Assessing the Integration of Skin Screening into a Mass Drug Administration Campaign against Neglected Tropical Diseases: A Cross-sectional Observational Study from two Districts in Côte d'Ivoire, 2023.

BACKGROUND: The World Health Organization advocates integrating neglected tropical diseases (NTDs) into common delivery platforms to combat them in resource-constrained settings. However, limited literature exists on the benefits of integration. This study examines the feasibility and impact of adding skin screening to a mass drug administration (MDA) campaign in Côte d'Ivoire. METHODS: In June 2023, the Ministry of Health and Public Hygiene of Côte d'Ivoire piloted screening for skin-related NTDs alongside a national MDA campaign targeting soil-transmitted helminthiases and schistosomiasis. Two districts, Fresco and Koro, were selected for the pilot. The study applied both quantitative and qualitative assessments. The quantitative aspect focused on campaign costs and outputs, using an ingredient approach for costing. The qualitative evaluation employed an empirical phenomenological approach to analyze the campaign's operational feasibility and appreciation by stakeholders. FINDINGS: MDA activities cost $ 0·66 per treated child and skin screening $ 0·62 per screened person, including medical products. The MDA campaign exceeded coverage targets in both districts, whereas skin screening coverage varied by locality and age group. Both the service delivery team and the beneficiaries expressed appreciation for the integrated campaign. However, opportunities for improvement were identified. CONCLUSION: Integrating MDA and skin NTD screening proved operationally feasible in this context but had not recorded cost-saving effects. The performance of the MDA campaign was not negatively affected by additional skin screening activities, but effective integration requires thorough joint planning, strengthened training, and proper supervision.

Research progress of propofol in alleviating cerebral ischemia/reperfusion injury.

Ischemic stroke is a leading cause of adult disability and death worldwide. The primary treatment for cerebral ischemia patients is to restore blood supply to the ischemic region as quickly as possible. However, in most cases, more severe tissue damage occurs, which is known as cerebral ischemia/reperfusion (I/R) injury. The pathological mechanisms of brain I/R injury include mitochondrial dysfunction, oxidative stress, excitotoxicity, calcium overload, neuroinflammation, programmed cell death and others. Propofol (2,6-diisopropylphenol), a short-acting intravenous anesthetic, possesses not only sedative and hypnotic effects but also immunomodulatory and neuroprotective effects. Numerous studies have reported the protective properties of propofol during brain I/R injury. In this review, we summarize the potential protective mechanisms of propofol to provide insights for its better clinical application in alleviating cerebral I/R injury.

Management of functional constipation-associated halitosis: a retrospective study.

The features of functional constipation (FC)-associated halitosis were identified in the author's previous report. In this report, the author aimed to further investigate its treatment and efficacy. This retrospective study reviewed 100 FC patients, including 82 (82%) halitosis patients and 18 (18%) non-halitosis patients. They underwent the organoleptic test (OLT) to diagnose halitosis, and the organoleptic score (OLS) (0-5) was used to evaluated halitosis severity. The Cleveland Clinical Constipation Score (CCCS) (0-30) was used to evaluate FC severity. Patients were treated with the laxative polyethylene glycol electrolyte powder (PGEP) for four weeks. These tests were performed before and after treatment. The author found that, before treatment, the CCCS was 20.00 (18.00-23.00) for all patients, 21.00 (19.00-24.00) for halitosis patients, and 18.00 (17.00-18.25) for non-halitosis patients. A significant difference was observed between halitosis patients and non-halitosis patients (P< 0.001). The OLS for halitosis patients was 3.00 (3.00-4.00). A positive correlation (r= 0.814, 95% CI: 0.732-0.872,P< 0.001) was found between OLS and CCCS. A CCCS ⩾18 predicted over 50% probability of halitosis. After treatment, the CCCS significantly decreased to 11.50 (6.00-14.75) (P< 0.001), and OLS significantly decreased to 1.00 (0.00-2.00) (P< 0.001). A positive correlation (r= 0.770, 95% CI: 0.673-0.841,P< 0.001) persisted between OLS and CCCS. A pre-treatment CCCS ⩾21 predicted over 50% probability of post-treatment halitosis, while a post-treatment CCCS ⩾12 predicted over 50% probability of post-treatment halitosis. The author concludes that the severity of FC parallels the severity of FC-associated halitosis, and can predict the probability of halitosis. Laxative treatment with PGEP is effective in improving FC-associated halitosis.

The roles of bacteria and viruses in COPD-Bronchiectasis association: A prospective cohort study.

