Inadequate Delivery Research Articles

A novel treatment modality for rheumatoid arthritis: Inflammation-targeted multifunctional metal-organic frameworks with synergistic phototherapy and chemotherapy

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease with complex pathogenesis. Single chemotherapy struggles to eliminate the disease permanently and reduce the pain owing to drug resistance and inadequate delivery to target cells. This study developed hyaluronic acid (HA)-modified and methotrexate (MTX)-load metal-organic frameworks (denoted as FT-HA-MTX NPs), combining photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy to inhibit the progression of RA. In vitro experiments proved that the obtained NPs exhibited good biocompatibility and commendable photothermal conversion efficiency of 36.3 %. Additionally, they promoted ∙OH and O2 production via the Fenton reaction, which dramatically alleviated hypoxia and enhanced ROS generation, and induced substantial mortality in activated RAW 264.7 cells, with cell viability of 31.72 %. Cellular uptake and in vivo imaging confirmed that the modification of HA enabled the NPs to specifically target activated macrophage, ensured prolonged retention of NPs in inflamed synovial tissues, and reduced systemic toxicity. In vivo, after FT-HA-MTX NPs treatment with laser irradiation, the levels of TNF-α and IL-1β in the synovial tissue were reduced by approximately 50 % compared to those in the inflamed synovium, demonstrating a significant enhancement in the anti-inflammatory effect (p < 0.001). In conclusion, FT-HA-MTX NPs are promising inflammation-targeted multifunctional nanoparticles that combine PTT, PDT, and chemotherapy, thereby significantly inhibiting the progression of RA while reducing systemic toxicity.

Redox-Sensitive Poly(lactic-co-glycolic acid) Nanoparticles of Palbociclib: Development, Ultrasound/Photoacoustic Imaging, and Smart Breast Cancer Therapy.

Breast cancer is one of the leading causes of mortality in women globally. The efficacy of breast cancer treatments, notably chemotherapy, is hampered by inadequate localized delivery of anticancer agents to the tumor site, resulting in compromised efficacy and increased systemic toxicity. In this study, we have developed redox-sensitive poly(lactic-co-glycolic acid) (PLGA) nanoparticles for the smart delivery of palbociclib (PLB) to breast cancer. The particle size of formulated PLB@PLGA-NPs (nonredox-sensitive) and RS-PLB@PLGA-NPs (redox-sensitive) NPs were 187.1 ± 1.8 nm and 193.7 ± 1.5 nm, respectively. The zeta potentials of nonredox-sensitive and redox-sensitive NPs were +24.99 ± 2.67 mV and +9.095 ± 1.87 mV, respectively. The developed NPs were characterized for morphological and various physicochemical parameters such as SEM, TEM, XRD, DSC, TGA, XPS, etc. The % entrapment efficiency of PLB@PLGA-NPs and RS-PLB@PLGA-NPs was found to be 85.48 ± 1.29% and 87.72 ± 1.55%, respectively. RS-PLB@PLGA-NPs displayed a rapid drug release at acidic pH and a higher GSH concentration compared to PLB@PLGA-NPs. The cytotoxicity assay in MCF-7 cells suggested that PLB@PLGA-NPs and RS-PLB@PLGA-NPs were 5.24-fold and 14.53-fold higher cytotoxic compared to the free PLB, respectively. Further, the cellular uptake study demonstrated that redox-sensitive NPs had significantly higher cellular uptake compared to nonredox-sensitive NPs and free Coumarin 6 dye. Additionally, AO/EtBr assay and reactive oxygen species analysis confirmed the superior activity of RS-PLB@PLGA-NPs over PLB@PLGA-NPs and free PLB. In vivo anticancer activity in dimethyl-benz(a)anthracene-induced breast cancer rats depicted that RS-PLB@PLGA-NPs was highly effective in reducing the tumor size, hypoxic tumor, and tumor vascularity compared to PLB@PLGA-NPs and free PLB. Further, hemocompatibility study reveals that the developed NPs were nonhemolytic to human blood. Moreover, an in vivo histopathology study confirmed that both nanoparticles were safe and nontoxic to the vital organs.

