Manifestations Of Disease Research Articles

The Recommendation of the Mediterranean-styled Japanese Diet for Healthy Longevity.

The Mediterranean diet, listed as the intangible cultural heritage of humanity by UNESCO, is known as healthy and consumed worldwide. The Japanese diet is also listed and considered healthy. This narrative review compares the Mediterranean diet with its Japanese counterpart. Research has reported that people in Mediterranean regions, such as Italy and Greece, have one-third of the mortality ratio from cardiovascular diseases compared to people in the United States and Northern Europe because of the difference in eating habits. Therefore, Mediterranean diets are considered as healthy. A typical Western diet containing high amounts of fat, sugar, and calories is responsible for several diseases like metabolic syndrome and obesity, which are induced by chronic inflammation. In contrast, Mediterranean and Japanese diets contain them only less. The similarity between Mediterranean and Japanese diets is the substantial intake of vegetables, beans, and fish. On the other hand, the Mediterranean diet consumes large amounts of olive oil, especially polyphenol-rich extra virgin olive oil and dairy products, but meat consumption is relatively small. In contrast, the Japanese diet does not use oil and fat, contains abundant fermented foods, and consumes seaweed. Japan is known for its longevity, and people think that a well-balanced diet daily is good for preventing and curing illness. In this regard, finding non-disease conditions, so-called "ME-BYO," and curing them before the manifestation of diseases is becoming more common. In this review, we discuss the healthy eating habit, "The Mediterranean-styled Japanese diet," which prevents ME-BYO condition and reduces the risk of various diseases. The Mediterranean-styled Japanese diet, a hybrid of Mediterranean and Japanese diets, reduces the risk of various diseases by suppressing chronic inflammation. This nutritional intervention prevents ME-BYO and is beneficial for healthy longevity. Hence, a Mediterranean-styled Japanese diet might be helpful for healthy longevity in Japan and around the world.

Harnessing adapted capsule networks for accurate lumpy skin disease diagnosis in cattle

Lumpy skin disease (LSD) poses a substantial risk to livestock, emphasizing the critical need for reliable diagnostic tools to ensure timely intervention. The considerable economic impact of LSD further accentuates the imperative for efficient diagnosis. In this context, artificial intelligence (AI) emerges as a transformative solution, playing a pivotal role in providing swift detection capabilities. Rapid identification of LSD not only alleviates economic burdens but also impedes the disease’s propagation with in herds. A ground breaking in iterative involves the implementation of an adapted capsule network (CapsNet) expressly designed for diagnosing LSD. This innovative strategy is finely tuned to discern intricate patterns in disease manifestation, achieving an impressive accuracy rateof 97.6%. The model’s effectiveness is evident in it is capacity to differentiate between infected and healthy cases, with precision, recall, and F1 score metrics registering at 9.65%, 97.1%, and 96.3%, respectively. This high level of precision underscores the model’s proficiency in minimizing errors, solidifying its role as a dependable tool for precise LSD diagnosis and intervention, contributing significantly to the overall health and economic well-being of livestock populations.

Mycoplasma pneumoniae incidence, phenotype, and severity in children and adolescents in Denmark before, during, and after the COVID-19 pandemic: a nationwide multicentre population-based cohort study

