Exposure to low-level ambient air pollution and the relationship with lung and bladder cancer in older men, in Perth, Western Australia.

BACKGROUND: Air pollution is a cause of lung cancer and is associated with bladder cancer. However, the relationship between air pollution and these cancers in regions of low pollution is unclear. We investigated associations between fine particulate matter (PM2.5), nitrogen dioxide, and black carbon (BC), and both these cancers in a low-pollution city. METHODS: A cohort of 11,679 men ≥65 years old in Perth (Western Australia) were followed from 1996-1999 until 2018. Pollutant concentrations, as a time-varying variable, were estimated at participants' residential addresses using land use regression models. Incident lung and bladder cancer were identified through the Western Australian Cancer Registry. Risks were estimated using Cox proportional-hazard models (age as the timescale), adjusting for smoking, socioeconomic status, and co-pollutants. RESULTS: Lung cancer was associated with PM2.5 and BC in the adjusted single-pollutant models. A weak positive association was observed between ambient air pollution and squamous cell lung carcinoma but not lung adenocarcinoma. Positive associations were observed with bladder cancer, although these were not statistically significant. Associations were attenuated in two-pollutant models. CONCLUSION: Low-level ambient air pollution is associated with lung, and possibly bladder, cancer among older men, suggesting there is no known safe level for air pollution as a carcinogen.

Adjuvant and concurrent temozolomide for 1p/19q non-co-deleted anaplastic glioma (CATNON; EORTC study 26053-22054): second interim analysis of a randomised, open-label, phase 3 study.

BACKGROUND: The CATNON trial investigated the addition of concurrent, adjuvant, and both current and adjuvant temozolomide to radiotherapy in adults with newly diagnosed 1p/19q non-co-deleted anaplastic gliomas. The benefit of concurrent temozolomide chemotherapy and relevance of mutations in the IDH1 and IDH2 genes remain unclear. METHODS: This randomised, open-label, phase 3 study done in 137 institutions across Australia, Europe, and North America included patients aged 18 years or older with newly diagnosed 1p/19q non-co-deleted anaplastic gliomas and a WHO performance status of 0-2. Patients were randomly assigned (1:1:1:1) centrally using a minimisation technique to radiotherapy alone (59·4 Gy in 33 fractions; three-dimensional conformal radiotherapy or intensity-modulated radiotherapy), radiotherapy with concurrent oral temozolomide (75 mg/m2 per day), radiotherapy with adjuvant oral temozolomide (12 4-week cycles of 150-200 mg/m2 temozolomide given on days 1-5), or radiotherapy with both concurrent and adjuvant temozolomide. Patients were stratified by institution, WHO performance status score, age, 1p loss of heterozygosity, the presence of oligodendroglial elements on microscopy, and MGMT promoter methylation status. The primary endpoint was overall survival adjusted by stratification factors at randomisation in the intention-to-treat population. A second interim analysis requested by the independent data monitoring committee was planned when two-thirds of total required events were observed to test superiority or futility of concurrent temozolomide. This study is registered with ClinicalTrials.gov, NCT00626990. FINDINGS: Between Dec 4, 2007, and Sept 11, 2015, 751 patients were randomly assigned (189 to radiotherapy alone, 188 to radiotherapy with concurrent temozolomide, 186 to radiotherapy and adjuvant temozolomide, and 188 to radiotherapy with concurrent and adjuvant temozolomide). Median follow-up was 55·7 months (IQR 41·0-77·3). The second interim analysis declared futility of concurrent temozolomide (median overall survival was 66·9 months [95% CI 45·7-82·3] with concurrent temozolomide vs 60·4 months [45·7-71·5] without concurrent temozolomide; hazard ratio [HR] 0·97 [99·1% CI 0·73-1·28], p=0·76). By contrast, adjuvant temozolomide improved overall survival compared with no adjuvant temozolomide (median overall survival 82·3 months [95% CI 67·2-116·6] vs 46·9 months [37·9-56·9]; HR 0·64 [95% CI 0·52-0·79], p<0·0001). The most frequent grade 3 and 4 toxicities were haematological, occurring in no patients in the radiotherapy only group, 16 (9%) of 185 patients in the concurrent temozolomide group, and 55 (15%) of 368 patients in both groups with adjuvant temozolomide. No treatment-related deaths were reported. INTERPRETATION: Adjuvant temozolomide chemotherapy, but not concurrent temozolomide chemotherapy, was associated with a survival benefit in patients with 1p/19q non-co-deleted anaplastic glioma. Clinical benefit was dependent on IDH1 and IDH2 mutational status. FUNDING: Merck Sharpe & Dohme.

