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Identifying the determinants of positive coping is a critical step in empowering the parents of children with intellectual disability. In this context, this study aims to develop a scale to assess the determinants of positive coping. Accordingly, culturally relevant items were pooled, got validated by experts and refined. The scale was administered to 150 parents of children with intellectual disability. Factor analysis done through polychoric correlation helped reduce the items. Cronbach’s alpha coefficients were established for reliability testing. The validity of the new scale was examined with the subjective wellbeing on a visual analogue scale and Family Interview for Stress and Coping in Mental Retardation. The new scale has a Cronbach’s alpha of 0.71 and an intraclass correlation of 0.64. After factor analysis, 12 items were retained in the final version. This study also identified specific factors associated with positive coping. The new scale can be used with parents of children with intellectual disabilities to identify the determinants of positive coping.

Breast cancer is considered one of the utmost neoplastic diseases globally, with a high death rate of patients. Over the last decades, many approaches have been studied to early diagnose and treat it, such as chemotherapy, hormone therapy, immunotherapy, and MRI and biomarker tests; do not show the optimal efficacy. These existing approaches are accompanied by severe side effects, thus recognizing these challenges, a great effort has been done to find out the new remedies for breast cancer. Main finding: Nanotechnology opened a new horizon to the treatment of breast cancer. Many nanoparticulate platforms for the diagnosis of involved biomarkers and delivering antineoplastic drugs are under either clinical trials or just approved by the Food and Drug Administration (FDA). It is well known that natural phytochemicals are successfully useful to treat breast cancer because these natural compounds are safer, available, cheaper, and have less toxic effects. Chitosan is a biocompatible and biodegradable polymer. Further, it has outstanding features, like chemical functional groups that can easily modify our interest with an exceptional choice of promising applications. Abundant studies were directed to assess the chitosan derivative-based nanoformulation's abilities in delivering varieties of drugs. However, the role of chitosan in diagnostics and theranostics not be obligated. The present servey will discuss the application of chitosan as an anticancer drug carrier such as tamoxifen, doxorubicin, paclitaxel, docetaxel, etc. and also, its role as a theranostics (i.e. photo-responsive and thermo-responsive) moieties. The therapeutic and theranostic potential of chitosan in cancer is promising and it seems that to have a good potential to get to the clinic.

There are limited options to treat psychotic symptoms during early recovery stage of neuroleptic malignant syndrome (NMS) and catatonic symptoms in adolescents because of restrictions on the use of electroconvulsive therapy (ECT). Add-on transcranial direct current stimulation (tDCS) treatment twice daily for five consecutive days showed improvement in auditory–visual hallucinations and cognitive and bio-social functioning during early recovery stages of NMS in an adolescent. The use of tDCS in another adolescent diagnosed with severe depressive episode with psychotic symptoms and catatonia showed improvement in staring, mutism, rigidity, and interaction with add-on tDCS. The improvement observed lasted for a short duration and tDCS treatment was well tolerated without any severe adverse effect.

The purpose of the study was to identify children at our institute who possibly suffered abusive head trauma (AHT). A retrospective study of CT imaging of children between one month to three years of age between January 2013 and May 2021 was carried out at a dedicated neurocentre in Southern India. We identified 48 cases of possible AHT. The demographics, clinical features at presentation, imaging and fundus findings were analyzed. Imaging revealed subdural hemorrhage (SDH) in 42 and sub dural effusion (SDE) in 5 cases, one case had only hypoxia. The location of SDH was studied as was hypoxia underlying SDH, global hypoxia and ischemia. Cases of subarachnoid hemorrhage (SAH), parenchymal hematomaintraventricular hemorrhage (IVH) were also noted. Skeletal survey, chest X-ray and CT spine were reviewed. AHT needs to be paid attention to in the Indian scenario. An extensive work up is required to substantiate the claim and to work on preventionmanagement of these cases subsequently.

