Vaccine-preventable meningitis in French children with incorrect vaccination status from 2011 to 2013.

The objective of this study was to determine the number of cases of pediatric meningitis or purpura fulminans associated with an incorrect vaccination status from 2011 to 2013 in France. A total of 48 children with vaccine-preventable meningitis or purpura fulminans, including three deaths, had an incorrect vaccination status: 26 cases were due to Neisseria meningitidis group C (54.2%), 19 to Streptococcus pneumoniae (39.6%), and three to Haemophilus influenzae type b (6.3%). The majority of patients (n=35, 72.9%) had received no injection of the vaccine concerned. Over a 3-year period, 48 cases of bacterial meningitis or purpura fulminans in children could have been avoided if the French immunization schedule had been followed.

Polyomaviruses of the skin: integrating molecular and clinical advances in an emerging class of viruses.

BACKGROUND: Human polyomaviruses (HPyVs) are small, nonenveloped, double-stranded DNA viruses that express tumour antigen proteins. Fourteen species of polyomaviruses have been discovered in humans, and since the 2008 discovery of the first cutaneous polyomavirus - Merkel cell polyomavirus (MCPyV) - six more species have been detected in the skin: trichodysplasia spinulosa-associated polyomavirus (TSPyV), HPyV6, HPyV7, HPyV9, HPyV10 and HPyV13. Of these cutaneous species, only MCPyV, TSPyV, HPyV6 and HPyV7 have been definitively associated with diseases of the skin, most commonly in immunocompromised individuals. MCPyV is a predominant aetiology in Merkel cell carcinomas. TSPyV is one of the aetiological factors of trichodysplasia spinulosa. HPyV6 and HPyV7 have been recently linked to pruritic skin eruptions. The roles of HPyV9, HPyV10 and HPyV13 in pathogenesis, if any, are still unknown, but their molecular features have provided some insight into their functional biology. RESULTS: In this review, we summarize the known molecular mechanisms, clinical presentation and targeted therapies of each of the eight cutaneous HPyVs. CONCLUSIONS: We hope that heightened awareness and clinical recognition of HPyVs will lead to increased reports of HPyV-associated diseases and, consequently, a more robust understanding of how to diagnose and treat these conditions.

Genetic Rodent Models of Huntington Disease.

The monogenic nature of Huntington disease (HD) has led to the development of a spectrum of useful genetically modified models. In particular, rodents have pioneered as the first HD model being generated and have since been the most widely used animal model for HD in both basic research and preclinical therapeutic studies. Based on the generation strategies, these rodent models can be classified into 3 major groups, the transgenic fragment models, the transgenic full-length models and the knock-in models. These models display a range of HD-like characteristics which resemble the clinical symptoms of HD patients. Their applications in research are thus regarded as an invaluable approach to speeding up the unraveling of the underlying pathological mechanisms of HD and for finding a disease-modifying treatment for this devastating disease. In this chapter, the similarities and differences of the most commonly used rodent HD models and their relevance to human HD will be compared and discussed. This also serves to guide the selection of an appropriate rodent HD model according to the nature of investigation.

Actikerall™ (5-Fluorouracil 0.5% and Salicylic Acid 10%) Topical Solution for Patient-directed Treatment of Actinic Keratoses.

Actinic keratosis (AK), a common cutaneous lesion with the potential to transform into squamous cell carcinoma, has traditionally been treated with ablative and/or surgical procedures. Recently, a topical formulation combining 0.5% 5-fluorouracil with 10% salicylic acid (5-FU-SA) was introduced in Europe under the trade name Actikerall™ for the treatment of grade I/II AKs. In a single randomized phase III trial, 5-FU-SA was shown to be superior to diclofenac 3% gel in hyaluronic acid, as measured by the histological clearance of one defined lesion (72% vs. 59.1%) and by complete clinical clearance (55.4% vs. 32.0%). 5-FU-SA should be applied once daily to a total area of up to 25 cm(2), which may include the lesion(s) and a small area of surrounding skin (rim of healthy skin should not exceed 0.5 cm), for up to 12 weeks. The most common side effects are local inflammation and pruritus at the application site, and no serious adverse effects have been reported to date. Now commercially available in Canada, 5-FU-SA represents a patientapplied therapeutic option for the treatment of both overt and subclinical AKs.

