Disease Symptoms Research Articles

Additional new species of Preussia from forest trees in Iran.

Forest trees were known to be hosts for a large number of pathogenic and non-pathogenic fungi. Species of Preussia have a cosmopolitan distribution and are geographically widespread, occurring in diverse ecosystems. In this study, 12 Preussia isolates were obtained from disease symptoms in three Zagrosian forest trees in Iran, including Cerasus microcarpa, Crataegus sp., and Pistacia atlantica. These isolates were identified based on morphological and phylogenetic analyses subjected to DNA sequencing of four DNA loci including the internal transcribed spacer regions 1 and 2 including the intervening 5.8S nuclear ribosomal DNA (ITS), partial nuclear 28S ribosomal DNA (LSU), partial translation elongation factor 1a (tef1), and part of the beta-tubulin (tub2). Accordingly, four new Preussia species within the family Sporormiaceae were proposed as follow: P. crataegi, P. iranica, P. pianica, and P. pistaciae spp. nov. Asexual morph of P. crataegi, P. pianica, and P. pistaciae were described and illustrated, as well as, sexual morph of P. iranica. Up to now, no other species of Preussia and its allied genera in the family Sporormiaceae have been reported from these hosts. This study expanded our knowledge of species diversity of Preussia in the world.

Forecasting the Incidence of Mumps Based on the Baidu Index and Environmental Data in Yunnan, China: Deep Learning Model Study.

Mumps is a viral respiratory disease characterized by facial swelling and transmitted through respiratory secretions. Despite the availability of an effective vaccine, mumps outbreaks have reemerged globally, including in China, where it remains a significant public health issue. In Yunnan province, China, the incidence of mumps has fluctuated markedly and is higher than that in mainland China, underscoring the need for improved outbreak prediction methods. Traditional surveillance methods, however, may not be sufficient for timely and accurate outbreak prediction. Our study aims to leverage the Baidu search index, representing search volumes from China's most popular search engine, along with environmental data to develop a predictive model for mumps incidence in Yunnan province. We analyzed mumps incidence in Yunnan Province from 2014 to 2023, and used time series data, including mumps incidence, Baidu search index, and environmental factors, from 2016 to 2023, to develop predictive models based on long short-term memory networks. Feature selection was conducted using Pearson correlation analysis, and lag correlations were explored through a distributed nonlinear lag model (DNLM). We constructed four models with different combinations of predictors: (1) model BE, combining the Baidu index and environmental factors data; (2) model IB, combining mumps incidence and Baidu index data; (3) model IE, combining mumps incidence and environmental factors; and (4) model IBE, integrating all 3 data sources. The incidence of mumps in Yunnan showed significant variability, peaking at 37.5 per 100,000 population in 2019. From 2014 to 2023, the proportion of female patients ranged from 41.3% in 2015 to 45.7% in 2020, consistently lower than that of male patients. After excluding variables with a Pearson correlation coefficient of <0.10 or P values of <.05, we included 3 Baidu index search term groups (disease name, symptoms, and treatment) and 6 environmental factors (maximum temperature, minimum temperature, sulfur dioxide, carbon monoxide, particulate matter with a diameter of 2.5 µm or less, and particulate matter with a diameter of 10 µm or less) for model development. DNLM analysis revealed that the relative risks consistently increased with rising Baidu index values, while nonlinear associations between temperature and mumps incidence were observed. Among the 4 models, model IBE exhibited the best performance, achieving the coefficient of determination of 0.72, with mean absolute error, mean absolute percentage error, and root-mean-square error values of 0.33, 15.9%, and 0.43, respectively, in the test set. Our study developed model IBE to predict the incidence of mumps in Yunnan province, offering a potential tool for early detection of mumps outbreaks. The performance of model IBE underscores the potential of integrating search engine data and environmental factors to enhance mumps incidence forecasting. This approach offers a promising tool for improving public health surveillance and enabling rapid responses to mumps outbreaks.

Nigrospora aurantiaca caused leaf spot disease in Bayberry in Guizhou, China.

