Poor Delivery Research Articles

Advanced Biomaterials for Cell-Specific Modulation and Restore of Cancer Immunotherapy.

The past decade has witnessed the explosive development of cancer immunotherapies. Nevertheless, low immunogenicity, limited specificity, poor delivery efficiency, and off‐target side effects remain to be the major limitations for broad implementation of cancer immunotherapies to patient bedside. Encouragingly, advanced biomaterials offering cell‐specific modulation of immunological cues bring new solutions for improving the therapeutic efficacy while relieving side effect risks. In this review, focus is given on how functional biomaterials can enable cell‐specific modulation of cancer immunotherapy within the cancer‐immune cycle, with particular emphasis on antigen‐presenting cells (APCs), T cells, and tumor microenvironment (TME)‐resident cells. By reviewing the current progress in biomaterial‐based cancer immunotherapy, here the aim is to provide a better understanding of biomaterials’ role in targeting modulation of antitumor immunity step‐by‐step and guidelines for rationally developing targeting biomaterials for more personalized cancer immunotherapy. Moreover, the current challenge and future perspective regarding the potential application and clinical translation will also be discussed.

Engineered EGCG‐Containing Biomimetic Nanoassemblies as Effective Delivery Platform for Enhanced Cancer Therapy

Nano‐based immunotherapy of therapeutic biomolecules is attractive but tremendously hampered by the poor delivery efficiency. This study reports a novel delivery system of fluorinated‐coordinative‐epigallocatechin gallate (EGCG), referring as FEGCG/Zn, through the integration of fluorination and zinc ions (Zn2+) into EGCG. The robust therapeutics of FEGCG/Zn are measured in terms of the regulating effect on programmed cell death ligand 1 (PD‐L1), the effective delivery of diverse biomolecules, and the hitchhiking ability using living cells. Taking small interfering RNA of PD‐L1 (siPD‐L1) and erythrocytes as an example, the fabricated biomimetic system achieves excellent siPD‐L1 delivery and further improves siPD‐L1 accumulation in tumors. Finally, the combination of FEGCG/Zn and siPD‐L1 promotes antitumor immunotherapy through alleviation of T cells exhaustion by regulating PD‐L1 expression in tumor cells. The results demonstrate that FEGCG/Zn substantially regulates PD‐L1 expression and improves immune‐biomolecule delivery by forming biomimetic nanoassemblies, offering a versatile platform for cancer immunotherapy.

Methods for CRISPR-Cas as Ribonucleoprotein Complex Delivery In Vivo.

The efficient delivery of CRISPR-Cas components is still a key and unsolved problem. CRISPR-Cas delivery in the form of a Cas protein+sgRNA (ribonucleoprotein complex, RNP complex), has proven to be extremely effective, since it allows to increase on-target activity, while reducing nonspecific activity. The key point for in vivo genome editing is the direct delivery of artificial nucleases and donor DNA molecules into the somatic cells of an adult organism. At the same time, control of the dose of artificial nucleases is impossible, which affects the efficiency of genome editing in the affected cells. Poor delivery efficiency and low editing efficacy reduce the overall potency of the in vivo genome editing process. Here we review how this problem is currently being solved in scientific works and what types of in vivo delivery methods of Cas9/sgRNA RNPs have been developed.

Apoptotic Body-Mediated Intracellular Delivery Strategy for Enhanced STING Activation and Improved Tumor Immunogenicity.

Agonists of stimulators of interferon genes (STING) are a promising class of immunotherapeutics that trigger potent innate immunity. However, the therapeutic efficacy of conventional STING agonists, such as 2',3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), is severely restricted to poor cytosolic delivery and lacks the capacity to promote the recognition of tumor-specific antigens. Here, we tackle these challenges through a nanovaccine platform based on Fenton-reactive and STING-activating nanoparticles, synergistically contributing to the generation of tumor-cell-derived apoptotic bodies (ABs). ABs loaded with exogenous cGAMP are readily phagocytosed by antigen-presenting cells (APCs), as a Trojan horse for rendering tumor cells with high immunogenicity instead of a noninflammatory response. This leads to enhanced STING activation and an improved tumor-specific antigen presentation ability, boosting the adaptive immunity in collaboration with innate immune. The strategy of exploiting a metal-based nanovaccine platform possesses great potential to be clinically translated into a trinitarian system of diagnosis, treatment, and prognosis.