Mycoplasma pneumoniae infections resurged globally in 2023-2024 after a three-year decline during the COVID-19 pandemic. We explored the incidence and severity of M pneumoniae infections in children and adolescents before, during, and after the pandemic. This nationwide, population-based cohort study included all Danish children and adolescents aged 0-17 years with a positive M pneumoniae PCR test from May 1, 2016, to April 30, 2024. We obtained clinical details for patients hospitalised for 24h or more. Risk ratios for infections, hospitalisations, and disease manifestations in 2023-2024 versus pre-COVID-19 seasons were calculated using Fisher's exact and Pearson's χ2 tests. A season was defined from May 1 to April30. Among the Danish population of 1,152,000 children and adolescents, 14,241 with a positive PCR test for Mpneumoniae were included. In 2023-2024, children and adolescents with a positive PCR rose 2.9-fold (95% CI 2.8-3.1; p<0.0001) compared to the pre-COVID-19 seasons, and hospitalisations rose 2.6-fold (95% CI 2.0-3.3; p<0.0001). Mpneumoniae-induced rash and mucositis increased 5.3-fold (95% CI 1.8-15.3; p=0.0007). In 2023-2024 compared to the pre-COVID-19 seasons, there was no difference in the proportion of hospitalisation (360 [4%] of 8165 versus 230 [4%] of 6009; p=0.09), the median duration of hospital stay (3 days [IQR 2-5] versus 3 days [IQR2-5]; p=0.84), or paediatric intensive care unit admission (14 [4%] of 360 versus 9 [4%] of 230 p=1.00). In Denmark, M pneumoniae infections and hospitalisations increased three-fold in 2023-2024 compared with the pre-COVID-19 seasons, indicating an immunity debt caused by the decline in M pneumoniae during the COVID-19 pandemic. While the severity of M pneumoniae infections did not change in 2023-2024, the five-fold increase in M pneumoniae-induced rash and mucositis in children and adolescents highlights Mpneumoniae as an important pathogen causing mucocutaneous eruptions. Innovation Fund Denmark and Rigshospitalets Forskningsfond.

The Beneficial Effects of Curcumin on Lipids: Possible Effects on Dyslipidemia-induced Cardiovascular Complications.

Dyslipidemia and altered lipid metabolism are closely involved in the pathogenesis and clinical manifestation of many metabolic and non-metabolic diseases. Therefore, mitigation of pharmacological and nutritional factors together with lifestyle modifications is paramount. One potential nutraceutical exhibiting cell signaling and lipid-modulating properties implicated in dyslipidemias is curcumin. Specifically, recent evidence suggest that curcumin may improve lipid metabolism and prevent dyslipidemia-induced cardiovascular complications via several pathways. Although the exact molecular mechanisms involved are not well understood, the evidence presented in this review suggests that curcumin can provide significant lipid benefits via modulation of adipogenesis and lipolysis, and prevention or reduction of lipid peroxidation and lipotoxicity via different molecular pathways. Curcumin can also improve the lipid profile and reduce dyslipidemia- dependent cardiovascular problems by impacting important mechanisms of fatty acid oxidation, lipid absorption, and cholesterol metabolism. Although only limited direct supporting evidence is available, in this review we assess the available knowledge regarding the possible nutraceutical effects of curcumin on lipid homeostasis and its possible impacts on dyslipidemic cardiovascular events from a mechanistic viewpoint.

Normative Population-Derived Data for MRI Manifestations of Cerebral Small Vessel Disease.

Cerebral small vessel disease (SVD) is manifested on magnetic resonance imaging (MRI) by white matter hyperintensities, lacunes, microbleeds, and atrophy. While these manifestations can be part of normal aging, a high burden has been associated with cognitive impairment and vascular events. Distinguishing between normal versus abnormal SVD lesion burden in clinical practice remains complex. Our objective is to establish age- and sex-specific normative data for MRI manifestations of SVD, to support clinical assessment in individual patients. We used 11 465 MRI scans from 5402 participants of the Rotterdam Study, the Netherlands, an ongoing prospective population-based cohort since 1990, to develop percentile curves for white matter hyperintensities and brain parenchymal fraction and probability curves for the prevalence and count of lacunes and microbleeds, across ages 45 to 100 years, stratified by sex. Participants were primarily White (≈97%), with a mean age at first scan of 64.7 (range, 45.7-97.9) years, and 55.7% being female participants. For all SVD MRI manifestations, the curves demonstrated nonlinear trends, with accelerating burden with advancing age (eg, doubling of white matter hyperintensity fraction every 10 years). Regarding brain parenchymal fraction, a decline was seen earlier in male participants (≈45 years) than female participants (≈60 years) and was more pronounced in male participants over time. Female participants had slightly higher white matter hyperintensity fractions compared with male participants across all ages. Lacunes and microbleeds were more frequently found in male participants than in female participants, and microbleeds were more prevalent than lacunes. We provide comprehensive normative data for different MRI manifestations of SVD, presented as percentile and probability curves by age, stratified by sex. This can aid clinicians to actually quantify the SVD burden on an individual patient's MRI scans and detect patterns of abnormality.

