Optimal Delivery Research Articles

The potential of a combined cell‐based therapy and rehabilitation approach for stroke recovery

AbstractActivation of neuroprotective and particularly later neurorestorative mechanisms after stroke attempts to restore or compensate for lost functions. This potentially opens a wide window for restorative therapies to promote brain repair and improve long‐term functional recovery. Although extensively demonstrated in the preclinical setting, the efficacy of cell‐based therapies in stroke patients has been modest at best, if any at all. Translational failure may be due to the ineffective survival and integration of transplanted cells in pro‐death stroke microenvironments that are not conducive for the structural reconstruction of damaged brain tissue and repair‐related network reorganization. Optimal systemic delivery, timing, cell product, and dose remain open as well. Fortunately, a better understanding of the brain plasticity mechanisms underlying stroke recovery has ushered in a combination approach of cell‐based therapy and rehabilitation that is aimed at achieving additive, synergistic, or even maximal beneficial effects. This novel combination therapy is not only targeted at promoting exogenous and endogenous cell survival and augmenting stand‐alone restorative mechanisms but also at utilizing rehabilitation to facilitate a graft–host structural and functional integration and plasticity that would effectively remodel stroke tissue and restitute lost functions. This review presents an overview of the combination of cell‐based therapy and experimental rehabilitation in stroke models. It also discusses associated shortcomings as well as proposes strategies to address them and help facilitate the advancement of this combination approach.

Crush syndrome-related acute kidney injury in earthquake victims

ABSTRACT Natural disasters are unpredictable and thousands of people are affected yearly. Currently, this risk persists, given the large population living in risk areas prone to suffering another seismic event. Generally, on-site mortality is high and occurs immediately from massive trauma or asphyxia. After surviving the first event, extricated patients are at risk of developing crush syndrome caused by direct physical trauma and compression of the human body with lesions in different tissues. This could lead to several systemic complications, including acute kidney injury (AKI), sepsis, acute respiratory distress syndrome, bleeding, hypovolemic shock, arrhythmias, electrolyte disturbances and disseminated intravascular coagulation. Hence, AKI in this scenario can occur due to many causes, such as rhabdomyolysis, direct renal trauma, hypovolemia and hemodynamic alterations. The most important measure to reduce crush syndrome mortality and prevent the development of crush syndrome-related AKI in disaster situations is the immediate start of treatment. Nevertheless, despite optimal therapy delivery, these previous efforts might not suffice the development and progression of AKI, consequently, the indication of extracorporeal blood purification techniques. This narrative review provides a focused overview of crush syndrome-related AKI, including etiology, mechanisms, diagnosis, current treatment, removal of myoglobin and their limitations.

Effects of gastrointestinal digestion on the cell bioavailability of sodium alginate coated liposomes containing DPP-IV inhibition active collagen peptides

Delivery matrices in foods need to be carefully designed for optimal delivery and to ensure that beneficial compounds are subsequently absorbed in the gut. It has been found that polysaccharide coating improved the cellular uptake of liposomes, but there is a lack of research on the effect of digestion on the cellular uptake of polysaccharide-coated liposomes. Herein, the sodium alginate-coated liposomes were prepared, combination of Caco-2, HT29 and Caco-2/HT29 cell models were used to assess the effect of digestion behavior on the bioavailability. Where, the bioavailability of digested liposomes was 1.60 times higher than that of undigested liposomes. Specifically, digestion firstly improved the ability of liposomes to penetrate the mucus layer by 1.43-fold. Secondly, digestion improved the uptake of liposomes into the intestinal cells by about 1.33-fold. Next, cellular uptake mechanisms were explored using uptake inhibition experiments. Proteomics and metabolic process experiments showed that liposomes pass intact through the small intestinal epithelium into the somatic circulation. This work suggested that digestive behavior enhanced liposome bioavailability in terms of penetration through the cellular mucus layer as well as uptake capacity. These results deepen the understanding of the specific role of digestion on polysaccharide-modified liposomes and favor a better design of delivery systems.

