted on databases (Medline, PubMed, Embase and ScienceDirect). Searches were performed using the following keywords: "Tai Chi or Qigong" and "immune system, immune function, immunity, Immun*, inflammation and cytokines". Studies published as full-text randomized controlled trials (RCTs) in English were included. Estimates of change in the levels of immune cells and inflammatory biomarkers were pooled using a random-effects meta-analysis where randomised comparisons were available for TQ versus active controls and TQ versus non-active controls. Results: Nineteen RCTs were selected for review with a total of 1686 participants and a range of 32 to 252 participants within the studies. Overall, a random-effects meta-analysis found that, compared with control conditions, TQ has a significant small effect of increasing the levels of immune cells (SMD, 0.28; 95% CI, 0.13 to 0.43, p = 0.00), I2 = 45%, but not a significant effect on reducing the levels of inflammation (SMD, -0.15; 95% CI, -0.39 to 0.09, p = 0.21), I2 = 85%, as measured by the systemic inflammation biomarker C-reactive protein (CRP) and cell mediated biomarker cytokines. This difference in results is due to the bidirectional regulation of cytokines. An overall risk of bias assessment found three RCTs with a low risk of bias, six RCTs with some concerns of bias, and ten RCTs with a high risk of bias. Conclusions: Current evidence indicates that practising TQ has a physiologic impact on immune system functioning and inflammatory responses. Rigorous studies are needed to guide clinical guidelines and harness the power of TQ to promote health and wellbeing.

The Inhibitory Properties of Ethanol Extracts of Some Culinary-Medicinal Mushrooms on the Secretion of Interleukin-8 and Vascular Endothelial Growth Factor by PC3 Cancer Cells.

Interleukin (IL)-8, a cytokine produced by immune and non-immune cells, induces angiogenesis via increased vascular endothelial growth factor (VEGF) secretion; both cytokines promote tumor growth. IL-8 and VEGF plasma levels correlate with prostate cancer severity, suggesting that therapeutic options aimed at their downregulation may modulate tumor growth. Available data suggest that Agaricus bisporus (white button mushroom [WBM]) extracts inhibit cancer cell proliferation through aromatase inhibition. However, the extent to which they affect IL-8 and VEGF remains to be elucidated. The aims of this study were to (1) investigate the antiproliferative properties of WBM, brown A. bisporus (portabella), and Lentinus edodes (shiitake mushroom) on PC3 cancer cells; (2) demonstrate that these properties are exerted through the regulation of both IL-8 and VEGF; and (3) determine the role of NFκB activation in the antiproliferative process of mushroom extracts. Cytokine secretion in the supernatant, NFκB activity, and cell proliferation were measured in PC3 cells incubated with 0-100 µg/mL of ethanol extracts of mushrooms. Mushroom extracts decreased IL-8 secretion and cell proliferation (P < .05), and also tended to decrease VEGF (P < .09). Decreased cell proliferation did not appear to result from cell death because trypan blue exclusion tests showed comparable cell viability among cultures. Mushroom extracts also decreased nuclear and total NFκB activity, and the ratio of nuclear to cytoplasmic activity (P < .05) suggesting altered translocation from the cytoplasm to the nucleus. Our data suggest that the three types of studied mushrooms may modulate tumor growth through inhibition of IL-8, VEGF, and NFκB pathways.

Montmorency tart cherry protects against age-related bone loss in female C57BL/6 mice and demonstrates some anabolic effects.

