Metabolome-based profiling of African baobab fruit (Adansonia digitata L.) using a multiplex approach of MS and NMR techniques in relation to its biological activity

Adansonia digitata L. also known as African baobab is one of the most important fruit-producing trees, widely distributed in the African continent. Baobab fruits are known to possess potential health benefits and nutritional value. This study aimed to holistically dissect the metabolome of A. digitata fruits using a novel comparative protocol using three different analytical platforms. Ultra high performance liquid chromatography coupled to high-resolution tandem mass spectrometry (UHPLC-HRMS/MS), and headspace solid-phase microextraction/gas chromatography coupled to mass spectrometry (HS-SPME/GC-MS) were respectively employed for phytonutrients and aroma profiling, whereas GC-MS post silylation provided an overview of nutrients i.e., sugars. UHPLC-HRMS/MS analysis allowed for the assignment of 77 metabolites, among which 50% are reported for the first time in the fruit. While GC-MS of silylated and aroma compounds led to the identification of 74 and 16 compounds, respectively. Finally, NMR-based metabolite fingerprinting permitted the quantification of the major metabolites for future standardization. In parallel, in vivo antidiabetic potential of the baobab fruit using a streptozotocin (STZ) induced diabetic rat model was assessed. Histopathological and immune-histochemical investigations revealed hepatoprotective and renoprotective effects of A. digitata fruit along with mitigation against diabetes complications. Moreover, the administration of A. digitata fruits (150 mg kg⁻¹) twice a week lowered fasting blood glucose levels.

Metabolites profiling of Adansonia digitata L. in relation to its biological activity.     

Design,synthesis, docking study and anticancer evaluation of new trimethoxyphenyl pyridine derivatives as tubulin inhibitors and apoptosis inducers

Microtubules have become an appealing target for anticancer drug development including mainly colchicine binding site inhibitors (CBSIs). A new series of novel trimethoxypyridine derivatives were designed and synthesized as tubulin targeting agents. In vitro anti-proliferative activities of the tested compounds compared to colchicine against hepatocellular carcinoma (HepG-2), colorectal carcinoma (HCT-116), and breast cancer (MCF-7) was carried out. Most of compounds showed significant cytotoxic activities. Compounds Vb, Vc, Vf, Vj and VI showed superior anti-proliferative activities to colchicine. Where compound VI showed IC₅₀ values of 4.83, 3.25 and 6.11 μM compared to colchicine (7.40, 9.32, 10.41 μM) against HCT 116, HepG-2 and MCF-7, respectively. The enzymatic activity against tubulin enzyme was carried out for the compounds that showed high anti-proliferative activity. Also, compound VI exhibited the highest tubulin polymerization inhibitory effect with an IC₅₀ value of 8.92 nM compared to colchicine (IC₅₀ value = 9.85 nM). Compounds Vb, Vc, Vf, Vj, & VIIIb showed promising activities with IC₅₀ values of 22.41, 17.64, 20.39, 10.75, 31.86 nM, respectively. Cell cycle and apoptosis test for compound VI against HepG-2 cells, indicated that compound VI can arrest cell cycle at G2/M phase, and can cause apoptosis at pre-G1 phase, with high apoptotic effect 18.53%. Molecular docking studies of the designed compounds confirmed the essential hydrogen bonding with CYS241 beside the hydrophobic interaction at the binding site compared to reference compounds which assisted in the prediction of the structure requirements for the detected antitumor activity.

Interaction of compounds VI (IC₅₀ = 8.92 nM) (A) and Vj (IC₅₀ = 10.75 nM) (B) with key amino acids of CBS.     

