798 research outputs found

    Parental Understanding of Mental Health in Early Childhood Development: A Human Capabilities Approach

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    Background: the family is central to a child’s development and well-being. Parental understanding of mental health or psychological distress have a significant effect on child development including their mental health. The aim of this qualitative study was to explore parents understanding of mental health in early childhood development. Methods: semi-structured interviews with 12 parents of children in early childhood development were conducted. Five themes emerged from the thematic analysis: (1) Understanding mental health; (2) Perceptions of parental mental health in relation to the child; (3) Child’s behaviour when experiencing different emotions; (4) Child’s behaviour when witnessing parent’s emotions; and (5) Child’s interaction, confidence, and attitude. Overall, parents were not clear in understanding mental health. They could understand and identify basic emotions but were unable to identify early childhood mental health signs. Recommendations enhancing the knowledge and skills of parents are provided within the capabilities framework

    Metagenomic discovery and directed evolution of genes that defend against chemotherapeutics

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    Adults\u27 Subjective Experiences of Exploitation in South Africa

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    The exploitation of people in the environments in which they live and work continues to be a challenge globally despite efforts by stakeholders at national and international levels to bring this to a halt. Exploitation has both short-term and long-term impacts on the lives of the survivors. Attention should be given to preventing new incidents and addressing ongoing exploitation. However, there is a lack of research that focuses on the subjective experiences of different forms of exploitation within the Western Cape, South Africa. Therefore, this paper explores individuals’ experiences of being exploited, focusing on the types of exploitative situations participants are exposed to. This study sample consists of 417 adults residing in Cape Town and surrounding areas, of which 84% were South African, and 16% were from other African countries. Data were collected using a structured survey with additional semi-structured interview questions. This report used only responses to specific semi-structured questions, which were analysed through thematic analysis. The findings reveal that study participants often experience situations that leave them vulnerable to multiple forms of exploitation. This includes experiences of abuse and economic vulnerability; specifically, participants reported working in abusive environments and their economic vulnerabilities being exploited. It was also found that the type of employment could create vulnerability, which left participants at an increased risk for exploitation. Considering this, the study calls for the collaboration of different stakeholders, including but not limited to the families, community, leaders, scholars, and governmental and non-governmental sectors, in developing and prioritising strategies to prevent exploitation. This is essential in protecting and safeguarding the rights of individuals and building a just South Africa where everyone can thrive free from exploitation by others

    Virtual screening for inhibitors of the human TSLP:TSLPR interaction

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    The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) plays a pivotal role in the pathophysiology of various allergy disorders that are mediated by type 2 helper T cell (Th2) responses, such as asthma and atopic dermatitis. TSLP forms a ternary complex with the TSLP receptor (TSLPR) and the interleukin-7-receptor subunit alpha (IL-7Ra), thereby activating a signaling cascade that culminates in the release of pro-inflammatory mediators. In this study, we conducted an in silico characterization of the TSLP: TSLPR complex to investigate the drugability of this complex. Two commercially available fragment libraries were screened computationally for possible inhibitors and a selection of fragments was subsequently tested in vitro. The screening setup consisted of two orthogonal assays measuring TSLP binding to TSLPR: a BLI-based assay and a biochemical assay based on a TSLP: alkaline phosphatase fusion protein. Four fragments pertaining to diverse chemical classes were identified to reduce TSLP: TSLPR complex formation to less than 75% in millimolar concentrations. We have used unbiased molecular dynamics simulations to develop a Markov state model that characterized the binding pathway of the most interesting compound. This work provides a proof-ofprinciple for use of fragments in the inhibition of TSLP: TSLPR complexation

    Molecular crowding defines a common origin for the Warburg effect in proliferating cells and the lactate threshold in muscle physiology

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    Aerobic glycolysis is a seemingly wasteful mode of ATP production that is seen both in rapidly proliferating mammalian cells and highly active contracting muscles, but whether there is a common origin for its presence in these widely different systems is unknown. To study this issue, here we develop a model of human central metabolism that incorporates a solvent capacity constraint of metabolic enzymes and mitochondria, accounting for their occupied volume densities, while assuming glucose and/or fatty acid utilization. The model demonstrates that activation of aerobic glycolysis is favored above a threshold metabolic rate in both rapidly proliferating cells and heavily contracting muscles, because it provides higher ATP yield per volume density than mitochondrial oxidative phosphorylation. In the case of muscle physiology, the model also predicts that before the lactate switch, fatty acid oxidation increases, reaches a maximum, and then decreases to zero with concomitant increase in glucose utilization, in agreement with the empirical evidence. These results are further corroborated by a larger scale model, including biosynthesis of major cell biomass components. The larger scale model also predicts that in proliferating cells the lactate switch is accompanied by activation of glutaminolysis, another distinctive feature of the Warburg effect. In conclusion, intracellular molecular crowding is a fundamental constraint for cell metabolism in both rapidly proliferating- and non-proliferating cells with high metabolic demand. Addition of this constraint to metabolic flux balance models can explain several observations of mammalian cell metabolism under steady state conditions

    Acquired constriction ring syndrome as a cause of inconsolable cry in a child: a case report

