ZRC3308 Monoclonal Antibody Cocktail Shows Protective Efficacy in Syrian Hamsters against SARS-CoV-2 Infection

We have developed a monoclonal antibody (mAb) cocktail (ZRC-3308) comprising of ZRC3308-A7 and ZRC3308-B10 in the ratio 1:1 for COVID-19 treatment. The mAbs were designed to have reduced immune effector functions and increased circulation half-life. mAbs showed good binding affinities to non-competing epitopes on RBD of SARS-CoV-2 spike protein and were found neutralizing SARS-CoV-2 variants B.1, B.1.1.7, B.1.351, B.1.617.2, and B.1.617.2 AY.1 in vitro. The mAb cocktail demonstrated effective prophylactic and therapeutic activity against SARS-CoV-2 infection in Syrian hamsters. The antibody cocktail appears to be a promising candidate for prophylactic use and for therapy in early COVID-19 cases that have not progressed to severe disease.     

Mucoadhesive nanoparticles for prolonged ocular delivery of natamycin: In vitro and pharmacokinetics studies

The aim of this study was to prepare natamycin encapsulated lecithin/chitosan mucoadhesive nanoparticles (NPs) for prolonged ocular application. These NPs were characterized by their mean particle size 213nm, encapsulation efficiency 73.57%, with a theoretical drug loading 5.09% and zeta potential +43. In vitro release exhibited a biphasic drug release profile with initial burst followed by a very slow drug release. The MIC(90) and zone of inhibition of NPs showed similar antifungal activity as compared to marketed suspension and free natamycin against Candida albicans and Aspergillus fumigates. The ocular pharmacokinetics of NPs and marketed formulation were evaluated in NZ rabbits. The NPs exhibit significant mucin adhesion. The AUC((0-∞)) was increased up to 1.47 fold and clearance was decreased up to 7.4-fold as compared to marketed suspension. The PK-PD and pharmacokinetic simulation was carried out to estimate optimum dosing regimen for good efficacy. Thus, lecithin/chitosan NPs could be considered useful approach aiming to prolong ocular residence and reduce dosing frequency.     

Endoscopic ultrasound-guided pelvic and prostatic abscess drainage: Experience in 30 patients

Background

Endoscopic ultrasound (EUS)-guided drainage is an effective treatment for many abscesses in the abdomen. We review our experience with EUS-guided drainage of pelvic abscesses.

Methods

Thirty consecutive patients who underwent EUS-guided pelvic abscess drainage were evaluated after excluding three patients with distance to transducer >2 cm or organized abscess.

Results

Thirty patients (25 male) aged 60?±?4.5 years (mean?±?SD) had 4 prostatic abscesses, 7 perisigmoid abscesses, and 19 perirectal abscesses with mean?±?SD sizes of 2.5?±?0.3, 4.7?±?0.6, and 5.4?±?0.4 cm, respectively. Surgery was the most common predisposing factor (n?=?14, 46.6 %) followed by diverticulitis (n?=?5, 16.6 %). Interventions included aspiration only (2 prostatic and 3 perisigmoid), aspiration and dilatation (2 patients in each group), and dilatation and stenting (2 perisigmoid and 17 perirectal). Five (16.6 %) patients needed re-intervention, and two (6.6 %) needed surgery. There were no recurrences. Technical success of EUS-guided pelvic abscess drainage overall was 90.9 % (30/33) and was 93.3 % (27/30) in patients in whom EUS-guided drainage was attempted, with 16.5 % (n?=?5) re-intervention rate.

Conclusion

EUS-guided drainage has an excellent success rate in drainage of pelvic abscesses.     

Low back pain: critical assessment of various scales

To study the various pain assessment tools based on their psychometric properties and ease of use. Published articles on psychometric properties of pain tools were accessed and data collected for low back pain (LBP)-specific tools, generic tools, neuropathic LBP tools, tools for cognitively impaired patients, and tools for acute LBP. Among the LBP-specific tools, Roland Morris Disability Questionnaire (RMDQ) and Oswestry Disability Index (ODI) have good construct validity and reliability, and responsiveness over short intervals. Quebec Back Pain Disability Scale (QBPDS) gauges only disability and sleep. Among the generic tools, McGill Pain Questionnaire (MPQ), West Haven-Yale Multidimensional Pain Inventory (MPI), and Brief Pain Inventory (BPI) show good responsiveness, but BPI is the only tool validated for LBP. Neuropathic Pain Scale (NPS) and Short Form-MPQ-2 (SF-MPQ-2) are both reliable tools for neuropathic LBP. For cognitively impaired patients, Pain Assessment in Advanced Dementia (PAINAD), Abbey Pain Scale (APS), and Doloplus-2 are all reliable tools, but PAINAD has good construct validity. For acute pain, Clinically Aligned Pain Assessment (CAPA) is reliable and responsive, but presently, unidimensional tools and SF-MPQ-2 are the tools most preferred. Based on psychometric properties and ease of use, the best tools for LBP seem to be RMDQ/ODI (among LBP-specific tools), BPI (among generic tools), SF-MPQ-2/NPS (for neuropathic LBP), PAINAD (for cognitively impaired patients), and unidimensional tools and SF-MPQ-2 (for acute pain). Overall, BPI seems to be a tool that can be relied upon the most. These slides can be retrieved under Electronic Supplementary Material.     

Bilateral epstein-barr virus-associated adrenal leiomyomas in a child without an established immunodeficiency

ABSTRACT Adrenal leiomyomas are rare, bilateral ones being rarer. Literature available on these rare tumors documents only 4 cases in children less than 12?years of age. Each case has been associated with acquired immune deficiency syndrome or some other immunodeficiency state. Here we present a rare case of large, bilateral, adrenal leiomyomas in a child with no known immunodeficiency. An 11-year-old girl with a past history of herpes zoster (1?year before the present complaints) was admitted with abdominal pain of 2?months' duration. Radiology revealed bilateral adrenal neoplasms, probably bilateral pheochromocytoma. Histology showed bilateral adrenal leiomyomas that were Epstein-Barr virus associated. We report this case to draw attention to the occurrence of a common pathologic entity at an uncommon site in a setting of no definite known immunodeficiency.     

Design,Synthesis, and Biological Evaluation of 1,4‐dihydropyridine Derivatives as Potent Antitubercular Agents

A series of novel 1,4‐dihydropyridine‐3,5‐dicarbamoyl derivatives bearing an imidazole nucleus at C‐4 position were synthesized in excellent yields via multicomponent Hantzsch reaction. The newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, and mass spectroscopy. The synthesized compounds 3a‐p were screened for antitubercular activity. Among all the screened compounds, compounds 3j and 3m showed most prominent activity against Mycobacterium tuberculosis with minimum inhibitory concentration of 0.02 μg/mL and SI > 500, making it more potent than first‐line antitubercular drug isoniazid. In addition, these compounds displayed relatively low cytotoxicity.