In Vitro and In Vivo Testing of Ultra-Small Gold Nanoparticles as a Novel Drug Delivery Platform for Enhancing the Brain Penetration and Receptor Binding Affiinity of Central Nervous System Drugs.

The endothelial cells of brain capillaries form the so-called blood brain barrier (BBB) which protects the central nervous system (CNS) from the entry of neurotoxins and blood components. Consequently, more than 98% of potential CNS drugs fail to cross the BBB. Therefore in this thesis, we describe the development and testing of ultra-small gold nanoparticles (AuNPs) that can traffic drugs across the BBB into brain parenchyma, with the potential of also increasing the receptor-binding affinity of CNS drugs. In chapter one, we provide an introduction to the global impact of CNS diseases and discuss the anatomy and function of the BBB. Various strategies for CNS drug delivery are presented. Finally, we describe unique features of AuNPs that make them attractive as drug carriers for CNS delivery. Chapter two describes a novel CNS drug-delivery strategy involving the conjugation of 6-mercaptopurine riboside to AuNPs (6-MPR-AuNPs). The 6-MPR-AuNPs drastically decreased the clearance of 6-MPR from 6190 to 22.45 mL/min/kg. Correspondingly, the half-life of 6-MPR increased from 13.8 to 44.16 minutes and the AUC increased about 100-fold. Studies using rat liver homogenate revealed that AuNPs directly inhibited liver xanthine oxidase to stabilize 6-MPR. Chapter three examines the brain penetration of 6-MPR-AuNPs using whole-body imaging and CNS distribution experiments. Compared to control, the fluorescence intensity of FITC-labeled AuNPs was highest in the brain and cerebrospinal fluid. The AUC of CNS and plasma were respectively 5.3 and 142-fold higher with 6MPR-AuNPs. TEM provided direct evidence that 6-MPR-AuNPs penetrated the BBB and was distributed into cerebral parenchyma. In chapter four, we use dopamine-conjugated AuNPs (DA-AuNPs) to overcome the poor brain permeability of dopamine. Binding studies using human dopamine-receptor cells revealed that the binding affinity of DA-AuNPs was 10-fold higher than dopamine. Rat ex vivo studies produced receptor occupancy of 100 and 80%, for DA-AuNPs and DA respectively. The RO of smaller DA-AuNPs (5, 15, 50 nm) were respectively 90, 60, and 20%, whereas larger particles(100, 200nm)had RO of 5%. Finally, in chapter five, key the findings of this thesis are summarized and perspectives on future research are presented.PHDChemical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/99801/1/pnkansah_1.pd

Rural-Urban Migration and Its Effects on Infant and Child Mortality in Ghana

This paper examines the socioeconomic characteristics of rural-urban migrants, child mortality and maternity child health care in Ghana. Data from the 1988 Ghana Demographic and Health Survey shows that infant mortality is lower among rural-urban migrants compared to rural non-migrants. Proportional hazards model estimates reveal that the survival chances of children of rural-urban migration persist after controlling for socioeconomic characteristics. However, these advantages disappear after demographic variables are included in the model in spite of the proximity and accessibility to medical facilities enjoyed by the migrants. This finding suggests that socioeconomic and demographic characteristics of migrants could be an important determinant of the survival of children of rural-urban migrants.Cet article examine les caract\ue9ristiques socio-\ue9conomiques des migrants ruraux-urbains, la mortalit\ue9 infantile et les soins de sant\ue9 infantile dans les maternit\ue9s au Ghana. Les donn\ue9es de l'Enqu\ueate d\ue9mographique et de Sant\ue9 du Ghana de 1988 ont montr\ue9 que la mortalit\ue9 infantile est plus faible parmi les migrants ruraux-urbains que parmi les non-migrants ruraux. Des estimations du mod\ue8le al\ue9atoire (Proportional hazards Model) ont montr\ue9 que les chances de survie des enfants issus de l'immigration rurale-urbaine augmentent si on prend en compte les caract\ue9ristiques socio-\ue9conomiques. Cependant, quand on fait intervenir les variables d\ue9mographiques dans ce mod\ue8le, ces avantages disparaissent malgr\ue9 la proximit\ue9 et l'accessibilit\ue9 des centres m\ue9dicaux. Ce r\ue9sultat prouve que les caract\ue9ristiques socio-\ue9conomiques et d\ue9mographiques des migrants constituent un d\ue9terminant important de la survie des enfants issus des migrants ruraux-urbains

Psychological impact of COVID-19 on diabetes mellitus patients in Cape Coast, Ghana: a cross-sectional study

Introduction: COVID-19 pandemic has had a greater psychological impact on patients with chronic ailments such as diabetes mellitus, tuberculosis, and HIV/AIDS compared to those without chronic conditions. We explored the psychological impacts of COVID-19 among people living with diabetes mellitus in Ghana. Methods: this study employed a hospital-based cross-sectional design involving 157 diabetes mellitus patients aged 20 years and above. We assessed diabetes distress by the seventeen-item diabetes stress (DDS17) scale and COVID-19 worries by 3 specific benchmarks: “worry about overly affected due to diabetes if infected with COVID-19”, “worry about people with diabetes characterized as a risk group” and “worry about not able to manage diabetes if infected with COVID-19”. A close-ended questionnaire was used in data collection. Results: of 157 diabetic patients interviewed, the majority had type 2 diabetes mellitus with known complications and only 42.7% were managing COVID-19 symptoms. The participants showed moderate to high level of COVID-19 specific worry, moderate fear of isolation, and low level of diabetes-associated distress. About 33.8% of the study population expressed a sense of worry towards the pandemic. The logistic regression showed that age, employment status, and presence of other chronic diseases were significantly associated with worries about being overly affected if infected with COVID-19 due to their diabetes status. Age and sex were associated with worries about people with diabetes being characterized as a risk group and age, sex and employment status were associated with participants who were worried about not being able to manage diabetes if infected with COVID-19. Conclusion: the general trend indicates a sense of worry among diabetes patients during the COVID-19 pandemic which is associated with poorer psychological health. Clients' education and counseling on COVID-19 are necessary to address some of their concerns to minimize the level of anxiety and emotional stress in these individuals

