Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1–4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0–8·4) while the total sum of global YLDs increased from 562 million (421–723) to 853 million (642–1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6–9·2) for males and 6·5% (5·4–7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782–3252] per 100 000 in males vs s1400 [1279–1524] per 100 000 in females), transport injuries (3322 [3082–3583] vs 2336 [2154–2535]), and self-harm and interpersonal violence (3265 [2943–3630] vs 5643 [5057–6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury

Value of Serum Thrombomodulin as a Marker and Predictor in Patients with Sepsis-Associated Acute Kidney Injury

Van Tri Nguyen,1,2 Hong Ngoc Nguyen-Phan,1 That Ngoc Ton,3 Bui Bao Hoang1 1Department of Internal Medicine, Hue University of Medicine and Pharmacy, Hue University, Hue City, Vietnam; 2Department of Anesthesiology of Hue International Medical Center, Hue Central Hospital, Hue City, Vietnam; 3Department of Biochemistry, Hue Central Hospital, Hue City, VietnamCorrespondence: Bui Bao Hoang, Department of Internal Medicine, Hue University of Medicine and Pharmacy, Hue University, 06 Ngo Quyen Street, Hue City, Vietnam, Tel +84905405005, Email [email protected]; [email protected]: To investigate the serum soluble thrombomodulin (sTM) concentration in patients with sepsis-associated acute kidney injury (AKI) and to determine the value of sTM in predicting AKI and mortality in sepsis patients.Methods: This prospective observational study was conducted on 71 patients diagnosed with sepsis according to Sepsis 3 at the Intensive Care Unit, Hue Central Hospital, Vietnam, from September 2021 to February 2023.Results: Among 71 sepsis patients, there were 38 (53.5%) AKI cases, including 16 (22.5%) cases of stage 1 AKI, 14 (19.7%) cases of stage 2 AKI, 8 (11.3%) cases of stage 3 AKI, 16 (22.5%) cases of renal replacement therapy, 28 (39.4%) cases of septic shock, and 21 (29.6%) cases of mortality within 28 days. The concentrations of lactate and IL-6 in the AKI and mortality groups were statistically significantly greater than those in the non-AKI and survival groups (p < 0.05). The serum sTM concentration was 4.33 ng/mL, the serum sTM level in the AKI group was statistically significantly higher than that in the non-AKI group (sTM [4.71 vs 2.54 ng/mL, p < 0.001]), and the serum sTM level in the mortality group was statistically significantly higher than the survival group (sTM [4.78 vs 3.87 ng/mL, p < 0.001]). The AUC of sTM for predicting AKI was 0.864; the AUCs of sTM, IL-6, SOFA, and APACHE II for predicting mortality were 0.811, 0.671, 0.816, and 0.705, respectively.Conclusion: AKI was a prevalent complication among sepsis patients at the ICU. In the AKI and mortality groups, sTM concentration was statistically significantly higher than that in the non-AKI and survival groups. sTM was the predictor of acute kidney injury and mortality in patients with sepsis.Keywords: thrombomodulin, sepsis, acute kidney injur

Energy Trading and Time Scheduling for Energy-Efficient Heterogeneous Low-Power IoT Networks

In this paper, an economic model is proposed to jointly optimize profits for participants in a heterogeneous IoT wireless-powered backscatter communication network. In the network under considerations, a power beacon and IoT devices (with various communication types and energy constraints) are assumed to belong to different service providers, i.e., energy service provider (ESP) and IoT service provider (ISP), respectively. To jointly maximize the utility for both service providers in terms of energy efficiency and network throughput, a Stackelberg game model is proposed to study the strategic interaction between the ISP and ESP. In particular, the ISP first evaluates its benefits from providing IoT services to its customers and then sends its requested price together with the service time to the ESP. Based on the request from the ISP, the ESP offers an optimized transmission power that maximizes its utility while meeting energy demands of the ISP. To study the Stackelberg equilibrium, we first obtain a closed-form solution for the ESP and propose a low-complexity iterative method based on block coordinate descent (BCD) to address the non-convex optimization problem for the ISP. Through simulation results, we show that our approach can significantly improve the profits for both providers compared with those of conventional transmission methods, e.g., bistatic backscatter and harvest-then-transmit communication methods

Bacterial bloodstream infections in a tertiary infectious diseases hospital in Northern Vietnam: aetiology, drug resistance, and treatment outcome

Background Bloodstream infections (BSIs) are associated with high morbidity and mortality worldwide. However their aetiology, antimicrobial susceptibilities and associated outcomes differ between developed and developing countries. Systematic data from Vietnam are scarce. Here we present aetiologic data on BSI in adults admitted to a large tertiary referral hospital for infectious diseases in Hanoi, Vietnam. Methods A retrospective study was conducted at the National Hospital for Tropical Diseases between January 2011 and December 2013. Cases of BSI were determined from records in the microbiology department. Case records were obtained where possible and clinical findings, treatment and outcome were recorded. BSI were classified as community acquired if the blood sample was drawn ≤48 h after hospitalization or hospital acquired if &gt;48 h. Results A total of 738 patients with BSI were included for microbiological analysis. The predominant pathogens were: Klebsiella pneumoniae (17.5%), Escherichia coli (17.3%), Staphylococcus aureus (14.9%), Stenotrophomonas maltophilia (9.6%) and Streptococcus suis (7.6%). The overall proportion of extended spectrum beta-lactamase (ESBL) production among Enterobacteriaceae was 25.1% (67/267 isolates) and of methicillin-resistance in S. aureus (MRSA) 37% (40/108). Clinical data was retrieved for 477 (64.6%) patients; median age was 48 years (IQR 36–60) with 27.7% female. The overall case fatality rate was 28.9% and the highest case fatality was associated with Enterobacteriaceae BSI (34.7%) which accounted for 61.6% of all BSI fatalities. Conclusions Enterobacteriaceae (predominantly K. pneumoniae and E. coli) are the most common cause of both community and hospital acquired bloodstream infections in a tertiary referral clinic in northern Vietnam