An in-silico approach to target Breast cancer with novel phytochemicals

Aging leads to the manifestation of various diseases. Cancer being one of the major illness that is associated with the age. Breast cancer is still a relatively global health concern as the leading cancer cause of death among women. The current study also utilizes an in-silico approach to discover and characterize new phytochemicals as potential therapeutic agents to breast cancer. Here, we explore the molecular basis driving the makeup of breast cancer, with an emphasis on the PI3K/AKT/mTOR pathway, a well-known signaling cascade implicated in cell growth and therapy response. Two candidates (Thalidasine (-8.80 Kcal/mol) and 7-Epiclusianone (-8.62 Kcal/mol)) were found to be promising leads displaying high binding affinity and therapeutic potential through screening a diverse library of phytochemicals against key breast cancer target proteins. These phytochemicals exhibit diverse antineoplastic effects as cell proliferation, angiogenesis, and metastasis inhibitors, and/or as inducers of apoptosis. Besides, their ability to specifically target breast cancer stem cells and to increase sensitivity to traditional therapies make them an appealing option for breast cancer adjuvant therapy. Taken together our data suggest that these phytochemicals should be further studied alone and in novel nano formulations that enhance bioavailability and reduce toxicity. This study adds to the evidence for the potential role of natural products in breast cancer and the role of lifestyle in cancer prevention.

Visium spatial transcriptomics and proteomics identifies novel hepatic cell populations and transcriptomic signatures of alcohol-associated hepatitis.

Alcohol-associated hepatitis (AH) is the clinical manifestation of alcohol-associated liver disease (ALD). AH is a complex disease encompassing the dysregulation of many cells and cell subpopulations. This study used a hepatic spatial transcriptomic and proteomic approach (10X Genomics Visium) to identify hepatic cell populations and their associated transcriptomic and proteomic alterations in human AH. Formalin-fixed paraffin-embedded liver tissue from AH patients (n = 2) and non-ALD controls (donors) (n = 2) were used for Visium spatial transcriptomic and proteomic analysis. AH cell clusters and cell markers were drastically different in regard to tissue pattern and number of cell types compared to non-ALD controls. Cholangiocytes, endothelial cells, macrophages, and stellate cells were more profuse in AH relative to non-ALD controls. Transcriptionally, proliferating cell nuclear antigen-positive (PCNA+) hepatocytes in AH more closely resembled cholangiocytes suggesting they were non-functional hepatocytes derived from cholangiocytes. Furthermore, mitochondria protein-coding genes were reduced in AH versus non-ALD control hepatocytes, suggesting reduced functionality and loss of regenerative mechanisms. Macrophages in AH exhibited elevated gene expression involved in exosomes as compared to non-ALD controls. The most upregulated macrophage genes observed in AH were those involved in exosome trafficking. Gene and protein signatures of disease-associated hepatocytes (ANXA2+/CXCL1+/CEACAM8+) were elevated in AH and could visually identify a pre-malignant lesion. This study identified global cell type alterations in AH and distinct transcriptomic changes between AH and non-ALD controls. These findings characterize cellular plasticity and profuse transcriptomic and proteomic changes that are apparent in AH and contribute to the identification of novel therapeutics.

MiR-1, miR-133a, miR-29b and skeletal muscle fibrosis in chronic limb-threatening ischaemia.

