Pusat Pengajian Sains Perubatan - Tesis

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Patient safety culture: development and evaluation of an intervention to enhance nurses’ perception on handoffs and safety in katsina state public hospitals, north-western Nigeria
(2024-07)
Kaware, Musa Sani
Patient safety entails preventing avoidable harm during healthcare delivery and has become a pressing concern in the healthcare sector due to growing awareness of potential risks and errors. In Nigeria, the burden of unsafe care carries profound consequences, including medical errors, infections, prolonged hospital stays, elevated healthcare costs, and reduced patient quality of life. This study determined the level of patient safety culture, identified factors linked to negative perceptions of this culture, developed and validated an educational intervention module, and evaluated its effectiveness among nurses in Katsina State Public Hospitals, North-West Nigeria. In Phase I, a cross-sectional study employing the Hospital Survey on Patient Safety Culture (HSOPSC) assessed patient safety culture among 430 nurses across 20 hospitals. Data analysis, performed using SPSS v.23, described the background and job-related characteristics of respondents and their perception of patient safety culture. Simple and multiple logistic regression analyses identified factors associated with negative perceptions. In Phase II, a Delphi technique validated the developed educational intervention module. In Phase III, a Quasi-Experimental design was employed to evaluate the intervention's effectiveness on nurses' perceptions of patient handoff and safety. Repeated-measures ANOVA was used to assess the intervention's impact, with a significance level set at α = 0.05. The study revealed that a majority of participants were female (59.8%), aged 30–39 years. Most had 1–5 years of hospital experience, with 46.4% working 40–59 hours per week. Nearly all (96.9%) had direct patient contact. The study identified four factors that were significantly associated with overall negative perceptions of patient safety culture. These include nurses who reported fewer events (five or less) in last 12 months with adjusted odds ratio of 2.66, (95% CI = 1.03–4.97), organizational learning and continuous improvement 2.39 (95% CI = 1.40–4.10), staffing 3.15 (95% CI = 1.34–7.17), and patient handoffs and transitions 1.48 (95% CI = 1.09–3.12). The educational module achieved good content validity. Repeated-measures ANOVA indicated significant mean differences across three assessment time points (pre-intervention, 3.05±0.32, post-intervention, 3.43±0.45, Follow-up, 3.34±0.40), with the educational intervention producing significant effects, F Stat 67.58, p<0.001. The post-hoc pairwise comparison, using the Bonferroni correction, revealed statistically significant mean differences in patient handoffs and safety perception scores across assessment time points. In conclusion, this study highlights the significance of addressing patient safety culture among nurses in Nigerian public hospitals. It identifies areas for improvement in patient safety culture and effectively develops, validates, and demonstrates the educational intervention module's ability to enhance patient handoff and safety perceptions among nurses. Thus, it should be integrated into nursing education and practice to enhance healthcare quality and reduce adverse events in Nigeria.
The effect of non-severe traumatic brain injury on the functional organisation of the default mode network
(2024-09)
Rahman, Muhammad Riddha Abdul
The organisation of the resting-state networks (RSNs) can provide insight into the functional aspects of the brain. The default mode network (DMN), one of the RSNs, is a set of brain regions that are active when the individual is not engaged in a specific task, but rather in a state of rest or introspection. The DMN has been implicated in various cognitive functions, such as memory, self-referential processing, and social cognition. Traumatic brain injury (TBI) is a common cause of neurological impairment that can affect the structure and function of the DMN. However, most studies on the impact of TBI on the DMN have focused on severe or moderate cases, while the effect of non-severe TBI remains unclear. This study explored the longitudinal effects of non-severe TBI on the functional integrity and network organisation of the DMN using functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), as well as neuropsychological assessments and reaction time tasks. All participants underwent resting-state scanning (fMRI: Healthy, n = 20, TBI, n = 20; EEG: Healthy, n = 25, TBI, n = 25), while a subset of the participants was assessed using a neuropsychological battery of tests and reaction time tasks. Additionally, a subset of the participants returned for the second and third time scanning and assessments. All functional data were preprocessed and entered into statistical analysis, while the off-scanning assessments were statistically analysed separately and then entered into correlation analysis with the fMRI functional connectivity. Four nodes of the DMN were analysed for their intra and internetwork functional organisation: the precuneus or posterior cingulate cortex (PCC), medial prefrontal cortex (MPFC), and bilateral inferior parietal lobules (IPL). Within and between-group analyses were conducted to explore the alteration of functional organisation between the healthy and TBI groups. Significant alterations were detected in activation, functional and effective connectivity, global EEG connectivity, neuropsychological performance, and reaction time scores within the TBI groups across time, compared to the healthy control. Evidence of plasticity was also observed, particularly in the six-month time point. Therefore, this study holds significance in elucidating the reorganisation of the DMN following non-severe TBI and its long-term effects on the functional aspect of the brain, both in connectivity and cognitive domains.
