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Diabetic foot ulcers and venous leg ulcers are chronic wounds frequently encountered by dermatologists. Choosing appropriate wound dressings can effectively promote wound healing and potentially reduce morbidity and financial burden experienced by patients. The objective of our systematic review and meta-analysis was to evaluate wound healing efficacies of synthetic active dressings in diabetic foot ulcer and venous leg ulcer management. For data collection, PubMed, Embase, Cochrane Library, CINAHL, and clinicaltrials.gov online databases were searched from database inception to 10 May 2015. Fixed and random effects modeling were used to calculate pooled risk ratios for complete ulcer healing from pairwise dressing comparisons. The results of our review showed moderate-quality level evidence that hydrogels were more effective in healing diabetic foot ulcers than basic wound contact dressings (RR 1.80 [95% CI, 1.27-2.56]). The other dressing comparisons showed no statistically significant differences between the interventions examined in terms of achieving complete diabetic foot ulcer healing. Non-adherent dressings were more cost-effective than hydrofiber dressings for diabetic foot ulcers in terms of mean total cost per patient of the dressings themselves. All venous leg ulcer pairwise dressing comparisons showed equivalent dressing efficacies in terms of promoting complete ulcer healing. Overall, most synthetic active dressings and traditional wound dressings are equally efficacious in treating diabetic foot ulcers and venous leg ulcers. For treating diabetic foot ulcers, hydrogels are more efficacious than basic wound contact dressings, and non-adherent dressings are more cost-effective than hydrofiber dressings. Ultimately, dressing choice should be tailored to the wound and the patient

G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ∼20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology.

Adenoid cystic carcinoma is a rare neoplasm that originates from secretory glands, most commonly from the salivary glands. We present a 76 year-old white man with a history of adenoid cystic carcinoma from the base of the tongue diagnosed 15 years prior to the development of the metastatic lesion on his mid-posterior scalp. The present case represents the second reported instance of an extracutaneous adenoid cystic carcinoma metastasizing to the scalp. Differentiating between a primary cutaneous adenoid cystic carcinoma and an extracutaneous adenoid cystic carcinoma metastasizing to cutaneous structures is crucial in determining prognosis and management.

Here, a method for presenting crystals of soluble and membrane proteins growing in the lipid cubic or sponge phase for in situ in situ diffraction data collection at cryogenic temperatures is introduced. The method dispenses with the need for the technically demanding and inefficient crystal-harvesting step that is an integral part of the lipid cubic phase or in meso in meso method of growing crystals. Crystals are dispersed in a bolus of mesophase sandwiched between thin plastic windows. The bolus contains tens to hundreds of crystals, visible with an in-line microscope at macromolecular crystallography synchrotron beamlines and suitably disposed for conventional or serial crystallographic data collection. Wells containing the crystal-laden boluses are removed individually from hermetically sealed glass plates in which crystallization occurs, affixed to pins on goniometer bases and excess precipitant is removed from around the mesophase. The wells are snap-cooled in liquid nitrogen, stored and shipped in Dewars, and manually or robotically mounted on a goniometer in a cryostream for diffraction data collection at 100 K, as is performed routinely with standard, loop-harvested crystals. The method is a variant on the recently introduced in meso in situ in meso in situ serial crystallography (IMISX) method that enables crystallographic measurements at cryogenic temperatures where crystal lifetimes are enormously enhanced whilst reducing protein consumption dramatically. The new approach has been used to generate high-resolution crystal structures of a G-protein-coupled receptor, α-helical and β-barrel transporters and an enzyme as model integral membrane proteins. Insulin and lysozyme were used as test soluble proteins. The quality of the data that can be generated by this method was attested to by performing sulfur and bromine SAD phasing with two of the test proteins. [ABSTRACT FROM AUTHOR]

Importance: Topical antibiotics are not indicated for postsurgical wound infection prophylaxis in clean and clean-contaminated dermatologic surgeries, yet many dermatologists continue to prescribe them. The objective of our systematic review and meta-analysis was to critically assess the efficacy of topical antibiotics in terms of preventing postsurgical wound infections in the dermatology outpatient setting. Methods: PubMed, Embase, MD Consult, Science Direct, Springer Link, DynaMed and Cochrane online medical databases were searched from 1980 to 2013. Results: Using random effects modeling, the pooled odds ratio of developing a postsurgical wound infection was 0.71 (95% CI, 0.42-1.19). Discussion: Pooled data of the four trials in the meta-analysis did not show a statistically significant difference in incidence of postsurgical wound infections between topical antibiotics and petrolatum/paraffin. In the setting of moist occlusive dressings, there is no statistically significant difference in prophylactic efficacy between applying and not applying ointment to surgical wounds. Wounds at increased risk of developing surgical site infections include wounds in diabetics, wounds located in certain anatomic regions, and wounds created by some surgical procedures. Conclusions: Petrolatum should be used instead of topical antibiotics as a prophylactic measure to prevent postsurgical wound infections in the outpatient dermatologic setting. [ABSTRACT FROM AUTHOR]

Somatostatins (SSs) are a family of peptide hormones that have been shown to inhibit pituitary growth hormone (GH) release. Extra-pituitary actions of SSs were suggested by previous studies that showed [...]

