Chldren's rights and corporal punishment in Assendabo town and the surrounding area, South West Ethiopia

Corporal punishment of children has been used as a disciplinary measure to modify undesirable behavior of children worldwide. This study was conducted with the aim of determining the knowledge, attitudes and the extent that corporal punishment is practiced in the study area. A cross-sectional study was conducted among the residents of Assendabo town and its surroundings area form January 8-12, 2003. A total of 368 residents with at least one child living with them were selected and interviewed using a structured questionnaire. Data were analyzed using SPSS for windows version 11.0. The study revealed 310 (87.6%) of the parents employed child corporal punishment as a method of disciplining out of which nearly half of them claimed their action was for the ultimate benefit of their children. Only 12 (3.5%) of the parents reported infliction of trauma while punishing their children. There was no significant parental difference both in attitude and practice of child corporal punishment. Family income is found to affect both attitude and practice of corporal punishment. From this study it is concluded that the knowledge about the existence of a legal framework which protects a child from any form of abuse is low. The attitude towards avoidance of child corporal punishment is unfavorable and there is a high prevalence of child corporal punishment practiced.     

When fear and misinformation go viral: Pharmacists' role in deterring medication misinformation during the 'infodemic' surrounding COVID-19

The world has faced an unprecedented challenge when coronavirus (COVID-19) emerged as a pandemic. Millions of people have contracted the virus and a significant number of them lost their lives, resulting in a tremendous social and economic shock across the globe. Amid the growing burden of the pandemic, there are parallel emergencies that need to be simultaneously tackled: the proliferation of fake medicines, fake news and medication misinformation surrounding COVID-19. Pharmacists are key health professionals with the required skills and training to contribute to the fight against these emergencies. Primarily, they can be a relevant source of accurate and reliable information to the public or other fellow health professionals thereby reducing the spread of COVID-19 medication misinformation. This can be achieved by providing accurate and reliable information based on recommendations given by relevant health authorities and professional associations to make sure the community understand the importance of the message and thus minimise the detrimental consequences of the pandemic. This commentary aims to summarise the existing literature in relation to the promising treatments currently under trial, the perils of falsified medications and medicine-related information and the role of pharmacists in taking a leading role in combating these parallel global emergencies.     

Aerosolised 5-azacytidine suppresses tumour growth and reprogrammes the epigenome in an orthotopic lung cancer model

Background:

Epigenetic silencing by promoter methylation and chromatin remodelling affects hundreds of genes and is a causal event for lung cancer. Treatment of patients with low doses of the demethylating agent 5-azacytidine in combination with the histone deacetylase inhibitor entinostat has yielded clinical responses. The subcutaneous dosing route for consecutive days and reduced bioavailability of 5-azacytidine because of inactivation by cytidine deaminase may limit the expansion of epigenetic therapy into Phase III trials. To mitigate these barriers, an aerosol of 5-azacytidine was generated and characterised.

Methods:

The effect of aerosol vs systemic delivery of 5-azacytidine on tumour burden and molecular response of engrafted lung tumours in the nude rat was compared.

Results:

Pharmacokinetics revealed major improvement in the half-life of 5-azacytidine in lung tissue with aerosol delivery. Aerosolised 5-azacytidine significantly reduced lung tumour burden and induced global demethylation of the epigenome at one-third of the comparable effective systemic dose. High commonality for demethylation of genes was seen in tumours sampled throughout lung lobes and across treated animals receiving the aerosolised drug.

Conclusion:

Collectively, these findings show that aerosolised 5-azacytidine targets the lung, effectively reprogrammes the epigenome of tumours, and is a promising approach to combine with other drugs for treating lung cancer.     

Cdk6-dependent regulation of G(1) length controls adult neurogenesis

The presence of neurogenic precursors in the adult mammalian brain is now widely accepted, but the mechanisms coupling their proliferation with the onset of neuronal differentiation remain unknown. Here, we unravel the major contribution of the G(1) regulator cyclin-dependent kinase 6 (Cdk6) to adult neurogenesis. We found that Cdk6 was essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Specifically, Cdk6 deficiency prevents the expansion of neuronally committed precursors by lengthening G(1) phase duration, reducing concomitantly the production of newborn neurons. Altogether, our data support G(1) length as an essential regulator of the switch between proliferation and neuronal differentiation in the adult brain and Cdk6 as one intrinsic key molecular regulator of this process.     

Household capacities, vulnerabilities and food insecurity: shifts in food insecurity in urban and rural Ethiopia during the 2008 food crisis

The global food crisis of 2008 led to renewed interest in global food insecurity and how macro-level food prices impact household and individual level wellbeing. There is debate over the extent to which food price increases in 2008 eroded food security, the extent to which this effect was distributed across rural and urban locales, and the extent to which rural farmers might have benefited. Ethiopia's food prices increased particularly dramatically between 2005 and 2008 and here we ask whether there was a concomitant increase in household food insecurity, whether this decline was distributed equally across rural, urban, and semi-urban locales, and to what extent pre-crisis household capacities and vulnerabilities impacted 2008 household food insecurity levels. Data are drawn from a random sample of 2610 households in Southwest Ethiopia surveyed 2005/6 and again in mid to late 2008. Results show broad deterioration of household food insecurity relative to baseline but declines were most pronounced in the rural areas. Wealthier households and those that were relatively more food secure in 2005/6 tended to be more food secure in 2008, net of other factors, and these effects were most pronounced in urban areas. External shocks, such as a job loss or loss of crops, experienced by households were also associated with worse food insecurity in 2008 but few other household variables were associated with 2008 food insecurity. Our results also showed that rural farmers tended to produce small amounts for sale on markets, and thus were not able to enjoy the potential benefits that come from greater crop prices. We conclude that poverty, and not urban/rural difference, is the important variable for understanding the risk of food insecurity during a food crisis and that many rural farmers are too poor to take advantage of rapid rises in food prices.     

