With a limited global supply of vaccines and an increasing vaccine hesitancy, improving vaccination coverage has become a priority. Current vaccination regimes require multiple doses to be ...administered in a defined schedule where missed doses may lead to incomplete vaccine coverage and failure of immunization programmes. As such, there is an ever-increasing demand to convert multi-dose injectable vaccines into single-dose formats, often called single administration vaccines (SAVs).
This review summarizes recent developments in the field of SAVs, with a focus on pulsatile or controlled-release formulations. It will identify the technical challenges, translational as well as commercial barriers to SAVs development. Furthermore, the progress of SAV formulations for hepatitis B and polio vaccines will be reviewed thoroughly as case studies, with a focus on the development challenges and the preclinical immunogenicity/reactogenicity data.
Despite the efforts to develop SAVs, few attempts have advanced to Phase-I trials. Considering the SAV development journey and bottlenecks, including commercial barriers from the early stages, may overcome some of the hurdles around the technology. The renewed global focus on vaccines since the COVID-19 pandemic could facilitate development of a new generation of technologies for pandemic preparedness including strategies for SAVs.
Safe drinking water scarcity is an acute problem in the coastal regions of Bangladesh which is mainly caused by salinity intrusion. In this context, drinking water sources are severely affected, ...including adverse effects on agriculture, health, fisheries and the ecosystem. This research investigates i) selected water quality parameters ii) local people's perception on drinking water scarcity iii) how local people's cope with safe drinking water scarcity. This research was conducted using local water samples, questionnaire survey of 200 households and 4 focus group discussions (FDGs) in Shyamnagar and Tala sub-district of Satkhira district. The study of the water quality parameters exposed the extreme conditions of the drinking water sources in the area. The average values of total dissolved solids (TDS), electrical conductivity (EC) and Chloride concentration (Cl−) were found respectively 4044.12 mg/L, 7186.7 μS/cm, and 3143.6 mg/L in Shyamnagar and 2313.60 mg/L, 4390.3 μS/cm, and 1402.1 mg/L in Tala. The result of community perception reveals that local people are aware of the safe water scarcity and nearly all of them perceive that salinity is the main reason behind it. Even though there are a number of socioeconomic factors, communities have their own adaptation technologies to cope with the problem. The study concludes with the development of a community based model defining the key responsibilities of the stakeholders, including local and central government, NGOs and community people to work in a well-coordinated manner which will be effective for reducing the scarcity of the safe drinking water.
•Water quality parameters were tested to find out the current salinity condition.•Spatial mapping of saline water quality parameters was plotted using GIS.•Examined people's perception and the adaptation measures to cope with water crisis.•An integrated community based model was proposed to combat drinking water scarcity.
Antimicrobial resistance (AMR) is emerging as a global threat to public health. One of the strategies employed to combat AMR is the use of adjuvants which act to enhance or reinstate antimicrobial ...activity by inhibiting resistance mechanisms. However, these adjuvants are themselves not immune to selecting resistant phenotypes. Thus, there is a need to utilise mechanisms which are either less likely to or unable to trigger resistance. One commonly employed mechanism of resistance by microorganisms is to prevent antimicrobial uptake or efflux the antibiotic which manages to permeate its membrane. Here we propose amino acids as antimicrobial adjuvants that may be utilizing alternate mechanisms to fight AMR. We used a modified ethidium bromide (EtBr) efflux assay to determine its efflux in the presence of ciprofloxacin within Staphylococcus aureus (NCTC 8325) and Pseudomonas aeruginosa (PAO1). In this study, aspartic acid and glutamic acid were found to inhibit growth of both bacterial species. Moreover, a reduced production of toxic pigments, pyocyanin and pyoverdine by P. aeruginosa was also observed. As evident from similar findings with tetracycline, these adjuvants, may be a way forward towards tackling antimicrobial resistance.
