Introduction: Congenital heart disease (CHD) is the leading birth anomaly and a major contributor to infant mortality, especially in low- and middle-income countries, including India. Its etiology is multifactorial, involving both genetic and environmental factors. Notably, approximately 30 % of CHD cases are associated with genetic syndromes, which often present with extracardiac anomalies. This study seeks to explore rare genetic syndromes linked to CHD, with a focus on the socio-demographic, socio-economic, and clinical profiles of the affected families.

Method: A hospital-based population screening study for CHD, including clinical dysmorphism examinations, was conducted from 2018 to 2024 at the Sri Sathya Sai Sanjeevani International Center for Child Heart Care & Research, Haryana (India), a totally free-of-cost pediatric cardiac care centre. Comprehensive data were collected at the Sri Sathya Sai Sanjeevani Research Centre and analyzed using SPSS software.

Results: A total of 442 syndromic cases were identified, with Down’s syndrome being the most common (61.7 %). Rare syndromes included Noonan (17), Marfan (11), Ellis-Van Creveld (8), DiGeorge (6), Williams (6), Pentalogy of Cantrell (3), Treacher Collins (3), MRKH (2), TAR (2), Congenital facial Nerve Palsy (2), Goldenhar (2), Alagille (1), Cornelia de Lange (1), Heterotaxy (1), Holt Oram (1), etc. The most prevalent CHD phenotype observed was ventricular septal defects (24 %). Geographically, a significant proportion of syndromic cases came from the highly populated Indian state of Uttar Pradesh (55.6 %), with a large number of affected families from the upper-lower socio-economic class (Class IV; 46.6 %).

Discussion: Identifying the clinical variability in syndromes associated with CHD can facilitate early diagnosis, which is crucial for timely intervention and improved outcomes. This study also highlights the socio-economic disparities in access to care, emphasizing the need for increased healthcare resources in underserved regions. Understanding the genetic basis of phenotypic features may help reduce disease-related mortality and morbidity.

Arthritis is a chronic inflammatory disorder characterized by progressive joint damage and immune dysregulation, significantly impacting patients’ quality of life. Conventional treatments, such as NSAIDs and corticosteroids, while effective, often cause adverse effects such as gastrointestinal bleeding, cardiovascular risks, and osteoporosis, particularly with long-term use. This study explores the anti-arthritic potential of Artemisia herba-alba, a medicinal plant with traditional anti-inflammatory uses, in carrageenan- and complete Freund's adjuvant (CFA)-induced arthritis models in rats.

Two arthritis models were used: (1) CFA-induced arthritis, where inflammation was triggered by means of a single subcutaneous CFA injection into the hind paw, evaluated over 15 days, and (2) carrageenan-induced arthritis, induced by means of repeated intra-articular carrageenan injections into the hind paw over 30 days. Male Wistar rats were divided into control, arthritic, and treatment groups. The treatment groups received oral A. herba-alba extracts (250 mg/kg or 500 mg/kg), while the positive control group received indomethacin (3 mg/kg). The hematological analysis quantified seric neutrophils and monocytes, and the histopathological examination assessed joint tissues using H&E staining.

A. herba-alba extracts demonstrated dose-dependent anti-inflammatory effects, with the 500 mg/kg dose outperforming indomethacin. The hematological analysis showed significant reductions in neutrophils and monocytes, indicating systemic immune modulation. The histopathological findings revealed reduced osteoclast activity, decreased neutrophil infiltration, and preserved synovial tissue integrity. The 500 mg/kg dose notably mitigated osteoclastic bone resorption and prevented synovial hyperplasia.

These results highlight Artemisia herba-alba as a potent natural anti-inflammatory agent with systemic and localized effects, offering a safer alternative for arthritis management. Its efficacy at 500 mg/kg, surpassing indomethacin, underscores its therapeutic potential. Further research, including clinical trials, is needed to confirm its safety and efficacy in humans and to elucidate its mechanisms of action.

Objective: We wished to study the state of the brain, the frequency of carotid artery stenosis, and the duration of hypertension in patients with ischemic strokes and dementia in the long-term period of coronary artery bypass grafting.

Methods: A total of 75 people were included, and their average age before surgery was 56 [52; 60] years. The operation was performed with the help of artificial blood circulation. The mean duration of the cardiopulmonary bypass was 86.0 [65.0; 105.0] min, and the surgery duration was 230.0 [190.0; 270.0] min. The follow-up period included hospital and five-year stages. Neuroimaging was performed on a Somatom Sensation 64 multispiral computed tomograph (MSCT) (Siemens, Germany). Color duplex scanning of the brachycephalic arteries was performed using an ultrasound scanner of the expert class "General Electric Vivid 7 Dimension LCD", USA.