Service Delivery Protests in the South African Government

The social insecurity present in the nation has impeded the desired democratic system from thriving in various communities due to the lack of progress since its inception. The municipal authorities continue to grapple with governance and service provision issues within their communities. The 1994 victory sparked anticipation and excitement in society, leading to the expectation of policy changes and the rectification of past imbalances. However, the situation has resulted in discourse, inequality, and conflict among communities and state institutions. Municipal authorities have been at the centre of service delivery protests and their inability to address the needs of the communities they serve. Protests have erupted at all levels of government, with the majority becoming violent and fueled by various motivations. This study aims to evaluate relative deprivation and community protests within the South African context and to explore their relationship. Furthermore, it seeks to provide possible recommendations on how to address this phenomenon. The study posits that service delivery protests are influenced by relative deprivation, which has persisted due to inadequate service delivery. The paper suggests that inclusive policies that encourage public participation and foster trust in state-society relations can alleviate deprivation and protests. The study used a qualitative approach, gathering data from secondary sources and materials.

Intranasal Administration of Mesenchymal Stem Cell-Derived Exosome Alleviates Hypoxic-Ischemic Brain Injury.

Hypoxic-ischemic brain injury arises from inadequate oxygen delivery to the brain, commonly occurring following cardiac arrest, which lacks effective treatments. Recent studies have demonstrated the therapeutic potential of exosomes released from mesenchymal stem cells. Given the challenge of systemic dilution associated with intravenous administration, intranasal delivery has emerged as a promising approach. In this study, we investigate the effects of intranasally administered exosomes in an animal model. Exosomes were isolated from the cell supernatants using the ultracentrifugation method. Brain injury was induced in Sprague-Dawley rats through a transient four-vessel occlusion model. Intranasal administration was conducted with 3 × 108 exosome particles in 20 µL of PBS or PBS alone, administered daily for 7 days post-injury. Long-term cognitive behavioral assessments, biodistribution of exosomes, and histological evaluations of apoptosis and neuroinflammation were conducted. Exosomes were primarily detected in the olfactory bulb one hour after intranasal administration, subsequently distributing to the striatum and midbrain. Rats treated with exosomes exhibited substantial improvement in cognitive function up to 28 days after the insult, and demonstrated significantly fewer apoptotic cells along with higher neuronal cell survival in the hippocampus. Exosomes were found to be taken up by microglia, leading to a decrease in the expression of cytotoxic inflammatory markers.

Emerging trends in disturbed function of the pancreas and dyspepsia: an Indian perspective

Disturbed function of the pancreas, especially exocrine pancreatic insufficiency (EPI) results in inadequate synthesis or delivery of the pancreatic enzyme leading to maldigestion. Due to the lack of specific symptoms and overlapping manifestations of EPI, it often goes undiagnosed and untreated. Dyspepsia is another common condition characterized by upper gastrointestinal symptoms caused by a heterogeneous group of disorders. This consensus aims at providing a comprehensive overview of the diagnosis and management of disturbed function of the pancreas and dyspepsia. A total of 95 gastroenterologists participated in expert group meetings organized via virtual focus group discussions. Recent evidence elaborating various aspects like diagnosis and management of EPI and dyspepsia, including the use of pancreatic enzyme replacement therapy (PERT) and issues with compliance were discussed. The experts emphasized that clinical symptoms of maldigestion should not be ignored, and physicians should not wait to diagnose EPI until steatorrhea occurs. Fecal elastase (FE) test and imaging should be performed to confirm diagnosis. If EPI is diagnosed or the patient experiences weight loss or steatorrhea, PERT should be initiated while ensuring compliance. Reducing pill burden, active education, monitoring, and support from healthcare programs may help ensure compliance. EPI is also a cause of dyspepsia. Further, consuming lipid-rich foods worsens symptoms of dyspepsia. First-line treatment includes dietary changes and lifestyle modifications. Digestive enzyme supplements play a significant role in alleviating symptoms of indigestion. Routine enzyme supplementation is beneficial in managing dyspepsia caused by EPI, such as, in patients with EPI due to pancreatitis or diabetes.

Estimation of the inferior caval vein saturation using high-fidelity non-invasive haemodynamic values and validation of modelled estimates.

