Miracle-dz/UniFAR-FTUs huggingface dataset:
Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis†

Abstract Diabetic foot is a severe public health issue, yet rare studies investigated its global epidemiology. Here we performed a systematic review and meta-analysis through searching PubMed, EMBASE, ISI Web of science, and Cochrane database. We found that that global diabetic foot ulcer prevalence was 6.3% (95%CI: 5.4–7.3%), which was higher in males (4.5%, 95%CI: 3.7–5.2%) than in females (3.5%, 95%CI: 2.8–4.2%), and higher in type 2 diabetic patients (6.4%, 95%CI: 4.6–8.1%) than in type 1 diabetics (5.5%, 95%CI: 3.2–7.7%). North America had the highest prevalence (13.0%, 95%CI: 10.0–15.9%), Oceania had the lowest (3.0%, 95% CI: 0.9–5.0%), and the prevalence in Asia, Europe, and Africa were 5.5% (95%CI: 4.6–6.4%), 5.1% (95%CI: 4.1–6.0%), and 7.2% (95%CI: 5.1–9.3%), respectively. Australia has the lowest (1.5%, 95%CI: 0.7–2.4%) and Belgium has the highest prevalence (16.6%, 95%CI: 10.7–22.4%), followed by Canada (14.8%, 95%CI: 9.4–20.1%) and USA (13.0%, 95%CI: 8.3–17.7%). The patients with diabetic foot ulcer were older, had a lower body mass index, longer diabetic duration, and had more hypertension, diabetic retinopathy, and smoking history than patients without diabetic foot ulceration. Our results provide suggestions for policy makers in deciding preventing strategy of diabetic foot ulceration in the future. Key messages Global prevalence of diabetic foot is 6.3% (95%CI: 5.4–7.3%), and the prevalence in North America, Asia, Europe, Africa and Oceania was 13.0% (95%CI: 10.0–15.9%), 5.5% (95%CI: 4.6–6.4%), 5.1% (95%CI: 4.1–6.0%), 7.2% (95%CI: 5.1–9.3%), and 3.0% (95% CI: 0.9–5.0%). Diabetic foot was more prevalent in males than in females, and more prevalent in type 2 diabetic foot patients than in type 1 diabetic foot patients. The patients with diabetic foot were older, had a lower body mass index, longer diabetic duration, and had more hypertension, diabetic retinopathy, and smoking history than patients without diabetic foot.
VEGF antagonism and age-related macular degeneration: too much of a good thing?

The discovery of the role of VEGF in retinal/choroidal neovascularization (CNV) and the subsequent development of VEGF antagonists to inhibit its activity were significant breakthroughs for treating neovascular eye diseases. Anti-VEGF therapies are widely used in the clinic to treat neovascular age-related macular degeneration (AMD) and, more recently, other proliferative vasculopathies. More potent and longer-lasting VEGF antagonists continue to be developed despite clear data from several groups working in multiple organ systems that VEGF also exerts critical potent vasculotrophic and neurotrophic effects. We recently reported that the targeted deletion of VEGF in adult murine retinal pigment epithelial (RPE) cells induces rapid and progressive vascular and neuronal cell atrophy in the retina. In this report, we will review the basic and clinical research reports that clearly demonstrate that endogenous VEGF in multiple tissues, including the retina, provides critical trophic support for neurons and vessels, and in the absence of this local, paracrine effect, there is significant anatomical and functional loss in the retina and other organ systems.
Effect of Systemic Monosodium Glutamate (MSG) on Headache and Pericranial Muscle Sensitivity

We conducted a double-blinded, placebo-controlled, crossover study to investigate the occurrence of adverse effects such as headache as well as pain and mechanical sensitivity in pericranial muscles after oral administration of monosodium glutamate (MSG). In three sessions, 14 healthy men drank sugar-free soda that contained either MSG (75 or 150 mg/kg) or NaCl (24 mg/kg, placebo). Plasma glutamate level, pain, pressure pain thresholds and tolerance levels, blood pressure (BP), heart rate and reported adverse effects were assessed for 2 h. No muscle pain or robust changes in mechanical sensitivity were detected, but there was a significant increase in reports of headache and subjectively reported pericranial muscle tenderness after MSG. Systolic BP was elevated in the high MSG session compared with low MSG and placebo. These findings add new information to the concept of MSG headache and craniofacial pain sensitivity.
Caffeine Intake, Coffee Consumption, and Risk of Cutaneous Malignant Melanoma