PURPOSE: Age-related bone loss is a consequence of endocrine and immune changes that disrupt bone remodeling. Functional foods (e.g., tart cherries) with antioxidant, anti-inflammatory and prebiotic activity can potentially counter this age-related phenomenon. The aim of this study was to determine if Montmorency tart cherry protects against early age-related bone loss and the culpable alterations in bone metabolism. METHODS: Female, 5-month-old, C57BL/6 mice were assigned to baseline or treatment groups: AIN-93M diet supplemented with 0, 1, 5, or 10% tart cherry for 90 days. Bone mineral density (BMD) and trabecular and cortical bone microarchitecture were assessed. Treatment effects on bone metabolism and regulators of bone formation, resorption and mineralization were determined. RESULTS: Mice consuming the 5% and 10% doses had higher vertebral and tibial BMD (p < 0.05) compared to controls. The age-related decrease in trabecular bone volume (BV/TV) of the distal femur was prevented with these doses. Vertebral trabecular BV/TV and cortical bone thickness of the femur mid-diaphysis were greater (p < 0.05) in the groups receiving the 5% and 10% cherry than the control diet. Notably, these improvements were significantly greater than the baseline controls, consistent with an anabolic response. Although no differences in systemic biomarkers of bone formation or resorption were detected at 90 days, local increases in Phex and decreases in Ppar-γ suggest a bone environment that supports increased mineralization. CONCLUSIONS: These findings demonstrate that cherry supplementation (5% and 10%) improves BMD and some indices of trabecular and cortical bone microarchitecture; these effects are likely attributed to increased bone mineralization.

Oral cannabinoid-rich THC/CBD cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting: a study protocol for a pilot and definitive randomised double-blind placebo-controlled trial (CannabisCINV).

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) remains an important issue for patients receiving chemotherapy despite guideline-consistent antiemetic therapy. Trials using delta-9-tetrahydrocannabinol-rich (THC) products demonstrate limited antiemetic effect, significant adverse events and flawed study design. Trials using cannabidiol-rich (CBD) products demonstrate improved efficacy and psychological adverse event profile. No definitive trials have been conducted to support the use of cannabinoids for this indication, nor has the potential economic impact of incorporating such regimens into the Australian healthcare system been established. CannabisCINV aims to assess the efficacy, safety and cost-effectiveness of adding TN-TC11M, an oral THC/CBD extract to guideline-consistent antiemetics in the secondary prevention of CINV. METHODS AND ANALYSIS: The current multicentre, 1:1 randomised cross-over, placebo-controlled pilot study will recruit 80 adult patients with any malignancy, experiencing CINV during moderate to highly emetogenic chemotherapy despite guideline-consistent antiemetics. Patients receive oral TN-TC11M (THC 2.5mg/CBD 2.5 mg) capsules or placebo capsules three times a day on day -1 to day 5 of cycle A of chemotherapy, followed by the alternative drug regimen during cycle B of chemotherapy and the preferred drug regimen during cycle C. The primary endpoint is the proportion of subjects attaining a complete response to CINV. Secondary and tertiary endpoints include regimen tolerability, impact on quality of life and health system resource use. The primary assessment tool is patient diaries, which are filled from day -1 to day 5. A subsequent randomised placebo-controlled parallel phase III trial will recruit a further 250 patients. ETHICS AND DISSEMINATION: The protocol was approved by ethics review committees for all participating sites. Results will be disseminated in peer-reviewed journals and at scientific conferences. DRUG SUPPLY: Tilray. PROTOCOL VERSION: 2.0, 9 June 2017. TRIAL REGISTRATION NUMBER: ANZCTR12616001036404; Pre-results.

Accreditation Standard Guideline Initiative for Tai Chi and Qigong Instructors and Training Institutions.

Evidence of the health and wellbeing benefits of Tai Chi and Qigong (TQ) have emerged in the past two decades, but TQ is underutilized in modern health care in Western countries due to lack of promotion and the availability of professionally qualified TQ instructors. To date, there are no government regulations for TQ instructors or for training institutions in China and Western countries, even though TQ is considered to be a part of Traditional Chinese medicine that has the potential to manage many chronic diseases. Based on an integrative health care approach, the accreditation standard guideline initiative for TQ instructors and training institutions was developed in collaboration with health professionals, integrative medicine academics, Tai Chi and Qigong master instructors and consumers including public safety officers from several countries, such as Australia, Canada, China, Germany, Italy, Korea, Sweden and USA. In this paper, the rationale for organizing the Medical Tai Chi and Qigong Association (MTQA) is discussed and the accreditation standard guideline for TQ instructors and training institutions developed by the committee members of MTQA is presented. The MTQA acknowledges that the proposed guidelines are broad, so that the diversity of TQ instructors and training institutions can be integrated with recognition that these guidelines can be developed with further refinement. Additionally, these guidelines face challenges in understanding the complexity of TQ associated with different principles, philosophies and schools of thought. Nonetheless, these guidelines represent a necessary first step as primary resource to serve and guide health care professionals and consumers, as well as the TQ community.