Chronic limb-threatening ischaemia (CLTI), the most severe manifestation of peripheral arterial disease (PAD), is associated with a poor prognosis and high amputation rates. Despite novel therapeutic approaches being investigated, no significant clinical benefits have been observed yet. Understanding the molecular pathways of skeletal muscle dysfunction in CLTI is crucial for designing successful treatments. This study aimed to identify miRNAs dysregulated in muscle biopsies from PAD cohorts. Using MIcroRNA ENrichment TURned NETwork (MIENTURNET) on a publicly accessible RNA-sequencing dataset of PAD cohorts, we identified a list of miRNAs that were over-represented among the upregulated differentially expressed genes (DEGs) in CLTI. Next, we validated the altered expression of these miRNAs and their targets in mice with hindlimb ischaemia (HLI). Our results showed a significant downregulation of miR-1, miR-133a, and miR-29b levels in the ischaemic limbs versus the contralateral non-ischaemic limb. A miRNA target protein-protein interaction network identified extracellular matrix components, including collagen-1a1, -3a1, and -4a1, fibronectin-1, fibrin-1, matrix metalloproteinase-2 and -14, and Sparc, which were upregulated in the ischaemic muscle of mice. This is the first study to identify miR-1, miR-133a, and miR-29b as potential contributors to fibrosis and vascular pathology in CLTI muscle, which supports their potential as novel therapeutic agents for this condition.

Pulmonary involvement in systemic sclerosis: can sex play a role?

Systemic sclerosis (SSc) is a rare and complex autoimmune disease with significant complications. During the last few years, research interest focuses on the differences between female and male patients. However, there is a lack of data regarding the role of sex in the presence of small airway disease (SAD). Therefore, we aimed to investigate the impact of sex on pulmonary involvement in a cohort of SSc patients, focusing primarily on small airways. For this retrospective study, consecutive patients with a diagnosis of SSc, that visited our department until January 2024, were recruited. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared between the two groups. In total 393 patients (female-to-male ratio 6:1) were included. Median time to diagnosis after the onset of Raynaud's was significantly longer for female patients. Electrocardiogram abnormalities were more common in male patients, while telangiectasias, calcinosis and arthralgias were more common in female individuals. Moreover, male SSc patients exhibited a higher prevalence of ILD and shorter time until the diagnosis of ILD. However, female individuals demonstrated a lower maximal-mid expiratory flow rate (MMEF) and higher ratio of residual volume to total lung capacity. Interestingly, sex remained an independent predictor of MMEF, in the multivariate analysis. Our results showed that, although ILD is more common in male SSc patients, SAD was more prevalent among female individuals. Importantly, female sex remained an independent predictor of SAD. This study further supports the presence of sex-related differences in SSc, with important implications in disease course and management.

Diagnostic and prognostic values of HCG15 and morrbid in acute myocardial infarction

BackgroundAcute myocardial infarction (AMI) represents the gravest manifestation of ischemic heart disease, with the primary cause of mortality and morbidity worldwide. Although timely and accurate diagnosis of AMI is crucial in clinical practice, they are impeded by the limitation of current biomarkers. We aimed to explore the potential predictive value of two novel long non-coding RNA (lncRNA) HCG15 and Morrbid in AMI diagnosis and prognosis.MethodWe measured the lncRNA levels in the blood samples of 412 AMI patients and 111 healthy volunteers with the RT-PCR method. Receiver operating characteristic (ROC) curves were plotted to access the diagnostic value of selected lncRNAs. Restricted cubic splines (RCS) and the Kaplan-Meier method were utilized to examine the predictive value of the selected lncRNAs in AMI diagnosis.ResultROC curves identified an acceptable diagnostic value of HCG15 and Morrbid (AUC for HCG15: 0.937; AUC for Morrbid: 0.940). RCS and Kaplan-Meier analysis revealed the cut-off value of 3.6 for HCG15 and 4.0 for Morrbid have a good predictive value in MACCE within 12 months once AMI was diagnosed (p-value for HCG15: p = 0.025; p-value for Morrbid: p &amp;lt; 0.0001).ConclusionHCG15 and Morrbid were confirmed as promising lncRNA biomarkers for both diagnosis and prognosis of AMI in this study. Additionally, their importance of application in real-world clinical practice and underlying mechanisms in AMI diagnosis and prognosis remain to be explored.

