Heparin-induced thrombocytopenia with very high antibody titer is associated with slower platelet recovery and higher risk of thrombosis.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder mediated by platelet-activating antibodies targeting platelet factor 4 (PF4) and heparin complex. A higher antibody titer is reflected in a higher optical density (OD) by enzyme-linked immunosorbent assay for heparin-PF4 antibodies. This single-institution retrospective study of 116 HIT patients examined the effect of heparin-PF4 OD on time to platelet recovery, vascular thrombosis, and in-hospital mortality. Patients were divided into 3 cohorts based on heparin-PF4 OD: cohort 1 had an OD ≥ 2 and ≤ 2.4, cohort 2 had an OD > 2.4 and ≤ 2.8, and cohort 3 had an OD > 2.8. A higher OD titer was associated with significantly increased time to platelet recovery when compared between cohorts 1 versus 2 (HR = 0.599, p = 0.0221) and 1 versus 3 (HR = 0.515, p = 0.0014), as well as an increased risk of thrombosis (79.4%-cohort 3 vs 53.8%-cohort 2 vs 46.1%-cohort 1, p = 0.04), but had no impact on mortality (2.62-alive vs 2.65-deceased, p = 0.7432). A higher OD titer can inform risk assessment and support decision-making in HIT patients; however, prospective studies are needed to further clarify the impact of heparin-PF4 OD on outcomes.

Barriers to physical activity in prostate cancer survivors.

AIMS: Despite the benefits of regular physical activity (PA), many prostate cancer (PCa) survivors are not engaging in sufficient PA to achieve health-related gain. This qualitative study sought to gain further insight regarding barriers to PA in older-aged PCa survivors. METHODS: Sixteen participants were individually interviewed, and data were analysed using an inductive thematic approach. RESULTS: Six main themes affecting perceived barriers for PA post diagnosis were identified: the effects of the PCa and PCa treatments on PA, urinary incontinence and bowel control, pre-existing comorbid conditions, increased age, time constraints and lack of proximity to PA or exercise venues. CONCLUSIONS: Only two of the six barriers identified directly related to having had PCa. With an increase in PCa survivorship, an active focus needs to be placed on the role that PA can have in helping maintain and improve both the physical and psychological health-related outcomes of PCa survivors.

Practicing in Both Worlds: Why two General Practitioners Decided to Become Traditional Chinese Medicine Practitioners.

In New Zealand, little is known about Western medicine practitioners, such as general practitioners (GPs), who have also trained in traditional Chinese medicine (TCM). The aim was to identify the reasons why two GPs decided to study TCM and become integrated health care practitioners. Data from two Auckland-based integrated (combined GP and TCM) health care practitioners were analyzed for the present study. Individual face-to-face interviews were conducted. An inductive thematic approach was used to analyze the data. One main theme emerged. Both participants discussed how they perceived certain limitations in relation to their practice within the Western medicine model and that TCM allowed them to provide a holistic form of treatment. Being an integrated health care practitioner was perceived by participants as allowing them to treat the whole person rather than just the symptoms of a condition. TCM was also perceived to be beneficial as it allowed participants to provide alternative methods in treating their patients.

The Integrated Treatment for Chronic Pain and Anxiety in a Patient with Breast Implant Illness Symptoms: A Case Report.

INTRODUCTION: Women with breast implants may experience breast implant illness (BII). BII is comprised of a collection of systemic symptoms, such as fatigue and pain, that are postulated to be related to having breast implants. CASE PRESENTATION: This case report documents the naturopathic treatment of a 35-year-old female patient diagnosed with fibromyalgia, tension headaches, and chronic anxiety, perceived to be linked to and exacerbated by her textured cohesive gel implants. The patient sought naturopathic treatment for support during the explant process of her breast implants.Naturopathic treatment was provided over a 3-month period in conjunction with prescribed medication for her anxiety and tension headaches. CONCLUSION: At 3 months post-naturopathic treatment, the patient experienced a reduction in anxiety, fatigue, and self-reported pain. The integration of alternative therapies with prescribed pharmaceutical treatment appeared to positively impact the health of this patient.

Older adults' evaluations of the standard and modified pedometer-based Green Prescription.

