Pathological Aspects Research Articles

Characterizing Oxidative Stress induced by Aβ Oligomers and the Protective Role of Carnosine in Primary Mixed Glia Cultures.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory loss. A critical aspect of AD pathology is represented by oxidative stress, which significantly contributes to neuronal damage and death. Microglia and astrocytes, the primary glial cells in the brain, are crucial for managing oxidative stress and supporting neuronal function. Carnosine is an endogenous dipeptide possessing a multimodal mechanism of action that includes antioxidant, anti-inflammatory, and anti-aggregant activities. The present study investigated the effects of Aβ1-42 oligomers (oAβ), small aggregates associated with the neurodegeneration observed in AD, on primary rat mixed glia cultures composed of both microglia and astrocytes, focusing on the ability of these detrimental species to induce oxidative stress. We assessed intracellular reactive oxygen species (ROS) and nitric oxide (NO) levels as markers of oxidative stress. Exposure to oAβ significantly elevated both ROS and NO intracellular levels compared to control cells. However, this effect was completely inhibited by the pre-treatment of mixed cultures with carnosine, resulting in ROS and NO levels similar to those observed in untreated (control) cells. Single-cell analysis of cellular responses to oAβ revealed heterogeneous ROS production, resulting in two distinct clusters of cells, one of which was very responsive to the treatment. The presence of carnosine counteracted the overproduction of ROS, also leading to a single, homogeneous cluster, similar to that observed in the case of control cells. Interestingly, unlike ROS response, single-cell analysis of NO production did not show any distinct clusters. Overall, our findings demonstrated the ability of carnosine to mitigate Aβ-induced oxidative stress in mixed glia cells, by rescuing ROS and NO intracellular levels, as well as to normalize the heterogeneous response to the treatment measured in terms of clusters' formation. The present study suggests a therapeutic potential of carnosine in pathologies characterized by oxidative stress including AD.

ALZHEIMER'S DISEASE: COMPREHENSIVE INSIGHTS INTO RISK FACTORS, BIOMARKERS, AND ADVANCED TREATMENT APPROACHES

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder primarily affecting individuals over 60. It is a multifactorial disease driven by both modifiable factors, such as lifestyle, diet, and prior health conditions, as well as non-modifiable factors, like age, genetics, and family history. The key pathological features of AD include the buildup of amyloid β plaques and neurofibrillary tangles resulting from hyperphosphorylated tau proteins in the brain. Biomarkers like amyloid β and tau protein levels in cerebrospinal fluid (CSF) and blood are essential for diagnosing and tracking AD progression. Current research focuses on developing drugs targeting multiple aspects of AD pathology, including inflammation, oxidative stress, synaptic dysfunction, and protein accumulation. These treatments aim to slow cognitive decline and neuronal damage. Given the complexity of AD, multi-targeted therapeutic approaches are being explored to enhance treatment efficacy. This review provides an overview of AD risk factors, key biomarkers used for diagnosis, and the latest advances in clinical drug development.

Prevalence and etiopathology of aspergillosis in broiler chickens: Analysis of risk factors in coastal Bangladesh

Background/Aim: Aspergillus fumigatus is a respiratory pathogen that causes brooder pneumonia in broilers. This study addresses the lack of comprehensive data on the frequency, risk factors, cultural, and pathological aspects of aspergillosis in the coastal region of Bangladesh. Methods: The study was conducted from July 2022 to June 2023, during which 37,230 broiler birds were examined. A total of 1956 birds (1,806 sick and 150 dead) from 35 broiler farms of Barishal district of coastal Bangladesh were evaluated. The clinical manifestations of this condition included gasping, tachypnea, dyspnea, and lethargy. Postmortem examination revealed firm nodular lesions in vthelungs, air sacs, kidney, intestine, and liver. Histopathology revealed granulomatous lesions and hyphae in the necrotic areas. Results: A. fumigatus colonies developed rapidly on Sabouraud Dextrose Agar (SDA), presenting a range of colors (white, yellow, brown to black, green). A. fumigatus displayed dichotomous branching-type hyphae that were stainable with lactophenol blue. The total prevalence was 5.25%, with greater vulnerability observed in birds between the ages of 6 and 10 days during the summer season and in integrated farming systems. Conclusion: The findings highlight the significance of Aspergillus fumigatus as a causative agent of brooder pneumonia in broilers in the coastal region of Bangladesh. The study underscores the importance of addressing identified risk factors such as age, seasonality, and farming practices to reduce the incidence of the disease and improve broiler health and productivity.

