Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis.

BACKGROUND: Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many studies have confirmed the symptoms similar to ME/CFS in the recovered individuals. To investigate the virus-related etiopathogenesis of ME/CFS, we conducted a systematic assessment of viral infection frequency in ME/CFS patients. METHODS: We conducted a comprehensive search of PubMed and the Cochrane Library from their inception through December 31, 2022, using selection criteria of viral infection prevalence in ME/CFS patients and controls. Subsequently, we performed a meta-analysis to assess the extent of viral infections' contribution to ME/CFS by comparing the odds ratio between ME/CFS patients and controls (healthy and/or diseased). RESULTS: Finally, 64 studies met our eligibility criteria regarding 18 species of viruses, including a total of 4971 ME/CFS patients and 9221 control subjects. The participants included healthy subjects and individuals with one of 10 diseases, such as multiple sclerosis or fibromyalgia. Two DNA viruses (human herpes virus (HHV)-7 and parvovirus B19, including their co-infection) and 3 RNA viruses (borna disease virus (BDV), enterovirus and coxsackie B virus) showed odds ratios greater than 2.0 compared with healthy and/or diseased subjects. Specifically, BDV exceeded the cutoff with an odds ratio of ≥ 3.47 (indicating a "moderate association" by Cohen's d test) compared to both healthy and diseased controls. CONCLUSION: This study comprehensively evaluated the risk of viral infections associated with ME/CFS, and identified BDV. These results provide valuable reference data for future studies investigating the role of viruses in the causation of ME/CFS.

Impact of annealing temperature on the remanent polarization and tunneling electro-resistance of ferroelectric Al-doped HfOx tunnel junction memory.

The ferroelectric characteristics of a metal-ferroelectric-metal (MFM) ferroelectric tunneling junction (FTJ) capacitor device are investigated herein. The device consists of an aluminum-doped hafnium oxide (HAO) insulator sandwiched between tungsten (W) and titanium nitride (TiN) metal electrodes. Rapid thermal annealing (RTA) is performed for 20 s under a nitrogen atmosphere at temperatures of 750 °C, 800 °C, and 850 °C to find that ferroelectricity with a large remanent polarization (Pr) of 41.28 µC cm-2 can be obtained at the optimum annealing temperature of 800 °C. The presence of ferroelectricity is confirmed by polarization-switching positive-up-negative-down (PUND) measurements and by the hysteric polarization-voltage (P-V) loop. All devices exhibit excellent reliability, with an endurance of up to ∼106 cycles and long retention characteristics. In addition, the interfacial paraelectric capacitance (Ci) values of the three HAO FTJs are investigated via pulse-switching measurements. The results indicate that the HAO film annealed at 800 °C for 20 s exhibits an excellent tunneling electro-resistance (TER) ratio of 186% and this is attributed to the extra paraelectric layer formed between the ferroelectric layer and the bottom electrode. The detailed findings of this study are expected to assist in the development of hafnium oxide-based ferroelectric non-volatile memory applications.

Comparison of assessment scores for fatigue between multidimensional fatigue inventory (MFI-K) and modified chalder fatigue scale (mKCFQ).

BACKGROUND: Because of the absence of biological parameters for fatigue, appropriate instruments for assessing the degree of fatigue are important in the diagnosis and management of people complaining of fatigue-like symptoms. This study statistically analyzed the fatigue scores from two typical questionnaire-based instruments: the Korean version of the Multidimensional Fatigue Inventory (MFI-K) and the modified Chalder Fatigue Scale (mKCFQ). METHODS: Seventy participants (males n = 40, females n = 30, median age 48 years old, range of 25-67) were grouped into three groups ('mild' = 20, 'moderate' = 42, and 'severe' = 8) according to self-reported fatigue levels using a 7-point Likert scale. The similarities and differences between two instrument-derived scores were analyzed using correlations (r) and multidimensional scaling (MDS). RESULTS: The total scores of the two assessments were significantly correlated (r = 75%, p < 0.001), as were the subscores ('Total Physical fatigue': r = 76%, p < 0.001, 'Total Mental fatigue': r = 56%, p < 0.001). Relative overestimation of the MFI-K (45.8 ± 11.3) compared to the mKCFQ (36.1 ± 16.2) was observed, which was especially prominent in the 'mild' group. The scores of the three groups were more easily distinguished by the mKCFQ than by the MFI-K. In terms of the five dimension scores, we found a higher correlation of the two assessments for 'general fatigue' (r = 79%, p < 0.001) and 'physical fatigue' (r = 66%, p < 0.001) than for the reductions in 'motivation' (r = 41%, p < 0.01) and 'activity' (r = 26%, p > 0.05). CONCLUSIONS: Our results may indicate the usefulness of the two instruments, especially for the physical symptoms of fatigue ('general' and 'physical' fatigue). Furthermore, the MFI-K may be useful for conditions of moderate-to-severe fatigue, such as chronic fatigue syndrome, but the mKCFQ may be useful for all spectra of fatigue, including in subhealthy people.

