The effects of improved sanitation on diarrheal prevalence, incidence, and duration in children under five in the SNNPR State, Ethiopia: study protocol for a randomized controlled trial.

BACKGROUND: Diarrhea is one of the leading causes of death, killing 1.3 million in 2013 across the globe, of whom, 0.59 million were children under 5 years of age. Globally, about 1 billion people practice open defecation, and an estimated 2.4 billion people were living without improved sanitation facilities in 2015. Much of the previous research investigating the effect of improved sanitation has been based on observational studies. Recent studies have executed a cluster-randomized controlled trial to investigate the effect of improved sanitation. However, none of these recent studies achieved a sufficient level of latrine coverage. Without universal or at least a sufficient level of latrine coverage, a determination of the effect of improved latrines on the prevention of diarrheal disease is difficult. This cluster-randomized trial aims to explore the net effect of improved latrines on diarrheal prevalence and incidence in children under five and to investigate the effect on the diarrheal duration. METHOD/DESIGN: A phase-in and factorial design will be used for the study. The intervention for improving latrines will be implemented in an intervention arm during the first phase, and the comparable intervention will be performed in the control arm during the second phase. During the second phase, a water pipe will be connected to the gotts (villages) in the intervention arm. After the second phase is completed, the control group will undergo the intervention of receiving a water pipe connection. For diarrheal prevalence, five rounds of surveying will be conducted at the household level. The first four rounds will be carried out in the first phase to explore the effect of improved latrines, and the last one, in the second phase to examine the combined effects of improved water and sanitation. For documentation of diarrheal incidence and duration, the mother or caregiver will record the diarrheal episodes of her youngest child on the "Sanitation Calendar" every day. Of 212 gotts in the project area, 48 gotts were selected for the trial, and 1200 households with a child under 5 will be registered for the intervention or control arm. Informed consent from 1200 households will be obtained from the mother or caregiver in written form. DISCUSSION: To our knowledge, this is the second study to assess the effects of improved latrines on child diarrheal reduction through the application of Community-Led Total Sanitation. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN82492848

Cost-benefit analysis of water source improvements through borehole drilling or rehabilitation: an empirical study based on a cluster randomized controlled trial in the Volta Region, Ghana.

BACKGROUND: Despite remarkable progress in water coverage improvements, diseases associated with poor water remain a considerable public health problem in many developing countries. OBJECTIVE: We aimed to estimate the costs and benefits of drilling or rehabilitating boreholes with handpumps in resource-poor settings and hard-to-reach areas. METHODS: Diarrheal reduction in the population was predicted on the basis of the empirical findings from a cluster randomized controlled trial. The full investment and estimated annual running costs were used to calculate the intervention costs. Direct economic benefits of avoiding child diarrheal disease, indirect economic benefits related to health improvements, and non-health benefits related to water improvement were estimated. One-way and multi-way sensitivity analyses were performed to determine the robustness of the findings. RESULTS: Our analysis found that the return on a US$1 investment was US$ 9.4 for borehole drilling and US$ 14.1 for borehole rehabilitation. Time savings were the main contributor, accounting for 68% of the benefits, followed by the economic benefits of averted child deaths, which contributed to 15% of the benefits. The sensitivity analyses suggested that improving water sources yields high returns under all circumstances, and that borehole rehabilitation is more efficient than borehole drilling. CONCLUSION: This study explicitly justifies increased investment in water improvement in rural areas and demonstrates the high returns of rehabilitating boreholes. We hope that this study will be used as evidence for informing the policy decisions of governments or international agencies regarding further investments in improved water coverage in rural areas and the selection of appropriately designed interventions

Injectable Hydrogel-Based Combination Cancer Immunotherapy for Overcoming Localized Therapeutic Efficacy

