Does testosterone influence the association between sleep and frailty in men: results from the European Male Aging Study.

BACKGROUND: Previous studies have suggested an association between sleep disturbance and frailty. The mechanism is unknown, although it has been suggested that hormonal factors may play a role. METHODS: The aim was to determine the association between sleep duration, sleep quality and frailty, and to determine whether testosterone influenced this association. Males aged 40-79 years were recruited from eight European centres to the European Male Aging Study (EMAS). Subjects completed an interviewer-assisted questionnaire including questions regarding sleep quality and duration. Sleep quality was scored 0-20 and categorised as 0-4, 5-9, 10-14, and 15-20, with higher scores indicating poorer quality. A 39-component frailty index (FI) was constructed. Total testosterone levels were measured. The association between sleep duration, sleep quality and the FI was assessed using negative binomial regression, with adjustment for putative confounders including testosterone level. RESULTS: Two thousand three hundred ninety-three participants contributed data to the analysis. The mean age was 63.3 years and mean sleep duration was 7.01 h. The mean frailty index was 0.15. Mean testosterone levels declined with decreasing sleep quality. After adjustment, compared to those with a sleep score of 0-4, the FI was 57% (95% CI 38%, 78%) higher among those with a sleep score of 15-20. After adjustment compared to those with normal sleep duration (6-9 h), those with a short (< 6 h) and long (≥ 9 h) sleep duration had a 16% (95% CI 6%, 28%) and 11% (95% CI 0%, 23%) higher FI, respectively. Adjustment for testosterone did not influence the strength of either association. CONCLUSION: Frailty is associated with impaired sleep quality and sleep duration. The association cannot, however, be explained by variation in testosterone levels.

A Novel and Accurate Method for Estimating Deaths and Cases During Outbreaks of Infectious Diseases Including COVID-19.

Introduction: Epidemiological modelling of infectious diseases plays an important role in driving public health policy. Commonly used models are described, including those based on exponential growth (Laplace and related distributions); susceptible-infected-removed; the Gompertz distribution; and the skew-reflected-Gompertz distribution. These are all sensitive to the timing of peak infection. The development of a novel method for forecasting the number of deaths occurring during epidemics of infectious diseases is described. Methods: The mathematical development of the authors' novel asymmetric difference model is detailed in this paper. Its predictions for mortality rates associated with the COVID-19 pandemic for 14 countries were compared with the corresponding published mortality data. Results: Forecasts by the asymmetric difference model of deaths from SARS-CoV-2 in different countries, actual recorded deaths to 30th June 2020, and corresponding errors included UK (42,700; 55,904; -24%); Poland (1490; 1444; +3%); Denmark (580; 605; -4%); Netherlands (6510; 6189; +5%); France (34,280; 29,836; +15%); Canada (1500; 8591; -78%); USA (44,540; 124,734; -64%); and Italy (22,020; 34,980; -37%). The model output was dependent upon forecast date accuracy for the peak of the disease outbreak. For Spain, the forecast date was one day early and for 10 (71%) countries the forecast peak occurred within seven days (inclusive) of the actual date. Discussion: Mortality prediction by the asymmetric difference model is relatively accurate. Furthermore, this new model does not appear to be as unduly sensitive to the timing of peak infection as other models. Indeed, its prediction of peak infection also appears to be relatively accurate.

Number of CAG repeats and mortality in middle aged and older men.

DESIGN: The androgen receptor (AR) mediates peripheral effects of testosterone. Previous data suggests an association between the number of CAG repeats in exon-1 of the AR gene and AR transcriptional activity. The aim of this analysis was to determine the association between the number of AR CAG repeats and all-cause mortality in men and the influence of testosterone level on the association. PATIENTS AND MEASUREMENTS: Follow-up data to 27 January 2018 were available for men aged 40-79 years recruited across six countries of the European Male Aging Study between 2003 and 2005. Cox proportional hazards modelling was used to determine the association between CAG repeat number/mortality. Results were expressed as hazard ratios (HR)/95% confidence intervals (CI). RESULTS: One thousand nine hundred and seventy-seven men were followed up. Mean baseline age was 60 ± 11.1 years. Mean duration of follow-up was 12.2 years. At follow up 25.1% of men had died. CAG repeat length ranged from 6 to 39, with the highest proportion of CAG repeat number at 21 repeats (16.4%). In a multivariable model, compared to men with 22-23 AR CAG repeats: for men with <22 and >23 AR CAG HR, 95% CI for mortality were, <22 CAG repeats 1.17 (0.93-1.49) and >23 CAG repeats 1.14 (0.88-1.47). In a post-hoc analysis, the association was significant for men in the lowest tertile of baseline testosterone (<14.2 nmol/L) with >23 CAG repeats: in the adjusted model for <22 and >23 CAG repeats, respectively, 1.49 (0.97-2.27) and 1.68 (1.06-2.67) versus 22-23 repeats. CONCLUSIONS: Our European-wide cohort data overall found no association of androgen receptor CAG repeat number and mortality in men. However, post hoc analysis suggested that an association might be present in men with lower baseline testosterone concentrations, which merits further investigation.

