SPRTN-dependent DPC degradation precedes repair of damaged DNA: a proof of concept revealed by the STAR assay.

DNA-protein crosslinks (DPCs), formed by the covalent conjugation of proteins to DNA, are toxic lesions that interfere with DNA metabolic processing and transcription. The development of an accurate biochemical assay for DPC isolation is a priority for the mechanistic understanding of their repair. Here, we propose the STAR assay for the direct quantification of DPCs, sensitive to physiologically relevant treatment conditions. Implementing the STAR assay revealed the formation of small cross-linked peptides on DNA, created by the proteolytic degradation of DPCs by SPRTN. The initial proteolytic degradation of DPCs is required for the downstream activation of DNA repair, which is mediated through the phosphorylation of H2Ax. This leads to the accumulation of DNA repair factors on chromatin and the subsequent complete removal of the cross-linked peptides. These results confirmed that the repair of DPCs is a two-step process, starting with proteolytic resection by SPRTN, followed by the repair of the underlying damage to the DNA.

Body composition parameters in systemic sclerosis-a systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review and meta-analysis was to summarize current evidence regarding body composition (BC) in SSc in order to gain new insights and improve clinical care in the context of the nutritional status of SSc patients. METHODS: The databases Web of Science, PubMed, Scopus and Cochrane Library were searched on 4 January 2023. Studies were included if they provided data regarding BC obtained by dual-energy X-ray absorptiometry (DXA) or bioelectrical impedance analysis (BIA) in patients with SSc and healthy controls (HC). The study design criteria for inclusion were cohort and observational studies. The risk of bias assessment was performed using the Newcastle-Ottawa scale. For meta-analysis, mean difference with a 95% confidence interval was obtained and all results were depicted as forest plots. RESULTS: The number of retrieved publications was 593, of which nine were included in a random-effects meta-analysis totalling 489 SSc patients and 404 HC. Overall, significantly lower body mass index, lean mass (LM), fat mass (FM) and phase angle values were found in SSc patients when compared with HC. Furthermore, FM and LM were significantly lower in SSc patients when the DXA method was applied, whereas the same parameters were comparable between two groups of participants when BIA was applied. CONCLUSION: Altered BC is characteristic of SSc patients indicating the need for regular nutritional status assessment in order to improve the quality of life and clinical care of patients with SSc.

Integrative miRNA-mRNA profiling of human epidermis: unique signature of SCN9A painful neuropathy.

Personalized management of neuropathic pain is an unmet clinical need due to heterogeneity of the underlying aetiologies, incompletely understood pathophysiological mechanisms and limited efficacy of existing treatments. Recent studies on microRNA in pain preclinical models have begun to yield insights into pain-related mechanisms, identifying nociception-related species differences and pinpointing potential drug candidates. With the aim of bridging the translational gap towards the clinic, we generated a human pain-related integrative miRNA and mRNA molecular profile of the epidermis, the tissue hosting small nerve fibres, in a deeply phenotyped cohort of patients with sodium channel-related painful neuropathy not responding to currently available therapies. We identified four miRNAs strongly discriminating patients from healthy individuals, confirming their effect on differentially expressed gene targets driving peripheral sensory transduction, transmission, modulation and post-transcriptional modifications, with strong effects on gene targets including NEDD4. We identified a complex epidermal miRNA-mRNA network based on tissue-specific experimental data suggesting a cross-talk between epidermal cells and axons in neuropathy pain. Using immunofluorescence assay and confocal microscopy, we observed that Nav1.7 signal intensity in keratinocytes strongly inversely correlated with NEDD4 expression that was downregulated by miR-30 family, suggesting post-transcriptional fine tuning of pain-related protein expression. Our targeted molecular profiling advances the understanding of specific neuropathic pain fine signatures and may accelerate process towards personalized medicine in patients with neuropathic pain.

Disease Activity, Inflammation Markers, and Quality of Life Are Associated with Muscle Strength in Croatian Rheumatoid Arthritis Patients-A National-Based Study.