Network p - median problems: theory and applications

The classical network p - median problem is the problem of identifying p (supply) points of the network minimizing some suitable measure of the collective "distances" of these p points from a finite number of designated possible "demand" points. This p - median problem has been generalized in this dissertation to the case where demand is continuously distributed, and then discussed in terms of points that are natural and distinguishing in the network context, i.e., "proper intersection" points and "interior" points, thus avoiding the less useful "vertices" and "nodes" terminologies commonly found in the literature;For the generalized 1 - median problem with uniformly distributed demand, and with the objective of minimizing distance, it is shown that membership of a "circuit" by an "edge" is sufficient for the disqualification of the interior points of the edge as possible supply point locations. For other versions, where demand is distributed in other than uniform fashion, and/or the objective is either a minimization of a suitable function of distance, or a minimization of travel cost, conditions are given to disqualify interior points of edges;For the generalized p - median problem (p (GREATERTHEQ) 2), with uniformly distributed demand and with the objective of minimizing distance, it is shown that the interior points of p edges belonging to p "disjoint minimal circuits" can be disqualified;As an example, a particular highway maintenance garage location problem has been modeled and analyzed as a generalized p - median problem.</p

Views of service users, their family or carers, and health care professionals on telerehabilitation for people with neurological conditions in Ghana: qualitative study

Background: Up to 50% of people in low- and middle-income countries do not receive the rehabilitation they require. Telerehabilitation has the potential to improve access to neurorehabilitation services especially in low- and middle-income countries. Although there are reports of the barriers and facilitators to telerehabilitation in such settings, almost all are anecdotal. Furthermore, family or carers have a significant influence on the adoption and success of telerehabilitation, but their views have not been reported.Objective: This study aimed to investigate the views of service users, their family or carers, and health care professionals (HCPs) on telerehabilitation for people with neurological conditions in Ghana.Methods: Two focus groups were held at Komfo Anokye Hospital in Kumasi, Ghana: one in person for service users (n=11) and their family or carers (n=9), conducted in the Ghanaian language of Twi, and one hybrid for HCPs (n=18) conducted in English. The mean (SD) age of the service users was 59.8 (8.6) years; 5 users had a stroke and 6 had Parkinson disease. The HCP group consisted of 7 speech and language therapists, 3 physiotherapists, 3 occupational therapists, 3 medical staff, 1 nurse, and 1 industry representative. Focus groups were semi-structured and explored previous experiences of telerehabilitation, perceived benefits and challenges, and solutions to overcome these challenges. Focus groups were audio transcribed, and the service user transcript was translated into English. The resulting transcripts were analyzed using thematic analysis.Results: Overall, participants were positive about the role of telerehabilitation but recommended hybrid delivery, with in-person rehabilitation in the early stages and telerehabilitation in the later stages. In relation to telerehabilitation in Ghana, there were 3 main themes: benefits, challenges or barriers, and implementation. Benefits included the convenience and lower cost for service users, the higher dose of therapy possible, and increased access for people in remote areas. However, challenges included lack of a stable internet connection, cost of phones and data packages, and low levels of literacy. Implementation issues included cultural relevance, information governance, and the platform used to deliver telerehabilitation, with most participants being familiar with WhatsApp.Conclusions: Telerehabilitation has the potential to be a useful method of delivering rehabilitation to people with neurological conditions in Ghana, especially in a hybrid rehabilitation model with telerehabilitation augmenting in-person sessions. However, many people were unaware of telerehabilitation, and challenges such as a reliable internet connection, cultural relevance, and costs need to be addressed. Clinical trials of low-cost telerehabilitation interventions contextualized to the specific user group are required

Urgent issues and prospects at the intersection of culture, memory, and witness interviews: Exploring the challenges for research and practice

The pursuit of justice increasingly relies on productive interactions between witnesses and investigators from diverse cultural backgrounds during investigative interviews. To date, the role of cultural context has largely been ignored by researchers in the field of investigative interviewing, despite repeated requests from practitioners and policymakers for evidence-based guidance for the conduct of interviews with people from different cultures. Through examining cultural differences in human memory and communication and considering specific contextual challenges for investigative interviewing through the lens of culture, this review and associated commentaries highlight the scope for considering culture and human diversity in research on, and the practice of, investigative interviewing with victims, witnesses, and other sources. Across 11 commentaries, contributors highlight the importance of considering the role of culture in different investigative interviewing practices (e.g., rapport building, questioning techniques) and contexts (e.g., gender-based violence, asylum seeking, child abuse), address common areas of cultural mismatch between interviewer–interviewee expectations, and identify critical future routes for research. We call for an increased focus in the investigative interviewing literature on the nature and needs of our global community and encourage constructive and collaborative discussion between researchers and practitioners from around the world to better identify specific challenges and work together towards evidence-based solutions