Nationwide epidemiological characteristics of chronic fatigue syndrome in South Korea.

BACKGROUND: Chronic fatigue syndrome (CFS) is a long-term disabling illness accompanied by medically unexplained fatigue. This study aimed to explore the epidemiological characteristics of CFS in South Korea. METHODS: Using the nationwide medical records provided by the Korean Health Insurance Review & Assessment Service (HIRA), we analyzed the entire dataset for CFS patients diagnosed by physicians in South Korea from January 2010 to December 2020. RESULTS: The annual mean incidence of CFS was estimated to be 44.71 ± 6.10 cases per 100,000 individuals [95% CI: 40.57, 48.76], and the prevalence rate was 57.70 ± 12.20 cases per 100,000 individuals [95% CI: 49.40, 65.79]. These two rates increased by 1.53- and 1.94-fold from 2010 to 2020, respectively, and showed an increasing trend with aging and an approximately 1.5-fold female predominance. CONCLUSIONS: This study is the first to report the nationwide epidemiological features of CFS, which reflects the clinical reality of CFS diagnosis and care in South Korea. This study will be a valuable reference for studies of CFS in the future.

Review of case definitions for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with unknown causes. From the perspectives on the etiology and pathophysiology, ME/CFS has been labeled differently, which influenced changes in case definitions and terminologies. This review sought to feature aspects of the history, developments, and differential symptoms in the case definitions. METHODS: A search was conducted through PubMed published to February 2020 using the following search keywords: case definition AND chronic fatigue syndrome [MeSH Terms]. All reference lists of the included studies were checked. Of the included studies, the number of citations and the visibility in the literatures of the definitions were considered for comparisons of the criteria. RESULTS: Since the first 'ME' case definition was developed in 1986, 25 case definitions/diagnostic criteria were created based on three conceptual factors (etiology, pathophysiology, and exclusionary disorders). These factors can be categorized into four categories (ME, ME/CFS, CFS, and SEID) and broadly characterized according to primary disorder (ME-viral, CFS-unknown, ME/CFS-inflammatory, SEID-multisystemic), compulsory symptoms (ME and ME/CFS-neuroinflammatory, CFS and SEID-fatigue and/or malaise), and required conditions (ME-infective agent, ME/CFS, CFS, SEID-symptoms associated with fatigue, e.g., duration of illness). ME and ME/CFS widely cover all symptom categories, while CFS mainly covers neurologic and neurocognitive symptoms. Fatigue, cognitive impairment, PEM, sleep disorder, and orthostatic intolerance were the overlapping symptoms of the 4 categories, which were included as SEID criteria. CONCLUSIONS: This study comprehensively described the journey of the development of case definitions and compared the symptom criteria. This review provides broader insights and explanations to understand the complexity of ME/CFS for clinicians and researchers.

Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) has been emerging as a significant health issue worldwide. This study aimed to systemically assess the prevalence of CFS/ME in various aspects of analyses for precise assessment. METHODS: We systematically searched prevalence of CFS/ME from public databases from 1980 to December 2018. Data were extracted according to 7 categories for analysis: study participants, gender and age of the participants, case definition, diagnostic method, publication year, and country of the study conducted. Prevalence data were collected and counted individually for studies adopted various case definitions. We analyzed and estimated prevalence rates in various angles: average prevalence, pooled prevalence and meta-analysis of all studies. RESULTS: A total of 1291 articles were initially identified, and 45 articles (46 studies, 56 prevalence data) were selected for this study. Total 1085,976 participants were enrolled from community-based survey (540,901) and primary care sites (545,075). The total average prevalence was 1.40 ± 1.57%, pooled prevalence 0.39%, and meta-analysis 0.68% [95% CI 0.48-0.97]. The prevalence rates were varied by enrolled participants (gender, study participants, and population group), case definitions and diagnostic methods. For example, in the meta-analysis; women (1.36% [95% CI 0.48-0.97]) vs. men (0.86% [95% CI 0.48-0.97]), community-based samples (0.76% [95% CI 0.53-1.10]) vs. primary care sites (0.63% [95% CI 0.37-1.10]), adults ≥ 18 years (0.65% [95% CI 0.43-0.99]) vs. children and adolescents < 18 years (0.55% [95% CI 0.22-1.35]), CDC-1994 (0.89% [95% CI 0.60-1.33]) vs. Holmes (0.17% [95% CI 0.06-0.49]), and interviews (1.14% [95% CI 0.76-1.72]) vs. physician diagnosis (0.09% [95% CI 0.05-0.13]), respectively. CONCLUSIONS: This study comprehensively estimated the prevalence of CFS/ME; 0.89% according to the most commonly used case definition CDC-1994, with women approximately 1.5 to 2 folds higher than men in all categories. However, we observed the prevalence rates are widely varied particularly by case definitions and diagnostic methods. An objective diagnostic tool is urgently required for rigorous assessment of the prevalence of CFS/ME.

PINK1 positively regulates HDAC3 to suppress dopaminergic neuronal cell death.

Deciphering the molecular basis of neuronal cell death is a central issue in the etiology of neurodegenerative diseases, such as Parkinson's and Alzheimer's. Dysregulation of p53 levels has been implicated in neuronal apoptosis. The role of histone deacetylase 3 (HDAC3) in suppressing p53-dependent apoptosis has been recently emphasized; however, the molecular basis of modulation of p53 function by HDAC3 remains unclear. Here we show that PTEN-induced putative kinase 1 (PINK1), which is linked to autosomal recessive early-onset familial Parkinson's disease, phosphorylates HDAC3 at Ser-424 to enhance its HDAC activity in a neural cell-specific manner. PINK1 prevents H2O2-induced C-terminal cleavage of HDAC3 via phosphorylation of HDAC3 at Ser-424, which is reversed by protein phosphatase 4c. PINK1-mediated phosphorylation of HDAC3 enhances its direct association with p53 and causes subsequent hypoacetylation of p53. Genetic deletion of PINK1 partly impaired the suppressive role of HDAC3 in regulating p53 acetylation and transcriptional activity. However, depletion of HDAC3 fully abolished the PINK1-mediated p53 inhibitory loop. Finally, ectopic expression of phosphomometic-HDAC3(S424E) substantially overcomes the defective action of PINK1 against oxidative stress in dopaminergic neuronal cells. Together, our results uncovered a mechanism by which PINK1-HDAC3 network mediates p53 inhibitory loop in response to oxidative stress-induced damage.

Comparison of integrative medicine centers in the USA and Germany: a mixed method study.

PURPOSE: Integrative medicine (IM) has received increasing attention since the 1990s, but few studies have explored the key factors of the IM model in health care. This study aimed to describe the IM model in leading centers operating in the USA and Germany. METHODS: A 28-item structured survey and semi-structured interviews were conducted in six centers providing integrative medicine in the USA and Germany, and were analyzed using a convergent mixed-method approach. RESULTS: The elements in common across all six centers were the following: (1) involvement of general physicians (GP) in delivering complementary and alternative medicine (CAM) services; (2) requirement for GP or medical referral or recommendation to CAM services; (3) involvement of an integrative physician (IP) as a "gatekeeper"; (4) focus on research, education, and clinical practice; and (5) ongoing academic activities. The key elements differentiating the two countries were the following: (1) level of requirements for GP referral to CAM services; (2) differences in IM service delivery, including treatment modalities used; (3) accessibility of CAM services to patients; (4) interaction between team members and patients; (5) perception of CAM/IM; and (6) perception of patient-centered care. Themes underpinning these elements are the following: cultural aspects in conceptualizing IM health care; communication within IM programs; and resource availability for delivering IM services, which impacts patient engagement and team collaboration in the IM framework. CONCLUSIONS: Delivering IM health care requires a model of care that encourages interaction between all stakeholders. Developing a comprehensive conceptual framework to support IM practice is required to facilitate efficient and safe patient care.