Merkel cell polyomavirus and human papilloma virus in proliferative skin lesions arising in patients treated with BRAF inhibitors.

The potential role of oncogenic viruses mediating development of proliferative skin lesions in patients treated with RAF inhibitors is poorly understood. The objective of this study was to investigate human papilloma virus (HPV) and Merkel cell polyomavirus (MCPyV) in skin lesions among patients treated with RAF inhibitors with the help of a case series describing prevalence of HPV, MCPyV, and RAS mutations in skin biopsies obtained from patients receiving RAF inhibitors and developing cutaneous lesions. HPV-DNA was amplified by PCR utilizing multiple nested primer systems designed for detection of a broad range of HPV types. MCPyV copy number determination with real time PCR technology was performed by a "Quantification of MCPyV, small t region" kit. Thirty-six patients were tested (squamous cell carcinoma (SCC) = 14; verruca vulgaris = 15; other = 11). Nine of 12 SCCs (75 %) and eight of 13 verruca vulgaris lesions (62 %) tested positive for MCPyV whereas none of the normal skin biopsies obtained from nine of these patients tested positive for MCPyV (p = 0.0007). HPV incidence in cutaneous SCCs was not different compared to normal skin (50 vs. 56 %, p = 0.86). The association between MCPyV and proliferative skin lesions after RAF inhibitor therapy merits further investigation.

Molecular insight into the viral biology and clinical features of trichodysplasia spinulosa.

Trichodysplasia spinulosa (TS) is a disfiguring skin disease that occurs most frequently in patients receiving immunosuppressive therapies, and is thus frequently associated with organ transplantation. TS is characterized clinically by folliculocentric papular eruption, keratin spine formation and development of leonine face; and histologically by expansion of the inner root sheath epithelium and high expression of the proliferative marker Ki-67. Recent discovery of the TS-associated polyomavirus (TSPyV) and emerging studies demonstrating the role of TSPyV tumour antigens in cell proliferation pathways have opened a new corridor for research on TS. In this brief review, we summarize the clinical and histological features of TS and evaluate the current options for therapy. Furthermore, we address the viral aetiology of the disease and explore the mechanisms by which TSPyV may influence TS development and progression. As reports of TS continue to rise, clinician recognition of TS, as well as accompanying research on its underlying pathogenesis and therapeutic options, is becoming increasingly important. It is our hope that heightened clinical suspicion for TS will increase rates of diagnosis and will galvanize both molecular and clinical interest in this disease.

Alternating-Current InGaN/GaN Tunnel Junction Nanowire White-Light Emitting Diodes.

The current LED lighting technology relies on the use of a driver to convert alternating current (AC) to low-voltage direct current (DC) power, a resistive p-GaN contact layer to inject positive charge carriers (holes) for blue light emission, and rare-earth doped phosphors to down-convert blue photons into green/red light, which have been identified as some of the major factors limiting the device efficiency, light quality, and cost. Here, we show that multiple-active region phosphor-free InGaN nanowire white LEDs connected through a polarization engineered tunnel junction can fundamentally address the afore-described challenges. Such a p-GaN contact-free LED offers the benefit of carrier regeneration, leading to enhanced light intensity and reduced efficiency droop. Moreover, through the monolithic integration of p-GaN up and p-GaN down nanowire LED structures on the same substrate, we have demonstrated, for the first time, AC operated LEDs on a Si platform, which can operate efficiently in both polarities (positive and negative) of applied voltage.

Shape control and compartmentalization in active colloidal cells.

