Nevin Manimala

Arch Pharm Res. 2024 Feb 28. doi: 10.1007/s12272-024-01486-1. Online ahead of print.

ABSTRACT

Gymnopilus orientispectabilis, also known as “big laughter mushroom,” is a hallucinogenic poisonous mushroom that causes excessive laughter upon ingestion. From the fruiting bodies of G. orientispectabilis, eight lanostane-type triterpenoids (1-8), including seven novel compounds: gymnojunols A-G (2-8), were isolated. The chemical structures of these new compounds (2-8) were determined by analyzing their 1D and 2D NMR spectra and HR-EISMS, and their absolute configurations were unambiguously assigned by quantum chemical ECD calculations and a computational method coupled with a statistical procedure (DP4+). Upon evaluating autophagic activity, compounds 2, 6, and 7 increased LC3B-II levels in HeLa cells to a similar extent as bafilomycin, an autophagy inhibitor. In contrast, compound 8 decreased the levels of both LC3B-I and LC3B-II, and a similar effect was observed following treatment with rapamycin, an autophagy inducer. Our findings provide experimental evidence for new potential autophagy modulators in the hallucinogenic poisonous mushroom G. orientispectabilis.

PMID:38416389 | DOI:10.1007/s12272-024-01486-1

Target Oncol. 2024 Feb 28. doi: 10.1007/s11523-024-01037-0. Online ahead of print.

ABSTRACT

BACKGROUND: Despite improvement in progression-free survival (PFS) with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) as maintenance treatment for patients with epithelial ovarian cancer (EOC), a comparative analysis of clinical events of interest (CEIs) of different PARPi is scarce.

OBJECTIVE: This study aimed to compare the safety of different PARPi in patients with EOC.

PATIENTS AND METHODS: Through analyzing the Korean National Health Insurance Service from January 2009 to January 2022, this study involved BRCA-mutated, platinum-sensitive patients with EOC treated with olaparib (tablet), niraparib, and olaparib (capsule) as first-line or second-line maintenance treatment. CEIs were identified using International Statistical Classification of Diseases (ICD) 9/10 codes, with additional outcomes being dose modification and persistence.

RESULTS: In the first-line maintenance treatment [118 niraparib, 104 olaparib (tablet) patients], no significant differences were noted in CEIs, dose reduction, or 6-month discontinuation rate. For second-line maintenance treatment [303 niraparib, 126 olaparib (tablet), and 675 olaparib (capsule) patients], niraparib was associated with a higher risk of hematologic CEIs, particularly anemia, compared with olaparib (tablet) (0.51 [0.26-0.98] and 0.09 [0.01-0.74], respectively), and higher rate of discontinuation rate at 6 months. Of note, patients over 60 years old showed an increased risk of CEIs with niraparib, as indicated by the hazard ratio divergence in restricted cubic spline plots.

CONCLUSIONS: No differences were observed among the PARPi during first-line maintenance treatment. However, in the second-line maintenance treatment, significant differences were observed in the risk of experiencing CEIs, dose alteration possibilities, and discontinuation of PARPi between niraparib and olaparib (tablets). Moreover, our findings suggest that an age of 60 years may be a critical factor in selecting PARPi to reduce CEI incidence.

PMID:38416378 | DOI:10.1007/s11523-024-01037-0

Phys Eng Sci Med. 2024 Feb 28. doi: 10.1007/s13246-024-01394-0. Online ahead of print.

ABSTRACT

The brain biomarker of irritable bowel syndrome (IBS) patients is still lacking. The study aims to explore a new technology studying the brain alterations of IBS patients based on multi-source brain data. In the study, a decision-level fusion method based on gradient boosting decision tree (GBDT) was proposed. Next, 100 healthy subjects were used to validate the effectiveness of the method. Finally, the identification of brain alterations and the pain evaluation in IBS patients were carried out by the fusion method based on the resting-state fMRI and DWI for 46 patients and 46 controls selected randomly from 100 healthy subjects. The results showed that the method can achieve good classification between IBS patients and controls (accuracy = 95%) and pain evaluation of IBS patients (mean absolute error = 0.1977). Moreover, both the gain-based and the permutation-based evaluation instead of statistical analysis showed that left cingulum bundle contributed most significantly to the classification, and right precuneus contributed most significantly to the evaluation of abdominal pain intensity in the IBS patients. The differences seem to suggest a probable but unexplored separation about the central regions between the identification and progression of IBS. This finding may provide one new thought and technology for brain alteration related to IBS.