Outbreak of ruminal acidosis in cattle caused by the ingestion of hedge lucerne (Desmanthus virgatus L. Willd.) in Northeastern Brazil

This study describes the epidemiological, clinical, and pathological aspects of an outbreak of ruminal acidosis and ruminitis caused by the ingestion of hedge lucerne (Desmanthus virgatus L.) in 70 cattle in the state of Paraiba, Northeastern Brazil. The herd had been transported from the state of Piauí to Paraiba. The deaths of the cattle occurred 15 days after the animals were introduced to a native pasture containing D. virgatus. All animals exhibited ruminal atony, which ranged from mild to severe. A total of 35 cattle died, with five undergoing necropsy. Initial clinical signs included apathy, followed by a marked increase in left abdominal volume, consistent with ruminal distension, absence of rumination (ruminal atony), lateral recumbency, and ultimately death. All affected animals were treated with oral administration of rumen fluid, enteral fluid therapy, and oral antacids. During this period, twenty animals succumbed to the condition, and an additional 15 died after being relocated, resulting in a 50% fatality rate. Significant gross pathological findings were observed primarily in the digestive system. The forestomachs were markedly distended, containing large amounts of reddish, pasty, and serous ingesta. A demarcation line was evident in the esophagus, separating the pale and bloodless distal esophagus from the congested proximal esophagus at the thoracic inlet, corresponding to the "bloat line." Frothy material was present in the tracheal lumen, indicating pulmonary edema. Additionally, rectal prolapse was noted. Histopathological examination revealed marked edema and severe hydropic (ballooning) degeneration of the basal layer in the forestomachs, along with intercellular edema. Separation of the epithelium from the lamina propria, forming multiple clefts, was observed, accompanied by areas of lymphoplasmacytic inflammatory infiltrate in the submucosa. This study demonstrates that this plant can cause severe gastrointestinal disturbances in cattle unaccustomed to its consumption and ingesting large quantities of the plant's shoots.

Variabilities in Retinal Hemodynamics Across the Menstrual Cycle in Healthy Women Identified Using Optical Coherence Tomography Angiography

Background: Numerous conditions, both physiological and pathological, can influence changes in the retinal vascular architecture. In order to be able to highlight pathological aspects of systemic diseases with ocular activity, it is necessary to understand how physiological fluctuations can influence circulation at the retinal level. The present study attempts to evaluate retinal and choroidal vascular and structural changes in healthy female subjects over the course of a menstrual cycle using OCT-A. Methods: We analyzed 22 eyes from healthy reproductive women with a regular menstrual cycle. We performed five OCT-A scans of the subjects every 7–8 days over the course of a month starting from the first day of the menstrual cycle and ending with the first day of the next cycle, measuring perfusion density in the superficial and deep vascular plexuses, choroidal thickness, and FAZ perimeter. Results: There are physiological variations in retinal hemodynamics that can be identified using OCT-A, choroidal thickness having statistically significant increased values in the parafoveal nasal sector during the ovulatory phase (289.18 µm) compared to the early follicular phase (281.9 µm), and the subfoveal sector during the ovulatory phase (319.04 µm) compared to the early follicular phase (308.27 µm). Conclusions: These findings along with abnormally small FAZ perimeters indicate that the menstrual cycle phase should be considered whenever interpreting OCT-A results. Further studies that include larger cohorts, control groups, and hormone serum levels are necessary to confirm and correlate retinal vascular alterations and the phase of the menstrual cycle using OCT-A.