The quest for service delivery: The case of a rural district municipality in the Mpumalanga province of South Africa

Background: In South Africa, poor service delivery has been a major problem in many municipalities, partly because of corruption, political patronage and skills deficits at local administrative levels.Aim: This study aimed to critically assess the extent of service delivery deficit and find ways to improve service delivery in the study area and beyond.Setting: This study is framed on the ideals of theory of social contract that states the relationship between the state and society. In this line, this study highlights Weber’s theory of bureaucracy and the new public management (NPM) that gets its theoretical foundations from public choice and principal–agent theories.Methods: The study used primary data collected from 120 respondents. A descriptive quantitative method was used using questionnaire and content analysis of official documentations.Results: The study finds that residents in the study area are not satisfied with the level of current municipal services provided. In addition, the study reveals that the municipality does not generate enough funds because of non-payment for the services rendered that will substantially reduce basic municipal services provision. Furthermore, contrary to the common belief that rural municipal residents demand free services, this study finds that residents are willing to pay modest fees for the quality services rendered.Conclusion: The residents in the Dr JS Moroka Local Municipality (DR JSMLM) value essential services such as water and electricity more than other services. The status of service delivery in the municipality is rated poor. However, the residents still believe that there are possibilities for the improvements in the service delivery if the municipality adheres to its Integrated Development Plan (IDP) for the years ahead.

Emerging systemic delivery strategies of oncolytic viruses: A key step toward cancer immunotherapy.

Oncolytic virotherapy (OVT) is a novel type of immunotherapy that induces anti-tumor responses through selective self-replication within cancer cells and oncolytic virus (OV)-mediated immunostimulation. Notably, talimogene laherparepvec (T-Vec) developed by the Amgen company in 2015, is the first FDA-approved OV product to be administered via intratumoral injection and has been the most successful OVT treatment. However, the systemic administration of OVs still faces huge challenges, including in vivo pre-existing neutralizing antibodies and poor targeting delivery efficacy. Recently, state-of-the-art progress has been made in the development of systemic delivery of OVs, which demonstrates a promising step toward broadening the scope of cancer immunotherapy and improving the clinical efficacy of OV delivery. Herein, this review describes the general characteristics of OVs, focusing on the action mechanisms of OVs as well as the advantages and disadvantages of OVT. The emerging multiple systemic administration approaches of OVs are summarized in the past five years. In addition, the combination treatments between OVT and traditional therapies (chemotherapy, thermotherapy, immunotherapy, and radiotherapy, etc.) are highlighted. Last but not least, the future prospects and challenges of OVT are also discussed, with the aim of facilitating medical researchers to extensively apply the OVT in the cancer therapy.

Hairpin-like siRNA-Based Spherical Nucleic Acids.

The therapeutic use of small interfering RNAs (siRNAs) as gene regulation agents has been limited by their poor stability and delivery. Although arranging siRNAs into a spherical nucleic acid (SNA) architecture to form siRNA-SNAs increases their stability and uptake, prototypical siRNA-SNAs consist of a hybridized architecture that causes guide strand dissociation from passenger strands, which limits the delivery of active siRNA duplexes. In this study, a new SNA design that directly attaches both siRNA strands to the SNA core through a single hairpin-shaped molecule to prevent guide strand dissociation is introduced and investigated. This hairpin-like architecture increases the number of siRNA duplexes that can be loaded onto an SNA by 4-fold compared to the original hybridized siRNA-SNA architecture. As a result, the hairpin-like siRNA-SNAs exhibit a 6-fold longer half-life in serum and decreased cytotoxicity. In addition, the hairpin-like siRNA-SNA produces more durable gene knockdown than the hybridized siRNA-SNA. This study shows how the chemistry used to immobilize siRNA on nanoparticles can markedly enhance biological function, and it establishes the hairpin-like architecture as a next-generation SNA construct that will be useful in life science and medical research.

