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Introduction: Psoriasis is a multisystem, chronic, inflammatory dermatological disease. In routine clinical practice, the management of psoriasis varies significantly. The current study aimed to develop a set of practice guidelines relevant to dermatology practice in Singapore. Method: The Psoriasis Therapeutic Guidelines Workgroup, comprising members of the Dermatological Society of Singapore with a subspecialisation in psoriasis, was convened to develop the guidelines. Clinical questions on selected topics were generated and refined by the workgroup. A literature search using PubMed was performed on their assigned topics from June 2013 to December 2023. The articles were included and graded based on the level of evidence. Results: The guidelines address topics ranging from clinical assessment to practical considerations in the management of mild, moderate and severe psoriasis, including delivery of care, referrals to specialists and adherence to treatment. The recommended therapies include phototherapy, methotrexate, acitretin, cyclosporine; apremilast; topical corticosteroids, calcipotriol, topical calcineurin inhibitors; and biologics (i.e. adalimumab, infliximab, secukinumab, ixekizumab, ustekinumab, etanercept) either in combination or as monotherapy. Common therapeutic concerns relating to biologic use were addressed. Recommendations on generalised pustular psoriasis, palmoplantar pustular psoriasis and psoriatic arthritis were also made. Patients on systemic therapy would receive appropriate vaccine counselling. Therapeutic implications in special populations, such as pregnant/lactating women, children, the elderly, those undergoing surgery and those suffering from specific infections and cancer were addressed. Conclusion: These guidelines were developed for dermatologists, family physicians, rheumatologists and other specialists to support their selection of appropriate management options.

Estrogens are a growing problem in wastewater discharges because they are continuously entering the environment and are biologically active at extremely low concentrations. Their effects on wildlife were first identified several decades before, but the environmental limits and the remedial measures are still not completely elucidated. Most conventional treatment processes were not designed with sufficiently long retention times to effectively remove estrogens. Nature-based wastewater treatment technologies such as treatment wetlands (TW) and high-rate algal ponds (HRAP) are economically feasible alternatives for decentralized wastewater treatment and have promise for removing steroid hormones including estrogens. For small communities with populations below 50,000, the overall cost of TWs and HRAPs is considerably lower than that of advanced decentralized treatment technologies such as activated sludge systems (AS) and sequencing batch reactors (SBR). This results from the simplicity of design, use of less materials in construction, lower energy use, operation and maintenance costs, and operation by non-skilled personnel. The nature-based technologies show high removal (>80%) for both natural and synthetic estrogens. Estrogen removal in TWs can be enhanced using alternative media such as palm mulch, biochar, and construction wastes such as bricks, instead of traditional substrates such as sand and gravel. While TWs are effective in estrogen removal, they have the disadvantage of requiring a relatively large footprint, but this can be reduced by using intensified multilayer wetland filters (IMWF). Using filamentous algae in HRAP (high-rate filamentous algal pond; HRFAP) is an emerging technology for wastewater treatment. The algae supply oxygen via photosynthesis and assimilate nutrients into readily harvestable filamentous algal biomass. Diurnal fluctuations in oxygen supply and pH in these systems provide conditions conducive to the breakdown of estrogens and a wide range of other emerging contaminants. The performance of these nature-based systems varies with seasonal changes in environmental conditions (particularly temperature and solar irradiation), however a greater understanding of operating conditions such as loading rate, hydraulic retention time (HRT), pond/bed depth, dissolved oxygen (DO) concentration and pH, which influence the removal mechanisms (biodegradation, sorption and photodegradation) enable TWs and HRAPs to be successfully used for removing estrogens.

Long-term conditions and accompanied co-morbidities now affect about a quarter of the UK population. Enabling patients and caregivers to communicate their experience of illness in their own words is vital to developing a shared understanding of the condition and its impact on patients’ and caregivers’ lives and in delivering person-centred care. Studies of patient language show how metaphors provide insight into the physical and emotional world of the patient, but such studies are often limited by their focus on a single illness. The authors of this study undertook a secondary qualitative data analysis of 25 interviews, comparing the metaphors used by patients and parents of patients with five longterm conditions. Analysis shows how similar metaphors can be used in empowering and disempowering ways as patients strive to accept illness in their daily lives and how metaphor use depends on the manifestation, diagnosis, and treatment of individual conditions. The study concludes with implications for how metaphorical expressions can be attended to by healthcare professionals as part of shared care planning.

