The Mould War: Developing an Armamentarium against Fungal Pathogens Utilising Thymoquinone,Ocimene, and Miramistin within Bacterial Cellulose Matrices

An increase in antifungal resistance has seen a surge in fungal wound infections in patients who are immunocompromised resulting from chemotherapy, disease, and burns. Human pathogenic fungi are increasingly becoming resistant to a sparse repertoire of existing antifungal drugs, which has given rise to the need to develop novel treatments for potentially lethal infections. Bacterial cellulose (BC) produced by Gluconacetobacter xylinus has been shown to possess many properties that make it innately useful as a next-generation biopolymer to be utilised as a wound dressing. The current study demonstrates the creation of a pharmacologically active wound dressing by loading antifungal agents into a biopolymer hydrogel to produce a novel wound dressing. Amphotericin B is known to be highly hepatotoxic, which reduces its appeal as an antifungal drug, especially in patients who are immunocompromised. This, coupled with an increase in antifungal resistance, has seen a surge in fungal wound infections in patients who are immunodeficient due to chemotherapy, disease, or injury. Antifungal activity was conducted via Clinical & Laboratory Standards Institute (CLSI) M27, M38, M44, and M51 against Candida auris, Candida albicans, Aspergillus fumigatus, and Aspergillus niger. This study showed that thymoquinone has a comparable antifungal activity to amphotericin B with mean zones of inhibition of 21.425 ± 0.925 mm and 22.53 ± 0.969 mm, respectively. However, the mean survival rate of HEp-2 cells when treated with 50 mg/L amphotericin B was 29.25 ± 0.854% compared to 71.25 ± 1.797% when treated with 50 mg/L thymoquinone. Following cytotoxicity assays against HEp-2 cells, thymoquinone showed a 71.25 ± 3.594% cell survival, whereas amphotericin B had a mean cell survival rate of 29.25 ± 1.708%. The purpose of this study was to compare the efficacy of thymoquinone, ocimene, and miramistin against amphotericin B in the application of novel antifungal dressings.     

Correction: A clinical and computational study on anti-obesity effects of hydroxycitric acid

Correction for ‘A clinical and computational study on anti-obesity effects of hydroxycitric acid’ by Manu Tomar et al., RSC Adv., 2019, 9, 18578–18588.

The authors regret that the name of one of the authors (Raghavendra Pralhada Rao) was shown incorrectly in the original article. The corrected author list is as shown above.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Clinical approach to severe Clostridium difficile infection: update for the hospital practitioner

The rising incidence of Clostridium difficile (C. difficile) infection or CDI is now a problem of pandemic proportions. The NAP1 hypervirulent strain of C. difficile is responsible for a majority of recent epidemics and the widespread use of fluoroquinolone antibiotics may have facilitated the selective proliferation of this strain. The NAP1 strain also is more likely to cause severe and fulminant colitis characterized by marked leukocytosis, renal failure, hemodynamic instability, and toxic megacolon. No single test suffices to diagnose severe CDI, instead; the clinician must rely on a combination of clinical acumen, laboratory testing, and radiologic and endoscopic modalities. Although oral vancomycin and metronidazole are considered standard therapies in the medical management of CDI, recently it has been demonstrated that vancomycin is the more effective antibiotic in cases of severe disease. Moreover, early surgical consultation is necessary in patients who do not respond to medical therapy or who demonstrate rising white blood cell counts or hemodynamic instability indicative of fulminant colitis. Subtotal colectomy with end ileostomy is the procedure of choice for fulminant colitis. When applied to select patients in a judicious and timely fashion, surgery can be a life-saving intervention. In addition to these therapeutic approaches, several investigational treatments including novel antibiotics, fecal bacteriotherapy and immunotherapy have shown promise in the care of patients with severe CDI.     