Demethylation of the human eotaxin-3 gene promoter leads to the elevated expression of eotaxin-3.

DNA demethylation has been primarily studied in the context of development biology, cell fate, and cancer, with less attention on inflammation. In this article, we investigate the association between DNA methylation and production of the chemoattractant cytokine eotaxin-3 in the tissue of patients with allergic disease. Regions of the human eotaxin-3 promoter were found to be hypomethylated in primary epithelial cells obtained from allergic tissue compared with normal control tissue. The demethylation of a specific CpG site (designated CpG 2), which is juxtaposed to a key cAMP-responsive element site, was significantly demethylated in patient-derived compared with normal control tissue-derived epithelial cells. Levels of methylation at CpG 2 inversely correlated with basal and IL-13-induced eotaxin-3 gene expression. Conversely, global inhibition of methylation with 5-azacytidine promoted eotaxin-3 production in association with decreasing CpG 2 methylation. In addition, the basal and IL-13-induced eotaxin-3 transcriptional activity was suppressed by promoter methylation using a methylation-free in vitro system. Furthermore, EMSAs demonstrated that the attachment of CREB binding protein and activating transcription factor 2 (ATF-2) to the cAMP-responsive element site was methylation dependent. Taken together, these data identify a contributory role for DNA methylation in regulating eotaxin-3 production in human allergic inflammation.

MiR-223 deficiency increases eosinophil progenitor proliferation.

Recently, microRNAs have been shown to be involved in hematopoietic cell development, but their role in eosinophilopoiesis has not yet been described. In this article, we show that miR-223 is upregulated during eosinophil differentiation in an ex vivo bone marrow-derived eosinophil culture system. Targeted ablation of miR-223 leads to an increased proliferation of eosinophil progenitors. We found upregulation of a miR-223 target gene, IGF1R, in the eosinophil progenitor cultures derived from miR-223(-/-) mice compared with miR-223(+/+) littermate controls. The increased proliferation of miR-223(-/-) eosinophil progenitors was reversed by treatment with an IGF1R inhibitor (picropodophyllin). Whole-genome microarray analysis of differentially regulated genes between miR-223(+/+) and miR-223(-/-) eosinophil progenitor cultures identified a specific enrichment in genes that regulate hematologic cell development. Indeed, miR-223(-/-) eosinophil progenitors had a delay in differentiation. Our results demonstrate that microRNAs regulate the development of eosinophils by influencing eosinophil progenitor growth and differentiation and identify a contributory role for miR-223 in this process.

MicroRNA-21 limits in vivo immune response-mediated activation of the IL-12/IFN-gamma pathway, Th1 polarization, and the severity of delayed-type hypersensitivity.

An altered balance between Th1 and Th2 cytokines is responsible for a variety of immunoinflammatory disorders such as asthma, yet the role of posttranscriptional mechanisms, such as those mediated by microRNAs (miRs), in adjusting the relative magnitude and balance of Th cytokine expression have been largely unexplored. In this study, we show that miR-21 has a central role in setting a balance between Th1 and Th2 responses to Ags. Targeted ablation of miR-21 in mice led to reduced lung eosinophilia after allergen challenge, with a broadly reprogrammed immunoactivation transcriptome and significantly increased levels of the Th1 cytokine IFN-γ. Biological network-based transcriptome analysis of OVA-challenged miR-21(-/-) mice identified an unexpected prominent dysregulation of IL-12/IFN-γ pathways as the most significantly affected in the lungs, with a key role for miR-21 in IFN-γ signaling and T cell polarization, consistent with a functional miR-21 binding site in IL-12p35. In support of these hypotheses, miR-21 deficiency led dendritic cells to produce more IL-12 after LPS stimulation and OVA-challenged CD4(+) T lymphocytes to produce increased IFN-γ and decreased IL-4. Further, loss of miR-21 significantly enhanced the Th1-associated delayed-type hypersensitivity cutaneous responses. Thus, our results define miR-21 as a major regulator of Th1 versus Th2 responses, defining a new mechanism for regulating polarized immunoinflammatory responses.

