Red dairy breeds are a valuable cultural and historical asset, and often a source of unique genetic diversity. However, they have difficulties competing with other, more productive, dairy breeds. ...Improving competitiveness of Red dairy breeds, by accelerating their genetic improvement using genomic selection, may be a promising strategy to secure their long-term future. For many Red dairy breeds, establishing a sufficiently large breed-specific reference population for genomic prediction is often not possible, but may be overcome by adding individuals from another breed. Relatedness between breeds strongly decides the benefit of adding another breed to the reference population. To prioritize among available breeds, the effective number of chromosome segments (Me) can be used as an indicator of relatedness between individuals from different breeds. The Me is also an important parameter in determining the accuracy of genomic prediction. The Me can be estimated both within a population and between 2 populations or breeds, as the reciprocal of the variance of genomic relationships. We investigated relatedness between 6 Dutch Red cattle breeds, Groningen White Headed (GWH), Dutch Friesian (DF), Meuse-Rhine-Yssel (MRY), Dutch Belted (DB), Deep Red (DR), and Improved Red (IR), focusing primarily on the Me, to predict which of those breeds may benefit from including reference animals of the other breeds. All of these breeds, except MRY, are under high risk of extinction. Our results indicated high variability of Me, especially between Me ranging from ∼3,500 to ∼17,400, indicating different levels of relatedness between the breeds. Two clusters are especially important, one formed by MRY, DR, and IR, and the other comprising DF and DB. Although relatedness between breeds within each of these 2 clusters is high, across-breed genomic prediction is still limited by the current number of genotyped individuals, which for many breeds is low. However, adding MRY individuals would increase the reference population of DR substantially. We estimated that between 11 and 133 individuals from other breeds are needed to achieve accuracy of genomic prediction equivalent to using one additional individual from the same breed. Given the variation in size of the breeds in this study, the benefit of a multibreed reference population is expected to be lower for larger breeds than for the smaller ones.
Polarisation-sensitive optical coherence tomography (PS-OCT) offers a novel, non-invasive method of assessing skin fibrosis in the multisystem disease systemic sclerosis (SSc) by measuring collagen ...retardance. This study aimed to assess retardance as a biomarker in SSc. Thirty-one patients with SSc and 27 healthy controls (HC) underwent PS-OCT imaging. 'Skin score' was assessed by clinical palpation (0-3 scale). A subset of ten patients and ten age/sex-matched HC had a biopsy and longitudinal imaging. Histological assessment included quantification of epidermal thickness, collagen content (to assess fibrosis) and matrix metalloproteinase (MMP) activity (in situ zymography). PS-OCT images were assessed for epidermal thickness (structure) and fibrosis (retardance). Positive correlation was observed between epidermal thickness as measured by histology and structural PS-OCT (r = 0.79; p < 0.001). Retardance was: HC mean 0.21 (SD 0.21) radian/pixel; SSc skin score 0, 0.30 (0.19); skin score 1, 0.11 (0.16); skin score 2, 0.06 (0.12); skin score 3, 0.36 (0.35). Longitudinal retardance decreased at one-week across groups, increasing at one-month for HC/skin score 0-1; HC biopsy site retardance suggests scarring is akin to fibrosis. Relationships identified between retardance with both biopsy and skin score data indicate that retardance warrants further investigation as a suitable biomarker for SSc-related fibrosis.
Summary
Background
Low vitamin D status is prevalent in wintertime in populations at northerly latitudes. Photosensitive patients are advised to practise sun avoidance, but their sunlight exposure ...levels, photoprotective measures and resulting vitamin D status are unknown.
Objectives
To examine seasonal vitamin D status in photosensitive patients relative to healthy individuals and to assess quantitatively behavioural and demographic contributors.
Methods
This was a longitudinal prospective cohort study (53·5°N) examining year‐round 25‐hydroxyvitamin D 25(OH)D levels, sun‐exposure behaviour and oral vitamin D intake in photosensitive patients diagnosed at a photoinvestigation unit (n = 53), compared with concurrently assessed healthy adults (n = 109).