Non-IDH1-R132H IDH1/2 mutations are associated with increased DNA methylation and improved survival in astrocytomas, compared to IDH1-R132H mutations.

Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at high frequency in several tumour types. Even though these mutations are confined to distinct hotspots, we show that gliomas are the only tumour type with an exceptionally high percentage of IDH1R132H mutations. Patients harbouring IDH1R132H mutated tumours have lower levels of genome-wide DNA-methylation, and an associated increased gene expression, compared to tumours with other IDH1/2 mutations ("non-R132H IDH1/2 mutations"). This reduced methylation is seen in multiple tumour types and thus appears independent of the site of origin. For 1p/19q non-codeleted glioma (astrocytoma) patients, we show that this difference is clinically relevant: in samples of the randomised phase III CATNON trial, patients harbouring tumours with IDH mutations other than IDH1R132H have a better outcome (hazard ratio 0.41, 95% CI [0.24, 0.71], p = 0.0013). Such non-R132H IDH1/2-mutated tumours also had a significantly lower proportion of tumours assigned to prognostically poor DNA-methylation classes (p < 0.001). IDH mutation-type was independent in a multivariable model containing known clinical and molecular prognostic factors. To confirm these observations, we validated the prognostic effect of IDH mutation type on a large independent dataset. The observation that non-R132H IDH1/2-mutated astrocytomas have a more favourable prognosis than their IDH1R132H mutated counterpart indicates that not all IDH-mutations are identical. This difference is clinically relevant and should be taken into account for patient prognostication.

Needlessly controversial: the reporting of pharmaco- and psycho-therapy for the treatment of depression in the UK media.

BACKGROUND: It is well-established that media influences public perceptions, and that media coverage of psychiatry is negative compared to the rest of medicine. No studies that we know of, have compared media reporting on antidepressants and talking therapies as treatments for depression. We hypothesised that coverage of antidepressants would be more negative than that of psychotherapies in both headlines and articles. METHODS: We identified online articles in The Sun, Daily Mirror, Daily Mail, Daily Express, and The Guardian between 11 June 2013 and 11 June 2018. Two raters independently evaluated their titles/content with regard to their portrayal of antidepressants and psychotherapies (positive/negative/neutral), with good inter-rater reliability. RESULTS: We identified 221 articles. Antidepressants featured in 184 articles, of which 27 (15%) portrayed them positively, 68 (37%) negatively, and 89 (48%) neutrally; and 173 headlines, of which 24 (14%) portrayed them positively, 64 (37%) negatively, and 85 (49%) neutrally. Antidepressants received more coverage than psychotherapy, which featured in 132 articles, of which 48 (36%) portrayed them positively, 3 (2%) negatively, and 81 (61%) neutrally; and 53 headlines, of which 16 (30%) portrayed them positively, 2 (4%) negatively, and 35 (66%) neutrally. A Fisher's exact test revealed a statistically significant difference between the portrayal of antidepressants and psychotherapies in both articles (p = 2.86 × 10-15) and headlines (p = 2.79 × 10-6). CONCLUSION: Despite the two treatments being similarly effective, the portrayal of antidepressants in the UK online media is more negative than that of psychotherapy. This could potentially discourage patients from considering taking antidepressants, and provoke patients currently taking antidepressants to stop abruptly.

Polyvalent Hybrid Virus-Like Nanoparticles with Displayed Heparin Antagonist Peptides.