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    Acute constriction ring syndrome (ACRS) is a rare clinical condition characterized by formation of a circumferential constriction ring around an appendage or genitalia. Cases are mostly reported in infants and young children. Early recognition and a definitive treatment are of paramount importance in order to avoid irreversible ischemia and possible auto-amputation. We describe a case of a 14-month-old child presented to casualty with a history of refusal to feed and inconsolable cry. Parents noticed a recent swelling of left third toe. On careful examination the child was found to have an acquired constriction ring secondary to a tightly wrapped hair around left third toe. An urgent surgical decompression was done by the orthopaedic team with complete resolution of symptoms. We summarized the pathophysiology of ACRS underlining the need of awareness in treating physicians. The possible medico legal implications should be kept in mind bearing a suggested link with non-accidental injury

    Neurotrophin receptors expression and JNK pathway activation in human astrocytomas

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    <p>Abstract</p> <p>Background</p> <p>Neurotrophins are growth factors that regulate cell growth, differentiation and apoptosis in the nervous system. Their diverse actions are mediated through two different transmembrane – receptor signaling systems: Trk receptor tyrosine kinases (TrkA, TrkB, TrkC) and p75<sup>NTR </sup>neurotrophin receptor. Trk receptors promote cell survival and differentiation while p75<sup>NTR </sup>induces, in most cases, the activity of JNK-p53-Bax apoptosis pathway or suppresses intracellular survival signaling cascades. Robust Trk activation blocks p75<sup>NTR </sup>-induced apoptosis by suppressing the JNK-p53-Bax pathway. The aim of this exploratory study was to investigate the expression levels of neurotrophin receptors, Trks and p75<sup>NTR</sup>, and the activation of JNK pathway in human astrocytomas and in adjacent non-neoplastic brain tissue.</p> <p>Methods</p> <p>Formalin-fixed paraffin-embedded serial sections from 33 supratentorial astrocytomas (5 diffuse fibrillary astrocytomas, WHO grade II; 6 anaplastic astrocytomas, WHO grade III; 22 glioblastomas multiforme, WHO grade IV) were immunostained following microwave pretreatment. Polyclonal antibodies against TrkA, TrkB, TrkC and monoclonal antibodies against p75<sup>NTR </sup>and phosphorylated forms of JNK (pJNK) and c-Jun (pc-Jun) were used. The labeling index (LI), defined as the percentage of positive (labeled) cells out of the total number of tumor cells counted, was determined.</p> <p>Results</p> <p>Moderate to strong, granular cytoplasmic immunoreactivity for TrkA, TrkB and TrkC receptors was detected in greater than or equal to 10% of tumor cells in the majority of tumors independently of grade; on the contrary, p75<sup>NTR </sup>receptor expression was found in a small percentage of tumor cells (~1%) in some tumors. The endothelium of tumor capillaries showed conspicuous immunoreactivity for TrkB receptor. Trk immunoreactivity seemed to be localized in some neurons and astrocytes in non-neoplastic tissue. Phosphorylated forms of JNK (pJNK) and c-Jun (pc-Jun) were significantly co-expressed in a tumor grade-dependent manner (p < 0.05). Interestingly, a statistically significant (p < 0.05) reverse relationship between Trk receptors LIs and pc-Jun/pJNK LIs was noted in some glioblastomas multiforme.</p> <p>Conclusion</p> <p>In the context of astrocytomas, Trk receptors (TrkA, TrkB, TrkC) expression may promote tumor growth independently of grade. Furthermore, activation of JNK pathway may contribute to progression towards malignancy. Considering the fact that regional tumor heterogeneity may be a limiting factor for immunohistochemical studies, the significance of the reverse relationship between Trk receptors and pc-Jun/pJNK LIs with respect to biological behavior of human astrocytomas requires further evaluation.</p

    Gefitinib in patients with progressive high-grade gliomas: a multicentre phase II study by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO)

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    To investigate the role of gefitinib in patients with high-grade gliomas (HGGs), a phase II trial (1839IL/0116) was conducted in patients with disease recurrence following surgery plus radiotherapy and first-line chemotherapy. Adult patients with histologically confirmed recurrent HGGs following surgery, radiotherapy and first-line chemotherapy, were considered eligible. Patients were treated with gefitinib (250 mgday−1) continuously until disease progression. The primary end point was progression-free survival at 6 months progression-free survival at 6 months (PFS-6). Tissue biomarkers (epidermal growth factor receptor (EGFR) gene status and expression, phosphorylated Akt (p-Akt) expression) were assessed. Twenty-eight patients (median age, 55 years; median ECOG performance status, 1) were enrolled; all were evaluable for drug activity and safety. Sixteen patients had glioblastoma, three patients had anaplastic oligodendrogliomas and nine patients had anaplastic astrocytoma. Five patients (17.9%, 95% CI 6.1–36.9%) showed disease stabilisation. The overall median time to progression was 8.4 (range 2–104+) weeks and PFS-6 was 14.3% (95% CI 4.0–32.7%). The median overall survival was 24.6 weeks (range 4–104+). No grade 3–4 gefitinib-related toxicity was found. Gefitinib showed limited activity in patients affected by HGGs. Epidermal growth factor receptor expression or gene status, and p-Akt expression do not seem to predict activity of this drug
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