BACKGROUND: Exacerbations are implicated in bronchiectasis and COPD, which frequently co-exist [COPD-Bronchiectasis association (CBA)]. We aimed to determine the bacterial and viral spectrum at stable-state and exacerbation onset of CBA, and their association with exacerbations and clinical outcomes of CBA as compared with bronchiectasis. METHODS: We prospectively collected spontaneous sputum from adults with CBA, bronchiectasis with (BO) and without airflow obstruction (BNO) for bacterial culture and viral detection at stable-state and exacerbations. RESULTS: We enrolled 76 patients with CBA, 58 with BO, and 138 with BNO (711 stable and 207 exacerbation visits). Bacterial detection rate increased from BNO, CBA to BO at steady-state (P = 0.02), but not at AE onset (P = 0.91). No significant differences in viral detection rate were found among BNO, CBA and BO. Compared with steady-state, viral isolations occurred more frequently at exacerbation in BNO (15.8 % vs 32.1 %, P = 0.001) and CBA (19.5 % vs 30.6 %, P = 0.036) only. In CBA, isolation of viruses, human metapneumovirus and bacteria plus viruses was associated with exacerbation. Repeated detection of Pseudomonas aeruginosa (PA) correlated with higher modified Reiff score (P = 0.032) in CBA but not in BO (P = 0.178). Repeated detection of PA yielded a shorter time to the first exacerbation in CBA [median: 4.3 vs 11.1 months, P = 0.006] but not in BO (median: 8.4 vs 7.6 months, P = 0.47). CONCLUSIONS: Isolation of any viruses, human metapneumovirus and bacterialplus viruses was associated with CBA exacerbations. Repeated detection of PA confers greater impact of future exacerbations on CBA than on BO.

Short- and Long-Term Outcome of Selective Reduction by Fetoscopy-Guided Bipolar Cord Coagulation in Monochronic Twin Pregnancies.

INTRODUCTION: The aim of this study was to assess the short- and long-term outcome of selective reduction by fetoscopy-guided bipolar cord coagulation in monochronic twin pregnancies. METHODS: Retrospective analysis was conducted of a consecutive cohort of all monochorionic twin pregnancies treated with fetoscopy-guided bipolar cord coagulation between December 2015 and December 2022 in a single center in China. RESULTS: A total of 43 monochronic twin pregnancies undergoing fetoscopy-guided bipolar cord coagulation were analyzed. There were 5 intrauterine deaths with an 88.4% (38/43) survival rate overall. The preterm premature rupture of the membranes rate was 13.2%, and the preterm birth before 37 and 32 weeks was 42.1% and 13.1%, respectively. An uptrend in the survival rate (78.9 vs. 95.8%, p = 0.086) and a downtrend of procedure time (30 vs. 16.5 min, p = 0.036) were observed over time (period 1 from December 2015 to December 2019 verses period 2 from January 2020 to December 2022). Long-term outcome was assessed in 94.6% (35/37) of survivors, and 91.4% (32/35) had normal neurodevelopmental outcome. CONCLUSION: Fetoscopy-guided bipolar cord coagulation for fetal reduction in complicated monochorionic twin pregnancies could achieve a favorable short- and long-term outcome, especially in experienced hands.

Carbon nitride reinforced chitosan/sodium alginate hydrogel as high-performance adsorbents for free hemoglobin removal in vitro and in vivo.

Removing free hemoglobin generated during extracorporeal circulation remains a challenge. Currently, there is no adsorbent with specificity and good biosafety for removing hemoglobin. In this study, a new chitosan/sodium alginate/carbon nitride (CS/SA/C3N4) hydrogel adsorbent was prepared by blending SA with C3N4 to drop into CS/CaCl2 solution. The physicochemical properties of CS/SA/C3N4 hydrogel were evaluated using some techniques, including scanning electron microscope, Zeta potential measurement, and thermogravimetric analysis. Hemoglobin adsorption in vitro, stability, hemocompatibility, cell compatibility, inflammatory reaction and blood extracorporeal circulation in vivo were also evaluated. The findings revealed that the CS/SA/C3N4-0.4 % hydrogel exhibited an impressive adsorption capacity of 142.35 mg/g for hemoglobin. The kinetic data of hemoglobin adsorption were well-described by pseudo second-order model, while the isothermal model data conformed to the Langmuir model. The hardness and modulus of CS/SA/C3N4-0.4 % was 11.7 KPa and 94.66 KPa respectively, which indicated robust resistance to breakage. CS/SA/C3N4 demonstrated excellent hemocompatibility, biocompatibility and anti-inflammatory properties. In addition, the results of in vivo rabbit extracorporeal blood circulation experiment demonstrated that CS/SA/C3N4 could adsorb free hemoglobin from blood while maintaining high biosafety standard. Consequently, CS/SA/C3N4 hydrogel emerges as a promising candidate for use as a hemoglobin adsorbent in extracorporeal blood circulation system.