Personalidad y usos de internet: Rasgos Normales vs. Continuos de la Personalidad

The aim of this research was to study the relation between Dual Personality Model’s trait continuums (combinations of pathological and positive traits; de la Iglesia & Castro Solano, 2021) and internet use, and to compare them with Five Factor Model traits (FFM; Costa & McCrae, 1984). Sample was composed by 745 internet users with an average age of 38.7 years old (SD = 14.4; 57% female). Internet use with leisure motive was higher in those with less emotional management (EMI) and those with lack of interest in others (IOI), and it was lower in those with high adherence to rules (ARI), impulse control (ICI) and greater environmental control (ECI). Additionally, utilitarian and work use was higher in those with higher IOI and ECI. Regarding personality adjustment (PAI) in a global assessment, healthy personality profiles are characterized by a utilitarian and work use, and those with pathological personality profiles use internet with recreational or social motives. Trait continuums significantly increased the explained variance regarding the use of utilitarian platforms and all kinds of internet use, when compared to FFM traits. Findings give further evidence of the utility of incorporating continuums traits assessment when studying personality, given that the conjointly association of pathological and positive aspects increases the explanation of the phenomenon in a significant manner.

Inhibition of Aβ Aggregation by Cholesterol-End-Modified PEG Vesicles and Micelles

Background/Objectives: This study aimed to design and evaluate Chol-PEG2000 micelles and Chol-PEG500 vesicles as drug delivery system (DDS) carriers and inhibitors of amyloid-β (Aβ) aggregation, a key factor in Alzheimer’s disease (AD). Methods: The physical properties of Chol-PEG assemblies were characterized using dynamic light scattering (DLS), electrophoretic light scattering (ELS), and transmission electron microscopy (TEM). Inhibitory effects on Aβ aggregation were assessed via thioflavin T (ThT) assay, circular dichroism (CD) spectroscopy, and native polyacrylamide gel electrophoresis (native-PAGE). Results: Chol-PEG2000 micelles and Chol-PEG500 vesicles were found to exhibit diameters of 20–30 nm and 70–80 nm, respectively, with neutral surface charges and those physical properties indicated the high affinity for Aβ. At a 10-fold molar ratio, thioflavin T (ThT) assay revealed that Chol-PEG2000 delayed Aβ fibril elongation by 20 hours, while Chol-PEG500 delayed it by 40 hours against Aβ peptide. At a 50-fold molar ratio, both Chol-PEG2000 and Chol-PEG500 significantly inhibited Aβ aggregation, as indicated by minimal fluorescence intensity increases over 48 hours. CD spectroscopy indicated that Aβ maintained its random coil structure in the presence of Chol-PEG assemblies at a 50-fold molar ratio. Native-PAGE analysis demonstrated a retardation in Aβ migration immediately after mixing with Chol-PEG assemblies, suggesting complex formation. However, this retardation disappeared within 5 min, implying rapid dissociation of the complexes. Conclusions: This study demonstrated that Chol-PEG500 vesicles more effectively inhibit Aβ aggregation than Chol-PEG2000 micelles. Chol-PEG assemblies perform as DDS carriers to be capable of inhibiting Aβ aggregation. Chol-PEG assemblies can deliver additional therapeutics targeting other aspects of AD pathology. This dual-function platform shows promise as both a DDS carrier and a therapeutic agent, potentially contributing to a fundamental cure for AD.

Exploring the Therapeutic Potential of 8-Prenyldaidzein: A Comprehensive Study of its Multi-Target Efficacy in Alzheimer's Disease

Background: Alzheimer's disease (AD) is marked by cognitive decline, amyloid plaques, neurofibrillary tangles, and cholinergic loss. Due to the limited success of amyloid-targeted therapies, attention has shifted to new non-amyloid targets like phosphodiesterases (PDE). This study investigates the potential of Flemingia vestita (FV) phytomolecules and derivatives, particularly 8-Prenyldaidzein, in AD treatment. Materials and Methods: Phytocompounds and derivatives were screened for drug-likeness, toxicity, BBB permeability, and ADME profiles. Molecular docking was conducted with PDE5A, BACE-1, and AChE, followed by molecular dynamics (MD) simulations on the best binding complexes. Results: 8-Prenyldaidzein, a derivative of daidzein, demonstrated favorable drug-likeness and ADME properties. It exhibited strong binding to PDE5A, BACE-1, and AChE, with MD simulations confirming stable protein-ligand interactions. Discussion: The multi-target potential of 8-Prenyldaidzein, particularly through non-amyloid pathways, offers a promising approach to AD therapy. Its inhibition of PDE5A, BACE-1, and AChE could address multiple aspects of AD pathology. Conclusion: 8-Prenyldaidzein shows strong potential as a multi-target inhibitor for AD treatment. While in-silico findings are promising, further experimental validation is needed to confirm its clinical applicability. conclusion: The in-silico results suggest that 8-Prenyldaidzein has potential as an anti-Alzheimer's drug, and further experimental validation is necessary to confirm its efficacy.