Trends in the surgical treatment of benign prostatic hyperplasia in a tertiary hospital.

BACKGROUND: To assess current treatment trends and perioperative outcomes of transurethral resection of the prostate (TURP) and photoselective vaporization of the prostate (PVP) in a tertiary institution. METHODS: We prospectively collected a database of all patients undergoing TURP and PVP for benign prostatic hyperplasia (BPH) at a tertiary hospital between January 2011 and December 2013. Patient characteristics such as length of stay, readmission, anticoagulation status, American Society of Anesthesiologists (ASA) score and need for blood transfusion were recorded and analysed. RESULTS: In total, 560 cases were included: 204 (36.4%) underwent TURP and 356 (63.6%) PVP. Patients undergoing PVP had higher ASA scores (P < 0.001) and were more frequently on continuing anticoagulant therapy (P < 0.001). With regards to non-aspirin/asasantin coagulation therapy, 61 (17.1%) patients underwent PVP with their anticoagulants continued while no patients who received TURP continued anticoagulation. Blood transfusion percentages were similar at 1.0% for TURP and 1.7% for PVP but readmission proportions were higher after PVP (32 patients, 9.0%) compared to TURP (10 patients, 4.9%). These differences were attenuated when excluding patients continuing anticoagulation during the procedure. CONCLUSION: At our institution, the use of PVP has been increasing on a year-by-year basis. The results of the current study demonstrated that PVP is safe in patients with increased anaesthetic risk or on active anticoagulation when compared to traditional TURP. While this makes PVP an attractive alternative to TURP in high-risk anticoagulated patients, these patients may have complex post-discharge issues that should be addressed during the informed consent process.

Acupuncture in Oncology: The Effectiveness of Acupuncture May Not Depend on Needle Retention Duration.

BACKGROUND: Guidelines surrounding optimum needle retention duration in acupuncture have not been established, despite a growing evidence base for acupuncture over recent decades. This retrospective study explored the effect of varying acupuncture needle retention durations in cancer patients. METHOD: Patients received either 2 (n = 35), 10 (n = 53), or 20 minutes (n = 54) of acupuncture once a week for 6 weeks. Outcomes of anxiety and depression, stress, fatigue, and quality of life (QOL), with the Hospital Anxiety and Depression Scale, Perceived Stress Scale, Functional Assessment of Cancer Therapy-Fatigue, and European Organization for Research and Treatment of Cancer Quality of Life, were measured at baseline and at 6 weeks following the intervention. RESULTS: The mean age of participants was 58 years (n = 152). The majority were female, diagnosed with breast cancer. Depression, stress, fatigue, and QOL were significantly improved in all 3 groups at 6 weeks postintervention. No significant differences in all outcomes were found between the 3 groups (≤2 vs 10 minutes vs 20 minutes). There were no differences with the satisfaction of the acupuncture services and perceived efficacy of acupuncture among the 3 groups. More than 95% of participants indicated that they would recommend acupuncture to other cancer patients, friends, and their family members. CONCLUSION: The efficacy of acupuncture may not only depend on needle retention duration, but may also be associated with multiple factors. Considering the limitations of this study design, robust randomized controlled studies are warranted to confirm the findings.

Ablation of ß,ß-carotene-9',10'-oxygenase 2 remodels the hypothalamic metabolome leading to metabolic disorders in mice.

