Search Results (203)

Laminosioptes cysticola (Vizioli, 1870), a tissue-dwelling mite responsible for nodular acariasis in birds, was identified from two hens reared in a rural backyard flock in Umbria, Italy. Adult mites were found in the subcutaneous tissue and on the serosal surface of various internal organs. Larval and first- and second-stage nymphal forms were observed beneath the skin and near the trachea and esophageal serosa. By comparing the existing literature with that reported in the present study, we propose a hypothetical reconstruction of the parasite’s life cycle. It is postulated that the entry of L. cysticola occurs through the cervical skin, where adults mate and larviparous females give birth to larvae. These larvae migrate into the loose connective tissues surrounding the trachea and esophagus, where they develop into nymphs. The immature forms then progress along the esophagus and trachea to reach the thoracic and abdominal cavities, colonizing the serosal surfaces of visceral organs. It remains unclear whether, or how, the mites return to the subcutaneous tissues to complete their maturation. Senescent specimens degenerate within the subcutis, where they are encased by a granulomatous inflammatory reaction that leads to the formation of characteristic calcified nodules. Full article

Background and Clinical Significance: Kaposi sarcoma (KS) is a rare angio-proliferative mesenchymal tumor that predominantly affects the skin and mucous membranes but may involve lymph nodes and visceral organs. Clinically, it manifests as red-purple-brown papules, nodules, or plaques, either painless or painful, often with disfiguring potential. The diagnosis is traditionally based on clinical and histopathological evaluation, although non-invasive imaging techniques are increasingly used to support diagnosis and treatment monitoring. We report a case of HHV-8-negative Kaposi sarcoma evaluated with multiple non-invasive imaging modalities to highlight their diagnostic utility. Case Presentation: An 83-year-old man presented with multiple painful, violaceous papulo-nodular lesions, some ulcerated, on the lateral aspect of his left foot. Dermoscopy revealed the characteristic rainbow pattern. Dynamic Optical Coherence Tomography (D-OCT) allowed real-time visualization of microvascular abnormalities, identifying large serpentine and branching vessels with clearly delineated capsules. Line-field Optical Coherence Tomography (LC-OCT) showed irregular dermal collagen, vascular lacunae, and the presence of spindle cells and slit-like vessels. Histological analysis confirmed the diagnosis of Kaposi sarcoma, revealing a proliferation of spindle-shaped endothelial cells forming angulated vascular spaces, with red blood cell extravasation and a mixed inflammatory infiltrate. Conclusions: Non-invasive imaging tools, including dermoscopy, D-OCT, and LC-OCT, have emerged as valuable adjuncts in the diagnosis and monitoring of KS. These techniques enable in vivo assessment of vascular architecture and tissue morphology, enhancing clinical decision-making while reducing the need for immediate biopsy. Dermoscopy reveals polychromatic vascular features, such as the rainbow pattern, while D-OCT and LC-OCT provide high-resolution insights into vascular proliferation, tissue heterogeneity, and cellular morphology. Dermoscopy, dynamic OCT, and LC-OCT represent promising non-invasive diagnostic tools for the assessment of Kaposi sarcoma. These technologies provide detailed morphological and vascular information, enabling earlier diagnosis and more personalized management. While histopathology remains the gold standard, non-invasive imaging offers a valuable complementary approach for diagnosis and follow-up, particularly in complex or atypical presentations. Ongoing research and technological refinement are essential to improve accessibility and clinical applicability. Full article

