Evaluation of the self-administration potential of high-density microarray patches to human skin: A preliminary study.

The high-density microneedle array patch (HD-MAP) is a novel vaccine delivery system with potential for self-administered vaccination. In this study, Vaxxas HD-MAPs were applied by both a trained user and self-administered with application sites compared to determine the response of skin and the level of engagement of the HD-MAP with human skin. Twenty healthy participants were enrolled, and the response of skin including erythema was observed at all application sites and no difference was found between trained user or self-administered applications. The majority of participants (70%) preferred the deltoid upper arm application site for applying HD-MAPs. Fluorescent dermatoscope images confirmed HD-MAPs engaged the skin surface and scanning electron microscopy (SEM) image analysis exhibited similar delivery characteristics for the upper arm and forearm sites when applied by either a trained user or self-administered. This study showed that noninvasive methods including dermatoscopy and SEM image analysis were able to estimate the engagement of HD-MAPs with human skin. HD-MAP self-vaccination technology has a unique proposition in pandemic preparedness by alleviating the need for health-care workers to administer vaccines, however greater awareness and understanding of the potential of this technology is required.

Atmospheric pressure X-ray photoelectron spectroscopy apparatus: Bridging the pressure gap.

One of the main goals in catalysis is the characterization of solid/gas interfaces in a reaction environment. The electronic structure and chemical composition of surfaces become heavily influenced by the surrounding environment. However, the lack of surface sensitive techniques that are able to monitor these modifications under high pressure conditions hinders the understanding of such processes. This limitation is known throughout the community as the "pressure gap." We have developed a novel experimental setup that provides chemical information on a molecular level under atmospheric pressure and in presence of reactive gases and at elevated temperatures. This approach is based on separating the vacuum environment from the high-pressure environment by a silicon nitride grid-that contains an array of micrometer-sized holes-coated with a bilayer of graphene. Using this configuration, we have investigated the local electronic structure of catalysts by means of photoelectron spectroscopy and in presence of gases at 1 atm. The reaction products were monitored online by mass spectrometry and gas chromatography. The successful operation of this setup was demonstrated with three different examples: the oxidation/reduction reaction of iridium (noble metal) and copper (transition metal) nanoparticles and with the hydrogenation of propyne on Pd black catalyst (powder).

Square ice in graphene nanocapillaries.

Bulk water exists in many forms, including liquid, vapour and numerous crystalline and amorphous phases of ice, with hexagonal ice being responsible for the fascinating variety of snowflakes. Much less noticeable but equally ubiquitous is water adsorbed at interfaces and confined in microscopic pores. Such low-dimensional water determines aspects of various phenomena in materials science, geology, biology, tribology and nanotechnology. Theory suggests many possible phases for adsorbed and confined water, but it has proved challenging to assess its crystal structure experimentally. Here we report high-resolution electron microscopy imaging of water locked between two graphene sheets, an archetypal example of hydrophobic confinement. The observations show that the nanoconfined water at room temperature forms 'square ice'--a phase having symmetry qualitatively different from the conventional tetrahedral geometry of hydrogen bonding between water molecules. Square ice has a high packing density with a lattice constant of 2.83 Å and can assemble in bilayer and trilayer crystallites. Molecular dynamics simulations indicate that square ice should be present inside hydrophobic nanochannels independently of their exact atomic nature.

Detection of a few metallo-protein molecules using color centers in nanodiamonds.

Nanometer-sized diamonds containing nitrogen-vacancy defect centers (NV) are promising nanosensors in biological environments due to their biocompatibility, bright fluorescence, and high magnetic sensitivity at ambient conditions. Here we report on the detection of ferritin molecules using magnetic noise induced by the inner paramagnetic iron as a contrast mechanism. We observe a significant reduction of both coherence and relaxation time due to the presence of ferritin on the surface of nanodiamonds. Our theoretical model is in excellent agreement with the experimental data and establishes this method as a novel sensing technology for proteins.

Twisted bi-layer graphene: microscopic rainbows.

