Use of digital media by adolescents for sexual and reproductive health and rights communication in sub-Saharan Africa: a protocol for systematic review.

BACKGROUND: Within the sub-Saharan African region, there is a growing concern for sexual and reproductive health and rights communication, and more particularly, for adolescents. Given the existing barriers associated with face-to-face access, the need to use digital media to access information and services has become desirable and imperative, especially so due to the COVID-19 pandemic. However, in sub-Saharan Africa, a synthesis of evidence that informs adolescents' digital media engagements for sexual and reproductive health and rights (SRHR) communication is limited. This systematic review therefore aims to examine and synthesize evidence on use of digital media for sexual and reproductive health and rights communication by adolescents in sub-Saharan Africa. METHODS: A search for peer-reviewed articles will be conducted in PubMed, ScienceDirect, Scopus, Embase, Web of Science, PsychINFO and Google Scholar with emphasis on those published between 2000 and 2023. Only observational and qualitative studies will be included. Quality assessment of included articles will be done using standardized checklists from the Joanna Briggs Institute. Both descriptive and narrative summaries will be used to appraise evidence from included studies. DISCUSSION: This review will be essential in providing information on the types of digital media adolescents use, the various SRHR issues they use this platform to address and their reasons for using it and associated challenges. It will also contribute to the advocacy for the inclusion of these technologies in the teaching and learning, provision of and access to SRHR information and services by teachers, public health providers and peer educators in the subregion. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020211491. This protocol follows the PRISMA-P guidelines for reporting systematic reviews.

Primary health care in practice: usual source of care and health system performance across 14 countries.

Primary health care (PHC) is central to attainment of the Sustainable Development Goals, yet comparable cross-country data on key aspects of primary care have not been widely available. This study analysed data from the People's Voice Survey, which was conducted in 2022 and 2023 in 14 countries. We documented usual source of care across countries and examined associations of usual source of care with core PHC services, quality ratings, and health system confidence. We found that 75% of respondents had a usual source of care, and that 40% of respondents accessed usual care in the public sector at primary level. 44% rated their usual source of care as very good or excellent. Access to PHC-linked screenings and treatments varied widely within and across countries. Having any usual source of care was associated with higher take-up of preventive services, greater access to treatment including mental health services, and greater health system endorsement. Strengthening links between health system users and primary care providers could improve take-up of preventive care and increase user satisfaction with health system performance.

Expression of HPV-16 E6 and E7 oncoproteins alters Chlamydia trachomatis developmental cycle and induces increased levels of immune regulatory molecules.

Introduction: Infection with Human Papillomavirus (HPV) is a recognized risk factor for Chlamydia trachomatis (CT) infection and vice versa. Coinfection of HPV and CT in women is a very common and usually asymptomatic finding that has been linked to increased risk of cervical cancer. It has been demonstrated that CT facilitates the entry of multiple high risk HPV genotypes, leading to damage of the mucosal barrier and interfering with immune responses and viral clearance, which ultimately favours viral persistence and malignant transformation. Although the facilitating effects elicited by CT infection on viral persistence have been reported, little is known about the consequences of HPV infection on CT development. Methods: Herein, we took advantage of a genetically modified human cervical cell line co-expressing HPV-16 major oncogenic proteins E6 and E7, as an experimental model allowing to investigate the possible effects that HPV infection would have on CT development. Results and discussion: Our results show that CT infection of HPV-16 E6E7 expressing cells induced an upregulation of the expression of E6E7 oncoproteins and host cell inhibitory molecules PD-L1, HVEM and CD160. Additionally, smaller chlamydial inclusions and reduced infectious progeny generation was observed in E6E7 cells. Ultrastructural analysis showed that expression of E6 and E7 did not alter total bacterial counts within inclusions but resulted in increased numbers of reticulate bodies (RB) and decreased production of infectious elementary bodies (EB). Our results indicate that during CT and HPV coinfection, E6 and E7 oncoproteins impair RB to EB transition and infectious progeny generation. On the other hand, higher expression of immune inhibitory molecules and HPV-16 E6E7 are cooperatively enhanced in CT-infected cells, which would favour both oncogenesis and immunosuppression. Our findings pose important implications for clinical management of patients with HPV and CT coinfection, suggesting that screening for the mutual infection could represent an opportunity to intervene and prevent severe reproductive health outcomes, such as cervical cancer and infertility.