RURAL SETTING: THE PARADOX OF ITS ACCESSIBILITY AND AFFORDABILITY IN THE URBAN PLANNING AND POLITICAL ACTIONING

The argument that rural areas or rurality will disappear in the face of undoubted urbanisation remains vague and inconclusive. However, the infrastructure poverty and poor service delivery that characterise rural spaces are evident. Using data from interview and focus group discussion (FGD) collected from sampled rural communities in Oyo State Nigeria, this study asks the question if there is no confusion or rather a paradox in what planning and politics ought to be in rural areas. The study concludes that planning and politics in the sampled community driving at opposite direction of public rural infrastructure and service good. The recommendation was for planning to be more rural oriented and the urban bias (as it relates to planning standards) corrected. The need for a more inclusive and responsive rural governance towards achieving inclusion that will promoted national rather than urban development was emphasised.

Batho Pele Principles in the 21st Century: The case of the Department of Home Affairs, South Africa

This article examined the relevance of the Batho Pele Principles in the 21st century. The Department of Home Affairs in South Africa was used as a case study. In 1997, the Batho Pele Principles were established as a mechanism to aid the improvement of service delivery in South Africa. However, there has been an increase in service delivery protests across the country over the last few years. Research has shown that the increased service delivery protests since the dawn of democracy in South Africa have often been linked to the fact that the needs of the general public have not been met by the incumbent government. The citizens, and more especially the poor, are not satisfied with the lack of service delivery (or poor service delivery in some instances) where service has been delivered. The unhappiness of the citizens towards government’s lack of, or poor service delivery, seems to be compounded by public officials, who refuse to be accountable and responsive to the needs of the public they are expected to serve when they were appointed in public offices. The methodology used in this article is qualitative and quantitative. It is based on content analysis of the literature available on the application of Batho Pele Principles in South Africa to determine whether these principles are being applied in the provision of services at the Department of Home Affairs.

Assessing the effectiveness and efficiency of the provincial MuniMEC forum inter-government relations structures in the Eastern Cape Province, South Africa

Background: This research examines the effectiveness and efficiency of the Provincial MuniMEC in facilitating the Inter-Government Relations (IGR) arrangements for improvement provincial service provision mandate in the Eastern Cape Province. Post-1994 local government reforms led to the establishment of wall-to-wall municipalities to accelerate municipal services provision and the introduction of systemic municipal service provision guidelines as part of socio-economic transformation. Objective: The effectiveness and efficiency of this plan remains unclear. This research intends to address this issue with the view to contribute on strategies that can be adopted to improve service provision through the integration of IGR structures. Method: The study adopted a qualitative approach by administering structured questionnaires to purposely selected participants and carefully reviewed various documents and policies in IGR and Local Government. The questionnaire analysis included theoretical propositions that incorporated the efficiency of the provincial MuniMEC IGR structures, the legal IGR framework, and the participatory approach in MuniMEC IGR structures by stakeholders. Result: One core finding is that the MuniMEC IGR structure has contributed to the coordination and integration of government service delivery interventions at municipalities, yet little empirical evidence explains this improvement. Research shows that government’s IGR obligation to coordinate the integration of government service delivery interventions to municipalities could have more impact on service delivery improvement than the utilisation of a single-oriented approach. This study provides lessons on the view that any regulation without a structured implementation plan leads to poor service delivery. A key recommendation is that both the national and provincial government need to promote shared service delivery through the enhancement of the IGR framework.

Governance and Cadre Deployment in South Africa

The former Minister of Cooperative Governance and Traditional Affairs, Dr Zweli Mkhize, painted a bleak picture about the state of local government. The minister stated that 87 municipalities – about a third of South Africa’s total of 257 – remain dysfunctional or distressed. Underpinning this dysfunctionality was mismanagement due to political instability or interference, corruption and incompetence. This then results in poor service delivery, thus prolonging the periods of underdevelopment and poor access to basic services. This paper argues that cadre deployment has hindered the effective service delivery in local municipalities, thus the domino effect has been riots, protests and wasteful expenditure at the local government level. This results in participatory exclusion when it comes to collective development. By strictly analysing relevant literature related to corruption, and cadre deployment within the local government domain in South Africa, it became evident that the quest for socio-economic development in rural areas is deeply dependent on local governance having competent and skilled personnel who would prioritise service delivery rather than political loyalty at the expense of development. Nonetheless, the main question going forward is to what extent will loyalty ahead of competence be at the core of municipal governance and what implications will this have for future developmental prospects, good governance and service delivery?