The potential applications for nanomaterials continue to grow as new materials are developed and environmental and safety concerns are more adequately addressed. In particular, virus-like particles (VLPs) have myriad applications in medicine and biology, exploiting both the reliable, symmetric self-assembly mechanism and the ability to take advantage of surface functionalities that may be appropriately modified through mutation or bioconjugation. Herein we describe the design and application of hybrid VLPs for use as potent heparin antagonists, providing an alternative to the toxic heparin antidote protamine. A two-plasmid system was utilized to generate VLPs that contain both the wild-type coat protein and a second coat protein with either a C- or N-terminal cationic peptide extension (4-28 amino acids). Incorporation of the modified coat proteins varied from 8 to 31%, while activated partial thromboplastin time (APTT) assays revealed a range of the heparin antagonist activity. Notably, when examined on the basis of the quantity of peptide delivered due to the varied incorporation rates, it appeared that the VLPs largely followed a similar trend, with the quantity of peptide delivered more closely correlating with heparin antagonist activity. The particle with the highest incorporation rate and best antiheparin activity displayed the C-terminal peptide ARK2A2KA, which corresponds to the Cardin-Weintraub consensus sequence for binding to glycosaminoglycans. Analysis of this particle using heparin affinity chromatography with fraction collection revealed that particles eluting at higher salt concentration had a greater proportion of peptide incorporation. Preliminary dual polarization interferometry experiments further support a strong interaction between this particle and heparin.

A preliminary report on the role of endoscopic endonasal nasopharyngectomy in recurrent rT3 and rT4 nasopharyngeal carcinoma.

Endoscopic endonasal nasopharyngectomy (EEN) has become increasingly used for recurrent nasopharyngeal carcinoma (rNPC) due to reduced functional and cosmetic morbidities compared to conventional external approach. Majority of the existing studies on EEN focused on patients with lower recurrent staging of rT1 and rT2. The aims of this study were to provide a preliminary report on the outcome of EEN performed in patients with advanced (rT3 and rT4) rNPC, and to determine the prognostic factors for patients' survival. All patients who underwent EEN for rNPC between January 2003 and December 2015 inclusive were analyzed. All surgeries were performed in University Malaya Medical Centre in Kuala Lumpur and Queen Elizabeth Hospital in Sabah, by a single surgeon. We reported the 2-year overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) and any related complications and significant prognostic factors. Fifteen patients with recurrent NPC (2 rT3 and 13 rT4 tumours) underwent EEN over the 13 years period. The mean age was 50.4 years (range 30-65) and the mean follow-up period was 28.7 months (range 9-81 weeks). The 2-year OS, DFS and DSS were 66.7 % (mean 19.4 months), 40 % (mean 15.7 months) and 73.3 % (mean 20.2 months), respectively. No severe operative complications were encountered. No independent prognostic factors for survival outcome were identified. This is the first preliminary report in English that exclusively looked at the use of EEN in advanced rT3 and rT4 NPCs, showing favourable patient outcome. However, further long-term follow-up of patients is required.

Rebound growth of hepatic colorectal metastases after neo-adjuvant chemotherapy: effect on survival after resection.

BACKGROUND: A period of recovery is commonly allowed between completion of chemotherapy for colorectal liver metastases (CRLM) and resection, during which tumour progression may occur. The study-aim is to assess the growth of CRLM in this interval and association with outcome. METHOD: Data on 146 patients were analysed. Change in tumour size was assessed by comparing size determined by imaging performed on completion of chemotherapy with that determined by examination of the resected specimen, categorised by RECIST criteria. RESULTS: In the interval before surgery sixteen patients (11%) fulfilled criteria for partial response (PR), 48 (33%) had stable disease (SD) and 82 (56%) had progressive disease (PD). Among patients with PD following chemotherapy the median disease-free survival of patients who initially responded (26 months) was longer than in those who initially had stable disease (7 months) (P = 0.002). No association was noted between rate of tumour growth after completion of chemotherapy and disease-free survival. CONCLUSION: Change in tumour size after completion of chemotherapy is variable and can be rapid, especially in patients who initially respond to treatment. However, disease-free survival is determined by tumour behaviour during treatment and not by change in size after completion of chemotherapy.

3 Tesla magnetic resonance imaging noise in standard head and neck sequence does not cause temporary threshold shift in high frequency.