Outcomes and Histological Variations of Neuroblastoma and Ganglioneuroblastoma with Paraneoplastic Syndromes.

BACKGROUND: Neuroblastomas are the most common extracranial solid malignancy in children with variable manifestations and complications depending on the presence of paraneoplastic syndromes. MATERIALS AND METHODS: We performed a single institution retrospective cohort study of all patients less than 18 years old diagnosed with neuroblastoma or ganglioneuroblastoma between January 2002 and July 2022. Patients were identified through the pathology and cancer registry and cross-referenced with pediatric records. Patient demographics, clinical presentation, treatment, and outcomes were collected. A univariate descriptive analysis of the collected data was conducted. RESULTS: In our study period, 130 children were diagnosed with neuroblastoma, and 15 were diagnosed with ganglioneuroblastoma. There were 12 children with a paraneoplastic syndrome identified, 8 with NBL and 4 with ganglioneuroblastoma (GNBL). The average age at diagnosis was 22 months. All but 1 underwent resection prior to treatment of paraneoplastic syndrome, and 4 children required neoadjuvant therapy. Neurological complications were the most common with 10 children (83%). The average time from symptom onset to diagnosis was 0.7 months. Eight children had complete resolution of their symptoms after treatment and resection, 2 children recently started treatment within a year, 1 had partial resolution, and 1 died during treatment. The presence of tumor-infiltrating lymphocytes occurred in 4 children with neurologic paraneoplastic syndromes. Six children had neuropil rich tumors. CONCLUSION: The histological profile of paraneoplastic syndromes of neuroblastoma and ganglioneuroblastoma and their treatment across a single institution can be highly variable. The presence of tumor-infiltrating lymphocytes and neuropil may have an impact on paraneoplastic pathology.

Antibiotic-Resistant Bacteria in Drinking Water from the Greater Accra Region, Ghana: A Cross-Sectional Study, December 2021-March 2022.

With safely managed water accessible to only 19% of the population in Ghana, the majority of its residents are at risk of drinking contaminated water. Furthermore, this water could be a potential vehicle for the transmission of antimicrobial-resistant bacteria. This study assessed the presence of bacteria and the antibiotic resistance profile of Escherichia coli and Pseudomonas aeruginosa in drinking-water sources using membrane filtration and Kirby-Bauer disc diffusion methods. A total of 524 water samples were analyzed for total coliforms, total heterotrophic bacteria, E. coli and P. aeruginosa. Samples included sachets, bottled water, tap water, borehole and well water. Most of the sachet and bottled water samples were within the limits of Ghana's standards for safe drinking water for the parameters tested. Over 50% of tap and borehole water was also free of E. coli and P. aeruginosa. Overall, of 115 E. coli isolates from tap and ground water samples, most were resistant to cefuroxime (88.7%), trimethoprim-sulfamethoxazole (62.6%) and amoxicillin-clavulanate (52.2%). P. aeruginosa isolates were most resistant to aztreonam (48%). Multidrug resistance was predominantly seen among E. coli isolates (58%). Evidence from this study calls for routine antimicrobial resistance surveillance in drinking water across the country and additional treatment of water sources at household levels.

Underutilized legumes, Cajanus cajan and Glycine max may bring about antisickling effect in sickle cell disease by modulation of redox homeostasis in sickled erythrocytes and alteration of its functional chemistry.

