Search Results (3,098)

This study presents a paleopathological analysis of individual T4.2 from the archaeological site of the castle of Zorita de los Canes (Guadalajara, Spain). The individual exhibits ultradolichocephaly and was dated between the 13th and 15th centuries. Based on the context, the individual could have been a member of the military–religious Order of Calatrava. Standard bioanthropological and paleopathological methods were applied. The results indicate a male aged between 45 and 49 years with a maximum cranial length and width of 230 mm and 122 mm, respectively. The cranial index (53%) allows him to be classified as ultradolichocephalic. The remains present craniosynostosis at the sagittal, squamosal and sphenofrontal sutures, together with underdevelopment of the skull base width and a dolichognathic mandible with the possible presence of type III prognathism. The left hemimandible and hemimaxilla display a large amount of tartar covering the occlusal, labial and lingual areas of the teeth completely. The right hemimandible and hemimaxilla exhibit almost no tartar, and some teeth were lost in vivo. In addition, two stab wounds—to the external occipital protuberance and to the left temple—as well as a contused injury in the left tibia, can be observed without evidence of bone remodeling. Differential diagnosis indicates a case consistent with Crouzon syndrome. This individual is of particular significance because he was a possibly knight of the Order of Calatrava who presents a syndromic craniosynostosis consistent with Crouzon syndrome and exhibits lesions, which may suggest that he could have died in battle. Full article

Alopecia areata (AA) is a chronic autoimmune disorder characterized by non-scarring hair loss, with subtypes ranging from patchy alopecia (AAP) to alopecia totalis and universalis (AT/AU). The aim of this research is to investigate molecular features across AA severity by performing an integrated analysis of scalp transcriptomic datasets (GSE148346, GSE68801, GSE45512, GSE111061) and matched serum proteomic data from GSE148346. Differential expression analysis indicated that, relative to normal scalp, non-lesional AA tissue shows early immune activation—including Type 1 (C-X-C motif chemokine ligand 9 (CXCL9), CXCL10, CD8a molecule (CD8A), C-C motif chemokine ligand 5 (CCL5)) and Type 2 (CCL13, CCL18) signatures—together with reduced expression of hair-follicle structural genes (keratin 32(KRT32)–35, homeobox C13 (HOXC13)) (FDR < 0.05, |fold change| > 1.5). Lesional AAP and AT/AU scalp showed stronger pro-inflammatory upregulation and greater loss of keratins and keratin-associated proteins (KRT81, KRT83, desmoglein 4 (DSG4), KRTAP12/15) compared with non-lesional scalp (FDR < 0.05, |fold change| > 1.5). Ferroptosis-associated genes (cAMP responsive element binding protein 5 (CREB5), solute carrier family 40 member 1 (SLC40A1), (lipocalin 2) LCN2, SLC7A11) and IRS (inner root sheath) differentiation genes (KRT25, KRT27, KRT28, KRT71–KRT75, KRT81, KRT83, KRT85–86, trichohyalin (TCHH)) were consistently repressed across subtypes, with the strongest reductions in AT/AU lesions versus AAP lesions, suggesting that oxidative-stress pathways and follicular structural integrity may contribute to subtype-specific pathology. Pathway analysis of lesional versus non-lesional scalp highlighted enrichment of IFN-α/γ, cytotoxic, and IL-15 signaling. Serum proteomic profiling, contrasting AA vs. healthy controls, corroborated scalp findings, revealing parallel alterations in immune-related proteins (CXCL9–CXCL10, CD163, interleukin-16 (IL16)) and structural markers (angiopoietin 1 (ANGPT1), decorin (DCN), chitinase-3-like protein 1 (CHI3L1)) across AA subtypes. Together, these data offer an integrated view of immune, oxidative, and structural changes in AA and found ferroptosis-related and IRS genes, along with immune signatures, as potential molecular indicators to support future studies on disease subtypes and therapeutic strategies. Full article

