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BMC Psychiatry Jun 2024Children and adolescents, after natural and man-made disasters, often exhibit various psychological, emotional, and behavioral issues, showing a range of clinical...
INTRODUCTION
Children and adolescents, after natural and man-made disasters, often exhibit various psychological, emotional, and behavioral issues, showing a range of clinical symptoms related to post-traumatic stress disorder (PTSD) and depression. This review used a network meta-analysis (NMA) approach to compare and rank psychological interventions for PTSD and depression in children and adolescents after exposure to natural and man-made disasters.
METHODS
Randomized studies of psychosocial interventions for PTSD and depression in children and adolescents exposed to natural and man-made disasters were identified. PTSD and depression symptoms at postintervention and 1-12 month follow-up are the outcomes. The standardized mean differences (SMDs) between pairs of interventions at postintervention and follow-up were pooled. Mean effect sizes with 95% credible intervals (CI) were calculated, and the ranking probabilities for all interventions were estimated using the surface under the cumulative ranking curve. Study quality was assessed with version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2).
RESULTS
In total, 26 studies with 4331 participants were included in this NMA. Eye movement desensitization and reprocessing therapy (EMDR) (SMD = - 0.67; 95% CI - 1.17 to - 0.17), exposure therapy (ET) (SMD = - 0.66; 95% CI - 1.11 to - 0.22), and cognitive behavioral therapy (CBT) (SMD = - 0.62; 95% CI - 0.90 to - 0.34) were significantly more effective for PTSD at postintervention than inactive intervention. EMDR (SMD = - 0.72; 95% CI - 1.11 to - 0.33) and ET (SMD = - 0.62; 95% CI - 0.97 to - 0.27) were associated with a higher reduction in PTSD symptoms at follow-up than inactive intervention. EMDR (SMD = - 0.40; 95% CI - 0.78 to - 0.03) and play therapy (PT) (SMD = - 0.37; 95% CI - 0.62 to - 0.12) were significantly more effective for depression at postintervention than inactive intervention. For all psychological interventions in reducing depression symptoms at follow-up compared with inactive intervention, the differences were not significant.
CONCLUSION
EMDR appears to be most effective in reducing PTSD and depression in children and adolescents exposed to natural and man-made disasters. In addition, ET and CBT are potentially effective in reducing PTSD symptoms at postintervention, while PT is beneficial in managing depression symptoms at the treatment endpoint.
PubMed: 38918741
DOI: 10.1186/s12888-024-05924-8 -
Asian Pacific Journal of Cancer... Jun 2024The miR-451 has been reported to play an important role in colorectal cancer (CRC) pathogenesis and can be a pivotal diagnosis biomarker of CRC. Given the contradictions...
BACKGROUND
The miR-451 has been reported to play an important role in colorectal cancer (CRC) pathogenesis and can be a pivotal diagnosis biomarker of CRC. Given the contradictions in the diagnosis value of the miR-451 in patients with CRC, deciphering the diagnostic/prognostic role of this miRNA in CRC will support the identification of a novel therapeutic target for CRC. Therefore, in the present meta-analysis, we evaluated the diagnostic value of miR-451 in CRC patients.
MATERIALS AND METHODS
The electronic databases of Embase, PubMed, ISI Web of Science, and Scopus systematically searched for relevant studies. The odds ratio (OR) with a 95% confidence interval (CI) was calculated to evaluate the association between miR-451 family expression and diagnosis of colorectal cancer. The parameters including sensitivity, specificity, and area under the curve (AUC) were obtained. The quality of evidence was evaluated using the Newcastle-Ottava Scale (NOS).
RESULTS
This study involved 510 patients (45% female and 55% male) with CRC. The pooled analysis of the studies showed a significant association between low expression levels of miR-451 in patients with CRC (OR = 7.59; 95% CI 2.39 - 24.07; p = 0.001). The overall sensitivity and specificity were 0.95 (0.61 - 1) and 0.83 (0.43 - 0.99), respectively. The pooled AUC was 0.97 (0.88 - 1; p < 0.006). Results showed if the pre-test probability is 50% for a patient, the post-test probability will be 85%. The indices demonstrated the high potency of miR-451 as a diagnostic biomarker in patients with CRC. No publication bias was observed using the Begg's (p=0.85) and Egger's tests (p=0.45).