Background and Objectives: Rheumatoid arthritis (RA) patients experience sarcopenia and decreased muscle mass and handgrip strength, leading to decreased quality of life and disability. The prevalence of RA varies across regions. This study aimed to evaluate the factors associated with RA in Croatian regional centres and explore correlations between clinical parameters and muscle strength. Materials and Methods: Included in this study were 267 stable RA patients from four Croatian clinical centres. The patients' mean age was 60.4 ± 12.0 years, with 12.7% of them being male. For each study participant, information was gathered on their anthropometric characteristics, clinical and laboratory indicators, quality of life, disease activity, and sociodemographics. Results: The main results showed that in the female RA participants, the significant positive predictors are weight, height, exercise, VAS, and haemoglobin level. The negative predictors are the use of conventional synthetic disease-modifying anti-rheumatic drugs, the use of biological disease-modifying anti-rheumatic drugs, the number of tender joints, the number of swollen joints, the estimated sedimentation rate, the C-reactive protein, the disease activity score, the parameters of the EQ5D, and being prescribed with three or more medications. In the male RA participants, significant predictors of muscle strength are only weight, height, and anxiety/depression difficulties, according to the EQ5D. Conclusions: This study showed correlations between muscle strength and the parameters of disease activity, inflammation parameters, health-related quality of life, therapy, and exercise in the female RA participants in Croatia.

Genome-Wide Meta-Analysis Identifies Multiple Novel Rare Variants to Predict Common Human Infectious Diseases Risk.

Infectious diseases still threaten global human health, and host genetic factors have been indicated as determining risk factors for observed variations in disease susceptibility, severity, and outcome. We performed a genome-wide meta-analysis on 4624 subjects from the 10,001 Dalmatians cohort, with 14 infection-related traits. Despite a rather small number of cases in some instances, we detected 29 infection-related genetic associations, mostly belonging to rare variants. Notably, the list included the genes CD28, INPP5D, ITPKB, MACROD2, and RSF1, all of which have known roles in the immune response. Expanding our knowledge on rare variants could contribute to the development of genetic panels that could assist in predicting an individual's life-long susceptibility to major infectious diseases. In addition, longitudinal biobanks are an interesting source of information for identifying the host genetic variants involved in infectious disease susceptibility and severity. Since infectious diseases continue to act as a selective pressure on our genomes, there is a constant need for a large consortium of biobanks with access to genetic and environmental data to further elucidate the complex mechanisms behind host-pathogen interactions and infectious disease susceptibility.

Direct and cost-effective method for histone isolation from cultured mammalian cells.

Histones are an essential part of nucleosomes that regulate chromatin structure and function. Histone exchanges and modifications represent a scaffold for DNA transcription, repair, and replication. Studying histones and histone code is an important and fast-developing branch of epigenetic science. Here we propose a fast, efficient, and versatile assay for nucleosomal histone isolation from mammalian cells, without the use of acids or high salt solutions which are common for other histone isolation techniques. All components used in the protocol are common and inexpensive laboratory chemicals. The protocol has been evaluated on six commonly used cell lines and two animal tissue samples. The mild extraction conditions preserve delicate histone epigenetic changes, allowing its downstream analyses. We have demonstrated the assays' successful application during changes in the transcriptional activity of histone genes, cell cycle transitions, and DNA-damaging conditions. Histone fractions, obtained by the protocol, can be used for further applications, such as electrophoresis, immunoblot, and mass spectrometry. Therefore, the new proposed nucleosomal histone isolation method is sensitive, specific, and suitable for downstream applications of various kinds.

Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain.

Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry were included from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and from the UK Biobank interim data release. CBP cases were defined as those reporting back pain present for ≥3-6 months; non-cases were included as comparisons ("controls"). Each cohort conducted genotyping using commercially available arrays followed by imputation. GWAS used logistic regression models with additive genetic effects, adjusting for age, sex, study-specific covariates, and population substructure. The threshold for genome-wide significance in the fixed-effect inverse-variance weighted meta-analysis was p<5×10(-8). Suggestive (p<5×10(-7)) and genome-wide significant (p<5×10(-8)) variants were carried forward for replication or further investigation in the remaining UK Biobank participants not included in the discovery sample. The discovery sample comprised 158,025 individuals, including 29,531 CBP cases. A genome-wide significant association was found for the intronic variant rs12310519 in SOX5 (OR 1.08, p = 7.2×10(-10)). This was subsequently replicated in 283,752 UK Biobank participants not included in the discovery sample, including 50,915 cases (OR 1.06, p = 5.3×10(-11)), and exceeded genome-wide significance in joint meta-analysis (OR 1.07, p = 4.5×10(-19)). We found suggestive associations at three other loci in the discovery sample, two of which exceeded genome-wide significance in joint meta-analysis: an intergenic variant, rs7833174, located between CCDC26 and GSDMC (OR 1.05, p = 4.4×10(-13)), and an intronic variant, rs4384683, in DCC (OR 0.97, p = 2.4×10(-10)). In this first reported meta-analysis of GWAS for CBP, we identified and replicated a genetic locus associated with CBP (SOX5). We also identified 2 other loci that reached genome-wide significance in a 2-stage joint meta-analysis (CCDC26/GSDMC and DCC).

Multi-Omics Approach to Elucidate Cerebrospinal Fluid Changes in Dogs with Intervertebral Disc Herniation.

Herniation of the intervertebral disc (IVDH) is the most common cause of neurological and intervertebral disc degeneration-related diseases. Since the disc starts to degenerate before it can be observed by currently available diagnostic methods, there is an urgent need for novel diagnostic approaches. To identify molecular networks and pathways which may play important roles in intervertebral disc herniation, as well as to reveal the potential features which could be useful for monitoring disease progression and prognosis, multi-omics profiling, including high-resolution liquid chromatography-mass spectrometry (LC-MS)-based metabolomics and tandem mass tag (TMT)-based proteomics was performed. Cerebrospinal fluid of nine dogs with IVDH and six healthy controls were used for the analyses, and an additional five IVDH samples were used for proteomic data validation. Furthermore, multi-omics data were integrated to decipher a complex interaction between individual omics layers, leading to an improved prediction model. Together with metabolic pathways related to amino acids and lipid metabolism and coagulation cascades, our integromics prediction model identified the key features in IVDH, namely the proteins follistatin Like 1 (FSTL1), secretogranin V (SCG5), nucleobindin 1 (NUCB1), calcitonin re-ceptor-stimulating peptide 2 precursor (CRSP2) and the metabolites N-acetyl-D-glucosamine and adenine, involved in neuropathic pain, myelination, and neurotransmission and inflammatory response, respectively. Their clinical application is to be further investigated. The utilization of a novel integrative interdisciplinary approach may provide new opportunities to apply innovative diagnostic and monitoring methods as well as improve treatment strategies and personalized care for patients with degenerative spinal disorders.

What Patients, Students and Doctors Think About Permission to Publish Patient Photographs in Academic Journals: A Cross-Sectional Survey in Croatia.

Use of patient clinical photographs requires specific attention to confidentiality and privacy. Although there are policies and procedures for publishing clinical images, there is little systematic evidence about what patients and health professionals actually think about consent for publishing clinical images. We investigated the opinions of three stakeholder groups (patients, students and doctors) at 3 academic healthcare institutions and 37 private practices in Croatia (total 791 participants: 292 patients, 281 medical and dental students and 281 doctors of medicine or dental medicine). The questionnaire contained patient photographs with different levels of anonymization. All three respondent groups considered that more stringent forms of permission for were needed identifiable photographs than for those with higher levels of anonymization. When the entire face was presented in a photo only 33% of patients considered that written permission was required, compared with 88% of the students and 89% of the doctors. Opinions about publishing patient photographs differed among the three respondent samples: almost half of the patients thought no permission was necessary compared with one-third of students and doctors. These results show poor awareness of Croatian patients regarding the importance of written informed consent as well as unsatisfactory knowledge of health professionals about policies on the publication of patients' data in general. In conclusion, there is a need for increasing awareness of all stakeholders to achieve better protection of patient privacy rights in research and publication.

Effect of Tff3 Deficiency and ER Stress in the Liver.