Background and Clinical Significance: In hepatocellular carcinoma (HCC), numerous signaling pathways become aberrantly regulated, resulting in sustained cellular proliferation and enhanced metastatic potential. Tumors that lack PYGO2 may not show the same types of tissue remodeling or regenerative features driven by the Wnt/β-catenin pathway, which could make the tumor behave differently from others that are Wnt-positive. PIK3CA-positive tumors are often associated with worse prognosis due to the aggressive nature of the PI3K/AKT pathway activation. This is linked to higher chances of metastasis, recurrence, and resistance to therapies that do not target this pathway. Case presentation: In this paper we present a rare case of hepatocellular carcinoma with PIK3CA-positive and PYGO2-negative signaling pathways, several key aspects of the tumor’s behavior, prognosis, and treatment options. Although alpha-fetoprotein (AFP) levels were significantly elevated, the CT and MRI examination showed characteristics of malignancy, HCC with secondary hepatic lesions and associated perfusion disturbances. The case particularities and immunohistochemistry features are highlighted in the context of literature review, the PIK3CA mutation suggesting the activation of the PI3K/AKT/mTOR pathway, a critical signaling pathway involved in cell survival, proliferation, and metabolism. Conclusions: Due to the aggressive nature of PIK3CA mutations, close monitoring and consideration of immunotherapy and targeted treatments are of crucial importance. Full article

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide exerting, among others, strong trophic and protective effects. It plays a role in several physiological functions, including glucose homeostasis. The protective effects of PACAP are mainly mediated via its specific PAC1 receptor by stimulating anti-inflammatory, anti-apoptotic and antioxidant pathways. The aim of the present review is to summarize data on the protective effects of PACAP in the three major complications of diabetes, retinopathy, nephropathy and neuropathy, as well as some other complications. In type 1 and type 2 diabetic retinopathy models and in glucose-exposed cells of the eye, PACAP counteracted the degeneration of retinal layers and inhibited apoptosis and factors leading to abnormal vessel growth. In models of nephropathy, kidney morphology was better retained after PACAP administration, with decreased apoptosis and fibrosis. In diabetic neuropathy, PACAP protected against axonal–myelin lesions and less activation in pain processing centers. This neuropeptide has several other beneficial effects in diabetes-induced complications like altered vascular response, cognitive deficits and atherosclerosis. The promising therapeutic effects of PACAP in several pathological conditions have encouraged researchers to design PACAP-related drugs and to develop ways to enhance tissue delivery. These intentions are expected to result in overcoming the hurdles preventing PACAP from being introduced into therapeutic treatments, including diabetes-related conditions. Full article

This study aims to investigate whether a combined action observation–motor imagery practice may enhance the effects of conventional physical rehabilitation in a stroke survivor population. A total of 8 (7 male, 1 female) post-stroke patients with upper limb hemiparesis were enrolled into a single-blinded, randomised, study. Five times per week for three weeks, four patients experienced 60’ conventional physical therapy, while the other 4 experienced 30’ conventional physical therapy and 30’ action observation–motor imagery practice. The Fugl-Meyer Assessment-Upper Extremity and the Wolf Motor Function Test scores from the baseline and post-physiotherapy were used to evaluate upper extremity motor function. Patients who received the AO + MI alongside conventional physical rehabilitation benefitted more than those who received only conventional physical rehabilitation. However, the sample size was very small (only eight participants), which reduces both the statistical power and the ability to generalise the results. Moreover, there was no follow-up; therefore, it is unclear whether the observed improvements lasted over time. Finally, some potentially confounding factors, such as stroke type or lesion site, were not statistically controlled. Notwithstanding these limitations, our findings may serve as a basis for future large-scale, well-controlled studies on AO + MI in stroke rehabilitation. Full article