Serum level of IFN-λ is elevated in idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune disorders with uncertain pathogenesis. Interferon (IFN)-λ has recently been described as an important mediator of immune responses. The main purpose of this study is to find out whether IFN-λ is involved in IIM. The published RNA-seq data of dermatomyositis (DM) muscle and IIM double negative (DN) B cells were analyzed. Serum IFN-λ1, IFN-λ2, and IFN-λ3 levels of 59 IIM patients and 29 healthy persons were determined by enzyme-linked immunosorbent assay (ELISA). The proportion of DN B cells and subsets as well as phosphorylated STAT1 (p-STAT1) levels in peripheral B cells was measured by flow cytometry. Ex vivo induction of double negative 2 (DN2) B cells were performed for validation. Type III IFN signaling pathway was enriched in muscle tissue from DM patients. Serum IFN-λ1, IFN-λ2, and IFN-λ3 levels were significantly higher in the IIM patients, especially patients with interstitial lung disease (ILD) and skin manifestations. Moreover, serum IFN-λ1 level was positively correlated with the disease activity. In addition, IIM patients with positive anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibodies exhibited higher serum IFN-λ1, IFN-λ2, and IFN-λ3 levels. The frequency of DN2 B cells were elevated in IIM patients' blood. Interestingly, the type III IFN signaling pathway was enriched in circulating DN2 B cells from IIM patients, which could induce T-bet+CD19hi DN2 B cell differentiation ex vivo. IFN-λ may participate in the pathogenesis of IIM by acting on DN2 B cells and serve as a disease biomarker for IIM patients. Key Points • Type III IFN signaling pathway is enriched in the involved muscles of DM patients. • Serum IFN-λ in IIM patients is correlated with disease activity and is higher in patients with ILD, skin lesions, and positive anti-MDA5 antibodies. • DN2 B cells with enriched type III IFN signaling pathway are accumulated in the peripheral blood of IIM patients.

Advances of IGF-1R inhibitors in Graves' ophthalmopathy.

Graves' ophthalmopathy is the most common extra-thyroidal organ manifestation of Graves' disease. The mainstay of clinical treatment is glucocorticoids; however, side effects and relapse are common problems, and current treatment options cannot alter the disease progression. IGF-1R is an important component of the signaling pathway in Graves' ophthalmopathy, and downstream signaling of IGF-1 and IGF-1R plays a role in many immune-related diseases, possibly leading to disease occurrence through changes in immune phenotype and protein synthesis. Teprotumumab is a human monoclonal antibody targeting the insulin-like growth factor-I receptor (IGF-1R). Clinical trials have shown that teprotumumab reduces proptosis better than placebo, and may be beneficial for patients with worsening disease after steroid cessation. In this review, we discuss the role and prospects of IGF-1R inhibitors in thyroid-associated ophthalmopathy.

HUVECs-derived exosomes increase neovascularization and decrease limb necrosis in hindlimb ischemia

