Racial and ethnic disparities in Meniere's disease clinical trials: A systematic review.

Objective: Our study aims to shed light on racial, ethnic, and geographic disparities in phase 2/3 Meniere's disease (MD) clinical trials, with the ultimate goal of enhancing the inclusivity and effectiveness of future MD research.

Methods: We conducted a systematic review of phase 2/3 MD Randomized Controlled Trials (RCTs). Using the search terms "Meniere's Disease" and "Endolymphatic hydrops", we searched ClinicalTrials.

Leg Length Discrepancy After Hip Fracture Repair is Associated With Reduced Gait Speed.

Introduction: A negative correlation exists between functional outcomes and leg length discrepancy (LLD) following hip fracture repair. We have assessed the effects of LLD following hip fracture repair in elderly patients on 3-meter walking time, standing time, activities of daily living (ADL), and instrumental activities of daily living (IADL).

Methods: One hundred sixty-nine patients enrolled in the STRIDE trial were identified with femoral neck, intertrochanteric, and subtrochanteric fractures that were treated with partial hip replacement, total hip replacement, cannulated screws, or intramedullary nail.

Diagnosis and Treatment Options of Abductor Insufficiency After Total Hip Replacement.

Abductor insufficiency can cause abnormal gait, lateral hip pain, and abduction weakness in both native and prosthetic hips. In the setting of total hip arthroplasty (THA), abductor insufficiency may occur secondary to iatrogenic injury to the superior gluteal nerve or gluteus medius muscle, adverse local tissue reactions owing to metal-associated prosthetics, and osteolysis owing to bearing wear or infection. Surgical reconstruction of the abductor complex is indicated for patients with chronic tears who have pain, weakness, limp, and/or instability.

Repurposing primaquine as a polyamine conjugate to become an antibiotic adjuvant.

In our search for new antibiotic adjuvants as a novel strategy to deal with the emergence of multi-drug resistant (MDR) bacteria, a series of succinylprimaquine-polyamine (SPQ-PA) conjugates and derivatives of a cationic amphiphilic nature have been prepared. Evaluation of these primaquine conjugates for intrinsic antimicrobial properties and the ability to restore the antibiotic activity of doxycycline identified two derivatives, SPQ-PA3-8-3 and SPQ-PA3-10-3 that exhibited intrinsic activity against the Gram-positive bacteria Staphylococcus aureus and the yeast Cryptococcus neoformans. None of the analogues were active against the Gram-negative bacterium Pseudomonas aeruginosa.

An Acetylenic Lipid from the New Zealand Ascidian : Exemplification of an Improved Workflow for Determination of Absolute Configuration of Long-Chain 2-Amino-3-alkanols.

An acetylenic 2-amino-3-alcohol, distaminolyne B (), isolated from the New Zealand ascidian , is reported. The isolation and structure elucidation of and assignment of 2,3 absolute configuration (AC) using the exciton coupled circular dichroism technique are described. Using a methodologically facile workflow, the same AC was also established by analysis of specific rotation, terminal methyl C-1 δ chemical shift, and NH δ and values of the ,-diacetate derivative.

The Configuration of Distaminolyne A is S: Quantitative Evaluation of Exciton Coupling Circular Dichroism of N, O- Bis-arenoyl-1-amino-2-alkanols.

The 2 S configuration of the marine natural product distaminolyne A was recently disputed based upon total synthesis, yet paradoxically supported by a second independent total synthesis from a different research group. We now verify the 2 S configuration of distaminolyne A by extensive chiroptical studies and support the veracity of the EC ECD method originally used to prove it. The origin of the apparent paradox appears to lie in the limits of precision of polarimetry in the context of weakly rotatory molecules, which strikes a cautionary note on the reliability of "reassignment" of natural product configurations based solely on specific rotation.

Enantiomeric Variability of Distaminolyne A. Refinement of ECD and NMR Methods for Determining Optical Purity of 1-Amino-2-Alkanols.

Sample configurations of distaminolyne A (); isolated from the ascidians and , and collected at different sites in New Zealand, were investigated by two methods: Exciton coupled electronic circular dichroism (EC ECD) of the corresponding ,-dibenzoyl derivative ; and chiral reagent derivatization of with ()- and ()-α-methoxyphenylacetic acid (MPA), followed by ¹H-NMR analysis. Configuration and optical purity of (%ee) was found to vary depending on the geographic distribution of ascidian colonies. An improved method for preparing ,-diarenoyl derivatives of was optimized.

Synthesis and antimalarial evaluation of artesunate-polyamine and trioxolane-polyamine conjugates.

A series of artesunate-polyamine and trioxolane-polyamine conjugates have been prepared. The conjugates were evaluated for antimalarial activity towards the K1 dual drug resistant and NF54 chloroquine-sensitive strains of Plasmodium falciparum (Pf) and for cytotoxicity towards the rat myoblast cell line L6. (Bis)-Boc-(bis)-artesunate-polyamine and (tetra)-artesunate-polyamine conjugates exhibited potent in vitro activity towards both strains of Pf, with IC values in the range of 0.

Total Synthesis of (-)-Bicubebin A, B, (+)-Bicubebin C and Structural Reassignment of (-)-cis-Cubebin.

The first total synthesis of (-)-bicubebin A, and two previously unreported dilignans, (-)-bicubebin B and (+)-bicubebin C has been achieved through the dimerization of (-)-cubebin, confirming the structure and absolute stereochemistry of (-)-bicubebin A. Analysis of the data for (-)-bicubebin B showed it matched that of reported compound (-)-cis-cubebin. The NMR data of the subsequently synthesized proposed structure of cis-cubebin confirmed that its original proposed structure was incorrect.