CONCLUSION
A strong relationship between the low expression levels of miR-451 and CRC progression was observed. This finding suggests the miR-451 family may be helpful as a potential biomarker for the earlier diagnosis of colorectal cancer.
PubMed: 38918650
DOI: 10.31557/APJCP.2024.25.6.1903 -
The Journal of Medical Humanities Jun 2024At the outbreak of the Covid-19 pandemic, several countries declared "states of exception," that is, authorized legal devices that, in the face of circumstances deemed...
Global Political Logics and Mainstream Discourses on Illness in the Declarations of the State of Exception in the Context of the Covid-19 Pandemic: The Case of the USA, France, and Spain.
At the outbreak of the Covid-19 pandemic, several countries declared "states of exception," that is, authorized legal devices that, in the face of circumstances deemed catastrophic, permit the implementation of extraordinary measures and the temporary suspension of some rights in order to restore the previous state of affairs as soon as possible. This paper offers a comparative textual analysis of the different states of exception declared in the USA, France, and Spain. I argue that these texts constitute a privileged site to explore how prevalent global political logics and mainstream discourses on illness are interwoven. Regarding the global political logics in play, I hold that these declarations constitute an instantiation of democracy's autoimmune character; it attacks itself in order to protect itself. Regarding mainstream discourses on illness, I explore how illness is regarded as a threat to one's self (by something seemingly other) and the notion that therapy must consist of securing the self's triumph over anything seemingly other. This twofold analysis reveals that an aporetic dialectic between self and other-as regards politics and illness-operates in these declarations, most likely because it is, in fact, one and the same dialectic, upon which Western epistemology rests. Furthermore, I suggest that these texts reflect and promote these dominant logics, contributing to shape human relationships around the globe in a certain dangerous way.
PubMed: 38918250
DOI: 10.1007/s10912-024-09856-y -
American Journal on Intellectual and... Jul 2024The current study examines the efficacy of an 8-week pretend play intervention targeting social-cognitive abilities in children with Prader-Willi syndrome (PWS), ages...
The current study examines the efficacy of an 8-week pretend play intervention targeting social-cognitive abilities in children with Prader-Willi syndrome (PWS), ages 6-9. PWS is a rare disorder associated with various social, emotional, and cognitive challenges linked to pretend play impairments, and for which interventions are sparse. Nineteen children were quasi-randomized to receive the intervention or be part of a waitlist control group. Participants who received the intervention (n = 10) demonstrated significant improvements in various components of pretend play, most notably in organization of play, which may generalize to broader social-cognitive gains. These findings provide evidence of the intervention's efficacy in enhancing pretend play skills and related social-cognitive abilities during this critical period of development for children with PWS.
Topics: Humans; Prader-Willi Syndrome; Male; Female; Child; Play and Playthings; Play Therapy; Social Cognition; Social Skills
PubMed: 38917995
DOI: 10.1352/1944-7558-129.4.279 -
Journal of Neuroinflammation Jun 2024The microglia-mediated neuroinflammation have been shown to play a crucial role in the ocular pathological angiogenesis process, but specific immunotherapies for...