Background: Caffeine has been shown to prevent ultraviolet radiation-induced carcinogenesis and to inhibit growth of melanoma cells in experimental studies. We evaluated the association among caffeine intake, coffee consumption, and melanoma risk among three large cohort studies. Methods: The analysis used data from 89,220 women in the Nurses’ Health Study II (1991–2009), 74,666 women in the Nurses’ Health Study (1980–2008), and 39,424 men in the Health Professionals Follow-up Study (1986–2008). We used Cox proportional hazards models to estimate the hazard ratios (HR) with 95% confidence intervals (CIs) of melanoma associated with dietary intakes. Results: We documented 2,254 melanoma cases over 4 million person-years of follow-up. After adjustment for other risk factors, higher total caffeine intake was associated with a lower risk of melanoma (≥393 mg/day vs. <60 mg/day: HR = 0.78, 95% CI = 0.64, 0.96; Ptrend = 0.048). The association was more apparent in women (≥393 mg/day vs. <60 mg/day: HR = 0.70, 95% CI = 0.58, 0.85; Ptrend = 0.001) than in men (HR = 0.94, 95% CI = 0.75, 1.2; Ptrend = 0.81), and more apparent for melanomas occurring on body sites with higher continuous sun exposure (head, neck, and extremities; ≥393 mg/day vs. <60 mg/day: HR = 0.71, 95% CI = 0.59, 0.86; Ptrend = 0.001) than for melanomas occurring on body sites with lower continuous sun exposure (trunk including shoulder, back, hip, abdomen, and chest; HR = 0.90, 95% CI = 0.70, 1.2; Ptrend = 0.60). This pattern of association was similar to that for caffeinated coffee consumption, whereas no association was found for decaffeinated coffee consumption and melanoma risk. Conclusions: Increasing caffeine intake and caffeinated coffee consumption is associated with decreased risk of cutaneous malignant melanomas.
Prolyl 4-hydroxylases, key enzymes in the synthesis of collagens and regulation of the response to hypoxia, and their roles as treatment targets

Prolyl 4-hydroxylases (P4Hs) have central roles in the synthesis of collagens and the regulation of oxygen homeostasis. The 4-hydroxyproline residues generated by the endoplasmic reticulum (ER) luminal collagen P4Hs (C-P4Hs) are essential for the stability of the collagen triple helix. Vertebrate C-P4Hs are α2β2 tetramers with three isoenzymes differing in their catalytic α subunits. Another P4H family, the HIF-P4Hs, hydroxylates specific prolines in the α subunit of the hypoxia-inducible transcription factor (HIF), a master regulator of hypoxia-inducible genes, and controls its stability in an oxygen-dependent manner. The HIF-P4Hs are cytoplasmic and nuclear enzymes, likewise with three isoenzymes in vertebrates. A third vertebrate P4H type is an ER transmembrane protein that can act on HIF-α but not on collagens. All P4Hs require Fe2+, 2-oxoglutarate, O2, and ascorbate. C-P4Hs are regarded as attractive targets for pharmacological inhibition to control excessive collagen accumulation in fibrotic diseases and severe scarring, while HIF-P4H inhibitors are believed to have beneficial effects in the treatment of diseases such as myocardial infarction, stroke, peripheral vascular disease, diabetes, and severe anemias. Studies with P4H inhibitors in various animal models of fibrosis, anemia, and ischemia and ongoing clinical trials with HIF-P4H inhibitors support this hypothesis by demonstrating efficacy in many applications.
Within-subject Pooling of Biological Samples to Reduce Exposure Misclassification in Biomarker-based Studies