Bayberry (Myrica rubra) is one of the most important fruit in China. In July 2023, circular leaf spots were noted on spring bayberry (cv. Dongkui Arbutus) tree planted in Guanshanhu, Guiyang, Guizhou, China (26°37'3"N，106°39'59"E). The disease incidence (diseased plants/total plants × 100) varied from 55 to 60% with 15 to 20% disease severity (diseased leaf area/total leaf area × 100). Disease incidence and severity were calculated from five infected fields of bayberry using by SPSS Statistics 22.0 (IBM Corp., NY, USA). The abundance of leaf spots on the trees was predominantly observed on the young leaves. Symptoms included round or irregular spots on leaves with grayish-red during early infection and later transferred to brown dark spots on the edge of the leaves, accompanied by a pale yellow aperture on the periphery. Sixty diseased leaves (three leaves from each diseased plant) from twenty plants (four plants from each infected field) in the same growth period were collected randomly and cut into small pieces (2 mm × 2 mm), disinfected with 75% alcohol for 30 s and with 1% NaClO for 60 s and rinsed 3 times with ddH2O. The diseased tissues were plated on PDA plate having Streptomycin and then incubated at 25 ˚C for 2 d under 16: 8 h light and dark regime. The single hypha was picked from plates and transferred to a new PDA plate having Streptomycin for purification. Sixty five pure cultures were obtained through single spore isolation and purification. After ITS-BLAST, the results indicated that among the cultures, sixty were Nigrospora sp. (92.31%), two were Flavodon sp. (3.07%) and three were Aureobasidium sp. (4.62%). Thus, the detection rate of Nigrospora sp. was the highest. From sixty obtained isolates with same morphological characters, six isolates (GUCC 23-0016, GUCC23-0017, GUCC23-0018, GUCC24-0244, GUCC24-0245 and GUCC 24-0246) were selected for pathogenicity and identification. Conidia (n = 40) were black, oval or round, smooth and size range was 11-16 × 12-14.5 µm in diameter. Based on disease symptoms and morphological characters, the pathogen was primarily recognized as a Nigrospora sp. (Wang et al. 2017). PCR was performed for each of the six isolates to amplify the internal transcribed spacer (ITS), the large subunit rDNA (LSU), β-tubulin 2 (tub2) and translation elongation factor 1-alpha (tef1) genes with primers sets of ITS4/ITS5 (Innis et al. 1990), LR0R/LR5 (Vilgalys & Hester 1990), Bt2a/Bt2b (Glass and Donaldson 1995), EF1-728F/EF-986R (Carbone and Kohn 1999), respectively and then PCR products were sequenced. GenBank accession numbers are OR647487, OR647489, OR647490, PQ803982, PQ803983 and PQ804003 for ITS, PQ351182, PQ351183, PQ351185, PQ805435, PQ804004 and PQ805436 for LSU, OR670516, OR670517 OR670518, PQ807000, PQ807001 and PQ807002 for tub2 and OR725093, OR725094 , OR725095, PQ807003, PQ807004 and PQ807005 for tef1. The BLAST results showed that DNA sequences of the present isolates were 100% identical to the type strain of N. aurantiaca (CGMCC 3.18130: KX986064.1, NG_069394, KY019295.1, KY019465.1) and the phylogenetic tree with four gene loci also indicated that our isolates belonged to N. aurantiaca. The pathogenicity test was conducted following Koch's postulates. Ten bayberry trees of approximate ten years old were inoculated with six above isolates (GUCC 23-0016, GUCC23-0017, GUCC23-0018, GUCC24-0244, GUCC24-0245 and GUCC 24-0246) and two healthy trees were used as control. Twenty leaves from each tree were disinfected with 75% ethanol prior to pathogen inoculation. The leaves were inoculated by spraying a conidial suspension (1 × 105 spores/mL) of each isolate, while ddH2O was sprayed on forty control leaves from two trees. Pathogen inoculation was performed under natural field conditions. After 7 d, similar symptoms to those observed in the field were noted on inoculated leaves, while the control leaves were still healthy. We also inoculated bayberry detached leaves in vitro by spraying with conidia suspension (1 × 105 spores/mL) of each isolate, while ddH2O as control. Inoculated leaves were maintained in a greenhouse with temperature ranging from 23-25 ˚C at 75% relative humidity. After 7 d, similar symptoms were observed on the inoculated leaves, while the control remained healthy. Both experiments were repeated three times. The pathogen was re-isolated from both in vivo and in vitro inoculated leaves and were re-identified as N. aurantiaca through morphological identification and molecular identification by code amplification of ITS, LSU, tub2 and tef1. Thus, we proposed that N. aurantiaca caused the leaf spot of bayberry. Leaf spot diseases caused by N. aurantiaca on tobacco, Chinese chestnut and olive were reported in Guizhou (Huang et al. 2021), in Yanyuan (Luo et al. 2020) and Croatia (Petrović et al. 2023), respectively. However, to our knowledge, this is the first report of N. aurantiaca causing leaf spot diseases on bayberry in China. The identification of this disease offered a basis for further research on its proper management.

First Report of Lasiodiplodia theobromae Causing Wilt and Fruit Rot of Pepper in Hainan Province, China.