The Saudi Critical Care Society extracorporeal life support chapter guidance on utilization of veno-venous extracorporeal membrane oxygenation in adults with acute respiratory distress syndrome and special considerations in the era of coronavirus disease 2019

Extracorporeal membrane oxygenation (ECMO) is considered as a supportive treatment that provides circulatory and ventilatory support and can be thought off as a bridge to organ recovery. Since 2009, it has been applied as a rescue treatment for patients with severe adult respiratory distress syndrome (ARDS) mainly due to viral causes. In December 2019, several patients presented with a constellation of symptoms of viral pneumonia in China. A new strain of the corona virus family, called COVID-19, has been discovered to be the cause of this severe mysterious illness that was named severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2). This new virus continued to spread across the globe leading to the World Health Organization announcing it as a pandemic in the early 2020. By the end of March 2021, the number of COVID-19 cases worldwide exceeded 126 million cases. In Saudi Arabia, the first confirmed case of COVID-19 was reported in the 2nd March 2020. By the end of March 2021, the total number of confirmed COVID-19 cases in Saudi Arabia is just above 360,000. In anticipation of the need of ECMO for the treatment of patients with SARS‑CoV‑2 based on the previous Middle East respiratory syndrome coronavirus pandemic experience, the Saudi Extra-Corporeal Life Support (ECLS) chapter that is under the umbrella of the Saudi Critical Care Society (SCCS) convened a working group of ECMO experts. The mission of this group was to formulate a guidance for the use of ECMO as a last resort for patients with severe ARDS, especially with COVID-19 based on available evidence. The ECLS-SCCS chapter wanted to generate a document that can be used to simple guide, with a focus on safety, to provide ECMO service for patients with severe ARDS with a special focus on SARS‑CoV‑2.     

Radiographic features of COVID-19 based on an initial cohort of 96 patients in Singapore

INTRODUCTIONChest radiographs (CXRs) are widely used for the screening and management of COVID-19. This article describes the radiographic features of COVID-19 based on an initial national cohort of patients.METHODSThis is a retrospective review of swab-positive patients with COVID-19 who were admitted to four different hospitals in Singapore between 22 January and 9 March 2020. Initial and follow-up CXRs were reviewed by three experienced radiologists to identify the predominant pattern and distribution of lung parenchymal abnormalities.RESULTSIn total, 347 CXRs of 96 patients were reviewed. Initial CXRs were abnormal in 41 (42.7%) out of 96 patients. The mean time from onset of symptoms to CXR abnormality was 5.3 ± 4.7 days. The predominant pattern of lung abnormality was ground-glass opacity on initial CXRs (51.2%) and consolidation on follow-up CXRs (51.0%). Multifocal bilateral abnormalities in mixed central and peripheral distribution were observed in 63.4% and 59.2% of abnormal initial and follow-up CXRs, respectively. The lower zones were involved in 90.2% of initial CXRs and 93.9% of follow-up CXRs.CONCLUSIONIn a cohort of swab-positive patients, including those identified from contact tracing, we found a lower incidence of CXR abnormalities than was previously reported. The most common pattern was ground-glass opacity or consolidation, but mixed central and peripheral involvement was more common than peripheral involvement alone.     

One-year visual outcome of secondary piggyback pinhole device implantation in pseudophakic eyes with irregular corneal astigmatism and iris trauma

PurposeRetrospective case series evaluating the efficacy and safety of implanting XtraFocus^™ pinhole device in pseudophakic patients with irregular corneal astigmatism with concurrent or standalone iris defect.MethodsElectronic case records were searched for: uncorrected distance visual acuities (UDVA) and corrected distance visual acuities (CDVA), automatic or manifest refraction and spherical equivalent (SE). All main outcomes were evaluated preoperatively and postoperatively at 1, 3, 6, 9 and 12 months, along with patients’ satisfactory outcome and complications.ResultsEleven pseudophakic eyes of 11 patients with a mean age of 54 (range 27–81) years were included. Median UDVA improved significantly from logMAR 0.7 (range 0.1–1.22) pre-operatively to 0.4 (range 0–1.3) at 1-month (p = 0.002); median CDVA remained unchanged at logMAR 0.4 (range 0–0.1) pre-operatively and 0.4 (range 0–0.8) at 1-month (p = 0.36). There were no significant statistical differences in both UDVA and CDVA between the post-operative periods. Ten patients (90.9%) had initial UDVA improvement at 1-month post op. Eight (72.7%) patients expressed satisfaction with improved vision or reduction of glare/halos. Three (27.3%) patients had unsatisfactory visual outcome resulting in 2 requested for implant explantation due to worsening of glare and distressing floaters.ConclusionsXtraFocus^™ is effective in improving vision or reducing glare in pseudophakic patients with irregular corneal astigmatism or intragenic iris trauma, with over 70% expressed satisfactory outcome. Disturbing floaters and glare preclude its use in some resulting in implant explantation.Subject terms: Eye manifestations, Corneal diseases     

