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Twisted intramolecular charge transfer (TICT) based fluorescent probes and imaging agents
Get PDFTwisted Intramolecular charge transfer (TICT)-based fluorescent probes are crucial in chemical sensing due to their sensitivity and specificity. These probes undergo conformational changes upon interacting with target analytes, resulting in measurable fluorescence responses. Their environment-dependent emission characteristics make them ideal for detecting variations in solvent polarity, microviscosity, and specific chemical species. Recent advances have expanded their applications to organic optoelectronics and non-linear optics. This review discusses the design principles, mechanisms, and applications of TICT-based probes, emphasizing their role in detecting cations, anions, and neutral molecules. We describe their advantages, such as fluorescence turn-on or turn-off responses and potential for ratiometric detection, which inherently corrects for interferences. Challenges in developing these probes, including fluorescence quantum yield and photostability, are also addressed. Potential directions for future research are highlighted, including the need for improved biocompatibility and multimodal imaging capabilities, with the aim of enhancing their utility in environmental monitoring, biomedical research, and clinical diagnostics.</p
Evaluation of Performance of C-Reactive Protein (CRP) and Interferon-Gamma-Inducible Protein 10 (IP-10) as Screening for Active Tuberculosis
Get PDFBackground: Most of the currently approved TB diagnostics are sputum-based. However, due to unusual clinical presentations of TB among HIV patients, they may not have TB symptoms and be able to produce sputum. Hence, these diagnostics may not be able to detect as many TB cases as possible among these patients. Therefore, this study assessed the performance of C-reactive protein (CRP) and interferon-gamma-inducible protein 10 (IP-10) as a screening tool for TB. Methods: This prospective study was conducted by consecutively recruiting patients with TB symptoms, collecting their sputum and blood samples, using sputum culture as the reference standard, and determining the best cut-off point of serum levels of CRP and IP-10 (separately and in combination) for TB diagnosis. Findings: CRP and IP-10 were measured in 408 patients with TB symptoms, of which 21% had culture-confirmed TB. CRP’s sensitivity and specificity were (91.4% and 33.2%), (95.3% and 42.6%) and (84.8% and 22.1%) for the whole study population, HIV-negative and HIV-positive patients, respectively. The sensitivity and specificity of IP-10 were (87.3% and 40.9%), (87.5% and 50.3%) and (79.4% and 47.2%) for the patients’ categories, respectively. Combination of CRP and IP-10 slightly improved the performance of the biomarkers among HIV-negative patients, with sensitivity of 97.5% and specificity of 43.3%. Interpretation: Though CRP and IP-10 performed better in HIV-negative patients than among people living with HIV (PLHIV), the performance of the biomarkers is lower than what is recommended by the WHO (sensitivity ≥ 90% and specificity ≥ 70%) for a TB screening tool. Hence, there is a need for better non-sputum-based TB diagnostics.</p
Progress and Challenges in the Field of Snakebite Envenoming Therapeutics
Get PDFSnakebite envenoming kills and maims hundreds of thousands of people every year, especially in the rural settings of tropical regions. Envenomings are still treated with animal-derived antivenoms, which have prevented many lives from being lost but which are also medicines in need of innovation. Strides are being made to improve envenoming therapies, with promising efforts made toward optimizing manufacturing and quality aspects of existing antivenoms, accelerating research and development of recombinant antivenoms based on monoclonal antibodies, and repurposing of small-molecule inhibitors that block key toxins. Here, we review the most recent advances in these fields and discuss therapeutic opportunities and limitations for different snakebite treatment modalities. Finally, we discuss challenges related to preclinical and clinical evaluation, regulatory pathways, large-scale manufacture, and distribution and access that need to be addressed to fulfill the goals of the World Health Organization's global strategy to prevent and control snakebite envenoming.</p
Considerations in planning a controlled human infection model in at-risk groups in sub-Saharan Africa: the case for pneumococcal challenge in people living with HIV in Malawi and a report of stakeholder consultation