Incidence Rate of Bee Venom Acupuncture Related Anaphylaxis: A Systematic Review.

BACKGROUND: Bee venom acupuncture (BVA) is an effective treatment method for various diseases. Bee venom, however, can cause adverse effects, even rarely including life-threatening anaphylaxis, so safety-related evidence is required. In this study, we systematically estimated the incidence rate of anaphylaxis in response to BVA. METHODS: We searched eight databases (MEDLINE (Pubmed), EMBASE, Cochrane Central Register of Controlled, KISS, KMBASE, Koreamed, OASIS, and NDSL) and systematically reviewed the articles that met the inclusion/exclusion criteria. RESULTS: Among 225 potentially relevant articles, 49 were selected for this study. The overall incidence rate of anaphylaxis in response to BVA was 0.045% (95% CI 0.028-0.062). Women (0.083%, 95% CI 0.010-0.157) showed a higher incidence rate than men (0.019%, 95% CI -0.018 to 0.055), while the incidence for patients who had a skin test conducted (0.041%, 95% CI 0.011-0.072) was not significantly different compared to that obtained for patients for which there was no information about a skin test (0.047%, 95% CI 0.026-0.067). The publication year affected the incidence rate: it was highest before 1999 (1.099%, 95% CI -1.043 to 3.241), lower between 2000 and 2009 (0.049%, 95% CI 0.025-0.073), and lowest between 2010 and 2021 (0.037% 95% CI 0.014-0.060). CONCLUSIONS: In this study, we provide reference data about risk size and factors of BVA-related anaphylaxis, which is essentially required for BVA application in clinics.

Hippocampus-dependent spatial learning and memory are impaired in growth hormone-deficient spontaneous dwarf rats.

Growth hormone (GH)/insulin-like growth factor-I deficiencies are known to cause alterations in brain development resulting in impairment of cognitive function. In order to investigate the behavioral phenotype of GH-deficient spontaneous dwarf rats (SDRs), we examined the behavior of the SDRs in the Morris water maze and Y-maze tasks. The SDRs showed severe deficits in spatial learning and memory compared to normal rats. The possibility that the cognitive impairment is associated with alteration of neurotransmitter systems was examined histologically following completion of the behavioral tests, using choline acetyltransferase (ChAT), vesicular glutamate transporter 1 (VGlut1) and glutamic acid decarboxylase (GAD6) immunohistochemistry as markers. In the SDRs the number of ChAT-stained basal forebrain cholinergic neurons was decreased. ChAT staining was also decreased in the hippocampus, one of the target areas of basal forebrain cholinergic neurons. Next, we examined the number of glutamatergic and GABAergic boutons in the hippocampal molecular layer and found a significant reduction in the density of VGlut1+ boutons and an increase in GAD6+ profiles, leading to a significantly reduced ratio in glutamatergic/GABAergic synapses. Finally, the number of newly generated cells in the subgranular zone of the hippocampus was significantly lower than in normal rats. Taken together, our data suggest that GH is an important regulator of hippocampus-dependent spatial learning and memory. The behavioral deficits in the SDRs may be explained by altered basal forebrain cholinergic innervation, imbalance in hippocampal glutamatergic/GABAergic synapses, and decreased neurogenesis in the hippocampus.

