Search Results (190)

Defined natural products are often framed as intrinsically safer multi-target alternatives to selective drugs, but this assumption is not pharmacologically justified. This critical review evaluates product-specific adjunctive evidence in respiratory allergy, inflammatory bowel disease, type 2 diabetes, depression, and insomnia. MEDLINE/PubMed records published from 2020 to 23 June 2026 were prioritized, while earlier pivotal randomized trials and quantitative safety studies were retained. Evidence was gated by product identity, human exposure, exposure-compatible target engagement, incremental efficacy, and safety boundaries. Nigella sativa oil improved Asthma Control Test scores by 1.5 points over placebo after 4 weeks, although the clinical importance is uncertain and FEV1 was not significantly improved. Curcumin plus mesalamine induced remission in mild-to-moderate ulcerative colitis (53.8% versus 0%), whereas indigo naturalis produced strong response rates but is constrained by pulmonary arterial hypertension. Berberine improves glycemic surrogates but lacks cardiovascular or renal outcome evidence and shows commercial potency variability. Saffron has a short-term antidepressant signal, while St John’s wort combines extract-dependent efficacy with CYP3A4/P-glycoprotein induction. Overall, selected defined natural products may merit narrow adjunctive roles, but undefined mixtures should not be treated as mechanistically established interventions without batch-level characterization, human pharmacokinetics, objective endpoints, and prospective interaction surveillance. Full article

Background/Objectives: Vitamin D deficiency is commonly observed in patients with breast cancer and may affect disease course and treatment outcomes. The determinants of vitamin D status in this population remain incompletely understood, particularly with respect to lifestyle, psychosocial, and tumour-related factors. The aim of this study was to identify environmental and clinical factors associated with serum 25-hydroxyvitamin D [25(OH)D] concentrations in women with breast cancer, with particular emphasis on dietary patterns, psychological distress, sleep quality, and tumour molecular subtype. Methods: A cross-sectional observational study was conducted among 101 women with histopathologically confirmed invasive breast cancer, recruited at the St. John of Dukla Oncology Centre of the Lublin Region (COZL) in Lublin, Poland, between 2018 and 2019. Serum 25(OH)D concentrations were measured by electrochemiluminescence immunoassay (ECLIA; Roche Diagnostics) within 2–8 weeks after surgical treatment. Clinical and lifestyle data were collected using standardised questionnaires and medical records. Dietary patterns were assessed with the KomPAN questionnaire (pro-healthy diet index pHDI-10 and non-healthy diet index nHDI-14). Psychological distress was measured with the Distress Thermometer. Multiple linear regression with backward stepwise elimination was applied to identify factors independently associated with of 25(OH)D concentration. Results: Insufficient vitamin D status (25(OH)D < 30 ng/mL) was found in 56.4% of participants. The multivariable regression model was statistically significant (F(6,92) = 15.298; p < 0.001), explaining 49.9% of the variance in 25(OH)D concentrations. Factors independently associated with lower 25(OH)D included higher BMI (b = −0.715; p = 0.005), sleep disturbances (b = −6.257; p = 0.020), higher psychological distress score (b = −2.263; p < 0.001), and luminal B versus luminal A subtype (b = −5.909; p = 0.025). A higher pro healthy diet index (pHDI-10) was independently associated with higher 25(OH)D (b = 0.245; p = 0.040). Conclusions: Vitamin D status in patients with breast cancer is shaped by complex interactions among modifiable lifestyle factors and tumour characteristics. Targeted interventions addressing diet quality, psychological well-being, sleep health, and weight management may improve vitamin D status in this population. The association between molecular subtype and 25(OH)D concentrations warrants further prospective investigation. These findings should be interpreted with caution, as vitamin D supplementation and direct measures of sun exposure—both established determinants of 25(OH)D—could not be included as covariates and may account, at least in part, for the associations reported. Full article