High acoustic noise level is one of the unavoidable side effects of 3 T magnetic resonance imaging (MRI). A case of hearing loss after 3 T MRI has been reported in this institution and hence this study. The objective of this study was to determine whether temporary threshold shift (TTS) in high frequency hearing occurs in patients undergoing 3 T MRI scans of the head and neck. A total of 35 patients undergoing head and neck 3 T MRI for various clinical indications were tested with pure tone audiometry in different frequencies including high frequencies, before and after the MRI scan. Any threshold change from the recorded baseline of 10 dB was considered significant. All patients were fitted with foamed 3 M earplugs before the procedure following the safety guidelines for 3 T MRI. The mean time for MRI procedure was 1,672 s (range 1,040-2,810). The noise dose received by each patient amounted to an average of 3,906.29% (1,415-9,170%). The noise dose was derived from a normograph used by Occupational Noise Surveys. This was calculated using the nomograph of L eq, L EX, noise dose and time. There was no statistically significant difference between the hearing threshold before and after the MRI procedures for all the frequencies (paired t test, P > 0.05). For patients using 3 M foamed earplugs, noise level generated by 3 T MRI during routine clinical sequence did not cause any TTS in high frequency hearing.

Current Status of and Future Prospects for Drug-Eluting Stents and Scaffolds in Infrapopliteal Arteries.

Background: Chronic limb-threatening ischaemia can be a debilitating disease and may result in limb amputation if untreated. Atherosclerotic disease of the infra-popliteal arteries is particularly challenging to treat due to the small caliber of the vessels and the heavy burden of atherosclerotic plaque. Percutaneous transluminal angioplasty is the conventional first-line approach and is advantageous due to its minimal invasiveness, repeatability, and cost-effectiveness but is limited by high rates of elastic recoil, dissection, and short- to mid-term re-stenosis. Methods: This review analyses the growing body of published and presented clinical data from multiple randomised controlled trials that have investigated the role of coronary drug-eluting stents in the treatment of infrapopliteal disease. Results: Coronary drug-eluting stents demonstrate superior primary patency compared with angioplasty and/or bare metal stenting alone but are limited to application in short-segment disease and have not been widely adopted due to the nature of the permanent implant. Conclusions: Newer devices like drug-eluting resorbable scaffolds are promising as they allow the restoration of vessel wall vasomotion without a residual foreign body and can be used to treat longer, complex lesions.

A multi-centre stereotactic radiosurgery planning study of multiple brain metastases using isocentric linear accelerators with 5 and 2.5 mm width multi-leaf collimators, CyberKnife and Gamma Knife.

Objectives: This study compared plans of high definition (HD), 2.5 mm width multi-leaf collimator (MLC), to standard, 5 mm width, isocentric linear accelerator (linacs), CyberKnife (CK), and Gamma Knife (GK) for stereotactic radiosurgery (SRS) techniques on multiple brain metastases. Methods: Eleven patients undergoing SRS for multiple brain metastases were chosen. Targets and organs at risk (OARs) were delineated and optimized SRS plans were generated and compared. Results: The linacs delivered similar conformity index (CI) values, but the gradient index (GI) for HD MLCs was significantly lower (P-value <.001). Half the OARs received significantly lower dose using HD MLCs. CK delivered a significantly lower CI than HD MLC linac (P-value <.001), but a significantly higher GI (P-value <.001). CI was significantly improved with the HD MLC linac compared to GK (P-value = 4.591 × 10-3), however, GK delivered a significantly lower GI (P-value <.001). OAR dose sparing was similar for the HD MLC TL, CK, and GK. Conclusions: Comparing linacs for SRS, the preferred choice is HD MLCs. Similar results were achieved with the HD MLC linac, CK, or GK, with each delivering significant improvements in different aspects of plan quality. Advances in knowledge: This article is the first to compare HD and standard width MLC linac plans using a combination of single isocentre volumetric modulated arc therapy and multi-isocentric dynamic conformal arc plans as required, which is a more clinically relevant assessment. Furthermore, it compares these plans with CK and GK, assessing the relative merits of each technique.

Pentacam and Corvis ST findings in myopic Chinese patients with different corneal diameters in Singapore.