Small autonomous machines like biological cells or soft robots can convert energy input into control of function and form. It is desired that this behavior emerges spontaneously and can be easily switched over time. For this purpose we introduce an active matter system that is loosely inspired by biology and which we term an active colloidal cell. The active colloidal cell consists of a boundary and a fluid interior, both of which are built from identical rotating spinners whose activity creates convective flows. Similarly to biological cell motility, which is driven by cytoskeletal components spread throughout the entire volume of the cell, active colloidal cells are characterized by highly distributed energy conversion. We demonstrate that we can control the shape of the active colloidal cell and drive compartmentalization by varying the details of the boundary (hard vs. flexible) and the character of the spinners (passive vs. active). We report buckling of the boundary controlled by the pattern of boundary activity, as well as formation of core-shell and inverted Janus phase-separated configurations within the active cell interior. As the cell size is increased, the inverted Janus configuration spontaneously breaks its mirror symmetry. The result is a bubble-crescent configuration, which alternates between two degenerate states over time and exhibits collective migration of the fluid along the boundary. Our results are obtained using microscopic, non-momentum-conserving Langevin dynamics simulations and verified via a phase-field continuum model coupled to a Navier-Stokes equation.

Dental and Temporomandibular Joint Pathology of the Northern Fur Seal (Callorhinus ursinus).

Skulls from 145 northern fur seals (Callorhinus ursinus) were examined macroscopically according to predefined criteria. The museum specimens were acquired from strandings along the west coast of the USA between 1896 and 2008. Seventy-one skulls (49.0%) were from male animals, 56 (38.6%) from female animals and 18 (12.4%) from animals of unknown sex. Their age varied from juvenile to adult, with 58 adult animals (40.0%) and 87 juvenile animals (60.0%). The majority of teeth were available for examination (95.1%); 3.4% of teeth were artefactually absent, 0.8% were deemed absent due to acquired tooth loss and 0.6% were deemed congenitally absent. Males were no more likely than females to have either acquired tooth loss (P = 0.054) or congenitally absent teeth (P = 0.919). Adults had significantly more acquired tooth loss than juveniles (P = 0.0099). Malformations were seen in 11 teeth (0.2% of all 4,699 teeth available for examination). Two roots, instead of the typical one root, were found on 14 teeth (0.3%). Supernumerary teeth were associated with 14 normal teeth (0.3%) in eight specimens (5.5% of the total number of specimens). A total of 22 persistent deciduous teeth were found, 19 of which were associated with the maxillary canine teeth. Attrition/abrasion was seen on 194 teeth (3.9%); the canine teeth were most often affected, accounting for 39.7% of all abraded teeth. Adults were found to have a greater prevalence of abraded teeth than juveniles (P <0.0001). No significant difference was found in the appearance of attrition/abrasion between males and females (P = 0.072). Tooth fractures were found in 24 specimens (16.6%), affecting a total of 54 teeth (1.1%). Periapical lesions were found in two skulls (1.4%). None of the specimens showed signs of enamel hypoplasia. About a fifth (18.6%) of alveoli, either with or without teeth, showed signs of alveolar bony changes consistent with periodontitis. A total of 108 specimens (74.5%) had at least one tooth associated with mild periodontitis. Lesions consistent with temporomandibular joint osteoarthritis (TMJ-OA) were found in 29 specimens (20.0%). Both periodontal disease and TMJ-OA were significantly more common in adults than in juveniles (P <0.0001). Periodontitis was found to be more common in males than in females (P <0.012). Although the significance of the high incidence of periodontitis and TMJ-OA in the northern fur seal remains unknown, the occurrence and severity of these diseases found in this study may play an important role in this species morbidity and mortality.

Dental and Temporomandibular Joint Pathology of the Eastern Pacific Harbour Seal (Phoca vitulina richardii).