Background/Objectives: Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the GBA1 gene. Type 1 Gaucher disease is characterised by substrate accumulation in the visceral organs, which occurs in combination with acute and chronic neurodegeneration that distinguish type 2 and type 3 GD, respectively. We have previously shown the efficacy of neonatal AAV9 gene therapy for treating type 2 GD and aimed to investigate post-symptomatic administration into a model of type 1 disease. Current murine models of type 1 disease are limited in their recapitulation of early onset phenotypic manifestation and thus we aimed to create a novel model of type 1 in which to test the efficacy of adult gene therapy. Methods: The novel AAV-GD1 model was created through intracerebroventricular injection of AAV9 containing the human GBA1 gene under control of the neuron-specific synapsin promoter (AAV9.hSynI.hGBA1) to the pre-existing acute K14-lnl/lnl model of type 2 GD. Administration of AAV9.hSynI.hGBA1 aimed to restore glucocerebrosidase expression in the brain and extend the lifespan beyond 14 days, allowing the visceral pathology to develop further. The organ pathology was characterised by immunohistochemistry at various time points. Once visceral disease was confirmed, an intravenous injection of AAV9 containing a ubiquitously active CAG promoter driving hGBA1 (AAV9.CAG.hGBA1) was administered to post-symptomatic mice. Animals were aged for 2 and 4 months post-treatment with AAV9.CAG.hGBA1, and immunohistochemistry and enzymatic activity were assessed to investigate therapeutic efficacy. Results: The AAV-GD1 model displayed visceral pathology in the spleen, lung, and liver from 2 months of age. This allowed us to validate the efficacy of adult gene therapy; intravenous administration of AAV9.CAG.hGBA1 transiently ameliorated the lung pathology and rescued the spleen pathology up to 4 months post-administration. Conclusions: The creation of the novel AAV-GD1 model with more aggressive visceral pathology presents a unique opportunity for investigation of new therapies to treat type 1 GD. AAV9.CAG.hGBA1 represents a potential therapeutic option for all forms of Gaucher disease. Full article

Background/Objectives: Athonian fasting, a rigorous form of intermittent fasting practiced by Christian Orthodox nuns and a subset of the Mediterranean diet, has known health benefits, but its impact on the interplay of adipokines, inflammatory cytokines, and vitamin D status remains under-investigated. This study aimed to elucidate these relationships within this controlled dietary context. Methods: This cross-sectional study examined the interplay of leptin, interleukin-6 (IL-6), and vitamin D in 41 overweight, vitamin D-sufficient Christian Orthodox nuns practicing Athonian fasting. Anthropometric, biochemical, and inflammatory markers were assessed in the nuns (mean age 53.4 ± 17.1 years, median monastery stay 17 years, median BMI 26.8 kg/m²). Results: Analysis revealed significant positive correlations between age and monastery stay (r = 0.615, p < 0.001), age and visceral fat (ρ = 0.791, p < 0.001), age and IL-6 (ρ = 0.647, p < 0.001), and BMI and IL-6 (ρ = 0.622, p < 0.001). Strong associations existed between adiposity (BMI, body fat, visceral fat), leptin, and IL-6. Specifically, body fat showed substantial positive correlations with visceral fat (ρ = 0.858, p < 0.001), leptin (ρ = 0.538, p < 0.001), and IL-6 (ρ = 0.675, p < 0.001). Visceral fat demonstrated strong positive correlations with leptin (ρ = 0.613, p < 0.001) and IL-6 (ρ = 0.741, p < 0.001). A significant positive correlation was also observed between leptin and IL-6 (ρ = 0.507, p = 0.003). Conversely, a significant negative correlation was found between 25(OH)D and PTH (ρ = −0.380, p = 0.016). Multivariate regression analysis did not reveal independent effects of leptin or IL-6 after adjusting for other factors. Conclusions: This study reveals a complex interplay of adiposity, inflammation, and vitamin D status in this unique population of Orthodox monastery fasters. The strong correlations suggest potential targets for interventions aimed at improving metabolic health. Future research should investigate the effects of vitamin D within the context of Athonian fasting. Full article

Leishmania is a protozoan parasite causing a spectrum of pathologies in humans grouped under the name leishmaniasis. Clinical outcomes range from the self-healing cutaneous form to the visceral one that is fatal in the absence of treatment. The leishmaniases are endemic in 98 countries in the tropics, subtropics, and Southern Europe, where 3 million new cases and more than 50,000 deaths are recorded yearly. Control of this disease is challenging as there is no approved vaccine coupled with toxic chemotherapeutics and the development of parasite resistance to some available drugs. It is, therefore, evident that the identification of new control methods, including new therapeutics, should be strongly encouraged. In the present study, thiol organic compounds were synthesized and tested for their activity against Leishmania major, the causative agent of human cutaneous leishmaniasis. Of the 21 compounds tested, 13 were active against L. major promastigotes in vitro at 100 μg/mL. Selected compounds tested in a dose-response assay showed activity at concentration as low as 25 μg/mL, a level of activity similar to that of Amphotericin B, a drug of choice for the treatment of human leishmaniasis. Structure–activity analysis shows that the addition of certain substituents, such as a methoxy group, to a compound that is biologically active renders it inactive. Together, our data demonstrate that functionalized thiols have an in vivo anti-Leishmania activity that is directly linked to their chemical structure. Full article