Abstract Background Immune-related adverse events (irAEs) are a common phenomenon in cancer patients treated with immune checkpoint inhibitors (ICIs). Surprisingly, the toxicity burdens of these irAEs have not been illustrated clearly. In this study, we analyzed irAEs for seven FDA-approved ICIs in cancer treatment to show the pattern of toxicity burden among cancer patients. Methods irAEs associated with seven FDA-approved ICIs, including three PD-1 inhibitors (cemiplimab, nivolumab and pembrolizumab), three PD-L1 inhibitors (atezolizumab, avelumab and durvalumab), and one CTLA-4 inhibitor (ipilimumab), were analyzed based on data from 149,303 reported cases (from January 1, 2015 to June 30, 2022) collected from the FDA Adverse Events Reporting System (FAERS) public dashboard. Proportions of serious irAEs and correlations with tumor type, age and sex were assessed via R package and GraphPad software. Results irAEs related to anti-PD-1 ICIs required less hospital care resources compared with anti-PD-L1 and anti-CTLA-4 ICIs. Patients treated with pembrolizumab had relatively fewer serious cases. Treatment with ICIs led to the highest probability of serious irAEs in patients with lung cancer. ‘Respiratory, thoracic and mediastinal disorders’ and ‘gastrointestinal disorders’ were the two most common groups of disorders caused by the seven ICIs studied. ‘Cardiac disorders’ was the main type of disorders caused by these ICIs in cancer patients aged 65–85, while ‘reproductive system and breast disease’ was the main type of disorder in cancer patients aged 18–64. ‘Respiratory, thoracic, mediastinal diseases’ and ‘reproductive system and breast diseases’ were the main types of disorders associated with treatment with these ICIs in male and female patients, respectively. Conclusion Tissue and organ toxicities of ICIs are age and sex specific. There are risks of respiratory and urinary system toxicity in male patients and reproductive system toxicity in female patients treated with the ICIs studied. Future studies on the toxicity burden of ICIs should incorporate age and sex differences to better understand the relevance of ICI toxicity burden to human immune function to develop appropriate tumor immune and therapeutic intervention strategies.

Abstract Metabolic brain biomarkers have been incorporated in various diagnostic guidelines of neurodegenerative diseases, recently. To improve their diagnostic accuracy a biologically and clinically homogeneous sample is needed for their identification. Alzheimer’s disease-related pattern (ADRP) has been identified previously in cohorts of clinically diagnosed patients with dementia due to Alzheimer’s disease (AD), meaning that its diagnostic accuracy might have been reduced due to common clinical misdiagnosis. In our study, we aimed to identify ADRP in a cohort of AD patients with CSF confirmed diagnosis, validate it in large out-of-sample cohorts and explore its relationship with patients’ clinical status. For identification we analyzed 2-[18F]FDG PET brain scans of 20 AD patients and 20 normal controls (NCs). For validation, 2-[18F]FDG PET scans from 261 individuals with AD, behavioral variant of frontotemporal dementia, mild cognitive impairment and NC were analyzed. We identified an ADRP that is characterized by relatively reduced metabolic activity in temporoparietal cortices, posterior cingulate and precuneus which co-varied with relatively increased metabolic activity in the cerebellum. ADRP expression significantly differentiated AD from NC (AUC = 0.95) and other dementia types (AUC = 0.76–0.85) and its expression correlated with clinical measures of global cognition and neuropsychological indices in all cohorts.

Abstract Differential diagnosis of parkinsonism early upon symptom onset is often challenging for clinicians and stressful for patients. Several neuroimaging methods have been previously evaluated; however specific routines remain to be established. The aim of this study was to systematically assess the diagnostic accuracy of a previously developed 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) based automated algorithm in the diagnosis of parkinsonian syndromes, including unpublished data from a prospective cohort. A series of 35 patients prospectively recruited in a movement disorder clinic in Stockholm were assessed, followed by systematic literature review and meta-analysis. In our cohort, automated image-based classification method showed excellent sensitivity and specificity for Parkinson Disease (PD) vs. atypical parkinsonian syndromes (APS), in line with the results of the meta-analysis (pooled sensitivity and specificity 0.84; 95% CI 0.79–0.88 and 0.96; 95% CI 0.91 –0.98, respectively). In conclusion, FDG-PET automated analysis has an excellent potential to distinguish between PD and APS early in the disease course and may be a valuable tool in clinical routine as well as in research applications.