The COVID-19 pandemic generated unprecedented disruptions to the global tourism industry, severely affecting tourism-dependent economies and related employment. India, as one of the world’s major tourist destinations, experienced substantial declines in tourist arrivals during the pandemic period. This study investigates the effects of COVID-19-induced fear on tourism demand and economic performance in India using the COVID-19 Fear Index, which captures behavioural responses to pandemic-related uncertainty beyond conventional indicators such as infection rates, mortality, and lockdown restrictions. The COVID-19 Fear Index is constructed using reported COVID-19 cases and mortality data sourced from the European Centre for Disease Prevention and Control and the Johns Hopkins Coronavirus Resource Centre. Monthly data from January 2020 to October 2023 are analysed using autoregressive distributed lag (ARDL) and nonlinear autoregressive distributed lag (NARDL) models to examine both tourism demand dynamics and the asymmetric tourism–growth relationship. The results confirm a stable long-run cointegration relationship among tourism demand, the COVID-19 Fear Index, exchange rate, and ICT development. Pandemic-induced fear significantly reduces tourism demand in the long run ($-0.152$, $p=0.021$) and short run ($-0.084$, $p=0.000$), indicating that heightened uncertainty suppresses tourist arrivals. Exchange rate depreciation also negatively affects tourism demand ($-0.267$, $p=0.000$), whereas ICT development positively enhances tourism resilience ($0.463$, $p=0.000$). The error correction term ($-0.436$, $p=0.000$) confirms rapid adjustment toward long-run equilibrium. Furthermore, the nonlinear analysis reveals asymmetric effects, where positive tourism shocks increase economic growth by $0.088\%$ ($p=0.003$), while negative shocks exert a stronger contractionary effect ($0.409$, $p=0.000$). These findings highlight the vulnerability of tourism-dependent economies to uncertainty shocks and emphasise the importance of ICT-driven resilience strategies, adaptive tourism policies, and crisis-responsive economic planning. Full article

Johne’s disease (JD), caused by Mycobacterium avium subsp. paratuberculosis (MAP), is typically acquired early in life, yet detection of exposure during this period remains challenging. This study evaluated whether MAP-specific antibodies are passively transferred from dam to calf and detectable in neonatal calf serum, and whether these titres reflect early-life exposure to MAP. Neonatal calves (n = 38) from a commercial dairy herd were blood sampled within the first 10 days of life as part of routine assessment of passive transfer. Serum total protein (STP) was measured to assess colostrum intake, and residual serum was analysed for MAP antibody titres using an indirect ELISA. Multivariable linear regression was used to evaluate associations between calf MAP antibody titres, STP, and dam JD serological status. Calf serum MAP antibody titres were positively associated with STP (p < 0.001) and differed according to dam serological status, with higher titres observed in calves born to MAP-seropositive dams (p = 0.025). A significant interaction between STP and dam status indicated that the relationship between passive transfer efficiency and MAP antibody levels varied by dam infection status. These findings support the biological plausibility of passive transfer of MAP-specific antibodies via colostrum and suggest that neonatal calf serology may reflect exposure to an early-life epidemiological risk period associated with maternal MAP exposure and the calving environment rather than infection status within the calf itself. Given the modest sample size and single-herd design, these findings should be interpreted as exploratory and hypothesis-generating. Full article