Results: Within five years after coronary artery bypass grafting, four (5.3%) patients developed strokes, and two (2.7%) patients developed dementia. The duration of arterial hypertension in the group before coronary artery bypass grafting was 4 [1; 10] years. In patients with strokes, it was 8 [6; 15] years, and for those with dementia, it was 30 [20; 40] years. Before surgery, carotid artery stenoses of up to 50% according to the criteria of NASCET (North American Symptomatic Carotid Endarterectomy Trial) were detected in 37% of them, while after five years, they were found in 55% of patients, at p = 0.03. Among the stroke survivors, carotid artery stenosis was detected in four (100%) cases and dementia in one (50%) patient. Five years later, the expansion of the III ventricle of the brain was detected to range from 7.0 [5.5; 8.0] to 7.5 [6.0; 9.0] mm (p = 0.03). The number of people with leukoaraiosis increased from 25% to 71%, p=0.0001, as well as those with cysts and gliosis increasing from 4% to 20%, p=0.0001, indicating damage to the small cerebral arteries.

Conclusions: It can be assumed that the presence of prolonged arterial hypertension and carotid artery stenosis increases the likelihood of strokes and dementia within five years after coronary bypass surgery.

1. Overview:

A global health concern is neurodegenerative illnesses, which are brought on by increasing loss of the neurons, one of the main causes of cognitive and physical deterioration in these illnesses. The death of brain cells or nervous system cells is the cause of this neurological loss. Huntington's disease, Parkinson's disease, and Alzheimer's disease are among the most common conditions that share protein misfolding and aggregation. According to a WHO news report, neurological disorders impact more than one in three people and are a leading cause of disability worldwide. Since 1990, the DALYs (Disability-Adjusted Life Years) for these illnesses have gone up by 18%. The prevalence of Alzheimer's disease is estimated to be 55 million people worldwide, and for Parkinson's disease, it is 10 million globally.

Objective

We wished to achieve the following:

To review and research protein misfolding and aggregation's role in neurodegenerative diseases.

To find common molecular mechanisms for neurological disorders and the target sites for a therapeutic effect.

To evaluate the effect of genetic, environmental, and lifestyle choices on protein misfolding.

Methods

A thorough search of the literature was conducted in several large medical databases. This study was carried out in the form of a meta-analysis of the available literature.

Key findings on protein misfolding and aggregation, the participant characteristics, and the study design were all included in the data extraction process. The data analysis was performed, and the results were presented.

Results

We determined common pathways and sites for protein misfolding in neurodegenerative disorders. The results reflect upon the different factors affecting the aggregation and misfolding of proteins, and using them, the target sites for a therapeutic effect can be confirmed.

Disorders of sex development (DSDs) arise from discrepancies between chromosomal, gonadal, or phenotypic characteristics. These genetically complex conditions exhibit a broad phenotypic spectrum, ranging from hypospadias to fully masculinized or feminized genitalia that are incongruent with the karyotype. DSDs result from disruptions in gonadal formation (sex determination) or function (sex differentiation). Although rare, they have significant clinical implications and require a multidisciplinary approach to care. An accurate diagnosis, facilitated by various molecular techniques, is essential for personalized management, genetic counseling, and prognostic prediction for fertility and the risk of tumor development.

In this study, we present a cohort of 14 children with 46,XY DSDs referred to the genetics department for molecular diagnosis. Their phenotypic spectrum ranged from hypospadias to severely atypical external genitalia and female-typical external genitalia with palpable gonads in the presence of a male karyotype. Patients were classified based on the underlying pathophysiological mechanisms of the 46,XY DSD and screened for mutations in the AR, SF1, SRD5A2, and HSD17B3 genes using Sanger sequencing.

We identified three variants of uncertain significance (VUSs) in four out of nine (4/9) patients with complete or partial androgen insensitivity syndrome. Additionally, two VUSs in the HSD17B3 and SRD5A2 genes were detected in 3 patients (3/14) with androgen biosynthesis defects. A genetic analysis of the SF1 gene in 2 patients (2/14) revealed no pathogenic mutations.

This study details the genetic diagnoses of a heterogeneous cohort of children with 46,XY DSDs undergoing evaluations for surgical management. Molecular genetic testing enhances our understanding of the etiology and improves the diagnostic accuracy. However, identifying the underlying cause of 46,XY DSDs remains challenging, and in many cases, their etiology remains unknown.

