Myeloid cell replacement is neuroprotective in chronic experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination of the central nervous system (CNS). Autologous hematopoietic cell transplantation (HCT) shows promising benefits for relapsing-remitting MS in open-label clinical studies, but the cellular mechanisms underlying its therapeutic effects remain unclear. Using single-nucleus RNA sequencing, we identify a reactive myeloid cell state in chronic experimental autoimmune encephalitis (EAE) associated with neuroprotection and immune suppression. HCT in EAE mice results in an increase of the neuroprotective myeloid state, improvement of neurological deficits, reduced number of demyelinated lesions, decreased number of effector T cells and amelioration of reactive astrogliosis. Enhancing myeloid cell incorporation after a modified HCT further improved these neuroprotective effects. These data suggest that myeloid cell manipulation or replacement may be an effective therapeutic strategy for chronic inflammatory conditions of the CNS.

Partial facial paralysis induced by sialolithiasis of the parotid gland: a case report.

BACKGROUND: Facial paralysis due to parotid sialolithiasis-induced parotitis is a unusual clinical phenomenon that has not been reported in prior literature. This scenario can present a diagnostic challenge due to its rarity and complex symptomatology, particularly if a patient has other potential contributing factors such as facial trauma or bilateral forehead botox injections as in this patient. This case report elucidates such a complex presentation, aiming to increase awareness and promote timely recognition among clinicians. CASE PRESENTATION: A 56-year-old male, with a medical history significant for hyperlipidemia, recurrent parotitis secondary to parotid sialolithiasis, and recent bilateral forehead cosmetic Botox injections presented to the emergency department with right lower facial drooping. This onset was about an hour after waking up and was of 4 h duration. The patient also had a history of a recent ground level fall four days prior that resulted in facial trauma to his right eyebrow without any evident neurological deficits in the region of the injury. A thorough neurological exam revealed sensory and motor deficits across the entirety of the right face, indicating a potential lesion affecting the buccal and marginal mandibular branches of the facial nerve (CN VII). Several differential diagnoses were considered for the lower motor neuron lesion, including soft tissue trauma or swelling from the recent fall, compression due to the known parotid stone, stroke, and complex migraines. An MRI of the brain was conducted to rule out a stroke, with no significant findings. A subsequent CT scan of the neck revealed an obstructed and dilated right Stensen's duct with a noticeably larger and anteriorly displaced sialolith and evidence of parotid gland inflammation. A final diagnosis of facial palsy due to parotitis secondary to sialolithiasis was made. The patient was discharged and later scheduled for a procedure to remove the sialolith which resolved his facial paralysis. CONCLUSIONS: This case emphasizes the need for a comprehensive approach to the differential diagnosis in presentations of facial palsy. It underscores the potential involvement of parotid sialolithiasis, particularly in patients with a history of recurrent parotitis or facial trauma. Prompt recognition of such uncommon presentations can prevent undue interventions, aid in timely appropriate management, and significantly contribute to the patient's recovery and prevention of long-term complications.

Isogenic human trophectoderm cells demonstrate the role of NDUFA4 and associated variants in ZIKV infection.

Population-based genome-wide association studies (GWAS) normally require a large sample size, which can be labor intensive and costly. Recently, we reported a human induced pluripotent stem cell (hiPSC) array-based GWAS method, identifying NDUFA4 as a host factor for Zika virus (ZIKV) infection. In this study, we extended our analysis to trophectoderm cells, which constitute one of the major routes of mother-to-fetus transmission of ZIKV during pregnancy. We differentiated hiPSCs from various donors into trophectoderm cells. We then infected cells carrying loss of function mutations in NDUFA4, harboring risk versus non-risk alleles of SNPs (rs917172 and rs12386620) or having deletions in the NDUFA4 cis-regulatory region with ZIKV. We found that loss/reduction of NDUFA4 suppressed ZIKV infection in trophectoderm cells. This study validated our published hiPSC array-based system as a useful platform for GWAS and confirmed the role of NDUFA4 as a susceptibility locus for ZIKV in disease-relevant trophectoderm cells.

Enhancing LED spectral output with perylene dye-based remote phosphor.