Endoplasmic reticulum (ER) stress, a cellular condition caused by the accumulation of unfolded proteins inside the ER, has been recognized as a major pathological mechanism in a variety of conditions, including cancer, metabolic and neurodegenerative diseases. Trefoil factor family (TFFs) peptides are present in different epithelial organs, blood supply, neural tissues, as well as in the liver, and their deficiency has been linked to the ER function. Complete ablation of Tff3 expression is observed in steatosis, and as the most prominent change in the early phase of diabetes in multigenic mouse models of diabesity. To elucidate the role of Tff3 deficiency on different pathologically relevant pathways, we have developed a new congenic mouse model Tff3-/-/C57BL6/N from a mixed background strain (C57BL6/N /SV129) by using a speed congenics approach. Acute ER stress was evoked by tunicamycin treatment, and mice were sacrificed after 24 h. Afterwards the effect of Tff3 deficiency was evaluated with regard to the expression of relevant oxidative and ER stress genes, relevant proinflammatory cytokines/chemokines, and the global protein content. The most dramatic change was noticed at the level of inflammation-related genes, while markers for unfolded protein response were not significantly affected. Ultrastructural analysis confirmed that the size of lipid vacuoles was affected as well. Since the liver acts as an important metabolic and immunological organ, the influence of Tff3 deficiency and physiological function possibly reflects on the whole organism.

Impact of stress response in development of first-episode psychosis in schizophrenia: An overview of systematic reviews.

BACKGROUND: To summarize all available evidence from systematic reviews about the impact of stress response in development of first-episode psychosis (FEP) in schizophrenia. METHODS: An overview of systematic reviews of any type of primary studies was performed. An electronic search of five databases was conducted in February 2017 (CDSR, DARE, Embase, MEDLINE and PsychINFO). Quality of included systematic reviews was assessed using the AMSTAR checklist. RESULTS: Eight systematic reviews were included. The main findings of the included reviews point out a possible alteration of the stress response in a subgroup of persons with proneness to psychosis. However, the evidence is limited by the inadequate quality of studies, as well as lack of standardization of outcomes and assessment methods. CONCLUSIONS: Given the heterogeneity of current results, there is no solid evidence for uniform alterations of stress response found in persons with FEP in suggestive of schizophrenia that may serve as a marker of vulnerability to stress and possibly proneness to psychotic state in response to daily hassles.

Cryptic diversity in the Western Balkan endemic copepod: Four species in one?

We use mitochondrial (mtCOI) and nuclear (nH3) sequence data to investigate differentiation of Eudiaptomus hadzici, a freshwater copepod endemic to the Western Balkans. E. hadzici has a disjunct distribution and morphological differences were observed at regional scale. In the current study 6 out of 7 known populations are included. We applied several species delimiting approaches, distance based methods (K2P p-distance and Automatic Barcode Gap Discovery, ABGD) using the mtCOI, Bayesian phylogeny and the Bayesian method implemented in bPTP and BPP programs using the concatenated sequences of both genes. Phylogenetic and species delimitation analyses all suggest that the nominal species E. hadzici consists of four isolated, cryptic evolutionary lineages in the Western Balkans. Each of the four lineages inhabits a single lake or a group of lakes in close proximity. They exhibit major differences in secondary sexual characters, e.g. right antennule in males. Denticulation of spine on 13th segment is substantially distinct among the four lineages, having different number and shape of tooth-like protrusions. Gene flow and dispersal are restricted to very small spatial scale, but with local differences, implying that diverse historical and contemporary processes are operating at small spatial scales in E. hadzici. In order to further examine spatial and temporal diversification patterns, we constructed a dated species tree analysis using (*)BEAST. Due to lack of reliable calibration points and taxa specific evolutionary rates, two evolutionary rates were applied and the faster one (2.6% myr) seems more plausible considering the geological history of the region. The divergence of E. hadzici lineages is dated from Early Miocene onwards with geographically close lineages diverging more recently, Late Miocene to Pleistocene and Pleistocene, respectively. Overall, our findings shed light on cryptic genetic complexity of endemics in one of European biodiversity hotspots. Moreover, this study represents one further example of integrative taxonomy, linking DNA methodology and classical taxonomy based on morphology. Therefore, it lays groundwork for future taxonomy and biogeography of freshwater microcrustaceans in the region.

Host genetics and susceptibility to congenital and childhood cytomegalovirus infection: a systematic review.