The antisickling and anti-oxidative effect of the Cajanus cajan, Glycine max, and their blends were investigated in sickled erythrocytes. The powdered samples were analyzed for their nutritional and anti-nutritional constituents. Their aqueous extracts were analyzed for in vitro antioxidant activities. The extracts were incubated with sickled erythrocytes at 37°C for 6 hours and the antisickling effect examined via microscopic analysis. The blend was the most active and its incubated cells were subjected to anti-oxidative analysis which covers for GSH, SOD, catalase, and lipid peroxidation (LPO). Chemical functional group of the treated cells was analyzed with FTIR spectroscopy. The in silico binding of the predominant amino acid to hemoglobin was also investigated. An increased concentration of leucine was observed in the blend compared to that of C. cajan and G. max, respectively. Vitamins C, B6, and B9 were the only vitamins observed in the blend. Phytate and oxalate were present in all samples. All extracts displayed significant (p < .05) scavenging activities. Treatment with the blend exacerbated SOD and catalase activities as well as the GSH level, while suppressing LPO. FTIR analysis of the treated cells showed the presence of hydrophobic functional groups. Leucine was the predominant amino acid, and it showed a potent molecular interaction with HIS-87 residue of the alpha chain of 1HCO. C. cajan and G. max blend inhibited sickling activities of sickle erythrocytes, while concomitantly exacerbating their endogenous antioxidant enzymes activity and modification of the functional chemistry. PRACTICAL APPLICATIONS: Cajanus cajan and Glycine max are among the common underutilized legumes in Nigeria. Aside their nutritional properties, these legumes have been used from time immemorial for the treatment and management of various ailments. Sickle cell anemia is a class of hemoglobinopathy common in Sub-Saharan Africa. There have been concerns about its treatment owing to the increasing scourge of the disease coupled to the financial burden of its management. This study reports the ability of the potentials of the legumes to prevent sickling activities of sickled erythrocytes and the possible biochemical mechanism involved.

Effects of Intrauterine Infusion of Micronised Purified Flavonoid Fraction (MPFF) in Metritis-Diagnosed Dairy Cows Naturally Infected by E. coli during the Early Postpartum.

The occurrence of metritis during the postpartum period causes serious economic losses in dairy cattle. The Micronised Purified Flavonoid Fraction (MPFF) is a polyphenolic flavonoid compound which is considered to have many health-related properties such as antibiotic, anti-inflammatory, phlebotonic, and several vascular-protecting activities. The aim was to evaluate the effects of a new strategic therapy for metritis based on MPFF intrauterine infusions during the early postpartum in dairy cows naturally infected by Escherichia coli. The clinical effects on reproductive anatomical structures and chronological involution dynamics were monitored until day 24 postpartum by ultrasonography. Moreover, uterine bacteriological and cytological (polymorphonuclear neutrophils; PMNs) profiles were analysed before and after MPFF infusion. The results showed that the success rate (% cure) at day 24 postpartum was improved significantly when using higher MPFF doses (p < 0.05). Moreover, MPFF treatment acutely diminished the size of the cervix and uterus and improved the involution process during the first 24 days (p < 0.05). The prevalence of pathogenic bacteria found in in vitro cultures was significantly variable (p < 0.01), as were the antibiotic sensitivity patterns. Pathogenic bacteria isolates decreased after MPFF applications in a dose−response fashion (p < 0.01), while isolates obtained from controls and low-dose-MPFF-treated animals were stable and similar (p > 0.05). The sensitivity patterns of pathogenic bacteria isolated in in vitro cultures from MPFF-treated animals were variable, although resistance to E. coli, Staphylococcus aureus, Bacillus spp., and coliforms was shown irrespective of the MPFF doses used. However, MPFF-treated cows showed a dose−response effect regarding PMN rates (p < 0.05). The calving-first service, calving−conception interval, and conception rate improved significantly from using higher MPFF doses (p < 0.05). In conclusion, this study shows that MPFF treatment differentially affects uterine involution, bacteriological profiles, cytological traits, and reproductive performance in metritis-positive dairy cows naturally infected by E. coli.

Validation of automated fluorescent-based technology for measuring total nucleated cell viability of hematopoietic progenitor cell products.