Blue, pink, and yellow colorations appear from twisted bi-layer graphene (tBLG) when transferred to a SiO2 /Si substrate (SiO2 = 100 nm-thick). Raman and electron microscope studies reveal that these colorations appear for twist angles in the 9-15° range. Optical contrast simulations confirm that the observed colorations are related to the angle-dependent electronic properties of tBLG combined with the reflection that results from the layered structure tBLG/100 nm-thick SiO2 /Si.

Electrical impedance scanning for melanoma diagnosis: a validation study.

BACKGROUND: A multicenter study was conducted to test the ability of electrical impedance scanning to differentiate between benign and malignant skin lesions. The performance of a dual electrical impedance scanning/image analysis device was also assessed. METHODS: Electrical impedance scanning measurements of 449 preoperative lesions found on 382 patients and including 53 melanomas from the trunk and extremities were performed. Results were correlated with histopathologic findings. In addition, ABCD parameters for the lesions were automatically calculated by the system. RESULTS: Electrical impedance scanning detected melanomas of the trunk and extremities with 91 percent sensitivity and 64 percent specificity. Moreover, sensitivity of electrical impedance scanning was increased to 100 percent for in situ and thin melanomas of smaller size (n = 27). Visual examination identified as malignant only 67 percent of these early tumors (p = 0.002). Clinical examination detected 96 percent of the larger or thicker melanomas (n = 26), whereas electrical impedance scanning detected only 81 percent of them. Combined electrical impedance scanning and image analysis detected 100 percent of the melanomas, independent of their thickness, and with no significant decrease of specificity. Because of electrical differences between the head/neck and the rest of the body, the assessed electrical impedance scanning parameters were not adequate for the diagnosis of melanomas from the head and neck. CONCLUSIONS: A validation study proved the value of electrical impedance scanning as a noninvasive technique for detection of melanoma lesions of the trunk and extremities, specifically, of in situ and thin type. In addition, image analysis was shown to be a valuable, complementary procedure. New parameters should be designed to optimize the performance of electrical impedance scanning for melanomas of the head and neck.

A novel mutation in the L12 domain of keratin 5 in the Köbner variant of epidermolysis bullosa simplex.

We have identified a novel mutation within the linker L12 region of keratin 5 (K5) in a family with the Köbner variant of epidermolysis bullosa simplex. The pattern of inheritance of the disorder in this family is consistent with an autosomal dominant mode of transmission. Affected individuals develop extensive and generalized blistering at birth or early infancy but in later years clinical manifestations are largely confined to palmoplantar surfaces. Direct sequencing of polymerase chain reaction products revealed a T to C transition within codon 323 of K5 in affected individuals, resulting in a valine to alanine substitution of the seventh residue within the L12 linker domain. This mutation was not observed in unaffected family members or in 100 K5 alleles of unrelated individuals with normal skin. The other critical regions of K5 and K14 were unremarkable in this family except for common polymorphisms that have been previously described. The valine at position 7 of the L12 domain is absolutely conserved in all type II keratins, and in other intermediate filament subunits as well, which suggests that this residue makes an important contribution to filament integrity. Secondary structure analysis revealed that alanine at this position markedly reduces both the hydrophobicity and the beta-sheet nature of the L12 domain. This is the first report of a mutation at this position in an intermediate filament subunit and reinforces the importance of this region to filament biology.

Idiopathic multiple miliary osteomas of the face.

A case of multiple miliary osteomas of the face arising in a 45-year-old Caucasian female with no history of skin disease is reported. Spontaneous development of numerous asymptomatic, skin-coloured facial papules had occurred over a 3 year period. Originally described in association with long-standing acne vulgaris, multiple miliary osteomas of the face has recently been reported in patients without prior skin disease. The pathogenesis, classification and treatment of this rare condition are discussed.

Minocycline-induced oral pigmentation.