Results
Photosensitive patients achieved seasonal 25(OH)D variation, but insufficient (< 20 ng mL−1; 50 nmol L−1) and even deficient (< 10 ng mL−1; 25 nmol L−1) levels occurred at the summer peak in 47% and 9% of patients, respectively, rising to 73% and 32% at the winter trough. Adjusting for demographic factors, the mean values were lower than for healthy volunteers by 18% 95% confidence interval (CI) 4–29 in summer (P = 0·02) and 25% (95% CI 7–39) in winter (P = 0·01). Behavioural factors explained 25(OH)D differences between cohorts. Patients demonstrated lower weekend ultraviolet B doses (P < 0·001), smaller skin surface area exposure (P = 0·004) and greater sunscreen use (P < 0·001), while average oral vitamin D intake was low in both groups (photosensitive: 2·94 μg per day). Supplementation and summer surface area exposure predicted summer peak and winter trough 25(OH)D levels. A 1 μg per day increment in supplementary vitamin D raised summer and winter 25(OH)D by 5% (95% CI 3–7) and 9% (95% CI 5–12), respectively (both P < 0·001).
Conclusions
Photosensitive patients are, through their photoprotective measures, at high risk of year‐round low vitamin D status. Guidance on oral measures should target this patient group and their physicians.
What's already known about this topic?
Low vitamin D status in wintertime is prevalent at northerly latitudes.
Photosensitive patients are advised to minimize sun exposure, but the impact on the risk of inadequate vitamin D status is unknown.
What does this study add?
This longitudinal study determined sunlight exposure, photoprotective behaviour and vitamin D status in patients with moderate‐to‐severe photosensitivity in comparison with healthy adults.
Patients demonstrated lower weekend ultraviolet B doses, smaller skin area exposure and greater sunscreen use than healthy adults.
Photosensitive patients are at high risk of year‐round low vitamin D status, contrasting with seasonal lows in healthy adults, with potential for enhanced adverse health impact.
In this article, the biological evaluation and interaction of three selenium-based trans-palladium complexes (Pd-Se1, Pd-Se2, and Pd-Se3) with small biomolecules were performed. The UV-Vis kinetic ...studies on substitution reaction of synthesized complexes with selected biologically important N- and S-bonding ligands (L-Cys, GSH, L-Met, 5′-GMP, L-His) has emphasized greater affinity of sulphur-based ligands for complex-binding, while the general order of the reactivity was L-Cys > GSH > L-Met > 5′-GMP > L-His. The complex reactivity toward small biomolecules is influenced by ligand flexibility, i.e. the steric hindrances of their corresponding ligands near the coordination site (Se-Pd) during the substitution process. The in vitro cytotoxicity of the investigated complexes against colorectal carcinoma HCT-116 and healthy fibroblast MRC-5 cells exhibited moderate prooxidative and significant cytotoxic character against HCT-116 cells, while such effect on MRC-5 was much weaker. Antioxidant activity (DPPH assay) indicated that all three complexes and their ligands have significant antioxidant activity, with Pd-Se2 being significantly stronger than its ligand L2 or the other complexes. Molecular docking simulations on tyrosinase (Tyr) singled out Pd-Se1 as the most compatible to bind to the cavity of Tyr. At all concentrations, the tested compounds demonstrated genotoxic effects (comet assay) compared to negative control.
Osteopenia and osteoporosis are conditions characterised by a reduction in bone mineral density. There is contradictory evidence whether osteoporotic patients have greater tooth loss than ...non-osteoporotic patients.
To investigate the association between tooth number and osteoporotic status, taking into account the effect of other confounding variables such as age, smoking status, alcohol consumption and the use of hormone replacement therapy.
Three hundred and fifty-nine patients were recruited from the Manchester region between March 2008 and June 2010.
Data were collected on osteoporotic status, smoking status, alcohol consumption, age and the use of hormone replacement therapy. Dental panoramic tomographs were taken for each patient and the teeth present were charted and counted. Data were analysed using SPSS software (version 19).
Complete data was available for 333 patients. Twenty-seven percent of individuals (90) were classified as osteoporotic. There was a significant relationship between molar tooth number and osteoporotic status (p = 0.017, 95% CI -1.339 to -0.137).
Clinicians should inform osteoporotic patients they may be at greater risk of tooth loss and instigate more intensive preventive regimens for these individuals.