Monitoring venous saturation allows identification of inadequate systemic oxygen delivery. The aim was to develop a model using non-invasive haemodynamic variables to estimate the inferior caval vein saturation and to determine its prognostic utility. This is a single-centre, retrospective study. A Bayesian Pearson's correlation was conducted to model the inferior caval vein saturation. Next, a Bayesian linear regression was conducted for data from all the patients and from only those with parallel circulation. Venous saturation estimations were developed. The correlation of these estimates to the actual inferior caval vein saturation was assessed. The resulting models were then applied to two validation cohorts: biventricular circulation (arterial switch operation) and parallel circulation (Norwood operation). One hundred and thirteen datasets were collected across 15 patients. Of which, 65% had parallel circulation. In all patients, the measured and estimated inferior caval vein saturations had a moderate and significant correlation with a coefficient of 0.64. In patients with parallel circulation, the measured and estimated inferior caval vein saturation had a moderate and significant correlation with a coefficient of 0.61. In the biventricular circulation cohort, the estimated inferior caval vein saturation had an area under the curve of 0.71 with an optimal cut-off of 49. In the parallel circulation cohort, the estimated interior caval vein saturation had an area under the curve of 0.83 with an optimal cut-off of 24%. The inferior caval vein saturation can be estimated utilising non-invasive haemodynamic data. This estimate has correlation with measured inferior caval vein saturations and offers prognostic utility.

Fostering Economic Sustainability within Rural Families in South Africa through Visual Arts and Crafts

This paper investigated interventions that can restore the importance of visual arts and crafts in fostering economic sustainability within rural families, in particular, young rural community members. Prior to colonization, visual arts and crafts played a significant role in providing economic subsistence for many households in South Africa. During the inception of formal education, that practice was replaced by scholastic education, prioritizing theoretical knowledge over practical experiential learning, leading to a gradual decline in the subsistence lifestyle. Marxism Theory (1848), which underpins this study, posits that within a capitalist economic framework, workers are exploited whilst company owners amass additional money. Craft manufacturing has the potential to augment self-generated income, making a valuable contribution to economic growth whilst avoiding any form of exploitation. The qualitative convenient sample comprised fifteen school dropouts and graduates from both South Africans and foreign nationals and was studied through face-to-face and telephonically informal conversations. The findings revealed that insufficient application of traditional visual arts and crafts skills in elementary education; inadequate delivery of government services to promote visual arts and crafts entrepreneurship; and the divergent perspectives in defining the concept of “civilization and freedom” impede efforts to achieve economic sustainability. The study recommended that community members should not only rely on government support services but instead utilize government grants to acquire knowledge, develop skills, and adopt subsistence lifestyles that rely on natural resources for sustainable economic growth. The government should also support the establishment of training centres where skilled individuals can impart knowledge and skills to the younger generation and monitor the efficacy of non-governmental organizations. This study not only enhances the well-being of people and communities but also offers valuable material for academic research in several fields. It strengthens comprehension of cultural, economic, and social phenomena within the framework of sustainable development. Keywords: Visual Arts and Crafts, Economic Development, Skills Development, Rural Families

Impact of Hemoglobin Level in Ex Vivo Heart Perfusion on Donation After Circulatory Death Hearts: A Juvenile Porcine Experimental Model.

Ex vivo heart perfusion (EVHP) of donation after circulatory death (DCD) hearts has become an effective strategy in adults; however, the small circulating volume in pediatrics poses the challenge of a low-hemoglobin (Hb) perfusate. We aimed to determine the impact of perfusate Hb levels during EVHP on DCD hearts using a juvenile porcine model. Sixteen DCD piglet hearts (11-14 kg) were reperfused for 4 h in unloaded mode followed by working mode. Metabolism, cardiac function, and cell damage were compared between the low-Hb (Hb, 5.0-5.9 g/dL; n = 8) and control (Hb, 7.5-8.4 g/dL; n = 8) groups. Between-group differences were evaluated using 2-sample t -tests or Fisher's Exact tests. During unloaded mode, the low-Hb group showed lower myocardial oxygen consumption ( P < 0.001), a higher arterial lactate level ( P = 0.001), and worse systolic ventricular function ( P < 0.001). During working mode, the low-Hb group had a lower cardiac output (mean, 71% versus 106% of normal cardiac output, P = 0.010) and a higher arterial lactate level ( P = 0.031). Adjusted cardiac troponin-I ( P = 0.112) did not differ between the groups. Morphological myocyte injury in the left ventricle was more severe in the low-Hb group ( P = 0.028). Low-Hb perfusate with inadequate oxygen delivery induced anaerobic metabolism, resulting in suboptimal DCD heart recovery and declined cardiac function. Arranging an optimal perfusate is crucial to organ protection, and further endeavors to refine the priming volume of EVHP or the transfusion strategy are required.

