-
Biological Psychiatry Apr 2024Responding to social signals by expressing the correct behavior is not only challenged in autism, but also in diseases with high prevalence of autism, like Prader-Willi...
Disengagement of somatostatin neurons from lateral septum circuitry by oxytocin and vasopressin restores social-fear extinction and suppresses aggression outbursts in Prader-Willi syndrome model.
BACKGROUND
Responding to social signals by expressing the correct behavior is not only challenged in autism, but also in diseases with high prevalence of autism, like Prader-Willi Syndrome (PWS). Clinical evidence suggests aberrant pro-social behavior in patients can be regulated by intranasal oxytocin (OXT) or vasopressin (AVP). However, what neuronal mechanisms underlie impaired behavioral responses in a socially-aversive context, and how can they be corrected, remains largely unknown.
METHODS
Using the knocked-out (KO) mouse model of PWS (crossed with CRE-dependent transgenic lines), we devised optogenetic, physiological and pharmacological strategies in a social-fear-conditioning paradigm. Pathway specific roles of OXT and AVP signaling were investigated converging on the lateral septum (LS), a region which receives dense hypothalamic inputs.
RESULTS
OXT and AVP signaling promoted inhibitory synaptic transmission in the LS, which failure in KO mice disinhibited somatostatin (SST) neurons and disrupted social-fear extinction. The source of OXT and AVP deficits mapped specifically in the supraoptic nucleus→LS pathway of KO mice disrupting social-fear extinction, which could be corrected by optogenetic or pharmacological inhibition of SST-neurons in the LS. Interestingly, LS SST-neurons also gated the expression of aggressive behavior, possibly as part of functional units operating beyond local septal circuits.
CONCLUSIONS
SST cells in the LS play a crucial role in integration and expression of disrupted neuropeptide signals in autism, thereby altering the balance in expression of safety versus fear. Our results uncover novel mechanisms underlying dysfunction in a socially-aversive context, and provides a new framework for future treatments in autism-spectrum disorders.
Topics: Animals; Oxytocin; Somatostatin; Fear; Extinction, Psychological; Neurons; Mice; Prader-Willi Syndrome; Mice, Knockout; Disease Models, Animal; Vasopressins; Aggression; Male; Social Behavior; Septal Nuclei; Optogenetics; Mice, Inbred C57BL; Intracellular Signaling Peptides and Proteins; Intrinsically Disordered Proteins
PubMed: 38952926
DOI: 10.1016/j.biopsych.2023.10.016 -
Nigerian Medical Journal : Journal of... 2023Alcohol plays a significant role in road traffic accidents in Ghana. However, little is known about the perspectives of victims who suffer road traffic accidents, RTAs,...
BACKGROUND
Alcohol plays a significant role in road traffic accidents in Ghana. However, little is known about the perspectives of victims who suffer road traffic accidents, RTAs, and the extent to which alcohol use disorder is involved.
METHODOLOGY
We conducted a three-month cross-sectional study in a teaching hospital involving 102 patients involved in a road accident and presented to the hospital's emergency. The Alcohol Use Disorder Identification Test, AUDIT, was used to assess for Alcohol Use Disorder, AUD, at a score of 8. In addition, we used open-ended questionnaires to assess their perception of alcohol use and road accidents.
RESULTS
Of the 102 respondents, 75% were males, and 60% were between 15 and 35 years old. About 69% of respondents admitted to using alcohol, while 31%, including a single female, screened positive for alcohol use disorder. A significant majority of about 90% of respondents believed in some myths of alcohol use in Ghana, and a similar percentage were aware of the risks alcohol use posed to road use. Over 30% of respondents, mainly drivers or riders, had used alcohol within 12 hours of the accident. All but three respondents knew alcohol-induced aggression and poor coordination of movements. A similar number of respondents knew alcohol made people cross roads carelessly and were hyperactive or disinhibited.
CONCLUSION
Alcohol use and alcohol use disorder are significantly high among persons presenting with RTA to the emergency. Knowledge of the deleterious effects of alcohol is high, yet their behavior did not reflect the knowledge. Therefore, a significant reduction in RTA can be achieved by enforcing blood alcohol concentration limits for road users and intensive education to the populace.
PubMed: 38952875
DOI: 10.60787/NMJ-64-4-324 -
Behavioral Ecology : Official Journal... 2024It is well known that maternal age at reproduction affects offspring lifespan and some other fitness-related traits, but it remains understudied whether maternal...