Skulls from 214 Eastern Pacific harbour seals (Phoca vitulina richardii) were examined macroscopically according to predefined criteria. The museum specimens were acquired from strandings along the west coast of the USA between 1909 and 2014. Ninety-eight skulls (45.8%) were from male animals, 108 (50.5%) from female animals and eight (3.7%) from animals of unknown sex. Their age varied from neonate to adult, with 101 adult animals (47.2%), 93 juvenile animals (43.5%) and 20 neonatal animals (9.3%). The majority of teeth were available for examination (90.0%); 7.5% of teeth were absent artefactually, 2.3% were deemed absent due to acquired tooth loss and 0.2% were absent congenitally. Males were no more likely than females to have either acquired tooth loss (P = 0.492) or congenitally absent teeth (P = 0.494). Adults had significantly more acquired tooth loss than juveniles (P <0.0001). All teeth were normal in morphology, except for four teeth from one skull that exhibited macrodontia. An unusual number of roots were found in most maxillary molar teeth; three roots were counted on six maxillary molar teeth and almost all other maxillary molar teeth available for examination had a fused root. Only 26 maxillary molar teeth exhibited two roots. Supernumerary teeth were associated with 13 normal teeth in nine specimens. The most common sites associated with supernumerary teeth were the left and right mandibular first premolar teeth (53.9% of all supernumerary teeth). No persistent deciduous teeth were found in any of the juvenile or adult specimens. Of the total number of teeth available for examination, 22.1% were abraded; six adult specimens showed attrition/abrasion on all of their teeth present. Adults were found to have a greater prevalence of abraded teeth than juveniles (P <0.0001). No significant difference was found in the appearance of attrition/abrasion between males and females (P = 0.518). Tooth fractures were uncommon, affecting 11 teeth (0.2%) in seven animals. Periapical lesions were found in four skulls (2.1% of the total number of specimens). None of the specimens showed signs of enamel hypoplasia. More than half (55.6%) of alveoli, either with or without teeth, showed signs of alveolar bony changes consistent with periodontitis. A total of 178 specimens (91.8%) had at least one tooth associated with mild periodontitis. Lesions consistent with temporomandibular joint osteoarthritis (TMJ-OA) were found in 67 specimens (34.5%). The most common articular surface to be affected was the left mandibular fossa of the temporal bone, with lesions in 44 cases (32.8% of all lesions). In 13 specimens (6.7%) all articular surfaces were affected. Both periodontal disease and TMJ-OA were significantly more common in adults than in juveniles (P <0.0001). Although the significance of the high incidence of periodontitis and TMJ-OA in the Eastern Pacific harbor seal remains unknown, the occurrence and severity of these diseases as found in this study may play an important role in the morbidity and mortality of this species.

Sugar Sag: Glycation and the Role of Diet in Aging Skin.

First described in the context of diabetes, advanced glycation end products (AGEs) are formed through a type of non-enzymatic reaction called glycation. Increased accumulation of AGEs in human tissue has now been associated with end stage renal disease, chronic obstructive pulmonary disease, and, recently, skin aging. Characteristic findings of aging skin, including decreased resistance to mechanical stress, impaired wound healing, and distorted dermal vasculature, can be in part attributable to glycation. Multiple factors mediate cutaneous senescence, and these factors are generally characterized as endogenous (e.g., telomere shortening) or exogenous (e.g., ultraviolet radiation exposure). Interestingly, AGEs exert their pathophysiological effects from both endogenous and exogenous routes. The former entails the consumption of sugar in the diet, which then covalently binds an electron from a donor molecule to form an AGE. The latter process mostly refers to the formation of AGEs through cooking. Recent studies have revealed that certain methods of food preparation (i.e., grilling, frying, and roasting) produce much higher levels of AGEs than water-based cooking methods such as boiling and steaming. Moreover, several dietary compounds have emerged as promising candidates for the inhibition of glycation-mediated aging. In this review, we summarize the evidence supporting the critical role of glycation in skin aging and highlight preliminary studies on dietary strategies that may be able to combat this process.

Improvement of the emission properties from InGaN/GaN dot-in-a-wire nanostructures after treatment in the flowing afterglow of a microwave N2 plasma.

