Kinetic and Structural Characterization of Sialidases (Kdnases) from Ascomycete Fungal Pathogens.

Sialidases catalyze the release of sialic acid from the terminus of glycan chains. We previously characterized the sialidase from the opportunistic fungal pathogen, Aspergillus fumigatus, and showed that it is a Kdnase. That is, this enzyme prefers 3-deoxy-d-glycero-d-galacto-non-2-ulosonates (Kdn glycosides) as the substrate compared to N-acetylneuraminides (Neu5Ac). Here, we report characterization and crystal structures of putative sialidases from two other ascomycete fungal pathogens, Aspergillus terreus (AtS) and Trichophyton rubrum (TrS). Unlike A. fumigatus Kdnase (AfS), hydrolysis with the Neu5Ac substrates was negligible for TrS and AtS; thus, TrS and AtS are selective Kdnases. The second-order rate constant for hydrolysis of aryl Kdn glycosides by AtS is similar to that by AfS but 30-fold higher by TrS. The structures of these glycoside hydrolase family 33 (GH33) enzymes in complex with a range of ligands for both AtS and TrS show subtle changes in ring conformation that mimic the Michaelis complex, transition state, and covalent intermediate formed during catalysis. In addition, they can aid identification of important residues for distinguishing between Kdn and Neu5Ac substrates. When A. fumigatus, A. terreus, and T. rubrum were grown in chemically defined media, Kdn was detected in mycelial extracts, but Neu5Ac was only observed in A. terreus or T. rubrum extracts. The C8 monosaccharide 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) was also identified in A. fumigatus and T. rubrum samples. A fluorescent Kdn probe was synthesized and revealed the localization of AfS in vesicles at the cell surface.

Contact Dermatitis and Medical Adhesives: A Review.

In more recent years, the use of medical adhesives in lieu of sutures or staples has become increasingly common for the closure of post-surgical and traumatic incisions in areas of the skin where tension is low. While medical adhesives possess many advantages and little risk of adverse side effects, there are increasing numbers of accounts in the medical literature of allergic contact dermatitis (ACD) caused by specific components contained within the medical adhesives. The goal of this paper is to provide physicians with a differential diagnosis when faced with complications after the use of medical adhesives for wound closure. Additionally, this paper aims to delineate the differences among the most commonly used adhesives, provide a rationale for assessing an individual's personal risk of developing ACD, and to highlight the unique advantages and disadvantages of each adhesive.  Dermabond® appears to be the most versatile adhesive with the lowest risk of ACD. However, because of its high cost, it may not be appropriate for all patients. While Mastisol® can only be utilized in combination with a dressing, such as Steri-Strips®, it is much more affordable than Dermabond and is still capable of providing an effective wound closure. Due to these factors, it is our recommendation that Dermabond is considered the first-line medical adhesive due to its versatility and strength, while Mastisol can be readily employed in situations with financial consideration. As the number of patients treated with medical adhesives continues to grow, physicians should anticipate an increase in the number of cases of ACD secondary to adhesive sensitization. It is imperative for physicians to be able to differentiate between a case of ACD and another potentially more serious complication, such as cellulitis. We hope that this paper will assist providers in distinguishing adhesive-induced ACD and other complications, identifying patients at risk of ACD from adhesive use, and provide a basis for which adhesives are most appropriate for any given patient.

Keloid Scars: An Updated Review of Combination Therapies.

Keloid scars are a common yet poorly understood complication of wound healing that can cause a diminished quality of life. Currently, there is little agreement amongst the medical community regarding the best treatment modality for keloids. For this reason, we have created an updated review of the most successful combination therapies for keloid scars and compared their efficacy based on rates of recurrence following treatment. Additionally, these combination therapies have been compared with intralesional triamcinolone acetonide corticosteroid (TAC), which is considered the mainstay monotherapy for keloids. All combination therapies included in our review were shown to produce superior outcomes than TAC monotherapy. We have also found that certain combination therapies are known to produce superior results when used in specific anatomic locations. Intralesional TAC plus intralesional cryotherapy appeared to have the most promising results for non-auricular keloids, and the authors suggest considering this as a first-line treatment. Additionally, the use of surgical excision plus compression therapy achieved superior results for auricular keloids and should be considered first-line for keloids in these locations.

Halogen-Bonded Guanine Base Pairs, Quartets and Ribbons.

Halogen bonding is studied in different structures consisting of halogenated guanine DNA bases, including the Hoogsteen guanine-guanine base pair, two different types of guanine ribbons (R-I and R-II) consisting of two or three monomers, and guanine quartets. In the halogenated base pairs (except the Cl-base pair, which has a very non-planar structure with no halogen bonds) and R-I ribbons (except the At trimer), the potential N-X•••O interaction is sacrificed to optimise the N-X•••N halogen bond. In the At trimer, the astatines originally bonded to N1 in the halogen bond donating guanines have moved to the adjacent O6 atom, enabling O-At•••N, N-At•••O, and N-At•••At halogen bonds. The brominated and chlorinated R-II trimers contain two N-X•••N and two N-X•••O halogen bonds, whereas in the iodinated and astatinated trimers, one of the N-X•••N halogen bonds is lost. The corresponding R-II dimers keep the same halogen bond patterns. The G-quartets display a rich diversity of symmetries and halogen bond patterns, including N-X•••N, N-X•••O, N-X•••X, O-X•••X, and O-X•••O halogen bonds (the latter two facilitated by the transfer of halogens from N1 to O6). In general, halogenation decreases the stability of the structures. However, the stability increases with the increasing atomic number of the halogen, and the At-doped R-I trimer and the three most stable At-doped quartets are more stable than their hydrogenated counterparts. Significant deviations from linearity are found for some of the halogen bonds (with halogen bond angles around 150°).

An Evidence-Based Model for the Successful Treatment of Flank and Lateral Abdominal Wall Hernias.

BACKGROUND: Lateral abdominal wall defects are a significant contributor to patient morbidity and mortality in the United States. Reconstruction involving flank hernias and bulges is relatively scarce in the literature despite its serious consequences. The authors aim to identify an objective approach for the evaluation and successful repair of defects of the lateral abdominal wall. METHODS: A retrospective analysis was carried out on patients presenting for open repair of a lateral wall defect performed by a single surgeon. Over a 5-year period, there were 29 consecutive patients with a mean follow-up period of 21.2 months. Patient demographics including body mass index, number of hernia defects, number of previous repairs/abdominal operations, defect size, operative time, blood loss, and complications (e.g., recurrence/bulge, seroma, hematoma, wound infection, persistent pain, skin breakdown, and fascial dehiscence) were collected. RESULTS: Patients who underwent flank hernia repairs using an inlay/underlay nonbridged technique with the use of acellular dermal matrix had low recurrence and overall complication rates. Only one patient (3.4 percent) had a recurrence at follow-up, and another patient (3.4 percent) had developed a bulge. CONCLUSIONS: The authors' data indicate successful results when their technique is applied. Proper patient selection is essential, along with a thorough understanding of anatomy and techniques for successful reconstruction. The authors recommend using an inlay (preferred) or underlay repair with acellular dermal matrix to reinforce the surrounding musculofascial closure. This technique, in conjunction with the authors' holistic abdominal wall reconstruction protocol, has optimized outcomes and identified a successful multidisciplinary strategy for the reconstruction of lateral wall defects. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.