Prevalence of Chronic Fatigue Syndrome (CFS) in Korea and Japan: A Meta-Analysis.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness accompanied by fatigue unsolved by rest. However, ME/CFS is a poorly understood illness that lacks a universally accepted pathophysiology and treatment. A lack of CFS-related studies have been conducted in Asian countries. This study aimed to estimate and compare the prevalence of ME/CFS in Korea and Japan and conducted a meta-analysis. METHODS: We searched PubMed, EMBASE, Cochrane, and KMBASE for population-based prevalence studies of the two countries and synthesized the data according to the Fukuda case definition. RESULTS: Of the eight studies (five in Korea, three in Japan) included, the total prevalence rate of Korean studies was 0.77% (95% CI 0.34-1.76), and 0.76% (95% CI 0.46-1.25) for the Japanese studies. The prevalence rate in females was approximately two-fold higher than males in Korean studies (1.31% female vs. 0.60% male), while the gender difference was less obvious in Japanese studies (0.76% female vs. 0.65% male). CONCLUSIONS: Further epidemiology studies on the female ME/CFS prevalence rate between countries may be required.

The Prospects of the Two-Day Cardiopulmonary Exercise Test (CPET) in ME/CFS Patients: A Meta-Analysis.

BACKGROUND: The diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is problematic due to the lack of established objective measurements. Postexertional malaise (PEM) is a hallmark of ME/CFS, and the two-day cardiopulmonary exercise test (CPET) has been tested as a tool to assess functional impairment in ME/CFS patients. This study aimed to estimate the potential of the CPET. METHODS: We reviewed studies of the two-day CPET and meta-analyzed the differences between ME/CFS patients and controls regarding four parameters: volume of oxygen consumption and level of workload at peak (VO2peak, Workloadpeak) and at ventilatory threshold (VO2@VT, Workload@VT). RESULTS: The overall mean values of all parameters were lower on the 2nd day of the CPET than the 1st in ME/CFS patients, while it increased in the controls. From the meta-analysis, the difference between patients and controls was highly significant at Workload@VT (overall mean: -10.8 at Test 1 vs. -33.0 at Test 2, p < 0.05), which may reflect present the functional impairment associated with PEM. CONCLUSIONS: Our results show the potential of the two-day CPET to serve as an objective assessment of PEM in ME/CFS patients. Further clinical trials are required to validate this tool compared to other fatigue-inducing disorders, including depression, using well-designed large-scale studies.

The absence of the clathrin-dependent endocytosis in rod bipolar cells of the FVB/N mouse retina.

The high rate of exocytosis at the ribbon synapses is balanced by following compensatory endocytosis. Unlike conventional synaptic terminals where clathrin-mediated endocytosis (CME) is a predominant mechanism for membrane retrieval, CME is thought to be only a minor mechanism of endocytosis at the retinal ribbon synapses, but CME is present there and it works. We examined the clathrin expression in the FVB/N rd1 mouse, which is an animal model of retinitis pigmentosa. The broadly distributed pattern of clathrin immunoreactivity in the inner plexiform layer was similar in both the control and FVB/N mouse retinas, but the immunoreactive punta within the rod bipolar axon terminals located in the proximal IPL were decreased in number and reduced in size at postnatal days 14 and they came to disappear at postnatal days 21. This preferential decrease of the clathrin expression at ribbon synapses in the rod bipolar cell axon terminals of the FVB/N mouse retina demonstrates another plastic change after photoreceptor degeneration and this suggests that clathrin may be important for normal synaptic function at the rod bipolar ribbon synapses in the mammalian retina.

Identification and characterization of SMI32-immunoreactive amacrine cells in the mouse retina.

Mammalian neurons express the neural intermediate filament protein neurofilament (NF). In the retina, NFs have been detected primarily in the axons and processes of retinal ganglion and horizontal cells. We found an amacrine cell type that was immunolabeled with an antibody against SMI32, a non-phosphorylated epitope on neurofilament proteins of high molecular weight, in the mouse retina. This type of amacrine cell was non-randomly distributed, and these cells exhibited a central-peripheral density gradient. Most of these cells co-expressed GABA and ChAT, but not glycine or any other amacrine cell marker. These results suggest that some SMI32-immunoreactive amacrine cells belong to a GABAergic population, and that SMI32 can therefore be used as a marker for a subset of amacrine cells in addition to ganglion cells and horizontal cells in the mouse retina.

Mixed Method Study to Investigate Models of Australian Integrative Oncology.