Perception on constraining factors impacting recruitment and selection practices of building contractors in Dar Es Salaam, Tanzania

The acknowledged approach of securing workers by contractors is through recruitment process. Nevertheless, the recruitments and selections undertaken by contractors in developing countries are fraught with a number of constraints often leading to poor project delivery arising from unqualified employed labour force. Therefore, in the pursuit to better understand these constraining factors (CFs), this paper identified the key CFs impacting recruitment and selection practice of building contractors in Dar es Salaam, Tanzania, and propose advocated solutions. Convergence concurrent mixed methods approach comprising questionnaire and semi structured interview was used data collection. Stratified simple random sampling with 42 responses and purposive sampling with 8 responses were used. The quantitative data were analysed using descriptive statistics and inferential statistics (one sample t-tests). Directed content analysis method was employed for the qualitative data. The quantitative results showed that, ‘location of site’, ‘lack of experienced labourers’, ‘lack of policy to govern recruitment and selection process’ and ‘Low skill levels of construction workers as the highly ranked CFs. The qualitative results revealed ‘Location of site’ and ‘Payment differences between one company and another’ as the major CFs’. The advocated solutions were human resources and strategic management in nature and included provision of training, skills recognition and impartment, early preparation of recruitment plan, development of recruitment and selection policy, and motivation. The paper provides some useful insights into the constraints of recruitment and selection practice and proposes appropriate solutions. The implications drawn from the study are that, building contractors are put in a better position to comprehend the CFs and their associated practical solutions. This would improve performance outcomes in the construction sector and the economy as a whole. The findings would provide a basis for policy direction by the governments with respect to skilled labor recruitment in the construction industry.

Delivery strategies of RNA therapeutics to leukocytes

Harnessing RNA-based therapeutics for cancer, inflammation, and viral diseases is hindered by poor delivery of therapeutic RNA molecules. Targeting leukocytes to treat these conditions holds great promise, as they are key participants in their initiation, drug response, and treatment. The various extra- and intra-cellular obstacles that impediment the clinical implementation of therapeutic RNA can be overcome by utilizing drug delivery systems. However, delivery of therapeutic RNA to leukocytes poses an even greater challenge as these cells are difficult to reach and transfect upon systemic administration. This review briefly describes the existing successful delivery strategies that efficiently target leukocytes in vivo and discuss their potential clinical applicability.

Natural Small Molecules Enabled Efficient Immunotherapy through Supramolecular Self-Assembly in P53-Mutated Colorectal Cancer.

Nanomedicine, constructed from therapeutics, presents an advantage in drug delivery for cancer therapies. However, nanocarrier-based treatment systems have problems such as interbatch variability, multicomponent complexity, poor drug delivery, and carrier-related toxicity. To solve these issues, the natural molecule honokiol (HK), an anticancer agent in a phase I clinical trial (CTR20170822), was used to form a self-assembly nanoparticle (SA) through hydrogen bonding and hydrophobicity. The preparation of SA needs no molecular precursors or excipients in aqueous solution, and 100% drug-loaded SA exhibited superior tumor-targeting ability due to the enhanced permeability and retention (EPR) effect. Moreover, SA significantly enhanced the antitumor immunity relative to free HK, and the mechanism has notable selectivity to the p53 pathway. Furthermore, SA exhibited excellent physiological stability and inappreciable toxicity. Taken together, this supramolecular self-assembly strategy provides a safe and "molecular economy" model for rational design of clinical therapies and is expected to promote targeted therapy of HK, especially in colorectal cancer patients with obvious p53 status.