Background: The management of diabetic foot disease and knee osteoarthritis (OA) with smart orthotics holds significant importance during the early stages of these conditions, given their potential consequences, including functional impairment, chronic pain, and economic burden. Real-time monitoring of plantar foot pressure enables early detection of abnormal force distribution and gait biomechanics, allowing for the redirection of forces away from affected ulcers or arthritic joints. This is the first systematic review to synthesise clinical evidence for smart orthotics technology with real-time plantar pressure sensor biofeedback across both diabetic foot ulcer prevention and knee osteoarthritis management simultaneously. A search of the PROSPERO register confirmed no existing registration covers this specific combination. Objectives: To examine the clinical evidence for the use of standard and smart orthotics in the prevention and management of diabetic foot ulcers (DFUs) and knee OA, and to evaluate their impact on plantar pressure redistribution, ulcer recurrence, pain, biomechanics, and economic burden. Eligibility criteria: Studies published in English involving human adult participants (≥18 years) with a clinical diagnosis of diabetes mellitus (at risk of DFU or with peripheral neuropathy) or knee OA, where the intervention involved any orthotic device or smart/intelligent insole with clinical outcomes reported, were included. Studies on healthy individuals only, those not reporting participant age, and non-weight-bearing protocols not differentiated from weight-bearing were excluded. Information sources: Five databases were searched: CINAHL (EBSCO Information Services, Ipswich, MA, USA), PubMed Advanced (National Library of Medicine, Bethesda, MD, USA), Wiley Online Library (John Wiley & Sons, Hoboken, NJ, USA), Cochrane Library (Cochrane Collaboration, London, UK), and Google Scholar (Google LLC, Mountain View, CA, USA). Searches were completed in May 2026. Methods: We conducted a comprehensive literature review. This review was structured and reported with reference to the PRISMA 2020 statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis; University of Ottawa, Ottawa, ON, Canada) to guide transparency of reporting. It does not constitute a full Cochrane-style systematic review; risk of bias assessment was applied to key included studies and GRADE (Grading of Recommendations Assessment, Development and Evaluation; McMaster University, Hamilton, ON, Canada) certainty ratings were applied informally and narratively rather than as formal per-outcome evidence profiles. Five databases were searched yielding 92,637 records. After removal of 398 duplicates by Rayyan, 92,239 records remained. A subsequent automated keyword-based relevance filter applied within Rayyan (Rayyan AI, Doha, Qatar), prior to human screening, excluded 84,572 records that did not contain any terms related to orthotics, diabetic foot, or knee osteoarthritis, yielding 7667 records for human title/abstract screening. A narrative synthesis approach was adopted owing to the heterogeneity of study designs and outcome measures across included studies, which precluded meta-analysis. This review was not prospectively registered. A complete list of all 78 included studies, including those not individually discussed in the results and discussion. Results: The available clinical studies report promising findings for orthotics and smart orthotics in pain reduction, ulcer prevention, and potential reduction in economic burden, though conclusions are limited by small sample sizes, heterogeneity, and predominantly open-label designs. Recent research found that orthotics can be used to alter the gait pattern that influences knee OA by reducing excessive force on the affected joint. A randomised controlled trial demonstrated an 80% relative risk reduction in DFU recurrence (RR = 0.20; 95% CI: 0.06–0.79; p = 0.022), with absolute event rates of 6.3% in the intervention group versus 30.8% in controls (ARR = 24.5%); a second trial reported a 71% reduction in ulcer incidence over 18 months; and a third randomised controlled trial demonstrated statistically significant plantar pressure reduction (p < 0.01) in patients with diabetic neuropathy. Conclusions: The available evidence suggests that orthotics may be associated with improved pressure redistribution, reduced ulcer incidence, and benefit in the management of knee OA. Although the number of studies directly comparing smart orthotics with standard orthotics remains limited, the limited comparative studies suggested that smart orthotics showed promising results in reducing ulcer incidence, providing the patient with real-time feedback to offload via their electronic devices. These findings, while preliminary, highlight the potential of smart orthotic technology as an adjunct to standard orthotic care in reducing the overall burden of diabetic foot disease and knee osteoarthritis. Limitations: The primary methodological limitation of this review is the open-label design of all included smart orthotic trials, which precludes participant blinding and introduces performance bias. However, this limitation is structural and inherent to the wearable technology field—analogous to surgical trials—and is substantially mitigated by the use of objective primary outcome measures (plantar pressure and ulcer recurrence) across the three included RCTs, the consistency of effect direction across independent RCTs conducted in different countries, and a narrative sensitivity analysis confirming robustness of findings (Risk of Bias Across Studies Section). Formal per-outcome GRADE evidence profiles were not produced; overall certainty of evidence was assessed narratively with reference to GRADE domains and is judged to be low to moderate for smart orthotics in DFU prevention and low for knee OA management, consistent with the Level 2–3 evidence base and open-label study designs. Future adequately powered, multi-site RCTs with standardised outcome reporting, minimum 24-month follow-up, and integrated health economic modelling are the highest priority to extend these preliminary findings. Registration: This review was not prospectively registered. Full article

