In vitro antibacterial activity of the volatile oil of Nigella sativa seeds against multiple drug-resistant isolates of Shigella spp. and isolates of Vibrio cholerae and Escherichia coli

The antibacterial activity of the volatile oil of Nigella sativa seeds was studied against 37 isolates of Shigella dysenteriae 1, Shigella flexneri, Shigella sonnei and Shigella boydii and 10 strains of Vibrio cholerae and Escherichia coli. Most of the strains were clinically resistant to ampicillin, co-trimoxazole and tetracycline. All the strains tested showed promising sensitivity to the volatile oil. The minimum inhibitory concentration (MIC) of the volatile oil for Shigella, Vibrio and Escherichia strains tested was between 50–400 μg/mL.     

Effect of nutrition counselling with a digital job aid on child dietary diversity: Analysis of secondary outcomes from a cluster randomised controlled trial in rural Bangladesh

Adequate dietary diversity among infants is often suboptimal in developing countries. We assessed the impact of nutrition counselling using a digital job aid on dietary diversity of children aged 6–23 months using data from a cluster randomised controlled trial in Bangladesh. The trial had five arms, each with 25 clusters. The four intervention arms provided counselling using a digital job aid and different prenatal and post-natal combinations of lipid-based supplements and the comparison arm with usual practice. We enrolled 1500 pregnant women and followed them until the children reached their second birthday. We developed a tablet-based system for intervention delivery, data collection and project supervision. We combined the four intervention arms (n = 855), in which community health workers (CHWs) provided age-appropriate complementary feeding counselling, to compare against the comparison arm (n = 403). We calculated the outcome indicators from the children's 24-h dietary recalls. Overall, the intervention increased the mean dietary diversity score by 0.09 (95% confidence interval [CI]: 0.2–0.16) and odds of minimum dietary diversity by 18% (95% CI: 0.99–1.40). However, there was a significant interaction on the effect of the intervention on dietary diversity by age. The mean dietary diversity score was 0.24 (95% CI: 0.11–0.37) higher in the intervention than in the comparison arm at 9 months and 0.14 (95% CI: 0.01–27) at 12 months of age. The intervention effect was non-significant at an older age. Overall, consumption of flesh food was 1.32 times higher in the intervention arm (odds ratio [OR] 1.32, 95% CI: 1.11–1.57) in 6–23 months of age. The intervention significantly improved child dietary diversity score in households with mild and moderate food insecurity by 0.27 (95% CI: 0.06–0.49) and 0.16 (0.05–27), respectively, but not with food-secure and severely food-insecure households. Although the study did not evaluate the impact of digital job aid alone, the findings indicate the utility of nutrition counselling by CHWs using a digital job aid to improve child feeding practices in broader programmes.     

Newly designed analogues from SARS-CoV inhibitors mimicking the druggable properties against SARS-CoV-2 and its novel variants

The emerging variants of SARS coronavirus-2 (SARS-CoV-2) have been continuously spreading all over the world and have raised global health concerns. The B.1.1.7 (United Kingdom), P.1 (Brazil), B.1.351 (South Africa) and B.1.617 (India) variants, resulting from multiple mutations in the spike glycoprotein (SGp), are resistant to neutralizing antibodies and enable increased transmission. Hence, new drugs might be of great importance against the novel variants of SARS-CoV-2. The SGp and main protease (M^pro) of SARS-CoV-2 are important targets for designing and developing antiviral compounds for new drug discovery. In this study, we selected seventeen phytochemicals and later performed molecular docking to determine the binding interactions of the compounds with the two receptors and calculated several drug-likeliness properties for each compound. Luteolin, myricetin and quercetin demonstrated higher affinity for both the proteins and interacted efficiently. To obtain compounds with better properties, we designed three analogues from these compounds and showed their greater druggable properties compared to the parent compounds. Furthermore, we found that the analogues bind to the residues of both proteins, including the recently identified novel variants of SARS-CoV-2. The binding study was further verified by molecular dynamics (MD) simulation and molecular mechanics/Poisson Boltzmann surface area (MM/PBSA) approaches by assessing the stability of the complexes. MD simulations revealed that Arg457 of SGp and Met49 of M^pro are the most important residues that interacted with the designed inhibitors. Our analysis may provide some breakthroughs to develop new therapeutics to treat the proliferation of SARS-CoV-2 in vitro and in vivo.

Three designed inhibitors with potential inhibition efficacy against the emerging variants of SARS coronavirus-2 (SARS-CoV-2).     