LEDs offer a wide range of spectral output with high efficiencies. However, the efficiencies of solid-state LEDs with green and yellow wavelengths are rather low due to the lack of suitable direct bandgap materials. Here, we introduce and develop perylene-enhanced green LEDs that produce a higher wall-plug efficiency of 48% compared to 38% for a solid-state green LED. While the wall-plug efficiency of the perylene-enhanced red LED is still lower than that of a solid-state red LED, we demonstrate that remote phosphor colour converters are effective solutions for targeted spectral tuning across the visible spectrum for horticultural lighting. In this work, we retrofit existing white LEDs and augment photosynthesis via spectral output tuning to achieve a higher red-to-blue ratio. Our results show a significant improvement in plant growth by up to 39%, after a 4-month growth cycle. We observe no visible degradation of the colour converter even under continuous illumination with a current of 400 mA. This opens up new opportunities for using perylene-based colour converters for tuneable illumination with high brightness.

Augmentation of a neuroprotective myeloid state by hematopoietic cell transplantation.

Multiple sclerosis (MS) is an autoimmune disease associated with inflammatory demyelination in the central nervous system (CNS). Autologous hematopoietic cell transplantation (HCT) is under investigation as a promising therapy for treatment-refractory MS. Here we identify a reactive myeloid state in chronic experimental autoimmune encephalitis (EAE) mice and MS patients that is surprisingly associated with neuroprotection and immune suppression. HCT in EAE mice leads to an enhancement of this myeloid state, as well as clinical improvement, reduction of demyelinated lesions, suppression of cytotoxic T cells, and amelioration of reactive astrogliosis reflected in reduced expression of EAE-associated gene signatures in oligodendrocytes and astrocytes. Further enhancement of myeloid cell incorporation into the CNS following a modified HCT protocol results in an even more consistent therapeutic effect corroborated by additional amplification of HCT-induced transcriptional changes, underlining myeloid-derived beneficial effects in the chronic phase of EAE. Replacement or manipulation of CNS myeloid cells thus represents an intriguing therapeutic direction for inflammatory demyelinating disease.

Diabetes, Ramadan, and driving - Ensuring patient safety while respecting religious autonomy: A qualitative study.

BACKGROUND AND AIMS: Hypoglycaemia due to fasting during Ramadan may affect the ability to perform complex activities among people with type 2 diabetes mellitus (T2D), but it is unclear how this affects one's ability to drive. This study aims to explore driving experiences and coping strategies to ensure safe driving among people with T2D who fast during Ramadan. METHODS: We conducted an exploratory qualitative study and purposefully selected people with T2D who drove and fasted during the past Ramadan period in 2019. In-depth face-to-face interviews were conducted and transcribed verbatim. Data were analysed thematically using a constant comparative method until saturation was achieved (n = 16). RESULTS: Two major themes were identified, namely: (1) knowing oneself and (2) voluntary self-restriction. Participants described the importance of understanding how Ramadan fasting affected them and their level of alertness. As such, participants often adjusted their daily activities and tested their blood glucose levels to prevent experiencing hypoglycaemia. Other coping strategies reported include adjusting their medications and driving restrictions or driving in the mornings when they were more alert. Findings from this study shed light on participants' experiences and coping mechanisms while driving during Ramadan. CONCLUSION: Given the risks and effects of hypoglycaemia among those who fast, there is a need to provide appropriate and focused patient education during Ramadan to people with T2D to ensure they can perform complex activities such as driving safely, especially in Muslim majority countries.

Early onset of senescence and imbalanced epidermal homeostasis across the decades in photoexposed human skin: Fingerprints of inflammaging.

Inflammaging is a theory of ageing which purports that low-level chronic inflammation leads to cellular dysfunction and premature ageing of surrounding tissue. Skin is susceptible to inflammaging because it is the first line of defence from the environment, particularly solar radiation. To better understand the impact of ageing and photoexposure on epidermal biology, we performed a system biology-based analysis of photoexposed face and arm, and photoprotected buttock sites, from women between the ages of 20s to 70s. Biopsies were analysed by histology, transcriptomics, and proteomics and skin surface biomarkers collected from tape strips. We identified morphological changes with age of epidermal thinning, rete ridge pathlength loss and stratum corneum thickening. The SASP biomarkers IL-8 and IL-1RA/IL1-α were consistently elevated in face across age and cis/trans-urocanic acid were elevated in arms and face with age. In older arms, the DNA damage response biomarker 53BP1 showed higher puncti numbers in basal layers and epigenetic ageing were accelerated. Genes associated with differentiation and senescence showed increasing expression in the 30s whereas genes associated with hypoxia and glycolysis increased in the 50's. Proteomics comparing 60's vs 20's confirmed elevated levels of differentiation and glycolytic-related proteins. Representative immunostaining for proteins of differentiation, senescence and oxygen sensing/hypoxia showed similar relationships. This system biology-based analysis provides a body of evidence that young photoexposed skin is undergoing inflammaging. We propose the presence of chronic inflammation in young skin contributes to an imbalance of epidermal homeostasis that leads to a prematurely aged appearance during later life.