PURPOSE: To study the effect of corneal white-to-white diameter on Pentacam Scheimpflug cornea tomography and Corvis ST corneal visualization Scheimpflug technology parameters in myopic eyes. METHODS: In this retrospective cross-sectional study, 190 eyes of 190 Chinese myopic patients (spherical equivalent range: -1.25 D to -11.00 D) assessed for refractive surgery using Pentacam and Corvis ST devices were included. Patients were divided into groups based on corneal diameter: group A <12 mm, and group B ≥12 mm. Age, gender, spherical equivalent, Pentacam variables, and Corvis ST variables were collected. Statistical analysis was performed using IBM SPSS Statistics (Version 28.0). RESULTS: There were 110 patients in group A and 80 patients in group B, with no statistically significant difference in age, gender, or spherical equivalence. For Pentacam data, group A had significantly higher Belin/Ambrosio Enhanced Ectasia Display (BAD-D) scores than group B (0.88 vs. 0.44) and pachymetric progression index (minimum, average, and maximum), and steeper front keratometric values, whereas group B had larger anterior chamber depth and maximum Ambrosio-relational thickness (ARTmax) (462.54 vs. 503.93). BAD-D indices, pachymetric progression indices, and front keratometric values had negative correlations with corneal diameter, whereas ARTmax and back keratometric values had positive correlations. For Corvis ST data, group A had a significantly higher corneal biomechanical index (CBI) (negatively correlated) while group B had a higher Ambrosio relational thickness to the horizontal profile (ARTh) (473.60 vs. 570.78) (positively correlated). CONCLUSION: Corneal diameter influences both Pentacam and Corvis ST parameters, with smaller corneal diameters having a higher BAD-D and a lower ARTmax and ARTh. In addition, this is the first study to report a correlation between posterior surface corneal power and corneal diameter. As refractive surgery evaluation relies on these parameters, taking corneal diameter into account would improve both sensitivity and specificity in pre-refractive surgery screening for ectasia/keratoconus.

A highly divergent Encephalomyocarditis virus isolated from nonhuman primates in Singapore.

BACKGROUND: In 2001 and 2002, fatal myocarditis resulted in the sudden deaths of four, two adult and two juvenile, orang utans out of a cohort of 26 in the Singapore Zoological Gardens. METHODS: Of the four orang utans that underwent post-mortem examination, virus isolation was performed from the tissue homogenates of the heart and lung obtained from the two juvenile orang utans in Vero cell cultures. The tissue culture fluid was examined using electron microscopy. Reverse transcription and polymerase chain reaction with Encephalomyocarditis virus (EMCV)-specific primers targeting the gene regions of VP3/VP1 and 3D polymerase (3Dpol) confirmed the virus genus and species. The two EMCV isolates were sequenced and phylogenetic analyses of the virus genes performed. Serological testing on other animal species in the Singapore Zoological Gardens was also conducted. RESULTS: Electron microscopy of the two EMCV isolates, designated Sing-M100-02 and Sing-M105-02, revealed spherical viral particles of about 20 to 30 nm, consistent with the size and morphology of members belonging to the family Picornaviridae. In addition, infected-Vero cells showed positive immunoflorescence staining with antiserum to EMCV. Sequencing of the viral genome showed that the two EMCV isolates were 99.9% identical at the nucleotide level, indicating a similar source of origin. When compared with existing EMCV sequences in the VP1 and 3Dpol gene regions, the nucleotide divergence were at a maximum of 38.8% and 23.6% respectively, while the amino acid divergence were at a maximum of 33.9% and 11.3% respectively. Phylogenetic analyses of VP1 and 3Dpol genes further grouped the Sing-M100-02 and Sing-M105-02 isolates to themselves, away from existing EMCV lineages. This strongly suggested that Sing-M100-02 and Sing-M105-02 isolates are highly divergent variants of EMCV. Apart from the two deceased orang utans, a serological survey conducted among other zoo animals showed that a number of other animal species had neutralizing antibodies to Sing-M105-02 isolate, indicating that the EMCV variant has a relatively wide host range. CONCLUSIONS: The etiological agent responsible for the fatal myocarditis cases among two of the four orang utans in the Singapore Zoological Gardens was a highly divergent variant of EMCV. This is the first report of an EMCV infection in Singapore and South East Asia.

Influence of hip flexion angle on strength and gluteal muscle activities in the clinical pilates clamshell exercise.