Get PDFControlled human infection models offer a unique opportunity to understand infectious disease pathogenesis and have accelerated vaccine development and evaluations in malaria and typhoid. One major limitation of most CHIMs is that they are typically conducted in healthy young adults who are generally the population least affected by infectious disease, and who exhibit distinct disease profiles to more at-risk populations such as people living with HIV, young children, and older adults. However, the added value of studying these populations with high relevance is only desirable if it can be done safely, robustly and acceptably. We present a framework to guide the conduct of a controlled human infection model in people living with HIV using a case-example of an experimental human pneumococcal carriage model in a setting of high disease-burden and transmission.</p
Molecular xenomonitoring of Schistosoma mansoni infections in Biomphalaria choanomphala at Lake Victoria, East Africa: Assessing roles of abiotic and biotic factors
Get PDFLake Victoria is a well-known hot spot for intestinal schistosomiasis, caused by infection with the trematode Schistosoma mansoni. The snail intermediate hosts of this parasite are Biomphalaria snails, with Biomphalaria choanomphala being the predominant intermediate host within Lake Victoria. The prevalence of S. mansoni infection within snail populations is influenced by both biotic and abiotic factors, including the physical and chemical characteristics of their environment, the incidence of infection in human populations (and reservoir hosts) and the level of genetic compatibility between the parasite and the host. Using molecular xenomonitoring, we measured the prevalence of S. mansoni infection within B. choanomphala populations along the Kenyan, Tanzanian and Ugandan shorelines of Lake Victoria and related this to the abiotic (habitat type, water depth, turbulence, temperature, conductivity, total dissolved solids, salinity, pH level) and biotic (B. choanomphala abundance, genetic diversity of host snail populations) factors of the lake. The overall mean prevalence of S. mansoni infection at Lake Victoria was 9.3%, with the highest prevalence of infection occurring on the Tanzanian shoreline (13.1%), followed by the Ugandan (8.2%) and Kenyan (4.7%) shorelines. There was a significant difference in B. choanomphala abundance, water temperature, conductivity, salinity, total dissolved solids and major anion/cation concentrations between the Kenyan, Tanzanian and Ugandan shorelines of Lake Victoria. A Spearman’s rank analysis found that the prevalence of S. mansoni infection had a significant, positive relationship with higher levels of B. choanomphala abundance, water acidity, and cation (Ca2+, Mg2+) concentrations. Additionally, we observed that sites with S. mansoni infection correlated with B. choanomphala populations with a higher mean haplotype diversity score compared to sites found without infection, though there was no significant relationship between the prevalence of infection and B. choanomphala haplotype diversity scores. Although our analysis is based upon an archival and unique collection of Biomphalaria snails, the abiotic and biotic relationships uncovered are useful for eco-epidemiological comparisons of intestinal schistosomiasis across Lake Victoria in future.</p
Tissue-specific modulation of CRISPR activity by miRNA-sensing guide RNAs
Get PDFNucleic acid nanostructures offer unique opportunities for biomedical applications due to their sequence-programmable structures and functions, which enable the design of complex responses to molecular cues. Control of the biological activity of therapeutic cargoes based on endogenous molecular signatures holds the potential to overcome major hurdles in translational research: cell specificity and off-target effects. Endogenous microRNAs (miRNAs) can be used to profile cell type and cell state, and are ideal inputs for RNA nanodevices. Here, we present CRISPR MiRAGE (miRNA-activated genome editing), a tool comprising a dynamic single-guide RNA that senses miRNA complexed with Argonaute proteins and controls downstream CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) activity based on the detected miRNA signature. We study the operation of the miRNA-sensing single-guide RNA and attain muscle-specific activation of gene editing through CRISPR MiRAGE in models of Duchenne muscular dystrophy. By enabling RNA-controlled gene editing activity, this technology creates opportunities to advance tissue-specific CRISPR treatments for human diseases.</p
A blended learning approach for capacity strengthening to improve the quality of integrated HIV, TB, and malaria services during antenatal and postnatal care in LMICs: a feasibility study