Background: Electrospinning has provided an excellent opportunity to develop nano-sized fibers with a broad range of applications, including nano-drug delivery systems for the treatment of cancer. This versatile and viable technique involves using various polymer solutions, strong electric fields to generate nanofibers with high surface area, high porosity, abundant pore connectivity, and distinct chemical compositions. On the other hand, natural products-based drugs show excellent results in preclinical settings but fail in a clinical setting due to poor pharmacokinetics, low solubility, high toxicity, and lack of targetability. Due to the remarkable properties of nanofibers, it opened new doors in the nanomedicine field to introduce novel nanofiber-based formulations for natural products delivery applications. Scope and approach: The present review describes the needle-based and needleless methods for the preparation of nanofibers. It summarizes the major application of these methods to formulate mostly investigated natural products in cancer therapy, like taxanes, curcumin, resveratrol, camptothecin, and doxorubicin. In summary, this review may help scientists to develop more efficient natural product-based nanofibers with improved pharmacokinetic properties for the effective treatment of cancer. Key findings and conclusions: Scientists used recent advances in nanotechnology to develop natural products loaded with electrospun nanocarriers to treat cancer therapy. They succeeded in preparing with high encapsulation and sustained slow release of several natural products, including curcumin, vinca alkaloids, taxanes, camptothecin, anthracyclins, etc. These nanocarriers demonstrated vast advantages over other delivery systems, including higher stability and improved bioavailability. Although several reports on the successful application of electrospinning for the delivery of natural compounds for cancer therapy, further developments towards commercialization and large scale-production need more optimization. 2-s2.0-85118879382 WOS:00074659470001 Q1

Ramcharan Singh Angom,1,* Jian Zhu,1,2,* Alexander TH Wu,3 Maryam Rachmawati Sumitra,4 Victoria Pham,1 Shamit Dutta,1 Enfeng Wang,1 Vijay Sagar Madamsetty,1 Gabriel D Perez-Cordero,1 Hsu-Shan Huang,4 Debabrata Mukhopadhyay,1 Ying Wang5,6 1Department of Biochemistry and Molecular Biology, College of Medicine and Science, Mayo Clinic, Jacksonville, FL, 32224, USA; 2Department of Cardiology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, People’s Republic of China; 3The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; 4Graduate Institute for Cancer Biology & Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, 110, Taiwan; 5Department of Cardiovascular Medicine, College of Medicine and Science, Mayo Clinic, Rochester, MN, USA; 6Department of Biochemistry and Molecular Biology, College of Medicine and Science, Mayo Clinic, Rochester, MN, 55905, USA*These authors contributed equally to this workCorrespondence: Ying WangDepartment of Cardiovascular Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, 200 1st ST SW, Rochester, MN, 55905, USAEmail wang.ying@mayo.eduObjective: Endothelial cell (EC) activation facilitates leukocyte adhesion to vascular walls, which is implicated in a variety of cardiovascular diseases and is a target for prevention and treatment. Despite the development of anti-inflammatory medications, cost-effective therapies with significant anti-inflammatory effects and lower organ toxicity remain elusive. The goal of this study is to identify novel synthetic compounds that inhibit EC inflammatory response with minimal organ toxicity.Methods and Results: In this study, we discovered LCC-09, a salicylanilide derivative consisting of the functional fragment of magnolol, 2,4-difluorophenyl, and paeonol moiety of salicylate, as a novel anti-inflammatory compound in cultured ECs and zebrafish model. LCC-09 was shown to inhibit pro-inflammatory cytokine tumor necrosis factor-α (TNFα)-induced expression of adhesion molecules and inflammatory cytokines, leading to reduced leukocyte adhesion to ECs. Mechanistically, LCC-09 inhibits the phosphorylation of signal transducer and activator of transcription 1 (STAT1), TNFα-induced degradation of NF-κ-B Inhibitor-α (IκBα) and phosphorylation of NFκB p65, resulting in reduced NFκB transactivation activity and binding to E-selectin promoter. Additionally, LCC-09 attenuated TNFα-induced generation of reactive oxygen species in ECs. Molecular docking models suggest the binding of LCC-09 to NFκB essential modulator (NEMO) and Janus tyrosine kinase (JAK) may lead to dual inhibition of NFκB and STAT1. Furthermore, the anti-inflammatory effect of LCC-09 was validated in the lipopolysaccharides (LPS)-induced inflammation model in zebrafish. Our results demonstrated that LCC-09 significantly reduced the LPS-induced leukocyte recruitment and mortality of zebrafish embryos. Finally, LCC-09 was administered to cultured ECs and zebrafish embryos and showed minimal toxicities.Conclusion: Our results support that LCC-09 inhibits EC inflammatory response but does not elicit significant toxicity.Keywords: endothelial cells, inflammation, salicylanilide derivative, tumor necrosis factor-α, lipopolysaccharides, toxicity