Background: This study investigates the incidence and radiological features of hyperechoic hepatic lesions in northern Saudi Arabia, using ultrasound (US) and computed tomography (CT). The aim is to evaluate the frequency of occurrence of these lesions and to describe the imaging characteristics of different focal hepatic lesions. Methods: A retrospective study was performed on 191 patients diagnosed with hyperechoic hepatic lesions at a single centre. Imaging data from ultrasound and CT scans were analyzed, including lesion number, segmental distribution, echogenicity, enhancement patterns, size, and type. Statistical methods included incidence calculation, variable correlation, and Pearson’s Chi-square test, with significance set at p < 0.05. Results: The incidence of hyperechoic hepatic lesions was 1.27%, with a higher prevalence in females (57.59%) and a median age of 40 years. Hemangiomas were the most common type of lesion (94.77%). Most lesions were solitary (87.43%) and benign (96.86%), with malignant lesions accounting for only 3.14%. A statistically significant age difference was observed between patients with benign and malignant lesions (p < 0.05). Conclusions: Focal hyperechoic hepatic lesions are relatively common in the northern Saudi population, with haemangiomas being the predominant benign entity. These lesions occur more frequently in women and are usually solitary. Ultrasound, complemented by problem-solving techniques such as contrast-enhanced ultrasound (CEUS) or triphasic CT, effectively characterizes hyperechoic hepatic lesions and guides clinical decisions regarding further evaluation or management. Full article

Cervical cancer remains a leading cause of mortality among women, particularly in regions with limited resources. Persistent high-risk human papillomavirus (HR-HPV) infection is the main etiological factor for CIN and cervical cancer. This study aimed to evaluate the association between HPV genotypes, age, and cytological findings and the presence of CIN2–3 in women presenting with abnormal cervical cytology. This cross-sectional study included 189 women with abnormal cytology who attended a tertiary center in Peru. All participants underwent partial HPV genotyping using the Cobas 4800 assay, colposcopic evaluation, and colposcopically directed biopsies, which served as the diagnostic reference. Sociodemographic characteristics and reproductive histories were also collected. Multiple logistic regression was performed to assess the associations among specific HPV genotypes, age, cytological results, and CIN2–3 outcomes. Most participants were between 30 and 59 years of age (76.7%), and multiparity was common (77.8%). The most frequent cytological abnormalities were ASC-US (36.0%) and LSIL (28.0%), followed by HSIL (20.1%). HPV16 was detected in 24.3% of cases, HPV18 in 2.1%, and other HR-HPV types in 73.6%. HSIL cytology showed high concordance with histological CIN2–3 (>95%). Logistic regression demonstrated that age ≥ 30 years (aOR 4.50, 95% CI 1.90–10.65) and HPV16 infection (aOR 4.19, 95% CI 1.95–9.00) were the strongest independent predictors of high-grade disease. HPV18 was rare and not significantly associated, whereas other HR-HPV types showed an inverse association with CIN2–3. HPV16 and age ≥ 30 years were the most significant predictors of CIN2–3 in women with abnormal cytology, underscoring the dominant oncogenic role of HPV16. Integrating HPV genotyping, cytological findings, and age into risk-stratified algorithms could optimize cervical cancer prevention, ensuring timely detection of high-grade lesions while minimizing overtreatment in low-risk populations. Full article

Background/Objectives: Adenomyosis is increasingly being identified in women of childbearing age as a cause of infertility and adverse pregnancy outcomes. As hysterectomies are not suitable for fertile women, conservative surgical management has become a promising solution. We aimed to synthesize current evidence on conservative uterus-sparing surgical techniques for adenomyosis, focusing on implications for infertility treatment and pregnancy outcomes. Methods: A search of PubMed, Google Scholar, and Europe PMC from 2022 to July 2025 was conducted using combinations of the words “adenomyosis,” “fertility,” “infertility,” “pregnancy outcomes,” “adenomyomectomy,” and “uterine-sparing surgery.” Sixteen high-relevance studies were chosen that included reproductive-aged women who had conservative surgery for adenomyosis. Results: Excisional techniques such as adenomyomectomy yield pregnancy rates of >50% and live birth rates of up to 70% in focal disease, with less success in diffuse disease. Non-excisional approaches—high-intensity focused ultrasound (HIFU), radiofrequency ablation (RFA), and uterine artery embolization (UAE)—yield equivalent pregnancy (40–53%) and live birth (35–74%) rates in selected patients, with fewer surgical complications. Adjunctive hormonal therapy, particularly GnRH agonists, appears to improve outcomes. Risks include placenta accreta spectrum disorders and uterine rupture (≤6%), especially in diffuse adenomyosis. The type of lesion, location, and junctional zone thickness are strong predictors of fertility outcomes. Conclusions: Conservative surgery can augment fertility in appropriately chosen women with adenomyosis, with removal being the preferred treatment for focal disease and non-removal techniques offering encouraging alternatives in mild or intracorporeal disease. The addition of adjunct hormonal therapy and standardized patient selection criteria will optimize results. The lack of European professional society guidelines underscores the need for harmonized protocols in order to standardize the diagnosis, surgery, and reporting of results. Full article