Comparison of hyperemic changes in carotid-radial pulse wave velocity by upper and lower arm cuff occlusion

Carotid-radial pulse wave velocity (PWV) normally decreases following release of upper arm cuff occlusion (hyperemia). Lower arm (LA) elicits less brachial artery dilation than upper arm (UA) occlusion but more closely reflects endothelial function. Using applanation tonometry, we compared changes (Δ) in PWV induced by UA and LA hyperemia in 65 healthy participants. Pulse wave velocity was measured serially. Both techniques decreased PWV maximally at 1 minute with gradual return to baseline by 9 minutes. ΔPWV(1min) was greater for UA than LA occlusion (-11.5% vs -6.8%, P = .02). Multivariate analysis showed arm location independently related to ΔPWV (P = .036). In participants with variable cardiovascular risk, PWV decline lessened with increasing Framingham risk for both techniques. In conclusion: UA and LA occlusion decrease PWV maximally at 1 minute after release of arterial occlusion. PWV(1min) decline are more marked after UA than LA occlusion and progressively lessens with increasing Framingham risk.     

Association Between Gut Microbial Abundance and Sight-Threatening Diabetic Retinopathy

PurposeTo study the association between gut microbial abundance and sight-threatening diabetic retinopathy among patients with a history of type 2 diabetes mellitus.MethodsAn observational case-control study was performed using a sample population of diabetics referred to a tertiary eye institute. Sample subjects were identified as cases if they were diagnosed with sight-threatening diabetic retinopathy and controls if they were not but had at least a 10-year history of diabetes. Fecal swabs for all patients were collected for enumeration and identification of sequenced gut microbes. Statistical analyses were performed to associate the clinically relevant Bacteroidetes to Firmicutes relative abundance ratio (B/F ratio) with sight-threatening diabetic retinopathy and an optimal cutoff value for the ratio was identified using Youden''s J statistics.ResultsA sample size of 58 diabetic patients was selected (37 cases, 21 controls). No statistically significant difference in the relative abundance among the predominant phyla between the groups were found. In our univariate analysis, the B/F ratio was elevated in cases compared to controls (cases, 1.45; controls, 0.94; P = 0.049). However, this statistically significant difference was not seen in our multivariate regression model. Optimal cutoff value of 1.05 for the B/F ratio was identified, and significant clustering of cases above this value was noted in beta diversity plotting.ConclusionsNo difference in gut microbial abundance for any particular phylum was noted between the control and diseased population. Increased gut microbial B/F ratio can be a potential biomarker for the development of sight-threatening diabetic retinopathy among type 2 diabetic patients.     

Resuming eye bank services during the COVID-19 pandemic: Experience and inferences

Purpose:The aim of this study was to formulate a methodological approach for resuming eye bank services during COVID-19 pandemic.Methods:Eye bank operations were temporarily halted in March after the government-mandated “Lockdown” in response to COVID-19 pandemic. Before restarting eye bank operations in May, we studied sources of exposure, performed risk assessment, instituted additional process validations and redefined the Standard Operating Procedures (SOPs) in consultation with the guidelines published by the Eye bank Association of India and All India Ophthalmological Society. The eye bank staff were rigorously trained before and after operations were restarted. We conducted a survey at the end of July to gauge staff attitude and reaction.Results:Eye banks services resumed on 20^th May 2020. Since reopening till the end of July total 41 keratoplasties have been done. 91.75% of all keratoplasties done were therapeutic surgeries and 17% of the surgeries were done using glycerine preserved tissues. No staff had COVID-19 symptoms when the operations restarted and none developed symptoms up to the end of July. All eye bank staff were aware of COVID-19 pandemic and 86% said they felt safe working at the eye bank. 86% of the staff said that they received adequate training and 66% of the staff expressed that they always received proper PPE and kits. Overall, 93% of the staff expressed that the measures taken by the eye bank ensured their safety.Conclusion:Based on our experience we suggest the following activities for planned resumption of eye bank services during the pandemic: Exposure Risk Analysis, Personal Protective Equipment usage training, SOP Revision and staff training on modified SOPs. Criteria based selection of donor sources, participatory planning involving the staff and double-checking at critical process junctions helped us in managing a smooth transition.     

Clinical Effectiveness of Liraglutide Across Body Mass Index in Patients with Type 2 Diabetes in the United States: A Retrospective Cohort Study

Introduction

Clinical trials have shown that liraglutide effectively lowers glycated hemoglobin A1c (A1C) levels in adult patients with type 2 diabetes (T2D). However, no studies have evaluated the effectiveness of liraglutide by body mass index (BMI) in the United States (US) in clinical practice. This study examined liraglutide’s clinical effectiveness to lower A1C and body weight after 6 months in T2D patients stratified by baseline BMI.