A human iPSC-array-based GWAS identifies a virus susceptibility locus in the NDUFA4 gene and functional variants.

Population-based studies to identify disease-associated risk alleles typically require samples from a large number of individuals. Here, we report a human-induced pluripotent stem cell (hiPSC)-based screening strategy to link human genetics with viral infectivity. A genome-wide association study (GWAS) identified a cluster of single-nucleotide polymorphisms (SNPs) in a cis-regulatory region of the NDUFA4 gene, which was associated with susceptibility to Zika virus (ZIKV) infection. Loss of NDUFA4 led to decreased sensitivity to ZIKV, dengue virus, and SARS-CoV-2 infection. Isogenic hiPSC lines carrying non-risk alleles of SNPs or deletion of the cis-regulatory region lower sensitivity to viral infection. Mechanistic studies indicated that loss/reduction of NDUFA4 causes mitochondrial stress, which leads to the leakage of mtDNA and thereby upregulation of type I interferon signaling. This study provides proof-of-principle for the application of iPSC arrays in GWAS and identifies NDUFA4 as a previously unknown susceptibility locus for viral infection.

The impact of deprescribing interventions on oral proton pump inhibitor utilisation in a Singapore tertiary hospital: A quality improvement initiative.

INTRODUCTION: Proton pump inhibitors (PPIs) are effective treatments for upper gastrointestinal pathologies and short-term courses are well-tolerated. However, indiscriminate use of PPIs is undesirable due to its potential harms. We implemented a series of deprescribing interventions between 2016 and 2017 to curb PPI overutilisation in our institution. The aim of this study was to evaluate the effectiveness and safety of these interventions. METHODS: An institutional PPI deprescribing guide was disseminated by email and educational roadshows were conducted to prescribers. Interrupted time series analysis was used to evaluate the effectiveness of the deprescribing interventions over a 7-year period from 2013 to 2019. To ascertain the safety of PPI deprescribing, we analysed the peptic ulcer disease incidence from 2015 to 2018 and conducted a retrospective chart review of 262 inpatients who were deprescribed PPIs. RESULTS: Following the first intervention, there was a significant decrease in mean oral PPI utilisation by 2,324.46 defined daily doses (DDD) per 1,000 prescriptions (95% confidence interval [CI] -3,542.66, -1,106.26) per month, followed by a month-to-month decrease of 302.61 DDD per 1,000 prescriptions per month thereafter (95% CI -473.95, -131.27). A second targeted educational intervention was only effective in sustaining the decline in the outpatient, but not in the inpatient setting. There were no significant changes in incidence of peptic ulcer disease. In the retrospective chart review, a majority (62.6%) of patients remained deprescribed at 6 months. CONCLUSION: We observed a sustained decrease in PPI utilisation in our institution for more than 12 months following our educational interventions. Cautious deprescribing of PPIs in eligible candidates was found to be safe with low recurrence rates of upper gastrointestinal events.

Nicotinamide Prevents UVB- and Oxidative Stress‒Induced Photoaging in Human Primary Keratinocytes.

Nicotinamide (NAM), a NAM adenine dinucleotide precursor, is known for its benefits to skin health. Under standard culture conditions, NAM delays the differentiation and enhances the proliferation of human primary keratinocytes, leading to the maintenance of stem cells. In this study, we investigated the effects of NAM on photoaging in two-dimensional human primary keratinocyte cultures and three-dimensional organotypic epidermal models. In both models, we found that UVB irradiation and hydrogen peroxide induced human primary keratinocyte premature terminal differentiation and senescence. In three-dimensional organotypics, the phenotype was characterized by a thickening of the granular layer expressing filaggrin and loricrin, but thinning of the epidermis overall. NAM limited premature differentiation and ameliorated senescence, as evidenced by the maintenance of lamin B1 levels in both models, with decreased lipofuscin staining and reduced IL-6/IL-8 secretion in three-dimensional models, compared to those in UVB-only controls. In addition, DNA damage observed after irradiation was accompanied by a decline in energy metabolism, whereas both effects were partially prevented by NAM. Our data thus highlight the protective effects of NAM against photoaging and oxidative stress in the human epidermis and pinpoint DNA repair and energy metabolism as crucial underlying mechanisms.