PMID:38416373 | DOI:10.1007/s13246-024-01394-0

J Endocrinol Invest. 2024 Feb 28. doi: 10.1007/s40618-024-02340-3. Online ahead of print.

ABSTRACT

PURPOSE: In acromegaly, skeletal complications resulted to be associated with low quality of life (QoL) and high risk of falls. The aim of the present study was to perform a quantitative assessment of movement through gait analysis technique in patients with acromegaly.

STUDY POPULATION: Thirty-three acromegalic patients [9 with active disease (AD), 14 with controlled disease (CD) and 10 with disease remission (RD)] and 20 healthy subjects were enrolled for the study.

MEASUREMENTS: Kinetic and kinematic data were collected with 3D-gait analysis. Kinematic data were processed to compute the Gait Profile Score (GPS), a parameter that summarizes the overall deviation of kinematic gait data relative to unaffected population.

RESULTS: The acromegalic group showed longer stance phase duration (p < 0.0001) compared to controls. The GPS and several gait variable scores resulted to be statistically higher in the acromegalic group compared to healthy controls. GPS values were significantly higher in AD compared to CD (p < 0.05) and RD groups (p = 0.001). The AD group presented significantly higher values in terms of hip rotation and ankle dorsiflexion compared to CD and RD groups and with regard to the foot progression compared to RD. Interestingly, patients with RD exhibited a more physiological gait pattern.

CONCLUSION: Acromegalic patients showed quantitative alterations of gait pattern, suggesting instability and increased risk of falls. Arthropathy, along with its associated abnormal joint loading, proprioceptive impairment and hyperkyphosis could be contributing factors. Disease control and remission appear to improve postural balance. A better knowledge on walking performance in acromegaly would help to develop specific rehabilitation programmes to reduce falls’ risk and improve QoL.

PMID:38416368 | DOI:10.1007/s40618-024-02340-3

Indian J Gastroenterol. 2024 Feb 28. doi: 10.1007/s12664-023-01495-w. Online ahead of print.

ABSTRACT

BACKGROUND: Gastric cancer (GC) is associated with a significant global health burden and high mortality rates when diagnosed at later stages. The diagnosis often occurs at advanced stages when treatment options are limited and less effective. Early detection strategies are crucial to improving survival rates and outcomes for patients. Blue laser imaging (BLI) is an image-enhanced endoscopy technique that utilizes white light and narrow-band light to detect pathological changes in the mucosal architecture. This study aims at investigating the diagnostic performance of BLI for the detection of GC.

METHODS: A comprehensive search was conducted across multiple databases from inception until March 2023. Studies assessing the diagnostic efficacy of BLI for GC detection were included. The sensitivity, specificity and accuracy of BLI were calculated using pooled proportions and 95% confidence intervals (CI) with a random-effects model. Heterogeneity among the included studies was assessed using the I² statistic.

RESULTS: Six studies were included in the pooled analysis. There were 708 patients with 380 GC lesions. Most of the lesions involved the lower two-thirds of the stomach. The pooled performance metrics of BLI for GC detection were as follows: sensitivity of 91.9% (95% CI 83.3-96.3%; I² = 82.3%), specificity of 93.4% (95% CI 82.0-97.8%; I² = 87.9%) and accuracy of 95.4% (95% CI 72.6-99.8%; I² = 73.6%).

CONCLUSION: BLI demonstrates high diagnostic efficacy for the detection of GC. BLI can be a valuable tool in clinical practice. However, large-scale, randomized controlled studies are needed to further establish the role of BLI in routine clinical practice for GC detection.

PMID:38416344 | DOI:10.1007/s12664-023-01495-w

Acta Parasitol. 2024 Feb 28. doi: 10.1007/s11686-024-00802-5. Online ahead of print.