INTRODUCTION The Green Prescription is a primary care programme designed to increase physical activity in individuals with low activity levels. Older adults tend to engage in insufficient physical activity to obtain health-related gain. AIM To examine participants' ratings of the Healthy Steps intervention and to assess how participants rated the use of a pedometer-based Green Prescription in aiding their physical activity. METHODS In total, 330 community-dwelling older adults who have low levels of activity were randomised to receive either a standard time-based Green Prescription or a modified pedometer-based Green Prescription. Post-intervention, 259 participants completed the participant evaluation questionnaire via postal survey. Data were analysed using descriptive statistics and Chi-squared analyses. RESULTS The standard components of the Green Prescription (general practitioner consultations and telephone counselling) received similar and higher ratings across both allocation groups than the use of print materials. A pedometer-based Green Prescription was rated as being helpful in aiding physical activity. DISCUSSION This study supports the importance of general practitioners' initial role in prescribing physical activity for older adults and of ongoing telephone support for longer-term adherence. Incorporating a pedometer can be effective in helping low-active older adults initiate and maintain regular physical activity.

Influences on health-care practitioners' promotion of physical activity to their patients with prostate cancer: a qualitative study.

INTRODUCTION Physical activity is beneficial for the physical and psychological health of patients with prostate cancer (PCa). Health-care practitioners are ideally positioned to promote physical activity to their patients. AIM To identify factors that influenced health care practitioners to either promote or not promote physical activity to their patients with PCa. METHODS Individual interviews were conducted with 16 Auckland-based health-care practitioners, including specialists (oncologists and urologists), physiotherapists and complementary and alternative (acupuncturists) health-care practitioners. Data were analysed using an inductive thematic approach. RESULTS Treatment-related factors (ie counteracting side-effects of hormone suppression treatment), longer life expectancy and risk factors for other conditions appeared to influence the promotion of physical activity to patients. Time constraints of consultations and complex medical issues were barriers to the promotion of physical activity. CONCLUSIONS This study found that a variety of health-care practitioners are providing some degree of physical activity advice to their patients with PCa. Collaborative practice among health-care practitioners to verbally reinforce the benefits of physical activity, coupled with referral to experts in physical activity promotion/rehabilitation (such as physiotherapists), should be encouraged for best practice care.

Proteomics analysis reveals a potential new target protein for the lipid-lowering effect of Berberine8998.

Berberine8998 is a newly synthesized berberine derivative with better lipid-lowering activity and improved absorption. The objective of this study was to investigate the effects of berberine8998 on serum cholesterol and lipid levels in vivo and to examine the mechanisms involved. Hamsters on high-fat diet (HFD) were administered berberine or berberine8998 (50 mg·kg-1·d-1, ig) for 3 weeks. Berberine8998 administration significantly lowered the total cholesterol, triglycerides and LDL-C levels in HFD hamsters. Bioinformatics revealed that berberine and berberine8998 shared similar metabolic pathways and fatty acid metabolism was the predominant pathway. Western blot validation results showed that peroxisomal acyl-coenzyme A oxidase 1 (ACOX1) and long-chain fatty acid-CoA ligase 1 (ACSL1), two proteins involved in fatty acid metabolism, were expressed differently in the berberine8998 group than in the untreated group and the berberine treatment group. Biochemistry results showed that berberine8998 significantly lowered the non-esterified fatty acid (NEFA) levels, which may lead to a reduction in TG levels in the berberine8998 treatment group and the differences observed in proteomics analyses. Pharmacokinetic analysis conducted in rats. After administration of berberine or berberine8998 (50 mg/kg, ig), berberine8998 exhibited a remarkably improved absorption with increasing bioavailability by 6.7 times compared with berberine. These findings suggest that berberine8998 lowers cholesterol and lipid levels via different mechanisms than berberine, and its improved absorption makes it a promising therapeutic candidate for the treatment of hypercholesterolemia and obesity.

Patients' reasons for seeking traditional Chinese medicine: a qualitative study.

INTRODUCTION Acupuncture is one of the most well-known and utilised forms of traditional Chinese medicine (TCM). Very little is known about the factors that influence individuals to seek this type of treatment. The aim of this study was to identify and examine patients' reasons for seeking TCM treatment, which was mainly in the form of acupuncture. METHODS Participants were 15 Auckland-based patients who attended a student acupuncture clinic. Participants were individually interviewed. An inductive thematic approach was used to analyse data. RESULTS Three main themes were identified regarding factors that influenced individuals to seek TCM: the perceived limitations of pharmaceutical treatment for certain conditions; a previous positive experience of acupuncture; and word-of-mouth regarding the perceived effectiveness of acupuncture in the treatment of certain conditions. DISCUSSION Users perceive TCM-based acupuncture to be an effective form of treatment for their condition, especially after having previously received conventional medical treatment. Past and present users of TCM appear to have an advocate-based role with family and friends regarding the promotion of TCM-based acupuncture.