AIM: To summarize available evidence on the role of host genetics in the susceptibility to congenital and childhood cytomegalovirus (CMV) infections by conducting a systematic review of published studies. METHODS: We searched online databases (PubMed, Web of Science, Scopus and HuGe Navigator) for relevant studies with well-defined inclusion and exclusion criteria and assessed the risk of bias using novel Confounding-Selection-Information bias score (CSI). RESULTS: 5105 studies were initially identified, but only 5 met all the inclusion criteria and were analyzed in detail. Polymorphisms of the toll-like receptors (TLRs) and mannose-binding lectin (MBL) genes were shown to have an impact on the CMV infection in infants. Polymorphisms of the TLR2 (rs3804100, rs1898830), TLR4 (rs4986791), and TLR9 (rs352140) were shown to have a role in congenital CMV infection. Low MBL levels were associated with CMV infection in Chinese individuals, a finding that was not replicated in Caucasians. The overall credibility of evidence was weak. CONCLUSIONS: Based on currently available very limited amount of evidence, it is uncertain whether congenital and childhood CMV infections are under host genetic control. Additional primary studies are needed with more specific research hypotheses that will enable gradual understanding of specific mechanisms of the CMV pathogenesis. More genetic studies in the future will facilitate better understanding of host susceptibility and likely enable novel preventative and curative measures.

Mediterranean diet in the southern Croatia - does it still exist?

AIM: To assess the adherence to the Mediterranean diet in the population of Dalmatia in southern Croatia. METHODS: A cross-sectional study was performed within the 10001 Dalmatians cohort, encompassing 2768 participants from Korcula and Vis islands and the City of Split, who were recruited during 2011-2014. Using the data obtained from food frequency questionnaire we calculated the Mediterranean Diet Serving Score (MDSS). Multivariate logistic regression was used to identify the characteristics associated with the adherence to the Mediterranean diet, with age, sex, place of residence, education attainment, smoking, and physical activity as covariates. RESULTS: The median MDSS score was 11 out of maximum 24 points (interquartile range 8-13), with the highest score recorded on the island of Vis. Participants reported a dietary pattern that had high compliance with the Mediterranean diet guidelines for consumption of cereals (87% met the criteria), potatoes (73%), olive oil (69%), and fish (61%), moderate for consumption of fruit (54%) and vegetables (31%), and low for consumption of nuts (6%). Overall, only 23% of the participants were classified as being adherent to the Mediterranean diet, with a particularly low percentage among younger participants (12%) compared to the older ones (34%). Men were less likely to show good adherence (odds ratio 0.52, 95% confidence interval 0.42-0.65). CONCLUSION: This study revealed rather poor compliance with the current recommendations on the Mediterranean diet composition in the population of Dalmatia. Public health intervention is especially needed in younger age groups and in men, who show the greatest departure from traditional Mediterranean diet and lifestyle.

Is Arterial Stiffness Interconnected with Cardiovascular Drug Prescription Patterns, Body Composition Parameters, and the Quality of Blood Pressure Regulation in Hypertensive Patients?

BACKGROUND: Arterial hypertension (AH) is a significant risk factor for cardiovascular disease and is associated with increased arterial stiffness, particularly as measured by pulse wave velocity (PWV). This study aims to explore the relationships between age groups, antihypertensive and new oral antidiabetic drugs, body composition, and arterial stiffness parameters in hypertensive patients. METHODS: A single-center cross-sectional study was conducted including 584 participants who underwent 24 h ambulatory blood pressure monitoring (including central blood pressure (BP) and PWV measurement), body composition analysis, and provided medical history and current pharmacotherapy data. RESULTS: The study found that PWV was significantly higher in patients with poorly regulated BP in those aged 65 years and older. Significant PWV predictors included systolic BP, heart rate, peripheral mean arterial pressure, peripheral pulse pressure, augmentation index, calcium channel blockers, moxonidine, sodium-glucose co-transporter 2 inhibitors, urapidil, and statin prescription. Also, statistically significant negative correlations were found between PWV and visceral fat level, fat-free mass, and the percentage of muscle mass. CONCLUSIONS: The findings suggest that arterial stiffness is interconnected with peripheral and central blood pressure parameters, body composition parameters, and prescribed hypertensive and new antidiabetic drugs.