Background/Objectives: Extramedullary disease (EMD) is an aggressive and treatment-resistant manifestation of multiple myeloma with limited therapeutic options, particularly in heavily pretreated patients. Methods: We conducted a retrospective study to evaluate the efficacy and safety of concurrent immune checkpoint inhibitors (ICIs) and radiation therapy (RT) in patients with EMD treated at Hackensack University Medical Center and John Theurer Cancer Center between January 2016 and May 2025. Patients were included if they had confirmed EMD and received nivolumab or pembrolizumab with concurrent RT. Results: A total of 21 patients were included, representing a high-risk cohort with a median of 6 prior lines of therapy (range 2–13), including 47.6% triple-class refractory and 19.0% penta-refractory disease. The overall response rate (ORR) was 47.6%, with a clinical benefit rate of 57.1%. Despite these responses, median progression-free survival (PFS) and overall survival (OS) were 4 and 12 months, respectively. Notably, two patients achieved complete responses with nivolumab and RT early in their treatment course following cellular therapy and remain disease-free at last follow-up. The combination of ICIs and RT was generally well-tolerated, with manageable immune-related adverse events and no treatment-related deaths. Conclusions: These findings suggest that concurrent ICI and RT may provide a signal of treatment responses in a subset of patients with advanced EMD, although durability remains limited. Further prospective studies are warranted to further define the role of this combination and identify patients most likely to benefit. Full article

Objective: Electrocorticography can serve as an intraoperative research tool during deep brain stimulation procedure, when patients are awake to participate in behavioral tasks or to allow recordings while awake but at rest. This report aims to describe the electrocorticography methods used in awake patients undergoing deep brain stimulation surgery at a single center and to describe the feasibility, safety, and usefulness of high-density electrocorticography for capturing high-resolution neurophysiological data during deep brain stimulation surgery. We hypothesize that the use of high-density electrocorticography and multi-subject integration of cortical data enables improved spatial resolution and data analysis compared to prior studies employing lower-density electrodes and primarily single-subject analyses. Methods: Data were obtained from patients undergoing awake deep brain stimulation surgery for the treatment of Parkinson’s disease or essential tremor at Johns Hopkins Hospital between March 2022 and September 2024. Electrophysiological and anatomical data were analyzed, with localization in the anterior commissure and posterior commissure and Montreal Neurological Institute coordinate systems. Surgical complications were monitored for at least six months postoperatively. Results: Thirty-six patients (26 with Parkinson’s disease, 10 with essential tremor) were enrolled in the study. In one case, anatomical placement was inadequate for neurophysiological analysis. Postoperative complications included three infections (8.3%) and one chronic subdural hematoma (2.8%), with no permanent neurological deficits. Observed complication rates were within the range reported in the literature for standard deep brain stimulation surgeries without electrocorticography. Anatomical and neurophysiological analysis demonstrated high-resolution cortical mapping. Multiple-subject level analysis using high-density electrocorticography yielded over 1300 electrode positions. Conclusions: Electrocorticography during deep brain stimulation is a valuable research method for movement disorders and, based on a moderate sized consecutive clinic sample, appears safe with risks no greater than those associated with DBS surgery itself. Full article