The study aimed to investigate the presence of directional preference using the Clinical Pilates method of clamshell exercise among relatively healthy young adults, and the influence of hip flexion angles on maximum isometric strength (handheld dynamometer) and muscle activities (electromyography). The clamshell assessment involves testing in varying angles of hip flexion (0°, 30°, 60° and 90°) and 21 participants were tested. Directional preferences in the transverse and anteroposterior axes of movements were present among the participants. Gluteus medius activation was highest in the non-problem side across all hip flexion angles. In contrast, the problem side showed dysfunction of the gluteus medius, especially at the 60° hip flexion angle, 0.89 unit (ratio of maximal voluntary isometric contraction) reduction per 1 N force exerted, 95% CI -1.69 to -0.09, p = 0.031. Comparison against the non-problem side found gluteus medius activity lower on the problem side, mean difference (SD) was 26.2 (56.1), p = 0.045. Therefore, directional preference is not limited to people with injuries and can exist in healthy individuals or people who have recovered from injuries. The gluteus medius was identified to be dysfunctional on the problem side and Clinical Pilates clamshell assessment is potentially useful in assessing for motor coordination impairment.

Relationship between dry eye symptoms and quality of life: associations and mediation analysis.

PURPOSE: (1) To determine the independent association of dry eye symptoms with health-related quality of life (HRQoL) in the Singapore population and (2) to further investigate which factors mediate this association. METHODS: In this cross-sectional study, 7707 participants were included. The presence of dry eye symptoms was defined as experiencing at least one out of the six symptoms either 'often' or 'all the time'. The EuroQoL-5 dimensions (EQ-5D) utility instrument (raw scores converted to UK time trade-off (TTO) values) was used to assess generic HRQoL and the overall score from the Visual Functioning Questionnaire for visual functioning. The association between dry eye symptoms and EQ-5D was investigated using multivariable linear regression, adjusting for demographic and socioeconomic information, comorbidities, systemic and ocular examinations results. Mediation analysis was used to determine whether certain factors mediated this association. RESULTS: After adjusting for relevant factors, those with dry eye symptoms had significantly lower HRQoL (difference in EQ-5D TTO: -0.062 (95% CI -0.073 to -0.050)), with the inability to open eyes affected the most (-0.101 (95% CI -0.161 to -0.042)), followed by a sandy sensation (-0.089 (95% CI -0.121 to -0.058)), a burning sensation (-0.070 (95% CI -0.105 to -0.036)), red eyes (-0.059 (95% CI -0.082 to -0.036)), a dry sensation (-0.058 (95% CI -0.072 to -0.044)) and crusting of eyelids (-0.040 (95% CI -0.071 to -0.008)). Visual functioning and the presence of recent falls accounted for 8.63% (4.98%-14.5%) and 2.93% (0.04%-5.68%) of the indirect relationship between dry eye and HRQoL, respectively. CONCLUSION: Dry eye symptoms were independently associated with poor HRQoL. Moreover, this was partly mediated by reduced visual functioning and experiencing recent falls. Our results suggest that efforts to reduce severity of dry eye symptoms are essential to optimise patients' overall functioning and well-being.

Conjunctival T Cell Profile in Allogeneic Hematopoietic Stem Cell Transplant Patients after Instilling Topical Cyclosporine-A 0.1% Cationic Emulsion.