Obesity is among the most prevalent risk factors in the severe forms of Coronavirus disease 2019 (COVID-19) infection. COVID-19 patients with obesity often face severe complications that might be associated with overexpression of adiponectin, inflammatory cytokines, and angiotensin-converting enzyme 2 (ACE2) receptors in visceral fat. The pre-existing subclinical inflammation associated with obesity can also lead to severe inflammatory responses. Elevation of proinflammatory cytokines considerably activates coagulation cascades, including the tissue factor (TF) pathway. The hypercoagulable state in COVID-19 is presented with severe pulmonary complications such as venous thromboembolism (VTE), disseminated intravascular coagulation (DIC), and disruption of vascular endothelial cells, which can lead to severe complications and death. The interaction between inflammatory response and coagulation mechanism in COVID-19 patients with obesity warrants a further understanding of prognosis and potential therapeutic approaches. This review discusses the crosstalk between inflammation and coagulopathy in obesity-related severe COVID-19 infection. Full article

Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is fatal if left untreated in over 95% of cases. Leishmaniasis is one of the neglected tropical diseases that tend to thrive in developing regions of the world where inadequate access to healthcare makes it difficult for some people to even receive a diagnosis. This study examined the usefulness of oral swabs as specimens for VL diagnosis, by detecting Leishmania donovani DNA in oral swabs from both VL patients and L. donovani-infected mice. Eighty oral swab (OS) and blood buffy coat (BC) samples were collected from suspected VL cases in Bangladesh. These samples were evaluated using Leishmania kinetoplast minicircle DNA (kDNA) in real-time PCR, and the results showed that 62.5% (50/80) and 67.5% (54/80) of the cases tested positive for the BC specimen and OS, respectively. The OS positivity was statistically comparable to the BC. L. donovani DNA was also detected in an oral swab of all infected BALB/c mice by conventional PCR targeting the large subunit ribosomal RNA gene (LSUrRNA), while it was negative in uninfected mice. This study highlights the potential of practical methods for the molecular diagnosis of VL using oral swabs as a non-invasive, simple, and accurate approach. Full article

Children with a classic form of congenital adrenal hyperplasia (CCAH) have a potentially increased risk of unfavorable cardiometabolic events due to the interplay of corticosteroid treatment, hyperandrogenism, and other factors. Although readily recognized in adults, these aspects are frequently overlooked in children and youth with CCAH; Aim: To review the evidence available from studies regarding cardiometabolic health outcomes in CCAH patients; Methods: A review of the literature was performed following PRISMA guidelines, including studies published between 2000 and 2024. We included studies reporting cardiometabolic outcomes in children and adolescents (<18 years) with CCAH. Where pediatric data were sparse, additional data were obtained from studies with older adolescents and young adults (15–25 years). Cardiometabolic outcomes included risk factors, such as obesity, insulin resistance, lipids, blood pressure, and vascular markers; Results: Twenty-five studies were analyzed. The prevalence of obesity was found to be higher in children with CCAH, as well as of increased visceral adiposity. Higher indices of insulin resistance were also a frequent finding in children with CCAH. CCAH patients had higher systolic blood pressure and more frequently loss of nocturnal blood pressure dipping, particularly among salt-wasting subtypes and in younger children. Subclinical atherosclerosis was indicated by increased carotid intima–media thickness, elevated hs-CRP, and impaired endothelial function. Other findings suggested changes in lipid profiles, particularly decreased HDL-c and increased triglycerides, although the findings were less consistent; Conclusions: Compared with the general pediatric population, children with CCAH were found to have an increase in multiple cardiometabolic risk factors. It is therefore vital to monitor these risk factors in pediatric CCAH, as well as tailoring treatment with cardiometabolic health in mind, to achieve better long-term cardiovascular and metabolic outcomes. Future research should focus on longitudinal studies of cardiometabolic outcomes and innovative therapeutic approaches to reduce these risks in patients with CCAH. Full article