Background: For chemicals with high within-subject temporal variability, assessing exposure biomarkers in a spot biospecimen poorly estimates average levels over long periods. The objective is to characterize the ability of within-subject pooling of biospecimens to reduce bias due to exposure misclassification when within-subject variability in biomarker concentrations is high. Methods: We considered chemicals with intraclass correlation coefficients of 0.6 and 0.2. In a simulation study, we hypothesized that the chemical urinary concentrations averaged over a given time period were associated with a health outcome and estimated the bias of studies assessing exposure that collected 1 to 50 random biospecimens per subject. We assumed a classical type error. We studied associations using a within-subject pooling approach and two measurement error models (simulation extrapolation and regression calibration), the latter requiring the assay of more than one biospecimen per subject. Results: For both continuous and binary outcomes, using one sample led to attenuation bias of 40% and 80% for compounds with intraclass correlation coefficients of 0.6 and 0.2, respectively. For a compound with an intraclass correlation coefficient of 0.6, the numbers of biospecimens required to limit bias to less than 10% were 6, 2, and 2 biospecimens with the pooling, simulation extrapolation, and regression calibration methods (these values were, respectively, 35, 8, and 2 for a compound with an intraclass correlation coefficient of 0.2). Compared with pooling, these methods did not improve power. Conclusion: Within-subject pooling limits attenuation bias without increasing assay costs. Simulation extrapolation and regression calibration further limit bias, compared with the pooling approach, but increase assay costs.
Pleasant natural scent with unpleasant effects: Cluster headache-like attacks triggered by Umbellularia californica

Umbellularia californica, a shrub or tree indigenous to southwestern Oregon and northern California, is commonly known as headache tree, probably because it is reported that its scent can cause headache. Here, we report the case of a 69-year-old Italian gardener, affected during his young adult age by cluster headache, who, 10 years from his last cluster episode, developed shorter-lasting cluster-like headache attacks after and at any time he was exposed to U. californica scent. The present case indicates that, even though endogenous mechanisms causing the cluster headache were no longer present, susceptibility to exogenous triggers remains active in this patient, and suggests that identification of the constituent(s) of U. californica responsible for triggering cluster headache-like attacks may help in the understanding of the hitherto elusive mechanism of cluster headache.
Pregnancy as a time for dietary change?

It is thought that nutrition during pregnancy plays a key role in the well-being of the mother and the newborn infant, and further influences health during childhood and adulthood. Pregnancy is a time of increased nutritional requirements, but many of these requirements will be met by adaptive physiological changes that occur during gestation, with little need to alter maternal dietary intake. A modest increment of food which provides 0.8 MJ/d (above prepregnant requirements) during the third trimester is considered adequate to meet the needs of fetal and maternal growth, and to satisfy the small increase in requirements of many macro- and micronutrients. However, requirements for vitamin D and folic acid increase substantially, and should be met primarily by supplementation. Food selection may also be altered to avoid a range of food-borne diseases and toxic constituents. There are a number of psycho-social reasons why pregnancy might be considered a good time for promoting changes in dietary behaviour for the health of the wider family. However, pregnancy may be a bad time to promote dietary change if it is perceived to involve slimming, if nutritional requirements are greatest before pregnancy, or if dietary changes made are harmful. There is little evidence to support educational interventions as successful at changing dietary behaviour during pregnancy. Pregnancy may be best viewed as an opportunity for maintaining good dietary selections and for building knowledge for future action, and should not be seen as the only opportunity for promoting dietary change within the life course.
Independent and combined influence of AGTR1 variants and aerobic exercise on oxidative stress in hypertensives

Abstract Angiotensin II (AngII), via the AngII type 1 receptor (AT1R), contributes to oxidative stress. Aerobic exercise training (AEXT) reduces the risk of cardiovascular (CV) disease, presumably by reducing the grade of oxidative stress. We investigated the independent and combined influence of the AGTR1 A1166C and -825 T/A polymorphisms on oxidative stress and plasma AngII responses to AEXT in pre- and stage 1 hypertensives. Urinary 8-iso-PGF2α significantly increased with AEXT (p=0.002); however, there were no significant changes in superoxide dismutase activity or AngII levels. There was a significant difference in the change in AngII levels with AEXT between A1166C genotype groups (p=0.04) resulting in a significant interactive effect of the A1166C polymorphism and AEXT on the change in AngII (p<0.05). Only the TT genotype group of the -825 T/A polymorphism had a significant reduction in plasma AngII (p=0.02). Risk allele analysis revealed a significant reduction in plasma AngII (p=0.04) and a significant increase in urinary 8-iso-PGF2α (p=0.01) with AEXT in individuals with two risk alleles only. Our findings suggest that variation in the AGTR1 gene is associated with differential changes in plasma AngII but not oxidative stress.
Wheeze and Asthma in Children: Associations With Body Mass Index, Sports, Television Viewing, and Diet