Intracellular pathogens such as Neospora caninum, Brucella abortus, and Bovine Viral Diarrhea Virus (BVDV) are major contributors to bovine abortions, yet many cases remain without a definitive etiological diagnosis despite inflammatory evidence. This study aimed to characterize the immune response in bovine fetuses aborted due to these intracellular agents, comparing them with fetuses showing inflammatory lesions of probable infectious origin and with negative controls. We analyzed cytokine expression (IFN-γ, TNFα, IL-4, IL-8, IL-12) and haptoglobin levels in mid- and late-gestation fetuses. Mid-gestation fetuses infected with intracellular agents exhibited elevated IFN-γ and IL-8 expressions, suggesting a Th1-type immune response, while late-gestation fetuses showed decreased of these cytokines, indicating a shift toward a Th2-type response. Probable infectious abortions at late gestation also showed downregulation of IFN-γ. No significant differences were observed in TNF-α and IL-12 expressions. Additionally, haptoglobin levels were lower in mid-gestation infected fetuses compared to controls. These findings highlight gestational age-dependent immune modulation in response to intracellular infections and suggest that other unidentified pathogens may contribute to abortions with inflammatory lesions but no confirmed etiology. This study enhances our understanding of fetal immune responses in bovine abortions and may support improved diagnostic approaches for reproductive losses in cattle. Full article

Evidence of possible cerebellar involvement in spatial processing, place learning and other types of higher order functions comes mainly from clinical observations, as well as from mutant mice and lesion studies. The latter, in particular, have reported deficits in spatial learning and memory following surgical or neurotoxic cerebellar ablation. However, the low specificity of such manipulations has often made it difficult to precisely dissect the cognitive components of the observed behaviors. Likewise, due to conflicting data coming from lesion studies, it has not been possible so far to conclusively address whether a cerebellar dysfunction is sufficient per se to induce learning deficits, or whether concurrent damage to other regulatory structure(s) is necessary to significantly interfere with cognitive processing. In the present study, the immunotoxin 192 IgG-saporin, selectively targeting cholinergic neurons in the basal forebrain and a subpopulation of cerebellar Purkinje cells, was administered to adult rats bilaterally into the basal forebrain nuclei, the cerebellar cortices or both areas combined. Additional animals underwent injections of the toxin into the lateral ventricles. Starting from two–three weeks post-lesion, the animals were tested on paradigms of motor ability as well as spatial learning and memory and then sacrificed for post-mortem morphological analyses. All lesioned rats showed no signs of ataxia and no motor deficits that could impair their performance in the water maze task. The rats with discrete cerebellar lesions exhibited fairly normal performance and did not differ from controls in any aspect of the task. By contrast, animals with double lesions, as well as those with 192 IgG-saporin given intraventricularly did manifest severe impairments in both reference and working memory. Histo- and immunohistochemical analyses confirmed the effects of the toxin conjugate on target neurons and fairly similar patterns of Purkinje cell loss in the animals with cerebellar lesion only, basal forebrain-cerebellar double lesions and bilateral intraventricular injections of the toxin. No such loss was by contrast seen in the basal forebrain-lesioned animals, whose Purkinje cells were largely spared and exhibited a normal distribution pattern. The results suggest important functional interactions between the ascending regulatory inputs from the cerebellum and those arising in the basal forebrain nuclei that would act together to modulate the complex sensory–motor and cognitive processes required to control whole body movement in space. Full article