Financial hardship among patients suffering from neglected tropical diseases: A systematic review and meta-analysis of global literature.

INTRODUCTION: Neglected tropical diseases (NTDs) mainly affect underprivileged populations, potentially resulting in catastrophic health spending (CHS) and impoverishment from out-of-pocket (OOP) costs. This systematic review aimed to summarize the financial hardship caused by NTDs. METHODS: We searched PubMed, EMBASE, EconLit, OpenGrey, and EBSCO Open Dissertations, for articles reporting financial hardship caused by NTDs from database inception to January 1, 2023. We summarized the study findings and methodological characteristics. Meta-analyses were performed to pool the prevalence of CHS. Heterogeneity was evaluated using the I2 statistic. RESULTS: Ten out of 1,768 studies were included, assessing CHS (n = 10) and impoverishment (n = 1) among 2,761 patients with six NTDs (Buruli ulcer, chikungunya, dengue, visceral leishmaniasis, leprosy, and lymphatic filariasis). CHS was defined differently across studies. Prevalence of CHS due to OOP costs was relatively low among patients with leprosy (0.0-11.0%), dengue (12.5%), and lymphatic filariasis (0.0-23.0%), and relatively high among patients with Buruli ulcers (45.6%). Prevalence of CHS varied widely among patients with chikungunya (11.9-99.3%) and visceral leishmaniasis (24.6-91.8%). Meta-analysis showed that the pooled prevalence of CHS due to OOP costs of visceral leishmaniasis was 73% (95% CI; 65-80%, n = 2, I2 = 0.00%). Costs of visceral leishmaniasis impoverished 20-26% of the 61 households investigated, depending on the costs captured. The reported costs did not capture the financial burden hidden by the abandonment of seeking healthcare. CONCLUSION: NTDs lead to a substantial number of households facing financial hardship. However, financial hardship caused by NTDs was not comprehensively evaluated in the literature. To develop evidence-informed strategies to minimize the financial hardship caused by NTDs, studies should evaluate the factors contributing to financial hardship across household characteristics, disease stages, and treatment-seeking behaviors.

Dihydroquercetin alleviates dopamine neuron loss via regulating TREM2 activation.

BACKGROUND: Parkinson's disease (PD) is a prevalent neurodegenerative disorder, marked by the degeneration of dopamine (DA) neurons in the substantia nigra (SN). Current evidence strongly suggests that neuroinflammation, primarily mediated by microglia, contributes to PD pathogenesis. Triggering receptor expressed on myeloid cells 2 (TREM2) might serve as a promising therapeutic target for PD due to its ability to suppress neuroinflammation. Dihydroquercetin (DHQ) is an important natural dihydroflavone and confers apparent anti-inflammatory, antioxidant and anti-fibrotic effects. Recently, DHQ-mediated neuroprotection was exhibited. However, the specific mechanisms of its neuroprotective effects remain incompletely elucidated. METHODS: In this study, rat models were utilized to induce damage to DA neurons using lipopolysaccharide (LPS) and 6-hydroxydopamine (6-OHDA) to assess the impacts of DHQ on the loss of DA neurons. Furthermore, DA neuronal MN9D cells and microglial BV2 cells were employed to investigate the function of TREM2 in DHQ-mediated DA neuroprotection. Finally, TREM2 knockout mice were used to investigate whether the neuroprotective effects mediated by DHQ through a mechanism dependent on TREM2. RESULTS: The main findings demonstrated that DHQ effectively protected DA neurons against neurotoxicity induced by LPS and 6-OHDA and inhibited microglia-elicited neuroinflammation. Meanwhile, DHQ promoted microglial TREM2 signaling activation. Notably, DHQ failed to reduce inflammatory cytokines release and further present neuroprotection from DA neurotoxicity upon TREM2 silencing. Similarly, DHQ didn't exert DA neuroprotection in TREM2 knockout mice. CONCLUSIONS: These findings suggest that DHQ exerted DA neuroprotection by regulating microglia TREM2 activation.

