Background: Severe neurological involvement in systemic lupus erythematosus (NPSLE) is one of the most dreadful complications of the disease. Objective: To identify the best drug, dose, and ...treatment. Patients and methods: The study was a controlled clinical trial at two tertiary care centres of patients with SLE according to the ACR criteria, with incident (no more than 15 days) onset of severe NP manifestations such as seizures, optic neuritis, peripheral or cranial neuropathy, coma, brainstem disease, or transverse myelitis. Induction treatment with 3 g of IV methylprednisolone (MP) followed by either IV monthly cyclophosphamide (Cy) versus IV MP bimonthly every 4 months for 1 year and then IV Cy or IV MP every 3 months for another year. The primary end point was response to treatment: at least 20% improvement from basal conditions on clinical, laboratory, or specific neurological testing variables. Results: Overall, a response rate of 75% was observed. Of the 32 patients studied, 18/19 receiving Cy and 7/13 receiving MP responded to treatment (p<0.03). Conclusions: Cy seems to be more effective than MP in the treatment of acute, severe NPSLE.
Type 2 diabetes (T2DM) is associated with an increased risk of cardiovascular disease. This can be partly explained by large-artery dysfunction, which already occurs in prediabetes ("ticking clock ...hypothesis"). Whether a similar phenomenon also applies to microvascular dysfunction is not known. We therefore tested the hypothesis that microvascular dysfunction is already present in prediabetes and is more severe in T2DM. To do so, we investigated the associations of prediabetes, T2DM, and measures of hyperglycemia with microvascular function measured as flicker light-induced retinal arteriolar dilation and heat-induced skin hyperemia.
In the Maastricht Study, a T2DM-enriched population-based cohort study (n=2213, 51% men, aged mean±standard deviation 59.7±8.2 years), we determined flicker light-induced retinal arteriolar %-dilation (Dynamic Vessel Analyzer), heat-induced skin %-hyperemia (laser-Doppler flowmetry), and glucose metabolism status (oral glucose tolerance test; normal glucose metabolism n=1269, prediabetes n=335, or T2DM n=609). Differences were assessed with multivariable regression analyses adjusted for age, sex, body mass index, smoking, physical activity, systolic blood pressure, lipid profile, retinopathy, estimated glomerular filtration rate, (micro)albuminuria, the use of lipid-modifying and blood pressure-lowering medication, and prior cardiovascular disease.
Retinal arteriolar %-dilation was (mean±standard deviation) 3.4±2.8 in normal glucose metabolism, 3.0±2.7 in prediabetes, and 2.3±2.6 in T2DM. Adjusted analyses showed a lower arteriolar %-dilation in prediabetes (B=-0.20, 95% confidence interval -0.56 to 0.15) with further deterioration in T2DM (B=-0.61 -0.97 to -0.25) versus normal glucose metabolism (P for trend=0.001). Skin %-hyperemia was (mean±standard deviation) 1235±810 in normal glucose metabolism, 1109±748 in prediabetes, and 937±683 in T2DM. Adjusted analyses showed a lower %-hyperemia in prediabetes (B=-46 -163 to 72) with further deterioration in T2DM (B=-184 -297 to -71) versus normal glucose metabolism (P for trend=0.001). In addition, higher glycohemoglobin A1c and fasting plasma glucose were associated with lower retinal arteriolar %-dilation and skin %-hyperemia in fully adjusted models (for glycohemoglobin A1c, standardized B=-0.10 -0.15 to -0.05, P<0.001 and standardized B=-0.13 -0.19 to -0.07, P<0.001, respectively; for fasting plasma glucose, standardized B=-0.09 -0.15 to -0.04, P<0.001 and standardized B=-0.10 -0.15 to -0.04, P=0.002, respectively).
Prediabetes, T2DM, and measures of hyperglycemia are independently associated with impaired microvascular function in the retina and skin. These findings support the concept that microvascular dysfunction precedes and thus may contribute to T2DM-associated cardiovascular disease and other complications, which may in part have a microvascular origin such as impaired cognition and heart failure.