Block copolymer self-assembly assisted fabrication of laterally organized- and stacked- nanoarrays.

Block copolymer (BCP) self-assembly processes are often seen as reliable techniques for advanced nanopatterning to achieve functional surfaces and create templates for nanofabrication. By taking advantage of the tunability in pitch, diameter and feature-to-feature separation of the self-assembled BCP features, complex, laterally organized- and stacked- multicomponent nanoarrays comprising of gold and polymer have been fabricated. The approaches not only demonstrate nanopatterning of up to two levels of hierarchy but also investigate how a variation in the feature-to-feature gap at the first hierarchy affects the self-assembly of polymer features at the second. Such BCP self-assembly enabled multicomponent nanoarray configurations are rarely achieved by other nanofabrication approaches and are particularly promising for pushing the boundaries of block copolymer lithography and in creating unique surface architectures and complex morphologies at the nanoscale.

Methadone rotation for cancer pain: an observational study.

CONTEXT: Methadone is a useful option in the treatment of cancer pain. Despite its advantages, methadone use is complicated due to high interindividual variability in pharmacokinetics. Various rotation methods from other opioids have been proposed in mostly Caucasian populations. OBJECTIVES: This study aims to describe our experience with opioid rotation to methadone for management of cancer pain in a predominantly Asian population. METHODS: A retrospective review of 52 inpatients initiated on methadone for cancer pain from June 2015 to June 2018 was conducted. Our institution protocol for methadone rotation involves either one of two methods ('Stop-and-go' or the Edmonton 3-day rotation) based on the morphine-equivalent daily dose (MEDD), using an equianalgesic ratio of 10:1 for MEDD <1000 mg. To account for incomplete cross-tolerance, we further reduce the calculated dose by 30%. RESULTS: The majority of patients had mixed nociceptive-neuropathic pain (83%) and the predominant reason for methadone rotation was ineffective analgesia with other opioids (75%). The median MEDD before rotation was 104 mg. Effective analgesia (defined as a decrease in numerical rating scale (NRS) of ≥1 or attainment of NRS ≤3) was achieved within 3 days after rotation in 89% of patients. Patients with an MEDD ≤100 mg/day required a greater degree of uptitration of methadone dose after rotation compared with those with an MEDD >100 mg/day. CONCLUSION: Rotation to methadone according to our protocol is effective in achieving adequate analgesia in most patients experiencing nociceptive-neuropathic pain. Our results also suggest that a fixed equianalgesic ratio of 10:1 may be adequate for patients at low-to-moderate MEDD <400 mg/day.

Colon Capsule Endoscopy in the Assessment of Mucosal Healing in Crohn's Disease.

BACKGROUND: Patients with Crohn's disease (CD) undergo frequent endoscopic procedures, with visualization of the gastrointestinal mucosa central to treatment decision-making. Subsequently, a noninvasive alternative to optical colonoscopy (OC) would be welcomed. One such technology is capsule endoscopy, including the PillCam COLON 2 (PCC2), though research validating its use in ileocolonic CD is limited. This study aims to compare PCC2 with ileocolonoscopy (OC) in assessing mucosal CD through use of a standardized scoring system. METHODS: At an Australian tertiary hospital, same-day PCC2 and ileocolonoscopy results of 47 CD patients, with known nonstricturing disease, were prospectively collected and analyzed for correlation and agreement. Deidentified recordings were reported by a single expert gastroenterologist. Mucosal disease was quantified using the Simple Endoscopic Score for Crohn's Disease (SES-CD). The SES-CD results of paired endoscopic modalities were compared in total per bowel segment and per SES-CD variable. RESULTS: Of 47 PCC2 recordings, 68% were complete, fully assessing terminal ileum to rectum, and OC was complete in 89%. Correlation (r) between total SES-CD scores was strongest in the terminal ileum (r = 0.77, P < .001), with the SES-CD variable of "ulcer detection" showing the strongest agreement. The PCC2 (vs OC) identified additional ulcers in the terminal ileum; ascending, transverse, and descending colon; and rectum; scores were 5 (1), 5 (3), 1 (1), 2 (1), and 2 (2), respectively. CONCLUSIONS: The PCC2 shows promise in assessing ileocolonic mucosa, especially in proximal bowel segments, with greater reach of visualization in the small bowel. Given the resource and safety considerations raised by the Coronavirus disease 2019 pandemic, capsule endoscopy has particular significance.This article aims to contribute to the limited body of research surrounding the validity of capsule endoscopy technology in assessing ileocolonic mucosa in Crohn's Disease patients. In doing so, an alternative option for patients enduring frequent endoscopies is given potential.