BACKGROUND: A reliable rapid method for measuring total nucleated cell (TNC) viability is essential for cell-based products manufacturing. The trypan blue (TB) exclusion method, commonly used to measure TNC viability of hematopoietic progenitor cell (HPC) products, is a subjective assay, typically uses a microscope, and includes a limited number of cells. The NucleoCounter NC-200 is an automated fluorescent-based cell counter that uses pre-calibrated cartridges with acridine orange and DAPI dyes to measure cell count and viability. This study describes the validation of the NC-200 for testing HPC's viability. METHODS: Samples from 189 fresh and 60 cryopreserved HPC products were included. Fresh products were tested for viability after collection by both TB and NC-200. 7-aminoactinomycin D (7AAD) CD45+ cell viability results were obtained from a flow cytometry test. Cryopreserved products thawed specimens were tested for viability by both TB and NC-200. The NC-200 viability results were compared with the other methods. Acceptability criteria were defined as ≤10% difference between the NC-200 method and the other methods for at least 95% of the samples. RESULTS: Fresh products' mean viability difference between NC-200 and TB or 7AAD CD45+ method was 4.9% (95%CI 4.6-5.4) and 2.8% (95%CI 2.2-3.4), respectively. Thawed products' mean viability difference between NC-200 and TB was 3.0% (95%CI 0.4-5.6). CONCLUSION: The NC-200 automated fluorescent-based method can be used effectively to determine HPC's viability for both fresh and cryopreserved products. It can help eliminate human bias and provide consistent data and operational ease.

Comparison of Conventional and Microwave Synthesis of Phenyl-1H-pyrazoles and Phenyl-1H-pyrazoles-4-carboxylic Acid Derivatives.

BACKGROUND: Privileged scaffolds are of high importance for molecules containing the pyrazole subunit due to their broad spectrum of pharmacological activities. For this reason, a method that is more efficient needs to be developed for the preparation of pyrazole derivatives. OBJECTIVE: The purpose of this study was the optimisation of the conventional synthesis of the pyrazole ring and the oxidation of phenyl-1H-pyrazole-4-carbaldehyde to phenyl-1H-pyrazole-4-carboxylic acid through Microwave- Assisted Organic Synthesis (MAOS). METHODS: We performed a comparison between conventional synthesis and conventional synthesis with microwave heating using the synthesis method of pyrazole ring described by Finar and Godfrey and for the oxidation of phenyl-1H-pyrazole-4-carbaldehyde, the method described by Shriner and Kleiderer was used. RESULTS: MAOS reduces the reaction time to obtain all compounds compared to conventional heating. At a temperature of 60°C, 5 minutes of reaction time, and power of 50 W, the yield of phenyl-1H-pyrazoles (3a-m) compounds was in the range of 91 - 98% using MAOS, which is better than conventional heating (72 - 90%, 75ºC, 2 hours). An improvement in the yield for the oxidation reaction was also achieved with MAOS. The compounds (5a-m) were obtained with yields ranging from 62 - 92% (80ºC, 2 minutes, 150 W), while the yields with conventional heating were in the range of 48 - 85% (80ºC, 1 hour). The 26 compounds were achieved through an easy work-up procedure with no chromatographic separation. The pure products were characterised by the spectral data obtained from IR, MS, 1H and 13C NMR or HSQC/HMBC techniques. CONCLUSION: The advantages of MAOS include short reaction time and increased yield, due to which it is an attractive option for pyrazole compounds synthesis.

Genome-based local dynamics of canine rabies virus epidemiology, transmission, and evolution in Davao City, Philippines, 2018-2019.