Abstract
A new variant of
Streptococcus pyogenes
serotype M1 (designated ‘M1
UK
’) has been reported in the United Kingdom, linked with seasonal scarlet fever surges, marked increase in invasive ...infections, and exhibiting enhanced expression of the superantigen SpeA. The progenitor
S. pyogenes
‘M1
global
’ and M1
UK
clones can be differentiated by 27 SNPs and 4 indels, yet the mechanism for
speA
upregulation is unknown. Here we investigate the previously unappreciated expansion of M1
UK
in Australia, now isolated from the majority of serious infections caused by serotype M1
S. pyogenes
. M1
UK
sub-lineages circulating in Australia also contain a novel toxin repertoire associated with epidemic scarlet fever causing
S. pyogenes
in Asia. A single SNP in the 5’ transcriptional leader sequence of the transfer-messenger RNA gene
ssrA
drives enhanced SpeA superantigen expression as a result of
ssrA
terminator read-through in the M1
UK
lineage. This represents a previously unappreciated mechanism of toxin expression and urges enhanced international surveillance.
Daily glucose variability may contribute to vascular complication development irrespective of mean glucose values. The incremental glucose peak (IGP) during an oral glucose tolerance test (OGTT) can ...be used as a proxy of glucose variability. We investigated the association of IGP with arterial stiffness, arterial remodeling, and microvascular function, independent of HbA
and other confounders.
IGP was calculated as the peak minus baseline plasma glucose value during a seven-point OGTT in 2758 participants (age: 60 ± 8 years; 48% women) of The Maastricht Study, an observational population-based cohort. We assessed the cross-sectional associations between IGP and arterial stiffness (carotid-femoral pulse wave velocity cf-PWV, carotid distensibility coefficient carDC), arterial remodeling (carotid intima-media thickness cIMT; mean CWS
and pulsatile CWS
circumferential wall stress), and microvascular function (retinal arteriolar average dilatation; heat-induced skin hyperemia) via multiple linear regression with adjustment for age, sex, HbA
, cardiovascular risk factors, lifestyle factors, and medication use.
Higher IGP was independently associated with higher cf-PWV (regression coefficient B: 0.054 m/s 0.020; 0.089) and with higher CWS
(B: 0.227 kPa 0.008; 0.446). IGP was not independently associated with carDC (B: - 0.026 10
/kPa - 0.112; 0.060), cIMT (B: - 2.745 µm - 5.736; 0.245), CWS
(B: 0.108 kPa - 0.054; 0.270), retinal arteriolar average dilatation (B: - 0.022% - 0.087; 0.043), or heat-induced skin hyperemia (B: - 1.380% - 22.273; 19.513).
IGP was independently associated with aortic stiffness and maladaptive carotid remodeling, but not with carotid stiffness, cIMT, and microvascular function measures. Future studies should investigate whether glucose variability is associated with cardiovascular disease.
Abstract Background Adolescents with previous self-injurious thoughts and behaviors (SITB) have over 2-fold risk of dying by suicide, higher than older ages. This meta-analysis aims to disentangle ...the association of each SITB with subsequent suicidal behavior in adolescence/young adulthood, the contribution of each SITB, and the proportion of suicide deaths with no previous suicide attempt. Methods We searched 6 databases until June 2015. Inclusion criteria: 1. Assessment of any previous SITB a) suicidal thoughts and behaviors (ideation; threat/gesture; plan; attempt); b) non-suicidal thoughts and behaviors (thoughts; threat/gesture; self-injury); c) self-harm as a risk factor of suicide attempt or suicide death; 2. Case-control or cohort studies; 3. Subjects aged 12-26y. Random effect models, metaregression analyses including mental health and environmental variables, and population attributable risks (PAR)s were estimated. Results From 23,682 potentially eligible articles, 29 were included in the meta-analysis (1,122,054 individuals). While 68% of all youth suicide deaths had no previous suicide attempt, suicide death was very strongly associated with any previous SITB (OR= 22.53, 95%CI: 18.40–27.58). Suicide attempts were also associated with a history of previous SITB (OR= 3.48, 95%CI: 2.71–4.43). There were no moderating effects for mental health and environmental features. The PAR of previous SITB to suicide attempts is 26%. Limitations There is considerable heterogeneity between the available studies. Due to limitations in the original studies, an over-estimation of the proportion dying at their first attempt cannot be ruled out, since they might have missed unrecognized previous suicide attempts. Conclusions Although more than two thirds of suicide deaths in adolescence/young adulthood have occurred with no previous suicidal behavior, previous SITBs have a much higher risk of dying by suicide than previously reported in this age group.