Leishmaniasis is a neglected tropical disease caused by a protozoan of the genus Leishmania, which has visceral and cutaneous forms. The symptoms of leishmaniasis include high fever and weakness, and the cutaneous infection also causes lesions under the skin. The drugs used to treat leishmaniasis have become less effective due to the resistance mechanisms of the protozoa. In addition, the current compounds have low selectivity for the pathogen, leading to various side effects, which results in lower adherence to treatment. Various strategies were developed to solve this problem. The bioconjugation between natural compounds with antimicrobial activity and cell-penetrating peptides could alleviate the resistance and toxicity of current treatments. This work aims to conjugate the cell penetration peptide TAT to the guanidine GVL1. The GVL1-TAT bioconjugate exhibited leishmanicidal activity against Leishmania amazonensis and Leishmania infantum with a high selectivity index. In addition, the bioconjugate was more active against the intracellular enzyme CPP than the individual compounds. This target is very important for the viability and virulence of the parasite within the host cell. Docking studies confirmed the higher interaction of the conjugate with CPP and suggested that other proteins, such as trypanothione reductase, could be targeted. Thus, the data indicated that guanidines conjugated with cell-penetrating peptides could be a good approach for developing antileishmanial molecules. Full article

Background and Objectives: Regular physical activity (PA) and Mediterranean diet (MeDi) adherence independently improve glycemic control and clinical outcomes in type 2 diabetes mellitus (T2DM). This study examined the associations between PA, body composition (BC), MeDi adherence, and glycemic control in Dalmatian T2DM patients. Materials and Methods: A cross-sectional study was conducted at the University Hospital of Split (November–December 2023) during an open call for T2DM patients. Data collected included blood/urine samples, blood pressure, BC, and anthropometrics. MeDi adherence and PA were assessed via the Mediterranean Diet Service Score and the International PA Questionnaire-Short Form. Results: Among 252 participants (median age: 67 years, IQR: 60–73; 51.6% women; median T2DM duration: 10 years, IQR: 6–20), PA levels were low (31.4%, N = 79), moderate (45.2%, N = 114), and high (23.4%, N = 59), with uniformly low MeDi adherence across groups. Low PA was associated with higher body mass index (BMI) and lower phase angle (PhA). PA negatively correlated with fat mass (FM; %) and visceral adiposity. Positive BMI predictors included FM (kg), total body water, visceral fat level, and PhA, while fat-free mass, intracellular water, and FM (%) were negative predictors. The estimated glomerular filtration rate was the only positive predictor of the total metabolic equivalent of the task score. Conclusions: PA enhances BC and metabolic health, but inadequate MeDi adherence limits these benefits in the T2DM population. To optimize glucose control and health outcomes, public health initiatives must emphasize MeDi adherence and a combination of aerobic and resistance training. Full article

Phlebotomus sichuanensis, considered a potential vector for visceral leishmaniasis (VL), is distributed in the southern Gansu and northern Sichuan regions in China. However, the high similarity in the morphology of P. sichuanensis and P. chinensis s.s. poses unresolved taxonomic challenges. In this study, phlebotomine sand flies were collected from three locations in the southern Gansu and northern Sichuan regions (SCB group) and three locations that are the dominant distribution areas of P. chinensis s.s. (ZHB group). Their whole mitochondrial genomes were sequenced and analyzed. The differential analysis revealed that there were 339 fixed differential sites in the mitochondrial genome-coding region of P. chinensis s.s. and P. sichuanensis, among which the COI gene had the most differential sites (57), followed by ND5 (46), ND4 (38), and CYTB (37), while ATP8 had the least differential sites (4). The molecular genetic p-distance was calculated based on 13 protein-coding regions, and the genetic distance ranged from 0.001 to 0.018 in the ZHB group and from 0.001 to 0.006 in the SCB group, while the interspecies molecular genetic distance was 0.464–0.466 between the two groups. A phylogenetic maximum likelihood tree was constructed from 16 samples via tandem sequence of 13 protein-coding regions, and the topology showed that the ZHB and SCB groups formed separate clusters. A real-time PCR method was established based on the differences in the COI fragment, which can identify P. sichuanensis from P. chinensis s.s. effectively. This study presents objective evidence of the genetic differentiation between P. sichuanensis and P. chinensis s.s., and provides a method for identifying these two morphologically highly similar VL-transmitting sandflies. Full article