Association between psoriatic disease and lifestyle factors and comorbidities: cross-sectional analysis and Mendelian randomization.

OBJECTIVES: To examine associations between PsA and psoriasis vs lifestyle factors and comorbidities by triangulating observational and genetic evidence. METHODS: We analysed cross-sectional data from the UK Biobank (1836 PsA, 8995 psoriasis, 36 000 controls) to describe the association between psoriatic disease and lifestyle factors (including BMI and smoking) and 15 comorbidities [including diabetes and coronary artery disease (CAD)] using logistic models adjusted for age, sex and lifestyle factors. We applied bidirectional Mendelian randomization (MR) to genome-wide association data (3609 PsA and 7804 psoriasis cases, up to 1.2 million individuals for lifestyle factors and 757 601 for comorbidities) to examine causal direction, using the inverse-variance weighted method. RESULTS: BMI was cross-sectionally associated with risk of PsA (OR 1.31 per 5 kg/m2 increase; 95% CI 1.26, 1.37) and psoriasis (OR 1.23; 1.20, 1.26), with consistent MR estimates (PsA OR 1.38; 1.14, 1.67; psoriasis OR 1.36; 1.18, 1.58). In both designs, smoking was more strongly associated with psoriasis than PsA. PsA and psoriasis were cross-sectionally associated with diabetes (OR 1.35 and 1.39, respectively) and CAD (OR 1.56 and 1.38, respective). Genetically predicted glycated haemoglobin (surrogate for diabetes) increased PsA risk (OR 1.18 per 6.7 mmol/mol increase; 1.02, 1.36) but not psoriasis. Genetic liability to PsA (OR 1.05; 1.003, 1.09) and psoriasis (OR 1.03; 1.001, 1.06) were associated with increased risk of CAD. CONCLUSION: Observational and genetic evidence converge to suggest that BMI and glycaemic control are associated with increased psoriatic disease risk, while psoriatic disease is associated with increased CAD risk. Further research is needed to understand the mechanism of these associations.

The impact of frailty on patient-reported outcomes following hip and knee arthroplasty.

AIM: to determine the impact of frailty on patient-reported outcomes following hip and knee arthroplasty. METHODS: we used linked primary and secondary care electronic health records. Frailty was assessed using the electronic frailty index (categorised: fit, mild, moderate, severe frailty). We determined the association between frailty category and post-operative Oxford hip/knee score (OHS/OKS) using Tobit regression. We calculated the proportion of patients in each frailty category who achieved the minimally important change (MIC) in OHS (≥8 points) and OKS (≥7 points) and the proportion who reported a successful outcome (hip/knee problems either 'much better' or 'a little better' following surgery). RESULTS: About 42,512 people who had a hip arthroplasty and 49,208 who had a knee arthroplasty contributed data. In a Tobit model adjusted for pre-operative OHS/OKS, age, sex and quintile of index of multiple deprivation, increasing frailty was associated with decreasing post-operative OHS and OKS, respectively, ß-coefficient (95% CI) in severely frail versus fit, -6.97 (-7.44, -6.49) and - 5.88 (-6.28, -5.47). The proportion of people who achieved the MIC in OHS and OKS, respectively, decreased from 92 and 86% among fit individuals to 84 and 78% among those with severe frailty. Patient-reported success following hip and knee arthroplasty, respectively, decreased from 97 and 93% among fit individuals to 90 and 83% among those with severe frailty. CONCLUSION: frailty adversely impacts on patient-reported outcomes following hip and knee arthroplasty. However, even among those with severe frailty, the large majority achieved the MIC in OHS/OKS and reported a successful outcome.