Ornamental pepper (Capsicum annuum L.) is an economically important plant with extensive genetic diversity (Zhang et al. 2020). In September 2022, symptoms of wilt and fruit rot were identified in approximately 0.02 hectares of an ornamental pepper plantation in Haikou, Hainan Province, China (110°32' E, 20°06' N). Disease severity reached 85%, with an incidence rate of 90%. Symptoms started as black foliar spots that expanded into large lesions, spreading to fruits and stems, causing wilting (Fig. S1). Samples from symptomatic leaves, fruits, and stems of 27 plants were surface-sterilized with 75% ethanol for 30 s, rinsed five times with sterile water, air-dried, plated on potato dextrose agar (PDA), and incubated at 28°C for 5 to 6 days. To obtain pure fungal cultures, initial isolates were subcultured onto fresh PDA. Among the 27 fungal cultures, 11 isolates from leaves and fruits consistently formed gray to olivaceous colonies. Isolate LJY224 initially produced grayish-white, fluffy mycelia with radiating aerial hyphae. Over time, the colony became grayish-black and produced black, nearly spherical pycnidia. The conidia were oval, initially transparent, and single-celled. Mature conidia were dark brown, septate, with longitudinal striations, averaging 11.55 ± 0.75 µm in width and 24.93 ± 1.50 µm in length (n=35) (Fig. S2), indicating Lasiodiplodia spp. Genomic DNA was extracted using a fungal DNA extraction kit (OMEGA BIO-TEK, GZ Feiyang Biotech Co., Ltd., Guangzhou, China). Molecular identification involved sequencing the rRNA internal transcribed spacer (ITS) region and genes encoding β-tubulin (TUB) and translation elongation factor 1-α (TEF1) with primers ITS1/ITS4, Bt2a/Bt2b, and EF1-983F/EF1-2218R, respectively (White et al. 1990; Rosado et al. 2016; Rehner and Buckley 2005). BLASTn searches with the obtained ITS, TUB, and TEF1 sequences (GenBank accessions OQ612711, OR039814, OR039813) revealed 98% to 100% identity with Lasiodiplodia theobromae reference sequences from the NCBI database (OR018404, KR260830, MN461169), matching 541/548, 446/446, and 947/955 base pairs, respectively. A phylogenetic tree was constructed using concatenated multi-locus sequence analysis (MLSA) of ITS, TUB, and TEF1 (Fig. S3). To fulfill Koch's postulates, healthy 3-month-old ornamental pepper plants were inoculated by spraying the entire plant with a conidial suspension (50 ml, 107 conidia/L) of LJY224, using sterile water as a negative control. Each treatment included three replicates. Plants were maintained at 25°C, 75% humidity, under a 12-h light/dark cycle, and monitored daily. After 14 days, inoculated plants developed black foliar spots that expanded into large lesions, spreading to fruits and stems, and causing wilting, consistent with initial symptoms, while control plants remained healthy (Fig. S4). The re-isolated pathogen showed identical morphology to the original strain. In contrast, no fungi were isolated or recovered from the plants inoculated with water. Results from disease symptoms, colony and spore morphology, pathogenicity tests, and multi-locus DNA sequence analysis suggest that L. theobromae was the pathogen responsible for the disease symptoms on ornamental peppers. L. theobromae is closely related to Botryosphaeria dothidea, both of which cause fruit rot in peppers (Rui et al. 2023). To our knowledge, this is the first report of L. theobromae causing leaf wilt and fruit rot in ornamental pepper in Hainan Province, China, offering insights to mitigate crop losses.

Motor Symptom Variability in Parkinson's Disease: Implications for Personalized Trial Outcomes?

The Movement Disorders Society Unified Parkinson Disease Rating Scale (MDS-UPDRS), Part III, is the gold standard for assessing motor symptoms in Parkinson's disease (PD). However, motor symptoms fluctuate significantly from day to day, potentially limiting the sensitivity of this scale for trials with short duration and crossover designs. This study investigated whether day-to-day variability in motor symptoms exceeds the minimal clinically important difference (MCID) in the MDS-UPDRS, Part III. Twenty PD participants (Hoehn & Yahr stages 1.5-3) underwent 10 weekly off-medication assessments by one assessor on the same morning. Several determinants of day-to-day variability were explored. Symptom variability often exceeded the MCID for worsening and improvement. Current mental stress and fatigue did not correlate with worse scores, nor did physical activity and sleep quality in the previous week. These findings suggest that day-to-day symptom variability impacts MDS-UPDRS scores in smaller and shorter-duration trials of symptomatic interventions. Continuous monitoring using wearable sensors may offer more accurate and reliable measures for evaluating PD motor symptoms in clinical studies. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

SOX9: a key transcriptional regulator in organ fibrosis

The SOX9 gene locus is not only extensive but also intricate, and it could promote fibrosis in different organs or tissues, including cardiac fibrosis, liver fibrosis, kidney fibrosis, pulmonary fibrosis, as well as other organ fibrosis. Many disorders are associated with the process of fibrosis; moreover, fibrosis is a common symptom of chronic inflammatory diseases, characterized by the accumulation of excessive components in the extracellular matrix through different signaling pathways. The advanced stage of the fibrotic process leads to organ dysfunction and, ultimately, death. In this review, we first give an overview of the original structure and functions of SOX9. Second, we will discuss the role of SOX9 in fibrosis in various organs or tissues. Third, we describe and reveal the possibility of SOX9 as an antifibrotic treatment target. Finally, we will focus on the application of novel technologies for SOX9 and the subsequent investigation of fibrosis.