Oral mucosal pigmentation is an infrequently reported side effect of minocycline. Two patients with minocycline deposition within teeth and bone, demonstrated by fluorescence microscopy, are described. Minocycline is the only tetracycline reported to cause discoloration of the oral mucosa. This may be the result of deposition of an insoluble degradation product of minocycline in the underlying bone. Pigmentation is not necessarily dose-dependent and may take months or years to resolve.

Kinetics and specificity of nickel hypersensitivity in the murine model.

Nickel contact dermatitis appears to be almost exclusively a disease of females despite the increasing exposure of males to nickel. Successful murine models of nickel allergic contact dermatitis have been described. The purpose of this study is to investigate the kinetics and specificity of the response in this model and to examine if any differences exist between male and female. Mice were sensitised epicutaneously with nickel sulphate in aqueous solution of varying concentration, volume and duration of application. Following intradermal challenge, dose dependent response kinetics which approximated linearity were demonstrated upto the point of toxicity. Sensitised mice were challenged with Cobaltous chloride, Chromic chloride and Cupric sulphate and demonstrated no evidence of cross sensitivity to cobalt or chrome. Copper produced an irritant response making interpretation difficult. Earlier and stronger responses were observed in female mice, however these differences fell short of statistical significance. The results of the present study therefore establishes a reliable model for nickel hypersensitivity, that demonstrates both specificity and dose dependent kinetics without significant sex differences.

Glucagonoma syndrome with increased lactate dehydrogenase isoenzymes: octreotide treatment.

Glucagonoma Syndrome is a rare syndrome comprising hyperglucagonemia, diabetes mellitus, necrolytic migratory erythema and hypoaminoacidemia in the setting of a glucagon producing, alpha cell tumour of the pancreas. We report a case of Glucagonoma Syndrome palliatively treated successfully with octreotide. In addition to classical clinical and biochemical findings, this patient also had a Glomus Jugulare tumour, and Empty Sella Syndrome and demonstrated an unusual pattern of plasma lactate dehydrogenase isoenzymes, features not previously reported in this syndrome.

Timing of prophylactic antibiotics in abdominal surgery: trial of a pre-operative versus an intra-operative first dose.

When prophylactic antibiotics are used in abdominal surgery it is customary to give the first dose before the operation. Whilst intra-operative antibiotics may be effective in elective surgery, there may be an advantage to starting pre-operatively when there is already an infective focus such as appendicitis. Antibiotics started pre-operatively (group P) have been compared with antibiotics started after initial abdominal exploration (group T). Three intravenous doses of 500 mg metronidazole plus 1 g cephazolin were given in a randomized, double-blind study of 700 emergency and elective high-risk abdominal operations. Antibiotic plasma concentrations at the end of the operation were significantly lower in group P but lay well within the therapeutic range. Wound infection rates, which included minor and delayed infections, were similar in both groups (group P, 57 of 342, 16.7 per cent; group T, 55 of 358, 15.4 per cent; 95 per cent confidence intervals for the difference being -4.1 to +6.7 per cent. In appendicitis, wound infection rates were 12.1 and 13.9 per cent for groups P and T respectively. However, non-fatal deep sepsis was more common in group P (nine cases) than in group T (two cases) (chi 2 = 4.9, P less than 0.05). Postoperative infection was twice as common in obese patients whose body mass index (BMI) was greater than or equal to 26 (39 of 132, 30 per cent) than in thin patients whose BMI was less than 24 (41 of 288, 14 per cent; chi 2 = 13.8, P less than 0.001). This study failed to show any advantage to starting antibiotics pre-operatively, even in appendicitis.

Fournier's gangrene. Experience in the treatment of gangrenous inflammation of the male genitals.

Four cases of acute gangrenous inflammation of the male genitals are discussed, after a brief review of the literature, with reference to the authors' own experience. In addition to dermal and fascial necrosis the disease causes severe sepsis and shock. Characteristics include rapid progression, occasionally in a matter of hours, and high rate of mortality. Attention is called to the importance of early surgical intervention and to the difficulties in combatting the septic shock.