Breast organoid suspension cultures maintain long-term estrogen receptor expression and responsiveness

Organoid cultures offer a powerful technology to investigate many different aspects of development, physiology, and pathology of diverse tissues. Unlike standard tissue culture of primary breast epithelial cells, breast organoids preserve the epithelial lineages and architecture of the normal tissue. However, existing organoid culture methods are tedious, difficult to scale, and do not robustly retain estrogen receptor (ER) expression and responsiveness in long-term culture. Here, we describe a modified culture method to generate and maintain organoids as suspension cultures in reconstituted basement membrane (™Matrigel). This method improves organoid growth and uniformity compared to the conventional Matrigel dome embedding method, while maintaining the fidelity of the three major epithelial lineages. Using this adopted method, we are able to culture and passage purified hormone sensing (HS) cells that retain ER responsiveness upon estrogen stimulation in long-term culture. This culture system presents a valuable platform to study the events involved in initiation and evolution of ER-positive breast cancer.

Breast-Related Herniation: A Call for Multidisciplinary Awareness and a Proposal for a Classification.

Breast-related herniation (BRH) is a vague term for many clinicians. The absence of a universal nomenclature and the different nature of the herniation process involved, being true or false, contribute to this vagueness. BRH includes a spectrum of disorders ranging from a few congenital breast disorders to commoner herniation processes related to acquired breast diseases. We aim to raise multidisciplinary awareness about BRH by reviewing the related literature and reviewing our experience with BRH. We will also propose a classification for BRH. PubMed and Scopus databases were searched for any herniation disorders that are related to the breast in any clinical or pathological aspect. The literature review revealed 12 various groups of BRHs that we could classify into two anatomical categories: pectoral (mammary) BRH, in which the herniations occur at the pectoral site of the chest wall, and extra-pectoral BRH, in which the herniations occur at an extra mammary site but are related to breast pathologies. Pectoral BRH was further divided into clinicopathological subcategories, including congenital BRH, pulmonary BRH complicating breast cancer and breast infections, factitious BRH, and iatrogenic BRH. Extra-pectoral BRH was further divided into clinicopathological subcategories, including abdominal wall hernias following autologous breast reconstruction (ABR) and herniated siliconomas. Our study group included 19 patients with BRHs, among which congenital BRHs and pulmonary BRHs were the most common. Congenital BRHs are rare and are of main interest to plastic surgeons. However, abdominal wall hernias following ABR, pulmonary BRH, and factitious BRHs are relatively common complications of breast cancer treatment. This calls for a multidisciplinary approach to ameliorate the morbidity of BRHs. Further studies are needed to refine our proposed classification.

Case Report: Anencephaly in an Unidentified Baby

Anencephaly is a congenital disorder affecting the central nervous system, characterized by the absence of a major portion of the brain, skull, and scalp, with an estimated prevalence of 0.5–2 per 1,000 births globally. This condition is a subset of Neural Tube Defects (NTDs), which affect approximately 300,000 newborns annually. This study aims to investigate the pathological and forensic aspects of a case of anencephaly in a female infant found deceased in Lingsar, West Lombok, on June 23, 2023. The methods employed case study included external and internal examinations to identify the structural abnormalities and potential cause of death. The external examination revealed open wounds on several parts of the body, and discoloration of the chest and abdominal cavities. Internal examination confirmed the absence of brain tissue, consistent with anencephaly. The findings indicate that the cause of death was directly attributed to the severe congenital anomaly, with no evidence of external factors contributing to mortality. The study concludes that anencephaly, while rare, remains a significant congenital disorder with profound implications for prenatal care and early detection. This case emphasizes the necessity of improving maternal nutrition, particularly folic acid supplementation, as a preventive strategy to reduce the incidence of NTDs. The findings also underscore the importance of interdisciplinary collaboration in handling forensic and medical investigations of congenital disorders, aiding in better understanding and management of similar cases in the future.