There is a paucity of literature on neuropsychological functions in youth with obsessive-compulsive disorder (OCD). Most studies have small sample sizes and have yielded inconsistent results. A recent meta-analysis failed to identify any significant impairments. We studied neuropsychological functions (attention, verbal fluency, working memory, set-shifting, response inhibition, planning and visuospatial abilities) in a large sample of youth with OCD (n = 97) in comparison with controls who did not have OCD (n = 50). After controlling for the confounding effects (age, sex, severity of depression and anxiety, presence of comorbid attention-deficit hyperactivity disorder, any tic disorder, number of comorbidities, and non-verbal intelligence measured by the standard progressive matrices), the youth with OCD significantly underperformed with large effect sizes compared to controls, only on the test of 'behavioral reversal', measured by the Object Alternation Test (trials to reach criterion p 0.001, Cohen's d = 1.49; perseverative errors p 0.001, Cohen's d = 1.31). Patients also underperformed on a task of planning, but it was statistically insignificant. Certain comorbid disorders, antipsychotic use and age of onset did not influence neuropsychological performance significantly. Our study demonstrates that youth with OCD may have impaired 'set-shifting' in the form of 'behavioral reversal' and possibly planning, findings broadly consistent with the literature in adults and with the fronto-striatal model of OCD. It is possible that youth may accumulate more neuropsychological impairments over a period, as the illness continues into adulthood.

Background: Studies are sparse on caretaker perceptions about self-cutting (SC) in institutionalised adolescents. Methods: Five caretakers in a shelter home for adolescent girls were interviewed and the data were analysed using interpretative phenomenological analysis. Results: Nine major themes emerged: expected reactions from others led to secrecy; reasons were relational and academic difficulties; benefits were control of emotions/thoughts or to get others’ attention; learning happened by witnessing and change in thinking; challenges were systemic contagion, counselling repeaters of SC and adolescent infatuation; responses were ‘we are empathetic’ and ‘friends are helpful, but have a limit’; goals for self and reflection were helpful to stop SC; vulnerabilities were lack of skills and problems faced; and protective factors were good skills and family relations. These novel findings contribute to the existing sparse literature and are useful for gaining a deeper understanding about and better management of SC.

Dexamethasone (DEX) has been widely used to treat a variety of diseases, including autoimmune diseases, allergies, ocular disorders, cancer, and, more recently, COVID-19. However, DEX usage is often restricted in the clinic due to its poor water solubility. When administered through a systemic route, it can elicit severe side effects, such as hypertension, peptic ulcers, hyperglycemia, and hydro-electrolytic disorders. There is currently much interest in developing efficient DEX-loaded nanoformulations that ameliorate adverse disease effects inhibiting advancements in scientific research. Various nanoparticles have been developed to selectively deliver drugs without destroying healthy cells or organs in recent years. In the present review, we have summarized some of the most attractive applications of DEX-loaded delivery systems, including liposomes, polymers, hydrogels, nanofibers, silica, calcium phosphate, and hydroxyapatite. This review provides our readers with a broad spectrum of nanomedicine approaches to deliver DEX safely.