The importance of psychological support for parents and caregivers of children with a rare disease at diagnosis

Rare diseases are complex and difficult to diagnose, with parents and caregivers often reporting significant delays in receiving a definitive diagnosis. Following diagnosis, parents and caregivers often feel overwhelmed with emotions, including relief, guilt, and shock. The culmination of this emotional burden may lead to a deterioration of psychological health, ultimately reaching a stage where the parents struggle to cope. A systematic literature review was conducted of the articles on this topic by searching the electronic database, PubMed. Further studies were retrieved from a reference listing of relevant articles and consultation with experts in the field. The review was based on the guidance in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. The initial search identified 1276 articles, of which 37 met the inclusion criteria and were included in this review. The literature revealed key factors that appeared to contribute to psychological stress, including prolonged diagnostic odyssey, poor diagnostic delivery, lack of information and specialist knowledge, and convoluted healthcare systems. This review reinforces the need for psychological support amongst parents and caregivers of children with a rare disease at the time of diagnosis. The results of this literature review will be used to develop a statement of good practice for the support of parents and caregivers when a rare disease diagnosis is given.

TASK SHIFTING-AN EVALUATION OF THE NURSE-INITIATED MANAGEMENT OF PATIENTS ON ANTIRETROVIRAL TREATMENT (NIMART) STRATEGY

Ponte Academic JournalFeb 2022, Volume 78, Issue 2 TASK SHIFTING-AN EVALUATION OF THE NURSE-INITIATED MANAGEMENT OF PATIENTS ON ANTIRETROVIRAL TREATMENT (NIMART) STRATEGYAuthor(s): Pradeep Brijlal ,Oladeji Daramola, Prisicilla BrijlalJ. Ponte - Feb 2022 - Volume 78 - Issue 2 doi: 10.21506/j.ponte.2022.2.3 Abstract:The Nurse Initiated Management of Patients on Antiretroviral Treatment (NIMART) is a strategic management intervention that is intended to increase the number of HIV patients having access to treatment by task-shifting the administration of anti-retroviral drugs (ARV) from doctors to nurses. This study evaluated the efficiency of the implementation of the NIMART strategy, conducted at a primary health care clinic. The data was captured through an administered questionnaire for the patients and semi-structured interviews for the staff. The implementation of the NIMART strategy appeared to be affected by fragile leadership, lack of effective communication in the team, and poor service delivery at key points in the clinic. The common perception amongst the service providers was that the NIMART strategy was poorly formulated, marketed, managed, and evaluated. To improve the delivery of NIMART there must be a reorientation of the current ART service delivery at the primary health care clinic. Download full text:Check if you have access through your login credentials or your institution Username Password

Corporate Governance and the Quality of Service Delivery in Local Authorities: Case of Masvingo Municipality

It is arguably true that local authorities are expected to play a pivotal role in improving the economy of any nation in general and the standard of living for the citizens. However, governance challenges have been reported as one of the causes of poor performance and lack of sustainability in institutions. In recent years, local authorities have been experiencing poor governance, deplorable service delivery, misuse of public funds and failure to comply with laws. Upon realising that the quality of life of the urban residents in any country is to some extent related to the quality of service delivery by the local municipality of that city, the researchers felt primed to explore corporate governance (CG) issues. The main objective of the study was to examine the impact of CG on the quality of service delivery in Masvingo city. In probing the problem at hand, the study adopted a mixed methodology to generate data from a sample size of 70 research participants drawn from Masvingo Municipality. Questionnaires and interviews were administered to collect data from municipality employees, the Town Clerk, auditor, Councilors and residents of Masvingo city. The study revealed that CG impacts the quality of service delivery both positively and negatively. It was noted that failure to uphold the elements of CG could translate to poor service delivery while religious implementation of the elements of CG could create a conducive environment for achieving enhanced quality service delivery. Challenges such as nepotism, corruption, political interference and lack of financial resources were identified as rampant in Masvingo city. Measures to improve the quality of service delivery were suggested, namely, employees to be trained to improve their professional competence; nepotism, political interference and corruption be shunned to encourage good CG. It was also recommended that an all-stakeholder approach be put in place so that the elements of CG are taken into consideration for the sake of improving the quality of service delivery in Masvingo city

Training as a Tool for Service Delivery: A Case Study of Health Care Workers in Gwanda, Zimbabwe