The impact of frailty on short-term mortality following primary total hip and knee arthroplasty due to osteoarthritis.

BACKGROUND: We determined the association between frailty and short-term mortality following total hip and knee arthroplasty (THA/TKA) for osteoarthritis and also the impact of THA/TKA on short-term mortality compared with a control population. METHODS: Frailty was assessed using a frailty index (categorised: fit, mild, moderate, severe frailty). The association between frailty and short-term mortality following THA/TKA was assessed using Cox regression. Mortality following THA/TKA was also compared with a control population with osteoarthritis but no previous THA/TKA, matched on year of birth, sex and quintile of index of multiple deprivation. RESULTS: A total of 103,563 cases who had a THA, 125,367 who had a TKA and matched controls contributed. Among those who had surgery, mortality increased with increasing frailty; adjusted hazard ratio (HR) (95% CI) at 30 days in severely frail versus fit: following THA, 2.85 (1.84, 4.39) and following TKA, 2.14 (1.29, 3.53). The predicted probability of 30-day mortality following THA/TKA varied by age, sex and frailty: following THA, from 0.05% among fit women aged 60-64 years to 6.55% among men with severe frailty aged ≥90 years. All-cause 30-day mortality was increased in fit cases following THA and TKA, respectively, versus fit controls (adjusted HR (95% CI), 1.60 (1.15, 2.21) and 2.98 (1.81, 4.89)), though not among cases with mild, moderate or severe frailty versus controls in the same frailty category. CONCLUSION: Short-term mortality increased with increasing frailty following THA/TKA. Comparison of mortality among cases and controls may be affected by a 'healthy surgery' selection effect.

The association between lower socioeconomic position and functional limitations is partially mediated by obesity in older adults with symptomatic knee osteoarthritis: Findings from the English Longitudinal Study of Ageing.

Objective: To assess the longitudinal associations of socioeconomic position (SEP) with functional limitations and knee joint replacement surgery (JRS) in people with symptomatic knee osteoarthritis (OA), and whether body mass index (BMI) mediated these relationships. Methods: Data came from the English Longitudinal Study of Ageing, a national longitudinal panel study of adults aged ≥50 years. A total of 1,499 participants (62.3% female; mean age 66.5 (standard deviation (SD) 9.4) years; 47.4% obese) self-reporting an OA diagnosis and knee pain, with at least one BMI measurement were included. Mixed effect models estimated longitudinal associations of each SEP variable (education, occupation, income, wealth and deprivation index) and obesity (BMI ≥30.0 kg/m2) with repeated measures of functional limitations. Cox regression analyses estimated associations between SEP indicators and obesity at baseline and risk of knee JRS at follow-up. Structural equation modeling estimated any mediating effects of BMI on these relationships. Results: Lower SEP and obesity at baseline were associated with increased odds of functional limitations in people with knee OA [e.g., difficulty walking 100 yards: no qualification vs. degree adjOR 4.33 (95% CI 2.20, 8.55) and obesity vs. no obesity adjOR 3.06 (95% CI 2.14, 4.37); similar associations were found for the other SEP indicators]. A small proportion of the association between lower SEP and functional limitations could be explained by BMI (6.2-12.5%). Those with lower income, lower wealth and higher deprivation were less likely to have knee JRS [e.g., adjHR most vs. least deprived 0.37 (95% CI 0.19, 0.73)]; however, no clear association was found for education and occupation. Obesity was associated with increased hazards of having knee JRS [adjHR 1.87 (95% CI 1.32, 2.66)]. As the direction of the associations for SEP and obesity with knee JRS were in opposite directions, no mediation analyses were performed. Conclusions: Lower SEP was associated with increased odds of functional limitations but lower hazards of knee JRS among people with knee OA, potentially indicating underutilization of JRS in those with lower SEP. Obesity partially mediated the relationship between lower SEP and increased odds of functional limitations, suggesting adiposity as a potential interventional target.

Increased Frailty in Individuals With Osteoarthritis and Rheumatoid Arthritis and the Influence of Comorbidity: An Analysis of the UK Biobank Cohort.