Isomeric Porous Cu(I) Triazolate Frameworks Showing Periodic and Aperiodic Flexibility for Efficient CO Separation.

Guest-induced (crystal-to-crystal) transformation, i.e., periodic flexibility, is a typical feature of molecule-based crystalline porous materials, but its role for adsorptive separation is controversial. On the other hand, aperiodic flexibility is rarely studied. This work reports a pair of isomeric Cu(I) triazolate frameworks, namely, α-[Cu(fetz)] (MAF-2Fa) and ß-[Cu(fetz)] (MAF-2Fb), which show typical periodic and aperiodic flexibility for CO chemical adsorption, respectively. Quantitative mixture breakthrough experiments show that, while MAF-2Fa exhibits high adsorption capacity at high pressures but negligible adsorption below the threshold pressure and with leakage concentrations of 3-8%, MAF-2Fb exhibits relatively low adsorption capacity at high pressures but no leakage (residual CO concentration <1 ppb). Tandem connection of MAF-2Fa and MAF-2Fb can combine their advantages of high CO adsorption capacities at high and low pressures, respectively. MAF-2Fa and MAF-2Fb can both keep the separation performances unchanged at high relative humidities, but only MAF-2Fb shows a unique coadsorption behavior at a relative humidity of 82%, which can be used to improve purification performances.

Non-coding transcribed ultraconserved region uc.290 in colon mucosa promotes intestinal fibrosis in chronic active ulcerative colitis.

BACKGROUND AND AIMS: TGF-ß1 induces epithelial-mesenchymal transition (EMT) and leads to intestinal fibrosis in ulcerative colitis (UC). We aimed to investigate the expression of transcribed ultraconserved region uc.290 in chronic UC and its role in intestinal fibrosis. METHODS: Colon specimens were taken from thirty chronic active UC, chronic inactive UC and healthy controls respectively. Modified Mayo score, expressions of uc.290, TGF-ß1, EMT biomarkers (Vimentin, α-SMA and E-cadherin) and intestinal fibrosis biomarker (collagen Ⅲ) in colon biopsy specimens were determined in human. Expressions of TGF-ß1, EMT biomarkers and collagen Ⅲ were determined in uc.290 overexpressed or silenced epithelial colon cells (HT29). RESULTS: Uc.290, TGF-ß1 and collagen Ⅲ were overexpressed, and EMT was prominent in chronic active UC. Uc.290 level had a positive correlation with modified Mayo score in chronic active UC. TGF-ß1 and collagen Ⅲ were overexpressed, and EMT was prominent in uc.290 overexpressed HT29 cells. CONCLUSIONS: Uc.290 was overexpressed in chronic active UC and might promote intestinal fibrosis by TGF-ß1/EMT/collagen Ⅲ pathway.

MASLD can cause halitosis by small intestinal bacterial overgrowth.

OBJECTIVES: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) exhibit varying degrees of halitosis. The author speculated that small intestinal bacterial overgrowth (SIBO) might lead to MASLD and subsequent extra-oral halitosis and aimed to test this hypothesis. METHODS: This retrospective cross-sectional study reviewed 885 extra-oral halitosis patients. Halitosis and exhaled dimethyl sulfide (DMS) were measured by organoleptic score (OLS) (0-5) and OralChroma, respectively. SIBO and MASLD were diagnosed by hydrogen breath test and Fibroscan combined with cardiometabolic criteria. RESULTS: In this study, 133/885 (15.05%) of the halitosis patients otherwise healthy had MASLD, while 87/133 (65.41%) of the MASLD patients were SIBO-positive. No significant differences were observed in physical parameters such as age, serum biochemical parameters such as lipids, or Fibroscan parameters between the SIBO-positive and SIBO-negative patients. However, the OLS was 4 (interquartile range: 3-4) and exhaled DMS level was 56 (43-75) parts per billion (ppb) in the SIBO-positive patients, significantly greater than 2 (2-3) and 43 (25-51) ppb in the SIBO-negative patients (both p < 0.001). Exhaled hydrogen levels positively correlated with the OLS and exhaled DMS levels (r = 0.774, r = 0.740, both p < 0.001). CONCLUSION: MASLD can cause halitosis by SIBO.

[Characteristics of VOCs Emissions and Ozone Formation Potential for Typical Chemicals Industry Sources in China].