Investigation of optimal schedule of concurrent radiotherapy with S-1 for oral squamous cell carcinoma

In the present study, we examined the appropriate schedule of S-1 medication in the combination with radiation by investigating the safety, the clinical efficacy, and antitumor effects on tumors in nude mice. In the patients with oral squamous cell carcinoma (OSCC), S-1 was given orally according to a 4-week application followed by 2-week rest regimen (4-week regimen), or a 2-week application followed by a 1-week rest regimen (2-week regimen). Radiation was given (2 Gy/day; 5 days/week) for a total of 60 Gy. In nude mouse models, human oral cancer cell lines were used as subcutaneous xenografts in nude mice. The mice were treated by S-1 (10 mg/kg) and radiation (1 Gy) with a 4-week regimen or a 2-week regimen. Apoptotic cells were detected by TUNEL method. In the patients with OSCC, the response rate with the 4-week regimen was 100% and the response rate with the 2-week regimen was 92.3%. However, a high frequency of adverse effect was found in the 4-week regimen when compared to the 2-week regimen. Grade 3 toxicity of leukopenia, neutropenia and stomatitis were seen in 3 cases, grade 3 toxicity of anorexia and nausea were seen in 2 cases, and grade 3 toxicity of decrease of hemoglobin level, heartburn/dyspepsia and increase of bilirubin level were seen in a case of the 4-week regimen. On the other hand, grade 3 toxicity of stomatitis, anorexia, nausea, heartburn/dyspepsia and increase of bilirubin level were seen in a case of the 2-week regimen. In nude mouse models, the 2-week regimen was more effective than the 4-week regimen. In addition, significant increase in the percentage of apoptotic cells was observed in the tumors treated with the 4-week regimen when compared with the tumors treated with the 2-week regimen. No loss of body weight was observed in mice treated with the 2-week regimen during the experimental period. These results suggested that the 2-week regimen might reduce adverse effects, and enhance therapeutic effects compared to the 4-week regimen. Briefly, this 2-week regimen may be a useful concurrent chemo-radiotherapy improving the quality of life (QOL) of patients with OSCC.     

Utility and control of proteoglycans in tissue engineering

This review addresses various methods of integrating proteoglycans (PGs) into the design of engineered tissues and provides insight for designing tissue-engineered disease models that leverage current knowledge of PG biology. Even though PGs show immense possibilities in tissue-engineering applications, they have seldom been used to their full potential. The most common tissue-engineering application of PGs has been in scaffolds (matrigels and collagen-chondroitin sulfate matrices), in which PGs or their glycosaminoglycan (GAG) chains are incorporated into the scaffold to promote cell growth, tissue remodeling, and intracellular signaling. In addition, many studies have reported the total amount of PGs synthesized within engineered tissues but have not delineated which specific PGs or GAG classes are involved in engineered tissue development. In native tissues, various PGs are dynamically and differentially regulated to achieve specific biophysical and biological functions, such as compressibility and transparency. Therefore, the targeted modulation of specific PGs (via exogenous addition, endogenous stimulation with growth factors, or mechanical stimulation) may help engineered tissues to achieve native tissue properties. The PG composition of engineered tissues could also be modified to achieve disease models in vitro and thus provide a way to study the effect of external agents on PG-related disease mechanisms.     

An Examination of Some Factors which Influence the Stability of in Vitro Platelet Responses

Platelet sensitivity to ADP and adrenaline was determined after storage of platelet-rich plasma (PRP) under various conditions to establish those yielding optimal platelet stability. The effects of the exclusion of air from the storage syringes, temperature, PRP dilution and duration of storage were tested. Storage at room temperature (22° C) in the absence of air stabilised PRP pH over 24 h and stabilised platelet sensitivity to ADP up to 4 h. Storage at 4°C and 13 C caused platelet activation and eventually spontaneous aggregation, as evidenced by significant reductions in platelet counts. Samples stored at 37° C were less responsive to ADP and adrenaline than samples maintained at 22 C. Platelet count adjustment to 200 × 10(9)/L reduced platelet sensitivity as reflected by increased agonist EC(50) values and threshold concentrations. Positive correlations between agonist EC(50) values (and between threshold concentrations) for diluted and undiluted samples were obtained, indicating that platelet count adjustment did not affect the ranking order of platelet sensitivity within the subject group. No correlations between platelet count and indices of platelet sensitivity were seen suggesting that differences in platelet aggregation arise from intrinsic differences in platelet sensitivity rather than differences in platelet count. With time of storage the responses to ADP (EC(50) and threshold concentration) and adrenaline (EC(50)) declined to a greater extent for undiluted PRP than for diluted PRP. No changes in the platelet-poor plasma concentrations of the dense granular component, serotonin, occurred in diluted or undiluted samples over 24 h. We conclude that in order to ensure optimal stability of platelets, PRP should be stored at room temperature (22°C) in the absence of air and tested within 4 h of preparation. A decision on platelet count adjustment is also required dependent upon the experimental objectives.     

Repair of cleft lip and simultaneous repair of cleft hard palate with vomer flap in unilateral complete cleft lip and palate: a comparative study

Abstract  

Repair of anterior palate after repairing the cleft lip in complete cleft lip and palate patient is sometimes very difficult. It needs wide, extensive and difficult dissection, and has later chances of wound infection, wound dehiscence, complete wound disruption, recurrent oronasal fistula formation and also maxillary hypoplasia. In this study, we compare the outcome of simultaneous repair of cleft lip and cleft hard palate with vomer flap against cleft lip repair alone in patients with unilateral complete cleft lip and palate (UCLP).