It is well known that maternal age at reproduction affects offspring lifespan and some other fitness-related traits, but it remains understudied whether maternal senescence affects how offspring respond to their environments. Early environment often plays a significant role in the development of an animal's behavioral phenotype. For example, complex environments can promote changes in cognitive ability and brain morphology in young animals. Here, we study whether and how maternal effect senescence influences offspring plasticity in cognition, group behavior, and brain morphology in response to environmental complexity. For this, juvenile 3-spined sticklebacks from young and old mothers (i.e. 1-yr and 2-yr-old) were exposed to different levels of environmental enrichment and complexity (i.e. none, simple, and complex), and their behavior, cognitive ability, and brain size were measured. Exposing fish to enriched conditions improved individual learning ability assessed by a repeated detour-reaching task, increased the size of the whole brain, and decreased aggressive interactions in the shoal. Maternal age did not influence the inhibitory control, learning ability, and group behavioral responses of offspring to the experimental environmental change. However, maternal age affected how some brain regions of offspring changed in response to environmental complexity. In offspring from old mothers, those exposed to the complex environment had larger telencephalons and cerebellums than those who experienced simpler environments. Our results suggest that maternal effect senescence may influence how offspring invest in brain functions related to cognition in response to environmental complexity.
PubMed: 38952837
DOI: 10.1093/beheco/arae049 -
Frontiers in Psychology 2024The purpose of this study was to analyze the relationships between cybervictimization in social networks, problematic smartphone use, aggressive behaviors, and prosocial...
The purpose of this study was to analyze the relationships between cybervictimization in social networks, problematic smartphone use, aggressive behaviors, and prosocial altruistic tendencies in young adults. The sample consisted of 601 young adults (mean age = 19.96 years; SD = 2.27; 69.1% female) who were administered online assessments of experiences of humiliation on networks, problematic smartphone use, prosocial altruistic tendencies, and aggressiveness. Results indicated significant indirect effects of cyber victimization on aggressiveness and prosocial altruistic tendencies through problematic smartphone use. Problematic cell phone use explained the relationships between online humiliation and aggressive and prosocial altruistic behaviors. The results confirmed the positive relationship between cybervictimization and problematic cell phone use, consistent with previous research. However, the negative relationship between cybervictimization and altruistic prosocial tendencies was not corroborated. The findings emphasize the need to promote actions that foster social connectedness and interdependence among young individuals to develop their identity within the community.
PubMed: 38952829
DOI: 10.3389/fpsyg.2024.1368336 -
Respirology Case Reports Jul 2024Primary pulmonary choriocarcinoma is a highly aggressive germ cell neoplasm and an extremely rare, especially in males. It is characterized by a poor response to therapy...
Primary pulmonary choriocarcinoma is a highly aggressive germ cell neoplasm and an extremely rare, especially in males. It is characterized by a poor response to therapy and shortened survival times. We present the case of primary pulmonary choriocarcinoma in a 46-year-old male. The patient was referred to our institute with cough, worsening dyspnea and hemoptysis. The contrast-enhanced chest computed tomography revealed an avid enhanced 15 × 14 cm sized nodular lesion, in the left lower lung, which invaded into the diaphragm. After the embolization of the intercostal arteries, the tumour was resected successfully. However, the patient had died suddenly on the 28th day after the surgery. Autopsy was conducted and revealed that his cause of the death was the tumour emboli in the right coronary artery.
PubMed: 38952741
DOI: 10.1002/rcr2.1400 -
Mechanical characterization of porcine ureter for the evaluation of tissue-engineering applications.Frontiers in Bioengineering and... 2024Clinics increasingly require readily deployable tubular substitutes to restore the functionality of structures like ureters and blood vessels. Despite extensive...