ABSTRACT

PURPOSE: The Government of Indonesia committed to eliminating schistosomiasis by 2025. Collaboratively snail control became one of the crucial strategies to ensure that the prevalence of Schistosoma japonicum in Oncomelania hupensis lindoensis reaches zero by the end of the program. This research investigated the spatial cluster change of S. japonicum transmission foci in Indonesia between 2017 and 2021.

METHODS: We mapped the snail foci, collected the snails, and calculated the snail density. We also conducted laboratory tests to detect the existence of cercariae in the snails. Identified infected snails were used to calculate the infection rate (IR) or snails’ prevalence of schistosome cercariae among freshwater snails. We then analysed the spatial cluster using the Getis-Ord Gi* statistic to identify the hot and cold spots.

RESULTS: The 5-year schistosomiasis elimination program successfully declined 18.84% of the snail foci and reduced 40.37% of the infected snail foci. Local spatial autocorrelation of snail density and infection rate identified that in 2017 and 2021, the number of cold spots decreased by 53.91% and 0%, while hot spots increased by 2.63% and 56.1%. The presence of more hot spots suggests a rise in the number of foci with high snail density and infection rates. The implementation of snail control was not optimal, and the parasite transmission through domestic animals still existed, causing the spatial cluster of hot spots to change during this period. Most hotspots have been observed near settlements, primarily in cocoa plantations, developed and deserted rice fields, grassland, and bush wetlands.

CONCLUSION: During the schistosomiasis elimination program, the number of hot spots increased while cold spots decreased, and there were notable changes in the geographical distribution of hot spots, indicating a shift in the clustering pattern of schistosomiasis cases. The findings become essential for policymakers, particularly in selecting priority areas for intervention. In the Discussion section, we demonstrated the selection process based on the existence of hot and cold spots. Furthermore, we proposed that enhancing cross-sector integration is crucial, particularly in connection with the management of S. japonicum transmission through domestic animals.

PMID:38416327 | DOI:10.1007/s11686-024-00802-5

J Prev (2022). 2024 Feb 28. doi: 10.1007/s10935-024-00772-4. Online ahead of print.

ABSTRACT

Gambling risk behaviour is an emerging problem among adolescents. “Unplugged” is an effective Social Influence curriculum for preventing substance use among students. This study aims to develop and test a new component focused on gambling added to the Unplugged program. Schools of Piedmont region and Rome city were invited to participate in the study. A self-completed anonymous questionnaire including questions on socio-demographic characteristics, addictive behaviours, beliefs, attitudes and risk perceptions about gambling, normative perceptions, parental practices, school climate, refusal skills, impulsiveness, self-esteem, antisocial behaviours and sensation seeking was prepared for baseline and follow-up surveys. The protocol of the study was submitted and approved by the Novara Ethical Committee and registered in ClinicalTrials.gov (NCT05630157, Protocol ID: 080.742, 11/17/2022). Twenty-nine schools accepted to participate in the study. Sixty-three classes (1325 students) satisfied the eligibility criteria for intervention and were allocated to the intervention arm, and the other 61 (1269 students) were allocated to the control arm. Because of drop-out, absentees, refusals, and invalid questionnaires, data on 1874 students (998 in the intervention and 876 in the control arm), were available for the analysis at baseline. Data management of follow-up questionnaires is in progress. Results of the present study will be useful to clarify the effectiveness of prevention interventions in reducing gambling behaviours among adolescents. Moreover, this will be the first experience of evaluating a new component focused on a different risk behaviour, added to a curriculum previously shown as effective on other risk behaviours.

PMID:38416313 | DOI:10.1007/s10935-024-00772-4

Curr Neurol Neurosci Rep. 2024 Feb 28. doi: 10.1007/s11910-024-01335-0. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: This review summarizes previous and ongoing neuroprotection trials in multiple system atrophy (MSA), a rare and fatal neurodegenerative disease characterized by parkinsonism, cerebellar, and autonomic dysfunction. It also describes the preclinical therapeutic pipeline and provides some considerations relevant to successfully conducting clinical trials in MSA, i.e., diagnosis, endpoints, and trial design.