Review of pediatric emergency care and the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic posed new challenges in health care delivery for patients of all ages. These included inadequate personal protective equipment, workforce shortages, and unknowns related to a novel virus. Children have been uniquely impacted by COVID-19, both from the system of care and socially. In the initial surges of COVID-19, a decrease in pediatric emergency department (ED) volume and a concomitant increase in critically ill adult patients resulted in re-deployment of pediatric workforce to care for adult patients. Later in the pandemic, a surge in the number of critically ill children was attributed to multisystem inflammatory syndromein children. This was an unexpected complication of COVID-19 and further challenged the health care system. This article reviews the impact of COVID-19 on the entire pediatric emergency care continuum, factors affecting ED care of children with COVID-19 infection, including availability of vaccines and therapeutics approved for children, and pediatric emergency medicine workforce innovations and/or strategies. Furthermore, it provides guidance to emergency preparedness for optimal delivery of care in future health-related crises.

Effects of Silver Nanoparticles on Growth of E. coli: A Study Examining Various Antibiotic Factors

Nanomedicine, an emerging and revolutionary scientific field, warrants greater scientific investigation on the antibacterial applications of AgNPs; hence, this research serves to assess AgNPs’ antibacterial effectiveness on the growth of E. coli while establishing the antibiotic’s optimal conditions for drug delivery. The hypothesis expects that optimal drug delivery of AgNPs will occur at higher concentrations of AgNPs and neutral pHs. To demonstrate this, 1:10 serial AgNP dilutions were placed in E. coli cultures and were treated with the varying environmental factors of concentration and pHs. The results supported our hypotheses with the exception of our pH hypothesis, for the data showed that having a basic pH increased the efficiency of the nanoparticles for all concentrations, except for the 500 µg/L concentration. Nevertheless, higher concentrations of nanoparticles have the highest and fastest increases in their zones of inhibitions. The concentration and pH experiments yielded statistical significance. With nanomedicine’s ability to diagnose, detect, and deliver drugs, its research applications are endless, proving it has a significant impact in the fields of cancer drug delivery, E. coli toxicity, and ectopic pregnancies, and ultimately, having the potential to save over two million lives every year.

Referral Versus Embedded Palliative Care Consultation Among People Hospitalized With Heart Failure: A Report From a Single Center Pilot Program

ContextDespite calls for integration into routine heart failure (HF) care, optimal palliative care delivery for people living with HF remains unclear. ObjectivesDescribe an innovative model of an embedded palliative care nurse practitioner (NP) within a HF team. Compare demographics and utilization among people hospitalized with HF receiving referral or embedded consultation. MethodsUsing an electronic health record-based palliative care registry, we conducted descriptive analyses and t‐tests and χ2 tests, as appropriate, to examine bivariate associations between sociodemographic, clinical and utilization data of hospitalized people with HF receiving a traditional, referral-based palliative care consultation generated exclusively by the primary team vs. a novel, embedded-based consultation generated by collaboration between a palliative care NP and the advanced HF team at an urban, quaternary care academic medical center in New York City. ResultsDuring the study period from January 1, 2019–December 31, 2021, consultation volume nearly doubled with 363 consults from traditional referrals and an additional 317 consults from the newly embedded NP. People in the embedded group, as compared to referral, were younger (mean age: 60.1 vs. 71.9 years (2019); 59.2 vs. 70.4 (2020); 61.3 vs. 69.6 (2021), p-value < 0.001), more functional (median Karnofsky Performance Status: 40% vs. 30%, p-value = 0.01 (2019); 40% vs 20%, p-value < 0.0001 (2020); 40% vs. 20%, p-value = 0.02 (2021)), more likely had capacity to designate a medical decision maker (56.4% vs. 20.6%, p-value < 0.001 (2020); 76.3% vs. 49.5%, p-value < 0.001 (2021)), received earlier consultation (median days before discharge: 9.5 vs. 4 (2019); 11 vs. 5 (2020); 7 vs. 3 (2021), p-value ≤ 0.001), and more likely to discharge home (60% vs. 26%, p-value ≤ 0.001 (2019); 62.7% vs 20.6%, p-value ≤ 0.001 (2020); 42.3% vs. 28%, p-value = 0.03 (2021)). ConclusionHospitalized people living with advanced HF who received an embedded palliative care consult were younger, had higher functional status and less illness severity compared to those served by a traditional, referral-based consult.