Rabies is a fatal zoonotic and neglected tropical disease caused by the rabies virus (RABV) and is associated with neuronal dysfunction and death, with dogs as the predominant carrier. The Philippines plans to eradicate rabies by 2022, but this is challenged with sub-optimal coverage of vaccination programs coupled with sustained transmission chains, making it unable to eradicate the disease. We investigated the dynamics of canine rabies in the highly urbanized Davao City of the Philippines and its neighboring localities by assessing genetic relationships, transmission patterns, selection pressure, and recombination events using the whole genome sequence of 49 RABV cases from June 2018 to May 2019, majority of which (46%) were from the district of Talomo, Davao City. Although phylogeographic clustering was observed, local variants also exhibited genetic sub-lineages. Phylogenetic and spatial transmission analysis provided evidence for intra- and inter-city transmission predominantly through the Talomo district of Davao City. Around 84% of the cases were owned dogs, but the genetic similiarity of RABVs from stray and owned dogs further alluded to the role of the former as transmission vectors. The high rate of improper vaccination among the affected dogs (80%) was also a likely contributor to transmission. The RABV population under Investigation is generally under strong purifying selection with no evidence of vaccine evasion due to the genetic homogeneity of viruses from vaccinated and improperly vaccinated dogs. However, some homologous recombination (HR) events were identified along the G and L genes, also predominantly associated with viruses from Talomo. The complementary findings on epidemiology, transmission, and recombination for Talomo suggest that high incidence areas can be seeds for virus dispersal and evolution. We recommend further Investigations on the possibility of HR in future large-scale genome studies. Finally, districts associated with these phenomena can be targeted for evidence-based local strategies that can help break RABV transmission chains and prevent emergence of novel strains in Davao City.

The Prolactin Inducible Protein Modulates Antitumor Immune Responses and Metastasis in a Mouse Model of Triple Negative Breast Cancer.

The prolactin inducible protein (PIP) is expressed to varying degrees in more than 90% of breast cancers (BCs). Although high levels of PIP expression in BC has been shown to correlate with better prognosis and patient response to chemotherapy, some studies suggest that PIP may also play a role in metastasis. Here, we investigated the role of PIP in BC using the well-established 4T1 and E0771 mouse BC cell lines. Stable expression of PIP in both cell lines did not significantly alter their proliferation, migration, and response to anticancer drugs in vitro compared to empty vector control. To assess the effect of PIP expression on breast tumorigenesis in vivo, the 4T1 syngeneic transplantable mouse model was utilized. In immunocompetent syngeneic BALB/c mice, PIP-expressing 4T1 primary tumors displayed delayed tumor onset and reduced tumor growth, and this was associated with higher percentages of natural killer cells and reduced percentages of type 2 T-helper cells in the tumor environment. The delayed tumor onset and growth were abrogated in immunodeficient mice, suggesting that PIP-mediated modulation of primary tumor growth involves an intact immune system. Paradoxically, we also observed that PIP expression was associated with a higher number of 4T1 colonies in the lungs in both the immunocompetent and immunodeficient mice. Gene expression analysis of PIP-expressing 4T1 cells (4T1-PIP) revealed that genes associated with tumor metastasis such as CCL7, MMP3 and MMP13, were significantly upregulated in 4T1-PIP cells when compared to the empty vector control (4T1-EV) cells. Collectively, these studies strongly suggest that PIP may possess a double-edge sword effect in BC, enhancing both antitumor immunity as well as metastasis.

Prevalence of CYP2C19 polymorphism in Bogotá, Colombia: The first report of allele *17.