Autoimmune diseases are characterized by an exacerbated immune response against the body's own tissues. The main pathologies include rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, psoriasis and inflammatory bowel disease. All these pathologies are based on oxidative stress and chronic inflammation. Therefore, the search for alternative therapies based on natural compounds with antioxidants, anti-inflammatory and immunomodulatory properties has become highly relevant in biomedical research. In this sense, polyphenols extracted from the skin of green kiwi (Actinidia deliciosa) have shown beneficial effects in the regulation of the immune system. This review aims to describe how polyphenols extracted from the skin of green kiwi interact with key enzymes and proteins in the human body to reach their therapeutic target. In this sense, kiwi polyphenols can exert positive effects on autoimmune diseases due to their ability to modulate proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β). On the other hand, kiwi polyphenols can act as potent scavengers of reactive oxygen species (ROS), reducing oxidative damage at the cellular level and protecting DNA, lipids and proteins. Finally, green kiwi polyphenols have the ability to modulate the adaptive immune response, influencing the differentiation and activation of T lymphocytes, decreasing the activation of Th1 and Th17 cells, which are involved in the chronic inflammation of various autoimmune diseases. Preclinical studies provide evidence on the beneficial effects of polyphenols extracted from kiwifruit peel in autoimmune diseases; however, clinical studies in humans are needed to determine their efficacy, safety and possible therapeutic applications. The findings of this review contribute to elucidate the biochemical interactions of polyphenols extracted from green kiwifruit in autoimmune pathologies, highlighting the opportunities and limitations of their use as a natural strategy for the treatment of autoimmune diseases.

Despite numerous studies investigating plaque psoriasis, there exists a paucity of literature regarding scientometric analysis. This document presents a scientific analysis and historical overview of plaque psoriasis research. This study employs the prior methodology to analyze plaque psoriasis research from 2000 to 2025. It identifies hotspots, patterns of plaque psoriasis, and keyword trends. A scholarometric analysis identified the primary research domains of plaque psoriasis: field distribution, knowledge structure, subject evolution, and topic emergence. The induction factor, comorbidity, etiology, therapy, and animal models illustrate the incidence, progression, and treatment of depression. A scientometric analysis identified 13,646 documents on plaque psoriasis over a span of 25 years. These results establish a robust basis for subsequent research. We identified 13,646 articles on plaque psoriasis. Multiple journals addressed plaque psoriasis, including the British Journal of Dermatology, the American Academy Journal, and the European Academy Journal. Manchester University was the most productive, with 399 publications. Research on psoriasis was most abundant in the United States, yielding 4,141 publications across dermatology, pharmacology, rheumatology, and health care. Comorbidities, interleukin-23, drug survival, nail and plaque psoriasis, myocardial infarction, weight loss, diabetes, obesity, metabolic syndrome, cyclosporine, depression, IL-17, IL-23, adherence, and arthritis seem to be interconnected.
The citation analysis delineated the foremost researchers, institutions, and publications in plaque psoriasis, offering a thorough overview. The increase in publications indicates that this topic has attracted academic interest. The results underscore the significance of collaboration, interdisciplinary approaches, and resource allocation in marginalized sectors for researchers, funding organizations, and governmental entities. This study advocates for the utilization of traditional Chinese medicine and herbal remedies in the treatment of plaque psoriasis, citing their reduced side effects.

Background-

Neurobrucellosis is a rare and potentially life-threatening complication of brucellosis, a zoonotic infection caused by Brucella species. It can present with a wide range of neurological symptoms, making diagnosis challenging.

Case Presentation-

We report a rare and challenging case of neurobrucellosis presenting as pyrexia of unknown origin (PUO) and meningoencephalitis in a 45-year-old male. The patient presented with a 2-month history of fever, headache, and confusion. Extensive investigations, including blood cultures, imaging studies, and serological tests, were inconclusive. Brucella serology was eventually performed, revealing high titers of anti-Brucella antibodies.

Diagnosis and Treatment-

The patient was diagnosed with neurobrucellosis and treated with a combination of antibiotics, including doxycycline, rifampicin, and streptomycin. He showed significant clinical improvement, with resolution of fever, headache, and confusion.