INTRODUCTION: To profile conjunctival T cell populations in allogeneic hematopoietic stem cell transplant (HSCT) patients after instillation of daily topical cyclosporine-A (CsA) 0.1% cationic emulsion (Ikervis), and to evaluate patients' tolerance to these eye drops. METHODS: Nineteen participants were prescribed Ikervis prophylaxis once daily to both eyes from 3-5 weeks pre-HSCT to 12 months post-HSCT. The outcome measure was conjunctival T cell proportions from flow cytometry after impression cytology. Covariates included visual acuity, intraocular pressure, slit lamp and fundal examination, dry eye (SPEED) and quality of life questionnaires, non-invasive keratograph tear break-up time (NIKBUT), conjunctival redness, meibography, lipid thickness, Schirmer test, tear cytokines, fluorescein staining, tear osmolarity, and meibomian gland expressibility. RESULTS: The conjunctival T cell analysis showed either stable or decreased proportions of conjunctival CD4 T cells at the last visit from baseline in compliant patients. CD4 proportions were increased in non-compliant patients and in the single patient who developed ocular graft-versus-host disease (GVHD). All patients were tolerant to Ikervis but 6/19 were not compliant. In the majority of patients, vision did not affect activities of daily living. Pre- and post-HSCT up to the last study visit, there was no statistically significant change in clinical covariates. Only one participant developed ocular GVHD at 9 months post-HSCT. CONCLUSION: Superficial conjunctival T cell profile reflects compliance to daily topical Ikervis eye drops and clinical ocular surface parameters in allogenic HSCT patients. Tolerance is comparable to other formulations of topical CsA in the first 12 months. GOV IDENTIFIER: NCT04636918. URL: https://clinicaltrials.gov/ct2/show/NCT04636918?cond=ocular+Graft+Versus+Host+Disease&cntry=SG&draw=2&rank=2 .

Long-term exposure to low-concentration PM2.5 and heart disease in older men in Perth, Australia: The Health in Men Study.

Exposure to particulate matter with an aerodynamic diameter less than or equal to 2.5 µm (PM2.5) is associated with increased risk of heart disease, but less is known about the relationship at low concentrations. This study aimed to determine the dose-response relationship between long-term PM2.5 exposure and risk of incident ischemic heart disease (IHD), incident heart failure (HF), and incident atrial fibrillation (AF) in older men living in a region with relatively low ambient air pollution. Methods: PM2.5 exposure was estimated for 11,249 older adult males who resided in Perth, Western Australia and were recruited from 1996 to 1999. Participants were followed until 2018 for the HF and AF outcomes, and until 2017 for IHD. Cox-proportional hazards models, using age as the analysis time, and adjusting for demographic and lifestyle factors were used. PM2.5 was entered as a restricted cubic spline to model nonlinearity. Results: We observed a mean PM2.5 concentration of 4.95 µg/m3 (SD 1.68 µg/m3) in the first year of recruitment. After excluding participants with preexisting disease and adjusting for demographic and lifestyle factors, PM2.5 exposure was associated with a trend toward increased incidence of IHD, HF, and AF, but none were statistically significant. At a PM2.5 concentration of 7 µg/m3 the hazard ratio for incident IHD was 1.04 (95% confidence interval [CI] = 0.86, 1.25) compared with the reference category of 1 µg/m3. Conclusions: We did not observe a significant association between long-term exposure to low-concentration PM2.5 air pollution and IHD, HF, or AF.

Fatal ingestion of Taxus baccata: English yew.

Poisoning from consumption of foraged alternative medicine products is an uncommon yet recognized occurrence. Here, presented is the case of a 40-year-old woman who was witnessed to collapse with labored breathing and subsequently died despite emergency medical personnel attendance and resuscitation efforts. Autopsy revealed the presence of plant matter that was visually identified as leaves from Taxus baccata - the English Yew. Isolation of alkaloids from the plant material and subsequent identification of the same alkaloids in the decedent's blood by liquid chromatography-tandem mass spectrometry indicated a toxicological cause of death. This case illustrates a collaborative team approach among subject matter experts to unexpectedly discover and then confirm the sudden death of this woman from T. baccata toxicity.

Current perspectives in the management of keratoconus with contact lenses.

Our aim is to review current and significant articles on contact lens wear in keratoconus patients. A comprehensive literature search of PubMed was performed for the following topics on contact lens wear in keratoconus patients: (1) characteristics of contact lens wearers, (2) safety and efficacy, (3) complications, (4) fitting techniques, (5) contact lens wear after procedures/surgeries, (6) patient satisfaction. A total of 104 studies were finally selected and reviewed. Gas permeable (GP) lens wear provided significantly better vision than glasses. Special cone design lenses had better patient comfort levels though there was no difference in best corrected visual acuity among the GP lenses. Soft lenses showed good efficacy for the treatment of mild-to-moderate keratoconus with newer designs improving visual performance such as customised hydrogel and novel pinhole lenses. Scleral and hybrid lenses provide good visual acuity and comfort for keratoconic patients previously intolerant to RGP lenses. RGP lens wear post-cross linking (CXL) is relatively well-tolerated. Contact lenses may still be required post intrastromal corneal ring procedures and post keratoplasty. Scheimpflug imaging and anterior segment optical coherent tomography (ASOCT) are useful in contact lens fitting. Computerized contact lens fitting techniques could reduce the chair time of lens fitting as well as improve comfort and visual performance. Contact lenses play an important role in the visual rehabilitation of keratoconus patients. New contact lens designs and materials have significantly expanded the available fitting options for keratoconus patients. Imaging technology can be utilized to guide contact lens fitting.

