Search Results (2,344)

Members of the microsporidial genus Encephalitozoon have the capacity to infect both mammals and birds, and E. cuniculi is most commonly found in rabbits. With a seroprevalence ranging up to 85%, E. cuniculi can be a problem in pet rabbits as well as in food production and laboratory animal science. While most infections are likely subclinical, there are three main clinical presentations: neurological, renal, and ocular. Typical clinical signs including vestibular disease and phacoclastic uveitis may develop with initial or relapsing infection, while renal infection is usually progressive and associated with non-specific clinical signs. High-sensitivity/specificity ante mortem diagnostic options are lacking, and serological testing most often provides adjunct rather than definitive information such that physical examination and other diagnostics are used more so for ruling out other differentials and comorbidities, rather than confirming infection. In the veterinary community, treatment regimens are variable given the lack of thorough studies and a consensus. The aim of this document is to present the available literature to give a concise review of this organism and its infection of rabbits as well as to propose guidelines and protocols for diagnostics and treatment regimens. In addition, the current challenges and recommendations for further studies are discussed. Full article

Natural products have an invaluable therapeutic effect on human health. Natural antioxidants, including beta-carotene, turmeric, and polyphenols, are recognised for their health benefits but face significant barriers related to insufficient solubility, instability, volatility, and diminished bioavailability, which limit their therapeutic efficacy in drug delivery systems. Therefore, encapsulation of natural products in a carrier addresses the above concern. Drug delivery systems, such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), are promising carriers for effective release, consisting of solid and liquid lipids, which enhance efficiency, stability, and controlled release, thereby minimising bioavailability limitations. This review consolidates current studies on the formulation methodologies, mechanisms of action, and therapeutic applications of NLCs, emphasizing their use in the treatment of conditions such as cancer, neurological disorders, and cardiovascular diseases. The results demonstrate that NLCs substantially enhance the bioavailability and therapeutic efficacy of antioxidants, thereby improving their targeted administration and clinical effects. Nonetheless, difficulties in clinical translation remain, including drug loading capacity, regulatory authorisation, and the need for pervasive research on cytotoxicity. This article highlights important areas for future inquiry, specifically the optimisation of NLC formulations, the enhancement of targeting accuracy, and the resolution of safety issues to enhance their clinical application. Full article

Background/Objectives: Respiratory dysfunction in Parkinson’s disease (PD) is frequently underrecognized, particularly when resting oxygen saturation is preserved. Dynamic stress testing, however, may reveal exercise-induced oxygen desaturation, reflecting a latent functional respiratory impairment. The relationship between exertional oxygen desaturation and cognitive performance in PD remains insufficiently explored. Objective: To investigate the association between exercise-induced oxygen desaturation and global cognitive performance in patients with PD, and to explore the contribution of pulmonary gas exchange impairment assessed by diffusing capacity of the lung for carbon monoxide (DLCO). Methods: This prospective, cross-sectional, single-center observational study with consecutive enrollment included 50 patients with idiopathic Parkinson’s disease undergoing multidisciplinary respiratory evaluation following neurological assessment. Participants underwent cognitive evaluation using the Romanian version of the Montreal Cognitive Assessment (MoCA), pulmonary function testing including DLCO and total lung capacity (TLC), and a supervised 6-min walk test (6MWT) with continuous pulse oximetry. Exercise-induced oxygen desaturation was defined as a decrease in SpO₂ of ≥4% from baseline. Correlation analyses and multivariable regression models were applied. Results: Exercise-induced oxygen desaturation was frequent, with 60% of patients exhibiting a ≥4% decrease in SpO₂ during the 6MWT. Greater desaturation was significantly associated with lower MoCA scores (Spearman’s r = −0.383, p = 0.006). No significant associations were found between exertional desaturation and resting pulmonary function parameters, including DLCO and TLC. In multivariable analysis, lower MoCA score and levodopa–carbidopa intestinal gel treatment independently predicted greater oxygen desaturation during exercise. Conclusions: Exercise-induced oxygen desaturation is common in patients with PD despite preserved resting oxygenation and is associated with poorer cognitive performance. These findings suggest that exertional desaturation may reflect a dynamic functional impairment and may be associated with increased physiological vulnerability. Functional exercise testing with oxygen saturation monitoring may provide complementary information beyond resting pulmonary assessments. Full article