Impact of the Mexican Healthcare Reform on Optimal Treatment Delivery, Survival, and Response Rates Among a Cohort of Patients with Diffuse Large B Cell Lymphoma in a Single National Reference Institution

Introduction: The creation of Seguro Popular (SP) in Mexico, back in 2003, was the first step towards creating a universal healthcare system. After it was implemented, there was a 4-times boost in health spend and the creation of the Protection Fund Against Catastrophic Expenses, a fund meant for covering the costs of illnesses with a high financial burden, such as most cancers. As of January 2020, the Health Institute for Wellbeing (INSABI, Spanish acronym) has taken its place with promises to provide free health coverage for everyone. This scheme has been accompanied by multiple shortages of cancer medications due to its lack of planning and budget allocation. As a consequence, a proportion of lymphoma patients haven't been able to receive full treatment regimens. Our study aims to identify differences in survival and response rates among patients with diffuse large B cell lymphoma (DLBCL) receiving R-CHOP as first line treatment under SP and INSABI, in the National Cancer Institute (INCan) in Mexico City. Methods: This is a retrospective study where two groups with histologically documented DLBCL were compared. Group A consisted of a cohort of adult patients treated at INCan from 2011 to 2018 under the SP scheme, receiving full funding for diagnostic approach and treatment with R-CHOP as first line therapy. Group B consisted of a cohort of adult patients treated at INCan from 2020 to 2021 under INSABI's gratuity policy, receiving R-CHOP as first line therapy. Variables collected included sex, age at diagnosis, comorbidities, B-symptoms, molecular subtype, stage, bulky disease, and IPI, among others. Optimal treatment was evaluated and defined as the proportion of patients who received full drugs' dosage according to the recommendation of the attending physician. Response was assessed with 18F-FDG PET-CT according to the Lugano classification, and was defined as the proportion of patients with complete remission (CR) for all patients evaluable for response. Event free survival (EFS) was defined as time to relapse or progression during treatment. Overall survival (OS) was defined as time to death in years from the date of primary diagnosis. The significance of variation in the distribution of outcomes with healthcare regime (SP, INSABI) was assessed with Pearson's Chi-square tests or Fisher's Exact test as appropriate. Survival distributions were done with Kaplan-Meier methodology. Cox regression analysis was used to evaluate factors influencing on relapse rate and survival. All statistical testing was two sided and differences between groups were regarded as significant for p values &amp;lt;0.05. Results: Group A consisted of 505 patients, 258 were female (51%), with a mean age of 55.5 ± 13.6 years. Group B consisted of 169 patients, 94 were female (55%), with a mean age of 55.9 ± 12.7 years. Other demographic and clinical prognostic factors were similar in both groups, as shown in table 1. While both groups received treatment in 100%, 14.2% patients in group A received diminished doses of chemotherapy due to attending physicians' criteria, no other causes of dose modifications were found. In group B, 11.2% of patients received diminished doses of chemotherapy due to medical reasons as indicated by attending physicians, while 33.7% of patients received diminished doses of chemotherapy due to drug shortages. Overall response rate (ORR) for group A was 82.7%, while for group B was 73% (p = 0.05). CR for group A was 75.2%, and for group B was 60.4% (p = 0.00). Progression rate for group A was 14.8%, while for group B was 13%; relapse rate for group A was 14.6%, while for group B was 12.4%, not statistically significant (p = 0.5). EFS for group A was 85.3% and for group B was 87.6%, while OS for group A was 75.8% and for group B was 78.1%. Conclusion: Our study shows important differences in optimal treatment delivery for first-line R-CHOP in DLBCL during the INSABI era, compared to the SP era. Under the SP regime, the only reason for diminishing chemotherapy doses were medical reasons, usually in relation to cardiac comorbidities or patient's performance status. During the INSABI era, drug shortages account for incomplete treatment delivery in 33.7% of the cases. After Cox regression analysis, the administration of an optimal treatment was a factor that tends to influence EFS (p = 0.34). However, a longer follow-up time and further research is needed to assess the long term effects of the incomplete chemotherapy administration in group B.

Same-day delivery time-guarantee problem in online retail

This study introduces the same-day delivery time-guarantee (SDDTG) problem for supporting online retail. In the SDDTG, orders are placed online and are processed and delivered from a depot to customer locations in the same day. The problem seeks optimal delivery time guarantees to offer customers as they consider making purchases to increase purchase decision likelihood while accounting for delivery-related, supply-side costs that can affect profits. Time guarantees are decision variables rather than parameters (as is typical) and are designed around anticipated customer satisfaction levels and purchase likelihoods. Delivery deadlines are not merely given to customers once they make their purchases, but rather the attractiveness of the offered delivery guarantees affects whether they make their purchases, i.e., whether demand is realized. The problem is conceptualized as a multi-stage, stochastic, mixed-integer program in which uncertainties associated with customer reaction to delivery time guarantee offers and their arrival over time are captured. Given a shrinking horizon over a fixed planning horizon, the multi-stage program is approximated by a series of two-stage programs. A parallelized progressive hedging solution methodology is proposed and insights from its application on a case study. The problem recognizes tradeoffs between meeting promised delivery times and capturing the market.

