Gender Parity Analysis of the Editorial Boards of Influential Dermatology Journals: Cross-Sectional Study.

This study underscores the persistent underrepresentation of women in academic dermatology leadership positions by examining the gender composition of editorial boards across top dermatology journals, emphasizing the urgent need for proactive strategies to promote diversity, equity, and inclusion.

Complete Genome Sequence of a Staphylococcus epidermidis Isolate from Healthy Skin with Upregulation of Protease EcpA.

Staphylococcus epidermidis is a ubiquitous skin commensal that has the potential to become pathogenic and cause disease. Here, we report the complete genome sequence of a S. epidermidis strain isolated from adult healthy skin that shows high expression of the virulence factor extracellular cysteine protease A (EcpA).

Boosting neuregulin 1 type-III expression hastens SMA motor axon maturation.

Intercellular communication between axons and Schwann cells is critical for attaining the complex morphological steps necessary for axon maturation. In the early onset motor neuron disease spinal muscular atrophy (SMA), many motor axons are not ensheathed by Schwann cells nor grow sufficiently in radial diameter to become myelinated. These developmentally arrested motor axons are dysfunctional and vulnerable to rapid degeneration, limiting efficacy of current SMA therapeutics. We hypothesized that accelerating SMA motor axon maturation would improve their function and reduce disease features. A principle regulator of peripheral axon development is neuregulin 1 type III (NRG1-III). Expressed on axon surfaces, it interacts with Schwann cell receptors to mediate axon ensheathment and myelination. We examined NRG1 mRNA and protein expression levels in human and mouse SMA tissues and observed reduced expression in SMA spinal cord and in ventral, but not dorsal root axons. To determine the impact of neuronal NRG1-III overexpression on SMA motor axon development, we bred NRG1-III overexpressing mice to SMA∆7 mice. Neonatally, elevated NRG1-III expression increased SMA ventral root size as well as axon segregation, diameter, and myelination resulting in improved motor axon conduction velocities. NRG1-III was not able to prevent distal axonal degeneration nor improve axon electrophysiology, motor behavior, or survival of older mice. Together these findings demonstrate that early SMA motor axon developmental impairments can be ameliorated by a molecular strategy independent of SMN replacement providing hope for future SMA combinatorial therapeutic approaches.

Zinc deficiency alters the susceptibility of pancreatic beta cells (INS-1) to arsenic exposure.

Pancreatic beta cells produce and release insulin, a hormone that regulates blood glucose levels, and their dysfunction contributes to the development of diabetes mellitus. Zinc deficiency and inorganic arsenic exposure both independently associate with the development of diabetes, although the effects of their combination on pancreatic beta cell health and function remain unknown. We hypothesized zinc deficiency increases the toxicity associated with arsenic exposure, causing an increased susceptibility to DNA damage and disruption of insulin production. Zinc deficiency decreased cell proliferation by 30% in pancreatic INS-1 rat insulinoma cells. Arsenic exposure (0, 50 or 500 ppb exposures) significantly decreased cell proliferation, and increased mRNA levels of genes involved in stress response (Mt1, Mt2, Hmox1) and DNA damage (p53, Ogg1). When co-exposed to both zinc deficiency and arsenic, zinc deficiency attenuated this response to arsenic, decreasing the expression of Mt1, Hmox1, and Ogg1, and significantly increasing DNA double-strand breaks 2.9-fold. Arsenic exposure decreased insulin expression, but co-exposure did not decrease insulin levels beyond the arsenic alone condition, but did result in a further 33% decline in cell proliferation at the 500 ppb arsenic dose, and a significant increase in beta cell apoptosis. These results suggest zinc deficiency and arsenic, both independently and in combination, adversely affect pancreatic beta cell health and both factors should be considered in the evaluation of health outcomes for susceptible populations.

Membrane-Active Hydantoin Derivatives as Antibiotic Agents.

Hydantoin (imidazolidinedione) derivatives such as nitrofurantoin are small molecules that have aroused considerable interest recently due to their low rate of bacterial resistance. However, their moderate antimicrobial activity may hamper their application combating antibiotic resistance in the long run. Herein, we report the design of bacterial membrane-active hydantoin derivatives, from which we identified compounds that show much more potent antimicrobial activity than nitrofurantoin against a panel of clinically relevant Gram-positive and Gram-negative bacterial strains. These compounds are able to act on bacterial membranes, analogous to natural host-defense peptides. Additionally, these hydantoin compounds not only kill bacterial pathogens rapidly but also prevent the development of methicillin-resistant Staphylococcus aureus (MRSA) bacterial resistance under the tested conditions. More intriguingly, the lead compound exhibited in vivo efficacy that is much superior to vancomycin by eradicating bacteria and suppressing inflammation caused by MRSA-induced pneumonia in a rat model, demonstrating its promising therapeutic potential.

Antimicrobial AApeptides.