Get PDFBackground: The blended learning (BL) approach to training health care professionals is increasingly adopted in many countries because of high costs and disruption to service delivery in the light of severe human resource shortage in low resource settings. The Covid-19 pandemic increased the urgency to identify alternatives to traditional face-to-face (f2f) education approach. A four-day f2f antenatal care (ANC) and postnatal care (PNC) continuous professional development course (CPD) was repackaged into a 3-part BL course; (1) self-directed learning (16 h) (2) facilitated virtual sessions (2.5 h over 3 days) and (3) 2-day f2f sessions. This study assessed the feasibility, change in healthcare providers’ knowledge and costs of the BL package in Nigeria, Tanzania, and Kenya. Methods: A mixed methods design was used. A total of 89 healthcare professionals, were purposively selected. Quantitative data was collected through an online questionnaire and skills assessments, analyzed using STATA 12 software. Qualitative data was collected through key informant interviews and focus group discussions, analysed using thematic analysis. Results: Majority of participants (86%) accessed the online sessions using a mobile phone from home and health facilities. The median (IQR) time of completing the self-directed component was 16 h, IQR (8, 30). A multi-disciplinary team comprising of 42% nurse-midwives, 28% doctors, 20% clinical officers and 10% other healthcare professionals completed the BL course. Participants liked the BL approach due to its flexibility in learning, highly educative/relevant content, mixing of health worker cadres and CPD points. Aspects that were noted as challenging were related to personal log-in details and network connectivity issues during the self-directed learning and facilitated virtual sessions respectively. Conclusion: The blended learning approach to ANC-PNC in-service training was found to be acceptable, feasible and cost less to implement compared to face-to-face training approach in the study settings. The BL training approach was effective in improving the knowledge and skills of healthcare providers who participated in the training.</p
The Association Between Egg and Egg-Derived Cholesterol Consumption, and Their Change Trajectories, with Obesity Among Chinese Adults: Results from the China Health and Nutrition Survey
Get PDFBackground/Objectives: As a widely consumed, nutritious, and affordable food, eggs and their derivatives’ impacts on obesity remain inconclusive. In this study, we aimed to determine the association between egg and egg-derived cholesterol consumption, and their change trajectories, with obesity among Chinese adults. Methods: Longitudinal data collected by the China Health and Nutrition Survey from 1997 to 2015 were analyzed. The latent growth mixture model was used to identify eggs and egg-derived cholesterol consumption trajectories. Cox proportional hazard models with shared frailty were used to analyze the association between egg and egg-derived cholesterol consumption, and their change trajectories, with obesity. Results: Data from 10,971 and 9483 participants aged ≥18 years old were used for the analyses of general obesity and central obesity, respectively. Compared to participants with an average egg intake of 0.1–50.0 g/d during the follow-up period, adults who never consumed eggs or those with an average egg intake of 50.1–100.0 g/d and >100.0 g/d had a higher risk of general obesity, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.31 (1.08, 1.58), 1.30 (1.07, 1.60), and 1.98 (1.17, 3.35), respectively, and had a higher risk of central obesity, with HRs (95% CIs) of 1.17 (1.04, 1.31), 1.31 (1.14, 1.50), and 1.64 (1.15, 2.36), respectively. Participants with a “Baseline Low-Significant Rising Pattern” or a “Baseline High-Rising then Falling Pattern” of egg consumption trajectories during the follow-up period had a higher risk of general obesity, with HRs (95% CIs) of 1.56 (1.25, 1.93) and 1.38 (1.13, 1.69), respectively, and central obesity, with HRs (95% CIs) of 1.47 (1.29, 1.68) and 1.52 (1.34, 1.72), respectively. Compared to the second quartile (Q2) group of the average egg-derived cholesterol intake during the follow-up period, Q1, Q3, and Q4 groups had a higher risk of general obesity, with HRs (95% CIs) of 1.28 (1.06,1.54), 1.21 (1.02, 1.44), and 1.43 (1.19, 1.71), respectively, and a higher risk of central obesity, with HRs (95% CIs) of 1.20 (1.08, 1.33), 1.11 (1.01, 1.23), and 1.32 (1.19, 1.46), respectively. Participants with a “Baseline Low-Significant Rising Pattern” or with a “Baseline High-Rising then Falling Pattern” of egg-derived cholesterol consumption during the follow-up period had a higher risk of general obesity, with HRs (95% CIs) of 1.54 (1.25, 1.92) and 1.37 (1.15, 1.64), respectively, and a higher risk of central obesity, with HRs (95% CIs) of 1.46 (1.28, 1.68) and 1.47 (1.32, 1.64), respectively. Conclusions: Both the insufficient and excessive intake of eggs and egg-derived cholesterol tended to be associated with a higher risk of general and central obesity. Suddenly increasing or consistently high levels of egg and egg-derived cholesterol intake seemed to be associated with a higher risk of obesity. To prevent obesity, people should consume a moderate amount of eggs and egg-derived cholesterol.</p
Clinical features of puff adder envenoming: case series of Bitis arietans snakebites in Kenya and a scoping review of the literature.