Integrated Data Mining and Animal Experiments to Investigate the Efficacy and Potential Pharmacological Mechanism of a Traditional Tibetan Functional Food Terminalia chebula Retz. in Hyperuricemia.

Hyperuricemia (HUA), a common metabolic disorder associated with gout, renal dysfunction, and systemic inflammation, necessitates safer and more comprehensive therapeutic approaches. Traditional Tibetan medicine has a rich history of treating HUA. This study aimed to identify novel anti-hyperuricemic herb derived from traditional Tibetan medicine. Traditional Tibetan medicine prescriptions for HUA were analyzed using data mining techniques, identifying T. chebula as a high-frequency herb. Its phytochemical composition was characterized by UPLC-QE-Orbitrap-MS. Hyperuricemic rat models were treated with T. chebula to assess its effects on serum uric acid (UA) levels, renal inflammation, intestinal barrier integrity, and gut microbiota composition. Molecular and histological analyses evaluated its impact on key biomarkers. Through data mining, we identified T. chebula as a promising candidate for HUA treatment. T. chebula demonstrated dose-dependent inhibition of xanthine oxidase (XOD) in vitro and significantly reduced serum UA levels and XOD activity in vivo. It restored gut barrier function by upregulating tight junction proteins (ZO-1, Occludin, Claudin-1) and reduced pro-inflammatory cytokines (IL-6, TNF-α). T. chebula improved renal function, reducing serum creatinine (Cre) and blood urea nitrogen (BUN) levels. Gut microbiota analysis revealed a favorable shift in microbial composition, with reductions in harmful bacteria (eg, Clostridium spp.) and increases in beneficial bacteria (eg, Roseburia). These effects aligned with the modulation of the gut-kidney axis. This study highlights the multi-target therapeutic potential of T. chebula in HUA management. By regulating the gut-kidney axis, T. chebula alleviates systemic inflammation, enhances intestinal and renal health, and addresses critical aspects of HUA pathology. These findings underscore the value of integrating traditional medicine with modern scientific methodologies to develop innovative treatments.

Effects of menopause in a mouse model of Alzheimer’s disease and comorbid metabolic disease

AbstractBackgroundAbout two‐thirds of those with Alzheimer’s disease (AD) are women, most of whom are post‐menopausal. Menopause accelerates the risk for dementia by increasing the risk for metabolic, cardiovascular, and cerebrovascular diseases. Mid‐life metabolic disease (e.g. obesity, diabetes, or prediabetes) is a well‐known risk factor for dementia. A high fat diet can lead to poor metabolic health in both humans and rodents. The goal of this study was to determine the effects of menopause and high fat diet on metabolic, cognitive, and pathological outcomes in the AppNL‐F knock‐in mouse model of Alzheimer’s disease.MethodTo model menopause, we used an accelerated ovarian failure model (4‐vinylcyclohexene diepoxide, VCD). This ovary‐intact model is more clinically relevant than an ovariectomy model, as mice go through a perimenopausal period. At 3 months of age, AppNL‐F mice were administered VCD or vehicle (oil) and then placed on either a control diet (10% fat) or a high fat diet (HF; 60% fat) and maintained on the diets until 10 months of age.ResultMenopause led to metabolic impairment (weight gain and glucose intolerance) and further exacerbated obesity in response to a high fat diet. Menopause had independent effects on some serum metabolic health biomarkers (insulin) and synergic effects with HF diet on other markers (glucagon). An interaction between HF diet and menopause led to an impaired episodic‐like memory. When examining the underlying pathology, we did not detect any changes in amyloid levels, however, we observe changes in neurogenesis and microglia response.ConclusionMenopause and HF diet have independent and synergistic effects on metabolic, cognitive and pathological aspects of AD. This work highlights the need to model endocrine aging in animal models of dementia and will contribute to further understanding the interaction between menopause and metabolic health in the context of AD.

