タンジール病

This work examines a nonlinear stochastic SIRS epidemic model evolving in a randomly changing environment described by a finite-state Markov chain. The transmission mechanism incorporates regime-dependent nonlinear incidence rates, where the contact interaction between susceptible and infectious individuals is modeled by the term [Formula: see text] . This switching nonlinearity allows the model to capture varying environmental effects and heterogeneous transmission patterns more accurately, thereby providing a more realistic description of epidemic dynamics. To the best of our knowledge, the sufficient criteria governing the persistence and extinction of stochastic SIRS models with transmission rate exponents governed by Markovian switching have not yet been established in the existing literature. The principal contribution of the present study is the derivation of the rigorous sufficient conditions that characterize both the extinction and the long-term persistence of disease dynamics. Specifically, a threshold parameter Λ, expressed in terms of the switching exponents ρξ(t) and ζξ(t), is derived. That is, if Λ > 0, the disease exhibits strong stochastic persistence; conversely, if Λ < 0, the disease-free equilibrium state becomes globally asymptotically stable in probability, leading to eventual disease extinction. In the special case where there is no regime switching and ρξ(t)=ζξ(t)=1, our model recovers the classical threshold found in the literature. To support and validate the theoretical findings, numerical simulations are provided to demonstrate the dynamical behavior of the model under different environmental regimes.

Pelvic osteomyelitis is rare in children, and sacral involvement is particularly unusual. Due to its deep anatomical location, clinical presentation is often nonspecific, frequently leading to diagnostic delays or misdiagnosis as hip arthritis or abdominal pathology. We report the case of a 10-year-old boy who presented with high-grade fever, right hip pain, and inability to bear weight. Initial hip ultrasonography was normal, but careful clinical examination revealed sacral tenderness, prompting pelvic magnetic resonance imaging (MRI). MRI demonstrated acute osteomyelitis of the right hemi-sacrum associated with a small paravertebral collection, diffuse iliopsoas muscle infiltration, and a minimal sacroiliac joint effusion, without spinal canal or neural foraminal involvement. Blood cultures remained negative. The patient was treated with 10 days of intravenous antibiotics followed by 3 weeks of oral therapy, resulting in complete clinical, biological, and radiological recovery. Follow-up MRI confirmed resolution of the marrow edema and disappearance of the paravertebral collection. This case highlights the diagnostic challenge of sacral osteomyelitis presenting as hip pathology and emphasizes the pivotal role of MRI in establishing an early diagnosis, assessing disease extent, and guiding appropriate management.

Hydatid disease is an endemic parasitic infection that primarily affects the liver and lungs. Hydatid pulmonary embolism is an exceptional and potentially severe complication, usually resulting from the rupture of a hydatid cyst into the venous circulation. We report the case of a 64-year-old patient, a former smoker from a rural area, who had been diagnosed with hepatopulmonary hydatid disease complicated by chronic bilateral hydatid pulmonary embolism two years before the current admission. Echinococcosis serology was positive. Thoracic computed tomography (CT) angiography revealed arterial hydatid involvement associated with multiple pulmonary and hepatic cystic lesions. Management included therapeutic anticoagulation, empirical antibiotics, and the cautious reintroduction of albendazole with close biological monitoring, followed by hepatic surgery. Pulmonary embolism is a rare presentation of hydatid disease. Because of its nonspecific clinical features, careful diagnostic assessment and individualized management are required.