Low Vision Practice and Service Provision Among Optometrists in Ghana: A Nationwide Survey

ABSTRACT Purpose To characterize practice patterns of low vision services among Optometrists in Ghana. Methods The nationwide cross-sectional survey identified entities through the Ghana Optometrists Association (GOA) registry and utilized a semi-structured questionnaire to consolidate survey information that comprises practitioners’ demographics, available services, diagnostic equipment, barriers to service provision and utilization, and interventions. Results 300 Optometrists were identified, with 213 surveyed (71% response rate). About fifty percent (52.6%) were in private practice, and more than two-thirds (77%) did not provide low vision services. Most (≥70%) reported lack of assistive devices, and basic eye care examination kits as the main barriers to low vision service provision. Similarly, practitioners reported unawareness of the presence of low vision centres (76.1%), and high cost of low vision aids (75.1%) as the prime perceived barriers for patients to utilize low vision services. Continuous professional development and public education (89–90%) were suggested as interventions to improve the uptake of low vision services. After statistical adjustment, private facility type (Adjusted odds ratio [AOR] = 0.35, p = 0.010) and lack of basic eye examination kits (AOR = 0.32, p = 0.002) were significantly associated with reduced odds of low vision service provision. Conversely, ≥15 years of work experience (AOR = 6.37, p = 0.011) was significantly associated with increased odds of low vision service provision. Conclusions Overall, the results indicate inadequate low vision coverage and service delivery. Government policies must be directed towards equipping practitioners with equipment and subsidize patient cost of treatment to optimize low vision care.

Automatic nutrient estimator: distributing nutrient solution in hydroponic plants based on plant growth.

The primary objective is to address the specific needs of plants at different growth stages by delivering precise nutrient concentrations tailored to their developmental requirements. Challenges such as uneven nutrient distribution, fluctuations in pH and electrical conductivity, and inadequate nutrient delivery pose potential hindrances to achieving optimal plant health and yield in hydroponic systems. By overcoming these challenges, the hydroponic farming community aims to enhance the accuracy of nutrient dosing, streamline automation processes, and minimize resource wastage. Hydroponics, a cultivation technique without soil, facilitates the growth of organic vegetation while concurrently minimizing water use and eliminating the necessity for pesticides. In order to achieve effective cultivation of hydroponic plants, it is essential to maintain a controlled environment that encompasses essential factors such as temperature, carbon dioxide (CO2) levels, oxygen availability, and appropriate lighting conditions. Additionally, it is crucial to ensure the provision of vital nutrients to maximize output and productivity. Due to the demanding nature of a hydroponic farmer's schedule, it is necessary to minimize the amount of time dedicated to nutrient management, as well as pH and EC adjustments. In order to determine and deliver the proper amount of vital nutrients, such as nitrogen, phosphorus, and potassium, based on the plant growth stage, we presented an automatic hydroponic nutrient estimator in this system. We noticed that the plant's nutrient consumption varies depending on its stage of growth according to plant psychology. Four peristaltic pumps with the necessary sensors are controlled by an Arduino board in the suggested system. Both filling and draining the water are done using each pump. To identify the plant stage, we apply the Plant Growth Stage Identification algorithm to encompass the seedling, vegetative, flowers, and fruit stages. The experimental results reveal that the Growth Stage Identification algorithm obtains 97.5% accuracy for the first 5 weeks with 1,715 ppm of nutrition ingestion, identifying the vegetative state. The flowering stage is identified with 97.5% accuracy in the 6-9th week with 2,380 ppm of nutrition consumption, and the fruiting location is determined with 99.4% accuracy in the last 10-15th week with 2,730 ppm of nutrition consumption.