OBJECTIVE: To determine the association between osteoarthritis (OA), rheumatoid arthritis (RA), and frailty and to determine whether comorbidities interact with OA and RA to further increase the likelihood of frailty. METHODS: Participants of the UK Biobank age 40-69 years at baseline were included. Demographic, lifestyle, and clinical data were collected at baseline and follow-up in a subset. Frailty was assessed using a frailty index (FI) (continuous) and a modified frailty phenotype (robust, pre-frail, frail). The association between RA and OA and frailty at baseline and follow-up was assessed using multiple regression models. We looked at whether comorbidities, including cardiovascular disease, diabetes mellitus, chronic obstructive pulmonary disease, and depression interacted additively with OA and RA to increase the likelihood of frailty. RESULTS: In total, 457,561 participants contributed data. Those with (versus without) RA (n = 4,894) and OA (n = 35,884), respectively, were more likely to be frail (adjusted relative risk ratio 10.7 [95% confidence interval (95% CI) 9.7, 11.7] and 3.4 [95% CI 3.3, 3.6]) and were more likely to have a higher FI at baseline. There was evidence of additive interaction between RA, OA, and common comorbidities increasing the occurrence of prevalent frailty. Among 25,163 participants included in longitudinal analysis, patients with RA (n = 202) and OA (n = 1,811) at baseline had an increased adjusted frailty incidence rate ratio (2.8 [95% CI 1.7, 4.6] and 1.7 [95% CI 1.3, 2.1], respectively) and also a higher FI during follow-up. CONCLUSION: Individuals with RA and OA are more likely to have, or develop, frailty. Common comorbidities interact with OA and RA to further increase the likelihood of frailty.

Incidence of Paget's disease of bone in the UK: evidence of a continuing decline.

OBJECTIVES: To characterize the incidence of clinically diagnosed Paget's disease of bone in the UK during 1999-2015 and to determine variations in the incidence of disease by age, sex, geography and level of deprivation. METHODS: Incident cases of Paget's disease occurring between 1999 and 2015 were identified from primary care records. Overall crude incidence and incidence stratified by age and sex was calculated each year from 1999 to 2015. Direct age- and sex-standardized incidence was also calculated. We used Poisson regression to look at variations in incidence by deprivation and UK region. RESULTS: A total of 3592 incident cases of Paget's disease were identified between 1999 and 2015. Incidence increased with age and at all ages was greater in men than women. In women and men, respectively, crude incidence increased from 0.037 and 0.074/10 000 population per year among those 45-49 years of age to 3.7 and 6.3/10 000 population per year among those ≥85 years. The overall standardized incidence decreased from 0.75/10 000 person-years in 1999 to 0.20/10 000 person-years in 2015. After adjustment for age and sex, incidence was >30% higher in the most- compared with least-deprived quintile of deprivation. There was evidence of geographic variation, with the highest incidence in the North West of England, which persisted after adjustment for age, sex and level of deprivation. CONCLUSION: The incidence of clinically diagnosed Paget's disease has continued to decrease since 1999. The reason for the decline in incidence remains unknown, although the rapidity of change points to an alteration in one or more environmental determinants.

Estimates for Lyme borreliosis infections based on models using sentinel canine and human seroprevalence data.

Two models were developed to estimate Lyme borreliosis (LB) cases. One was based on the seroprevalence of Borrelia infections in human samples. This model used corrections for false negative and false positive results from published test sensitivity and specificity measures. A second model based on Borrelia infections in sentinel dogs was used to quantify the prevalence of Lyme disease Borrelia infections in humans; the reference baseline for this model was human and canine infections in Germany. A comparison of the two models is shown and differences discussed. The relationships between incidence, prevalence and total infection burden for LB were derived from published data and these were used in both models to calculate annual incidence, prevalence and total LB infections. The modelling was conservative and based on medical insurance records coded for erythema migrans. Linear model growth rates were used in place of the commonly adopted exponential growth. The mean of the two models was used to create estimates for various countries and continents. Examples from the analyses for LB estimated for 2018 include: incidence - USA 473,000/year, Germany 471,000/year, France 434,000/year and UK 132,000/year; prevalence - USA 2.4 million, Germany 2.4 million, France 2.2 million and UK 667,000; total infections - USA 10.1 million, Germany 10.0 million, France 9.3 million and UK 2.8 million. Estimates for the world for 2018 are: incidence 12.3 million/year; prevalence 62.1 million; and total infection burden 262.0 million. These figures are far higher than officially published data and reflect not only the underestimation of diagnosed cases, which is acknowledged by health agencies, but also undiagnosed and misdiagnosed cases.