Chronic limb-threatening ischemia (CLTI) is the most severe manifestation of peripheral arterial disease (PAD) and imposes a significantly high burden due to its high risk of mortality and amputation. Revascularization is the first-line treatment for CLTI; however, the amputation rate remains high, and approximately one-third of patients are not eligible for this treatment. Therefore, there is an urgent need for more effective therapeutic strategies. The aim of this study was to investigate the effects and mechanisms of human umbilical vein endothelial cells (HUVECs)-derived exosomes on neovascularization and the degree of necrosis in a hindlimb ischemia model and to study the biological processes underlying their mechanisms. This is an in vivo experimental study with a post-test-only control group design. Forty BALB/c mice were randomized to receive injections of exosomes, conditioned media, and phosphate-buffered saline (PBS) one day after unilateral double ligation. A sham-operated group was also included as a control. Capillary density, arteriole lumen diameter, and histopathological necrosis were measured after seven days, while clinical necrosis was observed daily. MicroRNA profiling, in silico analysis, and transcriptomic analysis of vascular endothelial growth factor (VEGF) mRNA expression were performed to determine the possible biological processes. No amputation was found in the exosome group, as well as in the conditioned media and sham-operated groups, compared to three out of seven mice (43%) in the PBS group. The capillary density was higher in the exosome than in the PBS group (p=0.026). The arteriole lumen diameter in the exosome group was larger than in the PBS (p=0.033) and sham-operated (p=0.034) groups. The scores of clinical necrosis and histopathological necrosis in the exosome group were lower than the PBS group (p=0.005), while the histopathological necrosis scores were also lower but statistically insignificant. In silico analysis showed improvement in neovascularization and necrosis, possibly through energy regulation, PI3K/AKT and TGF-β activation, the ubiquitin-proteasome system, and tyrosine kinases receptors. HUVEC exosomes were associated with lower VEGF mRNA expression, which may indicate a more effective compensatory mechanism under ischemic conditions. The exosome group had the lowest VEGF mRNA expression compared to other groups, although the difference was not statistically significant. This study highlights that HUVECs-derived exosomes improve neovascularization and decrease necrosis in a hindlimb ischemia mice model, potentially by modulating several possible mechanisms.

Phenotype driven molecular genetic test recommendation for diagnosing pediatric rare disorders

Patients with rare diseases often experience prolonged diagnostic delays. Ordering appropriate genetic tests is crucial yet challenging, especially for general pediatricians without genetic expertise. Recent American College of Medical Genetics (ACMG) guidelines embrace early use of exome sequencing (ES) or genome sequencing (GS) for conditions like congenital anomalies or developmental delays while still recommend gene panels for patients exhibiting strong manifestations of a specific disease. Recognizing the difficulty in navigating these options, we developed a machine learning model trained on 1005 patient records from Columbia University Irving Medical Center to recommend appropriate genetic tests based on the phenotype information. The model achieved a remarkable performance with an AUROC of 0.823 and AUPRC of 0.918, aligning closely with decisions made by genetic specialists, and demonstrated strong generalizability (AUROC:0.77, AUPRC: 0.816) in an external cohort, indicating its potential value for general pediatricians to expedite rare disease diagnosis by enhancing genetic test ordering.

Targeting Hsp90α to inhibit HMGB1-mediated renal inflammation and fibrosis.

Renal fibrosis, a terminal manifestation of chronic kidney disease, is characterized by uncontrolled inflammatory responses, increased oxidative stress, tubular cell death, and imbalanced deposition of extracellular matrix. 5,2'-Dibromo-2,4',5'-trihydroxydiphenylmethanone (LM49), a polyphenol derivative synthesized by our group with excellent anti-inflammatory pharmacological properties, has been identified as a small-molecule inducer of extracellular matrix degradation. Nonetheless, the protective effects and mechanisms of LM49 on renal fibrosis remain unknown. Here, we report LM49 could effectively alleviate renal fibrosis and improve filtration function. Furthermore, LM49 significantly inhibited macrophage infiltration, pro-inflammatory cytokine production and oxidative stress. Interestingly, in HK-2 cells induced by tumour necrosis factor alpha under oxygen-glucose-serum deprivation conditions, LM49 treatment similarly yielded a reduced inflammatory response, elevated cellular viability and suppressed cell necrosis and epithelial-to-mesenchymal transition. Notably, LM49 prominently suppressed the high-mobility group box 1 (HMGB1) expression, nucleocytoplasmic translocation and activation. Mechanistically, drug affinity responsive target stability and cellular thermal shift assay confirmed that LM49 could interact with the target heat shock protein 90 alpha family class A member 1 (Hsp90α), disrupting the direct binding of Hsp90α to HMGB1 and inhibiting the nuclear export of HMGB1, thereby suppressing the inflammatory response, cell necrosis and fibrogenesis. Furthermore, molecular docking and molecular dynamic simulation revealed that LM49 occupied the N-terminal ATP pocket of Hsp90α. Collectively, our findings show that LM49 treatment can ameliorate renal fibrosis through inhibition of HMGB1-mediated inflammation and necrosis via binding to Hsp90α, providing strong evidence for its anti-inflammatory and anti-fibrotic actions.

