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Cilostazol, an anti-platelet aggregation medicine, is also known to have vasodilation properties and is commonly used for treating muscle soreness and cramps by increasing the muscle oxygen supply. The medication has limited oral bioavailability, is prone to pre-systemic metabolism, and is poorly soluble in aqueous media. A transdermal administration was planned to increase the drug’s solubility and therapeutic efficacy. The current work intended to develop cilostazol niosome-loaded transdermal gel, which was prepared, and with the use of Fourier transform infrared and differential scanning calorimetry analyses, drug-excipient interactions were observed. The medication was formulated utilizing Carbopol-934, Pluronic-F-127, and HPMC gel bases for the transdermally delivered niosomal gels. The produced niosomes had a maximum percentage of drug entrapment at 96.4%, with a particle size of 102 ± 11.30 nm and polydispersity index of 0.29 ± 0.069. The highest percentage of the medication that was entrapped was 96.4%, and the Carbopol-934 gel basis released the major part of the drug under in vitro conditions. A maximum transdermal flux was recorded at 3850.92 μg after 4 h, indicating a 10% increase in cilostazol permeation through rat skin. The flux rate for the niosomal preparation containing the drug ranged from 14.85 to 28.02 μg/cm2 h−1. In comparison to the pure cilostazol-loaded gels, the pharmacokinetics investigation showed that the niosomal gel formulations had considerably greater C max, T max, and AUC0. The niosomes loaded with cilostazol exhibited greater solubility, higher bioavailability, and improved effectiveness. Better therapeutic results may be achieved with systemic and site-directed delivery of cilostazol using the designed transdermal niosomal gel with appropriate molecular tagging modification/(s).

Abstract Background In the UK National Health Service (NHS), the patient’s vital signs are monitored and summarised into a National Early Warning Score (NEWS) score. A set of computer-aided risk scoring systems (CARSS) was developed and validated for predicting in-hospital mortality and sepsis in unplanned admission to hospital using NEWS and routine blood tests results. We sought to assess the accuracy of these models to predict the risk of COVID-19 in unplanned admissions during the first phase of the pandemic. Methods Adult ( > = 18 years) non-elective admissions discharged (alive/deceased) between 11-March-2020 to 13-June-2020 from two acute hospitals with an index NEWS electronically recorded within ± 24 h of admission. We identified COVID-19 admission based on ICD-10 code ‘U071’ which was determined by COVID-19 swab test results (hospital or community). We assessed the performance of CARSS (CARS_N, CARS_NB, CARM_N, CARM_NB) for predicting the risk of COVID-19 in terms of discrimination (c-statistic) and calibration (graphically). Results The risk of in-hospital mortality following emergency medical admission was 8.4% (500/6444) and 9.6% (620/6444) had a diagnosis of COVID-19. For predicting COVID-19 admissions, the CARS_N model had the highest discrimination 0.73 (0.71 to 0.75) and calibration slope 0.81 (0.72 to 0.89) compared to other CARSS models: CARM_N (discrimination:0.68 (0.66 to 0.70) and calibration slope 0.47 (0.41 to 0.54)), CARM_NB (discrimination:0.68 (0.65 to 0.70) and calibration slope 0.37 (0.31 to 0.43)), and CARS_NB (discrimination:0.68 (0.66 to 0.70) and calibration slope 0.56 (0.47 to 0.64)). Conclusions The CARS_N model is reasonably accurate for predicting the risk of COVID-19. It may be clinically useful as an early warning system at the time of admission especially to triage large numbers of unplanned admissions because it requires no additional data collection and is readily automated.