Is the use of antibiotic-loaded bone cement associated with a lower risk of revision after primary total hip arthroplasty?

AIMS: The aim of this study was to investigate whether the use of antibiotic-loaded bone cement influenced the risk of revision surgery after primary total hip arthroplasty (THA) for osteoarthritis. METHODS: The study involved data collected by the National Joint Registry (NJR) for England and Wales, Northern Ireland and the Isle of Man between 1 September 2005 and 31 August 2017. Cox proportional hazards were used to investigate the association between use of antibiotic-loaded bone cement and the risk of revision due to prosthetic joint infection (PJI), with adjustments made for the year of the initial procedure, age at the time of surgery, sex, American Society of Anesthesiologists (ASA) grade, head size, and body mass index (BMI). We looked also at the association between use of antibiotic-loaded bone cement and the risk of revision due to aseptic loosening or osteolysis. RESULTS: The cohort included 418,857 THAs of whom 397,896 had received antibiotic-loaded bone cement and 20,961 plain cement. After adjusting for putative confounding factors, the risk of revision for PJI was lower in those in whom antibiotic-loaded bone cement was used (hazard ration (HR) 0.79; 95% confidence interval (CI) 0.64 to 0.98). There was also a protective effect on the risk of revision due to aseptic loosening or osteolysis, in the period of > 4.1 years after primary THA, HR 0.57, 95% CI 0.45, 0.72. CONCLUSION: Within the limits of registry analysis, this study showed an association between the use of antibiotic-loaded bone cement and lower rates of revision due to PJI. The findings support the continued use of antibiotic-loaded bone cement in cemented THA. Cite this article: Bone Joint J 2020;102-B(8):997-1002.

A Clinical Diagnostic System for Late-Stage Neuropsychiatric Lyme Borreliosis Based upon an Analysis of 100 Patients.

Many late-stage chronic Lyme disease clinical findings are neuropsychiatric. A total clinical assessment is critical in diagnosis, especially since controversy surrounds the reliability of laboratory testing. The clinical findings of one hundred Lyme disease patients with chronic neuropsychiatric symptoms were entered into a database. The prevalence of each clinical finding pre-infection and post-infection was compared and calculated within the 95% confidence interval. Patients had minimal symptoms pre-infection, but a high post-infection prevalence of a broad spectrum of acquired multisystem symptoms. These findings included impairments of attention span, memory, processing, executive functioning, emotional functioning, behavior, psychiatric syndromes, vegetative functioning, neurological, musculoskeletal, cardiovascular, upper respiratory, dental, pulmonary, gastrointestinal, genitourinary, and other symptoms. The most prevalent symptoms included sustained attention impairments, brain fog, unfocused concentration, joint symptoms, distraction by frustration, depression, working memory impairments, decreased school/job performance, recent memory impairments, difficulty prioritizing multiple tasks, fatigue, non-restorative sleep, multitasking difficulties, sudden mood swings, hypersomnia, mental apathy, decreased social functioning, insomnia, tingling, word finding difficulties, name retrieval, headaches, sound hypersensitivity, paresis, anhedonia, depersonalization, cold intolerance, body temperature fluctuations, light sensitivity and dysfluent speech. The average patient had five symptoms pre-infection and 82 post-infection. Pattern recognition is critical in making a diagnosis. This study was used to develop three clinical assessment forms.

Task-related functional magnetic resonance imaging activations in patients with acute and subacute mild traumatic brain injury: A coordinate-based meta-analysis.

Task-based functional magnetic resonance imaging (fMRI) has been used to examine neuroanatomical and functional changes following mild traumatic brain injury (mTBI). Prior studies have lacked consistency in identifying common regions of altered neural activity during cognitive tasks. This may be partly due to differences in task paradigm, patient heterogeneity, and methods of fMRI analysis. We conducted a meta-analysis using an activation likelihood estimation (ALE) method to identify regions of differential brain activation in patients with mTBI compared to healthy controls. We included experiments that performed scans from acute to subacute time points post-injury. The seven included studies recruited a total sample of 174 patients with mTBIs and 139 control participants. The results of our coordinate based meta-analysis revealed a single cluster of reduced activation within the right middle frontal gyrus (MFG) that differentiated mTBI from healthy controls. We conclude that the cognitive impairments in memory and attention typically reported in mTBI patients may be associated with a deficit in the right MFG, which impacts the recruitment of neural networks important for attentional control.