Get PDFIntroductionThe puff adder (Bitis arietans) is a medically important snake species found across much of Africa, yet there is limited literature on the clinical features and pathophysiology of envenoming after a puff adder bite.MethodsWe conducted a case-series study to describe the clinical features of patients with puff adder bites who were treated in two primary healthcare facilities in Kenya and complemented our case-series with a scoping review of all published cases of puff adder envenoming that contained sufficient clinical details to highlight the major features.ResultsBetween December 2020 and September 2021, 15 patients were admitted with a suspected puff adder bite (based on the patient’s description of the biting snake or confirmed in patients who brought the dead snake or a picture of the biting snake for identification) at the Chemolingot and Mwingi sub-county hospitals in Baringo and Kitui counties, central Kenya. Common local and systemic features on admission included pain (n=15, 100%), swelling (n=14, 93%), and haemorrhage (n=9, 60%). Coagulopathy (n=2, 13%), blistering (n=1, 8%) and shock (n=1, 8%) were less common. In addition, we conducted a literature review and identified 23 studies with detailed descriptions of the clinical features of puff adder envenoming from 37 patients. Local features were common and consistent across cases—swelling (100%, n=37) and pain (95%, n=35). Systemic features were less consistent, with 10 (27%) patients exhibiting hypotension on admission, 10 (27%) patients reporting a fever, and 13 (35%) developing anaemia. Some complications were more common in patients with bites by captive snakes (amputations), compared to patients with bites by wild snakes (hypotension). Snake identification was easier and more accurate after bites by captive snakes, but more challenging for patients bitten in community settings.ConclusionWe combined clinical cases and a literature review to describe the common and less common clinical features of puff adder envenoming. Further clinical research incorporating serial laboratory assays of patients with definitively identified puff adder bites is crucial to better understand the pathophysiology of envenoming by this medically important snake species.</p
Optimising a novel biofilm-based process using Neurospora discreta for enhanced treatment of lignin-rich wastewater
Get PDFPaper and pulp mills generate substantial volumes of wastewater containing lignin-derived compounds that are challenging to degrade using conventional wastewater treatment methods. This study presents a novel biofilm-based process for enhanced lignin removal in wastewater using the fungus Neurospora discreta, which effectively degrades lignin and forms robust biofilms at the air–liquid interface under specific conditions. The process was optimised using the Taguchi design of experiments approach, and three factors including pH, copper sulphate concentration, and trace element concentration were evaluated at three levels. Experimental data were analysed against three responses: lignin degradation efficiency and the activities of two ligninolytic enzymes (polyphenol oxidase and versatile peroxidase). The results indicated that wastewater pH was the most significant parameter affecting lignin degradation efficiency and enzyme activities. Over 70% lignin degradation was achieved at pH levels of 5 and 6 with copper sulphate concentrations above 4 mg/L, while degradation efficiency drastically dropped to 45% at a pH value of 7. Reversed-phase high-performance liquid chromatography analysis demonstrated the effects of the three factors on the polar and non-polar components of lignin in wastewater, revealing a clear decrease in all peak areas after treatment. Additionally, significant relationships were observed between biofilm properties (including porosity, water retention value, polysaccharide content, and protein content) and lignin removal efficiency. This study also reported for the first time the presence of versatile peroxidase, a ligninolytic enzyme, in Neurospora sp.</p