Background: Obesity, physical activity, and dietary habits are distinct but strongly interrelated lifestyle factors that may be relevant to the prevalence of wheeze and asthma in children. Our goal was to analyze the relationship of body mass index (BMI), regular sports participation, TV viewing, and diet with current wheezing and asthma. Methods: We investigated 20,016 children, aged 6–7 years, who were enrolled in a population-based study. Parents completed standardized questionnaires. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), while adjusting for several confounders and simultaneously considering BMI, regular sports activity, TV viewing and selected dietary items. Results: A total of 1575 children (7.9%) reported current wheezing and 1343 (6.7%) reported current asthma. In a multivariate model, an elevated BMI was associated with wheeze and current asthma: children from the highest quintile (compared with the lowest quintile) had an increased risk of wheeze (OR = 1.47; CI = 1.20–1.82) or current asthma (1.61; 1.28–2.01). Wheeze or asthma was not associated with regular sports activity. Subjects who spent 5 or more hours per day watching television were more likely to experience wheeze (1.53; 1.08–2.17) or current asthma (1.51; 1.04–2.2) compared with those who viewed TV less than 1 hour a day. Adding salt to food was strongly and independently associated with current wheeze (2.58; 1.41–4.71) and current asthma (2.68; 1.41–5.09). Conclusions: Our data support the hypothesis that high body weight, spending a lot of time watching television, and a salty diet each independently increase the risk of asthma symptoms in children.
Expression of extracellular RNA in synovial tissue and RNase activity in synovial fluid of rheumatoid arthritis patients

Background RNA is required for protein biosynthesis. However, extracellular RNA (exRNA) is also present within tissues and actively secreted by cells. Examples for the exRNA-activity are a pro-coagulative effect and an enhanced permeability of the blood-brain-barrier by exRNA. Furthermore, specific exRNAs are accumulated in the serum in cancer and these exRNA have actually been identified as tumour-markers. A pro-inflammatory effect of extracellular DNA due to tissue damage has been described in rheumatoid arthritis (RA). Therefore, the authors analysed the presence and the expression pattern of exRNA in the joint as well as the activity of RNase in the synovial fluid of RA patients. Methods Synovium from RA and OA patients (n=3 each) were stained with 4′,6-diamidin-2-phenylindole (DAPI) to locate DNA and SYTO RNASelect Green Fluorescent Stain to locate RNA in the tissue. A serial tissue section was stained with H&E to identify the lining layer and sublining. The expression pattern of RNA was analyed by comparing the RNA and DNA staining with the HE-staining on serial sections. In addition, the RNase activity of the synovium of different patient groups (RA: n=4; OA: n=3 and psoriatic arthritis (PsA): n=5) was measured using the Quant-iT RNA Assay Kit. Results RNA and DNA signals were detectable in all areas of the synovium. Merging the RNA and DNA signals showed a co-localisation of the signals within the nucleus of the cell. Interestingly, an intensive cytoplasmatic and exRNA signal could be observed in the lining layer of RA and OA patients with stronger signal intensity in the RA lining. Due to the increased thickness of the lining layer in RA patients, an increased amount of exRNA in RA patients when compared to OA was detectable. This signal was not co-localised with the DNA. A reduced RNase activity was measured in the synovial fluid of patients with RA (20.1±3.61) and PsA (21.3±2.5) in comparison to OA patients (35.8±4.5), reaching statistical significance when comparing PsA to OA patients (p=0,033). In addition, RNase activity was inversely correlated to CRP serum level (r=−0.43). Conclusion In OA and especially RA patients, exRNA is present in the synovial lining layer. RNase activity in the synovial fluid seems to be reduced in patients with chronic inflammation (RA and PSA) in contrast to OA. The increased amounts of exRNA could demonstrate a new pro-inflammatory mechanism active in chronic inflamed tissue that could be important for the perpetuation and chronification of inflammation.
Residential Exposure to Urban Air Pollution, Ankle–Brachial Index, and Peripheral Arterial Disease