Peptide directed phthalocyanine-gold nanoparticles for selective photodynamic therapy of EGFR overexpressing cancers.

Gold nanoparticles, covalently functionalised with the photosensitiser C11Pc and PEG, were actively targeted towards epidermal growth factor receptor overexpressing cancers using the peptide FITC-ßAAEYLRK. Selective phototoxicity was observed at nanomolar concentrations with minimal dark toxicity.

Statins, bone biology and revision arthroplasty: review of clinical and experimental evidence.

Osteoarthritis is a painful, disabling condition which is increasing in prevalence as a result of an ageing population. With no recognized disease-limiting therapeutics, arthroplasty of the hip and knee is the most common and effective treatment for lower limb osteoarthritis, however lower limb arthroplasty has a finite life-span and a proportion of patients will require revision arthroplasty. With increasing life expectancy and an increasing proportion of younger (<65 years) patients undergoing arthroplasty, the demand for revision arthroplasty after implant failure is also set to increase. Statins are cholesterol-modulating drugs widely used for cardiovascular risk reduction which have been noted to have pleiotropic effects including potentially influencing arthroplasty survival. In vitro studies have demonstrated pleiotropic effects in human bone cells, including enhancement of osteoblastogenesis following simvastatin exposure, and in vivo studies have demonstrated that intraperitoneal simvastatin can increase peri-implant bone growth in rats following titanium tibial implant insertion. There is evidence that statins may also influence osseointegration, enhancing bone growth at the bone-implant interface, subsequently improving the functional survival of implants. Data from the Danish Hip Arthroplasty Registry and the Clinical Practice Research Datalink in the UK suggest a reduction in the risk of lower limb revision arthroplasty in statin ever-users versus never-users, and a time-dependent effect of statins in reducing the risk of revision. In this article we review the clinical and experimental evidence linking statins and risk of revision arthroplasty.

Effect of Timing and Duration of Statin Exposure on Risk of Hip or Knee Revision Arthroplasty: A Population-based Cohort Study.

OBJECTIVES: To determine whether the timing and duration of statin exposure following total hip/knee arthroplasty (THA/TKA) influence the risk of revision arthroplasty. METHODS: Subjects from the Clinical Practice Research Datalink, a large population-based clinical database, who had THA/TKA from 1988 to 2016, were included. Propensity score adjusted Cox regression models were used to determine the association between statin exposure and the risk of revision THA/TKA, (1) at any time, and (2) if first exposed 0-1, 1-5, or > 5 years following THA/TKA. We also investigated the effect of duration of statin exposure (< 1, 1-2, 2-3, 3-4, 4-5, > 5 yrs). RESULTS: The study included 151,305 participants. There were 65,032 (43%) exposed to statins during followup and 3500 (2.3%) had revision arthroplasty. In a propensity score adjusted model, exposure to statins was associated with a reduced risk of revision arthroplasty (HR 0.82, 95% CI 0.75-0.90). Participants first exposed within 1 year and between 1 and 5 years following THA/TKA (vs unexposed) had a reduced risk of revision arthroplasty (HR 0.82, 95% CI 0.74-0.91 and HR 0.76, 95% CI 0.65-0.90, respectively). In relation to duration of statin therapy, participants exposed for more than 5 years in total (vs < 1 yr) had a reduced risk of revision (HR 0.74, 95% CI 0.62-0.88). CONCLUSION: Statin therapy initiated up to 5 years following THA/TKA may reduce the risk of revision arthroplasty.

Proposed Lyme Disease Guidelines and Psychiatric Illnesses.

The Infectious Disease Society of America, American Academy of Neurology, and American Academy of Rheumatology jointly proposed Lyme disease guidelines. Four areas most relevant to psychiatry were reviewed-the disclaimer, laboratory testing, and adult and pediatric psychiatric sections. The disclaimer and the manner in which these guidelines are implemented are insufficient to remove the authors and sponsoring organizations from liability for harm caused by these guidelines. The guidelines and supporting citations place improper credibility upon surveillance case definition rather than clinical diagnosis criteria. The guidelines fail to address the clear causal association between Lyme disease and psychiatric illnesses, suicide, violence, developmental disabilities and substance abuse despite significant supporting evidence. If these guidelines are published without very major revisions, and if the sponsoring medical societies attempt to enforce these guidelines as a standard of care, it will directly contribute to increasing a national and global epidemic of psychiatric illnesses, suicide, violence, substance abuse and developmental disabilities and the associated economic and non-economic societal burdens. The guideline flaws could be improved with a more appropriate disclaimer, an evidence-based rather than an evidence-biased approach, more accurate diagnostic criteria, and recognition of the direct and serious causal association between Lyme disease and psychiatric illnesses.