Effects of whole-head 810 nm near-infrared therapy on cognitive and neuropsychiatric symptoms in Alzheimer's disease: A pilot study.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by significant cognitive and behavioral impairments. Near-infrared (NIR) light treatment has shown potential in cognitive improvement in previous studies. However, clinical trials of NIR for AD remain limited. This study investigated the safety and effects of whole-head 810 nm NIR therapy in AD patients, including long-term efficacy. An open-label pilot study on whole-head NIR treatment for AD patients was conducted. Nine AD patients completed 4-month treatment (810 nm, 100 mW/cm², 30 min/session, 6 sessions weekly). Safety and efficacy were evaluated at baseline, months 2 and 4, and 2-month post-treatment. After four months of whole-head NIR treatment, mean changes from baseline on the Mini-Mental State Examination were 3.2 (p = 0.02). Mean changes from baseline on the Alzheimer's Disease Assessment Scale-Cognitive were -5.0 (p = 0.05), mean changes from baseline on the Montreal Cognitive Assessment were 1.9 (p = 0.12). Mean changes from baseline on the Neuropsychiatric Inventory were -4.2 (p = 0.47). These benefits were sustained two months at least. With no device-related adverse effects were reported. Whole-head 810 nm NIR light is safe and offers promising benefits for AD patients. To fully confirm its efficacy, durability, and underlying mechanisms, further large-scale randomized controlled trials are necessary.

First report of genotypes of citrus tristeza virus breaking resistance in sweet orange and clementine in Spain.

Citrus tristeza virus (CTV) classified as Closterovirus tristezae within the genus Closterovirus, family Closteroviridae is broadly distributed in the major citrus-growing regions. CTV has eight main strains (genotypes or phylogenetic groups): T36, T30, T3, T68, VT, RB, HA16-5, and S1, that can induce different symptoms (Sun et al., 2024) with RB isolates being the only variants able to infect and spread within Poncirus trifoliata (Yokomi et al., 2017). In Spain, most isolates belong to the biologically mild T30 strain. Citriculture relies on CTV-resistant P. trifoliata rootstock and its hybrids to prevent virus-induced graft incompatibility. Only rarely, severe VT isolates inducing stem pitting on sweet orange have been reported (Moreno et al., 2008). From February to June 2023, citrus orchards in 4 areas in the Valencian Community were surveyed for monitoring circulanting strains. Five plants (3 sweet orange and 2 clementine trees) showing symptoms of tristeza disease and decline, grafted onto the resistant rootstock Carrizo citrange (Citrus sinensis (L.) Osb. × Poncirus trifoliata (L.) Raf.) were individually analyzed by high-throughput sequencing (HTS): sweet orange trees 137.4 in Moncada, 141.4 and 141.5 in Sagunto and clementine trees 142.13 in Nules and 152.7 in Burriana. Five leaves showing vein chlorosis and leaf cupping were pooled and analyzed per tree. Total RNA purified from leaf tissue was sequenced in a Novaseq 6000 platform using TrueSeq Illumina methodology with ribo-depletion. Bioinformatic analysis by CLC Genomics Workbench 10.1.1, according to Ruiz-García et al. (2019), allowed the recovery of 13 near full-length CTV genomes from different strains. Interestingly, 3 isolates belonged to the RB strain, 5 to the VT strain and 5 to the T30 strain. Sweet orange trees exhibited co-infections with CTV isolates from different strains: VT and T30 (OQ714508 and PQ576736) in 137.4; RB, VT and T30 (PQ538530, PQ576743 and PQ576742) in 141.4; and RB, VT and T30 (OQ848758, PQ576738 and PQ576737) in 141.5. In clementine trees CTV co-infections were also observed: RB, VT and T30 (PQ538529, PQ576740 and PQ576739) in 142.13; and VT and T30 (PQ576741 and PQ576744) in 152.7. BLASTn analysis showed that the RB isolates PQ538530 and OQ848758 belong to RB2 group, with the highest nucleotide identity of 99.63% (19198/19269 nt) and 99.62% (19197/19270 nt), respectively, to the isolate B390-5 (KU883265); whereas RB isolate PQ538529 belongs to RB1 group, with the highest nucleotide identity of 99.1% (19082/19255 nt) to the isolate B301 (JF957196). Supplementary Table 1 shows data from the HTS analysis, including additional viruses and viroids detected for which no association with the symptoms was established. The presence of the RB isolates found by HTS was confirmed by RT-PCR analysis and Sanger sequencing, using CTV-RB specific primers previously reported (Cook et al., 2016). In a survey of 147 citrus trees with tristeza symptoms across 7 orchards in Burriana, Nules, and Sagunto, the presence of RB isolates was evaluated. The results identified 46 CTV-RB-infected plants: 35 belonging to RB1 group and 11 to RB2 group, indicating that RB isolates are widespread. To our knowledge, this is the first report of CTV-RB isolates in Spain. The co-infection of biologically mild symptomless RB isolates with Spanish severe VT isolates poses a potential risk for the emergence of recombinant strains, threatening the Spanish citrus industry.

Epicardial Fat Tissue: A Potential Marker for Coronary Microvascular Dysfunction.