Biologically Active Acetylenic Amino Alcohol and N-Hydroxylated 1,2,3,4-Tetrahydro-β-carboline Constituents of the New Zealand Ascidian Pseudodistoma opacum.

The first occurrence of an acetylenic 1-amino-2-alcohol, distaminolyne A (1), isolated from the New Zealand ascidian Pseudodistoma opacum, is reported. The isolation and structure elucidation of 1 and assignment of absolute configuration using the exciton coupled circular dichroism technique are described. In addition, a new N-9 hydroxy analogue (2) of the known P.

Discovery and evaluation of thiazinoquinones as anti-protozoal agents.

Pure compound screening has identified the dioxothiazino-quinoline-quinone ascidian metabolite ascidiathiazone A (2) to be a moderate growth inhibitor of Trypanosoma brucei rhodesiense (IC₅₀ 3.1 μM) and Plasmodium falciparum (K1 dual drug resistant strain) (IC₅₀ 3.3 μM) while exhibiting low levels of cytotoxicity (L6, IC₅₀ 167 μM).

Synthesis and in vitro and in vivo evaluation of antimalarial polyamines.

We recently reported that 1,14-diphenylacetamide derivatives of spermine exhibit potent nM in vitro growth inhibition properties of Plasmodium falciparum. In an effort to expand the structure-activity relationship of this compound class towards malaria, we have prepared and biologically tested a library that includes benzamide and 3-phenylpropanamide 'capping acid' groups, and polyamines that include spermine (PA3-4-3) and chain extended analogues PA3-8-3 and PA3-12-3. 2-Hydroxy and 2,5-dimethoxy analogues were typically found to exhibit the most potent activity towards the dual drug resistant strain K1 of P.

Investigation of the electrophilic reactivity of the cytotoxic marine alkaloid discorhabdin B.

The mechanisms of action of the cytotoxic marine pyrroloiminoquinone alkaloids the discorhabdins are unknown. We have determined that discorhabdin B acts as an electrophile towards biomimetic thiol nucleophiles leading to debrominated adducts. In contrast, less potent cytotoxins discorhabdins D and Q failed to react, supporting an SAR model of cytotoxicity requiring an orchestrated combination of an electrophilic Δ(1) carbon centre and a nucleophilic N-18 amine for potent activity.

Anti-inflammatory and antimalarial meroterpenoids from the New Zealand ascidian Aplidium scabellum.

Bioassay-directed fractionation of an extract of the New Zealand ascidian Aplidium scabellum has afforded the anti-inflammatory secondary metabolite 2-geranyl-6-methoxy-1,4-hydroquinone-4-sulfate (1) and a family of pseudodimeric meroterpenoids scabellones A (2)-D (5). The benzo[c]chromene-7,10-dione scaffold contained within scabellones A-D is particularly rare among natural products. The structures were elucidated by interpretation of NMR data.

Antimalarial β-carbolines from the New Zealand ascidian Pseudodistoma opacum.

One tetrahydro-β-carboline, (-)-7-bromohomotrypargine (1), and three alkylguanidine-substituted β-carbolines, opacalines A, B, and C (2-4), have been isolated from the New Zealand ascidian Pseudodistoma opacum. The structures of the metabolites were determined by analysis of mass spectrometric and 2D NMR spectroscopic data. Natural products 2 and 3, synthetic debromo analogues 8 and 9, and intermediate 16 exhibited moderate antimalarial activity toward a chloroquine-resistant strain of Plasmodium falciparum, with an IC50 range of 2.

Didemnidines A and B, indole spermidine alkaloids from the New Zealand ascidian Didemnum sp.

Two new indole spermidine alkaloids, didemnidines A (1) and B (2), have been isolated from the New Zealand ascidian Didemnum sp. The structures of the metabolites, determined by analysis of 2D NMR spectra and confirmed via synthesis, embody an indole-3-glyoxylamide moiety linked to the N(1) position of spermidine, the latter motif being particularly rare among marine natural products. Didemnidine B and a synthetic precursor exhibited mild in vitro growth inhibition of Plasmodium falciparum with IC(50)'s of 15 and 8.

Isolation and characterization of diastereomers of discorhabdins H and K and assignment of absolute configuration to discorhabdins D, N, Q, S, T, and U.

Investigations of four different sponge populations of Latrunculia species collected in New Zealand waters has led to the characterization of a new diastereomer of discorhabdin H, named discorhabdin H2, confirmation of the structure of discorhabdin K ((+)-7), and presentation of a new diastereomer, discorhabdin K2 ((-)-8). In each case the structures were established by extensive NMR and MS studies and the absolute configurations interrogated by electronic circular dichroism (ECD). Absolute configurations were assigned to the known metabolites discorhabdins H, D, 2-hydroxy-D, N, and Q by comparison of ECD spectra with those recorded for discorhabdin alkaloids of defined absolute configuration, while the configurations of discorhabdins S, T, and U were assigned by semisynthesis from (+)-(6S,8S)-discorhabdin B.

Synthesis and anti-inflammatory structure-activity relationships of thiazine-quinoline-quinones: inhibitors of the neutrophil respiratory burst in a model of acute gouty arthritis.

Sixteen new thiazine-quinoline-quinones have been synthesised, plus one bicyclic analogue. These compounds inhibited neutrophil superoxide production in vitro with IC(50)s as low 60 nM. Compounds with high in vitro anti-inflammatory activity were also tested in a mouse model of acute inflammation.