ß,ß-Carotene-9',10'-oxygenase 2 (BCO2) is a protein localized to the inner membrane of mitochondria. It was initially discovered as an enzyme that catalyzes the asymmetric cleavage of carotenoids. Systemic depletion of BCO2 causes increased food intake and impaired hepatic lipid metabolism in mice. The aim of this current study was to determine the extent to which BCO2 exerts its role in hypothalamic nutrient metabolism and feeding behavior through remodeling the hypothalamic metabolome in mice. Male BCO2 knockout (KO) and the isogenic wild-type 129S6 (WT) mice at 6 weeks of age were used for metabolic and cytokine and hypothalamic metabolomics and biochemical analysis. Compared to the WT, BCO2 KO mice exhibited widespread disruptions in metabolism and metabolite homeostasis, an increase in fasting blood glucose, a decrease in circulating glucagon and leptin, an elevation of plasma interleukin 1 beta and tumor necrosis factor alpha, and impaired AMP-activated protein kinase signaling. The global hypothalamic metabolomic results revealed that depletion of BCO2 resulted in striking metabolic changes, including suppression of long-chain fatty acids transport into mitochondria, inhibition of the metabolism of dipeptides and sulfur-containing amino acids, and stimulation of local oxidative stress and inflammation in the hypothalamus of BCO2 KO mice. These findings suggest that BCO2 regulates hypothalamic mitochondrial function, nutrient metabolism, and local oxidative stress and inflammation. Complex interplay between the hormone signaling and impaired lipid and glucose metabolism could account for initiation of oxidative stress, inflammation and eventual metabolic disorders in BCO2 KO mice.

Factors affecting whether or not cancer patients consider using acupuncture.

OBJECTIVE: To explore the factors associated with utilisation of an acupuncture service in a tertiary oncology setting in an Australian public hospital. METHOD: Cancer patients attending oncology clinics at a university teaching hospital were invited to participate in the evaluation of acupuncture services from June 2014 to May 2015. Patients had a prior diagnosis of cancer (albeit at different stages) and were planning to receive, or were already receiving, systemic and/or radiation cancer treatment. RESULTS: The majority (81%) of participants indicated that they would consider the use of acupuncture during their cancer treatment. The most common reasons given for not considering acupuncture included adequate control of symptoms already with medical treatment, inconvenient clinic timing, and needle phobia. The main reasons given for considering acupuncture use included its perceived capability of reducing fatigue, boosting energy levels, improving immune function, and reducing pain and anxiety. Patients considering acupuncture use also demonstrated significantly higher levels of stress (p<0.001), anxiety and depression (p<0.001), fatigue (p<0.001), and lower global quality of life (p<0.01) compared to those who were not considering acupuncture. CONCLUSIONS: The findings show that demand for acupuncture by cancer patients is high. A substantial proportion of cancer patients intend to use acupuncture to manage cancer and/or cancer treatment-related symptoms. Discussion with patients about acupuncture and other complementary therapies during the consultation may improve cancer care.

Mango Supplementation Modulates Gut Microbial Dysbiosis and Short-Chain Fatty Acid Production Independent of Body Weight Reduction in C57BL/6 Mice Fed a High-Fat Diet.

BACKGROUND: High-fat (HF) diet-induced obesity is associated with changes in the gut microbiota. Fiber and other bioactive compounds in plant-based foods are suggested to prevent gut dysbiosis brought on by HF feeding. Mango is high in fiber and has been reported to have anti-obesogenic, hypoglycemic, and immunomodulatory properties. OBJECTIVES: We investigated the effects of freeze-dried mango pulp combined with an HF diet on the cecal microbial population and its relation to body composition, lipids, glucose parameters, short-chain fatty acid (SCFA) production, and gut inflammatory markers in a mouse model of diet-induced obesity. METHODS: Six-wk-old male C57BL/6 mice were randomly assigned to 1 of 4 dietary treatment groups: control (AIN-93M, 10% fat kcal), HF (60% fat kcal), and HF + 1% or 10% mango (HF+1%M or HF+10%M, wt:wt) for 12 wk. The cecal microbial population was assessed by use of 16S rDNA sequencing. Body composition, plasma glucose and lipids, cecal and fecal SCFAs, and mRNA abundance of inflammatory markers in the ileum and colonic lamina propria were assessed. RESULTS: Compared with the control group, HF feeding significantly reduced (P < 0.05) 1 operational taxonomic unit (OTU) of the genus Bifidobacteria (64-fold) and 5 OTUs of the genus Akkermansia (≥16-fold). This reduction was prevented in the HF+10%M group, members of which had 10% higher final body weight compared with the HF group (P = 0.01) and similar fasting blood glucose concentrations (P = 0.24). The HF+10%M group had 135% (P = 0.004) and 133% (P < 0.0001) greater fecal acetic and n-butyric acids concentrations than the HF group, suggesting greater microbial fermentation. Furthermore, a 59% greater colonic interleukin 10 (Il10) gene expression was observed in the HF+10%M group than in the HF group (P = 0.048), indicating modulation of gut inflammation. The HF+1%M group generally did not differ from the HF group. CONCLUSIONS: The addition of mango to an HF diet modulated the gut microbiota and production of SCFAs in C57BL/6 mice; these changes may improve gut tolerance to the insult of an HF diet.