Are There Differences in Skin Autofluorescence-Measured Advanced Glycation End-Product Levels between Chronic Kidney Disease and Kidney Transplant Recipients?

The aim of this cross-sectional study was to evaluate the differences in the levels of advanced glycation end products (AGE) between patients with chronic kidney disease (CKD) and kidney transplant recipients (KTRs) and to investigate the risk factors for the AGE levels in each group of these patients. There were 217 participants total, of which 99 (45.6%) were KTRs and 118 (54.4%) had CKD. Data on the levels of AGE, body mass composition, anthropometric parameters, central and peripheral blood pressure, and clinical and laboratory parameters were gathered for each study participant. The AGE values of the CKD and KTRs groups did not differ from one another. In both groups, a lower estimated glomerular filtration rate, male sex, and older age were positive predictors for increased AGE values. Furthermore, higher levels of AGE were linked to lower central systolic blood pressure (cSBP) in the CKD group, whilst, in the KTRs group, higher levels of AGE were linked to a shorter time since kidney transplantation (KTx), more years of dialysis prior to KTx, lower levels of trunk visceral fat, the presence of arterial hypertension, and the absence of prescriptions for the antihypertensive medications urapidil and angiotensin II receptor blockers. Further studies are needed to better understand the above associations. Consequently, a personalised multidisciplinary approach to assess the cardiovascular as well as dietary and lifestyle risk factors to reduce the AGE levels in both KTRs and CKD patients may be implemented.

Biomarker and proteome analysis of milk from dairy cows with clinical mastitis: Determining the effect of different bacterial pathogens on the response to infection.

Antimicrobial usage (AMU) could be reduced by differentiating the causative bacteria in cases of clinical mastitis (CM) as either Gram-positive or Gram-negative bacteria or identifying whether the case is culture-negative (no growth, NG) mastitis. Immunoassays for biomarker analysis and a Tandem Mass Tag (TMT) proteomic investigation were employed to identify differences between samples of milk from cows with CM caused by different bacteria. A total of 94 milk samples were collected from cows diagnosed with CM across seven farms in Scotland, categorized by severity as mild (score 1), moderate (score 2), or severe (score 3). Bovine haptoglobin (Hp), milk amyloid A (MAA), C-reactive protein (CRP), lactoferrin (LF), α-lactalbumin (LA) and cathelicidin (CATHL) were significantly higher in milk from cows with CM, regardless of culture results, than in milk from healthy cows (all P-values <0.001). Milk cathelicidin (CATHL) was evaluated using a novel ELISA technique that utilises an antibody to a peptide sequence of SSEANLYRLLELD (aa49-61) common to CATHL 1-7 isoforms. A classification tree was fitted on the six biomarkers to predict Gram-positive bacteria within mastitis severity scores 1 or 2, revealing that compared to the rest of the samples, Gram-positive samples were associated with CRP < 9.5 µg/ml and LF ≥ 325 µg/ml and MAA < 16 µg/ml. Sensitivity of the tree model was 64%, the specificity was 91%, and the overall misclassification rate was 18%. The area under the ROC curve for this tree model was 0.836 (95% bootstrap confidence interval: 0.742; 0.917). TMT proteomic analysis revealed little difference between the groups in protein abundance when the three groups (Gram-positive, Gram-negative and no growth) were compared, however when each group was compared against the entirety of the remaining samples, 28 differentially abundant protein were identified including ß-lactoglobulin and ribonuclease. Whilst further research is required to draw together and refine a suitable biomarker panel and diagnostic algorithm for differentiating Gram- positive/negative and NG CM, these results have highlighted a potential panel and diagnostic decision tree. Host-derived milk biomarkers offer significant potential to refine and reduce AMU and circumvent the many challenges associated with microbiological culture, both within the lab and on the farm, while providing the added benefit of reducing turnaround time from 14 to 16 h of microbiological culture to just 15 min with a lateral flow device (LFD).

Biomarkers for subclinical bovine mastitis: a high throughput TMT-based proteomic investigation.