INTRODUCTION: Proton pump inhibitors (PPIs) are a group of drugs that are essential for the treatment of acid-related disorders, such as gastroesophageal reflux (GERD), dyspepsia, gastric ulcers and Helicobacter pylori (H. pylori) infection. PPIs such as omeprazole, esomeprazole, pantoprazole and lansoprazole are metabolized by the CYP2C19 enzyme, which is encoded by a polymorphic gene. Four polymorphisms have an impact on the speed of PPI metabolism: CYP2C19*1/*1 (extensive metabolizers), CYP2C19*2/*2 (intermediate metabolizers), CYP2C19*3/*3 (poor metabolizers) and CYP2C19*17/*17 (ultrarapid metabolizers). Extensive and ultrarapid metabolizers inactivate PPIs quickly, which consequently causes low plasma concentrations of PPIs, while intermediate or poor metabolizers have higher plasma concentrations of PPIs and, therefore, PPIs have greater therapeutic efficacy in individuals with these polymorphisms. OBJECTIVE: To determine the frequency of genetic polymorphisms of the CPY2C19 enzyme in Bogotá, Colombia. METHODS: This observational study was conducted in Bogotá between 2012 and 2015 and was part of a clinical trial (ID: NCT03650543). It included 239 subjects with dyspepsia, H. pylori infection, or GERD symptoms. CYP2C19 genotyping was performed on gastric biopsy samples. Polymorphisms *1, *2, and *3 were analyzed by real-time PCR (Roche®), and PCR-RFLP was used to determine the presence of polymorphism *17. RESULTS: The distribution of different types of PPI metabolizers was as follows: extensive (70.7%), ultrarapid (12.9%), intermediate (8.8%) and poor (0.8%). CONCLUSION: The population studied consisted mainly of extensive and ultrarapid PPI metabolizers. These findings show that it is necessary to increase PPI doses in this group of subjects or to use PPIs that are not metabolized by CYP2C19 (rabeprazole). This is the first Colombian work to identify ultrarapid metabolizers.

Semaphorin 3E Promotes Susceptibility to Leishmania major Infection in Mice by Suppressing CD4+ Th1 Cell Response.

Protective immunity to cutaneous leishmaniasis is mediated by IFN-γ-secreting CD4+ Th1 cells. IFN-γ binds to its receptor on Leishmania-infected macrophages, resulting in their activation, production of NO, and subsequent destruction of parasites. This study investigated the role of Semaphorin 3E (Sema3E) in host immunity to Leishmania major infection in mice. We observed a significant increase in Sema3E expression at the infection site at different timepoints following L. major infection. Sema3E-deficient (Sema3E knockout [KO]) mice were highly resistant to L. major infection, as evidenced by significantly (p < 0.05-0.01) reduced lesion sizes and lower parasite burdens at different times postinfection when compared with their infected wild-type counterpart mice. The enhanced resistance of Sema3E KO mice was associated with significantly (p < 0.05) increased IFN-γ production by CD4+ T cells. CD11c+ cells from Sema3E KO mice displayed increased expression of costimulatory molecules and IL-12p40 production following L. major infection and were more efficient at inducing the differentiation of Leishmania-specific CD4+ T cells to Th1 cells than their wild-type counterpart cells. Furthermore, purified CD4+ T cells from Sema3E KO mice showed increased propensity to differentiate into Th1 cells in vitro, and this was significantly inhibited by the addition of recombinant Sema3E in vitro. These findings collectively show that Sema3E is a negative regulator of protective CD4+ Th1 immunity in mice infected with L. major and suggest that its neutralization may be a potential therapeutic option for treating individuals suffering from cutaneous leishmaniasis.

Isolation and Preparation of Bone Marrow-Derived Immune Cells for Metabolic Analysis.

The isolation of immune cells from the bone marrow is important for obtaining sufficient numbers for downstream analysis. Immune cells derived from the bone marrow may be subjected to metabolic assays for analysis or used to test the effect of infectious agents on immune cells. Here, we describe a process for the isolation of macrophages, dendritic cells, and neutrophils from mice. Using the methods described herein, specific immune cells with purity above 85-90% can be obtained from the bone marrow of mice.

Leishmania Immunity: Advancing Immunotherapy and Vaccine Development.

Parasitic diseases still constitute a major global health problem affecting billions of people around the world. These diseases are capable of becoming chronic and result in high morbidity and mortality. Worldwide, millions of people die each year from parasitic diseases, with the bulk of those deaths resulting from parasitic protozoan infections. Leishmaniasis, which is a disease caused by over 20 species of the protozoan parasite belonging to the genus Leishmania, is an important neglected disease. According to the World Health Organization (WHO), an estimated 12 million people are currently infected in about 98 countries and about 2 million new cases occur yearly, resulting in about 50,000 deaths each year. Current treatment methods for leishmaniasis are not very effective and often have significant side effects. In this review, we discussed host immunity to leishmaniasis, various treatment options currently being utilized, and the progress of both immunotherapy and vaccine development strategies used so far in leishmaniasis. We concluded with insights into what the future holds toward the fight against this debilitating parasitic disease.