Traditional Chinese medicine practitioners in New Zealand: differences associated with being a practitioner in New Zealand compared to China.

AIMS: While New Zealand has experienced an increase in the use of traditional Chinese medicine (TCM) based acupuncture, very little is known about the practitioners who provide this type of treatment modality. Therefore, this study was designed to identify differences associated with being a TCM practitioner in New Zealand compared to China. METHODS: Ten Auckland-based TCM practitioners were individually interviewed. The interview schedule comprised of questions that were designed to identify any potential differences in practising TCM in New Zealand compared to China. Data were analysed using an inductive thematic approach. RESULTS: The main differences in practising between the two countries were related to the role and authority that a TCM practitioner had. This in turn resulted in differences between the conditions that were treated in these two countries. Differences in patient demography were also identified between the two countries. CONCLUSIONS: TCM is used as a form of alternative healthcare treatment in New Zealand for non-Chinese individuals. Acupuncture is the most utilised form of TCM treatment in New Zealand, and is predominantly used for pain management purposes. TCM treatment has been utilised by individuals from a number of different ethnic groups, reflecting the ethnic diversity of the New Zealand population.

Impact of Routine Surveillance Imaging on Outcomes of Patients With Diffuse Large B-Cell Lymphoma After Autologous Hematopoietic Cell Transplantation.

BACKGROUND: For patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), autologous hematopoietic cell transplantation (auto-HCT) is commonly used. After auto-HCT, DLBCL patients are often monitored with surveillance imaging. However, there is little evidence to support this practice. PATIENTS AND METHODS: We performed a multicenter retrospective study of DLBCL patients who underwent auto-HCT (n = 160), who experienced complete remission after transplantation, and who then underwent surveillance imaging. Of these, only 45 patients experienced relapse after day +100 after auto-HCT, with relapse detected by routine imaging in 32 (71%) and relapse detected clinically in 13 (29%). RESULTS: Baseline patient characteristics were similar between the 2 groups. Comparing the radiographic and clinically detected relapse groups, the median time from diagnosis to auto-HCT (389 days vs. 621 days, P = .06) and the median follow-up after auto-HCT (2464 days vs. 1593 days P = .60) were similar. The median time to relapse after auto-HCT was 191 days in radiographically detected relapses compared to 492 days in clinically detected relapses (P = .35), and median postrelapse survival was 359 days in such patients compared to 123 days in patients with clinically detected relapse (P = .36). However, the median posttransplantation overall survival was not significantly different for patients with relapse detected by routine imaging versus relapse detected clinically (643 vs. 586 days, P = .68). CONCLUSION: A majority (71%) of DLBCL relapses after auto-HCT are detected by routine surveillance imaging. Overall, there appears to be limited utility for routine imaging after auto-HCT except in select cases where earlier detection and salvage therapy with allogeneic HCT is a potential option.

Cell-free DNA as a molecular tool for monitoring disease progression and response to therapy in breast cancer patients.

Due to the spatial and temporal genomic heterogeneity of breast cancer, genomic sequencing obtained from a single biopsy may not capture the complete genomic profile of tumors. Thus, we propose that cell-free DNA (cfDNA) in plasma may be an alternate source of genomic information to provide comprehensive data throughout a patient's clinical course. We performed a retrospective chart review of 100 patients with stage 4 or high-risk stage 3 breast cancer. The degree of agreement between genomic alterations found in tumor DNA (tDNA) and cfDNA was determined by Cohen's Kappa. Clinical disease progression was compared to mutant allele frequency using a two-sided Fisher's exact test. The presence of mutations and mutant allele frequency was correlated with progression-free survival (PFS) using a Cox proportional hazards model and a log-rank test. The most commonly found genomic alterations were mutations in TP53 and PIK3CA, and amplification of EGFR and ERBB2. PIK3CA mutation and ERBB2 amplification demonstrated robust agreement between tDNA and cfDNA (Cohen's kappa = 0.64 and 0.77, respectively). TP53 mutation and EGFR amplification demonstrated poor agreement between tDNA and cfDNA (Cohen's kappa = 0.18 and 0.33, respectively). The directional changes of TP53 and PIK3CA mutant allele frequency were closely associated with response to therapy (p = 0.002). The presence of TP53 mutation (p = 0.0004) and PIK3CA mutant allele frequency [p = 0.01, HR 1.074 (95 % CI 1.018-1.134)] was excellent predictors of PFS. Identification of selected cancer-specific genomic alterations from cfDNA may be a noninvasive way to monitor disease progression, predict PFS, and offer targeted therapy.