Shedding light on microglial dysregulation in Alzheimer's disease: exploring molecular mechanisms and therapeutic avenues.

Alzheimer's disease (AD) stands out as the foremost prevalent neurodegenerative disorder, characterized by a complex etiology. Various mechanisms have been proposed to elucidate its onset, encompassing amyloid-beta (Aβ) toxicity, tau hyperphosphorylation, oxidative stress and reactive gliosis. The hallmark of AD comprises Aβ and tau aggregation. These misfolded protein aggregates trigger the activation of glial cells, primarily microglia. Microglial cells serve as a major source of inflammatory mediators and their cytotoxic activation has been implicated in various aspects of AD pathology. Activated microglia can adopt M1 or M2 phenotypes, where M1 promotes inflammation by increasing pro-inflammatory cytokines and M2 suppresses inflammation by boosting anti-inflammatory factors. Overexpressed pro-inflammatory cytokines include interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in adjacent brain regions.Furthermore, microglial signaling pathways dysregulated in AD are myeloid differentiation primary-response protein 88 (Myd 88),colony-stimulating factor-1receptor (CSF1R) anddedicator of cytokinesis 2 (DOCK2), which alter the physiology. Despite numerous findings, the causative role of microglia-mediated neuroinflammation in AD remains elusive. This review concisely explores cellular and molecular mechanisms of activated microglia and their correlation with AD pathogenesis. Additionally, it highlights promising therapeutics targeting microglia modulation, currently undergoing preclinical and clinical studies, for developing effective treatment for AD.

Immune system regulation of physiological and pathological aspects of the ovarian follicle pool throughout the female reproductive lifespan.

The immune system plays a major role in ovarian physiology by regulating the ovarian follicle pool through complex signaling of different growth factors, cytokines, and chemokines. These may promote follicle activation and further growth but could also trigger follicle atresia and clearance of aging or damaged cells within the ovarian cortex. Moreover, extraglandular steroidogenesis potentially occurring in different immune cells like macrophages and natural killer cells might be another way of modulating follicle growth. Ovarian macrophages have recently been found to contain two different populations, namely resident macrophages and monocyte-derived cells, with potentially different roles. The immune system also plays a role in the development of pathological conditions, including premature ovarian insufficiency (POI). Indeed, autoimmune activation against various ovarian antigen targets results in lymphocytic oophoritis mainly targeting early growing follicles, but later leading to complete follicle pool depletion. Immune-mediated ovarian damage may also be caused by viral infection or be the consequence of iatrogenic damage. Certain novel cancer immunotherapies like checkpoint inhibitors have recently been shown to induce ovarian reserve damage in a murine model. Studies are needed to corroborate these findings and further investigate the potential of newly developed immunotherapies to treat POI. Technological advances such as single-cell analyses of less represented cell populations like immune cells inside the ovary are now contributing to valuable new information, which will hopefully lead to the development of new therapeutic strategies for women with fertility issues.

New rabbit model for benign biliary stricture formation with repeatable administration

BACKGROUND The treatment of benign biliary strictures (BBS) is a challenging clinical problem. At present, there is a lack of ideal models for the study of BBS treatment. AIM To develop a novel animal model of BBS to simulate studies on the processes and mechanisms in the human condition. METHODS A rabbit model of benign bile duct stricture was established by surgical injury of the bile duct. After removal of the gallbladder, a drainage tube was placed through the cystic duct at the stump, and a BBS model was induced by surgical injury at the lower end of the common bile duct. RESULTS Compared with the control group, the model rabbits showed gross jaundice, increased serum bilirubin, and decreased liver function. Cholangiography showed segmental bile duct stenosis in the model rabbits. Pathological staining showed inflammatory cell infiltration and fibrosis in the biliary tract of rabbits in the model group. This was consistent with the clinical manifestations of BBS. This model provided serology, imaging, pathology, and other aspects of BBS. CONCLUSION We have successfully established an animal model of benign stricture of the lower bile duct with repeatable administration, which is consistent with the clinical manifestations of BBS.