Diagnostic challenges for a novel SH2D1A mutation associated with X‐linked lymphoproliferative disease

Mutations in SH2D1A, encoding the intracellular adaptor signaling lymphocyte activation molecule associated protein (SAP), are associated with X‐linked lymphoproliferative disease type 1 (XLP1). We identified a novel hemizygous SH2D1A c.49G > A (p.E17K) variant in a 21‐year‐old patient with fatal Epstein‐Barr virus infection–associated hemophagocytic lymphohistiocytosis. Cellular and biochemical assays revealed normal expression of the SAP variant protein, yet binding to phosphorylated CD244 receptor was reduced by >95%. Three healthy brothers carried the SH2D1A c.49G > A variant. Thus, data suggest that this variant represents a pathogenic mutation, but with variable expressivity. Importantly, our results highlight challenges in the clinical interpretation of SH2D1A variants and caution in using functional flow cytometry assays for the diagnosis of XLP1.     

Adapalene gel 0.1% vs ketoconazole cream 2% and their combination in treatment of pityriasis versicolor: A randomized clinical study

Pityriasis versicolor (PV) is a chronic superficial fungal infection. Management using azole drugs leads to drug resistance. The present study aimed to compare the clinical outcome of 0.1% adapalene gel vs 2% ketoconazole cream and their combination in PV. This randomized double‐blinded study was conducted on 90 PV patients divided into three equal groups. GI was treated with topical ketoconazole 2% cream twice daily and placebo, GII was treated with topical 0.1% adapalene gel twice daily and placebo and GIII was treated with topical combination of 0.1% adapalene gel (at night) and ketoconazole 2% cream (in the morning). All patients received medications for 4 weeks. Evaluation was done at 2 and 4 weeks and included clinical assessment, laboratory assessment, and patient satisfaction. We found that after 4 weeks of treatment, all groups showed significant improvement. There was better response in GIII in terms of lower rate of positive potassium hydroxide staining, higher rate of significantly improved cases and higher rate of well‐satisfied patients. However, the difference fell short of statistical significance. We concluded that a combination of adapalene gel and ketoconazole cream is very effective in treatment of PV with no or mild side effects.     

In vitro antifungal susceptibility testing of fungi in patients with onychomycosis

Onychomycosis is the most common nail disorder. To examine in vitro antifungal susceptibility of fungi among onychomycosis patients. The study included 68 patients with onychomycosis. Nail specimens were cultured on Sabouraud dextrose agar and Dermasel agar base‐media. Isolated fungi were subjected to antifungal susceptibility tests against terbinafine, itraconazole, fluconazole, and griseofulvin. Candida species (Candida spp.) were detected in 32.4% of the cases of candidal onychomycosis (n = 37), 23.5% of the cases of distal and lateral subungual onychomycosis (n = 17), and 21.4% of the cases of total dystrophic onychomycosis (n = 14). Candida spp. were sensitive to fluconazole in 73.5%, itraconazole in 58.8%, and terbinafine in 5.9% of the cases. Aspergillus spp. were sensitive to itraconazole in all cases, and terbinafine in 87.5% of cases. Penicillium spp. were sensitive to itraconazole and terbinafine in 88.9% and 77.8% of cases, respectively. Trichophyton spp. were sensitive to terbinafine and resistant to itraconazole. Microsporum spp. were sensitive to itraconazole and resistance to terbinafine. All isolated fungi were resistant to griseofulvin. An increasing proportion of Candida spp. was observed among patients with different clinical varieties of onychomycosis. Candida spp. were highly sensitive to fluconazole and a lesser extent to itraconazole.