Appraisal of selected ethnomedicinal plants as alternative therapies against onychomycosis: Evaluation of synergy and time-kill kinetics.

Introduction: This study aims at the biological profiling of Allium sativum, Zingiber officinale, Nigella sativa, Curcuma longa, Mentha piperita, Withania somnifera, Azadirachta indica, and Lawsonia inermis as alternatives against onychomycosis to combat the treatment challenges. Methods: An extract library of aqueous (DW), ethyl acetate (EA), and methanol (M) extracts was subjected to phytochemical and antioxidant colorimetric assays to gauge the ameliorating role of extracts against oxidative stress. RP-HPLC quantified therapeutically significant polyphenols. Antifungal potential (disc diffusion and broth dilution) against filamentous (dermatophytes and non-dermatophytes) and non-filamentous fungi (yeasts; Candida albicans), synergistic interactions (checkerboard method) with terbinafine and amphotericin-B against resistant clinical isolates of dermatophytes (Trichophyton rubrum and Trichophyton tonsurans) and non-dermatophytes (Aspergillus spp., Fusarium dimerum, and Rhizopus arrhizus), time-kill kinetics, and protein estimation (Bradford method) were performed to evaluate the potential of extracts against onychomycosis. Results: The highest total phenolic and flavonoid content along with noteworthy antioxidant capacity, reducing power, and a substantial radical scavenging activity was recorded for the extracts of Z. officinale. Significant polyphenolics quantified by RP-HPLC included rutin (35.71 ± 0.23 µg/mgE), gallic acid (50.17 ± 0.22 µg/mgE), catechin (93.04 ± 0.43 µg/mgE), syringic acid (55.63 ± 0.35 µg/mgE), emodin (246.32 ± 0.44 µg/mgE), luteolin (78.43 ± 0.18 µg/mgE), myricetin (29.44 ± 0.13 µg/mgE), and quercetin (97.45 ± 0.22 µg/mgE). Extracts presented prominent antifungal activity against dermatophytes and non-dermatophytes (MIC-31.25 µg/ml). The checkerboard method showed synergism with 4- and 8-fold reductions in the MICs of A. sativum, Z. officinale, M. piperita, L. inermis, and C. longa extracts and doses of amphotericin-B (Amp-B) and terbinafine (against non-dermatophytes and dermatophytes, respectively). Furthermore, the synergistic therapy showed a time-dependent decrease in fungal growth even after 9 and 12 h of treatment. The inhibition of fungal proteins was also observed to be higher with the treatment of synergistic combinations than with the extracts alone, along with the cell membrane damage caused by terbinafine and amp-B, thus making the resistant fungi incapable of subsisting. Conclusion: The extracts of A. sativum, Z. officinale, M. piperita, L. inermis, and C. longa have proven to be promising alternatives to combat oxidative stress, resistance, and other treatment challenges of onychomycosis.

Invasive fungal disease in critically ill and Immunocompromised patients.

OBJECTIVE: To study the frequency and type of invasive fungal disease in critically ill and immunocompromised patients. Method: The prospective, cross-sectional, descriptive study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from January 2017 to December 2020, and comprised pathological samples from immunocompromised and critically ill patients for fungal culture. Data regarding demographics, comorbidities, results of direct microscopy and fungal culture was recorded. Data was analysed using SPSS 22. RESULTS: Of the 8285 patients' specimens, 4722(57%) belonged to males and 3563(43%) to females. The mean age of the patients was 48.32±5.42 years (range: 14-98 years). Out of total 8285, 3465(41.82%) were related to blood, 2640(32%) endobronchial washing, 837(10%) sputum, 623(7.5%) tissue, 332(4%) body fluids, 288(3.5%) bronchoalveoar lavage and 100(1.2%) cerebrospinal fluid. Aspergillus flavus (20.7%) and candida albicans (14.5%) were the two most commonly isolated fungal species. CONCLUSIONS: A high index of suspicion for invasive fungal disease should be maintained in immunocompromised and critically ill patients.

Effect of prepregnancy maternal BMI on adverse pregnancy and neonatal outcomes: results from a retrospective cohort study of a multiethnic population in Qatar.

BACKGROUND: Given the small number of studies on the topic, we aimed to identify the impact of prepregnancy maternal body mass index (BMI) on adverse pregnancy outcomes (POs) in a low-risk, multiethnic population, and to calculate related population attributable fractions (PAFs). METHODS: This retrospective cohort study included 1134 nulliparous women of 50 nationalities (classified into Arab and non-Arab ethnicity) in Qatar who had their first antenatal visit at a Primary Healthcare Corporation (PHCC) facility in June 2016-March 2017 and their PO at a Hamad Medical Corporation facility before 10 November 2017. We used multiple imputation to handle missing values and multivariate logistic regression to calculate adjusted ORs (aORs) for adverse POs in overweight and women with obesity. RESULTS: Overweight Arab women and women with obesity were at high risk for gestational diabetes mellitus (GDM) (aOR=2.38, 95% CI 1.51 to 3.84) and caesarean section (aOR=1.57, 95% CI 1.00 to 2.48). Non-Arab women with obesity were at high risk for pre-eclampsia (aOR=3.83, 95% CI 1.00 to 15.00). PAFs showed that 41.63% of pre-eclampsia, 17.36% of pregnancy-induced hypertension, 17.17% of large for gestational age, 15.89% of preterm deliveries, 14.75% of GDM and 13.99% of caesarean sections could be avoided if all mothers had normal prepregnancy BMI. There were no major differences in PAFs by ethnicity. CONCLUSION: Adverse POs were attributable to maternal obesity. This suggests that, in contrast to existing PHCC protocol, overweight and women with obesity in Qatar should be targeted earlier in their pregnancy; preferably prior to getting pregnant. We observed ethnic differences in the risk of adverse POs.