RECENT FINDINGS: Over 30 compounds have been tested in clinical trials in MSA. While this illustrates a strong treatment pipeline, only two have reached their primary endpoint. Ongoing clinical trials primarily focus on targeting α-synuclein, the neuropathological hallmark of MSA being α-synuclein-bearing glial cytoplasmic inclusions. The mostly negative trial outcomes highlight the importance of better understanding underlying disease mechanisms and improving preclinical models. Together with efforts to refine clinical measurement tools, innovative statistical methods, and developments in biomarker research, this will enhance the design of future neuroprotection trials in MSA and the likelihood of positive outcomes.

PMID:38416311 | DOI:10.1007/s11910-024-01335-0

Brain Topogr. 2024 Feb 28. doi: 10.1007/s10548-024-01038-2. Online ahead of print.

ABSTRACT

Over the past years, different studies provided preliminary evidence that Disorganized Attachment (DA) may have dysregulatory and disintegrative effects on both autonomic arousal regulation and brain connectivity. However, despite the clinical relevance of this construct, few studies have investigated the specific alterations underlying DA using electroencephalography (EEG). Thus, the main aim of the current study was to investigate EEG microstate parameters of DA in a non-clinical sample (N = 50) before (pre) and after (post) the administration of the Adult Attachment Interview (AAI). Two EEG eyes-closed Resting State (RS) recordings were performed before and after the AAI, which was used for classifying the participants [i.e., Disorganized/Unresolved (D/U) or Organized/Resolved (O/R) individuals] and to trigger the attachment system. Microstates parameters (i.e., Mean Duration, Time Coverage and Occurrence) were extracted from each recording using Cartool software. EEG microstates clustering analysis revealed 6 different maps (labeled A, B, C, D, E, F) in both groups (i.e., D/U and O/R individuals) and in both conditions (i.e., pre-AAI and post-AAI). In the pre-AAI condition, compared to O/R individuals, D/U participants showed a shorter Mean Duration and Time Coverage of Map F; in the post-AAI condition, a significant reduction in the Mean Duration of Map E was also observed in D/U individuals. Finally, in the “within” statistical analysis (i.e., pre-AAI vs. post-AAI), only the D/U group exhibited a significant increase in Time Coverage of Map F after the AAI. Since these maps are associated with brain networks involved in emotional information processing and mentalization (i.e., Salience Network and Default Mode Network), our result might reflect the deficit in the ability to mentalize caregiver’s interaction as well as the increased sensitivity to attachment-related stimuli typically observed in individuals with a D/U state of mind.

PMID:38416284 | DOI:10.1007/s10548-024-01038-2

Environ Monit Assess. 2024 Feb 28;196(3):315. doi: 10.1007/s10661-024-12459-8.

ABSTRACT

The estimation of exposures to humans from the various sources of radiation is important. Radiation hazard indices are computed using procedures described in the literature for evaluating the combined effects of the activity concentrations of primordial radionuclides, namely, ²³⁸U, ²³²Th, and ⁴⁰ K. The computed indices are then compared to the allowed limits defined by International Radiation Protection Organizations to determine any radiation hazard associated with the geological materials. In this paper, four distinct radial basis function artificial neural network (RBF-ANN) models were developed to predict radiation hazard indices, namely, external gamma dose rates, annual effective dose, radium equivalent activity, and external hazard index. To make RBF-ANN models, 348 different geological materials’ gamma spectrometry data were acquired from the literature. Radiation hazards indices predicted from each RBF-ANN model were compared to the radiation hazards calculated using gamma spectrum analysis. The predicted hazard indices values of each RBF-ANN model were found to precisely align with the calculated values. To validate the accuracy and the adaptability of each RBF-ANN model, statistical tests (determination coefficient (R²), relative absolute error (RAE), root mean square error (RMSE), Nash-Sutcliffe Efficiency (NSE)), and significance tests (F-test and Student’s t-test) were performed to analyze the relationship between calculated and predicted hazard indices. Low RAE and RMSE values as well as high R², NSE, and p-values greater than 0.95, 0.71, and 0.05, respectively, were found for RBF-ANN models. The statistical tests’ results show that all RBF-ANN models created exhibit precise performance, indicating their applicability and efficiency in forecasting the radiation hazard indices of geological materials. All the RBF-ANN models can be used to predict radiation hazard indices of geological materials quite efficiently, according to the performance level attained.

PMID:38416264 | DOI:10.1007/s10661-024-12459-8