EMT and stem cell-like properties associated with miR-205 and miR-200 epigenetic silencing are early manifestations during carcinogen-induced transformation of human lung epithelial cells

Epithelial-to-mesenchymal transition (EMT) is strongly associated with cancer progression, but its potential role during premalignant development has not been studied. Here, we show that a 4-week exposure of immortalized human bronchial epithelial cells (HBEC) to tobacco carcinogens can induce a persistent, irreversible, and multifaceted dedifferentiation program marked by EMT and the emergence of stem cell-like properties. EMT induction was epigenetically driven, initially by chromatin remodeling through H3K27me3 enrichment and later by ensuing DNA methylation to sustain silencing of tumor-suppressive microRNAs (miRNA), miR-200b, miR-200c, and miR-205, which were implicated in the dedifferentiation program in HBECs and also in primary lung tumors. Carcinogen-treated HBECs acquired stem cell-like features characterized by their ability to form spheroids with branching tubules and enrichment of the CD44(high)/CD24(low), CD133, and ALDH1 stem cell-like markers. miRNA overexpression studies indicated that regulation of the EMT, stem-like, and transformed phenotypes in HBECs were distinct events. Our findings extend present concepts of how EMT participates in cancer pathophysiology by showing that EMT induction can participate in cancer initiation to promote the clonal expansion of premalignant lung epithelial cells.     

SULF2 methylation is prognostic for lung cancer survival and increases sensitivity to topoisomerase-I inhibitors via induction of ISG15

The heparan sulfate 6-O-endosulfatase (SULF2) promotes growth and metastasis of solid tumors. We recently identified that cytosine methylation of the SULF2 promoter is associated with better survival of resected lung adenocarcinoma patients, and now also demonstrates a marginal improvement in survival of advanced non-small cell lung cancer (NSCLC) patients receiving standard chemotherapy (hazard ratio=0.63, P=0.07). Subsequent studies focused on investigating the effect of methylation on SULF2 expression and its genome-wide impact. The genes and pathways modulated by epigenetic inactivation of SULF2 and the effects on sensitivity to chemotherapy were characterized in vitro and in vivo. Silencing SULF2 through small interfering RNA or methylation primarily increased expression of interferon-inducible genes including ISG15, a marker for increased sensitivity to topoisomerase-1 inhibitors such as camptothecin (CPT). NSCLC cell lines with methylated SULF2 (SULF2M) express 60-fold higher ISG15 compared with SULF2 unmethylated (SULF2U) NSCLC cell lines and normal human bronchial epithelial cells. In vitro, SULF2M and high ISG15 (ISG15H)-expressing NSCLC cell lines were 134-fold more sensitive to CPT than SULF2U and low ISG15 (ISG15L)-expressing cell lines. Topotecan, a soluble analog of CPT and FDA-approved anticancer drug, dramatically arrested the growth of SULF2M-ISG15H, but not SULF2U-ISG15L lung tumors in nude mice (P<0.002). Similarly, high ISG15 expression that is comparable to the topotecan (TPT)-sensitive NSCLC cell lines was found in tumors from 25% of NSCLC patients compared with normal lung, indicating a potential to identify and target the most sensitive NSCLC subpopulation for personalized TPT therapy.     

Assessment of community pharmacy professionals’ knowledge and counseling skills achievement towards headache management: a cross-sectional and simulated-client based mixed study

Background

Headache is one of the most common disabling medical condition affecting over 40% of adults globally. Many patients with headache prefer to alleviate their symptom with a range of over-the-counter analgesics that are available in community medicine retail outlets (CMROs). However, data regarding how community pharmacists respond to headache presentation and their analgesic dispensing behaviors in Ethiopia is scarce. The present study aimed to assess the self-reported and actual practice of community pharmacists toward management of a headache in Gondar town, Ethiopia.

Methods

A dual-phase mixed-methods research design, including pseudo-client visits (between April 1 and 30, 2018) followed by a questionnaire-based cross-sectional study (between May 1 and 20, 2018) was conducted among CMROs in Gondar town, Ethiopia.

Results

Among the 60 pseudo-client visits, 95% of them dispensed medications. The overall counseling approach was found to be 42.6% which improved to 58.3% when the pseudo-clients demanded it. Duration (73.3%) and signs/symptoms (45%) of headache were asked before dispensing the medications. Dosing frequency (86.7%), indication (60%) and dosage form (35%) were the most discussed items. Ibuprofen (45%) and diclofenac (41.5%) were primarily added to paracetamol for better headache treatment. Effectiveness (61.7%) and cost (21.7%) were the main criteria to choose drugs. In the cross-sectional survey, 60 participants were requested and 51 of them agreed to participate (response rate of 85%). Of these participants, 64.7% agreed that managing headache symptomatically is challenging. Patient lack of confidence in dispensers (41.2%) and lack of updated medical information (31.4%) were reported as the primary barriers to counsel clients.

Conclusion

This study demonstrated the practical gaps in counseling practices and poor headache management of community pharmacies in Gondar city. National stakeholders in collaboration with academic organizations should be involved in continuous clinical training and education regarding proper counseling practices.