Studies on the physicochemical, biomechanical and biological properties of novel decellularized bovine scaffold for bone regeneration
(2024-09)
Qabbani, Ali Abdul Qader Hameed Al
Bone grafting, the second most common transplant practice after blood transfusion, involves significant challenges in transferring xenogeneic donor bone cells to recipients due to potential immunological responses. This study aimed to explore the efficacy of producing bovine cancellous bone scaffolds by preserving the extracellular matrix (ECM) while eliminating native bone cells, comparing their physicochemical, mechanical, and biological properties with demineralized cancellous bone scaffolds. The study was conducted in three phases. In Phase I, cancellous bone blocks harvested from the bovine femoral head were physically cleansed, chemically defatted, and processed into two types of scaffolds: demineralized bovine cancellous bone (DMB) and decellularized bovine cancellous bone (DCC). Both scaffolds were freeze-dried and gamma-radiated. Various analyses, including histology, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy, were performed to evaluate the scaffolds. Recellularization studies was done using human osteoblast cells showed that DCC scaffolds produced a complete acellular ECM with wider pores, retained collagen fibrils, and exhibited better cell attachment, proliferation, and mineralization compared to DMB. In Phase II, the immuno-compatibility of DMB and DCC scaffolds was tested in male Balb/c mice models following peritoneal implantation. The results revealed that DCC scaffolds elicited significantly lower white blood cell counts and systemic inflammation compared to DMB and untreated native bone. Immunotoxicity analyses showed that the DMB group had higher CD4+ counts and increased pro-inflammatory cytokine expression, while the DCC group exhibited a more favourable immune response, with more CD8+ T cells and normal organ morphology, indicating better immuno-compatibility. Phase III focused on the bone regeneration capabilities of DMB and DCC scaffolds in male Sprague-Dawley rat calvarial critical-size defects. The study found that DCC scaffolds significantly promoted new bone formation, with enhanced defect closure and higher bone density observed in micro-CT analyses compared to DMB. DCC sites also demonstrated elevated mRNA levels of osteogenic markers such as osteonectin, osteopontin, and osteocalcin. RAMAN spectroscopy showed an increased abundance of collagen and bone minerals, particularly phosphate ions (PO43-), in DCC scaffolds. In conclusion, the decellularization technique effectively produced an acellular DCC scaffold with minimal ECM damage and superior osteogenic potential in both in vitro and in vivo models. DCC scaffolds demonstrated better immuno-compatibility and greater bone regeneration potential than DMB, making them a promising option for bone grafting applications.
Effects of ifenprodil treatment on pain behaviour, inflammation, and nociceptive responses in the spinal cord of complete freund’s adjuvant-induced chronic polyarthritis rat
(2024-09)
Noh, Ain’ Sabreena Mohd
Rheumatoid arthritis (RA) is a chronic inflammatory condition characterised by frequent reports of pain. Ifenprodil, a selective N-methyl-D-aspartate receptor-2B (NMDAR-2B) antagonist, has demonstrated a significant anti-nociceptive effect in chronic pain models. This study aimed to investigate the effect of Ifenprodil as a selective NMDAR-2B antagonist on pain behaviour, inflammation, and nociceptive responses in the spinal cord of CFA-induced polyarthritis, as well as its possible side effect on memory function. Arthritic rats received intrathecal treatment of either Ifenprodil (0.5 or 1.0 μg/μL) or Sodium Diclofenac (6 μg) (positive control) whereas arthritic (A) and non-arthritic (C) control groups were administered with 0.9% normal saline for 7 days (day-16 to -22 post-arthritic induction). Ankle joint diameter and circumference, pain behaviour assessments including von-Frey and hot-plate tests, mobility scoring, and memory test were conducted on day-0 (baseline), day-15 (pre-intervention) and day-23 (post-intervention). Histopathological examination was performed on the ipsilateral ankle joint while the lumbar region of the spinal cord (L4-L5) was collected for ELISA, immunohistochemistry and RT-qPCR analyses. The group receiving Ifenprodil (0.5 μg/μL) showed a non-significant trend of increased body weight with no change in total food intake, attenuation of thermal hyperalgesia, tactile allodynia and improved mobility and significant improvement in the morphology of the ipsilateral hind paws and ankle joints when compared to the arthritic rats receiving Ifenprodil at 1.0 μg/μL. Meanwhile, Ifenprodil has significantly decreased the level of NMDAR-2B, substance P, BDNF and TNF-α proteins with attenuation on the total and phosphorylated NMDAR-2B, BDNF, activated microglia (Iba-1) and P2X4 receptor (P2X4R) mRNA and proteins expression in the polyarthritis rats. Furthermore, pro-apoptotic caspase-3, caspase-8, PKB, and PI3Kcb markers were decreased with no change in the anti-apoptotic Bcl-2 level in the spinal cord compared to the arthritis control group. A significant improvement in the memory discriminative index observed in the polyarthritis rats, especially at the concentration of 0.5 µg/µL implies a beneficial influence of Ifenprodil on memory enhancement. Thus, Ifenprodil, particularly at 0.5 μg/μL demonstrated significant anti-nociceptive and anti-inflammatory effects comparable to those of Sodium Diclofenac. These results underscore the potential involvement of NMDAR-2B activation in the pathogenesis of chronic arthritic pain.