Background/Objectives: Following lumbar fusion procedures, adjacent segment degeneration (ASD) at cranial levels presents as a well-documented long-term complication, manifesting through recurrent pain, neurological deficits, and progressive functional decline. The prone single-position technique for lateral lumbar interbody fusion (PSP-LLIF) streamlines surgical workflow by eliminating the need for intraoperative patient repositioning; however, comprehensive evidence supporting its clinical and radiological effectiveness in managing cranial ASD remains insufficient. Material and Methods: This retrospective cohort study examined 30 consecutive patients presenting with symptomatic cranial adjacent segment disease who were treated with PSP-LLIF at a single institution. Patient-reported outcome measures included visual analog scale (VAS) assessments for axial and radicular pain, alongside the Oswestry Disability Index (ODI) for functional status evaluation. Radiological parameters included overall and segmental lumbar lordotic measurements, anterior and posterior disk height, fusion status, and instrumentation-related complications. Results: At 12-month postoperative evaluation, substantial clinical improvements were demonstrated. Mean VAS reductions measured 4.7 points for axial pain and 6.5 points for radicular pain, while ODI decreased by 28.5 points (p < 0.05). Radiological assessment demonstrated mean increases of 6.3° in lumbar lordosis and 5.1° in segmental lordosis, along with significant gains in both anterior and posterior disk height (p < 0.05). Solid fusion was radiographically confirmed at all instrumented levels. Temporary postoperative neurological symptoms developed in several patients but resolved spontaneously without requiring revision surgery. Conclusions: PSP-LLIF yields substantial clinical benefit and reliable radiological correction in patients with symptomatic cranial ASD. Optimal outcomes necessitate rigorous adherence to position-specific technical modifications, particularly maintenance of perpendicular fluoroscopic trajectories and implementation of continuous neural monitoring to account for prone-induced anatomical shifts. This approach represents a viable treatment strategy for patients with symptomatic cranial ASD. Full article

Background/Objectives: Von Hippel–Lindau (VHL) disease is a rare autosomal dominant hereditary disorder. Central nervous system hemangioblastomas are one of the most common tumor types associated with VHL disease. Although these tumors are histologically benign, delayed diagnosis and treatment may result in severe neurological dysfunction, permanent disability, and even death. However, little is known about the experiences of patients with VHL disease. The aim of this study was to gain a better understanding of the illness experiences and psychological responses of patients with VHL disease accompanied by central nervous system hemangioblastomas. Methods: A qualitative study based on a semi-structured guide was conducted. Twelve participants were recruited. Data were collected through face-to-face interviews and analyzed using the constant comparative method. Results: Four themes and their subthemes were identified: 1. powerlessness—unpredictable disease progression and uncontrollable continuity; 2. negative emotional experiences—guilt and self-blame, depression, and low self-esteem; 3. compromise—acceptance of fate, positive outlook, and sense of hope; and 4. persistent worry—worries about family members, anxiety regarding finances and employment, and uncertainty regarding the future. Conclusions: This study identified four major themes in the illness experiences of patients with VHL disease accompanied by central nervous system hemangioblastomas, which provided deep insights into the care needs of individuals with VHL disease. Healthcare providers should develop effective measures to enhance patients’ ability to maintain a good quality of life and confront the future with resilience. Full article

Background and Objectives: Behçet’s disease (BD) is a multisystem inflammatory disorder with significant physical, psychological, and social burdens. However, patient-reported outcomes and subjective symptom experiences remain under-recognized in clinical practice. This study aimed to provide a patient-centric analysis of the disease burden, treatment challenges, and unmet needs in BD. Materials and Methods: A multinational cross-sectional study was conducted using a structured questionnaire among 528 BD patients recruited from online support groups and a specialized clinic. The questionnaire gathered information about participants’ backgrounds, medical histories, how symptoms affected them, psychological and social factors, side effects of treatments, and their suggestions for better care. Data were analyzed descriptively. Results: The mean age of the participants was 41.4 years, and 69.3% were male. The most common symptoms that significantly affected daily life were severe fatigue (82.8%), joint pain and swelling (79.0%), and neurological issues (74.1%). Nearly half of patients perceived that fatigue (49.1%) and neurological symptoms (45.1%) were underestimated by healthcare providers. Psychological distress was prevalent, with 74.1% of participants reporting either depression or anxiety. Side effects related to treatment were frequently encountered (56.3%), resulting in treatment discontinuation for 53.4% of the individuals. The main unmet needs identified were fatigue reduction (59.1%), pain management (43.0%), and the minimization of side effects (59.1%). Furthermore, patients expressed a desire for enhanced communication (62.9%), validation of their unobserved symptoms (74.1%), and comprehensive disease education (67.6%). Conclusions: BD imposes a profound multidimensional burden, with a significant disconnect between patient experiences and their perception of clinical recognition. Fatigue, pain, psychological distress, and treatment-related challenges contribute substantially to unmet needs. A patient-centered approach emphasizing communication, symptom validation, and holistic support is essential to improving care and quality of life in BD. Full article