Exosomes for CRISPR-Cas9 Delivery: The Cutting Edge in Genome Editing.

Gene mutation correction was challenging until the discovery of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas). CRISPR is a new era for genome modification, and this technology has bypassed the limitations of previous methods such as zinc-finger nuclease and transcription activator-like effector nuclease. Currently, this method is becoming the method of choice for gene-editing purposes, especially therapeutic gene editing in diseases such as cardiovascular, neurological, renal, genetic, optical, and stem cell, as well as blood disorders and muscular degeneration. However, finding the optimum delivery system capable of carrying this large complex persists as the main challenge of this technology. Therefore, it would be ideal if the delivery vehicle could direct the introduction of editing functions to specific cells in a multicellular organism. Exosomes are membrane-bound vesicles with high biocompatibility and low immunogenicity; they offer the best and most reliable way to fill the CRISPR/Cas9 system delivery gap. This review presents the current evidence on the molecular mechanisms and challenges of CRISPR/Cas9-mediated genome modification. Also, the role of CRISPR/Cas9 in the development of treatment and diagnosis of numerous disorders, from malignancies to viral infections, has been discussed. Lastly, the focus is on new advances in exosome-delivery technologies that may play a role in CRISPR/Cas9 delivery for future clinical settings.

Efficiency Optimization in Multi-Branch Converters through Dynamic Control

As the global emphasis on solar energy intensifies, optimizing the efficiency of photovoltaic panels becomes crucial in meeting energy demands sustainably. Addressing this, our research delves deeply into advancing maximum power point tracking (MPPT), a pivotal component in perfecting the energy conversion process. Leveraging state-of-the-art mathematical modeling, in-depth simulations, and comprehensive experimental validation, we set out to markedly refine the performance of non-isolated multi-branch buck DC–DC converters. In this pursuit, we introduce an innovative algorithm meticulously designed to adjust the number of active branches. This adjustment is rooted in robust efficiency metrics, ensuring optimal power delivery even under dynamic and fluctuating conditions. We place a distinct emphasis on the transformative role of current in determining converter efficiency. Drawing from our findings, we advocate for an adaptive control strategy, precisely engineered to thrive in a spectrum of operational contexts. With this study, we not only present pivotal contributions to the domain of photovoltaic technology but also chart out clear expectations for future endeavors. Our hope is that these advancements serve as foundational steps, guiding the evolution of sustainable energy generation.

Patient and Care Provider Perspectives on the Management of Fecal Incontinence: A Qualitative Rapid Review

Patient and Care Provider Perspectives on the Management of Fecal Incontinence: A Qualitative Rapid Review

Optimization of guideline-directed medical therapies in patients with diabetes and chronic kidney disease.

Diabetes is the leading cause of chronic kidney disease (CKD) and kidney failure worldwide. CKD frequently coexists with heart failure and atherosclerotic cardiovascular disease in the broader context of cardio-kidney-metabolic syndrome. Diabetes and CKD are associated with increased risk of all-cause and cardiovascular death as well as decreased quality of life. The role of metabolic and hemodynamic abnormalities has long been recognized as an important contributor to the pathogenesis and progression of CKD in diabetes, while a more recent and growing body of evidence supports activation of both systemic and local inflammation as important contributors. Current guidelines recommend therapies targeting pathomechanisms of CKD in addition to management of traditional risk factors such as hyperglycemia and hypertension. Sodium-glucose cotransporter-2 inhibitors are recommended for treatment of patients with CKD and type 2 diabetes (T2D) if eGFR is ≥20ml/min/173m2 on a background of renin-angiotensin system inhibition. For patients with T2D, CKD, and atherosclerotic cardiovascular disease, a glucagon-like peptide-1 receptor agonist is recommended as additional risk-based therapy. A non-steroidal mineralocorticoid receptor antagonist is also recommended as additional risk-based therapy for persistent albuminuria in patients with T2D already treated with renin-angiotensin system inhibition. Implementation of guideline-directed medical therapies is challenging in the face of rapidly accumulating knowledge, high cost of medications, and lack of infrastructure for optimal healthcare delivery. Furthermore, studies of new therapies have focused on T2D and CKD. Clinical trials are now planned to inform the role of these therapies in people with type 1 diabetes (T1D) and CKD.