Discussion-

This case highlights the importance of considering neurobrucellosis in the differential diagnosis of PUO and meningoencephalitis, particularly in patients with a history of exposure to animals or consumption of unpasteurized dairy products. Early diagnosis and treatment are crucial to prevent long-term neurological sequelae and improve outcomes. A thorough medical history, physical examination, and diagnostic workup are essential for early detection and treatment of this potentially life-threatening condition.

Conclusion-

Neurobrucellosis is a rare and challenging diagnosis that requires a high index of suspicion. This case report emphasizes the importance of considering neurobrucellosis in the differential diagnosis of PUO and meningoencephalitis, and highlights the need for prompt treatment to improve outcomes. Clinicians should be aware of the clinical manifestations and diagnostic challenges of neurobrucellosis to ensure timely and effective management.

Neurodegenerative diseases, including Alzheimer’s, dementia, and Parkinson’s, pose significant global health challenges, leading to cognitive decline, motor impairment, and reduced quality of life. While conventional therapies can alleviate symptoms, they do not provide a cure. Therefore, there remains a need for more effective treatment strategies that can enhance drug bioavailability and therapeutic outcomes. A major challenge in treating these diseases is the blood–brain–barrier (BBB), which restricts the passage of many central nervous system (CNS) active drugs, limiting their effectiveness. Intranasal drug delivery has emerged as a promising alternative, allowing drugs to bypass the BBB efficiently, ensuring rapid absorption while minimizing systemic side effects. Many CNS drugs suffer from poor solubility, stability, and permeability, reducing their therapeutic impact. Nanocarriers, specifically liposomes—nanoscale, lipid-based vesicles—offer a solution by protecting drugs from enzymatic degradation, enhancing absorption, and facilitating transport across the BBB. Liposomes provide advantages such as targeted drug delivery, controlled release, and improved bioavailability, making them ideal for CNS drug delivery via the nasal route. Our research focuses on developing and characterizing liposomal formulations for three CNS drugs, i.e., dopamine, vinpocetine, and donepezil, which suffer from low stability or bioavailability. By encapsulating these drugs in liposomes, we aim to enhance their solubility, stability, and BBB permeability, thereby improving therapeutic potential. We focus on the impact of liposome surface charge on critical factors such as mucoadhesion, drug release, and permeability, optimizing nasal applicability. We also evaluated the chemical and physical stability for long-term storage and clinical use. The results showed that we succeeded in developing robust, stable, and effective nasal liposomal drug delivery systems to improve treatment outcomes for neurodegenerative diseases. This research could lead to more efficient, non-invasive treatments, offering hope to millions worldwide.
Acknowledgement: Project No. TKP2021-EGA-32 was implemented with the support provided by the Ministry of Innovation and Technology of Hungary, financed under the TKP2021-EGA funding scheme.

Introduction: Melanostatin is a short neuropeptide with the amino acid sequence Pro-Leu-Gly-NH₂ that acts as a positive allosteric modulator (PAM) of the dopamine D₂ receptors (D₂R) in the central nervous system (CNS). Its therapeutic potential for dopamine-related disorders, such as Parkinson's disease, is hampered by its poor gastrointestinal absorption and susceptibility to CNS proteases due to its intrinsic peptide nature. This project aims to overcome these limitations by developing novel melanostatin-based derivatives using a "lipophilic bullet" approach to enhance lipophilicity and PAM potency.

Methodology: Adamantane-1-amine (Am) was selected for conjugation via an amide bond at the C-terminal of melanostatin. The conjugates were synthesised in solution-phase, starting with the coupling between Am and Boc-Gly-OSu, followed by linear C-to-N synthesis using classical reactions in peptide chemistry. Functional assays were conducted in Chinese hamster ovary cells expressing human D₂R. The PAM activity of the conjugates was evaluated in terms of potency (EC₅₀) and efficacy (E_max) by measuring cAMP mobilization in response to D₂R dopamine-mediated activation using quantification by homogeneous time-resolved fluorescence.

Results: Conjugates 1 and 2 exhibited a statistically significant increase in dopamine potency (EC₅₀ = 87.08 ± 24.87 nM), with EC₅₀ values of 26.39 ± 3.37 and 17.82 ± 4.24 nM, respectively, at 0.01 nM, comparing favorably to the parent neuropeptide. Both conjugates showed no agonistic effect in the absence of dopamine, confirming their PAM mechanism. Using the shake-flask method, conjugates also showed and increased log P_o/w when compared to melanostatin.

Conclusions: These findings suggest that conjugation with adamantane-1-amine effectively enhances the therapeutic potential of melanostatin, offering a promising strategy for treating dopamine-related disorders.