Glioblastoma multiforme (GBM) is a highly proliferative and locally invasive cancer with poor prognosis and a high recurrence rate. Although anti-VEGF (vascular endothelial growth factor) therapy offers short-term benefit to GBM patients, this approach fails as the tumor develops into a more invasive and drug-resistant phenotype and ultimately recurs. Recently, both glioma stemlike cells (GSCs) and brain tumor-initiating cells (BTICs) have been implicated in GBM recurrence and its resistance to therapy. We observed that patient-derived GBM cells expressing shRNAs of VEGF or neuropilin-1 (NRP-1) attenuate cancer stem cell markers, inhibit the tumor-initiating cell's neurosphere-forming capacity, and migration. Furthermore, both VEGF and NRP-1 knockdown inhibit the growth of patient-derived GBM xenografts in both zebrafish and mouse models. Interestingly, NRP-1-depleted patient-derived GBM xenografts substantially prolonged survival in mice compared to that of VEGF depletion. Our results also demonstrate that NRP-1 ablation of patient-derived GBM cells improves the sensitivity of TMZ and enhances the overall survival of the respective tumor-bearing mice. This improved outcome may provide insight into the inhibition of GBM progression and effective treatment strategies by targeting NRP-1 in addition to chemotherapy and radiotherapy.

Children constitute 40% of India’s population. Large number of children with psychiatric disorders and neurodevelopmental conditions are unable to access mental health services due to factors such as unavailability of these services in smaller urban and rural centres and lack of training for primary care providers. Given the relatively easy access to video conferencing technology, feasibility and acceptability of Telepsychiatry, there is an urgent need to invest resources and strengthen the use of Telepsychiatry for child and adolescent mental health training and serviced delivery . This viewpoint article discusses the need,scope,experiences and challenges related to use of Telepsychiatry in the area of child mental health.

Targeted drug delivery remains an active area of investigation in hematologic cancers. We have previously reported on a novel nanoparticle formulation (D1X) that can encapsulate drugs within a liposome whose lipid bilayer contains dexamethasone, which serves as a targeting ligand for drug delivery to tumor cells that express glucocorticoid receptors. We tested the activity of D1X-encapsulated bortezomib (D1XB) in combination with D1X-encapsulated nutlin (D1XN) in B-lymphoma/Waldenstrom macroglobulinemia (WM) cells. WM cells treated with D1XB + D1XN experienced cell cycle arrest, ER stress and apoptosis. In mice xenografted with bortezomib-resistant WM cells, D1XB + D1XN treatment resulted in significantly lower tumor burden compared to vehicle or nonliposomal parent drugs.

Background Tic disorders (TDs) are common neurodevelopmental disorders in children and adolescents. To date, there is very scant literature on TDs in children and adolescents in the Indian setting. Aim The objectives of this study were to characterize the clinical profile, including comorbidities and pattern of medication use in the treatment of TDs, in children and adolescents. Materials and methods The present study is a retrospective chart review of children and adolescents up to age 18 years diagnosed with TD in a tertiary care center in India. Data were derived from case records of patients with a diagnosis of TD, coded as F 95 according to ICD 10, from 1st January 2014 to 31st December 2017. Results We recruited 85 subjects. The majority (95.29%, n = 81) of them were male, and the mean age of onset was 8.4 years. Chronic tic disorder was the most common subtype, followed by Tourette syndrome and provisional or transient tic disorder. Eighty patients (94%) had a comorbid disorder, with attention deficit hyperactivity disorder being the most common, followed by obsessive compulsive disorder. Eighty-two percent of patients received pharmacotherapy. Risperidone was the most frequently used medication, followed by clonidine, haloperidol, and aripiprazole. Moderate to significant improvement with medications was seen in 88% of the patients. Conclusion The present study of children and adolescents with TDs highlights very high rate of comorbidity and a favorable short-term course with medication use.

