Piscidins were the first antimicrobial peptides discovered in the mast cells of vertebrates. While two family members, piscidin 1 (p1) and piscidin 3 (p3), have highly similar sequences and α-helical structures when bound to model membranes, p1 generally exhibits stronger antimicrobial and hemolytic activity than p3 for reasons that remain elusive. In this study, we combine activity assays and biophysical methods to investigate the mechanisms underlying the cellular function and differing biological potencies of these peptides, and report findings spanning three major facets. First, added to Gram-positive (Bacillus megaterium) and Gram-negative (Escherichia coli) bacteria at sublethal concentrations and imaged by confocal microscopy, both p1 and p3 translocate across cell membranes and colocalize with nucleoids. In E. coli, translocation is accompanied by nonlethal permeabilization that features more pronounced leakage for p1. Second, p1 is also more disruptive than p3 to bacterial model membranes, as quantified by a dye-leakage assay and (2)H solid-state NMR-monitored lipid acyl chain order parameters. Oriented CD studies in the same bilayers show that, beyond a critical peptide concentration, both peptides transition from a surface-bound state to a tilted orientation. Third, gel retardation experiments and CD-monitored titrations on isolated DNA demonstrate that both peptides bind DNA but p3 has stronger condensing effects. Notably, solid-state NMR reveals that the peptides are α-helical when bound to DNA. Overall, these studies identify two polyreactive piscidin isoforms that bind phosphate-containing targets in a poised amphipathic α-helical conformation, disrupt bacterial membranes, and access the intracellular constituents of target cells. Remarkably, the two isoforms have complementary effects; p1 is more membrane active, while p3 has stronger DNA-condensing effects. Subtle differences in their physicochemical properties are highlighted to help explain their contrasting activities.

Reinforced venous aneurysmorrhaphy is effective in controlling venous dilation and achieving patency. Reduction of high-flow rates was not always achieved. Further study is needed to evaluate long-term efficacy of this treatment.

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The number of times an article has been cited is thought to correspond with its level of academic influence. Within the orthopaedic literature, several citation analyses have been performed, including a recent investigation on the most commonly cited articles on femoroacetabular impingement (FAI); however, no study has determined the most cited investigations on extracapsular hip pathologies, including osteitis pubis, athletic pubalgia, and muscle strains. Such pathologies constitute a significant proportion of lower extremity injuries among athletes. The purpose of this study was to determine the 50 most cited investigations on extra-articular hip injuries by performing a systematic query of the Institute for Scientific Information (ISI) Web of Science (Thomson Reuters, Philadelphia, PA). The following characteristics were determined for each article: number of citations, citation density, journal and publication year, country of origin, language, article type, article subtype, and level of evidence. The number of citations ranged from 46 to 202 (mean 84.4), and the citation densities ranged from 1.7 to 28.4 citations per year (mean: 7.9). Sixty-eight percent of the selected articles involved hamstring strains. The majority of articles were published in the American Journal of Sports Medicine (58%), followed by the Journal of Orthopaedic and Sports Physical Therapy (12%). Most articles were published during the 2000s, originated from the United States, and 100% were written in English. Eighty percent were clinical studies; the majority of which had Level IV evidence. This collection of academic investigations on athletic extra-articular hip injuries can aid in the establishment of a reading curriculum for trainees participating in orthopaedic training programs.

Background: The effectiveness of operating on local recurrence of adenocarcinoma within the pancreatic parenchyma is poorly understood, because recurrence is more typically systemic. Under the latter circumstance, care is limited to palliative chemotherapy or best supportive care. When recurrence is localized to the pancreas, the benefit of resection is swayed by concerns for endocrine and exocrine insufficiency related to completion pancreatectomy and quiescent disease. This study aimed to define survival probabilities based on interval between index pancreatectomy and completion pancreatectomy. Methods: All completion pancreatectomies for isolated recurrence in the remnant pancreas at our institution from May 2003 with follow-up through August 2018 were identified from our institutional database. All patients had confirmed pancreatic adenocarcinoma at both the index and completion pancreatectomies, and none had distant metastatic disease. Perioperative outcome, survival, and prognostic parameters were assessed. The data naturally fit three inflection points that were used to compare overall survival from time of partial pancreatectomy using Kaplan-Meier methodology. Results: Fifteen males and 13 females were studied; median age at time of index pancreatectomy was 61.6 (IQR: 57.3, 67.7) years. Median follow-up for the sample was 34.7 (IQR 16.75, 84.9) months. 24% received neoadjuvant therapy prior to their index pancreatectomy, and 36% received adjuvant therapy; 24% received radiation therapy. 79% of index pancreatectomies were pancreaticoduodenectomies. Tumors were primarily high grade (80%) and node positive (57.7%). The overall median time to completion pancreatectomy was 23.59 (IQR: 5.9, 58.5) months. 12% received neoadjuvant therapy prior to their completion pancreatectomy, and 50% received adjuvant therapy; 12% received radiation therapy. Tumors were again primarily high grade (80%), but were majority node negative (53.9%). The median overall survival estimate was 64.43 (95% CI 30.9e113.2) months. When the data was trichotomized at 12 (n = 11), 12-36 (n = 6) and >36 (n = 11) months, a significant difference in overall survival probabilities emerged (p = 0.0028): the median overall survival probabilities were 17.98, 30.91 and 97.52 months from index pancreatectomy, respectively (Figure 1). The median time to recurrence by interval was 2.44, 20.67 and 75.38 months, respectively. At 24 months after completion pancreatectomy, 23%, 56% and 32% of patients remained alive, if the interval to completion pancreatectomy was less than 12 months, 12e36 months, or >36 months, respectively. This suggests individuals with isolated local recurrence undergoing completion pancreatectomy 12e36