Design and Development of a Low Cost, Non-Contact Infrared Thermometer with Range Compensation.

Fever is a common symptom of many infections, e.g., in the ongoing COVID-19 pandemic, keeping monitoring devices such as thermometers in constant demand. Recent technological advancements have made infrared (IR) thermometers the choice for contactless screening of multiple individuals. Yet, even so, the measurement accuracy of such thermometers is affected by many factors including the distance from the volunteers' forehead, impurities (such as sweat), and the location measured on the volunteers' forehead. To overcome these factors, we describe the assembly of an Arduino-based digital IR thermometer with distance correction using the MLX90614 IR thermometer and HC-SR04 ultrasonic sensors. Coupled with some analysis of these factors, we also found ways to programme compensation methods for the final assembled digital IR thermometer to provide more accurate readings and measurements.

The Polyamine Regulator AMD1 Upregulates Spermine Levels to Drive Epidermal Differentiation.

Maintaining tissue homeostasis depends on a balance between cell proliferation, differentiation, and apoptosis. Within the epidermis, the levels of the polyamines putrescine, spermidine, and spermine are altered in many different skin conditions, yet their role in epidermal tissue homeostasis is poorly understood. We identify the polyamine regulator, Adenosylmethionine decarboxylase 1 (AMD1), as a crucial regulator of keratinocyte (KC) differentiation. AMD1 protein is upregulated on differentiation and is highly expressed in the suprabasal layers of the human epidermis. During KC differentiation, elevated AMD1 promotes decreased putrescine and increased spermine levels. Knockdown or inhibition of AMD1 results in reduced spermine levels and inhibition of KC differentiation. Supplementing AMD1-knockdown KCs with exogenous spermidine or spermine rescued aberrant differentiation. We show that the polyamine shift is critical for the regulation of key transcription factors and signaling proteins that drive KC differentiation, including KLF4 and ZNF750. These findings show that human KCs use controlled changes in polyamine levels to modulate gene expression to drive cellular behavior changes. Modulation of polyamine levels during epidermal differentiation could impact skin barrier formation or can be used in the treatment of hyperproliferative skin disorders.

Intrinsic hospital factors: overlooked cause for variations in delay to transfer for endovascular thrombectomy.

BACKGROUND: Intrinsic hospital factors leading to time delay to inter-hospital transfer for endovascular thrombectomy (EVT) have not been adequately investigated, leading to uncertainty in generalizability of hub and spoke EVT services. We investigated the contribution of intrinsic hospital factors to variations in time delay in a multicenter, retrospective study. METHODS: The setting was a hub and spoke EVT state-wide system for a population of 6.3 million and 34 spoke hospitals. We collected data on acute large vessel occlusion strokes transferred from spoke to hub for consideration of EVT between January 2016 and December 2018. The primary endpoint was the proportion of variability in delay-time in transfer cases contributed to by intrinsic hospital factors estimated through variance component analysis implemented as a mixed-effect linear regression model with hospitals as random effects. RESULTS: We included 434 patients. The median age was 72 years (IQR 62-79), 44% were female, and the median baseline National Institutes of Health Stroke Scale (NIHSS) was 16 (IQR 11-20). The median onset to CT time was 100 mins (IQR 69-157) at the spoke hospitals and CT acquisition at the spoke hospital to time of transfer was 93 min (IQR 70-132). 53% of the observed variability in time from CT acquisition at the spoke hospital to transfer to the EVT center was explained by intrinsic hospital factors, as opposed to patient-related factors. CONCLUSIONS: Intrinsic hospital factors explained more than half of the observed variability in time from CT acquisition at the spoke hospital to departure for transfer. We recommend that the design of hub and spoke EVT services should account for intrinsic hospital factors to minimize hospital transfer delay.

Feasibility and safety of orbital atherectomy for the treatment of in-stent restenosis secondary to stent under-expansion.