Mastitis represents the biggest threat to the health and productivity of dairy cows, leading to substantial economic losses in milk production. It manifests in two forms: clinical mastitis, easily diagnosed by visible symptoms, and subclinical mastitis (SCM), which lacks overt clinical signs. SCM's elusive nature often results in it going undetected, thus facilitating the spread of the disease-causing agent due to lack of treatment. Finding a reliable biomarker for early SCM would reduce the possibility of mastitis spreading in the herd, reduce the need for antibiotic use and ultimately reduce milk losses for producers. Utilizing state-of-the-art proteomics techniques, 138 milk samples from dairy cows in continental Croatia underwent analysis. These samples were categorized into four groups based on the Zagreb Mastitis Test (ZMT) and microbiological analysis: lowSCC- (n = 20), lowSCC + (n = 20), medSCC + (n = 79), and highSCC + (n = 19). A total of 386 proteins were identified and quantified, with 76 proteins showing significant differential abundances among the groups. Many of these proteins are linked to the innate immune system, as well as neutrophil and platelet degranulation processes. Through fold changes observed between groups, 15 proteins exhibiting biomarker characteristics for subclinical mastitis (SCM) were identified. Among these, five proteins-cathelicidins (-1, -4, and -7), lactoferrin, and haptoglobin-showed particular promise.

Risk factors of severe periodontitis in kidney transplant recipients: A case-control study.

BACKGROUND: Kidney transplant recipients (KTRs) represent a vulnerable group of patients who develop a number of comorbidities. Severe periodontitis (SP) is associated with the most common chronic systemic diseases including kidney diseases. The objective of this study was to explore the risk factors for SP in KTRs. METHODS: In this study, KTRs were divided into those with or without periodontitis and in relation to the severity of periodontitis. A comprehensive medical and periodontal examination was performed and evaluated. Multivariate logistic regression was performed to examine possible risk factors for SP among KTRs. RESULTS: A total of 100 KTRs were included in the analysis, of which 87% had periodontitis. Significant predictors of periodontitis were older age (OR = 1.07, 95% CI [1.01, 1.13], p = 0.016) and lower skeletal muscle mass (OR = 0.88, 95% CI [0.78, 0.99], p = 0.035). When examining periodontitis severity, predictors of SP (n = 21, 24%) were increased levels of uric acid (OR = 1.01, 95% CI [1.00, 1.02], p = 0.022) and dental plaque (OR = 1.04, 95% CI [1.01, 1.07], p = 0.013). In the subset analysis that included only KTRs with measured advanced glycation end products (AGE) (n = 47), 34% (n = 16) had SP. The predictors of SP were AGE (OR = 3.89, 95% CI [1.28, 11.82], p = 0.017) and dental plaque (OR = 1.07, 95% CI [1.01, 1.13], p = 0.028). CONCLUSIONS: KTRs with SP had significantly higher uric acid levels and AGE, which may contribute to the systemic health status of this patient population.

Vitamin D in psoriatic arthritis - A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to summarize current evidence on vitamin D status in patients with psoriatic arthritis (PsA) with a particular focus on disease activity. METHODS: PubMed, Web of Science, Scopus and Cochrane Library databases were searched for studies that investigated vitamin D levels in PsA. The search was conducted on 12th October 2022. Included studies were cohorts, RCTs or observational studies, those assessing the level of 25(OH)D3 with control group consisting of healthy or psoriasis (Pso) patients. Nottingham-Ottawa Quality Scale was used to assess methodological quality. Random effects meta-analysis model was applied with inverse variance weighting and mean difference with 95% CI was calculated. RESULTS: Of 356 retrieved studies, 76 duplicates and 270 studies were excluded according to the exclusion criteria with one study unavailable. Four studies including 264 PsA patients and 287 healthy controls and five studies including 225 PsA patients and 391 Pso patients assessing vitamin D levels were eligible for meta-analysis. Vitamin D levels were lower in PsA patients compared to the healthy group (MD = -6.42; 95 % CI -8.31, -4.53; P < 0.01), while higher compared to Pso patients (MD = 2.37; 95 % CI 0.97, 3.78; P < 0.01). Included studies had moderate to low risk of bias. CONCLUSION: In conclusion, PsA patients have lower vitamin D levels than the general population. However, further studies are essential to understand the role of vitamin D in the development and treatment of PsA and the differences in vitamin D metabolism in PsA and Pso.