Antibiotic resistance is one of the biggest public concerns in the 21st century. Host-defense peptides (HDPs) can potentially mitigate the problem through bacterial membrane disruption; however, they suffer from moderate activity and low stability. We recently developed a new class of peptidomimetics termed "AApeptides". This class of peptidomimetics can mimic the mechanism of action of HDPs, and effectively arrest the growth of multidrug resistant Gram-positive and Gram-negative bacteria. As they are built on unnatural backbone, they are resistant to proteolytic degradation. In this review, we summarize the development of this class of antimicrobial peptidomimetics, and discuss the future perspective on how they can move forward on combating antibiotic resistance.

Small Antimicrobial Agents Based on Acylated Reduced Amide Scaffold.

Prevalence of drug-resistant bacteria has emerged to be one of the greatest threats in the 21st century. Herein, we report the development of a series of small molecular antibacterial agents that are based on the acylated reduced amide scaffold. These molecules display good potency against a panel of multidrug-resistant Gram-positive and Gram-negative bacterial strains. Meanwhile, they also effectively inhibit the biofilm formation. Mechanistic studies suggest that these compounds kill bacteria by compromising bacterial membranes, a mechanism analogous to that of host-defense peptides (HDPs). The mechanism is further supported by the fact that the lead compounds do not induce resistance in MRSA bacteria even after 14 passages. Lastly, we also demonstrate that these molecules have therapeutic potential by preventing inflammation caused by MRSA induced pneumonia in a rat model. This class of compounds could lead to an appealing class of antibiotic agents combating drug-resistant bacterial strains.

Nitinol stent implantation vs. balloon angioplasty for lesions in the superficial femoral and proximal popliteal arteries of patients with claudication: three-year follow-up from the RESILIENT randomized trial.

PURPOSE: To evaluate longer outcomes of primary nitinol stenting for the treatment of femoropopliteal lesions up to 15 cm long after these stents were found to have superior short-term patency vs. balloon angioplasty. METHODS: Two hundred and six patients (143 men; mean age 67 years) with intermittent claudication due to superficial femoral and proximal popliteal artery lesions were randomized (2:1) to treatment with nitinol stents or balloon angioplasty at 24 US and European centers and followed for 3 years. In that time, 15 patients died, 20 withdrew consent, and 10 were lost to follow-up, leaving 161 (78.2%) patients for 36-month assessment. RESULTS: The 12-month freedom from target lesion revascularization (TLR) was 87.3% for the stent group vs. 45.2% for the angioplasty group (p<0.0001). At 3 years, there was no difference in survival (90.0% vs. 91.7%, p=0.71) or major adverse events (75.2% vs. 75.2%, p=0.98) between the stent and angioplasty groups. Duplex ultrasound was not mandated after the first year, so stent patency could not be ascertained beyond 1 year, but freedom from TLR at 3 years was significantly better in the stent group (75.5% vs. 41.8%, p<0.0001), as was clinical success (63.2% vs. 17.9%, p<0.0001). At 18 months, a 4.1% (12/291) stent fracture rate was documented. CONCLUSION: In this multicenter trial, primary implantation of a nitinol stent for moderate-length lesions in the femoropopliteal segment of patients with claudication was associated with better long-term results vs. balloon angioplasty alone.

Clostridium difficile Colitis: Reduced Time to Diagnosis in a Community-Based Outpatient Setting Between 1997 and 2004.

OBJECTIVE: We studied antibiotic use prior to the onset of Clostridium difficile colitis (CDC) and time interval between onset of gastrointestinal symptoms and diagnosis for two historical time periods with separate comparisons for inpatients and outpatients to determine whether time to diagnosis had decreased and whether previous metronidazole use is associated with CDC. METHOD: We performed a retrospective chart review of adult patients (those 18 years or older) with positive findings on Clostridium difficile (CD) stool toxin tests performed at a Kaiser Permanente Southern California medical center. Independent assessments were compared for 1997-1998 and for 2004 time periods. These assessments used similar enrollment and exclusion criterion. Study populations were evaluated for previous antibiotic use and to determine time from clinical presentation of symptoms to diagnosis of CDC during each of the time periods, with assessments made separately for inpatients and outpatients. RESULTS: Findings showed a reduction in the average time from symptom presentation to diagnosis among outpatients with CDC from 17 days in the first time period (1997-1998) to ten days during the second time period (2004). No significant difference in the average time from symptom presentation to diagnosis of CDC was evident among inpatients (5.33 days for 1997-1998 and 6.00 days for 2004). Multiple antibiotic use prior to diagnosis of CDC was evident among both outpatients and inpatients in this study. Metronidazole had been used prior to the onset of CDC in approximately 15% of cases. CONCLUSION: The time from symptom onset to a CDC diagnosis decreased by seven days between the 1997-1998 and 2004 time periods among outpatients in this health care setting. Previous metronidazole use appeared to be associated with some cases of CDC.