Effectivity and adherence of secondary prevention on clinical outcome of rheumatic heart disease in high-burden setting: a systematic review and meta-analysis

Abstract Background Rheumatic heart disease (RHD) is often diagnosed late in low-resource settings due to limited health-seeking behavior and varied presentations. Optimal delivery of regular antibiotics prescribed as secondary prevention is vital to preventing disease progression. However, poor adherence of secondary prevention remains a significant challenge to these populations. Objective To assess the efficacy and adherence of patients to secondary prevention of rheumatic heart disease. Methods This systematic review and meta-analysis was carried out according to the PRISMA statement. Literature search was performed on four databases using keywords "Rheumatic heart disease", "secondary prevention", and their synonyms. Adherence and disease progression were the primary outcome. The overall proportion was estimated with R software (version 4.1.3) using a random-effects model of proportional meta-analysis. Results Thirteen studies were included in this study. Benzathine Penicillin G (BPG) injection every 4 weeks was the most common secondary prophylaxis regimen used. In 2052 patients, only 46% (27-66%) patients received &amp;gt;80% BPG prophylaxis injection. The effectiveness of secondary prophylaxis was powerful, evidenced by only 7% (2-12%) patients having disease progression of rheumatic heart disease. Conclusions BPG was found to be effective in the secondary prevention of rheumatic heart disease. Nonetheless, patient adherence to injection remains extremely low. Methods to improve patient adherence are imminently required.Figure 1Figure 2

Abstract 18968: Safety and Efficacy of Shockwave Intravascular Lithotripsy in the Management of Calcified Coronary Arteries: A Systematic Review and Meta-Analysis

Introduction: Shockwave intravascular lithotripsy (SWL) aims to facilitate optimal stent delivery and expansion for improved blood flow in treating calcified coronary artery disease. We sought to assess the safety and efficacy of SWL in managing de novo calcified lesions, lesions after failed/sub-optimal pre-dilatation with conventional balloon-based devices, under-expanded stents, and in-stent restenosis. Methods: A comprehensive literature search (Medline, Embase, Web of Science, Cochrane, and Google Scholar) was performed for studies that evaluated SWL in managing calcified coronary lesions. Efficacy outcomes included residual stenosis &lt;30% and successful stent delivery with a low incidence of device delivery failure. Safety outcomes included procedural complications and major adverse cardiovascular events (MACE). MACE is a composite outcome of all-cause mortality, cardiac mortality, myocardial infarction, target vessel/lesion revascularization, and stent thrombosis. Event rates across the included studies were pooled in a meta-analysis using the random effects model. An overall estimate and 95% confidence interval were reported for each outcome. Heterogeneity was estimated using the I-squared statistic. Results: Out of the 1446 identified studies, 40 were included, with a total of 2718 patients. Residual stenosis &lt;30% was achieved in 91.3% of patients (95% confidence interval 89.7% to 92.6%). Device delivery failure occurred in 6.7% of patients (95% CI 5% to 9%). In-hospital MACE occurred in 6.1% of patients (95% CI 5% to 7.4%), 30-day MACE in 7.4% (95% CI 6.2% to 8.8%), 6-month MACE in 8.3% (95% CI 7.1% to 9.6%), and 1-year MACE in 10% (95% CI 8.7% to 11.4%). Conclusions: SWL is a safe and efficient calcium modification intervention with high clinical success, minimal angiographic complications, and a low adverse event rate. Direct comparisons with the standard of care are needed in larger studies to establish clinical utility and superiority.