Background: Increasing rates of behavioral problems among children in India necessitates newer ways of managing them with medical and nonmedical approaches. Music add-on therapy is a method for treating mental disturbances. This study examines the effectiveness of music add-on therapy in managing children with behavioral problems. Methods and Materials: A randomized controlled design was adopted with a random allocation of 40 children (20 each in experimental and control groups) aged between 6 and 12 years with behavioral disorders as per the International Statistical Classification of Diseases and Related Health Problems (ICD)-10. After the pretest, both the groups received treatment as usual (TAU), while the experimental group alone additionally received music add-on intervention with eight Hindustani ragas for 3 weeks. As clinical outcome measures, we used the Childrens Global Assessment Scale, Nisonger Child Behavior Rating Form typical IQ (NCBRF-TIQ) version, and visual analogue scale (VAS) for a parent to monitor the behavioral improvement. Results: Children exposed to the music add-on therapy had improved score in the Children Global Assessment Scale (CGAS) and the VAS as compared with the control group (F [2,76] = 34.307, P < 0.001 and F [2,76] = 72.4, P < 0.001, respectively). Further, the NCBRF-TIQ version revealed improvement in positive social behavior (F [2,76] = 13.089, P < 0.001) and reduction in problem behaviors in the experimental group. Conclusion: Music add-on therapy is effective in improving positive social behavior and reducing problem behaviors among children.

In an all-van der Waals heterostructure, the active layer, gate dielectrics, and gate electrodes are all assembled from two-dimensional crystals. Owing to the absence of dangling bonds within their two-dimensional bulk, these devices host ultraclean electron systems. Here, we describe methods for implementing nanoscale electrostatic control without contaminating critical interfaces. Using a resist-free local anodic oxidation process, we pattern sub-100nm features in graphite gates which are then integrated into the heterostructure. Using a quantum point contact as a benchmark device, we demonstrate selective partitioning of both integer and fractional quantum Hall edge modes at high magnetic fields. Furthermore, we find evidence for fragile interaction-driven edge reconstruction effects, including the formation of a quantum dot at an electrostatic potential saddle point. Our results pave the way for precision nanoscale experiments on correlated states in these materials, including single anyon control in the fractional quantum Hall regime., Comment: Main Text: 12 pages, 6 figures | Extended Data: 6 figures | Supplementary Info: 6 pages, 5 figures; added additional acknowledgments

Background: Recovery in mental illness is not synonymous with cure. Personal recovery approach consider recovery as a process and not as an outcome. This approach takes into account the subjective meaning of recovery by assessing how a person has learned to accommodate and live with an illness. Aim: To study the personal meaning of recovery among persons with schizophrenia. Method: This article presents the findings of a qualitative study about what ‘recovery’ means to persons with schizophrenia. A semi structured interview schedule was prepared based on literature review and expert opinion. Twenty participants who met the inclusion criteria and personally consider themselves recovering/recovered from schizophrenia were selected for the in-depth qualitative interviews. Data was analyzed using Interpretative Phenomenological Analysis (IPA). Meaning of recovery from each participant’s perspective was recorded. Findings: The results indicate factors that patients deem important for their recovery are, absence of symptoms, regaining functioning, being able to work, having adequate emotional stability and not being on medicines. The findings are examined in the background of the previous studies and suggestions for clinical practice and research is also discussed. Conclusion: Recovery is far more than remission of symptoms. Persons with mental illness has their own criteria of recovery, which could be very distinct from the clinical definition. Current study findings can help in identifying meaning of recovery through the perspectives of persons with mental illness and in developing and implementing recovery-oriented services.

Since its first clinical application, methotrexate (MTX) has been widely used for the treatment of human diseases. Despite great advantages, some properties such as poor absorption, short plasma half-life and unpredictable bioavailability have led researchers to seek novel delivery systems to improve its characteristics for parenteral and oral administration. Recently, great attention has been directed to hydrogels for the preparation of MTX formulations. This review describes the potential of hydrogels for the formulation of MTX to treat cancer, rheumatoid arthritis, psoriasis and central nervous system diseases. We will delineate the state-of-the-art and promising potential of hydrogels for systemic MTX delivery as well as transdermal delivery of the drug-using hydrogel-based formulations.