Anaesthetic management of an infant with MEGD(H)EL syndrome undergoing cochlear implant

BackgroundThe syndrome has these features: 3-methylglutaconic aciduria (MEG), deafness(D), encephalopathy (E), Leigh-like syndrome (L). This disorder is caused by biallelic mutations in serine active site-containing protein 1 (SERAC1) gene. When these patients experience hepatopathy (H) in addition to the above manifestations, the syndrome is referred to as MEGD(H)EL. The pathology of this syndrome shares features with diverse types of inborn errors of metabolism.Case presentationWe discussed the anaesthetic management of an infant 2-year-old suffering from MEGD(H)EL syndrome undergoing cochlear implant. We discuss the pathology, genetics and significant aspects of this sporadic disease which is important for anaesthesiologist.ConclusionsThe usage of dexmedetomidine as the main anaesthetic drug might have the benefit of a non-triggering anaesthetic agent in patients with a mitochondrial disease. Mixture of dexmedetomidine and ketamine provide an effective combination for procedural sedation, predominantly in select populations who are at a high risk of perioperative complications due to underlying co-morbid conditions.

PHYSIOLOGICAL AND PATHOLOGICAL CONSIDERATIONS ON THE GALL BLADDER

This paper examines the physiological and pathological aspects of the gallbladder, with a particular focus on original research concerning the pathology of gallstones. A comprehensive understanding of the mechanisms underlying gallbladder disease requires an in-depth analysis of its anatomical structure and physiological functions. Furthermore, the study addresses predisposing factors, genetic determinants, and lifestyle influences, which are integral to the pathogenesis of gallbladder disorders and provide a basis for their prevention and management. The research also evaluates various surgical interventions for the treatment of prevalent gallbladder pathologies, comparing their efficacy in a specific patient cohort. Emphasis is placed on the gallbladder's critical role in the digestive process, as it contributes to the integrated functioning of the body's organs.

Neuromuscular Organoids to Study Spinal Cord Development and Disease.

Many aspects of neurodegenerative disease pathology remain unresolved. Why do certain neuronal subpopulations acquire vulnerability to stress or mutations in ubiquitously expressed genes, while others remain resilient? Do these neurons harbor intrinsic marks that make them prone to degeneration? Do these diseases have a neurodevelopmental component? Lacking this fundamental knowledge hampers the discovery of efficacious treatments. While it is well established that human organoids enable the modeling of brain-related diseases, we still lack an organoid model that recapitulates the regionalization complexity and physiology of the spinal cord. Here, we describe an advanced experimental protocol to generate neuromuscular organoids composed of a wide rostro-caudal (RC) diversity of spinal motor neurons (spMNs) and mesodermal progenitor-derived muscle cells. This model therefore allows for the robust and reproducible study of neuromuscular unit development and disease.

Mutations Matter: Unravelling the Genetic Blueprint of Invasive Lobular Carcinoma for Progression Insights and Treatment Strategies.

Invasive Lobular Carcinoma (ILC) presents a distinct subtype of breast cancer, representing 10-15% of cases, with unique clinical and molecular features. Characterized by a non-cohesive, single-file invasion pattern, ILC is typically estrogen receptor (ER)- and progesterone receptor (PR)-positive but human epidermal growth factor receptor 2 (HER2)-negative. Despite favorable prognostic features, its highly metastatic nature and predilection for atypical sites contribute to lower long-term survival compared to invasive breast carcinoma of no special type (NST). ILC's genetic landscape includes mutations in various genes (CDH1, BRCA2, ATM, etc.) and signaling pathways that impact treatment responses, especially in endocrine treatment. Furthermore, the diverse ILC subtypes complicate its management. Current challenges in chemotherapy, along with the targeted therapies, are also discussed. The present article aims to comprehensively review the recent literature, focusing on the pathological and molecular aspects of ILC, including associated genetic mutations influencing disease progression and drug resistance.