The microglia-mediated neuroinflammation have been shown to play a crucial role in the ocular pathological angiogenesis process, but specific immunotherapies for neovascular ocular diseases are still lacking. This study proposed that targeting GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) might be a novel immunotherapy for these angiogenesis diseases. We found a significant upregulation of CGAS and STING genes in the RNA-seq data derived from retinal tissues of the patients with proliferative diabetic retinopathy. In experimental models of ocular angiogenesis including laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), the cGAS-STING pathway was activated as angiogenesis progressed. Either genetic deletion or pharmacological inhibition of STING resulted in a remarkable suppression of neovascularization in both models. Furthermore, cGAS-STING signaling was specifically activated in myeloid cells, triggering the subsequent RIP1-RIP3-MLKL pathway activation and leading to necroptosis-mediated inflammation. Notably, targeted inhibition of the cGAS-STING pathway with C-176 or SN-011 could significantly suppress pathological angiogenesis in CNV and OIR. Additionally, the combination of C-176 or SN-011 with anti-VEGF therapy led to least angiogenesis, markedly enhancing the anti-angiogenic effectiveness. Together, our findings provide compelling evidence for the importance of the cGAS-STING-necroptosis axis in pathological angiogenesis, highlighting its potential as a promising immunotherapeutic target for treating neovascular ocular diseases.
PubMed: 38918759
DOI: 10.1186/s12974-024-03155-y -
Asian Pacific Journal of Cancer... Jun 2024The alterations of EGFR and HER2/neu as growth factor receptors and the cytoplasmic signal transduction proteins of RAS/RAF/MAP kinases including its end effector...
Evaluation of the Expression EGFR, HER2/NEU and the End Effector ERK of the RAS/RAF/MAP Kinase Pathway in Prostatic Adenocarcinoma for a Possible Role as New Target Therapy.
UNLABELLED
The alterations of EGFR and HER2/neu as growth factor receptors and the cytoplasmic signal transduction proteins of RAS/RAF/MAP kinases including its end effector molecule (ERK) are important in the carcinogenesis of many tumors. The activation of these protooncogenes in prostate cancer is still under investigation. The aim of this work was to study EGFR, HER2- neu, inactive (non-phosphorylated) and active (phosphorylated) ERK expression in prostatic adenocarcinomas in correlation to the clinical and pathological parameters.
METHODS
Immunohistochemistry- using tissue microarrays- for EGFR, HER2/neu, non-phosphorylated, and phosphor-ERK, was performed on tissues from 166 patients- with primary prostatic adenocarcinoma with no prior treatment-. The results of different markers expression were correlated with the clinical and pathological parameters and were analyzed statistically.
RESULTS
The prostatic tissue showed EGFR, HER2 neu, phosphorylated and non-phosphorylated ERK expression in 8.4%, 1.4%, 78.2%, and 83.4% respectively whether low (patchy) or high expression (diffuse). There were no significant correlations found between patient characteristics and expression of the tested markers. The negative immune reactivity for non-phosphorylated ERK and EGFR- was significantly correlated with high tumor stage (p values 0.03 and 0.01, respectively).
CONCLUSION
EGFR and HER2/neu may play a limited role in prostatic adenocarcinoma as they showed positive expression in a limited number of the examined tissues specifically HER2neu. The expression of non-phosphorylated ERK (mostly weak to moderate) and phosphorylated ERK (mostly moderate to strong)- was appreciated in most cases. Thus, we suggest that anti-EGFR drugs may have a limited role in the treatment of castrate-resistant prostate cancer, but anti-MEK/ERK drugs may have more promising role as a target therapy. It is recommended to perform further molecular testing to elucidate the exact mechanism and significance of these markers.
PubMed: 38918683
DOI: 10.31557/APJCP.2024.25.6.2193 -
The American Journal of Occupational... Jul 2024Play is the primary occupation in childhood and fundamental to occupational therapy practice.
IMPORTANCE
Play is the primary occupation in childhood and fundamental to occupational therapy practice.
OBJECTIVE
To evaluate a play intervention in special school settings.
DESIGN
Pre- and postinvolvement of a 7-mo play program.
SETTING
Four special schools in Victoria, Australia, for children with IQs < 70.
PARTICIPANTS
Thirty-eight children with diagnoses including intellectual disability, autism, and global developmental delay, 7 teachers, 2 speech pathologists, and 2 occupational therapists.
INTERVENTION
Learn to Play Therapy for 1 hr per week over a 7-mo period.
OUTCOMES AND MEASURES
Pre-post outcome measures included children's pretend play skills, language, social skills, emotional regulation, and academic competence.