Using expanded diagnostic criteria mitigates gender disparities in diagnosis of sleep-disordered breathing.

Mitigating gender inequality in the diagnosis and management of sleep-disordered breathing (SDB) is of paramount importance. Historically, the diagnostic criteria for SDB were based on male physiology and did not account for variations in disease manifestation based on sex. Some payors use a definition of hypopnea that requires a 4% oxygen desaturation (AHI-4) to determine coverage for treatment, while the criteria recommended by the American Academy of Sleep Medicine requires either a 3% oxygen desaturation or an arousal (AHI-3A). This study examined the diagnostic implications of these two definitions for men and women in a clinical setting. We reviewed polysomnography (PSG) reports for all patients who completed a diagnostic PSG study at one sleep disorders center in 2019. Every PSG was scored using both sets of criteria to determine AHI-4 and AHI-3A. Data from 279 women (64.7%), and 152 men (34.3%) were analyzed. Overall, the mean AHI-4 was 21.9±27.3, and the mean AHI-3A was 34.7±32.3 per hour of sleep. AHI-3A resulted in a diagnostic increase of 30.4% (p=0.001) for women and 21.7% (p=0.006) for men. Women saw a greater increase in diagnosis of mild and moderate SDB, while men saw a greater increase in severe SDB with the AHI-3A compared to the AHI-4 definition. The definition of hypopnea used in the AHI-3A criteria is more consistent with the pathophysiology of SDB in women and results in higher rates of diagnosis. Use of the AHI-4 criteria may create a sex-based disparity in diagnosis, leading to symptomatic women remaining undiagnosed and untreated.

Caregiver perspectives enable accurate diagnosis of neurodegenerative disease.

The history from a relative or caregiver is an important tool for differentiating neurodegenerative disease. We characterized patterns of caregiver questionnaire responses, at diagnosis and follow-up, on the Cambridge Behavioural Inventory (CBI). Data-driven multivariate analysis (n=4952 questionnaires) was undertaken for participants (n=2481) with Alzheimer's disease (typical/amnestic n=543, language n=50, and posterior cortical n=50 presentations), Parkinson's disease (n =740), dementia with Lewy bodies (n=55), multiple system atrophy (n=55), progressive supranuclear palsy (n=422), corticobasal syndrome (n =176), behavioral variant frontotemporal dementia (n=218), semantic (n=125) and non-fluent variant progressive aphasia (n=88), and motor neuron disease (n=12). Item-level support vector machine learning gave high diagnostic accuracy between diseases (area under the curve mean 0.83), despite transdiagnostic changes in memory, behavior, and everyday function. There was progression in CBI subscores over time, which varied by diagnosis. Our results highlight the differential diagnostic information for a wide range of neurodegenerative diseases contained in a simple, structured collateral history. We analyzed 4952 questionnaires from caregivers of 2481 participants with neurodegenerative disease. Behavioral and neuropsychiatric manifestations of neurodegenerative disease had overlapping diagnostic boundaries. Simple questionnaire response patterns were sufficient for accurate diagnosis of each disease. We reinforce the value of a collateral history to support a diagnosis of dementia. The Cambridge Behavioural Inventory is sensitive to change over time and suitable as an outcome measure in clinical trials.