Complete or partial loss of smell (anosmia), sometimes in association with distorted olfactory perceptions (parosmia), is a common neurological symptom affecting nearly 60% of patients suffering from post-acute neurological sequelae of COronaVIrus Disease of 2019 (COVID-19) syndrome, called long COVID. Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) may gain access from the nasal cavity to the brain (neurotropism), and the olfactory route has been proposed as a peripheral site of virus entry. COVID-19 is a risk factor for developing Alzheimer’s Disease (AD), an age-dependent and progressive neurodegenerative disorder characterized in affected patients by early olfaction dysfunction that precedes signs of cognitive decline associated with neurodegeneration in vulnerable brain regions of their limbic system. Here, we summarize the recent literature data supporting the causal correlation between the persistent olfactory deterioration following SARS-CoV-2 infection and the long-delayed manifestation of AD-like memory impairment. SARS-CoV-2 infection of the olfactory neuroepithelium is likely to trigger a pattern of detrimental events that, directly and/or indirectly, affect the anatomically interconnected hippocampal and cortical areas, thus resulting in tardive clinical dementia. We also delineate future advancement on pharmacological and rehabilitative treatments to improve the olfactory dysfunction in patients recovering even from the acute/mild phase of COVID-19. Collectively, the present review aims at highlighting the physiopathological nexus between COVID-19 anosmia and post-pandemic mental health to favor the development of best-targeted and more effective therapeutic strategies in the fight against the long-term neurological complications associated with SARS-CoV-2 infection. Full article

Background: Primary fibula tumours are rare, representing approximately 0.25% of all primary bone tumours. While benign lesions are often asymptomatic, malignant ones typically present with pain and functional impairment. Most tumours arise in the proximal third of the fibula, yet the literature regarding their epidemiology and clinicopathological features remains limited. This systematic review aims to synthesise current evidence on presentation, diagnosis, management, and prognosis of primary malignant tumours of the proximal fibula. Methods: A systematic review was conducted following PRISMA guidelines. PubMed, Scopus, and the Cochrane Register were searched on 28 October 2025 for English-language case reports and case series on primary malignant tumors of the proximal fibula. Two reviewers independently performed study selection and data extraction, collecting information on demographics, tumor characteristics, diagnostic approaches, treatments, and outcomes, with disagreements resolved by a third reviewer. Results: Thirty-three papers involving 228 patients (78 females, 128 males, 22 unknown) were included. The mean age at diagnosis was 22.8 years (range 4–79). The most common symptoms were painful mass and neurological complaints. Osteosarcoma and Ewing’s sarcoma were predominant histological types. Limb-sparing surgeries were most common, although 16 patients underwent amputation. At mean follow-up of 48.9 months, local recurrence occurred in 44 cases, and 12 developed distant metastases, most commonly in the lungs. Overall, 38 patients died, 37 due to disease progression. Conclusions: Primary malignant tumours of the proximal fibula, while rare, pose significant therapeutic challenges. Accurate diagnosis, appropriate multimodal treatment, and careful surgical planning are crucial to optimise oncological control and functional outcomes. Full article

Background: H3K27-altered diffuse midline glioma (DMG) is a highly aggressive central nervous system malignancy with limited therapeutic options and poor prognosis. Precision medicine strategies that integrate molecular profiling with individualized treatment selection represent a critical avenue for improving outcomes. Case presentation: We describe a 31-year-old woman with H3K27-altered DMG who, after standard chemoradiotherapy, was treated with a personalized, mechanism-guided combination regimen based on her tumor’s molecular profile. Next-generation sequencing identified pathogenic alterations in ATRX, H3F3A, and NF1, with a high NF1 mutation allelic fraction indicating RAS/MAPK pathway activation. Immunohistochemistry demonstrated elevated phosphorylated mTOR consistent with PI3K/AKT/mTOR pathway upregulation. The individualized regimen comprised trametinib and everolimus for dual pathway inhibition, the tissue-agnostic agent dordaviprone (ONC201), metabolic modulation with 2-deoxy-D-glucose, and electric field-based therapy. At seven months, MRI showed approximately a 60% volumetric reduction in the enhancing tumor component, accompanied by marked T2-weighted signal regression. Clinically, the patient remained neurologically intact with a Karnofsky Performance Score of 100%. Conclusions: This case illustrates the potential clinical value of a genomics-guided, multimodal treatment strategy in H3K27-altered DMG. The systematic integration of comprehensive molecular profiling with mechanistically rational treatment selection may contribute to meaningful radiological and clinical benefit in this otherwise uniformly fatal disease. These observations support further investigation of individualized, pathway-targeted approaches in prospective studies and N-of-1 trial frameworks. Full article