Background: Long-term exposure to particulate air pollution has been associated with increased cardiovascular disease. Biologic pathways for this association are not fully understood. Methods: We examined the association of urban air pollution with atherosclerosis of the peripheral vascular bed, using baseline data (2000–2003) from 4348 participants in a population-based cohort study in the German Ruhr Area. Levels of annual fine particulate matter (PM2.5) exposure, derived from a dispersion and chemistry transport model, were assigned to the participants’ home addresses. Residential traffic exposure was assessed by the distance between residence and major roads (federal and state highways). Using multiple regression analyses and controlling for individual level risk factors, we examined the association of PM2.5 and traffic with the ankle–brachial index and prevalence of peripheral arterial disease, defined as an index of less than 0.9 or a history of treatment for peripheral artery disease. Results: Living within 101–200, 51–100, and 50 m of a major road was associated with an adjusted absolute decrease in ankle–brachial index of −0.015 (95% confidence interval [CI] = −0.030 to 0.0), −0.002 (−0.021 to 0.016) and –0.024 (−0.047 to −0.001), respectively. Stronger associations were seen in women, whereas no clear association was found in men. Individuals living within 50 m of a major road had an OR of 1.77 (1.01–2.1) for peripheral arterial disease compared with those living more than 200 m away. Associations with PM2.5 were inconsistent. Conclusions: This study adds to the evidence that long-term residential exposure to traffic is associated with atherosclerosis.
Parent-reported symptoms, impairment, helpfulness of treatment, and unmet service needs in a follow-up of outpatient children with attention-deficit/hyperactivity disorder

Abstract Background: Limited information exists regarding the associations between impairment, symptoms, helpfulness of treatments, and service needs after initial treatment of children with attention-deficit/hyperactivity disorder (ADHD). Aims: The aims of this study were to examine persistence rates and associations between parent-reported symptoms, impairment, helpfulness of treatments, and service needs in a retrospective follow-up study of children with ADHD. Methods: Parents of 214 children with a mean age of 12.6 years (SD = 2.1) who were diagnosed with ADHD at five child and adolescent mental health clinics (CAMHS) completed questionnaires 1–10 years (mean = 3.7 years, SD = 2.2) after baseline assessment. The response rate was 43.4%. A community comparison group (n = 110) was recruited from the same area. Results: Approximately two-thirds (60.3%) of the sample fulfilled the DSM-IV symptom criteria of ADHD at follow-up, 84.3% were functionally impaired, and most children (84.7%) were on medication. Inattentive and emotional symptoms were the strongest predictors of impairment across impairment areas. Perceived helpfulness of different treatments varied from 71.8–88.7%, and no significant difference was found between the ADHD sub-groups regarding reported helpfulness. ‘Adjustment of the school situation’ was the most frequent service need, and approximately half of the parents reported needs for care co-ordination. Children fulfilling the symptom criteria of the ADHD Combined sub-group were most impaired and had most service needs. Conclusions: At follow-up, children were highly symptomatic and impaired, despite a high rate of persistent medication treatment. The findings underline the need for more tailored treatment and co-ordinated care over time.
The Effective Reproduction Number of Pandemic Influenza: Prospective Estimation

Background: Timely estimation of the transmissibility of a novel pandemic influenza virus was a public health priority in 2009. Methods: We extended methods for prospective estimation of the effective reproduction number (Rt) over time in an emerging epidemic to allow for reporting delays and repeated importations. We estimated Rt based on case notifications and hospitalizations associated with laboratory-confirmed pandemic (H1N1) 2009 virus infections in Hong Kong from June through October 2009. Results: Rt declined from around 1.4–1.5 at the start of the local epidemic to around 1.1–1.2 later in the summer, suggesting changes in transmissibility perhaps related to school vacations or seasonality. Estimates of Rt based on hospitalizations of confirmed H1N1 cases closely matched estimates based on case notifications. Conclusion: Real-time monitoring of the effective reproduction number is feasible and can provide useful information to public health authorities for situational awareness and calibration of mitigation strategies.