Talpid3 is a basal body protein required for the formation of primary cilia, an organelle involved in signal transduction. Here, we asked if Talpid3 has a role in the regulation of differentiation and/or self-renewal of ES cells and whether cells lacking cilia due to a deletion in Talpid3 can be reprogrammed to induced pluripotent stem (iPS) cells. We show that mouse embryonic limb fibroblasts which lack primary cilia with a targeted deletion in the Talpid3 (Ta3) gene can be efficiently reprogrammed to iPS cells. Furthermore, vector-free Ta3^−/− iPS cells retain ES cell features and are able to self-renew. However, both Ta3^−/− iPS and ES cells are unable to form visceral endoderm and differentiate poorly into neurons. The observed defects are not a consequence of reprogramming since Ta3^−/− ES cells also exhibit this phenotype. Thus, Talpid3 and primary cilia are required for some differentiation events but appear to be dispensable for stem cell self-renewal and reprogramming. Full article

Background/Objectives: Individuals with severe mental disorders often face challenges in maintaining a healthy lifestyle, including proper dietary habits. Educational nutrition workshops, as a form of nutritional intervention, may play an important role in improving their nutritional status. This study aims to assess the impact of nutritional workshops on the dietary habits and nutritional status of individuals with severe mental disorders and their caregivers. Methods: This study involved 65 participants, namely 46 individuals with mental disorders living in organized settings (beneficiaries) and 19 caregivers. The nutritional intervention consisted of two cycles of workshops, encompassing a total of four educational workshops. Results: Results before and after the intervention showed positive changes in nutritional status and dietary intake. Beneficiaries lost on average 3.5 kg of body weight, while body fat decreased by 3.5% and visceral fat by 1.9 points. In the group of caregivers, body fat decreased by 3.2%. Energy intake (p < 0.05), total fat (p < 0.01), saturated fatty acid (p < 0.05), polyunsaturated fatty acid (p < 0.05), and sodium (p < 0.05) intake decreased in beneficiaries compared to intake before workshops, while dietary fiber (p < 0.05), vitamin C (p < 0.05), and fruit (p < 0.01) intake increased. In caregivers, the decrease in carbohydrate (p < 0.05), total sugar (p < 0.01), and dietary fiber (p < 0.05) intake was recorded. Conclusion: This study provides a strong foundation for future research and the implementation of educational programs as part of comprehensive care for individuals with severe mental disorders. Full article

Background/Objectives: Kaposi sarcoma (KS) is a common lymphatic endothelial cancer among children with and without HIV in central and eastern Africa. Despite its clinical heterogeneity, its various clinical phenotypes are often grouped together in staging and treatment algorithms. Patients with KS tumor-associated edema, referring to hard, non-pitting lesions which often lead to chronic disability, represent a unique, understudied subgroup of children with KS. To continue our work defining the distinct phenotypes of pediatric KS, this study aimed to assess the clinical progression and outcomes of KS edema in children. Methods: A retrospective cohort study was conducted at Kamuzu Central Hospital in Lilongwe, Malawi, focusing on children diagnosed with KS edema between 2010 and 2023. Results: We identified 52 children with KS edema, representing 27% of all patients with KS. Initial chemotherapy resulted in a clinical response in 92% of patients, but 46% experienced relapse or disease progression with a median time to first relapse of 12 months. Multiple progressions were common, with 31% of patients experiencing two or more events. Event-free survival at two years was 32%, dropping to 24% at five years, while overall survival was 73% at two years and 57% at five years. Relapse was more common among patients with KS edema versus those without it (relative risk = 2.1; 95%CI, 1.4–3.2; p < 0.001). Eight patients (15%) relapsed with visceral disease, five of whom originally presented with KS edema alone. Conclusions: Patients with KS edema have a unique, relapsing-remitting pattern of disease with a high risk of relapse relative to other forms of KS with subsequent long-term mortality, even after initial positive treatment responses. Late relapse and mortality with visceral disease are possible even among children presenting initially with KS edema alone. Children with KS edema require long-term follow-up, and novel treatment approaches tailored towards preventing frequent relapse are needed. Full article