Background: Diabetes mellitus is a heterogeneous chronic disease with an increasing global prevalence. In Romania, 11.6% of the population is affected, yet only 6.46% receive treatment. Among diabetic patients, 15–25% develop skin lesions that may progress to ulceration and necrosis, significantly impairing quality of life and increasing the risk of complications. Methods: We conducted a prospective study including 28 patients (14 in the control group and 14 in the intervention group) with type I or II diabetes and chronic ulcers of the calf or foot (>4 cm²). The control group received standard therapy with debridement, dressings, antibiotics when indicated, and local and systemic ozone therapy. The intervention group was treated with an Integrative Therapeutic Protocol combining ozone therapy, pulsed electromagnetic field therapy (PEMF), colon hydrotherapy with probiotic supplementation, and an anti-inflammatory alkaline diet. Wound healing (reduction in ulcer surface area) was the primary endpoint; secondary endpoints included changes in glycemia and inflammatory biomarkers. Results: After 8 weeks, the intervention group achieved 86.2% re-epithelialization versus 58.2% in controls (p < 0.01). Significant improvements were also observed in blood glucose level (−38%), HbA1c (−25%), CRP (−26%), and fibrinogen (−28%) relative to baseline, with differences versus controls reaching statistical significance. Conclusions: The Integrative Therapeutic Protocol accelerated wound healing and improved glycemic and inflammatory profiles compared with ozone therapy alone. Although an alkaline diet was recommended, adherence and its specific contribution were not objectively monitored; therefore, this component should be interpreted with caution. Full article

Human papillomavirus (HPV) is common in both sexes and is also detected in male urine and semen. However, its exact origin and its etiological role in the male genital tract remain unclear. A total of 157 formalin-fixed paraffin-embedded tissues from 156 primary prostate cancer lesions and one metastatic lesion were analyzed. HPV-DNA was detected using a nested PCR, and HPV genotyping was performed using flow-through hybridization for positive cases. In situ hybridization (ISH) was used to localize HPV-DNA, whereas HPV-E6/E7 mRNA ISH and p16^INK4a immunohistochemistry were conducted on high-risk (HR) HPV-positive samples. A nested PCR analysis demonstrated that HPV-DNA was detected in 9.6% of prostate cancers and 0% of seminal vesicles. HR-HPV was observed in 4.5% of the samples. Unknown type was the most common genotype. Of the genotypes which could be identified in the genotyping assay, HPV44 was the most prevalent. HPV prevalence was significantly higher in patients with high-grade groups. Among 15 HPV-positive cases, HPV-DNA was found in 9 cancerous and 10 non-cancerous lesions. E6/E7 mRNA was expressed in 6 of 7 HR-HPV-positive cases, while p16^INK4a expression was weak or absent in all cases. HPV can infect prostate tissue and may contribute to carcinogenesis in some cases, but p16^INK4a was not a consistent surrogate for E7 expression. Full article

Introduction. Cervical artery dissection (CAD) is a rare condition, being one of the leading causes of stroke in patients under the age of 45, with a reported prevalence of up to 20%. The management of CAD remains controversial due to its rarity and the lack of large-scale randomized controlled trials. The aim of this study was to report the long-term outcomes of CAD in a real-world setting. Methods. This retrospective, observational, single-center study included patients diagnosed with CAD between 2010 and 2019 (approval number: 153/2015/U/Oss/AOUBo). Clinical presentation, risk factors, and medical therapies were prospectively analyzed. Management strategies included both medical and interventional approaches. Follow-up consisted of annual clinical visits and carotid duplex ultrasound (DUS), with telephone interviews every six months. The primary endpoint was defined by the overall long-term stroke/death rate and in relation to the type of medical treatment, localization of the dissection and clinical manifestations. Results. A total of 62 patients were included, predominantly male (65%) with a mean age of 58 (±2) years. Thirteen dissections (21%) were trauma-related. CAD locations included the common carotid artery in 6 cases (10%), extracranial internal carotid artery in 29 (46%), intracranial internal carotid artery in 9 (14%), and vertebral artery in 16 (25%). One patient (2%) had dissections in both the extracranial internal carotid and vertebral arteries, and another (2%) in both the vertebral and basilar arteries. Bilateral dissections were observed in 5 patients (8%). Ischemic manifestations occurred in 43 patients (68%): 10 transient ischemic attacks (16%), 17 minor strokes (27%), and 16 major strokes (25%), with ischemic lesions on cerebral CT in 31 cases (72%). Fifty-eight (93%) patients were treated medically (anticoagulants and/or antiplatelets), while 4 patients (7%) underwent surgical or endovascular intervention. The mean follow-up was 81 ± 35 months. During this period, 2 patients (4%) experienced stroke and 15 (24%) died. The estimated 10-year survival rate was 71%, and the 10-year stroke/death-free survival rate was 70%. Among medically treated patients, the 10-year stroke/death-free survival was 86% for those on anticoagulation and 67% for those on antiplatelet therapy (p = 0.1). Patients presenting with ischemic symptoms had a lower estimated 10-year stroke/death-free survival rate compared to those with non-ischemic presentations (61% vs. 69%, p = 0.7). Patients with dissection of the common carotid artery had a significantly lower estimated 10-year stroke/death-free survival rate (25%), compared to dissections in other cervical arteries (p = 0.001). Conclusions. In this real-world, single-center experience, cervical artery dissection was associated with a favorable long-term prognosis in most cases, especially among patients managed conservatively with medical therapy. Stroke and mortality rates were relatively low during extended follow-up. Although no statistically significant difference was observed between anticoagulation and antiplatelet therapy, the trend favored anticoagulation for stroke/death-free survival. Patients with CCA dissections had significantly worse 10-year stroke/death-free survival compared to those with dissections in other cervical arteries. Full article