Coronary microvascular dysfunction (CMD), which mimics symptoms of obstructive coronary artery disease, has significant prognostic implications. While epicardial adipose tissue normally has a protective role, increased epicardial adipose tissue is associated with inflammation and may contribute to CMD. However, a direct correlation remains unclear. We aimed to investigate this association. The CMDR (Coronary Microvascular Disease Registry) is a prospective, 2-center registry that is enrolling patients with angina and nonobstructive coronary artery disease who underwent invasive hemodynamic assessment of the coronary microvasculature. Patients with chest computed tomography within 1 year of CMD evaluation were included. We measured epicardial fat volume (EFV) and calculated the EFV index. Logistic regression analysis was used to investigate the association between EFV and EFV index to CMD. Our study included 130 CMDR patients with associated chest CT; 35 were diagnosed with CMD. The CMD-negative patients were younger than the CMD-positive patients (58.52±11.97 versus 63.37±9.56 years; P=0.033), with numerically fewer women (64.2% versus 74.3%; P=0.279). Univariate regression analysis demonstrated a statistically significant association between EFV index and CMD diagnosis (odds ratio, 1.037 [95% CI, 1.014-1.063]; P=0.003), while no significance was observed for EFV (odds ratio, 1.006 [95% CI, 0.995-1.017]; P=0.292). Our results suggest a strong association between EFV index (a significant risk factor) and the presence of CMD. Future studies involving larger cohorts are needed to confirm the association of epicardial adipose tissue with CMD and investigate therapeutic targets to prevent CMD. URL: https://www.clinicaltrials.gov; unique identifier: NCT05960474.

The Multifaceted Chemistry Of Chili Peppers: A Biodiversity Treasure For Nutrition And Biomedicine.

Chili pepper (Ch-p), a spice-utilizing fruit, is rich in natural medicinally bioactive compounds, such as flavonoids, capsaicinoids, and many other phytochemicals and phytonutrients. Operating in synergy and consortium, these compounds demonstrate their functionality, in comparison to lonely treatment, as active agents in handling many disorders. These may include abnormal coagulation, oxidative stress, obesity, diabetes, inflammation, cancer, and microbe-inducing diseases. Recently, capsaicinoids, particularly capsaicin, have been shown to manage the symptoms of significant viral diseases, including COVID-19. Capsaicin also has the potential to be an effective anesthetic agent and enables Ch-p to be expandedly employed as a topical preparation in relieving pain as well. The phytochemicals of Ch-p are not only beneficial and inexpensive phyto-alternatives in disease management, but they can also be used as scaffolds for the production of novel medicines. The study also substantiates the role of the TRPV1 receptor in the mitigation of chronic diseases in conjunction with capsaicin.The nutritional and biomedical prospection of Ch-p-derived products has been addressed in an accessible format in this artifact, with the potential to precisely enhance and enrich our pharmaceutical industries in the pursuit of human well-being.

The Relationship Between Work Shifts And Work Stress Among Nurses In The Maternity Ward At Permata Bunda Hospital

Background and Objective: Stress is a symptom of the biggest disease of the modern century that is often experienced by nurses in hospitals. Stress in the workplace is where employees encounter conditions of overwork, low levels of job satisfaction. One of the causes of work stress is work shift arrangements. The data obtained is that nurses complain of work stress due to the continuing shift schedule or nurses replacing their colleagues' work shifts due to the lack of manpower in the room. The purpose of this study was to determine the relationship between work shifts and nurses' work stress in the maternity ward of Permata Bunda Hospital Purwodadi. Method: This is quantitative research with a cross sectional research method, with a correlation approach, the sampling technique used total sampling, which amounted to 26 respondents. Results: The test results using spearman rank between work shifts and nurses' work stress, obtained p value (0.000) &lt; α (0.05) which means H0 is rejected and Ha is accepted. With a correlation result of 0.723, it’s concluded that there is a significant relationship between work shifts and work stress. Conclusion: There is a relationship between work shifts and nurses' work stress, meaning that there is a positive correlation between work shifts and work stress. This means that the more inappropriate the work shift, the heavier the nurse's work stress.

The Use and Understanding of Mild Cognitive Impairment in Routine Specialist Care: A Survey Among German Memory Clinics

Objectives: Mild cognitive impairment (MCI) is a heterogeneous clinical syndrome and is important for the diagnosis and management of Alzheimer’s disease (AD). With the expansion of biomarker-based diagnostics, the aim of this study is to clarify the current attitudes towards and the use of MCI, and MCI due to AD, in German memory clinics. Methods: An online survey (50 items) was performed in 2022 among specialized clinicians (N = 45) in German memory clinics to assess the use of MCI and biomarkers in current diagnosis and treatment. Attitudinal and frequency items were assessed with a five-point numeric scale (strongly disagree = 1 to completely agree = 5 and never = 1 to always = 5, respectively). Results: All respondents used MCI as a clinical diagnosis. The benefits of diagnosing MCI were labeling deficits as disease symptoms (M = 4.4, SD = 0.7), improving coping with symptoms (M = 4.1, SD = 0.9), and motivating risk reduction activities (M = 4.0, SD = 0.9). Overall, 37 respondents used specialized diagnostic criteria for MCI due to AD, and all had access to biomarker diagnostics. Patients with MCI due to AD received more frequent counseling on memory training (p &lt; 0.001), other non-pharmacological treatments (p &lt; 0.001), and antidementive drug treatment (p &lt; 0.001) than patients with MCI of other etiologies. Acetylcholinesterase inhibitors were prescribed significantly more frequently to patients with MCI due to AD (p &lt; 0.001) compared to other MCI patients. Conclusions: MCI is commonly used as a clinical diagnosis in German memory clinics. AD biomarker assessment is well established and influences patient counseling and treatment recommendations.