Liver Manifestations in Autosomal Dominant Polycystic Kidney Disease (ADPKD) and their impact on quality of life

Abstract Background ADPKD is the most prevalent monogenic kidney disease with an estimated incidence of 1:1000. The condition is characterized by the formation of kidney cysts, which can cause kidney function loss and bears a significant risk of advancing to kidney failure. This study examined the prevalence of hepatic cysts in individuals with ADPKD, and the possible influence of these cysts on liver function and quality of life. Furthermore, the relationship between hepatic cysts and genotype was analysed. Methods Clinical data from 880 patients with ADPKD were analysed, including longitudinal patient data, genetic information, and laboratory parameters. Results The prevalence of hepatic cysts in adult ADPKD patients was 81.71%, consistent with previous studies. Prevalence increased with age, particularly in male patients. No clear association was observed between ADPKD genotype and the presence of liver cysts. Among male patients with liver cysts, glutamic-pyruvic transaminase (GPT) levels significantly decreased with age, while female patients showed a significant increase in gamma-glutamyl transferase (γ-GT) levels. Overall, hepatic cysts had minimal impact on liver enzymes. Quality of life assessments using the SF-12 questionnaire revealed no significant influence of hepatic cysts on physical or mental well-being. However, physical quality of life was significantly lower in patients showing polycystic liver disease as a manifestation of ADPKD compared to all other patients, both with and without liver cysts. Conclusions Hepatic cysts are highly prevalent in adult patients with ADPKD, increasing with age. ADPKD genotype does not appear to be associated with the presence of hepatic cysts. Liver function, as indicated by enzyme levels, is minimally affected by hepatic cysts in most ADPKD patients. The quality of life of ADPKD patients is generally unaffected by the presence of hepatic cysts, except in severe cases of polycystic liver disease (PLD). Further research is needed to develop effective treatments for severe PLD and gain a better understanding of the factors influencing hepatic cyst incidence and progression in patients with ADPKD.

Type 2 Diabetes Mellitus and Parkinson's Disease: An Emerging Link

Parkinson’s Disease (PD) is a common neurodegenerative disease, characterized by motor deficit. Diabetes Mellitus (DM) is a metabolic condition characterized by high glucose levels in the blood. The prevalence of chronic disorders like PD has significantly risen in recent decades. Emerging research has increasingly linked PD with Type 2 Diabetes Mellitus (T2DM) in recent years. Apart from the β-cells of the pancreas, insulin is secreted by the choroid plexus in the human brain which is essential for neuroprotection which regulates neurogenesis, oxidative stress, synaptic plasticity, neuronal survival, and neuro-inflammation. The abnormalities in the insulin signaling pathway may be responsible for neurodegeneration via insulin dysregulation, from the aggregation of α-synuclein, neuroinflammation, mitochondrial dysfunction, and altered synaptic plasticity. DM or Insulin resistance is considered a risk factor for the development of PD. Due to the lack of treatment options for PD, consistent research is going on to find a potential drug as a treatment option for PD, and due to its molecular links, the antidiabetic drugs are considered as potential candidates for PD. This review will discuss the potential cellular mechanisms shared between T2DM and PD as well as the role of antidiabetics in this disease and clinical manifestations such as its severity and prognosis.

NMDA Receptors in Neurodevelopmental Disorders: Pathophysiology and Disease Models.

N-methyl-D-aspartate receptors (NMDARs) are critical components of the mammalian central nervous system, involved in synaptic transmission, plasticity, and neurodevelopment. This review focuses on the structural and functional characteristics of NMDARs, with a particular emphasis on the GRIN2 subunits (GluN2A-D). The diversity of GRIN2 subunits, driven by alternative splicing and genetic variants, significantly impacts receptor function, synaptic localization, and disease manifestation. The temporal and spatial expression of these subunits is essential for typical neural development, with each subunit supporting distinct phases of synaptic formation and plasticity. Disruptions in their developmental regulation are linked to neurodevelopmental disorders, underscoring the importance of understanding these dynamics in NDD pathophysiology. We explore the physiological properties and developmental regulation of these subunits, highlighting their roles in the pathophysiology of various NDDs, including ASD, epilepsy, and schizophrenia. By reviewing current knowledge and experimental models, including mouse models and human-induced pluripotent stem cells (hiPSCs), this article aims to elucidate different approaches through which the intricacies of NMDAR dysfunction in NDDs are currently being explored. The comprehensive understanding of NMDAR subunit composition and their mutations provides a foundation for developing targeted therapeutic strategies to address these complex disorders.