Radiotherapy Administration Checklist for Patients Undergoing Radiotherapy: Development and Validation

Background: Radiotherapy is the use of high energy ionizing radiation to treat diseases. With newer technological advancements, the application of radiotherapy in cancer treatment is increasing. Administration of radiation therapy requires great precision and competency, hence tools should be available to implement uniformity of care in the procedure of radiotherapy and to reduce medical errors. This necessitates the need of a checklist to serve as a standard guide for the procedure of radiotherapy. The objective of present study was to develop radiotherapy administration checklist for patients undergoing radiotherapy. Materials and methods: Radiotherapy administration checklist was developed by using methodological research design. The checklist was developed in five phases: i) the preliminary phase (including literature review, focused group discussion, assessment of current practices, generation of item pool and preparation of preliminary draft), ii) the validation phase (content validity by modified Delphi technique and construct validation by factor analysis), iii) pilot testing, iv) final try out followed by establishment of reliability (internal consistency and inter-rater reliability), v) evaluation phase. Results: The final draft of Radiotherapy administration Checklist consisting of 29 items was developed and the validity and reliability of the developed tool were established. In content validity, S-CVI/Avg. and S-CVI/UA were 0.97 and 0.79 respectively. Cronbach’s coefficient alpha, and interrater reliability were 0.64 and 0.76 respectively. All 29 items in final checklist were loaded under 8 factors. The checklist developed was found to be a valid and reliable tool for the procedure of Radiotherapy administration. Conclusion: Radiotherapy administration Checklist is a valid and reliable tool with psychometric properties within expected range. The Radiotherapy administration Checklist can be used as a standard tool to ensure safe, uniform and optimal delivery of radiotherapy.

Psychedelics and treatment of mental disorders: A survey of attitudes and knowledge among psychiatrists, general practitioners and psychologists in Iceland

Interest in the use of psychedelics has increased following reports of their possible therapeutic potential. However, little is known about the knowledge of and attitudes towards the substances among health care professional who provide treatment for mental disorders in Iceland. An online survey was therefore conducted among members of the Icelandic associations of psychiatrists, general practitioners and psychologists. Respondents were 256 in total, including 177 psychologists, 38 psychiatrists and 41 general practitioners that provided information on their background, type of work, knowledge of and attitude towards different types of psychedelic substances and their views on optimal service delivery if psychedelics were approved by licencing authorities and used for treatment. Around half of psychiatrists reported having received questions about treatment with psychedelics in their clinical work, compared to only 14,6% of general practitioners and 17,5% of psychologists. The majority of respondents had little, or no knowledge of the substances targeted in the survey. A majority also expressed negative attitudes towards treatment with psilocybin mushrooms, but was positive towards ongoing scientific research and felt that such a treatment should be prescribed and provided by psychiatrists. Moreover, the majority view was that psilocybin treatment should be provided in specialised clinics or psychiatric units in a hospital setting. Scientific articles on the topic, discussions with colleagues and information in the media were identified as having had most influence on respondents´ attitudes towards psychedelics. Most respondents were interested in further education on psychedelics. Respondents among these three professions felt that the time has not yet come to use psychedelics in the treatment of mental disorders in Iceland but thought more education on psychedelics, their potential efficacy and adverse health effects is important given the increased interest in psychedelics.

ISX9 loaded thermoresponsive nanoparticles for hair follicle regrowth

There is a high demand for an optimal drug delivery system to treat androgenetic alopecia. Topical application of ISX9, which is a neurogenesis inducer, has been found to stimulate hair follicle (HF) regrowth by upregulating the Wnt/β-catenin signaling pathway, an essential pathway involved in initiating HF growth and development. In the present study, a temperature-sensitive, biopolymer-based, biocompatible, and eco-friendly drug-delivery system was synthesized. This system comprised chitosan-grafted poly(glycidyl methacrylate-co-N-isopropyl acrylamide) (Poly(GMA-co-NIPAAm)@CS-PGNCS) as the shell component and PF127 as the core polymer. The hydrophobic nature of the PF127 block copolymer efficiently dissolved the partially water-soluble drug, ISX9, and the thermos-responsive shell polymer effectively released the drug at a definite skin temperature. The optimized spherical nanoparticles demonstrated the lowest critical solution temperature (LCST) at 32 ± 2 °C with a diameter of 100–250 nm, which delivered encapsulated ISX9 with greater precision than topical ISX9. In a series of in vivo experiments, we demonstrated that ISX9-coated TBNPs upregulated the expression of β-catenin, active β-catenin, Wnt target genes, stemness marker genes, proliferating cell nuclear antigen, HF stem cell markers, and HF markers including VEGF, TGF, and IGF-1 more effectively than topical ISX9. These results suggest that TBNPs could be employed as a platform for effective transdermal delivery of various hydrophobic drugs.