Parkinson's disease (PD) is characterised by the pathological aggregation of α-synuclein (α-syn) into Lewy body inclusions, yet no disease-modifying therapy exists. To address this, we developed an integrated computational pipeline combining quantitative structure-activity relationship (QSAR) modelling, structure-based virtual screening, molecular dynamics (MD) simulation, and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy calculations to repurpose FDA-approved drugs as α-syn fibril inhibitors. Two complementary QSAR model families were trained on 501 α-syn binding affinity records from BindingDB: Morgan extended-connectivity fingerprint (ECFP4) classifiers and a frozen ChemBERTa-77M-MLM transformer encoder, each using Random Forest and Logistic Regression. The applicability domain (AD) was assessed using Morgan-Tanimoto similarity (Tc ≥ 0.40) and calibrated ChemBERTa cosine distance (θ ≤ 0.367). A three-stage funnel applying central nervous system (CNS) permeability filters, a consensus QSAR probability threshold (≥0.80), and AD gating reduced 2241 FDA-approved drugs to 205 candidates for AutoDock Vina 1.2.6 docking against two sites on the cryo-electron microscopy (cryo-EM) α-syn fibril structure, PDB 6SSX: the inter-protofilament cleft (Site 1) and the non-amyloid-beta component (NAC) groove (Site 2). The Morgan fingerprint models achieved an area under the receiver operating characteristic curve (AUROC) of up to 0.940 and a balanced accuracy of 0.810; the ChemBERTa models achieved an AUROC of 0.785 and a balanced accuracy of 0.728. Notably, ChemBERTa AD covered 76.8% of the FDA drugs versus only 5.5% for Morgan-Tanimoto, enabling broad-spectrum screening. The top docking candidates were Olaparib (-7.91 kcal/mol), Paliperidone (-7.75 kcal/mol), Niraparib (-7.18 kcal/mol), Dordaviprone (-7.06 kcal/mol), and Parecoxib (-6.89 kcal/mol). The MD simulations over 200 ns across three independent replicates confirmed stable NAC groove binding, and replicate-averaged MM-PBSA calculations yielded ΔG = -20.6 ± 1.9 kcal/mol for Olaparib at Site 2, -17.1 ± 0.9 kcal/mol for Risperidone, and -16.9 ± 0.8 kcal/mol for Paliperidone, reported as the mean ± standard error of the mean (SEM) across replicates. Olaparib additionally formed five hydrogen bonds in the representative pose, while MD trajectories maintained approximately 2-5 hydrogen bonds, together with a halogen bond within the NAC groove, the largest contact count of any screened compound. These findings identify Olaparib as a novel high-affinity repurposing lead, while Paliperidone and Risperidone are reported as chemically informative secondary NAC-groove binders rather than proposed antiparkinsonian therapeutics, given that their dopamine D2-antagonist pharmacology is clinically associated with drug-induced parkinsonism. All of the candidates warrant experimental validation via thioflavin-T fluorescence or nuclear magnetic resonance (NMR) spectroscopy.

Non-secretory multiple myeloma is an uncommon plasma cell neoplasm in which serum and urine electrophoresis and immunofixation fail to identify a measurable monoclonal component. This phenotype may delay diagnosis and make conventional biochemical monitoring difficult. We report three cases of clinically non-secretory multiple myeloma presenting with anemia and multifocal skeletal involvement despite negative monoclonal protein studies. Case 1 was a 33-year-old man with progressive fatigue, normocytic anemia, normal renal function and calcium levels, negative serum and urine monoclonal studies, and a normal serum free light chain ratio. Bone marrow aspiration showed 19% plasma cells, whereas bone marrow biopsy demonstrated extensive CD138-positive plasma cell infiltration; 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) revealed multifocal medullary lesions. Case 2 was a 63-year-old woman with low back pain and anemia, negative serum and urine immunofixation, and a normal serum free light chain ratio. Bone marrow aspiration showed 94% plasma cells, and 18F-FDG PET/CT demonstrated hypermetabolic skeletal lesions. She achieved partial remission after eight cycles of bortezomib, lenalidomide, and dexamethasone. Case 3 was a 68-year-old woman with fatigue, diffuse bone pain, anemia, negative serum and urine immunofixation, a normal serum free light chain ratio, 18% marrow plasma cells, and extensive PET/CT-positive skeletal disease. These cases emphasize that negative electrophoresis and immunofixation should not exclude multiple myeloma when the clinical, marrow, and imaging findings are suggestive. Bone marrow evaluation and whole-body imaging are central to diagnosis and follow-up in this rare entity.