Various immunotherapeutic agents that can elicit antitumor immune responses have recently been developed with the potential for improved efficacy in treating cancer. However, insufficient delivery efficiency at the tumor site, along with severe side effects after systemic administration of these anticancer agents, have hindered their therapeutic application in cancer immunotherapy. Hydrogels that can be directly injected into tumor sites have been developed to help modulate or elicit antitumor responses. Based on the biocompatibility, degradability, and controllable mechanochemical properties of these injectable hydrogels, various types of immunotherapeutic agents, such as hydrophobic anticancer drugs, cytokines, antigens, and adjuvants, have been easily and effectively encapsulated, resulting in the successful elicitation of antitumor immune responses and the retention of long-term immunotherapeutic efficacy following administration. This review summarizes recent advances in combination immunotherapy involving injectable hydrogel-based chemoimmunotherapy, photoimmunotherapy, and radioimmunotherapy. Finally, we briefly discuss the current limitations and future perspectives on injectable hydrogels for the effective combination immunotherapy of tumors

Tumor-targeting glycol chitosan nanocarriers: Overcoming the challenges posed by chemotherapeutics

Introduction: In the past decade, the glycol chitosan nanocarriers (GCNCs) have been widely used for tumor-targeted delivery of anticancer agents such as chemo drugs, peptides, and genes due to their biocompatibility, biodegradability, and easy fabrication. In particular, GCNCs can effectively solubilize water-insoluble chemo drugs as well as improve the delivery efficiency of chemo drugs to the tumor, resulting in maximizing therapeutic efficacy and minimizing side effect. In this review, we introduce the various applications of GCNCs for cancer treatment and these GCNCs demonstrate the great potential in overcoming challenges of chemotherapeutics. Areas covered: Various designs of GC nanocarriers have been reviewed. The current state of GC nanocarriers for delivering chemotherapeutics with a focus on their physicochemical properties including solubilization of anti-cancer drugs, sustained release, and tumor-selectivity. Furthermore, state of the art in delivery and therapeutic strategy using GC nanocarriers also introduced for overcoming challenges of chemotherapeutics. Expert opinion: Based on the reviewed literature, physicochemical properties of GC nanocarriers will have a great potential to overcome challenges posed by chemotherapeutics.N

Hypoalbuminemia and Albumin Replacement during Extracorporeal Membrane Oxygenation in Patients with Cardiogenic Shock

Background: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with cardiorespiratory failure. The serum albumin level is an important prognostic marker in critically ill patients. We evaluated the efficacy of using pre-ECMO serum albumin levels to predict 30-day mortality in patients with cardiogenic shock (CS) who underwent venoarterial (VA) ECMO. Methods: We reviewed the medical records of 114 adult patients who underwent VA-ECMO between March 2021 and September 2022. The patients were divided into survivors and non-survivors. Clinical data before and during ECMO were compared. Results: Patients’ mean age was 67.8±13.6 years, and 36 (31.6%) were female. The proportion of survival to discharge was 48.6% (n=56). Cox regression analysis showed that the pre-ECMO albumin level independently predicted 30-day mortality (hazard ratio, 0.25; 95% confidence interval [CI], 0.11–0.59; p=0.002). The area under the receiver operating characteristic curve of albumin levels (pre-ECMO) was 0.73 (standard error [SE], 0.05; 95% CI, 0.63–0.81; p3.4 g/dL (68.9% vs. 23.8%, p<0.001). As the adjusted amount of albumin infused increased, the possibility of 30-day mortality also increased (coefficient=0.140; SE, 0.037; p<0.001). Conclusion: Hypoalbuminemia during ECMO was associated with higher mortality, even with higher amounts of albumin replacement, in patients with CS who underwent VA-ECMO. Further studies are needed to predict the timing of albumin replacement during ECMO

Sustained and Long-Term Release of Doxorubicin from PLGA Nanoparticles for Eliciting Anti-Tumor Immune Responses