Primary School Teachers’ Views on Integrating Technology in English Language Instruction in Rural School Contexts in the Lubombo Region of Eswatini

The realization that traditional methods of teaching have become inadequate hence can no longer be exclusively used when teaching, has seen technology being integrated in instruction for all curricula. This study intended to explore the views of primary school teachers on the integration of technology when teaching English language in rural school contexts in the Lubombo region of Eswatini. The study was based on the following research questions: What are the views of primary school English language teachers on the integration of technology in English language instruction in rural school contexts? What are the benefits of integrating technology in English language instruction in rural school contexts? How do primary school teachers integrate technology in English Language instruction in rural school contexts? What challenges do primary school English language teachers encounter when integrating technology in English language instruction in rural school contexts? The study adopted the interpretivist research paradigm which was used with the qualitative research approach and the case study research design. While the simple random sampling technique was used to select four (4) schools that took part in the study, purposive sampling was used to select eight (8) teachers that took part in the study (two teachers from each school). Data were gathered using an interview guide where teachers were interviewed on a one on one. The data were analyzed using Thematic Content Analysis. The study found that some teachers had a misconception about technology integration in instruction as they view it as the teaching of basic computer skills. Another finding was that integrating technology in English language instruction was viewed as very beneficial as it resulted in optimum lesson delivery since learners generally have a big interest in technology. Challenges that teachers encountered when integrating technology in instruction included lack of training and unavailability of technological gadgets as well as poor internet connections. The study therefore recommends that The Ministry of Education, through the In-service department should train the teachers on how they can integrate technology in their teaching. Another recommendation is that Headteachers should organize teachers from other schools who are known to be effectively using the approach to come and assist teachers in rural schools.

Mesenchymal stem cells: application in chronic lung disease

Chronic lung diseases such as asthma, chronic obstructive lung disease and idiopathic lung fibrosis have limited treatment options and researchers are exploring new avenues to improve patient outcomes. Mesenchymal stem cell therapy has shown promising potential as a treatment option for chronic lung diseases, however, it is essential to note that it is still considered an experimental approach. Studies in animal models and some small-scale clinical trials have shown encouraging results. Mesenchymal stem cell therapy can reduce inflammation, promote tissue repair and potentially slow disease progression. However, it is crucial to understand that stem cell therapy is still in its early stages and many challenges and questions need to be addressed before widespread clinical application. Some of these challenges include determining optimal dose and delivery methods, ensuring the safety of the procedure, understanding long-term effects and addressing potential ethical concerns.

A novel reverse micelle based cationic double nanoemulsion as a potential nanoplatform for enhancing the anitglucomal activity of betaxolol hydrochloride; formulation, in vitro characterization, ex vivo permeation and in vivo pharmacodynamic evaluation in glaucomatous rabbits’ eyes

Glaucoma is one of the most common causes of irreversible vision loss worldwide. The hydrophilic nature of the anti-glaucoma drug Betaxolol hydrochloride (BH) limits its ocular permeation necessitating repeated dosing. This can reduce patient compliance and increase the risk of experiencing adverse side effects. Our research is the first to encapsulate BH into reverse micelle-based cationic double W1/O/W2 nanoemulsions (RM-CDNEs) as a new platform capable of enhancing both the corneal permeability and IOP lowering efficacy of this drug. BH-loaded RM-CDNEs were prepared by a modified two-step emulsification method using sonication technique and applying 24 full factorial design to assess the impact of formulation variables and select the optimal delivery system. The in vitro drug-release, ex vivo permeation and in vivo performance of this novel nanocarrier were also assessed. The optimal delivery system (RM-CDNE 10) has mean DS, PDI, ZP and entrapment efficiency of 46.53 ± 1.30 nm, 0.217 ± 0.02, +40.9 ± 5.04 mV and 95.1 ± 2.44 %, respectively. A 90.77 % of drug was released over 7h. RM-CDNE 10 showed 2.5-fold increase in ex vivo corneal BH permeation with a prolonged IOP reduction of 58.77 % ± 1.18 % and AUC0-48 of 2537.82 ± 12.8%h. While, the marketed product (Epitaxol®) had only 33.63 ± 1.54 % IOP reduction with AUC0–48 h of 823.14 ± 3.67%h when tested in rabbits (P ≤ 0.05). Histopathological and Draize irritation studies confirmed that RM-CDNEs were non-irritant. These findings proved that the novel BH-loaded RM-CDNEs system improved the outcomes for patients suffering from glaucoma and thus decreasing the liability for disease progression into blindness.