This study selected five typical types of chemical industry volatile organic compounds (VOCs) emission characteristics in China for analysis. The results from 70 source samples showed that alkanes were the dominant VOCs category from synthetic material industry sources, petrochemical industry sources, and coating industry sources (accounting for 43%, 63%, and 68%, respectively); olefins were the main VOCs category from the daily supplies chemical industry (46%); and halogenated hydrocarbons were the dominate VOCs category from specialty chemicals industry account source emissions (43%). Additionally, the machine learning method was applied in this study to analyze the marker components of the above industries. The results showed that decane and tetrahydrofuran were the source markers of the synthetic material industry; n-butanol and toluene were the markers of the daily supplies industry source; 1,2,3-trimethylbenzene and 1,3,5-trimethylbenzene were the markers of the petrochemical industry source; propylene and 3-methyl pentane were the source markers of the coating industry; and P-Xylene and cumene were the markers of the specialty chemicals industry source. The maximum incremental reactivity method (MIR) was used to estimate the ozone formation potential (OFP) of different VOCs-sources. The calculation results showed that when considering per unit TVOCs concentration emissions, the contribution to the ozone generation potential was in the order of the daily supplies chemical industry, specialty chemical industry, petrochemical industry, synthetic material industry, and coating industry. Therefore, we suggest that more attention should be paid to the key active species emitted by various industry sources rather than only the total amount of VOCs emissions in future ozone prevention and control efforts.

Acquired Multidrug Resistance in AML Is Caused by Low Apoptotic Priming in Relapsed Myeloblasts.

In many cancers, mortality is associated with the emergence of relapse with multidrug resistance (MDR). Thus far, the investigation of cancer relapse mechanisms has largely focused on acquired genetic mutations. Using acute myeloid leukemia (AML) patient-derived xenografts (PDX), we systematically elucidated a basis of MDR and identified drug sensitivity in relapsed AML. We derived pharmacologic sensitivity for 22 AML PDX models using dynamic BH3 profiling (DBP), together with genomics and transcriptomics. Using in vivo acquired resistant PDXs, we found that resistance to unrelated, narrowly targeted agents in distinct PDXs was accompanied by broad resistance to drugs with disparate mechanisms. Moreover, baseline mitochondrial apoptotic priming was consistently reduced regardless of the class of drug-inducing selection. By applying DBP, we identified drugs showing effective in vivo activity in resistant models. This study implies evasion of apoptosis drives drug resistance and demonstrates the feasibility of the DBP approach to identify active drugs for patients with relapsed AML. SIGNIFICANCE: Acquired resistance to targeted therapy remains challenging in AML. We found that reduction in mitochondrial priming and common transcriptomic signatures was a conserved mechanism of acquired resistance across different drug classes in vivo. Drugs active in vivo can be identified even in the multidrug resistant state by DBP.

Activation of persulfate by g-C3N4/nZVI@SBC for degradation of total petroleum hydrocarbon in groundwater.

In this study, we synthesized a high removal efficiency catalyst using biochar-supported nanoscale zero-valent iron and g-C3N4, denoted as g-C3N4/nZVI@SBC, to activate persulfate (PS) for the degradation of total petroleum hydrocarbon (TPH) in groundwater. We characterized the morphology and physiochemical properties of g-C3N4/nZVI@SBC with scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR), BET surface area analysis, and X-ray photoelectron spectroscopy (XPS). To assess the performance of the g-C3N4/nZVI@SBC catalyst, we investigated various reaction parameters, such as the mass ratio of g-C3N4 to nZVI@SBC, PS concentration, initial pH, initial TPH concentration, and the presence of coexisting ions in the system. The results from batch experiments and repeated use trials indicate that g-C3N4/nZVI@SBC exhibited both excellent catalytic activation capability and impressive durability, making it a promising choice for TPH degradation. Specifically, when the PS concentration reached 1 mM, the catalyst dosage was 0.3 g/L, and the g-C3N4 to nZVI@SBC mass ratio was 2, we achieved a remarkable TPH removal efficiency of 93.8%. Through electron paramagnetic resonance (EPR) testing and quenching experiments, we identified sulfate radicals, hydroxyl radicals, and superoxide radicals as the primary active substance involved in the TPH degradation process. Moreover, the g-C3N4/nZVI@SBC composite proved highly effective for in-situ TPH removal from groundwater and displayed an 86% removal rate, making it a valuable candidate for applications in permeable reactive barriers (PRB) aimed at enhancing environmental remediation. In summary, by skillfully utilizing g-C3N4/nZVI@SBC, this study has made notable advancements in synthesis and characterization, presenting a feasible and innovative approach to addressing TPH pollution in groundwater.