The lipidic mesophase or in mesomethod for crystallizing membraneproteins has several high profile targets to its credit and is growingin popularity. Despite its success, the method is in its infancy asfar as rational crystallogenesis is concerned. Consequently, significanttime, effort, and resources are still required to generate structure-gradecrystals, especially with a new target type. Therefore, a need existsfor crystallogenesis protocols that are effective with a broad rangeof membrane protein types. Recently, a strategy for crystallizinga prokaryotic α-helical membrane protein, diacylglycerol kinase(DgkA), by the in meso method was reported (Cryst. Growth. Des.2013, 13, 2846−2857). Here, we describe its application to thehuman α-helical microsomal prostaglandin E2 synthase 1 (mPGES1).While the DgkA strategy proved useful, significant modifications wereneeded to generate structure-quality crystals of this important therapeutictarget. These included protein engineering, using an additive phospholipidin the hosting mesophase, performing multiple rounds of salt screening,and carrying out trials at 4 °C in the presence of a tight bindingligand. The crystallization strategy detailed here should prove usefulfor generating structures of other integral membrane proteins by thein meso method. [ABSTRACT FROM AUTHOR]

We describe a data collection method that uses a single crystal to solve X-ray structures by native SAD (single-wavelength anomalous diffraction). We solved the structures of 11 real-life examples, including a human membrane protein, a protein-DNA complex and a 266-kDa multiprotein-ligand complex, using this method. The data collection strategy is suitable for routine structure determination and can be implemented at most macromolecular crystallography synchrotron beamlines. [ABSTRACT FROM AUTHOR]

The lipid cubic phase or in meso method can be used to set up crystallization trials of soluble and membrane proteins. The cubic phase is noted for being a sticky and viscous mesophase. Dispensing the protein-laden mesophase by hand into wells on crystallization plates has been facilitated by the use of an inexpensive repeat dispenser. However, the assembled dispensing device is prone to damage. Specifically, the delicate plunger used to dispense the viscous mesophase by positive displacement can be bent and scarred when the locking nut that fixes the plunger to the ratchet-driven dispensing mechanism is inadvertently overtightened. A defective plunger can render the device useless as a dispensing tool. More importantly, it can lead to catastrophic loss of valuable protein and lipid due to leakage when the dispensing syringe is being recharged with fresh mesophase. This note describes two types of bushings designed to protect the plunger from mechanical damage, which provide facile and reliable dispenser performance. One is a split bushing in brass and is a highly durable solution. The other is a small sleeve made from readily available plastic tubing. While it lacks durability, the plastic sleeve is simple yet highly effective, and can be replaced as the need arises. [ABSTRACT FROM AUTHOR]

A correction to the article "Fast native-SAD phasing for routine macromolecular structure determination," by Vincent Olieric, Lirong Chen, and Hua Zhang that was published online on December 15, 2014 is presented.

Here, a method for presenting crystals of soluble and membrane proteins growing in the lipid cubic or sponge phase for in situ diffraction data collection at cryogenic temperatures is introduced. The method dispenses with the need for the technically demanding and inefficient crystal-harvesting step that is an integral part of the lipid cubic phase or in meso method of growing crystals. Crystals are dispersed in a bolus of mesophase sandwiched between thin plastic windows. The bolus contains tens to hundreds of crystals, visible with an in-line microscope at macromolecular crystallography synchrotron beamlines and suitably disposed for conventional or serial crystallographic data collection. Wells containing the crystal-laden boluses are removed individually from hermetically sealed glass plates in which crystallization occurs, affixed to pins on goniometer bases and excess precipitant is removed from around the mesophase. The wells are snap-cooled in liquid nitrogen, stored and shipped in Dewars, and manually or robotically mounted on a goniometer in a cryostream for diffraction data collection at 100 K, as is performed routinely with standard, loop-harvested crystals. The method is a variant on the recently introduced in meso in situ serial crystallography (IMISX) method that enables crystallographic measurements at cryogenic temperatures where crystal lifetimes are enormously enhanced whilst reducing protein consumption dramatically. The new approach has been used to generate high-resolution crystal structures of a G-protein-coupled receptor, α-helical and β-barrel transporters and an enzyme as model integral membrane proteins. Insulin and lysozyme were used as test soluble proteins. The quality of the data that can be generated by this method was attested to by performing sulfur and bromine SAD phasing with two of the test proteins.

In a relatively short timespan, a wealth of new skin substitutes made of synthetic and biologically derived materials have arisen for the purpose of wound healing of various etiologies. This review article focuses on providing an overview of skin substitutes including their indications, contraindications, benefits, and limitations. The result of this overview was an appreciation of the vast array of options available for clinicians, many of which did not exist a short time ago. Yet, despite the rapid expansion this field has undergone, no ideal skin substitute is currently available. More research in the field of skin substitutes and wound healing is required not only for the development of new products made of increasingly complex biomolecular material, but also to compare the existing skin substitutes.

The lipid-based bicontinuous cubic mesophase is a nanoporous membrane mimetic with applications in areas that include medicine, personal care products, foods and the basic sciences. An application of particular note concerns it use as a medium in which to grow crystals of membrane proteins for structure determination by X-ray crystallography. At least two variations of the mesophase exist. One is the highly viscous cubic phase, which has well developed long-range order. The other so-called sponge phase is considerably more fluid and lacks long-range order. The sponge phase has recently been shown to be a convenient vehicle for delivering microcrystals of membrane proteins to an X-ray free-electron laser beam for serial femtosecond crystallography (SFX). Unfortunately, the sponge phase approach calls for large amounts of protein that are not always available in the case of membrane proteins. The cubic phase offers the advantage of requiring significantly less protein for SFX but comes with its own challenges. Here, we describe the physico-chemical bases for these challenges, solutions to them and prospects for future uses of lipidic mesophases in the SFX arena.