Ascochyta blight is a disease that causes significant yield losses in chickpea crops in Turkey under favorable environmental conditions. The fungal pathogen Ascochyta rabiei is the causative agent of this disease. The antifungal activity of previous fungicides against A. rabiei was not effective due to the heterothallic nature of the fungus. The aim of this study was to determine the sensitivity of A. rabiei to fungicides (25.2 g kgˉ1 boscalid + 12.8 g kgˉ1 pyraclostrobin; 50 % tebuconazole + 25 % trifloxystrobin; 62.5 g Lˉ1 propiconazole + 37.5 g Lˉ1 azoxystrobin; 80 % thiram; 80 % kükürt (sulphur); 80 % mancozeb; 80 % maneb) under in vitro and field conditions. Pure cultures of A. rabiei were isolated from infected chickpea plants collected in Boğazlayan, Sarıkaya, Sorgun, Merkez and Yerköy. A total of 14 A. rabiei isolates and 4 references were evaluated. The field test was conducted at Yozgat Bozok University, Yerköy Agricultural Application and Research Center Station. The trials began on March 14, 2021. The experimental area was divided into plots and the susceptible chickpea variety Sarı98 was used for the study. Two artificial inoculations were carried out approximately on the 40th and 80th days after sowing. Twenty-four hours after inoculation, the chickpea plants were sprayed with the fungicides Nativo® WG 75, Bellis®, Dikotan® M45 and Thiovit Jet® using a handheld sprayer. In vitro testing revealed that A. rabiei was resistant to kükürt (sulphur), thiram, maneb, and mancozeb. A field study showed that the percentage of A. rabiei isolates treated with the mancozeb fungicide was between 14 and 21 % of the control. Therefore, effective disease management strategies should include not only the use of fungicides, but also alternative approaches such as the use of resistant varieties. Moreover, the study focused on phenotypic resistance and suggests that future research should investigate the genetic and molecular mechanisms underlying A. rabiei resistance to enable better resistance management.

The presence of major insect pests and microflora in stored sorghum and maize in West Hararghe, Ethiopia, poses a significant threat to food security and agricultural productivity, leading to postharvest losses and economic hardship for local farmers. This study aimed to evaluate and identify the main grain insect pests and diseases of stored maize and sorghum in West Hararghe, Ethiopia. The survey was carried out in five major sorghum and maize-producing districts of the surveyed areas, namely, Mieso, Gemechis, Tullo, Anchar, and Oda Bultum. The results revealed that maize and sorghum grains stored in sacks, ground pits, markets, and hanging (maize cob) storage containers were infested with insect species: maize weevil (S. zeamais), Angoumois grain moth (S. cerealella), rice weevil (S. oryzae), Red flour beetle (T. castaneum), confused flour beetle (T. confusum), and Lesser grain borer (R. dominica). The mean levels of major insect pest infestations and associated percentages of grain damage, weight loss, and germination loss were recorded across all traditional storage systems, including sacking, marketing, hanging or maize cob, and ground pit storage methods. The highest absolute frequency and relative frequency of F. oxysporum (14.53%), followed by A. flavus (13.08%), on maize seeds were recorded in the agar plate test. A total of eight species of fungi, including Fusarium species, A. parasiticus, and A. niger, were identified using the blotter and agar plate method. The incidence of fungal diseases was markedly high (98.33%) in maize grain stored in the Anchar district, followed closely by grain stored in the market in the same district, recording 98.33%. Therefore, it is recommended that further confirmatory identification using molecular tools be conducted to develop novel management strategies for these insect pests and diseases.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has created one of the largest global health crises in almost a century. Although the current rate of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has decreased significantly, the long-term outlook of COVID-19 remains a serious cause of morbidity and mortality worldwide, with the mortality rate still substantially surpassing even that recorded for influenza viruses. The continued emergence of SARS-CoV-2 variants of concern (VOCs), including multiple heavily mutated Omicron sub-variants, has prolonged the COVID-19 pandemic and underscores the urgent need for a next-generation vaccine that will protect from multiple SARS-CoV-2 VOCs.MethodsWe designed a multi-epitope-based coronavirus vaccine that incorporated B, CD4+, and CD8+ T- cell epitopes conserved among all known SARS-CoV-2 VOCs and selectively recognized by CD8+ and CD4+ T-cells from asymptomatic COVID-19 patients irrespective of VOC infection. The safety, immunogenicity, and cross-protective immunity of this pan-variant SARS-CoV-2 vaccine were studied against six VOCs using an innovative triple transgenic h-ACE-2-HLA-A2/DR mouse model.ResultsThe pan-variant SARS-CoV-2 vaccine (i) is safe , (ii) induces high frequencies of lung-resident functional CD8+ and CD4+ TEM and TRM cells , and (iii) provides robust protection against morbidity and virus replication. COVID-19-related lung pathology and death were caused by six SARS-CoV-2 VOCs: Alpha (B.1.1.7), Beta (B.1.351), Gamma or P1 (B.1.1.28.1), Delta (lineage B.1.617.2), and Omicron (B.1.1.529).ConclusionA multi-epitope pan-variant SARS-CoV-2 vaccine bearing conserved human B- and T- cell epitopes from structural and non-structural SARS-CoV-2 antigens induced cross-protective immunity that facilitated virus clearance, and reduced morbidity, COVID-19-related lung pathology, and death caused by multiple SARS-CoV-2 VOCs.