Epilepsy is one of the most common chronic neurological disorders in dogs, characterized by recurrent, unprovoked seizures. Epileptic seizures are typically classified as single generalized (SG), cluster seizures (CS), or status epilepticus (SE), with CS and SE representing neurological emergencies linked to high morbidity and mortality. This retrospective study analyzed 254 canine epilepsy cases from two veterinary clinics in Finland and Lithuania, aiming to evaluate the frequency and clinical associations of CS and SE. Patient data included age of seizure onset, sex, weight, neuter status, blood test results, clinical and neurological examinations, magnetic resonance imaging (MRI) findings, etiology classification and clinical outcome. Seizure type distribution was as follows: CS in 47.2%, SG in 26.8%, and SE in 26.0% of cases. SG seizures were significantly more common than CS in dogs aged 6–72 months (54.4% vs. 38.3%, p = 0.005), and more frequent in first-time cases compared to previously treated ones (p = 0.005). SE was significantly associated with inflammatory brain disease, abnormal clinical and neurological findings, and a higher rate of euthanasia (29.2%, p < 0.05). Dogs with structural epilepsy were older (median 108 months) and more likely to develop SE (35.5%). Most cases initially presented as SG (58.1%), but 44.5% progressed to CS and 24.6% to SE. MRI revealed lesions in 46.5% of cases, with SE more frequent in dogs with inflammatory changes and SG predominating in neoplastic cases. No significant associations were found between seizure type and sex, reproductive status, or body weight. These findings provide new insights into seizure presentation, progression, and underlying pathology, supporting the importance of early diagnosis and individualized clinical management in canine epilepsy. Full article

Lameness is a significant global welfare and economic problem in dairy farming. The objective of this study was to explore the relationship between various claw lesions and locomotion scores (LCS). A total of 491 cows from ten Austrian dairy farms were included in the study. Each cow’s gait was individually evaluated and an ascending locomotion score ranging from 1 to 5 was assigned. Subsequently, functional hoof trimming was conducted on all cows. During this procedure the claws were examined and all lesions electronically documented. For statistical analysis, the prevalence of each LCS was calculated and the distribution of LCS in relation to parity and lactation stage examined. Additionally, a simple chi-square test and a generalised linear mixed model (GLMM) were applied to identify associations between specific types of lesions and LCSs. The results from the GLMM showed significant associations (p < 0.05) between ‘other causes’, thin soles and interdigital hyperplasia with acute digital dermatitis on its surface (IH-DD-M2) and an LCS ≥ 2, between DD-associated claw horn lesions, thin soles, interdigital hyperplasia IH-DD-M2 and an LCS ≥ 3, and between DD-associated claw horn lesions, IH-DD-M2, and ‘infectious claw disorders’ and an LCS ≥ 4. The results emphasise the importance of early and accurate detection of lameness to promptly treat underlying painful claw lesions, thereby promoting improved animal welfare. Full article