Synthesis of three triterpene series and their activity against respiratory syncytial virus.

The human respiratory syncytial virus (hRSV) is a leading cause of hospitalization due to acute lower respiratory infection especially in infants and young children, sometimes causing fatal cases. The monoclonal antibody palivizumab is one of the available options for preventing this virus, and at the moment there are several hRSV vaccine trials underway. Unfortunately, the only drug option to treat hRSV infection is ribavirin, which can be used in severe high-risk cases. For this reason, new medicines are needed and, in this context, the triterpenes and their derivatives are promising alternatives, since many of them have shown important antiviral activity, such as bevirimat. Therefore, we report three series of triterpene (betulin (BE), betulinic acid (BA), and ursolic acid (UA)) derivatives tested against hRSV. The derivatives were synthesized by using commercial anhydrides in an easy and inexpensive step reaction. For the antiviral assay, A549 cells were infected by hRSV and after 96 h of compound or ribavirin (positive control) treatment, the cell viability was tested by MTT assay. DMSO, non-infected cells and infected cells without treatment were used as negative control. The triterpene esterification at the hydroxyl group resulted in 17 derivatives. The 3,28-di-O-acetylbetulin derivative (1a) showed the best results for cell viability, and real-time PCR amplification was performed for 1a treatment. Remarkably, one new anti-hRSV prototype was obtained through an easy synthesis of BE, which shall represent an alternative for a new lead compound for anti-hRSV therapy.

Fatty Acids Rich Extract From Clerodendrum volubile Suppresses Cell Migration; Abates Oxidative Stress; and Regulates Cell Cycle Progression in Glioblastoma Multiforme (U87 MG) Cells.

Glioblastoma multiforme (GBM) is a malignant primary type of brain cancer with high proliferation and metastasis rates due to involvement of the microglial cell. It is resistant against available chemotherapy. Many strategic protocols have been developed but prognosis and patient life has not improved substantially. In this study, the anti-metastatic and antioxidant effect of fatty acids from Clerodendrum volubile leaves were investigated in U87-MG (Human Glioblastoma Multiforme) cell lines. The extracted fatty acids were incubated with U87-MG cells for 48 h. The anti-proliferative effect was determined by MTT assay, while apoptosis and cell cycle were analyzed with BD FACSCalibur. The transwell assay protocol was utilized in the analysis of cell migration and invasion. The treated cell lines were also assessed for reduced glutathione (GSH) level, catalase, superoxide dismutase (SOD) and lipid peroxidation. The fatty acid extract showed significant inhibitory activity on cell proliferation and cell cycle progression, mitigated oxidative stress, and suppressed migration and invasion in U-87 MG cell lines. These results give credence to the therapeutic potential of this plant against cancer, especially GBM.

SERCA plays a crucial role in the toxicity of a betulinic acid derivative with potential antimalarial activity.

Malaria is one of the most significant infectious diseases that affect poor populations in tropical areas throughout the world. Plants have been shown to be a good source for the development of new antimalarial chemotherapeutic agents, as shown for the discovery of quinine and artemisinin derivatives. Our research group has been working with semisynthetic triterpene derivatives that show potential antimalarial activity toward different strains of Plasmodium falciparum by specifically modulating calcium pathways in the parasite. Promising results were obtained for nanomolar concentrations of the semisynthetic betulinic acid derivative LAFIS13 against the P. falciparum 3D7 strain in vitro, with a selectivity index of 18 compared to a mammalian cell line. Continuing these studies, we present here in vitro and in vivo toxicological evaluations of this compound, followed by docking studies with PfATP6, a sarco/endoplasmic reticulum Ca+2-ATPase (SERCA) protein. LAFIS13 showed an LD50 between 300 and 50 mg/kg, and the acute administration of 50 mg/kg (i.p.) had no negative effects on hematological, biochemical and histopathological parameters. Based on the results of the in vitro assays, LAFIS13 not exerted significant effects on coagulation parameters of human peripheral blood, but a hemolytic activity was verified at higher concentrations. According to the molecular docking study, the PfATP6 protein may be a target for LAFIS13, which corroborates its previously reported modulatory effects on calcium homeostasis in the parasite. Notably, LAFIS13 showed a higher selectivity for the mammalian SERCA protein than for PfATP6, thus impairing the selectivity between parasite and host. In summary, the direct interaction with calcium pumps and the hemolytic potential of the compound proved to be plausible mechanism of LAFIS13 toxicity.