Transcription factor NF-Y belongs to the embryonic stem cell transcription factor circuitry due to its role in the regulation of cell proliferation. We investigated the role of NF-Y in pluripotency ...maintenance using NT2/D1 cells as one of the best-characterized human embryonal carcinoma cell line. We investigated the efficiency of protein transduction and analyzed the effects of forced expression of short isoform of NF-Y A-subunit (NF-YAs) on NT2/D1 cell growth and expression of SOX2. We found that protein transduction is an efficient method for NF-Y overexpression in NT2/D1 cells. Next, we analyzed the effect of NF-YAs overexpression on NT2/D1 cell viability and detected significant reduction in cell growth. The negative effect of NF-YAs overexpression on NT2/D1 cell pluripotency maintenance was confirmed by the decrease in the level of the pluripotency marker SOX2. Finally, we checked the p53 status and determined that the NF-Y-induced inhibition of NT2/D1 cell growth is p53-independent.
Braces used to treat (PF) osteoarthritis (OA) may reduce contact stress across the PF joint. We hypothesised that in PF OA, braces would decrease knee pain and shrink PF bone marrow lesions (BMLs).
...Eligible subjects had painful PF OA. Subjects were randomly allocated to brace or no brace for 6 weeks. Knee MRIs were acquired at baseline and 6 weeks. We measured BMLs on post-contrast fat suppressed sagittal and proton density weighted axial images. The primary symptom outcome was change in pain at 6 weeks during a preselected painful activity, and the primary structural outcome was BML volume change in the PF joint. Analyses used multiple linear regression.
We randomised 126 subjects aged 40-70 years (mean age 55.5 years; 72 females (57.1%)). Mean nominated visual analogue scale (0-10 cm) pain score at baseline was 6.5 cm. 94 knees (75%) had PF BMLs at baseline. Subjects wore the brace for a mean of 7.4 h/day. 6 subjects withdrew during the trial. After accounting for baseline values, the brace group had lower knee pain than the control group at 6 weeks (difference between groups -1.3 cm, 95% CI -2.0 to -0.7; p<0.001) and reduced PF BML volume (difference -490.6 mm(3), 95% CI -929.5 to -51.7; p=0.03) but not tibiofemoral volume (difference -53.9 mm(3), 95% CI -625.9 to 518.2; p=0.85).
A PF brace reduces BML volume in the targeted compartment of the knee, and relieves knee pain.
UK. ISRCTN50380458.
Photoaggravated atopic dermatitis (PAD) is estimated to affect 1.4% to 16% of patients with AD but remains poorly characterized with limited published data.
To provide detailed clinical and ...photobiological characterization of PAD.
This case series study used cross-sectional data collected from 120 consecutive patients diagnosed with PAD from January 2015 to October 2019 at a tertiary center referral unit for photobiology.
Routinely collected standardized clinical and photobiological data were analyzed using descriptive statistics, and regression analysis explored associations between demographic and clinical data.
Of 869 patients who underwent photoinvestigation, 120 (14%) were diagnosed with PAD (69 female 58%; median age, 45 IQR, 31-61 years; range, 5-83 years; skin phototypes SPTs I-VI). Of these patients, 104 (87%) were adults. All patients had a history of AD, and most (62 of 104 60%) presented with sunlight-provoked or photodistributed eczema; median age at photosensitivity onset was 37 years (range, 1-72 years). Past-year Dermatology Life Quality Index score was greater than 10 for 80 of 103 adults (78%), and 82 of 119 (69%) had vitamin D (25-hydroxyvitamin D) level insufficiency or deficiency (<20 ng/mL; to convert ng/mL to nmol/L, multiply by 2.496). Broadband UV radiation provocation test results were positive for 112 patients (93%). In 28 patients (23%) with abnormal monochromator phototest findings, sensitivity occurred to UV-A, UV-B, and/or visible light, and UV-A of 350 ± 10 nm was the most prevalent wavelength. Photopatch test reactions were positive for 18 patients (15%). Patients with SPTs V to VI (31 26%) vs SPTs I to IV (89 74%) were younger at photosensitivity onset (median age, 24 years IQR, 15-37 years vs 40 years IQR, 25-55 years; P = .003), were more likely to be female (23 74% vs 46 52%; P = .03), and had a lower vitamin D status and a higher frequency of abnormal monochromator phototest findings.