Effects of nnav1.5 expression modulation on mhc I antigen processing machinery and invasion potential of breast cancer cells
(2024-08)
Din, Ahmad Hafiz Murtadha Noor
The increase in expression and activity of voltage-gated sodium channel’s (VGSC) isoform, neonatal Nav1.5 (nNav1.5) in breast cancer have been associated with enhanced metastatic ability. Loss of immune surveillance enables cancer cells to metastasize hence this study is to explore the possible role of nNav1.5 in regulating the expression of immune components, MHC I antigen processing machinery (APM), which is deregulated in breast cancer. Several reports link VGSC and APM in neurons, but the correlation between nNav1.5 and APM in breast cancer is unknown. In this study, the gene expression of APM components (PSMB8, PSMB9, PSMB10, TAP1, TAP2, B2M and MHC I) and CD274 were measured and compared in the highly aggressive MDA-MB-231, less aggressive MCF-7 and control, non-cancerous breast epithelial, MCF 10A via real-time PCR. Gene expression of nNav1.5 and two metastatic markers, MMP1 and FN1, were included. After 3D spheroids for MDA-MB-231 and MCF-7 were established via liquid overlay method, their target genes’ expression was compared with the monolayer counterparts. The spheroid volumes were analysed using SpheroidSizer. To block nNav1.5 expression, tetrodotoxin (TTX) and siRNA were employed in MDA-MB-231 monolayer and spheroids, while Trichostatin A and nNav1.5-plasmid were utilised to increase nNav1.5 expression in MCF-7 monolayer and spheroids. The effects of modulating nNav1.5 were assessed by profiling all target genes using real-time PCR and on spheroid invasion ability using Cultrex kit. In monolayer model, highest nNav1.5 gene level was detected in MDA-MB-231 > MCF-7 but absent in MCF 10A. In contrast, MHC I, B2M, PSMB8, PSMB9, TAP1 and TAP2 were at the highest level in MCF 10A > MDA-MB-231 > MCF-7, except for PSMB10 with MCF-7 > MDA-MB-231. For CD274, the highest level was in MDA-MB-231 > MCF 10A > MCF-7. In spheroids of MDA-MB-231 and MCF-7, the level of nNav1.5, MMP1, and FN1, were upregulated but there were no changes in almost all APM genes (except TAP1 downregulation), compared to their respective monolayer model. CD274 is downregulated in MDA-MB-231 spheroid but upregulated in MCF-7 spheroid, compared to their monolayer model. In nNav1.5 blocking monolayer experiments, TTX upregulated nNav1.5, TAP2, B2M, MMP1, and FN1 but downregulated PSMB9. Alternatively, siRNA knocked down nNav1.5 gene (73.22% after 48 hours, 10 nM siRNA) in MDA-MB-231, thus resulted in the upregulation of B2M and MHC I, and the downregulation of PSMB8, PSMB9, PSMB10, TAP2, and CD274, but unchanged MMP1 and FN1. However, in MDA-MB-231 spheroid, both TTX and siRNA failed to induce expressional changes. On the invasion ability, siRNA pre-treated spheroid failed to form. In MCF-7 monolayer and spheroid model, TSA induced nNav1.5, PSMB9, B2M, MHC I, CD274, and MMP1 expression. In monolayer MCF-7, nNav1.5 upregulation via plasmid transfection increased all target genes but in spheroid, only nNav1.5 and MHC I were upregulated, while PSMB10 and B2M were downregulated. TSA showed increased spheroid invasion, but nNav1.5-plasmid pre-transfected cells formed spheroids with lower relative perimeter diameter. In summary, modulating nNav1.5 gene expression affected MHC I APM, CD274, and cell behaviour, hence can potentially improve breast cancer immunotherapies by countering tumour immune escape mechanism via rescuing MHC I. Overall, the study’s current findings support the influence of nNav1.5 on the expression regulation of immune component molecules in breast cancer.

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