Therapeutic Contact Lenses in the Treatment of Corneal and Ocular Surface Diseases-A Review.

Therapeutic contact lenses (TCLs) are often used in the management of a wide variety of corneal and ocular surface diseases (OSDs). Indications of TCL include pain relief, enhancing corneal healing, corneal sealing, corneal protection, and drug delivery. For painful corneal diseases such as bullous keratopathy, epidermolysis bullosa, and epithelial abrasions/erosions, bandage contact lenses (BCLs) provide symptomatic relief. Postoperatively in photorefractive keratectomy or laser epithelial keratomileusis, BCLs also alleviate pain. In severe OSDs such as severe dry eye, Stevens-Johnson syndrome/toxic epidermal necrolysis, gas-permeable scleral contact lenses are often used to enhance corneal healing. BCLs are used post-keratoplasty, post-trabeculectomy, and post-amniotic membrane transplantation to enhance healing. BCLs, with or without glue adhesives, are used to seal small corneal perforations and sometimes also used as bridging treatment before penetrating keratoplasty in larger corneal perforations. In patients with eyelid conditions such as trichiasis, ptosis, and tarsal scarring, BCLs are also effective in forming a mechanical barrier to protect the cornea. A relatively new use for TCLs is in ocular drug delivery where TCLs are used to maintain therapeutic concentrations of medication on the ocular surface. Contraindications of the use of TCLs include infective keratitis, corneal anesthesia, and significant exposure keratopathy with inadequate eyelid position or movement. Complications of TCL include infective keratitis, corneal hypoxia and associated complications, corneal allergies and inflammation, and poor lens fit. Overall, TCLs are effective in the treatment of corneal and OSDs but contraindications and complications must be considered.

Low subjective socioeconomic status alters taste-based perceptual sensitivity to the energy density of beverages.

Lower socioeconomic status (SES) is associated with increased consumption of energy-dense foods and sugar-sweetened beverages. Recent findings suggest that the mere perception of having lower subjective SES (SSES) compared to others was sufficient to elicit heightened preferences and consumption of higher energy foods and meals. This increased drive for energy intake associated with low SSES may be accompanied by heightened perceptual sensitivity to the presence of energy in foods, which may aid discrimination and selection of energy-dense foods. The present study tested this prediction by investigating whether acute experiences of low SSES may produce subsequent shifts in perceptual sensitivity to the energy density of beverages. Participants performed two taste tests on 6 iced tea beverages that varied in energy density prior to (at baseline) and after an experimental SSES manipulation. There were no differences in general frequency of ice tea consumption across the SSES conditions. Results revealed that participants were better at perceiving beverages that were higher in energy to be more energy dense following the low SSES manipulation (compared to baseline evaluations). By contrast, participants in the high SSES and neutral control conditions exhibited no overall consistent change in sensitivity to perceived energy density across the beverages following the manipulation. Additionally, no effects of SSES manipulation were observed for rated palatability of the beverages. These findings demonstrate that subjective experiences of having inadequate socioeconomic resources may produce taste-based perceptual shifts that increase sensitivity to the presence of energy in foods, potentially through heightened attentiveness to or expectations of sensory characteristics that signal energy (i.e., sweetness, texture). Such perceptual shifts may have been adaptive for facilitating the discrimination and selection of energy-dense foods in the face of resource insecurity. Importantly, this study suggests that merely perceiving a socioeconomic disadvantage may enhance identification and consumption of energy-dense foods and beverages, which may represent a psychosocial process that contributes to socioeconomic disparities in consumption of energy dense foods, and may be operational via heightened perceptual sensitivity to sensory cues associated with the presence of energy in the consumed food.