One hundred priority questions for advancing seagrass conservation in Europe

Societal Impact StatementSeagrass ecosystems are of fundamental importance to our planet and wellbeing. Seagrasses are marine flowering plants, which engineer ecosystems that provide a multitude of ecosystem services, for example, blue foods and carbon sequestration. Seagrass ecosystems have largely been degraded across much of their global range. There is now increasing interest in the conservation and restoration of these systems, particularly in the context of the climate emergency and the biodiversity crisis. The collation of 100 questions from experts across Europe could, if answered, improve our ability to conserve and restore these systems by facilitating a fundamental shift in the success of such work.SummarySeagrass meadows provide numerous ecosystem services including biodiversity, coastal protection, and carbon sequestration. In Europe, seagrasses can be found in shallow sheltered waters along coastlines, in estuaries &amp; lagoons, and around islands, but their distribution has declined. Factors such as poor water quality, coastal modification, mechanical damage, overfishing, land‐sea interactions, climate change and disease have reduced the coverage of Europe’s seagrasses necessitating their recovery. Research, monitoring and conservation efforts on seagrass ecosystems in Europe are mostly uncoordinated and biased towards certain species and regions, resulting in inadequate delivery of critical information for their management. Here, we aim to identify the 100 priority questions, that if addressed would strongly advance seagrass monitoring, research and conservation in Europe. Using a Delphi method, researchers, practitioners, and policymakers with seagrass experience from across Europe and with diverse seagrass expertise participated in the process that involved the formulation of research questions, a voting process and an online workshop to identify the final list of the 100 questions. The final list of questions covers areas across nine themes: Biodiversity &amp; Ecology; Ecosystem services; Blue carbon; Fishery support; Drivers, Threats, Resilience &amp; Response; Monitoring &amp; Assessment; Conservation &amp; Restoration; Governance, Policy &amp; Management; and Communication. Answering these questions will fill current knowledge gaps and place European seagrass onto a positive trajectory of recovery.

Crystalloid Fluid Management of Non-Traumatic Hypotension by New South Wales Ambulance

Introduction Shock is circulatory insufficiency, inadequate oxygen delivery, and cellular hypoxia. Intravenous fluids are essential for shock management. Despite treatment, patients can face persistent shock with ongoing hypotension, contributing to higher mortality. This analysis aims to quantify hypotensive non-traumatic cases in an Australian ambulance service, determine persistent hypotension prevalence, and assess paramedic-administered intravascular fluids’ impact on blood pressure changes. Methods This study is a retrospective analysis of prehospital fluid resuscitation by New South Wales Ambulance paramedics during 2022. Hypotension is defined as a systolic blood pressure of ≤ 90 mmHg, and persistent hypotension is a systolic blood pressure consistently below 90 mmHg across all observations, with a final blood pressure below 90 mmHg. This study aimed to determine the volume of fluid resuscitation at which a plateau in population-level systolic blood pressure response is observed, by calculating the derivative of the fitted logistic regression model. Moreover, this analysis identified the relative contribution of factors influencing the probability of an attempt at intravenous or intraosseous access using machine learning. Results Among 796,865 attendances, 23,049 (2.9%) involved non-traumatic patients with hypotension. In total 7,388 (32.1%) of the hypotensive cases resulted in persistent hypotension, of which 3,235 (43.8%) received Hartmann’s solution and 1,745 (53.9%) received at least 500 ml of fluids but still had hypotension. The model showed that systolic blood pressure tends to stop increasing after 500–600 milliliters of fluid are given. This suggests that, on average, giving more fluid than this may not raise blood pressure further in a prehospital setting, though individual patient needs can differ. The top four factors from the machine learning shows that as initial respiratory rate goes up, the probability of intravascular access rises. Transport times less than 20 min are associated with a smaller chance of access and younger patients are less likely to receive an attempt. Finally, extremes of systolic blood pressure are more likely to receive access attempts. Conclusion This study found that three percent of non-traumatic attendances have at least one episode of hypotension, and that more than half of these have persistent hypotension. Only 44% of persistently hypotensive received fluids, and half of persistently hypotensive patients stayed hypotensive despite a reasonable volume of prehospital crystalloids.