Clinics increasingly require readily deployable tubular substitutes to restore the functionality of structures like ureters and blood vessels. Despite extensive exploration of various materials, both synthetic and biological, the optimal solution remains elusive. Drawing on abundant literature experiences, there is a pressing demand for a substitute that not only emulates native tissue by providing requisite signals and growth factors but also exhibits appropriate mechanical resilience and behaviour. This study aims to assess the potential of porcine ureters by characterizing their biomechanical properties in their native configuration through ring and membrane flexion tests. In order to assess the tissue morphology before and after mechanical tests and the eventual alteration of tissue microstructure that would be inserted in material constitutive description, histological staining was performed on samples. Corresponding computational analyses were performed to mimic the experimental campaign to identify the constitutive material parameters. The absence of any damages to muscle and collagen fibres, which only compacted after mechanical tests, was demonstrated. The experimental tests (ring and membrane flexion tests) showed non-linearity for material and geometry and the viscoelastic behaviour of the native porcine ureter. Computational models were descriptive of the mechanical behaviour ureteral tissue, and the material model feasible. This analysis will be useful for future comparison with decellularized tissue for the evaluation of the aggression of cell removal and its effect on microstructure. The computational model could lay the basis for a reliable tool for the prediction of solicitation in the case of tubular substitutions in subsequent simulations.
PubMed: 38952671
DOI: 10.3389/fbioe.2024.1412136 -
Frontiers in Bioengineering and... 2024Triple negative breast cancer (TNBC), a highly aggressive subtype accounting for 15-20% of all breast cancer cases, faces limited treatment options often accompanied by...
Triple negative breast cancer (TNBC), a highly aggressive subtype accounting for 15-20% of all breast cancer cases, faces limited treatment options often accompanied by severe side effects. In recent years, natural extracellular nanovesicles derived from plants have emerged as promising candidates for cancer therapy, given their safety profile marked by non-immunogenicity and absence of inflammatory responses. Nevertheless, the potential anti-cancer effects of .-derived extracellular nanovesicles (CLENs) for breast cancer treatment is still unexplored. In this study, we investigated the anti-cancer effects of CLENs on two TNBC cell lines (4T1 and HCC-1806 cells) under growth conditions in 2D and 3D culture environments. The cellular uptake efficiency of CLENs and their internalization mechanism were evaluated in both cells using confocal microscopy. Thereafter, we assessed the effect of different concentrations of CLENs on cell viability over time using a dual approach of Calcein-AM PI live-dead assay and CellTiter-Glo bioluminescence assay. We also examined the influence of CLENs on the migratory and evasion abilities of TNBC cells through wound healing and 3D Matrigel drop evasion assays. Furthermore, Western blot analysis was employed to investigate the effects of CLENs on the phosphorylation levels of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and extracellular signal- regulated kinase (ERK) expression. We found that CLENs were internalized by the cells via endocytosis, leading to decreased cell viability, in a dose- and time-dependent manner. Additionally, the migration and evasion abilities of TNBC cells were significantly inhibited under exposed to 40 and 80 μg/mL CLENs. Furthermore, down-regulated expression levels of phosphorylated phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK), suggesting that the inhibition of cancer cell proliferation, migration, and evasion is driven by the inhibition of the PI3K/AKT and MAPK/ERK signaling pathways. Overall, our results demonstrate the anti-tumor efficiency of CLENs against TNBC cells, highlighting their potential as promising natural anti-cancer agents for clinical applications in cancer treatment.
PubMed: 38952670
DOI: 10.3389/fbioe.2024.1390708 -
Pakistan Journal of Medical Sciences Jul 2024Approximately 3% to 4% of all newly diagnosed cancers are kidney tumours, which can develop from either the renal parenchymal tissue or the renal pelvis. Kidney cancer...
UNLABELLED
Approximately 3% to 4% of all newly diagnosed cancers are kidney tumours, which can develop from either the renal parenchymal tissue or the renal pelvis. Kidney cancer is one of the 13 most prevalent kinds of malignancy worldwide. 85% of all malignant kidney neoplasms are renal cell carcinomas (RCC). We present a rare instance of an RCC that had a thrombus in the ureter and had directly extended into the renal pelvicalyceal system. A thorough diagnostic workup was required because the patient had a number of symptoms, including flank pain, hematuria, and weight loss. Imaging tests identified a renal parenchymal-derived infiltrative tumour with remarkable pelvicalyceal penetration. Neovascularization was found within the tumour as a result of additional search. The discovery of ureteral extension, a peculiar characteristic, raised questions regarding both local and distant metastases. R.E.N.A.L nephrometry score was 11 with high complexity. Multidisciplinary management of the intricate clinical problem was employed. After removing the tumour mass, the ureteral involvement was treated with surgical resection, adjuvant therapy, and CT monitoring over the three-month high-risk follow-up period. With surgery, targeted treatment was employed to stop the cancer from growing.