Fixed-target serial oscillation crystallography at room temperature.

A fixed-target approach to high-throughput room-temperature serial synchrotron crystallography with oscillation is described. Patterned silicon chips with microwells provide high crystal-loading density with an extremely high hit rate. The microfocus, undulator-fed beamline at CHESS, which has compound refractive optics and a fast-framing detector, was built and optimized for this experiment. The high-throughput oscillation method described here collects 1-5° of data per crystal at room temperature with fast (10°â€…s-1) oscillation rates and translation times, giving a crystal-data collection rate of 2.5 Hz. Partial datasets collected by the oscillation method at a storage-ring source provide more complete data per crystal than still images, dramatically lowering the total number of crystals needed for a complete dataset suitable for structure solution and refinement - up to two orders of magnitude fewer being required. Thus, this method is particularly well suited to instances where crystal quantities are low. It is demonstrated, through comparison of first and last oscillation images of two systems, that dose and the effects of radiation damage can be minimized through fast rotation and low angular sweeps for each crystal.

The prevalence of co-morbidities and their impact on physical activity in people with inflammatory rheumatic diseases compared with the general population: results from the UK Biobank.

Objectives: To compare the prevalence and incidence of chronic co-morbidities in people with inflammatory rheumatic and musculoskeletal diseases (iRMDs), and to determine whether the prevalent co-morbidities are associated with physical activity levels in people with iRMDs and in those without iRMDs. Methods: Participants were recruited to the UK Biobank; a population-based cohort. Data were collected about demographics, physical activity, iRMDs (RA, PsA, AS, SLE) and other chronic conditions, including angina, myocardial infarction, stroke, hypertension, pulmonary disease, diabetes and depression. The standardized prevalence of co-morbidities in people with iRMDs was calculated. Cox regression was used to determine the relationship between the presence of an iRMD and an incident co-morbidity. The relationship between the presence (versus absence) of a (co-)morbidity and physical activity level (low, moderate, high) in people with iRMDs and in those without was assessed using multinomial logistic regression. Results: A total of 488 991 participants were included. The estimated prevalence of each co-morbidity was increased in participants with an iRMD, compared with in those without, particularly for stroke in participants with SLE (standardized morbidity ratio (95% CI), 4.9 (3.6, 6.6). Compared with people with no iRMD and no morbidity, the odds ratios (95% CI) for moderate physical activity were decreased for: no iRMD and morbidity, 0.87 (0.85, 0.89); iRMD and no co-morbidity, 0.71 (0.64, 0.80); and iRMD and co-morbidity, 0.58 (0.54, 0.63). Conclusion: Having a (co-)morbidity is associated with reduced physical activity in the general population, and to a greater extent in participants with an iRMD. Optimal management of both iRMDs and co-morbidities may help to reduce their impact on physical activity.

Towards optimisation of surface enhanced photodynamic therapy of breast cancer cells using gold nanoparticle-photosensitiser conjugates.

Gold nanoparticles (AuNPs; ca. 4 nm) were synthesised and functionalised with a mixed monolayer of polyethylene glycol (PEG) and one of two zinc phthalocyanines (ZnPcs), the difference between the two molecules was the length of the carbon chain that connects the Pc to the gold core. The chain was composed of either three (C3Pc) or eleven (C11Pc) carbon atoms. The C11Pc photosensitiser displayed higher fluorescence emission intensity than the C3Pc in solution. By contrast, the C3Pc photosensitiser exhibited higher fluorescence when bound to the surface of the AuNPs than the C11Pc, despite the shorter carbon chain which was expected to quench the fluorescence. In addition, the C3Pc nanoparticle conjugates exhibited an enhancement in the production of singlet oxygen (1O2). The metal-enhanced 1O2 production led to a remarkable photodynamic efficacy for the treatment of human breast cancer cells.