BACKGROUND: Debulking and ablative techniques are sometimes used for the treatment of in-stent restenosis (ISR) secondary to resistant stent under-expansion (SU). The safety and effectiveness of orbital atherectomy (OA) in this cohort of patients has not been reported. METHODS: We retrospectively evaluated consecutive patients treated with OA for ISR secondary to balloon undilatable SU at two academic tertiary care centers between October 2016 and June 2019. Angiographic or intravascular imaging identified SU. Technical success was defined as residual 0% stenosis with TIMI III flow. RESULTS: A total of 41 patients were included in the study. Patients had an average age of 65 ± 12 years; 73% male, 61% diabetic, 41% with prior coronary artery bypass grafting, 61% with a prior incident of ISR, 51% presented with stable angina, 17% unstable angina, and 32% non-ST elevation myocardial infarction (MI). Implantation of the under-expanded stents occurred between 2 months and 22 years prior to the index procedure. A total of 27% of patients had multiple layers of stents in the target lesion and 32% of patients had in-stent chronic total occlusion. Technical success was achieved in 40 (98%) patients. There were 2 (5%) major adverse cardiovascular events; both of them were periprocedural MI from the no-reflow phenomenon. There were 2 (5%) Ellis type II coronary perforations that required no intervention. CONCLUSIONS: OA can be effectively performed as an adjunctive tool in the treatment of ISR with balloon undilatable SU. The use of OA for SU is not approved by the U.S. Food and Drug Administration and is "off label" and caution must be used to limit any device/stent interaction.

Distribution of C-arm projections in native and bioprosthetic aortic valves cusps: Implication for BASILICA procedures.

OBJECTIVES: We sought to document aortic cusps fluoroscopic projections and their distributions using leaflet alignment which is a novel concept to optimize visualization of leaflets and for guiding BASILICA (bioprosthetic or native aortic scallop intentional laceration to prevent coronary artery obstruction) and determine whether these projections were feasible in catheter laboratory. BACKGROUND: Optimal fluoroscopic projections of aortic valve cusps have not been well described. METHODS: A total of 128 pre-transcatheter aortic valve replacement (pre-TAVR) computed tomographies (CT) (72 native valves and 56 bioprosthetic surgical valves) were analyzed. Using CT software (3Mensio, Pie medical imaging, the Netherlands), leaflet alignment was performed and the feasibility of these angles, which were defined as rate of obtainable with efforts (within LAO/RAO of 85° and CRA/CAU of 50°) were evaluated. RESULTS: High feasibility was seen in right coronary cusp (RCC) front view (100%) and left coronary cusp (LCC) side view (99.2%), followed by noncoronary cusp side view (95.3%). In contrast, low feasibility of RCC side view (7.8%) and LCC front view (47.6%) was observed. No statistical differences were seen between the distribution of native valves and bioprosthetic surgical valves. With patient/table tilt of 20°LAO and 10°CRA, the feasibility of RCC side view and LCC front view increased to 43.7 and 85.2%, respectively. CONCLUSION: Distributions of each cusp's leaflet alignment follows "sigmoid curve" which can provide better understanding of aortic valve cusp orientation in TAVR and BASILICA. RCC side view used in right cusp BASILICA is commonly unachievable in catheter laboratory and may improve with patient/table tilt.

Warfarin and food, herbal or dietary supplement interactions: A systematic review.

AIMS: To present an updated overview on the safety of concurrent use of food, herbal or dietary supplement and warfarin. METHODS: A systematic literature review was performed on 5 databases from inception up to 31 December 2019. These interactions were classified depending on the likelihood of interaction and supporting evidences. RESULTS: A total of 149 articles describing 78 herbs, food or dietary supplements were reported to interact with warfarin. These reports described potentiation with 45 (57.7%) herbs, food or dietary supplements while 23 (29.5%) reported inhibition and 10 (12.8%) reported limited impact on warfarin pharmacokinetics and pharmacodynamics. Twenty unique herb and dietary supplements also reported to result in minor bleeding events, such as purpura and gum bleeding as well as major events such as intracranial bleeding that led to death. CONCLUSION: While most food, herbs and supplements can be safely taken in moderation, healthcare professionals should be aware of the increased risk of bleeding when taking several food and herbs. These include Chinese wolfberry, chamomile tea, cannabis, cranberry, chitosan, green tea, Ginkgo biloba, ginger, spinach, St. John's Wort, sushi and smoking tobacco. Patients should be counselled to continue to seek advice from their healthcare professionals when starting any new herbs, food or supplement.