Johne’s disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is endemic in Saudi Arabia and contributes to substantial production losses in small-ruminant herds. This study investigated MAP infection in 388 locally raised small ruminants (151 sheep and 237 goats) using IS900 real-time PCR (qPCR) on fecal samples and indirect ELISA on serum samples. Ziehl–Neelsen (ZN) staining and pathological assessment were applied as supportive tools in necropsied cases. Overall, qPCR detected MAP DNA in 135/388 animals (34.8%), with higher positivity in goats (100/237; 42.1%) than in sheep (35/151; 23.1%). ELISA detected MAP antibodies in 120/388 animals (30.9%), including 90/237 goats (37.9%) and 30/151 sheep (19.8%). Based on clinical examination (presence/absence of clinical signs), qPCR-positive animals were categorized as subclinical (n = 15; 10 goats and 5 sheep) or clinically progressed (n = 120; 90 goats and 30 sheep). Gross and histopathological findings were assessed in a necropsied subset (n = 20; 10 subclinical and 10 clinically progressed), revealing mild focal granulomatous enteritis with scant acid-fast bacilli in subclinical cases and diffuse lepromatous-type granulomatous lesions with abundant bacilli in clinically progressed animals. Genotyping and subtyping were performed on tissue-derived DNA from six necropsied cases using DMC, IS900, and F57 targets, and IS900 sequencing confirmed the circulation of both Type C/II and Type S/I MAP strains. Collectively, these findings demonstrate widespread MAP infection among small ruminants in Saudi Arabia, with higher detection rates and more pronounced pathology in goats, and highlight the genetic heterogeneity of circulating MAP strains. Full article

Timely identification of infectious disease threats is essential for public health readiness. Conventional indicator-based surveillance systems, while dependable for tracking established pathogens, frequently lack the agility and sensitivity to detect new infections promptly. Syndromic surveillance, which examines pre-diagnostic and non-specific health indicators from many data sources in near real time, serves as a significant complementary method that improves early warning and situational awareness. This narrative study analysed selected experiences with syndromic surveillance, utilising peer-reviewed literature and institutional records. Four primary data streams were examined: emergency department and hospital records, pharmacy and over the counter (OTC) sales, participative citizen-generated data, and hybrid multi-source systems. Syndromic indicators were reported to identify outbreaks two to fourteen days before standard laboratory reporting across many trials. Data from the emergency department exhibited the highest sensitivity and specificity (47.34% and 91.95%, respectively), whereas pharmacy and participative data offered early indicators at the community level. Integrated systems like ESSENCE (Johns Hopkins University Applied Physics Laboratory, Laurel, MD, USA) and SurSaUD^® (Saint-Maurice cedex, Paris, France) attained enhanced accuracy yet necessitated significant data integration and governance capabilities. Syndromic surveillance enhances epidemic preparation by detecting atypical health-seeking behaviours and variations from baseline patterns prior to formal diagnosis. Nonetheless, its efficacy is contingent upon data quality, interoperability, and contextual adaptation. Countries like Bulgaria could improve national early-warning capabilities and overall health security through the gradual adoption of pilot projects and integration with existing surveillance networks. Full article

Inflammatory bowel disease (IBD) comprises mainly Crohn’s disease (CD) and Ulcerative Colitis (UC). The Western model suggests that environmental factors, immunological factors, the gut microbiome, and genetic disposition all contribute to the onset and sustained symptoms that define CD, although the pathogenesis of CD remains unresolved. Current studies propose that in individuals who are genetically susceptible, genetic factors linked to immune dysregulation, in combination with environmental exposure, can result in dysbiosis of the gut microbiome and intestinal barrier dysfunction, leading to immune dysregulation. In Malaysia, the incidence of IBD is rising with CD increasing disproportionally compared to UC, and the incidence of CD currently mirrors that of the United Kingdom in the 1930s, which now has one of the highest incidences worldwide. Given the suggested role of Mycobacterium avium subspecies paratuberculosis (MAP) in CD in Western countries, which is subject to some controversy, this review summarises for the first time the current evidence on genetic, environmental, and microbial factors that could contribute to the rise of Crohn’s disease in Malaysia and proposes preventive approaches. We note the increasing reliance of Malaysia on imported cattle and milk products from areas of high Johne’s Disease prevalence to meet increasing demand and changes in milk preferences in the Malaysian population, both key indicators for human-MAP exposure in the Western model. Therefore, should MAP be shown to be associated with CD in Malaysia, some preventative measures are suggested, such as screening imported and native beef and dairy cattle, dairy products and ultimately water, both recreational and potable. Full article