Clinical and genetic spectrums of Pompe disease in Duhok city, Kurdistan region, Iraq.

Pompe disease which is glycogen storage disease type II, is an autosomal recessive lysosomal storage disorder where GAA gene mutations cause deficiency of acid alpha-glucosidase leading to deposition of glycogen in various tissues. Chromosome 17q25.2-25.3 is the location of GAA gene. This study aims to collect information on the Pompe disease symptoms' severity and genotypes of 18 children who represented all infant patients with Pompe disease until March 1st, 2024. For diagnosis tandem mass spectrometry and genetic study were used. Muscle strength was assessed by hand-held dynamometry. Cardiac assessment was by echocardiography and electrocardiography. The feeding and swallowing difficulties in the patients were addressed. Statistical analysis was used P<0.05 was considered significant. Fifty percent had normal mental development, 27.8% had delayed mile stones 55.6% had weakness of extremities, 50% had heart problems in the first month,38.8% had respiratory problems in the first month and 12(66.6%) had feeding difficulties. The level of the enzyme alpha-1,4 Glucosidase level was Zero in two patients 66.7% and was 0.1µmol/L/h in 33.3% of the alive patients while it was 0.1 µmol/L/h in 73.3% and 0.2 µmol/L/h in 13.3% of the dead with a significant correlation. The genetic mutations were c. [258dupC]; [258dup] in 6 (33.3%) of the patients, c.258dup in 3(16.6%) and c.2237G>A in 11.1% of all the patients. Childhood Pompe disease course varies widely. It is important to consider Pompe disease in the differential diagnosis of patients with unexplained fatigue and weakness and cardiorespiratory involvement.

Sleep spindle variation in patients with Parkinson's disease on first nights of sub-optimal deep brain stimulation.

Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) is a common treatment for motor symptoms of Parkinson's disease but its influence on non-motor symptoms is less clear. Sleep spindles are known to be reduced in patients with Parkinson's disease, but the effect of STN DBS is unknown. The objective of our study was to address this knowledge gap. Polysomnograms were recorded for three consecutive nights in 15 patients with advanced Parkinson's disease (11 male, 4 female; age: 53-75years), including at least one night each of unilateral STN DBS stimulation ON and OFF. Stimulation ON was set to 70% of clinical amplitude to mitigate sleep being altered via changing motor symptoms or due to patient awareness of stimulation. Sleep spindles were detected in electroencephalogram (EEG) data by two previously published, validated automated sleep spindle detection algorithms: Ferrarelli et al. (2007) and Martin et al. (2013). Sleep spindle density was higher during stimulation ON than OFF nights in 11 of 12 subjects using either sleep spindle detection algorithm (p<=0.01, Wilcoxon rank sum). Stimulation ON versus OFF had no statistically significant effect on sleep spindle duration or amplitude. Our analysis indicates that a single night of sub-optimal STN stimulation significantly increases sleep spindle density in Parkinson's disease patients. These results further our understanding of how DBS impacts non-motor symptoms of Parkinson's disease.

American ginseng vesicles loaded hyaluronic acid hydrogel for ulcerative colitis.

The present study introduces a novel therapeutic approach for ulcerative colitis (UC) utilizing American ginseng vesicles encapsulated within a hyaluronic acid (HA) hydrogel matrix. UC, a prevalent form of inflammatory bowel disease, is characterized by chronic inflammation of the colonic mucosa, leading to significant morbidity and compromised quality of life. Existing therapeutic modalities such as 5-Aminosalicylic acid (5-ASA) are associated with substantial side effects and a high recurrence rate. Thus, there is an unmet need for alternative treatments that offer enhanced efficacy with reduced adverse effects. Leveraging the anti-inflammatory properties of American ginseng vesicles HA -hydrogels of HA hydrogel (5-ASA + ANPs@HA), this study presents a targeted drug delivery system designed to provide localized therapy for UC. We synthesized the hydrogel matrix by HA and 1,4-butanediol diglycidyl ether (BDDE) at concentrations of 1 % NaOH and 0.8 %, v/v, respectively. The water content of the hydrogel was about 80 % to 90 %, and 82 % of Rb1 was released in 61 min. Our results demonstrate a significant reduction in disease symptoms, a substantial decrease in pro-inflammatory cytokines, and marked enhancement in mucosal healing following treatment with the 5-ASA + ANPs@HA. Collectively, these results suggest that the 5-ASA + ANPs@HA represents a promising therapeutic strategy for UC, warranting further investigation for clinical application.

A pilot study for speech assessment to detect the severity of Parkinson's disease: An ensemble approach.