Purpose: Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia, that shares clinical and metabolic similarities with both Alzheimer’s and Parkinson’s disease. In this study we aimed to identify a DLB-related pattern (DLBRP), study its relationship with other metabolic brain patterns and explore its diagnostic and prognostic value. Methods: A cohort of 79 participants with DLB, 63 with dementia due to Alzheimer’s disease (AD) and 41 normal controls (NCs) and their 2-[18F]FDG PET scans were analysed for identification and validation of DLBRP. Voxel-wise correlation and multiple linear regression were used to study the relation between DLBRP and Alzheimer’s disease-related pattern (ADRP), Parkinson’s disease-related pattern (PDRP) and PD-related cognitive pattern (PDCP). Diagnostic and prognostic value of DLBRP and of modified DLBRP after accounting for ADRP overlap (DLBRP ⊥ ADRP), were explored. Results: The newly identified DLBRP shared topographic similarities with ADRP (R2 = 24%) and PDRP (R2 = 37%), but not with PDCP. We could accurately discriminate between DLB and NC (AUC = 0.99) based on DLBRP expression, and between DLB and AD (AUC = 0.87) based on DLBRP ⊥ ADRP expression. DLBRP expression correlated with cognitive impairment, but the correlation was lost after accounting for ADRP overlap. DLBRP and DLBRP ⊥ ADRP correlated with patients’ survival time. Conclusion: DLBRP has proven to be a specific metabolic brain biomarker of DLB, sharing similarities with ADRP and PDRP, but not PDCP. We observed a similar metabolic mechanism underlying cognitive impairment in DLB and AD. DLB-specific metabolic changes were more detrimental for overall survival.

Objective Resting Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) brain imaging and neuropsychological testing were used to investigate the usefulness of a spatial navigation task (SNT) as a performance benchmark for cognitive impairment related to anti-N-methyl D-aspartate (anti-NMDA) receptor antibodies (DNRAb) in SLE.Methods Neuropsychological assessments, including a desktop 3-D virtual SNT, were performed on 19 SLE participants and 9 healthy control (HC) subjects. SLE participants had stable disease activity and medication doses and no history of neuropsychiatric illness or current use of mind-altering medications. Resting FDG-PET scans were obtained on all SLE participants and compared with a historical set from 25 age-matched and sex-matched HCs. Serum DNRAb titres were measured by ELISA.Results 11/19 (58%) of SLE participants failed to complete the SNT (SNT−) compared with 2/9 (22%) of HCs. Compared with 7/9 (78%) in HCs, only 2/9 (22%; p=0.037) of SLE participants with high serum DNRAb titres completed the SNT, in contrast to 6/10 (60%; p=0.810) in SLE participants with low DNRAb titres. Voxel-wise comparison of FDG-PET scans between the 8 SLE participants successfully completing the SNT task (SNT+) and the 11 SNT− SLE participants revealed increased metabolism in the SNT+ participants (p

Abstract Intestinal pathogens use the host's excessive inflammatory cytokine response, designed to eliminate dangerous bacteria, to disrupt epithelial gut wall integrity and promote their tissue invasion. We sought to develop a non‐antibiotic‐based approach to prevent this injury. Molecular docking studies suggested that glycosylated dendrimers block the TLR4‐MD‐2‐LPS complex, and a 13.6 kDa polyamidoamine (PAMAM) dendrimer glucosamine (DG) reduced the induction of human monocyte interleukin (IL)‐6 by Gram‐negative bacteria. In a rabbit model of shigellosis, PAMAM‐DG prevented epithelial gut wall damage and intestinal villous destruction, reduced local IL‐6 and IL‐8 expression, and minimized bacterial invasion. Computational modelling studies identified a 3.3 kDa polypropyletherimine (PETIM)‐DG as the smallest likely bioactive molecule. In human monocytes, high purity PETIM‐DG potently inhibited Shigella Lipid A‐induced IL‐6 expression. In rabbits, PETIM‐DG prevented Shigella‐induced epithelial gut wall damage, reduced local IL‐6 and IL‐8 expression, and minimized bacterial invasion. There was no change in β‐defensin, IL‐10, interferon‐β, transforming growth factor‐β, CD3 or FoxP3 expression. Small and orally delivered DG could be useful for preventing gut wall tissue damage in a wide spectrum of infectious diarrhoeal diseases. –>See accompanying article http://dx.doi.org/10.1002/emmm.201201668