The experiences of nurse educators in implementing evidence-based practice in teaching and learning.

BACKGROUND: Nurse educators have a vital role to mentor student nurses in relation to developing evidence-based practice (EBP) skills, accessing research products and participating in research projects. This requires more innovative teaching approaches that promote active participation, creativity and critical thinking in students such as online teaching and learning, accessing electronic resources, video conferencing and research-based teaching and learning. AIM: To determine the nurse educators' experiences in implementing EBP in teaching and learning, and to describe the importance and benefits of EBP teaching and learning to the nursing profession, especially for nurse educators and student nurses. SETTING: Two chosen campuses from Umgungundlovu Health District under the KwaZulu-Natal College of Nursing (KZNCN) and offering a 4-year R425 training programme. METHODS: Qualitative research design and methods were followed in conducting the study. A non-probability purposive sampling technique was used to access the sample of 12 nurse educators. Data were collected using semi-structured interviews, the interview guide, and the digital voice recorder. RESULTS: Data were analysed manually, following a content thematic approach and two themes emerged as challenges experienced by nurse educators with the implementation of EBP in teaching and learning and benefits and value of EBP in teaching and learning. Findings revealed that, although most of the nurse educators are supportive and displayed a positive attitude towards implementing EBP in teaching and learning, the level of knowledge and skills was questionable. This was coupled with a lack of motivation and commitment towards research. CONCLUSIONS: Evidence-based practice has an essential potential role to play through incorporating more practice-based evidence of nurse educators in teaching and learning implementation. The nurse educators should use EBP to ensure that student nurses receive high-quality nursing education.

How do the expectations of patients compare with their surgeons regarding outcomes of periacetabular osteotomy?

Our objective was to determine the frequency and strength of agreement between patients and their surgeons on preoperative expectations of the outcomes of periacetabular osteotomy (PAO) surgery. We also sought to determine whether patient preoperative function and pain levels were associated with patients' and surgeons' expectations and to identify the motivating factors for patients to undergo PAO. Two surgeons and their combined 68 patients preoperatively completed 4-point Likert-scales rating their expectations of improvement in six domains representing different hip symptoms after surgery. Domains included pain, stiffness, locking, stability, walking ability and athletic ability. Concordance between patient and surgeon expectation was evaluated by the percent of exact and partial agreement. Correlation analyses were performed to investigate associations between expectations of improvement and patient factors. Exact agreement between patients and surgeons ranged from 18.2% (stiffness) to 55.9% (pain) and partial agreement between patients and surgeons ranged from 48.5% (stiffness) to 100% (pain). Patients with higher UCLA scores tended to have lower surgeon expectations of improving walking ability (r = -0.34; P = 0.007) but higher expectations for improved athletic ability (r = 0.25; P = 0.04), and surgeons anticipated more improvement in walking for patients with higher stiffness (r = 0.31, P = 0.01) and pain (r = 0.38, P = 0.002). Similarly, patients with higher Short Form-12 physical component summary had lower surgeon expectations of improvement in walking ability (r = -0.40, P = 0.002) and stiffness (r = -0.35, P = 0.006). In the most domains there was frequent discrepancy between patient and surgeon expectations, with patients being more optimistic than their surgeons in every domain. For the pain domain, patients and surgeons had similar expectations.