Adjuvant Iodine (131) Lipiodol after Resection of Hepatocellular Carcinoma.

Background. Survival after liver resection for HCC is compromised by a high rate of intrahepatic recurrence. Adjuvant treatment with a single, postoperative dose of intra-arterial I(131) lipiodol has shown promise, as a means of prolonging disease-free survival (DFS). Methodology. DFS and overall survival (OS) after a single dose of postoperative I(131) lipiodol were compared to liver resection alone, for treatment of hepatocellular carcinoma (HCC). Data were collected retrospectively for patients who had a curative resection for HCC between December 1993 and September 2011. Seventy-two patients were given I(131) lipiodol after surgery and 70 patients had surgery alone. Results. The DFS at 1, 3, and 5 years was 72%, 43%, and 26% in the surgery group and 70%, 39%, and 29% in the adjuvant I(131) lipiodol group (p = 0.75). The 1-, 3-, and 5-year OS was 83%, 64%, and 52% in the surgery group and 96%, 72%, and 61% in the adjuvant I(131) lipiodol group (p = 0.16). Conclusion. This retrospective study has found no significant benefit to survival, after adjuvant treatment with I(131) lipiodol.

Towards depersonalized abacavir therapy: chemical modification eliminates HLA-B*57 : 01-restricted CD8+ T-cell activation.

OBJECTIVE: Exposure to abacavir is associated with T-cell-mediated hypersensitivity reactions in individuals carrying human leukocyte antigen (HLA)-B57 : 01. To activate T cells, abacavir interacts directly with endogenous HLA-B57 : 01 and HLA-B57 : 01 expressed on the surface of antigen presenting cells. We have investigated whether chemical modification of abacavir can produce a molecule with antiviral activity that does not bind to HLA-B57 : 01 and activate T cells. DESIGN: An interdisciplinary laboratory study using samples from human donors expressing HLA-B57 : 01. Researchers were blinded to the analogue structures and modelling data. METHODS: Sixteen 6-amino substituted abacavir analogues were synthesized. Computational docking studies were completed to predict capacity for analogue binding within HLA-B57 : 01. Abacavir-responsive CD8 clones were generated to study the association between HLA-B57 : 01 analogue binding and T-cell activation. Antiviral activity and the direct inhibitory effect of analogues on proliferation were assessed. RESULTS: Major histocompatibility complex class I-restricted CD8 clones proliferated and secreted IFNγ following abacavir binding to surface and endogenous HLA-B57 : 01. Several analogues retained antiviral activity and showed no overt inhibitory effect on proliferation, but displayed highly divergent antigen-driven T-cell responses. For example, abacavir and N-propyl abacavir were equally potent at activating clones, whereas the closely related analogues N-isopropyl and N-methyl isopropyl abacavir were devoid of T-cell activity. Docking abacavir analogues to HLA-B57 : 01 revealed a quantitative relationship between drug-protein binding and the T-cell response. CONCLUSION: These studies demonstrate that the unwanted T-cell activity of abacavir can be eliminated whilst maintaining the favourable antiviral profile. The in-silico model provides a tool to aid the design of safer antiviral agents that may not require a personalized medicines approach to therapy.