Methods

This was a retrospective cohort study using the General Electric Centricity electronic medical records database. Adult patients with T2D (≥18 years and BMI≥ 25 kg/m²) and A1C >7% at baseline who started liraglutide between January 1, 2010 and January 31, 2013 and who did not use insulin or a glucagon-like peptide-1 analog 12 months before initiating liraglutide (N = 3,005) were selected. Changes from baseline, stratified by BMI, in A1C, body weight, A1C <7% goal attainment, and incidence of severe hypoglycemia at 6-month follow-up were examined.

Results

After 6 months, A1C levels decreased on average by 0.95%, 1.02%, 0.99%, and 0.84% for BMI categories 25.0–29.9 (n = 333), 30.0–34.9 (n = 793), 35.0–39.9 (n = 821), and ≥40.0 kg/m² (n = 1,058), respectively (P = 0.30). The proportions of patients achieving A1C <7% at 6 months were 38.2%, 37.0%, 40.9%, and 41.0% (P = 0.54). The absolute body weight decreased by 1.5 to 4.0 kg across BMI and the rate of severe hypoglycemia (0.2%) was low.

Conclusion

Patients with T2D experienced statistically significant decreases in A1C and body weight after initiating liraglutide regardless of their BMI. Liraglutide reduced A1C equally well across baseline BMI in clinical practice in the US.     

DAO-9 (2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazole) exhibits p53 induced apoptogenesis through caspase-3 mediated endonuclease activity in murine carcinoma

One of the main strategies to inhibit the tumor growth is to promote the biochemical events leading to DNA degradation, which would eventually culminate in apoptosis. We have earlier reported that the 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazole(DAO-9) possessed anti-cancer activity. To address the exact molecular mechanism underlying anti-cancer property, present study focused on evaluating the anti-tumor effect of the DAO-9 on murine ascites carcinoma cells using various in vivo and in vitro assays. The in vivo assays implicated a strong regression in tumor growth of ascites carcinoma after treatment which is due to apoptogenic efficacy as assessed through structural morphology of EAC cells by Giemsa, Acridine orange, Annexin V staining and FACS analysis. Nucleosomal DNA fragmentation induced by DAO-9 is due to activation of caspase-3 mediated DNAse as verified by endonuclease assays and immunoblot analysis. The caspase-3 activation mechanism is by induction of intrinsic cascade signaling molecules, such as p53, Bax, Bad and cytochrome c (cyt c) expression as verified by western blot. The results concluded that the tumor inhibiting activity of DAO-9 is due to activation of the apoptotic signaling cascade, which could be translated into targeted anti-cancer drug in the near future.     

Association between erectile dysfunction and cardiovascular risk in individuals with type-2 diabetes without overt cardiovascular disease

Background:

Erectile dysfunction in type-2 diabetes may be an independent marker for coronary artery disease. Present study was undertaken to investigate whether type-2 diabetic patients with erectile dysfunction without having overt cardiovascular disease had increased cardiovascular risk.

Aim:

To find out correlation between ED and cardiovascular risk in diabetic patients.

Methods:

Fifty type-2 diabetic patients were assessed for erectile dysfunction using international index of erectile dysfunction (IIEF-5), which include questionnaire and cardiovascular risk assessment by multiparameter cardiovascular analysis device (periscope).

Results:

The prevalence of erectile dysfunction in type-2 diabetics was very high (78%), mild, moderate and severe ED was present in 6, 36 and 36%, respectively. The total cardiovascular risk was more in patients with ED in comparison to patients without ED (34.87 ± 18.82 vs 20.91 ± 11.03 p = 0.002). The mean 10-years coronary risk and cardiac risk was 12.00 + 9.60 and 22.23 + 14.14 (p = 0.029) and 13.36 ± 1.22 and 28.85 ± 4.13 (p 0.002) in patients without ED and with ED respectively. The mean vascular and atherosclerosis risk was 28.73 ± 13.94 and 39.38 ± 19.51 (p > 0.05) and 26.18 ± 10.31 and 33.92 ± 13.40 (p > 0.05) in patients without ED and with ED, respectively. Total cardiovascular risk was found to increase with age, duration of diabetes and HbA1c levels.

Conclusion:

The total cardiovascular risk increases with increasing severity of erectile dysfunction in type-2 diabetic patients without having overt cardiovascular disease.