Pain is a sensation a humans sense as a protective mechanism against physical injury. This sensation is closely related to inflammation. It ranges from mild to highly obnoxious. It is well-known that ...the levels of the inflammatory biomarker, C-reactive protein (CRP), increase manifold in acute inflammation and pain. Olive oil, known to have many phytochemicals, has been traditionally used to alleviate pain. Amongst major phenolic compounds in olive oil are oleuropein (OLE), hydroxytyrosol (HT), tyrosol, and oleocanthal. Whether the analgesic and anti-inflammatory properties in olive oil are due to any specific interections is not known. Therefore, this study aimed to elucidate the possible anti-inflammatory and anti-nociceptive properties in those major phenolic compounds by using molecular docking software MOE 2015, comparing the energy value and binding site of phenolic compounds to that of well-known synthetic non-steroidal anti-inflammatory drugs (NSAIDs) and phosphocholine. The docking experiment showed that all compounds could directly interact with CRP. Oleuropein had the most potent interaction with CRP (-7.7580), followed by indomethacin (-6.0775), oleocanthal (-5.5734), ibuprofen (-5.3857), phosphocholine (-4.3876), HT (-4.2782), and tyrosol (-4.2329). Interestingly, the present study found other phytochemicals in olive oil that can be exploited as potential, safe, and cost-effective lead compound(s) for analgesic and anti-inflammatory activity, as supported by its molecular docking data.
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•Quinoline derivatives were synthesized from imines and aldehydes via iodine catalysis.•All the compounds were screened against h-NTPDase1, 2, 3 and 8.•Quinoline derivatives showed ...considerable activity against h-NTPDase1 and 8.•Selective inhibitors of h-NTPDase1 and h-NTPDase8 were found.•Molecular docking studies were performed to rationalize the results.
Nucleoside triphosphate diphosphohydrolases (NTPDases), an important class of ectonucleotidases, are responsible for the sequential hydrolysis of extracellular nucleotides. However, over-expression of NTPDases has been linked with various pathological diseases e.g. cancer. Thus, to treat these diseases, the inhibitors of this class of enzyme are of interest. The significance of this class of enzyme encouraged us to synthesize a new class of quinoline derivatives with the aim to find selective and potent inhibitors of NTPDases. Therefore, a mild and efficient synthetic route was established for the synthesis of quinoline derivatives. The reaction was catalyzed by molecular iodine to afford the substituted quinoline derivatives. All the synthetic derivatives (3a-3w) were evaluated for their potential to inhibit the h-NTPDase1, 2, 3 and 8. Most of the compounds were identified as dual inhibitors of h-NTPDase1 and 8 with lower effects on h-NTPDase2 and 3. Two compounds i.e.3f and 3t were identified as selective inhibitor of h-NTPDase1 whereas the compound 3s inhibited the h-NTPDase8 selectively. Moreover, the compounds 3p (IC50 = 0.23 ± 0.01 µM), 3j (IC50 = 21.0 ± 0.03 µM) 3d (IC50 = 5.38 ± 0.21 µM) and 3c (IC50 = 1.13 ± 0.04 µM) were found to be the most potent inhibitors of h-NTPDase1, 2, 3 and 8, respectively. To determine the binding interaction, molecular docking studies were also carried out.
The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this ...effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic.
To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold >75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold <0·03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold <1·0).
In 2019, there were 36·8 million (95% uncertainty interval UI 35·1–38·9) people living with HIV worldwide. There were 0·84 males (95% UI 0·78–0·91) per female living with HIV in 2019, 0·99 male infections (0·91–1·10) for every female infection, and 1·02 male deaths (0·95–1·10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28·52% decrease in incident cases, 95% UI 19·58–35·43, and a 39·66% decrease in deaths, 36·49–42·36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0·05 (95% UI 0·05–0·06) and the global incidence-to-mortality ratio was 1·94 (1·76–2·12). No regions met suggested thresholds for progress.
Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics.
The Bill & Melinda Gates Foundation, the National Institute of Mental Health of the US National Institutes of Health (NIH), and the National Institute on Aging of the NIH.