The agar diffusion method was used to test the antibacterial activity of 12 plant species against Agrobacterium tumefaciens, the bacterium that is responsible for crown gall disease. Leaf, root, or flower extracts were prepared, but not all parts were used for each of the 12 plants listed. Plant extracts from leaves exhibited higher antibacterial activity than those from flowers and roots. Furthermore, the type of solvent had a significant influence on both the antibacterial activity and the flavonoid and polyphenol content. Acetone and alcohol extracts contained higher contents of these compounds than water extracts. The strongest bacteriostatic effect was of the leaf extracts of eucalyptus (Eucalyptus nicholii L.) and St. John’s wort (Hypericum perforatum L.). Based on HPTLC analysis, eucalyptus extracts contained, among others, chlorogenic acid, hyperoside, and quercetin, while St. John’s wort extracts contained rutin, hyperoside, and quercetin. The tansy leaf extracts (Tanacetum vulgare L.) were also rich in flavonoids and phenolic acids, such as kaempferol-3-glucoside, luteolin, chlorogenic acid, cynarine, and rutin. However, a moderate inhibitory effect against the tested bacterium was found in tansy extracts, as well as hop (Humulus lupulus L.), wormwood (Artemisia absinthium L.), peppermint (Mentha piperita L.), yarrow (Achillea millefolium L.), and nettle (Urtica dioica L.) extracts. The least effective were the root extracts of dandelion (Taraxacum officinale F.H. Wiggers coll.) and valerian (Valeriana officinalis L.), as well as the flower extracts of chamomile (Matricaria chamomilla L.) and marigold (Calendula officinalis L.). Given the lack of effective chemical products and the unavailability of commercially resistant cultivars, the use of plant-based extracts for protecting against crown gall appears to be of particular interest. The preliminary results are promising and suggest that eucalyptus and St. John’s wort extracts are the most promising for controlling A. tumefaciens. Full article

Johne’s disease (JD) is a chronic infection of cattle that undermines herd productivity and profitability. While test-and-cull programs are commonly proposed for control, their effectiveness and economic feasibility remain uncertain in beef production systems. This study used an updated agent-based model (ABM) to simulate JD transmission in a representative 300-cow Western Canadian beef herd, coupled with a partial budget model to evaluate net present value (NPV) over a 10-year time horizon. Seven diagnostic test-and-cull strategies were compared, varying in test type (ELISA, individual PCR, and pooled PCR), sampling frequency (6, 12, or 24 mo), and risk-based sampling protocols. Results showed that, under baseline assumptions (6% starting prevalence; 1% prevalence in purchased stock), all strategies reduced JD prevalence relative to no testing, and six of seven yielded higher NPVs. Annual individual PCR testing provided the best balance between prevalence reduction and profitability, whereas semi-annual PCR most effectively reduced prevalence but at greater economic cost. Failure to implement control measures resulted in increasing prevalence and long-term economic losses. Sensitivity analyses demonstrated that strategy performance was consistent across variations in market conditions, cost of production, and replacement female management, although profitability declined substantially when JD prevalence in externally sourced stock was high (i.e., 10%). Collectively, these findings indicate that JD can be controlled economically in beef herds, with long-term application of various test-and-cull strategies offering robust options adaptable to management preferences. Full article

