Nanofabrication of citronellal with chitosan biopolymer to boost its efficacy against aflatoxin B1 and Aspergillus flavus mediated biodeterioration of active ingredient of Piper longum.

The study reports the efficacy of nanofabricated citronellal inside the chitosan biopolymer (NeCn) against Aspergillus flavus growth, aflatoxin B1 (AFB1) production, and active ingredient biodeterioration (Piperine) in Piper longum L. The prepared NeCn was characterized by Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS), and Fourier Transform Infrared Spectroscopy (FTIR). The results revealed that the NeCn exhibited distantly improved antifungal (1.25 µL/mL) and AFB1 inhibition (1.0 µL/mL) compared to free Cn. The perturbances in membrane function, mitochondrial membrane potential, antioxidant defense system, and regulatory genes (Ver-1 and Nor-1) of AFB1 biosynthesis were reported as probable modes of action of NeCn. The NeCn (1.25 µL/mL) effectively protects the P. longum from A. flavus (78.8%), AFB1 contamination (100%), and deterioration of Piperine (62.39%), thus demonstrating its potential as a promising novel antifungal agent for food preservation.

Use of rapid cardiac magnetic resonance imaging to guide chelation therapy in patients with transfusion-dependent thalassaemia in India: UMIMI study.

AIMS: To explore the impact of incorporating a faster cardiac magnetic resonance (CMR) imaging protocol in a low-middle-income country (LMIC) and using the result to guide chelation in transfusion-dependent patients. METHODS AND RESULTS: A prospective UK-India collaborative cohort study was conducted in two cities in India. Two visits 13 months apart included clinical assessment and chelation therapy recommendations based on rapid CMR results. Participants were recruited by the local patient advocate charity, who organized the patient medical camps. The average scanning time was 11.3 ± 2.5 min at the baseline and 9.8 ± 2.4 min (P < 0.001) at follow-up. The baseline visit was attended by 103 patients (mean age 25 years) and 83% attended the second assessment. At baseline, 29% had a cardiac T2* < 20 ms, which represents significant iron loading, and 12% had left ventricular ejection fraction <60%, the accepted lower limit in this population. Only 3% were free of liver iron (T2* ≥ 17 ms). At 13 months, more patients were taking intensified dual chelation therapy (43% vs. 55%, P = 0.002). In those with cardiac siderosis (baseline T2* < 20 ms), there was an improvement in T2*-10.9 ± 5.9 to 13.5 ± 8.7 ms, P = 0.005-and fewer were classified as having clinically important cardiac iron loading (T2* < 20 ms, 24% vs. 16%, P < 0.001). This is the first illustration in an LMIC that incorporating CMR results into patient management plans can improve cardiac iron loading. CONCLUSION: For thalassaemia patients in an LMIC, a simplified CMR protocol linked to therapeutic recommendation via the patient camp model led to enhanced chelation therapy and a reduction in cardiac iron in 1 year.

Anti-proliferative and anti-malarial activities of spiroisoxazoline analogues of artemisinin.

A series of spiroisoxazoline analogues of artemisinin was synthesized by employing 1,3-dipolar cycloaddition between various in situ generated nitrile oxides and artemisitene. All the synthesized compounds were tested for their anti-proliferative and anti-malarial activities. Among the compounds tested, compound 11a was found to be potent against the HCT-15 cancer cell line with IC50 = 4.04 µM when compared to 5-fluorouracil (IC50 = 35.53 µM). DNA cell cycle analysis shows that 11a was inhibiting cell proliferation at the G2/M phase. Compound 11b was found to be most active against Plasmodium falciparum with IC50 = 0.1 µM and also blocked host hemoglobin hydrolysis by the falcipain-3 receptor. It was demonstrated to have better dynamics of parasite killing efficiency than artemisinin. Molecular docking studies revealed that these compounds interacted with falcipain-3 receptor sites.

Clinical implications of anatomical wear characteristics in slipped capital femoral epiphysis and primary osteoarthritis.

BACKGROUND: This study compares the wear characteristics in slipped capital femoral epiphysis (SCFE) with those of primary osteoarthritis (OA) in adult patients with advanced arthritis. METHODS: One hundred femoral heads and proximal neck specimens were studied from SCFE patients (16 hips) and from primary OA (84 hips) patients undergoing total hip arthroplasties (THA). Grade 4 chondromalacia was plotted on a 2-dimensional (2-D) paper grid. Computer tomographic scans were used to create 3-D models of the femoral head and neck to trace the wear patterns. RESULTS: The SCFE group was characterized by (1) loss of neck-head offset, (2) acetabular neck impingement, and (3) loss of superior peripheral articular cartilage adjacent to superior neck. Whereas the primary OA group showed (1) preservation of head-neck offset, (2) absence of acetabular neck impingement, and (3) preservation of superior peripheral articular cartilage. The 3-D modeling in SCFE specimens demonstrated acetabular impingement on the superior lateral femoral neck causing the femur to externally rotate with flexion. The SCFE patients undergoing THA on average were 11 years younger than those with primary OA. The study strongly suggests that the abnormal rotation of the femoral head in SCFE patients causes thinner superior lateral articular cartilage on the femoral head to articulate with the acetabulum. The pistol-grip deformity of the proximal femur in the SCFE group results in hip impingement, which explains why hip flexion and internal rotation can be restricted. CONCLUSIONS: There was a premature development of advanced OA of the adult hip joint in SCFE patients. This was associated with hip impingement caused by loss of the head-neck offset and reorientation of the articular cartilage of the femoral head. Unless the femoral head is redirected in patients with SCFE, the benefits of limited hip preservation debridement procedures are not expected to delay the onset and progression of arthritis. LEVEL OF EVIDENCE: Prognostic study.