Changes in voice are a symptom of Parkinson's disease and used to assess the progression of the condition. However, natural differences in the voices of people can make this challenging. Computerized binary speech classification can identify people with PD (PwPD), but its multiclass application to detect the severity of the disease remains difficult. This study investigated six diadochokinetic (DDK) tasks, four features (phonation, articulation, prosody, and their fusion), and three machine learning models for four severity levels of PwPD. The four binary classifications were: (i) Normal vs Not Normal, (ii) Slight vs Not Slight, (iii) Mild vs Not Mild and (iv) Moderate vs. Not Moderate. The best task and features for each class were identified and the models were ensembled to develop a multiclass model to distinguish between Normal vs. Slight vs. Mild vs. Moderate. For Normal vs Not-normal, logistic regression (LR) using the prosody from "ka-ka-ka" task, Random Forest (RF) using articulation from "petaka" for Slight vs Not Slight, RF for the fusion from "ka-ka-ka" for Mild vs Not Mild and Gradient Boosting (GB) using prosody from "ta-ta-ta" for Moderate vs Not Moderate gave the best results. Combining these using LR achieved an accuracy of 72%. Dividing the multiclass problem into four binary problems gives the optimum speech features for each class. This pilot study, conducted on a small public dataset, shows the potential of computerized speech analysis using DDK to evaluate the severity of Parkinson's disease voice symptoms.

BreathCarer: Informal carers of patients with chronic breathlessness: a mixed-methods systematic review of burden, needs, coping, and support interventions

BackgroundBreathlessness is a common symptom in chronic and advanced diseases, and it poses a significant burden to patients and to their informal carers. They play a crucial role in sustainable care for patients living with breathlessness, but their challenges and needs are often neglected.ObjectiveTo provide a systematic overview of the literature on the burden, needs, coping and use of healthcare and social services by carers of patients suffering from chronic breathlessness due to any life-limiting disease.DesignA mixed-methods systematic review (PROSPERO CRD42022312989).Data sourcesMedline, CENTRAL, PsycINFO, and CINAHL were searched and complemented with forward and backward searches and expert consultation.Review methodsThe mixed-methods review included any study on burden, needs and coping among carers of patients with breathlessness published from the inception of the databases until July 2023. A narrative analysis of the quantitative results and a pragmatic meta-aggregation of the qualitative findings were performed, followed by a mixed-methods convergent segregated approach.FindingsA total of 53 studies with 4,849 carers were included. Breathlessness is highly burdensome for carers who live with and care for patients or for those who do not live with the patients and care for them. Breathlessness is a significant risk factor for high carers’ burden, contributing to deteriorating physical and mental health among carers and creating an urgent need for external support. A major challenge is the sense of being trapped in a state of constant alertness and anxiety, centred around managing the patient's breathlessness. Carers bear substantial emotional burden due to uncertainty, sleep disturbances, and social isolation, which leads to severe psychological distress. Their unmet needs for professional guidance, self-management strategies, and social interaction are high. While supportive interventions, such as specialized services and multidisciplinary approaches, can alleviate some of the burden, there remains a lack of targeted interventions specifically designed for carers.ConclusionsThis review highlights the substantial burden associated with caring for patients with chronic breathlessness, the unmet needs of carers and the lack of supportive care structures, leaving them with little option but to accept the situation.

Co-stimulating the left vmPFC compensates for apathy after levodopa withdrawal in Parkinson's patients with STN DBS.

Subthalamic nucleus deep brain stimulation (STN DBS) improves motor symptoms of Parkinson's disease (PD), but its effect on motivation is controversial. Apathy, the lack of motivation, commonly occurs in PD and is often exacerbated after surgery and its concomitant levodopa reduction. Apathy and reward processing are associated with the ventromedial prefrontal cortex (vmPFC), which standard targeting strategies avoid by targeting the dorsolateral STN. Since apathy can be a levodopa-responsive PD symptom, levodopa withdrawal could unmask apathy without sufficient stimulation of non-motor pathways, similar to the persistence of motor symptoms when motor pathways are underengaged with DBS. Using an individualized tractography model, maximized left-sided vmPFC engagement following a DBS adjustment improved apathy in a case example. We, therefore, retrospectively investigated the moderating role of stimulation-related left-sided vmPFC connectivity and levodopa reduction on changes in apathy after STN DBS (N=28). We measured apathy (Starkstein Apathy Scale) and levodopa dose pre- and post-surgery. Stimulation-related connectivity was quantified using patient-specific diffusion-weighted MRI and probabilistic tractography to test the interaction with levodopa reduction. Effective DBS of the dorsolateral STN included prefrontal non-motor connections. We found a significant interaction between levodopa dose change and STN-connections to the left vmPFC. Apathy severity negatively correlated with stimulation-related connectivity to the left vmPFC in patients with greater levodopa reductions. Apathy change was unrelated to motor pathway connectivity. Insufficient stimulation of the left vmPFC and associated limbic fronto-subthalamic connections combined with high levodopa reduction contributed to DBS-related apathy in PD, which may inspire novel personalized non-motor targeting strategies.

Pramipexole decreases allodynia and hyperalgesia via NF-κB in astrocytes in rats with Parkinson's disease.