RESULTS
Mean age of 38 children (15 girls and 23 boys) at baseline was 5 yr 7 mo (SD = 0.46 yr). Results showed significant changes in children's pretend play (p = .03), ability to recall sentences (p = .02), social skills (p = .022), and academic competence (p = .012). Learn to Play had a large effect on children's narrative skills (d = 2.72). At follow-up, object substitution at baseline influenced expressive language (p < .001), narrative mean language utterance (MLU; p = .015), social skills (p < .001), and academic competence (p < .001); elaborate play at baseline plus time influenced social skills (p < .001); and elaborate play at baseline influenced narrative MLU (p =. 016), sentence recall (p = .009), and academic competence (p = .001).
CONCLUSIONS AND RELEVANCE
Embedding pretend play within practice positively influenced children's language, narrative, social, and academic skills. Plain-Language Summary: This study adds to the limited research on play-based therapy programs in special school settings for children with an IQ of less than 70. Children participated in Learn to Play Therapy, during which an occupational therapist, who has observed and assessed the child's play and understands the child's play abilities, played beside the child. Learn to Play Therapy is a child-centered therapy that is used to increase a child's ability to self-initiate and enjoy pretend play. The positive impacts of supporting the children's pretend play ability were highlighted by increases in their pretend play, language, social skills, academic competence, and narrative language after participating in Learn to Play Therapy in their special schools.
Topics: Humans; Male; Female; Child; Social Skills; Occupational Therapy; Play Therapy; Child, Preschool; Intellectual Disability; Developmental Disabilities; Autistic Disorder; Education, Special; Play and Playthings; Schools
PubMed: 38917193
DOI: 10.5014/ajot.2024.050434 -
Naunyn-Schmiedeberg's Archives of... Jun 2024Chemotherapy resistance is a major obstacle in cancer therapy, and identifying novel druggable targets to reverse this phenomenon is essential. The exosome-mediated...
Chemotherapy resistance is a major obstacle in cancer therapy, and identifying novel druggable targets to reverse this phenomenon is essential. The exosome-mediated transmittance of drug resistance has been shown in various cancer models including ovarian and prostate cancer models. In this study, we aimed to investigate the role of exosomal miRNA transfer in chronic myeloid leukemia drug resistance. For this purpose, firstly exosomes were isolated from imatinib sensitive (K562S) and resistant (K562R) chronic myeloid leukemia (CML) cells and named as Sexo and Rexo, respectively. Then, miRNA microarray was used to compare miRNA profiles of K562S, K562R, Sexo, Rexo, and Rexo-treated K562S cells. According to our results, miR-125b-5p and miR-99a-5p exhibited increased expression in resistant cells, their exosomes, and Rexo-treated sensitive cells compared to their sensitive counterparts. On the other hand, miR-210-3p and miR-193b-3p were determined to be the two miRNAs which exhibited decreased expression profile in resistant cells and their exosomes compared to their sensitive counterparts. Gene targets, signaling pathways, and enrichment analysis were performed for these miRNAs by TargetScan, KEGG, and DAVID. Potential interactions between gene candidates at the protein level were analyzed via STRING and Cytoscape software. Our findings revealed CCR5, GRK2, EDN1, ARRB1, P2RY2, LAMC2, PAK3, PAK4, and GIT2 as novel gene targets that may play roles in exosomal imatinib resistance transfer as well as mTOR, STAT3, MCL1, LAMC1, and KRAS which are already linked to imatinib resistance. MDR1 mRNA exhibited higher expression in Rexo compared to Sexo as well as in K562S cells treated with Rexo compared to K562S cells which may suggest exosomal transfer of MDR1 mRNA.
PubMed: 38916832
DOI: 10.1007/s00210-024-03198-1 -
NEJM Evidence Jul 2024CD8+ T regulatory (Treg) cells that recognize the nonclassical class 1b molecule Qa-1/human leukocyte antigen E (Q/E CD8+ Treg cells) are important in maintaining... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
CD8+ T regulatory (Treg) cells that recognize the nonclassical class 1b molecule Qa-1/human leukocyte antigen E (Q/E CD8+ Treg cells) are important in maintaining self-tolerance. We sought to investigate the role that these T cells play in type 1 diabetes (T1D) pathogenesis and whether an intervention targeting this mechanism may delay T1D progression.