CONCLUSION
The importance of identifying unusual RCC presentations and employing a comprehensive diagnostic and treatment strategy is emphasised by this study. The complex interaction of ureteral extension, neovascularization, and pelvicalyceal penetration highlights the aggressiveness of advanced RCC. Since we are not aware of any literature documented instances including this combination, there are few studies explaining pelvicalyceal system invasion that defies commonly recognised diagnostic and treatment paradigms for renal cell carcinoma.
PubMed: 38952497
DOI: 10.12669/pjms.40.6.8715 -
Cancer Management and Research 2024Low-grade gliomas (LGG) are common brain tumors with high mortality rates. Cancer cell invasion is a significant factor in tumor metastasis. Novel biomarkers are...
PURPOSE
Low-grade gliomas (LGG) are common brain tumors with high mortality rates. Cancer cell invasion is a significant factor in tumor metastasis. Novel biomarkers are urgently needed to predict LGG prognosis effectively.
METHODS
The data for LGG were obtained from the Bioinformatics database. A consensus clustering analysis was performed to identify molecular subtypes linked with invasion in LGG. Differential expression analysis was performed to identify differentially expressed genes (DEGs) between the identified clusters. Enrichment analyses were then conducted to explore the function for DEGs. Prognostic signatures were placed, and their predictive power was assessed. Furthermore, the invasion-related prognostic signature was validated using the CGGA dataset. Subsequently, clinical specimens were procured in order to validate the expression levels of the distinct genes examined in this research, and to further explore the impact of these genes on the glioma cell line LN229 and HS-683.
RESULTS
Two invasion-related molecular subtypes of LGG were identified, and we sifted 163 DEGs between them. The enrichment analyses indicated that DEGs are mainly related to pattern specification process. Subsequently, 10 signature genes (, and ) were sifted out to construct a risk model. Besides, the survival (OS) in the high-risk group was lower. The performance of the risk model was verified. Furthermore, a highly reliable nomogram was generated. Cellular experiments revealed the ability to promote cell viability, value-addedness, migratory ability, invasive ability, and colony-forming ability of the glioma cell line LN229 and HS-683. The qRT-PCR analysis of clinical glioma samples showed that these 10 genes were expressed at higher levels in high-grade gliomas than in low-grade gliomas, suggesting that these genes are associated with poor prognosis of gliomas.
CONCLUSION
Our study sifted out ten invasion-related biomarkers of LGG, providing a reference for treatments and prognostic prediction in LGG.
PubMed: 38952353
DOI: 10.2147/CMAR.S463694 -
Archives of Pathology & Laboratory... Jul 2024Mesothelioma subtyping into epithelioid and nonepithelioid categories plays a crucial role in prognosis and treatment selection, with emerging recognition of the impact...
CONTEXT.—
Mesothelioma subtyping into epithelioid and nonepithelioid categories plays a crucial role in prognosis and treatment selection, with emerging recognition of the impact of various histologic patterns.
OBJECTIVE.—
To investigate the prognostic implications of transitional and pleomorphic patterns in sarcomatoid mesothelioma.
DESIGN.—
A total of 132 mesothelioma cases (87 biphasic, 45 sarcomatoid) were analyzed. Histologic slides were assessed, treatment data collected, and cases categorized into predominant epithelioid or sarcomatoid patterns. The sarcomatoid mesotheliomas were classified into usual, pleomorphic, and transitional patterns, with reticulin staining for the latter. Statistical analysis included Cox regression and Kaplan-Meier methods.
RESULTS.—
Younger age (P = .02) and receiving therapy (P < .001) correlated with improved survival for both histotypes. Advanced stage was associated with shorter survival in sarcomatoid cases (P = .02). Predominant epithelioid pattern in biphasic cases led to longer survival (P < .001). Transitional and pleomorphic patterns were indicative of worse prognosis, with significantly lower survival in cases with both patterns than with usual sarcomatoid (P = .046). Multivariate analysis identified independent survival factors, including predominant epithelioid component in biphasic mesothelioma (P = .001) and chemotherapy (P < .001).
CONCLUSIONS.—
Histologic subtyping in mesothelioma plays a pivotal role in prognosis. Transitional and pleomorphic patterns, even in low percentages, indicate poorer outcomes. This study highlights the need for standardized diagnostic support and suggests the potential utility of histochemical staining in identifying more aggressive morphologic aspects. Recognizing the significance of these patterns can guide treatment decisions and patient care strategies.
PubMed: 38952294
DOI: 10.5858/arpa.2023-0523-OA