The healthcare sector across most global south countries is challenged by various issues and this includes poor service delivery. The delivery of quality service within healthcare institutions is complicated by unprecedented emigration of healthcare workers to the global north. The other challenges include, poor funding and infrastructure, limited medical resources, equipment, and shortage of health care experts. As such this study examines how on and off the job training of healthcare workers impact service delivery. Adopting a quantitative paradigm, the paper identifies the training provided to healthcare workers and examines the effectiveness of the training for effective service delivery. A closed-ended structured questionnaire was used to elicit responses from 80 healthcare workers at Manama Mission Hospital in Gwanda, Zimbabwe. Findings revealed that practical hands-on experience (on-the-job training) supported with effective supervision and guidance from more experienced health workers aids effective service delivery. Training targeted at effective service delivery, constant assessment, and provision of constructive feedback from senior staff members are crucial measures for an effective healthcare system. Beyond constant training, measures must be put in place to ensure the retainment of healthcare experts within the country as an overstretched healthcare system will continue to battle with ineffective service delivery. This study adds to the body of knowledge related to employee training of healthcare workers within Zimbabwe.

Efficacy of Transformational Leadership on Performance of Mandera County Government in Kenya

This study investigated the efficacy of transformational leadership on performance of Mandera County government in Kenya based on the 4Is of transformational leadership. Mandera County has faced a plethora of challenges including its inability to marshal, develop, direct and control the human and financial resources leading to maladministration and poor service delivery, among others. The objective of the study was to examine the efficacy of the four dimensions of transformational leadership on performance on Mandera County government. The target population for the study comprised of the personnel elected and appointed and/or in the office of the Governor, Members of County Assembly and public service board employees of the county government (N=696). Stratified simple random sampling technique was applied to select the sample size from the total population (n=247). The study used structured questionnaires as the tool for collecting primary data. SPSS version 24 was applied to compute descriptive and inferential statistics. The study concluded that individualized consideration, inspirational motivation and idealized influence do not have a statistically significant influence on the performance of Mandera County Government (p>.05). In contrast, intellectual stimulation had a statistically significant association with performance of Mandera County Government (p>.05) In contrast, intellectual stimulation had a statistically significant association with performance of Mandera County Government (p>.05) However, the multiple linear regression analysis indicates that three of the 4Is of TL (individualized consideration, inspirational motivation, intellectual stimulation) excluding idealized influence were significantly associated with the performance of the County Government of Mandera. Leadership plays a central role in the success and failure of organizations and transformational leadership is the panacea for solving contemporary management and leadership challenges in sub-national levels in Kenya.

TEACHER-PUPIL CONFLICT IN SECONDARY SCHOOLS: EXPLANATORY TEACHERS’ NEEDS ANALYSIS IN ZIMBABWE

This study was motivated by the existence of reported teacher-pupil conflict in schools. Its purpose was to enhance teaching and learning interactive relation by exploring management strategies which reduce teacher-pupil conflicts. The study was guided by a qualitative research philosophy which used mixed data collection methods to capture social variables. The study design was a prescriptive seriation of three methods. First was a document analysis of school policies, rules and regulations to capture standards. This was followed by a survey to determine the problem distribution, contributing factors and possible management strategies. A self-reporting questionnaire gathered data from a stratified sample of 33 School Heads, 57 Deputy Heads, 241 Class Teachers and 274 School Prefects and 65 parents from 47 primary schools and 31secondary schools in Zimbabwe. Case studies of reported incidences were dominated by document analysis of reports and interviews for in-depth understanding. The study revealed that, Manicaland province had the highest number of teacher-pupil conflicts at secondary school level. The majority of them involved male teachers and male learners. Social factors such as Teachers’ failure to respect learners, verbal abuse and suspected favouritism practices were attached to teacher-pupil improper association. Cases linked to teachers’ poor lesson delivery included learner harassment, administering of corporal punishment and learner emotional abuse through unjustified punishments. The study deduced that young teachers have limited guidance and counselling skills ideal for adolescents. The study established the following strategic needs for the management of conflict between secondary school learners and teachers: first there is need for teacher in-service courses on adolescent class management. Course and workshop content to include human rights and conflict management. Learner participation in school governance need enhancement. Schools can improve teacher-learner communication skills and the use of collaborative decisions.