The Corporate Governance of South African State-Owned Enterprises (SOEs): Leadership and Compliance Issues

The financial, operational, and business issues facing SOEs have reduced the trust that investors and citizens have in the state's capacity to effectively promote national economic growth. Most countries, especially developing ones like South Africa, have been plagued by the issue of inadequate public service delivery. One key contributing factor to this problem has been identified as the poor governance practices of SOEs. The magnitude of these massive SOE business failures, which surpassed the failure of numerous other enterprises around the world, drew attention to the urgent need for new corporate governance studies. To contribute to this, the study explores the corporate governance of South African SOEs, with a focus on leadership and compliance. To achieve this, an online questionnaire was used to gather quantitative data from a sample of 288 internal audit professionals. The data collected was then analyzed using SPSS software, and descriptive statistics were employed to present the findings. The study found that corporate governance malpractices are common in SOEs, which include hiring managers and executives who lack the necessary qualifications and experience, high tender irregularities, and understaffing critical duties. This study is unique in that it employs stakeholder theory in an innovative approach to explain the findings, notably on the leadership issue. Besides, it contains critical recommendations for SOE leadership and policymakers on how to improve the corporate governance of SOEs to help them achieve their strategic goals, while also suggesting future study directions.

High Intraoperative Serum Lactate Level is Associated with Acute Kidney Injury after Brain Tumor Resection.

Postoperative acute kidney injury (AKI) is associated with poor clinical outcomes. Identification of risk factors for postoperative AKI is clinically important. Serum lactate can increase in situations of inadequate oxygen delivery and is widely used to assess a patient's clinical course. We investigated the association between intraoperative serum lactate levels and AKI after brain tumor resection. Demographics, medical and surgical history, tumor characteristics, surgery, anesthesia, preoperative and intraoperative blood test results, and postoperative clinical outcomes were retrospectively collected from 4131 patients who had undergone brain tumor resection. Patients were divided into high (n=1078) and low (n=3053) lactate groups based on an intraoperative maximum serum lactate level of 3.35mmol/L. After propensity score matching, 1005 patients were included per group. AKI was diagnosed using the Kidney Disease Improving Global Outcomes criteria, based on serum creatinine levels within 7 days after surgery. Postoperative AKI was observed in 53 (1.3%) patients and was more frequent in those with high lactate both before (3.2% [n=35] vs. 0.6% [n=18]; P < 0.001) and after (3.3% [n=33] vs. 0.6% [n=6]; P < 0.001) propensity score matching. Intraoperative predictors of postoperative AKI were maximum serum lactate levels > 3.35mmol/L (odds ratio [95% confidence interval], 3.57 [1.45-8.74], P = 0.005), minimum blood pH (odds ratio per 1 unit, 0.01 [0.00-0.24], P = 0.004), minimum hematocrit (odds ratio per 1%, 0.91 [0.84-1.00], P = 0.037), and mean serum glucose levels > 200mg/dL (odds ratio, 6.22 [1.75-22.16], P = 0.005). High intraoperative serum lactate levels were associated with AKI after brain tumor resection.

Proteolysis-targeting drug delivery system (ProDDS): integrating targeted protein degradation concepts into formulation design.

Targeted protein degradation (TPD) has emerged as a revolutionary paradigm in drug discovery and development, offering a promising avenue to tackle challenging therapeutic targets. Unlike traditional drug discovery approaches that focus on inhibiting protein function, TPD aims to eliminate proteins of interest (POIs) using modular chimeric structures. This is achieved through the utilization of proteolysis-targeting chimeras (PROTACs), which redirect POIs to E3 ubiquitin ligases, rendering them for degradation by the cellular ubiquitin-proteasome system (UPS). Additionally, other TPD technologies such as lysosome-targeting chimeras (LYTACs) and autophagy-based protein degraders facilitate the transportation of proteins to endo-lysosomal or autophagy-lysosomal pathways for degradation, respectively. Despite significant growth in preclinical TPD research, many chimeras fail to progress beyond this stage in the drug development. Various factors contribute to the limited success of TPD agents, including a significant hurdle of inadequate delivery to the target site. Integrating TPD into delivery platforms could surmount the challenges of in vivo applications of TPD strategies by reshaping their pharmacokinetics and pharmacodynamic profiles. These proteolysis-targeting drug delivery systems (ProDDSs) exhibit superior delivery performance, enhanced targetability, and reduced off-tissue side effects. In this review, we will survey the latest progress in TPD-inspired drug delivery systems, highlight the importance of introducing delivery ideas or technologies to the development of protein degraders, outline design principles of protein degrader-inspired delivery systems, discuss the current challenges, and provide an outlook on future opportunities in this field.