The blood–brain barrier (BBB) restricts therapeutic delivery to the central nervous system (CNS), hindering the treatment of neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, brain cancers, and stroke. Aptamers, short single-stranded DNA or RNA oligonucleotides that can fold into unique 3D shapes and bind to specific target molecules, offer high affinity and specificity, low immunogenicity, and promising BBB penetration via receptor-mediated transcytosis targeting receptors such as the transferrin receptor (TfR) and low-density lipoprotein receptor-related protein 1 (LRP1). This review examines aptamer design through the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) and its variants, mechanisms of BBB crossing, and applications in CNS disorders. Recent advances, including in silico optimization, in vivo SELEX, BBB chip-based MPS-SELEX, and nanoparticle–aptamer hybrids, have identified brain-penetrating aptamers and enhanced the brain delivery efficiency. This review highlights the potential of aptamers to transform CNS-targeted therapies. Full article

Mumps virus (MuV) is a single-stranded, negative-sense RNA virus of the Family Paramyxoviridae. MuV is a highly contagious human pathogen that causes primarily mild symptoms, including hallmark swelling of the parotid glands. Severe cases can occur, leading to neurological complications, including deafness, meningitis, and encephalitis. The mumps vaccine, now included in combination with measles and rubella vaccines (MMR), was first made available in the 1960s. After its introduction, mumps incidence dropped dramatically to less than 500 cases annually in the US. However, even with long-standing vaccination programs, MuV continues to challenge the landscape of public health due to a resurgence of cases in the past several decades and a still present lack of approved antiviral drugs and treatments available for the disease. This review will explore the biology of MuV, focusing on how MuV replicates and interacts with the host immune system. Recent studies have also shed light on the role of protein phosphorylation in regulating viral RNA synthesis—particularly the dynamic interactions between the nucleoprotein (NP) and phosphoprotein (P)—offering new insights into how the virus controls its replication machinery both mechanistically and through utilizing host cell advantages. We also examine how the immune system responds to mumps infection and vaccination, and how those responses may vary across viral genotypes. Although the Jeryl Lynn vaccine strain has played a key role in controlling mumps for decades, outbreaks among vaccinated individuals have raised questions about the present vaccine’s efficacy against circulating and emerging genotypes and if novel strategies will be required to prevent future outbreaks. We review current epidemiological data, highlighting shifts in MuV transmission and genotype distribution, and discuss the need for updated or genotype-matched vaccines. By connecting molecular virology with real-world trends in disease spread and vaccine performance, this review aims to support ongoing efforts to strengthen mumps control strategies and inform the development of next-generation vaccines. Full article

Background and Clinical Significance: Superior mesenteric artery syndrome (SMAS) is a rare and often underdiagnosed cause of proximal intestinal obstruction, resulting from compression of the third portion of the duodenum between the SMA and the aorta. It typically occurs in individuals with significant weight loss due to mesenteric fat depletion. CasePresentation: We report the case of a 14.5-year-old female presented with a 6-day history of intractable vomiting and epigastric pain, on a background of intermittent vomiting over the preceding six months associated with a 7 kg unintentional weight loss, culminating in inability to tolerate oral intake. Her clinical course was complicated by a transient episode of blurred vision, numbness, and incoherent speech, initially suspected to be a neurological event. Extensive gastrointestinal and neurological investigations were inconclusive. Elevated fecal calprotectin levels raised suspicion for inflammatory bowel disease, given her family history, though endoscopy and histopathology were unremarkable. Advanced imaging ultimately demonstrated a markedly reduced aortomesenteric angle (6°) and distance (4 mm), confirming the diagnosis of SMAS. The patient was initially managed conservatively with total parenteral nutrition (TPN), achieving partial weight gain of 5 kg after 8 weeks of TPN. Due to persistent duodenal compression, surgical intervention was required. At 7-month follow-up, the patient remained symptom-free with restored nutritional status and a good weight gain. Conclusions: This case highlights the importance of considering SMAS in adolescents with chronic upper gastrointestinal symptoms and significant weight loss. Early recognition and appropriate imaging are essential to diagnosis, and timely surgical management can lead to excellent outcomes when conservative treatment is insufficient. Full article