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) exhibits pronounced racial disparities in incidence and outcomes, yet the molecular basis remains poorly understood. Here, we examined racial differences in gene rearrangements (MYC, BCL2, BCL6), fusions (IGH::MYC, IGH::BCL2), and their interactions among White, Black, Asian, and Other-race groups in patients with DLBCL to uncover genetic drivers of disparities. Methods: We analyzed 919 DLBCL cases (2006–2023) from Johns Hopkins Hospital using fluorescence in situ hybridization to detect gene abnormalities. We used logistic regression and proportional odds models, adjusted for age and sex, to evaluate racial differences in five gene abnormalities and 10 gene–gene interaction pairs. Pearson’s Chi-squared and Goodman–Kruskal’s gamma tests assessed prevalence and interaction severity across racial groups. Results: MYC rearrangements and the MYC*IGH::MYC interaction were marginally more frequent in the White group than in Black and Other groups (p = 0.092, p = 0.098, respectively). IGH::BCL2 fusions were more prevalent in the Asian group than in the White group (p = 0.095), and the BCL2*IGH::BCL2 interaction was significantly higher in the Asian group (p = 0.049) than in the White group. Although high-grade B-cell lymphoma (HGBCL) prevalence showed no significant racial differences (p = 0.16), the Asian group exhibited a higher proportion of aggressive HGBCL with concurrent IGH::MYC and IGH::BCL2 fusions compared with the White group (p = 0.076). Age significantly influenced all gene abnormalities and interactions (p < 0.001–0.052), except for MYC rearrangements and specific pairs. Sex and sex–race interactions showed no significant effects. Conclusions: This study highlights molecular contributions to the racial differences in DLBCL disease. Further research collecting ancestry-specific biomarkers, treatment regimens, and clinical variables and outcomes is needed to advance personalized treatment strategies. Full article

Paratuberculosis (Johne’s disease) is a chronic enteric infection of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP), leading to significant economic losses in livestock production. While the solute carrier family 11 member 1 (SLC11A1) gene has been implicated in resistance to intracellular pathogens in several species, its role in ovine paratuberculosis remains largely uncharacterized. The present study investigated whether polymorphic variation in the SLC11A1 3′ untranslated region (3′UTR) (GT)_n microsatellite is associated with resistance or susceptibility to MAP infection in sheep. A total of 138 sheep from three breeds (Karagouniki, Boutsika, and Chios) were genotyped. Gene expression analysis was subsequently performed on a subset of 53 animals, which comprised rigorously phenotyped MAP-resistant (n = 18) and MAP-sensitive (n = 35) individuals from the Karagouniki breed. Four predominant alleles, (GT)₂₁, (GT)₂₂, (GT)₂₃, and (GT)₂₄, were identified. The (GT)₂₁ and (GT)₂₃ alleles were significantly enriched among resistant sheep, while (GT)₂₂ and (GT)₂₄ were more frequent in sensitive animals (χ² = 12.4, p = 0.006; Cramér’s V = 0.38). No significant differences in basal SLC11A1 mRNA expression were detected between phenotypic groups. These findings extend previous GWAS results in sheep by providing the first allele-level evidence linking SLC11A1 3′UTR microsatellite polymorphisms to paratuberculosis resistance in sheep. Although limited by sample size and single-breed representation, the results offer a foundation for future functional and genomic selection studies aimed at enhancing disease resilience in small ruminants. Full article

Paratuberculosis or Johne’s disease is caused by Mycobacterium avium subsp. paratuberculosis (MAP). The disease is characterized by a chronic and incurable enteritis in ruminants and it is responsible for significant economic losses, also raising concerns about food safety and animal welfare. Effective control is hindered by diagnostic limitations, long incubation periods, and the environmental resistance of the pathogen. This study aimed to reduce the apparent prevalence of paratuberculosis in a single intensive dairy herd through an integrated approach that combines diagnostics and management strategies. All cows over 24 months of age were tested using both fecal PCR and ELISA serology. Digital PCR (dPCR) was used to quantify MAP shedding in fecal-positive animals, enabling prioritization for removal based on environmental contamination risk. Integrating diagnostic tools allowed the precise identification and quantification of high-risk animals. Meanwhile, structural improvements and biosecurity measures were implemented on the farm. Preliminary outcomes suggest a marked reduction in herd-level MAP prevalence, lowering the seroprevalence from 7.6% to 4.5% and the fecal PCR prevalence from 6.5% to 2.8%. This case highlights the effectiveness of combining laboratory testing (serology and molecular diagnostics) and targeted changes in farm management to control paratuberculosis in high-density dairy systems. Full article