Pain is one of the principal non-motor symptoms of Parkinson's disease (PD), negatively impacting the patient's quality of life. This study aimed to demonstrate whether an effective dose of pramipexole (PPX) can modulate the NF-κB/p-p65 activation in glial cells (astrocytes and microglia) and diminish the hypersensitivity (allodynia and hyperalgesia) in male Wistar rats with PD. For this, 2μl of 6-hydroxydopamine (6-OHDA, 8μg/μL/0.2μl/min) was administered unilaterally in the Substantia Nigra of the Pars Compacta (SNpc) to establish a PD model rat. Motor behavioral tests were used to validate the PD model, and von Frey filaments were used to evaluate allodynia and hyperalgesia. Immunohistochemical and immunofluorescence were used to analyze the level of tyrosine hydroxylase in SNpc and striatum as well as the expression of GFAP, Iba-1, NF-κB/p-65 in the L4-L6 spinal cord dorsal horn. Unilateral 6-OHDA-lesion reduces motor capacity and produces long-term allodynia and hyperalgesia in both hind paws. L4-L6 spinal cord dorsal horn astrocytes and microglia were active in these 6-OHDA-lesioned rats. Moreover, PPX (1 and 3mg/Kg, i.p./10days, n=10 per group) inhibited the bilateral mechanical hypersensitivity, and PPX (3mg/Kg/i.p./10days) reduced 6-OHDA-induced astrocyte and microglia activation, as well as reduced NF-κB/p-p65 expression only in astrocytes of dorsal horn spinal cord in the L5-L6. These findings suggest that PPX could alleviate pain by decreasing the activation of microglia and astrocytes through the NF-κB/p-p65 pathway in the dorsal horn spinal cord. Therefore, PPX could be considered an optional tool for improving pain hypersensitivity in PD patients.

Real-world (RW) experience with atezolizumab + bevacizumab (A+B) for the treatment of unresectable HCC (uHCC): A multicenter study.

537 Background: A+B is the preferred first-line (1L) standard of care for uHCC, with emerging RW evidence supporting its use in a broad patient (pt) cohort. We evaluated pt characteristics, clinical and treatment outcomes in pts treated at five U.S. institutions: Mayo Clinic, Houston Methodist, Moffitt Cancer Center, Mays Cancer Center, and University of Arizona. Methods: This is a retrospective study of uHCC pts who initiated A+B after January 1, 2019. De-identified pt data were extracted by treating oncologists. Overall survival (OS) and real-world progression-free survival (rwPFS) were assessed using Kaplan-Meier methods for all pts and for a “trial-like” subgroup with characteristics similar to those in the IMbrave150 trial (ECOG performance status [PS] 0-1, Child-Pugh [CP] class A, albumin-bilirubin [ALBI] grade 1-2). HCC-related hospitalizations were evaluated within 1 year of A+B initiation. Results: A total of 300 eligible pts were treated with 1L A+B (median age 68 years, 79% male, 79% White, 82% BCLC C, 44% viral etiology,12% ECOG PS &gt;1). Liver function was CP A in 73% (36% A5, 31% A6, 6% not reported), CP B in 26% pts (15% B7, 7% B8, 5% B9), and CP C in 2 (&lt;1%) pts. Compared with CP A, more CP B pts had characteristics of compromised liver function (CP A vs B: cirrhosis: 61% vs 91%; ascites: 7% vs 46%; encephalopathy: 4% vs 17%; esophageal varices: 14% vs 32%), bile duct invasion (2% vs 11%), and ECOG PS&gt;1 (8% vs 22%), all Ps&lt;0.001. Over a median follow-up of 8.7 mos, 244 (81%) pts discontinued A+B, primarily due to disease progression. Toxicity-related treatment discontinuation and hospitalizations due to treatment-related adverse events (TRAE) were similar between the two groups (Table). Median OS (mOS) was 14.4 mos (95% CI: 12.3, 18.2) and median rwPFS was 6.8 mos (95% CI: 5.8, 8.4). In the trial-like subgroup (n=194), mOS was 19.5 mos (95%CI: 14.6, 24.7) and median rwPFS was 8.8 mos (95% CI: 7.6, 12.1). In the CP B subgroup, mOS was 5.6 mos (95% CI: 4.6, 11.3) and median rwPFS was 3.1 mos (95% CI: 2.4, 5.8). Conclusions: This study demonstrates the RW outcomes of 1L A+B in a diverse pt cohort. Results from the “trial-like” pts further confirm the reproducible efficacy of A+B in clinical practice. Although pts with CP-B had higher hospitalization rates due to disease progression or symptoms, consistent with their underlying liver complications, they had similar rates of toxicity-related treatment discontinuation and TRAE-related hospitalizations compared to CP-A. Further characterization of safety for A+B in CP B pts within a prospective, controlled trial is warranted. N (%) CP A (n=219) CP B (n=79) Treatment discontinuation* 167 (76) 75 (95) Atezolizumab-related toxicity 20 (12) 13 (17) Bevacizumab-related toxicity 26 (16) 16 (21) Hospitalization* 87 (40) 58 (73) Symptom-related 42 (48) 35 (60) Progression 8 (9) 11 (19) TRAE 7 (8) 6 (10) *P-value comparing CP A vs CP B &lt;0.001.