MTH1 expression is required for effective transformation by oncogenic HRAS.

Due to sustaining elevated reactive oxygen species (ROS), oncogenic RAS-transformed cells upregulate redox-protective genes, among them the mammalian 8-oxodGTPase, MutT Homolog 1 (MTH1). We previously showed MTH1 abrogates RAS oncogene-induced senescence (OIS) in normal cells and that its inhibition compromises the tumorigenicity of established oncogenic RAS-harboring cancer cells. Here, we investigated how pre-transformation MTH1 levels in immortalized cells influence HRASV12-induced oncogenic transformation. We find MTH1 suppression prior to HRASV12 transduction into BEAS2B immortalized epithelial cells compromised maintenance of high RASV12- and oncogenic ROS-expressing cell populations. Furthermore, pre-transformation MTH1 levels modulated the efficiency of HRASV12-mediated soft agar colony formation. Downstream transformation-associated traits such as the epithelial-mesenchymal transition (EMT) were also compromised by MTH1 inhibition. These collective effects were observed to a greater degree in cells harboring high vs. low RASV12 levels, suggesting MTH1 is required for tumor cells to accumulate RAS oncoprotein. This is significant as, a priori, one cannot ascertain whether tumor-promoting adaptations wrought by introducing oncogenic RAS into an immortalized cell are capable of overcoming pre-transformation deficiencies. Our results suggest nucleotide pool sanitization comprises an important transformation-promoting requirement that, if compromised, cannot be adequately compensated post-transformation and thus is likely to affect optimal development and progression of RAS-driven tumors.

General practitioners' views on the role of pedometers in health promotion.

INTRODUCTION: Regular pedometer use can help initiate and maintain regular walking activity that can lead to a number of health-related benefits. The primary health care setting has been found to be an ideal venue in which to counsel low-active individuals for physical activity. AIM: To examine general practitioners' (GPs) views on the role of pedometers in health promotion. METHODS: Fifteen GPs working in urban, primary care practices in Auckland, New Zealand were individually interviewed. The interview schedule focused on physical activity counselling and the Green Prescription programme. For this sub-study, the focus was on questions relating to pedometer use. An inductive thematic approach was used to analyse the data. FINDINGS: Four main themes were identified. Pedometers were viewed as motivational devices that could be used to encourage low-active patients to become more active, as they provided feedback on step counts. A pedometer was also viewed as a self-management tool, whereby the individual could set daily step count goals, which in turn could help increase their physical activity engagement. GPs who currently wore a pedometer discussed the practicalities of being able to show a patient how to use a pedometer. Also discussed was how cost could restrict pedometer access for some patients. CONCLUSIONS: Pedometers were viewed by GPs as being helpful devices that could help motivate and support low-active patients in becoming more active. Information regarding step counts was seen as important because it could make people aware how little physical activity they were engaging in.

Perceptions of physically active men with prostate cancer on the role of physical activity in maintaining their quality of life: possible influence of androgen deprivation therapy.

OBJECTIVE: The primary aim of this study was to examine the perceptions of older men with prostate cancer regarding their quality of life and physical activity post-diagnosis, and the potential benefits and risks associated with being physically active. A secondary aim was to gain some preliminary insight into how these perceptions may differ as a function of androgen deprivation therapy (ADT). METHODS: Two focus groups were conducted, consisting of six ADT and eight non-ADT men, respectively. The probe questions used assessed the link between quality of life and physical activity as well as the benefits and risks associated with physical activity. Data were transcribed verbatim and themes identified using a general inductive thematic approach. RESULTS: The primary themes identified were sexual health, 'plumbing' and non-urogenital side-effects, return to and increased levels of physical activity post-diagnosis, physical health/function and psychological benefits of physical activity as well as over-doing it and age-related risks of excessive physical activity. However, not all themes were present in both the ADT and the non-ADT sub-groups. CONCLUSIONS: These results further highlight the link between physical activity and quality of life in prostate cancer survivors and how they use physical activity as a part of their survivorship process. Of particular interest was how several men on ADT used resistance training to counteract ADT-related side-effects affecting their masculinity. As the evidence for physical activity for prostate cancer survivorship is increasing, cancer clinicians and service providers should consider ways to better assist these men, especially those on ADT become more active.