With the advent of medical technology and science, the number of animals used in research has increased. For decades, the use of animals in research and product testing has been a point of conflict. ...Experts and pharmaceutical manufacturers are harming animals worldwide during laboratory research. Animals have also played a significant role in the advancement of science; animal testing has enabled the discovery of various novel drugs. The misery, suffering, and deaths of animals are not worth the potential human benefits. As a result, animals must not be exploited in research to assess the drug mechanism of action (MOA). Apart from the ethical concern, animal testing has a few more downsides, including the requirement for skilled labor, lengthy processes, and cost. Because it is critical to investigate adverse effects and toxicities in the development of potentially viable drugs. Assessment of each target will consume the range of resources as well as disturb living nature. As the digital twin works in an autonomous virtual world without influencing the physical structure and biological system. Our proposed framework suggests that the digital twin is a great reliable model of the physical system that will be beneficial in assessing the possible MOA prior to time without harming animals. The study describes the creation of a digital twin to combine the information and knowledge obtained by studying the different drug targets and diseases. Mechanism of Action using Digital twin (MOA-DT) will enable the experts to use an innovative approach without physical testing to save animals, time, and resources. DT reflects and simulates the actual drug and its relationships with its target, however presenting a more accurate depiction of the drug, which leads to maximize efficacy and decrease the toxicity of a drug. In conclusion, it has been shown that drug discovery and development can be safe, effective, and economical in no time through the combination of the digital and physical models of a pharmaceutical as compared to experimental animals.
Educational data generated through various platforms such as e-learning, e-admission systems, and automated result management systems can be effectively processed through educational data mining ...techniques in order to gather highly useful insights into students’ performance. The prediction of student performance from historical academic data is a highly desirable application of educational data mining. In this regard, there is an urgent need to develop an automated technique for student performance prediction. Existing studies on student performance prediction primarily focus on utilizing the conventional feature representation schemes, where extracted features are fed to a classifier. In recent years, deep learning has enabled researchers to automatically extract high-level features from raw data. Such advanced feature representation schemes enable superior performance in challenging tasks. In this work, we examine the deep neural network model, namely, the attention-based Bidirectional Long Short-Term Memory (BiLSTM) network to efficiently predict student performance (grades) from historical data. In this article, we have used the most advanced BiLSTM combined with an attention mechanism model by analyzing existing research problems, which are based on advanced feature classification and prediction. This work is really vital for academicians, universities, and government departments to early predict the performance. The superior sequence learning capabilities of BiLSTM combined with attention mechanism yield superior performance compared to the existing state-of-the-art. The proposed method has achieved a prediction accuracy of 90.16%.
Thermostable alkaline serine protease gene of Geobacillus stearothermophilus B‐1172 was cloned and expressed in Escherichia coli BL21 (DE3) using pET‐22b(+), as an expression vector. The growth ...conditions were optimized for maximal production of the protease using variable fermentation parameters, i.e., pH, temperature, and addition of an inducer. Protease, thus produced, was purified by ammonium sulfate precipitation followed by ion exchange chromatography with 13.7‐fold purification, with specific activity of 97.5 U mg−1, and a recovery of 23.6%. Molecular weight of the purified protease, 39 kDa, was determined by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE). The enzyme was stable at 90 °C at pH 9. The enzyme activity was steady in the presence of EDTA indicating that the protease was not a metalloprotease. No significant change in the activity of protease after addition of various metal ions further strengthened this fact. However, an addition of 1% Triton X‐100 or SDS surfactants constrained the enzyme specific activity to 34 and 19%, respectively. Among organic solvents, an addition of 1‐butanol (20%) augmented the enzyme activity by 29% of the original activity. With casein as a substrate, the enzyme activity under optimized conditions was found to be 73.8 U mg−1. The effect of protease expression on the host cells growth was also studied and found to negatively affect E. coli cells to certain extent. Catalytic domains of serine proteases from eight important thermostable organisms were analyzed through WebLogo and found to be conserved in all serine protease sequences suggesting that protease of G. stearothermophilus could be beneficially used as a biocontrol agent and in many industries including detergent industry.
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