Immunogenic cell death (ICD) is a powerful trigger eliciting strong immune responses against tumors. However, traditional chemoimmunotherapy (CIT) does not last long enough to induce sufficient ICD, and also does not guarantee the safety of chemotherapeutics. To overcome the disadvantages of the conventional approach, we used doxorubicin (DOX) as an ICD inducer, and poly(lactic-co-glycolic acid) (PLGA)-based nanomedicine platform for controlled release of DOX. The diameter of 138.7 nm of DOX-loaded PLGA nanoparticles (DP-NPs) were stable for 14 days in phosphate-buffered saline (PBS, pH 7.4) at 37 &deg;C. Furthermore, DOX was continuously released for 14 days, successfully inducing ICD and reducing cell viability in vitro. Directly injected DP-NPs enabled the remaining of DOX in the tumor site for 14 days. In addition, repeated local treatment of DP-NPs actually lasted long enough to maintain the enhanced antitumor immunity, leading to increased tumor growth inhibition with minimal toxicities. Notably, DP-NPs treated tumor tissues showed significantly increased maturated dendritic cells (DCs) and cytotoxic T lymphocytes (CTLs) population, showing enhanced antitumor immune responses. Finally, the therapeutic efficacy of DP-NPs was maximized in combination with an anti-programmed death-ligand 1 (PD-L1) antibody (Ab). Therefore, we expect therapeutic efficacies of cancer CIT can be maximized by the combination of DP-NPs with immune checkpoint blockade (ICB) by achieving proper therapeutic window and continuously inducing ICD, with minimal toxicities

Doxorubicin-Loaded PLGA Nanoparticles for Cancer Therapy: Molecular Weight Effect of PLGA in Doxorubicin Release for Controlling Immunogenic Cell Death

Direct local delivery of immunogenic cell death (ICD) inducers to a tumor site is an attractive approach for leading ICD effectively, due to enabling the concentrated delivery of ICD inducers to the tumor site. Herein, we prepared doxorubicin (DOX)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) using different molecular weight PLGA (7000 g/mol and 12,000 g/mol), showing different drug release kinetics. The different release kinetics of DOX might differently stimulate a tumor cell-specific immune response by releasing damage-associated molecular patterns (DAMPs), resulting in showing a different antitumor response in the living body. DOX-PLGA7K NPs showed faster DOX release kinetics than DOX-PLGA12K NPs in the physiological condition. DOX-PLGA7K NPs and DOX-PLGA12K NPs were successfully taken up by the CT-26 tumor cells, subsequently showing different DOX localization times at the nucleus. Released DOX successfully lead to cytotoxicity and HMGB1 release in vitro. Although the DOX-PLGA7K NPs and DOX-PLGA12K NPs showed different sustained DOX release kinetics in vitro, tumor growth of the CT-26 tumor was similarly inhibited for 28 days post-direct tumor injection. Furthermore, the immunological memory effect was successfully established by the ICD-based tumor-specific immune responses, including DC maturation and tumor infiltration of cytotoxic T lymphocytes (CTLs). We expect that the controlled release of ICD-inducible chemotherapeutic agents, using different types of nanomedicines, can provide potential in precision cancer immunotherapy by controlling the tumor-specific immune responses, thus improving the therapeutic efficacy

Incidence, Predictive Factors and Long-Term Clinical Impact of Left Ventricular Remodeling According to the Completeness of Revascularization in Patients with ST-Elevation Myocardial Infarction and Multivessel Disease

In this study, we identified several factors related to left ventricular remodeling (LVR) and examined the impact of LVR on the prognosis of patients with ST-elevated myocardial infarction and multivessel disease treated with complete (CR) or incomplete (IR) revascularization. LVR was defined as an LV end-diastolic diameter &gt;55 mm. A total of 262 patients without LVR at presentation were followed up with echocardiography between 1 month and 1 year. The primary outcome was a composite of all-cause death (AD), MI, and heart failure (HF), referred to as a major adverse cardiovascular endpoint (MACE). Then, each variable was analyzed as a secondary outcome. Follow-up echocardiography identified 26 patients (9.9%) with LVR. LVR was associated with an initial LV ejection fraction &lt;50%, Killip 3 disease at presentation, and a peak troponin I level &gt;70 mg/dL. Survival analysis showed an association between LVR and adverse outcomes only in the IR group, in which the adjusted hazard ratio (HR) was increased for the MACE (HR = 3.22, 95% confidence interval (CI) = 1.19&ndash;8.71, p = 0.002) and HF (HR = 21.37, 95% CI = 4.47&ndash;102.09, p&lt; 0.001), but not for the CR group. In STEMI with MVD, LVR within the first year after percutaneous coronary intervention was associated with worse outcomes in the IR but not the CR group