Androgen deprivation-induced senescence promotes outgrowth of androgen-refractory prostate cancer cells.

Androgen deprivation (AD) is an effective method for initially suppressing prostate cancer (PC) progression. However, androgen-refractory PC cells inevitably emerge from the androgen-responsive tumor, leading to incurable disease. Recent studies have shown AD induces cellular senescence, a phenomenon that is cell-autonomously tumor-suppressive but which confers tumor-promoting adaptations that can facilitate the advent of senescence-resistant malignant cell populations. Because androgen-refractory PC cells emerge clonally from the originally androgen-responsive tumor, we sought to investigate whether AD-induced senescence (ADIS) affects acquisition of androgen-refractory behavior in androgen-responsive LNCaP and LAPC4 prostate cancer cells. We find that repeated exposure of these androgen-responsive cells to senescence-inducing stimuli via cyclic AD leads to the rapid emergence of ADIS-resistant, androgen-refractory cells from the bulk senescent cell population. Our results show that the ADIS phenotype is associated with tumor-promoting traits, notably chemoresistance and enhanced pro-survival mechanisms such as inhibition of p53-mediated cell death, which encourage persistence of the senescent cells. We further find that pharmacologic enforcement of p53/Bax activation via Nutlin-3 prior to establishment of ADIS is required to overcome the associated pro-survival response and preferentially trigger pervasive cell death instead of senescence during AD. Thus our study demonstrates that ADIS promotes outgrowth of androgen-refractory PC cells and is consequently a suboptimal tumor-suppressor response to AD.

The long-term effects of a primary care physical activity intervention on mental health in low-active, community-dwelling older adults.

OBJECTIVES: To examine the effect that physical activity delivered via two different versions of the Green Prescription (a primary care physical activity scripting program) had on depressive symptomatology and general mental health functioning over a 12-month period in non-depressed, low-active, community-dwelling older adults. METHOD: Two hundred and twenty-five participants from the Healthy Steps study took part in the present study. Healthy Steps participants were randomized to receive either the standard time-based or a modified pedometer-based Green Prescription. Depression, mental health functioning and physical activity were measured at baseline, post-intervention (3 months post-baseline) and at the 9-month follow-up period. RESULTS: At post-intervention, a positive association was found between increases in leisure-time physical activity and total walking physical activity and a decrease in depressive symptomatology (within the non-depressed range of the GDS-15) and an increase in perceived mental health functioning, regardless of intervention allocation. These improvements were also evident at the follow-up period for participants in both intervention allocation groups. CONCLUSION: Our findings suggest that the standard time-based Green Prescription and a modified pedometer-based Green Prescription are both effective in maintaining and improving mental health in non-depressed, previously low-active older adults.

Headspace, solid-phase micro-extraction, gas chromatographic-mass spectrometric analysis of terpenoids in the latex of Euphorbia species.

The volatile and semi-volatile terpenoids in the latex of Euphorbia amygdaloides, E. exigua, E. helioscopia, and E. peplus were analyzed by headspace, solid-phase micro-extraction (HS-SPME), coupled with gas chromatography-mass spectrometry. The volatiles were extracted using a 100 microm polydimethylsiloxane SPME fiber under optimized extraction conditions. The compounds detected encompassed a range of chemical classes, but only terpenoids were evaluated. Only sesquiterpene hydrocarbons were detected in the tested samples of E. exigua, E. helioscopia, and E. peplus, with beta-caryophyllene being the major one, but were never recorded in latex samples of E. amygdaloides, in which only the diterpene hydrocarbon kaur-16-ene was detected. Alpha-Humulene was consistently found in samples of E. helioscopia, and E. peplus, but never in those of the other two species. These preliminary results show that the developed procedure is suitable for the analysis of small samples of Euphorbia latex and that, for each individual species, there is very little qualitative difference between samples, regardless of either place or date of collection.