Background/Objectives: The first 1000 days of life represent a critical window for growth and neurodevelopment, during which nutrition strongly influences brain development and metabolic programming. In phenylketonuria (PKU), dietary management is essential to prevent neurological impairment and later-life risk of non-communicable diseases (NCDs). This review examines current evidence on PKU from pregnancy through complementary feeding, highlighting the impact of nutritional strategies on neurodevelopmental and metabolic outcomes. Methods: This narrative review, following PRISMA guidelines, used a systematic search of PubMed and Scopus with defined PICO questions. Original research, reviews, and guidelines on PKU nutrition during the first 1000 days were included, emphasizing neurological and metabolic outcomes. Results: Articles addressed prenatal and postnatal factors in PKU. Optimised metabolic control in women with PKU is critical to prevent maternal PKU syndrome, reducing risks of miscarriage, congenital heart defects, microcephaly, and neurocognitive impairment. Pre-conception dietary management, frequent blood Phe monitoring, supplementation with Phe-free protein substitutes (PSs), micronutrients, and emerging pharmacological therapies support maternal and foetal health. Following newborn screening, early dietary treatment in infants with PKU maintains plasma Phe within safe ranges, promoting growth and neurodevelopment. Breastfeeding, combined with Phe-free infant PSs, is feasible, and complementary feeding should be introduced carefully. Frequent monitoring and tailored dietary adjustments, including second-stage PSs, support metabolic control, while data on gut microbiota remain limited. Conclusions: Early multidisciplinary interventions are crucial to optimise metabolic and neurodevelopmental outcomes during this window of opportunity. Further research is needed to address remaining gaps and optimise PKU management across the first 1000 days. Full article

Background and Clinical Significance: Histiocytosis encompasses Langerhans cell histiocytosis (LCH) and non-LCH, such as Erdheim–Chester disease (ECD). ECD or a mixed type of histiocytosis (LCH/ECD) may initially involve the central nervous system (CNS), resulting in a delayed diagnosis. More recently, dabrafenib and trametinib (Dab/Tra regimen) have become available in its treatment. Case Presentation: A 46-year-old woman with CNS involvement of mixed histiocytosis (BRAF V600E-positive LCH/ECD) was treated with combination therapy using a Dab/Tra regimen. At initial presentation, she exhibited central diabetes insipidus, dysarthria, and gait disturbance with mild spasticity and ataxia, requiring walking assistance even for short distances. The interval from the onset of central neurological symptoms to diagnosis of mixed histiocytosis was 4 years. The introduction of targeted therapy was 2 years later. After seven months of Dab/Tra therapy, partial neurological improvement was observed, as reflected by a decrease in the SARA score from 21/40 to 13/40 and the ICARS score from 33/100 to 28/100. However, further neurological recovery remained significantly delayed. Conclusions: We suspect that the limited improvement may be attributable to the delayed initiation of targeted therapy, in contrast to the more rapid and pronounced responses reported in cases where treatment was started earlier. Full article

Background and Clinical Significance: Deficiency of Adenosine Deaminase 2 (DADA2) is a rare monogenic vasculopathy characterised by systemic inflammatory and immunodeficiency features. Although neurological and haematological manifestations are well-documented, hepatic vascular involvement remains underappreciated. This report aims to describe the clinical and imaging characteristics of hepatic vascular involvement in a patient with DADA2 and to illustrate the evolution of hepatic lesions during long-term Etanercept therapy. In addition, we provide a synthesis of the available evidence on hepatic manifestations in DADA2, emphasising vascular pathology, clinical presentation, and therapeutic implications. Case Presentation: We describe a girl with early-onset DADA2 presenting with recurrent systemic inflammation, hypogammaglobulinaemia, vasculopathy, and two childhood strokes, followed by the development of multiple FNH-like hepatic nodules on CEUS and MRI with persistently elevated GGT. Genetic testing confirmed biallelic ADA2 mutations, and treatment with Etanercept led to sustained clinical stabilisation and marked regression of liver lesions over a nine-year follow-up period. Her older sister, carrying the same mutations, showed a milder phenotype without hepatic involvement but experienced a mesenteric vascular event. Conclusions: Large regenerative nodules with an FNH-like appearance on CEUS or MRI have not been previously reported in this setting. In our patient, Etanercept therapy produced a favourable hepatic response, reflected by a significant reduction in both the number and size of the lesions. Our case contributes to the understanding of liver disease in DADA2 and the influence of imaging and treatment on the hepatic manifestations of the condition. Full article