Analysing farmer knowledge of the requirements of finance providers can provide valuable insights to policy makers about ways to improve farmers' access to finance. This study compares farmer ...knowledge of the requirements to obtain finance with the actual requirements set by different finance provider types, and investigates the relation between demographic and socioeconomic factors and farmer knowledge of finance requirements. We use a structured questionnaire to collect data from a sample of finance providers and farmers in Java Island, Indonesia. We find that the most important requirements to acquire finance vary among different finance provider types. We also find that farmers generally have little knowledge of the requirements, which are important to each type of finance provider. Awareness campaigns are needed to increase farmer knowledge of the diversity of requirements among the finance provider types.
Background
Tooth wear is a multifactorial condition, leading to the loss of dental hard tissues. Physiological tooth wear is a slow process that normally does not lead to any subjective symptoms. ...When the condition progresses, it can become pathological, and several signs and symptoms may occur. The Tooth Wear Evaluation System (TWES) was described to implement a systematic diagnostic and management approach. Recently, management guidelines were presented in a European Consensus Statement (ECS) as well.
Objectives
To evaluate the TWES in practice and to integrate the principles described in the ECS in order to compose a renewed TWES 2.0 and a new taxonomy.
Methods
The TWES and the recommendations of the ECS were used by dental clinicians, in order to test its applicability in practice.
Results
Agreement was reached that the TWES 2.0 will use a stepwise approach, with a straightforward Tooth Wear Screening part and a more detailed Tooth Wear Status part. Also, the assessment of pathology from the ECS is incorporated in the TWES 2.0 (both classification and taxonomy).
Conclusions
In the TWES 2.0 is described that tooth wear is pathological if moderate/severe/extreme tooth wear is present, in combination with one or several described signs and symptoms. Aetiology can be assessed by findings that indicate a chemical and/or a mechanical cause. The taxonomy may help to identify situations in which preventive (restorative) interventions in early stages of tooth wear can be indicated. The reliability and validity of the adapted parts must be proven.
Abstract
Microvascular dysfunction (MVD) is a common pathophysiological change that occurs in various diseases, such as type 2 diabetes mellitus (T2DM), heart failure, dementia, and depression. ...Recent technical advances have enabled noninvasive measurement and quantification of microvascular changes in humans. In this paper, we describe the protocols of the microvascular measurements applied in the Maastricht Study, an ongoing prospective, population-based cohort study of persons aged 40–75 years being carried out in the southern part of the Netherlands (baseline data assessment, November 2010–January 2020). The study includes a variety of noninvasive measurements in skin, retina, brain, and sublingual tissue, as well as plasma and urine biomarker assessments. Following this, we summarize our main findings involving these microvascular measurements through the end of 2018. Finally, we provide a brief perspective on future microvascular investigations within the framework of the Maastricht Study.
This book presents a comprehensive overview of the research and latest developments in the field of the dynamics of coupled and driven chaotic oscillators, aimed at a wide audience. Since 1990, there ...has been very active research devoted to the field, culminating in a considerable body of knowledge, while active research continues.The results presented in the book will be valuable for scientific analysis and explanation in various different scientific disciplines, with potential applications in medicine and engineering. The contents include a selection of the most basic theoretical results, as well as experiments and applications presented at a mathematical level suited to readers working in non-hard sciences. It will also be of interest to physicists and mathematicians looking for an introduction to the field.
PDF