OBJECTIVES: This study explored the models of services and experiences of coordinators and directors engaged in providing complementary and alternative medicine (CAM) or integrative medicine (IM) in oncology centers throughout Australia. DESIGN: Fourteen leaders of IM programs from ten systematically selected Australian oncology centers were interviewed. Participants described their center's service model. Interview transcripts were thematically analyzed to identify underlying themes. Results were merged using the matrix technique for triangulation. RESULTS: Ten oncology centers were reviewed. IM was perceived in the context of supportive care and wellness. IM program types provided included the following: body-mind programs (56%); body-energy programs (23%), and body programs (21%). All programs were outpatient focused, generally did not require a doctors' referral, were freely accessible to cancer patients and carers at no or minimal cost, were centralized by coordinators, and involved volunteers, nurses, allied health practitioners, third parties, and patients in their treatment planning. Interaction between medical and CAM/IM teams was limited and tended to be informal. The underlying structure comprised four main themes: cultural context, human components, systematic components, and resource availability. Human components and resources were considered important in influencing cultural context and systematic components in the IM structure. CONCLUSION: Australian integrative oncology models are based on the concept of wellness and individualized care, focused on patient empowerment and engagement. IM models are generally independent of conventional medical care. Building relationships and trust between stakeholders and open collaboration with conventional medical care will be important to integrate IM into the hospital system. Systemic changes to deliver patient centered care in the provision of IM healthcare will facilitate the incorporation of CAM and IM into cancer services in hospital settings.

Integration of complementary and alternative medicine into cancer-specific supportive care programs in Australia: A scoping study.

AIM: The main aim of this research was to describe the availability and integration of supportive care programs (SCPs), particularly complementary and alternative medicine (CAM) services, for adults in Australian oncology treatment centers. METHODS: We systematically searched 124 Australian hospitals listed as having an oncology department out of a total of 1157 hospitals listed in the Australian Hospitals and Aged Care Databases (2014), and assessed their website and relevant leaflets. Direct contact was made with a relevant staff member in each hospital. Data were collected regarding the range of SCP and CAM services available. RESULTS: Of the 124 hospitals, 89 (72%) provide nonspecific guidance to SCP or a staff member (e.g. social worker or care coordinator) who directs patients, advising them about SCP; 35 hospitals (28%) provide active referral to SCP, of which 24 of 35 (69%) include CAM in their service, with individual variation in how it is incorporated. Only 11 (46%) of these 24 CAM incorporated oncology centers in Australia provided systematically integrated CAM programs. CONCLUSION: The majority of Australian oncology departments do not have CAM incorporated into their services. In those that do, less than half had systemically integrated CAM. The types of CAM available, how they are accessed and how they are integrated varied across hospitals. Further research is required to understand how to successfully and systematically integrate cancer-specific supportive care such as CAM into Australian cancer services.

AII amacrine cells in the distal inner nuclear layer of the mouse retina.

We serendipitously found a distal Disabled-1 (Dab1)-immunoreactive cell in retina of the C57BL/6J black mouse. The somata of these cells are located in the outermost part of the inner nuclear layer (INL). Their processes extend toward the outer plexiform layer (OPL), receiving synaptic inputs from horizontal and interplexiform cells. In the current study, we name this cell the "distal Dab1-immunoreactive cell." Double-labeling experiments demonstrate that the distal Dab1-immunoreactive cell is not a horizontal cell. Rather, the distal Dab1 cell appears to be a misplaced AII cell, by being glycine transporter-1-immunoreactive and by resembling the latter cell in an electron microscopic analysis. A distal Dab1 cell had been reported in the FVB/N mouse retina, a model of retinitis pigmentosa (Park et al. [2004] Cell Tissue Res 315:407-412). However, here, we found this distal Dab1-immunoreactive cell in the adult and normal developing mouse retinas. Hence, we show that such cells do not require the loss of photoreceptors as suggested previously (Park et al. [2004] Cell Tissue Res 315:407-412). Instead, two other pieces of data suggest an alternative explanation sources for distal Dab1 cells. First, we find a correlation between the number of these cells in the left and right eyes Second, developmental analysis shows that the distal Dab1-immunoreactive cell is first observed shortly after birth. At the same time, AII cells emerge, extending their neurites into the inner retina. These data suggest that distal Dab1-immunoreactive cells are misplaced AII amacrine cells, resulting from genetically modulated anomalies owing to migration errors.