In this case series study, PAD affected patients with different ages and SPTs and was associated with substantially impaired quality of life. The findings suggest that confirming PAD through phototesting may provide better personalized care for patients through identification of provoking wavelengths, relevant photocontact allergies, and appropriate photoprotection advice.
Information about the prevalence of photodermatoses is lacking, despite their substantial impact on life quality. Our objective was to systematically review the literature to establish what is known ...regarding prevalence and incidence of photodermatoses. We searched Medline, CINAHL and Embase from inception to 2021 to identify original population‐based studies in English literature reporting the prevalence and/or incidence of photodermatoses. Information was extracted according to geographical location and risk of bias was assessed using a 10‐point risk of bias tool for prevalence studies. Primary outcome was the population prevalence of photodermatoses. Prevalence data for polymorphic light eruption (PLE) were used to calculate the global pooled prevalence of PLE. Twenty‐six studies were included; 15 reported prevalence of photodermatoses based on samples of the general population and 11 on prevalence and/or incidence from national and international registry data. The general population studies involved PLE (nine studies), unspecified photosensitivity (2), actinic prurigo (2), juvenile spring eruption (1), chronic actinic dermatitis (1) and variegate porphyria (1), while registry studies reported on cutaneous porphyrias and genophotodermatoses (nine and two studies, respectively). Worldwide the prevalence of PLE between countries ranged from 0.65% (China) to 21.4% (Ireland). The pooled estimated prevalence of PLE was 10% (95% CI 6%–15%) among the general population (n = 19,287), and PLE prevalence increased with distance from the equator (r = 0.78, p < 0.001). While several photodermatoses are rare, photosensitivity can be prevalent at wide‐ranging world locations, including Egypt where photosensitivity was found in 4% of children and 10% of adults. This study showed that PLE is highly prevalent in many populations and that its prevalence shows a highly significant correlation with increasing northerly or southerly latitude. Available population‐based studies for photodermatoses suggest they can be prevalent at a range of world locations; more attention is required to this area.
Synovitis occurring frequently in osteoarthritis (OA) may be a targeted outcome. There are no data examining whether synovitis changes following intra-articular intervention.
Persons aged 40 years ...and older with painful knee OA participated in an open label trial of intra-articular steroid therapy. At all time points they completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. They had a contrast-enhanced (CE) MRI immediately prior to an intra-articular steroid injection with a repeat scan within 20 days. Response status was assessed using the Osteoarthritis Research Society International (OARSI) response criteria. OARSI responders were followed until their pain relapsed either within 20% of baseline or 6 months, shortly after which a third MRI was performed. Synovial tissue volume (STV) was measured on postcontrast knee images. We looked at changes in the STV and in pain, and their association.
120 subjects with preinjection and postinjection CE MRI were followed. Their mean age was 62.3 years (SD=10.3) and 62 (52%) were women. The median time between injection and follow-up scan was 8 days (IQR 7-14 days). 85/120 (71%) were OARSI responders. Pain decreased (mean change in KOOS=+23.9; 95% CI 20.1 to 27.8, p<0.001) following steroid injection, as did mean STV (mean change=-1071 mm(3); 95% CI -1839 mm(3) to -303 mm(3), p=0.01). Of the 80 who returned for a third MRI, pain relapsed in 57, and in the 48 of those with MRI data, STV increased between follow-up and final visit (+1220 mm(3); 95% CI 25 mm(3) to 2414 mm(3), p=0.05). 23 were persistent responders at 6 months and, in these, STV did not increase (mean change=-202 mm(3); 95% CI -2008 mm(3) to 1604 mm(3), p=0.83). Controlling for variation over time, there was a significant association between synovitis volume and KOOS pain (b coefficient-change in KOOS pain score per 1000 mm(3) change in STV=-1.13; 95% CI -1.87 to -0.39, p=0.003), although STV accounted for only a small proportion of the variance in change in pain.
Synovial tissue volume in knee OA shrinks following steroid therapy, and rebounds in those whose pain relapses. It can be considered a treatment target in symptomatic knee OA.
ISRCTN07329370.
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