Stakeholder’s Involvement Practices and Devolved Administrative Structures in Selected Semi-Arid Counties in Kenya

Purpose: The existence of devolved administrative structures is critical in protecting public officials from abusing power. It is therefore essential to ensure that there is effective implementation and operation of these structures in Kenya now that devolution has been introduced. So far, the underlying cause of inadequate service delivery has been poor operationalization of structures in these devolved administrative entities that has been caused by ineffective managerial practices. The objective of the study intended to bridge the existing gap by establishing the scope of stakeholder involvement when it comes to devolved administrative structures; the effect of on the relationship of the stakeholder’s involvement on devolved administrative structures.&#x0D; Methodology: The study utilized Institutional Theory, which depicts an institution as networks that rely upon each other to build up unified systems that concern shared reliance. Target population was 500 participants from Taveta and Makueni counties. Purposive and Stratified Random Sampling techniques were utilized, where a sample ofi223 was drawn from the Target population. The design deployed in the study was descriptive research that sought to produce answers to phenomenon’s questions. Data was presented using tables and narrations.&#x0D; Findings: The instrument’s reliability was tested using Cronbach’s Alpha reliability of 0.7 that which was acceptably reliable. Quantitative and qualitative analytical methods were used, as data was coded in SPSS and analysed using the STATA. Multiple Linear Regression was used to test the effects of stakeholders’ involvement practices on the devolved administrative structures. Objectively, it was found that, a significant relationship existed between stakeholders’ involvement practices and devolved administrative structures.&#x0D; Recommendations: The study recommends that major decision-making processes adhere to prescribed guidelines and be guided by proper behaviour and clear principles.

Safety and Performance of the Subcutaneous Implantable Cardioverter Defibrillator Detection Algorithm INSIGHTTM in Pacemaker Patients.

The use of the S-ICD is limited by its inability to provide backup pacing. Combined use of the S-ICD with a pacemaker may be a good choice in certain situations, yet current experience concerning the compatibility is limited. The goal of this study was to determine the safety and efficacy of the S-ICD in patients with a pacemaker. A total of 74 consecutive patients with a bipolar pacemaker were prospectively enrolled. First, surface rhythm strips were recorded in all possible pacemaker stimulation modes, to screen for T-wave oversensing (TWOS). Second, a S-ICD functional dummy was placed epicutaneously on the patient in the typical implant position. The same standardized pacing protocol was used as mentioned above, and every stimulation mode was recorded via S-ECG in all vectors. In 16 patients (21.6%), programmed stimulation would have led to VT/VF detection. Triggered episodes were due to counting of the pacing spike(s), QRS complex, premature ventricular contractions, and/or additional TWOS. Three cases triggered in the bipolar stimulation mode. Oversensing was associated with lung emphysema and a reduced QRS amplitude in the S-ECG. The combination of an S-ICD and a pacemaker may lead to inadequate shock delivery due to oversensing, even under programmed bipolar stimulation. Oversensing cannot be sufficiently predicted by the screening tool in pacemaker patients. Testing with an epicutaneous S-ICD dummy in all vectors and stimulation settings is recommended in patients with pre-existing pacemakers.

