Surgical treatment of acute fingernail injuries

The fingernail has an important role in hand function, facilitating the pinch and increasing the sensitivity of the fingertip. Therefore, immediate and proper strategy in treating fingernail injuries is essential to avoid aesthetic and functional impairment. Nail-bed and fingertip injuries are considered in this review, including subungual hematoma, wounds, simple lacerations of the nail bed and/or matrix, stellate lacerations, avulsion of the nail bed, ungual matrix defect, nail-bed injuries associated with fractures of the distal phalanx, and associated fingertip injuries. All these injuries require careful initial evaluation and adequate treatment, which is often performed under magnification. Delayed and secondary procedures of fingernail sequelae are possible, but final results are often unpredictable

Estrogen Receptor β-Selective Agonists Stimulate Calcium Oscillations in Human and Mouse Embryonic Stem Cell-Derived Neurons

Estrogens are used extensively to treat hot flashes in menopausal women. Some of the beneficial effects of estrogens in hormone therapy on the brain might be due to nongenomic effects in neurons such as the rapid stimulation of calcium oscillations. Most studies have examined the nongenomic effects of estrogen receptors (ER) in primary neurons or brain slices from the rodent brain. However, these cells can not be maintained continuously in culture because neurons are post-mitotic. Neurons derived from embryonic stem cells could be a potential continuous, cell-based model to study nongenomic actions of estrogens in neurons if they are responsive to estrogens after differentiation. In this study ER-subtype specific estrogens were used to examine the role of ERα and ERβ on calcium oscillations in neurons derived from human (hES) and mouse embryonic stem cells. Unlike the undifferentiated hES cells the differentiated cells expressed neuronal markers, ERβ, but not ERα. The non-selective ER agonist 17β-estradiol (E2) rapidly increased [Ca2+]i oscillations and synchronizations within a few minutes. No change in calcium oscillations was observed with the selective ERα agonist 4,4′,4″-(4-Propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT). In contrast, the selective ERβ agonists, 2,3-bis(4-Hydroxyphenyl)-propionitrile (DPN), MF101, and 2-(3-fluoro-4-hydroxyphenyl)-7-vinyl-1,3 benzoxazol-5-ol (ERB-041; WAY-202041) stimulated calcium oscillations similar to E2. The ERβ agonists also increased calcium oscillations and phosphorylated PKC, AKT and ERK1/2 in neurons derived from mouse ES cells, which was inhibited by nifedipine demonstrating that ERβ activates L-type voltage gated calcium channels to regulate neuronal activity. Our results demonstrate that ERβ signaling regulates nongenomic pathways in neurons derived from ES cells, and suggest that these cells might be useful to study the nongenomic mechanisms of estrogenic compounds

Characterization of the Minimal DNA Binding Domain of the Human Papillomavirus E1 Helicase: Fluorescence Anisotropy Studies and Characterization of a Dimerization-Defective Mutant Protein

The E1 helicase of papillomaviruses is required for replication of the viral double-stranded DNA genome, in conjunction with cellular factors. DNA replication is initiated at the viral origin by the assembly of E1 monomers into oligomeric complexes that have unwinding activity. In vivo, this process is catalyzed by the viral E2 protein, which recruits E1 specifically at the origin. For bovine papillomavirus (BPV) E1 a minimal DNA-binding domain (DBD) has been identified N-terminal to the enzymatic domain. In this study, we characterized the DBD of human papillomavirus 11 (HPV11), HPV18, and BPV E1 using a quantitative DNA binding assay based on fluorescence anisotropy. We found that the HPV11 DBD binds DNA with an affinity and sequence requirement comparable to those of the analogous domain of BPV but that the HPV18 DBD has a higher affinity for nonspecific DNA. By comparing the DNA-binding properties of a dimerization-defective protein to those of the wild type, we provide evidence that dimerization of the HPV11 DBD occurs only on two appropriately positioned E1 binding-sites and contributes approximately a 10-fold increase in binding affinity. In contrast, the HPV11 E1 helicase purified as preformed hexamers binds DNA with little sequence specificity, similarly to a dimerization-defective DBD. Finally, we show that the amino acid substitution that prevents dimerization reduces the ability of a longer E1 protein to bind to the origin in vitro and to support transient HPV DNA replication in vivo, but has little effect on its ATPase activity or ability to oligomerize into hexamers. These results are discussed in light of a model of the assembly of replication-competent double hexameric E1 complexes at the origin

Prevention of symptomatic neuroma in traumatic digital amputation: a RAND/UCLA appropriateness method consensus study

Introduction: The appearance of a symptomatic neuroma following finger amputation is a devastating consequence for patient's quality of life. It could be cause of chronic neuropathic pain. The prevention of neuroma formation is a challenging effort for hand surgeons. The biological mechanisms leading to neuroma formation are mostly unknown and different preventing procedures have been tried without certain results. In this paper, a panel of Italian hand surgeons have been asked to express appropriateness about potentially preventive techniques of neuroma formation following the RAND/UCLA appropriateness protocol. Methods: A literature review was preliminarily performed identifying the most employed methods to reduce the pathologic nerve scar. Afterwards, the selected panelists were asked to score the appropriateness of each procedure in a double scenario: in case of a sharp amputation or in a tear injury. The appropriateness was evaluated according to RAND/UCLA protocol. Results: Nine Italian hand surgeons were included in the panel. Of them 5 were orthopaedic surgeons, 4 plastic surgeons. The identified appropriate procedures were: revision amputation should be done in operating room, the neurovascular bundles should be identified and is mandatory to treat surrounding soft tissues. Only in case of clean-cut amputation, it is appropriate to perform a proximal extension of the dissection, to use diathermocoagulation and coverage with local flaps. Procedures such as shortening in tension of the nerve stump, bone shortening, implantation of the nerve end in the soft tissue, treatment in the emergency room and, in both scenarios, certain results are evaluated as uncertain. Discussion: In order to prevent the formation of a distal stump neuroma few methods were judged appropriate. It is mandatory to identify the neurovascular bundles and treat also the surrounding tissues, but no certain results could be obtained with local flap, bone shortening and other ancillary surgical acts. Moreover, it is not possible to guarantee the non arising of neuroma in any cases, also when every procedure has been temped. Conlusions: The prevention of distal neuroma is actually a challenge, without a well known strategy due to the variability of response of nervous tissue to injury