Background Most children and adolescents in need of mental healthcare remain untreated even when services are available. This study evaluates the accuracy of a new tool, the Community Case Detection Tool (CCDT). The CCDT uses illustrated vignettes, two questions and a simple decision algorithm to support proactive community-level detection of children, adolescents and families in need of mental healthcare to improve help-seeking. Methods Trusted and respected community members in the Eastern Province of Sri Lanka used the CCDT in their daily routine. Children and families detected as potentially in need of mental healthcare based on utilizing the CCDT (N = 157, aged 6–18 years) were invited for a clinical interview by a mental health counsellor using the Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI-KID). The CCDT results were compared against the results of the clinical interview. The concurrent validity and performance of the CCDT were also evaluated by comparing the CCDT outcomes against the Strengths and Difficulties Questionnaire (SDQ). Results 7 out of 10 children and families detected by community members using the CCDT were confirmed to be in need for treatment (positive predictive value [PPV] = 0.69; 0.75 when compared to the SDQ). Detections based on the family problem vignette were most accurate (PPV = 0.76), followed by the internalising problem vignette (PPV = 0.71) and the externalising problem vignette (PPV = 0.62). Conclusions The CCDT is a promising low-cost solution to overcome under-detection of children and families in need of mental healthcare. Future research should focus on evaluating the effectiveness, as well as additional strategies to improve help-seeking.

Simple Summary Pancreatic cancer is among the most lethal cancers. The expression of PLEXIND1, a receptor, is upregulated in many cancers (including pancreatic cancer). Traditionally, PLEXIND1 is known to be involved in neuron development and mediate semaphorin signaling. However, its role and signaling in cancer is not fully understood. In our study, we present a new mechanism through which PLEXIND1 mediates its roles in cancer. For the first time, we demonstrate that it can function as a transforming growth factor beta coreceptor and modulate SMAD3 signaling. Around 90% of pancreatic cancer patients have mutant KRAS. Our work suggests that PLEXIND1 functions differently in pancreatic cancer cell lines, and the difference correlates with KRAS mutational status. Additionally, we demonstrate a novel peptide based therapeutic approach to target PLEXIND1 in cancer cells. Our work is valuable to both neuroscience and cancer fields, as it demonstrates an association between two previously unrelated signaling pathways. Abstract PLEXIND1 is upregulated in several cancers, including pancreatic ductal adenocarcinoma (PDAC). It is an established mediator of semaphorin signaling, and neuropilins are its known coreceptors. Herein, we report data to support the proposal that PLEXIND1 acts as a transforming growth factor beta (TGFβ) coreceptor, modulating cell growth through SMAD3 signaling. Our findings demonstrate that PLEXIND1 plays a pro-tumorigenic role in PDAC cells with oncogenic KRAS (KRASmut). We show in KRASmut PDAC cell lines (PANC-1, AsPC-1,4535) PLEXIND1 downregulation results in decreased cell viability (in vitro) and reduced tumor growth (in vivo). Conversely, PLEXIND1 acts as a tumor suppressor in the PDAC cell line (BxPC-3) with wild-type KRAS (KRASwt), as its reduced expression results in higher cell viability (in-vitro) and tumor growth (in vivo). Additionally, we demonstrate that PLEXIND1-mediated interactions can be selectively disrupted using a peptide based on its C-terminal sequence (a PDZ domain-binding motif), an outcome that may possess significant therapeutic implications. To our knowledge, this is the first report showing that (1) PLEXIND1 acts as a TGFβ coreceptor and mediates SMAD3 signaling, and (2) differential roles of PLEXIND1 in PDAC cell lines correlate with KRASmut and KRASwt status.