The first results of the international multicenter clinical study RheoSTAT-CP0669 on the effectiveness and safety of infusion solution Rheosorbilact® in the complex treatment of patients with burns

Mechanization and urbanization are accompanied by an increase in the prevalence of burns. A burn causes both local damage and systemic inflammatory response that leads to inadequate oxygen delivery to vital organs and inadequate elimination of metabolites. Infusion therapy for burns aims to restore perfusion and prevent ischemia. The implementation of effective dynamic schemes of infusion therapy has led to a decrease in mortality, however, an excessive amount of injected fluid does not improve the patient’s volumetric status, instead increasing tissue swelling and causing a number of complications. Therefore, doctors are faced with the question of choosing the optimal infusion therapy, which will allow maintaining the patient’s status at the needed level called normovolemia. According to the results of the open, blinded evaluation of the randomized controlled trial RheoSTAT-СР0669, administration of Rheosorbilact to patients with burns by intravenous infusion at a dose of 200-400 ml/day for 3 days significantly improves the clinical condition, reduces the manifestations of (poly-) organ failure and endogenous intoxication. Small-volume infusion therapy with Rheosorbilact causes a statistically significant decrease in the breathing rate, a decrease in endogenous intoxication and the intensity of inflammation, as well as positive dynamics of the blood gas composition. Administration of the drug in this mode has a favorable safety profile: it does not lead to fluid overload, associated complications, or other serious undesirable side effects, and does not cause a clinically significant increase in blood lactate level. The RheoSTAT-СР0669 study substantiates the feasibility of using Rheosorbilact in the complex therapy of burns.

Development of birth weight estimation model for Ethiopian population from sonographic evaluation

BackgroundFetal birth weight (FBW) estimation involves predicting the weight of a fetus prior to delivery. This prediction serves as a crucial input for ensuring effective, accurate, and appropriate obstetric planning, management, and decision-making. Typically, there are two methods used to estimate FBW: the clinical method (which involves measuring fundal height and performing abdominal palpation) or sonographic evaluation. The accuracy of clinical method estimation relies heavily on the experience of the clinician. Sonographic evaluation involves utilizing various mathematical models to estimate FBW, primarily relying on fetal biometry. However, these models often demonstrate estimation errors that exceed acceptable levels, which can result in inadequate labor and delivery management planning. One source of this estimation error is sociodemographic variations between population groups in different countries. Additionally, inter- and intra-observer variability during fetal biometry measurement also contributes to errors in FBW estimation.MethodsIn this research, a novel mathematical model was proposed through multiple regression analysis to predict FBW with an accepted level of estimation error. To develop the model, population data consisting of fetal biometry, fetal ultrasound images, obstetric variables, and maternal sociodemographic factors (age, marital status, ethnicity, educational status, occupational status, income, etc.) of the mother were collected. Two approaches were used to develop the mathematical model. The first method was based on fetal biometry data measured by a physician and the second used fetal biometry data measured using an image processing algorithm. The image processing algorithm comprises preprocessing, segmentation, feature extraction, and fetal biometry measurement.ResultsThe model developed using the two approaches were tested to assess their performance in estimating FBW, and they achieved mean percentage errors of 7.53% and 5.89%, respectively. Based on these results, the second model was chosen as the final model.ConclusionThe findings indicate that the developed model can estimate FBW with an acceptable level of error for the Ethiopian population. Furthermore, this model outperforms existing models for FBW estimation. The proposed approach has the potential to reduce infant and maternal mortality rates by providing accurate fetal birth weight estimates for informed obstetric planning.

Gender Disparities in E-commerce Adoption Barriers among Entrepreneurs in Sri Lanka

This research study investigates the gender-based differences in e-commerce adoption barriers among entrepreneurs in Sri Lanka. Employing a quantitative research approach, a sample of 460 entrepreneurs from the Hambantota District was selected using proportionate stratified random sampling. Primary data was collected through a validated questionnaire, and data analysis involved statistical techniques such as regression analysis. The findings highlight substantial disparities in the perception of e-commerce adoption barriers between male and female entrepreneurs in Sri Lanka. Female entrepreneurs encounter unique challenges in the realm of e-commerce adoption, underscoring the significant influence of gender on shaping adoption patterns. While both genders identify Lack of awareness and knowledge of e-commerce, Lack of qualified personnel to develop and support e-commerce, and Lack of popularity for online shopping as substantial and persistent barriers, Fear and reluctance to change and Inadequate delivery networks emerge as particularly noteworthy obstacles for female entrepreneurs. These research findings hold implications for the formulation of more effective government policies and strategic initiatives aimed at fostering a dynamic entrepreneurial ecosystem, particularly to empower female entrepreneurs in developing countries.