METHODS
We conducted a phase 1/2, randomized, double-blind, placebo-controlled trial of the autologous dendritic cell therapy AVT001 that included participants at least 16 years of age, within 1 year of T1D diagnosis, and with ex vivo evidence of a defect in Q/E CD8+ Treg function. Patients were randomly assigned in a 2:1 ratio to AVT001 or placebo, which was administered in three monthly intravenous infusions. The primary end point was safety; efficacy end points included changes from baseline in C-peptide area under the curve (AUC) during a 4-hour mixed meal, hemoglobin A1c (HbA1c), and insulin dose.
RESULTS
Sixteen patients received AVT001, and nine received placebo. Similar rates and severity of adverse events were observed in both groups. None of the patients in the AVT001 group had serious adverse events through visit day 360. Compared with placebo, treatment with ATV001 was associated with less decline from baseline log-transformed C-peptide AUC (nmol/l), with the treatment effect between AVT001 and placebo at day 150 of 0.09 (95% confidence interval [CI], 0.03 to 0.15) and at day 360 of 0.10 (95% CI, 0.04 to 0.15). No clear differences in change in HbA1c and insulin dose from baseline were observed between groups. Estimated treatment effects of AVT001 versus placebo at day 360 were -0.17% (95% CI, -0.60 to 0.26%) for HbA1c and -0.06 U/kg/day (95% CI, -0.14 to 0.02) for daily insulin dose.
CONCLUSIONS
In this phase 1/2 trial, AVT001 did not result in dose-limiting adverse events. Potential signals of efficacy observed here warrant further evaluation in a fully powered trial. (Funded by Avotres Inc. and the Division of Diabetes, Endocrinology, and Metabolic Diseases; ClinicalTrials.gov number, NCT03895996.).
Topics: Humans; Diabetes Mellitus, Type 1; Male; Female; Dendritic Cells; Double-Blind Method; Adult; Young Adult; Middle Aged; Glycated Hemoglobin; Adolescent; T-Lymphocytes, Regulatory; Insulin; C-Peptide
PubMed: 38916421
DOI: 10.1056/EVIDoa2300238 -
Cureus May 2024Supraspinatus tears are a common injury, particularly among athletes who engage in sports that include repetitive overhead motions, such as baseball players. Standard...
Supraspinatus tears are a common injury, particularly among athletes who engage in sports that include repetitive overhead motions, such as baseball players. Standard conservative therapies include rest and activity modification, physical therapy, non-steroidal anti-inflammatory drugs (NSAIDs), cold/heat therapy, and corticosteroid injections. Ongoing research and anecdotal evidence support using platelet-rich plasma (PRP) for supraspinatus/rotator cuff tears. Platelet releasate is obtained from PRP via the activation of platelets, subsequently releasing bioactive substances. Activation can be achieved through various methods, some of which include the addition of calcium chloride, thrombin, or exposure to low-level lasers. Platelet releasate has the potential to assist in the healing of tears by releasing growth factors that facilitate muscle and tendon repair. This case presentation discusses the outcomes of platelet releasate paired with extracorporeal shock wave therapy (ESWT) for the treatment of a partial-thickness supraspinatus tear in an 18-year-old male baseball athlete. After exploring conservative treatment options, the patient opted for a single platelet releasate injection along with a four-part series with ESWT. Four weeks post-procedure, the patient reported a 25% improvement. He was able to fully return to play for the entire baseball season. Although the effectiveness of platelet releasate is still a topic of debate and further investigation, this case demonstrates how platelet releasate shows promising results in accelerating the treatment recovery for a partial supraspinatus tear. Further investigation and research could support the benefit of this procedure for accelerated recovery of injuries compared to PRP.
PubMed: 38915987
DOI: 10.7759/cureus.61057