Nominally pure GaN nanowires (NWs) and InGaN/GaN dot-in-a-wire heterostructures were exposed to the flowing afterglow of a N2 microwave plasma and characterized by photoluminescence (PL) spectroscopy. While the band-edge emission from GaN NWs and the GaN matrix of the InGaN/GaN NWs strongly decreased due to the creation of non-radiative recombination centers in the near-surface region, the emission from the InGaN dots strongly increased. PL excitation measurements indicate that such an increase cannot be explained by a plasma-induced shift of the GaN absorption edge. It is rather ascribed to the passivation of grown-in defects and dynamic annealing due to the presence of plasma-generated N atoms and N2 metastables without excessive introduction of ion-induced damage.

Recent approval of Xerese in Canada: 5% acyclovir and 1% hydrocortisone topical cream in the treatment of herpes labialis.

Herpes labialis is a frequently occurring viral infection of the lips and oral mucosa. Recurring lesions are induced by viral reactivation and replication, but the symptoms leading to morbidity, such as pain and inflammation, are immune-mediated. The introduction of 5% acyclovir/1% hydrocortisone in a topical cream (Xerese™) represents a therapeutic strategy directed at both of these pathogenic processes. Applied at the onset of prodromal symptoms, this combination treatment has a good safety profile and is more effective in reducing healing time than antiviral or anti-inflammatory agents alone. Although it was US FDA-approved for herpes labialis in 2009, Xerese™ has only recently been approved for use in Canada in October 2013. Herein, we review the basic science and clinical studies that support the efficacy of this topical combination acyclovir-hydrocortisone product in treating herpes labialis and examine its safety profile, as well as touch upon other therapies that have been shown to be effective in treating this common viral condition.

p-Type dopant incorporation and surface charge properties of catalyst-free GaN nanowires revealed by micro-Raman scattering and X-ray photoelectron spectroscopy.

Micro-Raman scattering and X-ray photoelectron spectroscopy were employed to investigate Mg-doped GaN nanowires. With the increase of Mg doping level, pronounced Mg-induced local vibrational modes were observed. The evolution of longitudinal optical phonon-plasmon coupled mode, together with detailed X-ray photoelectron spectroscopy studies, show that the near-surface region of nanowires can be transformed from weakly n-type to p-type with the increase of Mg doping.

Tuning the surface Fermi level on p-type gallium nitride nanowires for efficient overall water splitting.

Solar water splitting is one of the key steps in artificial photosynthesis for future carbon-neutral, storable and sustainable source of energy. Here we show that one of the major obstacles for achieving efficient and stable overall water splitting over the emerging nanostructured photocatalyst is directly related to the uncontrolled surface charge properties. By tuning the Fermi level on the nonpolar surfaces of gallium nitride nanowire arrays, we demonstrate that the quantum efficiency can be enhanced by more than two orders of magnitude. The internal quantum efficiency and activity on p-type gallium nitride nanowires can reach ~51% and ~4.0 mol hydrogen h(-1) g(-1), respectively. The nanowires remain virtually unchanged after over 50,000 µmol gas (hydrogen and oxygen) is produced, which is more than 10,000 times the amount of photocatalyst itself (~4.6 µmol). The essential role of Fermi-level tuning in balancing redox reactions and in enhancing the efficiency and stability is also elucidated.

Phase behavior of Janus colloids determined by sedimentation equilibrium.

We investigate the phase behavior of short-range interacting isotropic particles and single-patch Janus particles via simulations of sedimentation equilibrium, which allows for a rapid assessment of the equation of state and phase behavior directly from simulation. The methodology is tested against results by traditional methods and is found to yield good agreement for isotropic interactions. The method is then used to study single-patch Janus particles with different interaction strengths and patch sizes with particle area coverage greater than ∼0.63. Our results show an interplay between translational and orientational order. We observe a lamellar phase, a fluid phase and a rotator close-packed structure. The lamellar phase is shown to have a different range of stability than previously observed in simulation studies for systems of similar and longer-ranged interactions.