Microneedle applications in improving skin appearance

Microneedles (MNs) are micron-sized, minimally invasive devices that breach the outermost layer of the skin, the stratum corneum (SC), creating transient, aqueous pores in the skin and facilitating the transport of therapeutic molecules into the epidermis. Following many years of extensive research in the area of MN-mediated trans- and intra-dermal drug delivery, MNs are now being exploited in the cosmeceutical industry as a means of disrupting skin cell architecture, inducing elastin and collagen expression and deposition. They are also being used as vehicles to deliver cosmeceutic molecules across the skin, in addition to their use in combinatorial treatments with topical agents or light sources. This review explores the chronology of microneedling methodologies, which has led to the emergence of MN devices, now extensively used in cosmeceutical applications. Recent developments in therapeutic molecule and peptide delivery to the skin via MN platforms are addressed and some commercially available MN devices are described. Important safety and regulatory considerations relating to MN usage are addressed, as are studies relating to public perception of MN, as these will undoubtedly influence the acceptance of MN products as they progress towards commercialisation.

De novo sequencing of two novel peptides homologous to calcitonin-like peptides, from skin secretion of the Chinese Frog, Odorrana schmackeri

An MS/MS based analytical strategy was followed to solve the complete sequence of two new peptides from frog (Odorrana schmackeri) skin secretion. This involved reduction and alkylation with two different alkylating agents followed by high resolution tandem mass spectrometry. De novo sequencing was achieved by complementary CID and ETD fragmentations of full-length peptides and of selected tryptic fragments. Heavy and light isotope dimethyl labeling assisted with annotation of sequence ion series. The identified primary structures are GCD[I/L]STCATHN[I/L]VNE[I/L]NKFDKSKPSSGGVGPESP-NH2 and SCNLSTCATHNLVNELNKFDKSKPSSGGVGPESF-NH2, i.e. two carboxyamidated 34 residue peptides with an aminoterminal intramolecular ring structure formed by a disulfide bridge between Cys2 and Cys7. Edman degradation analysis of the second peptide positively confirmed the exact sequence, resolving I/L discriminations. Both peptide sequences are novel and share homology with calcitonin, calcitonin gene related peptide (CGRP) and adrenomedullin from other vertebrates. Detailed sequence analysis as well as the 34 residue length of both O. schmackeri peptides, suggest they do not fully qualify as either calcitonins (32 residues) or CGRPs (37 amino acids) and may justify their classification in a novel peptide family within the calcitonin gene related peptide superfamily. Smooth muscle contractility assays with synthetic replicas of the S–S linked peptides on rat tail artery, uterus, bladder and ileum did not reveal myotropic activity.

pLR-HL: a novel amphibian Bowman-Birk-type trypsin inhibitor from the skin secretion of the broad-folded frog, Hylarana latouchii

In this study, we report a novel heptadecapeptide (LIGGCWTKSIPPKPCLV) of the pLR/ranacyclin family, named pLR-HL, whose structure was deduced from its biosynthetic precursor-encoding cDNA cloned from the skin secretion-derived cDNA library of the broad-folded frog, Hylarana latouchii, by employing a "shotgun" cloning technique. It contains a disulphide loop between Cys5 and Cys15 which is consistent with Bowman-Birk-type protease inhibitors. The primary structure of pLR-HL deduced from the cDNA sequence was confirmed by fractionating the skin secretion using reverse phase HPLC and subsequent analysis using MALDI-TOF mass spectrometry and LC/MS/MS fragmentation sequencing. On the basis of the establishment of unequivocal amino acid sequence, a synthetic replicate was synthesised by solid-phase Fmoc chemistry, and it displayed a moderately potent trypsin inhibition with a Ki of 143 nM. The substitution of Lys-8 by Phe (Phe8 -pLR-HL) resulted in abolition of trypsin inhibition but generation of modest inhibition on chymotrypsin with a Ki of 2.141 μM. Additionally, both the disulphide loops of pLR-HL and Phe8 -pLR-HL were synthesised and tested. Both of the catalytic loops retained similar inhibitory potencies towards trypsin or chymotrypsin in comparison with the original intact molecules. Thus, the replacement of reactive site residues could alter the specificity of these protease inhibitors, while the canonical reactive loop alone can independently constitute biologically-active moiety.

PH-sauvagine from the skin secretion of Phyllomedusa hypochondrialis: a novel CRF-like peptide with smooth muscle contraction activity

Amphibian skin, and particularly that of south/Central American phyllomedusine frogs, is supposed to be "a huge factory and store house of a variety of active peptides". The 40 amino acid amphibian CRF-like peptide, sauvagine, is a prototype member of a unique family of these Phyllomedusa skin peptides. In this study, we describe for the first time the structure of a mature novel peptide from the skin secretion of the South American orange-legged leaf frog, Phyllomedusa hypochondrialis, which belongs to the amphibian CRF/sauvagine family. Partial amino acid sequence from the N-terminal was obtained by automated Edman degradation with the following structure: pGlu-GPPISIDLNMELLRNMIEI-. The biosynthetic precursor of this novel sauvagine peptide, consisted of 85 amino acid residues and was deduced from cDNA library constructed from the same skin secretion. Compared with the standard sauvagine from the frog, Phyllomedusa sauvagei, this novel peptide was found to exert similar contraction effects on isolated guinea-pig colon and rat urinary bladder smooth muscle preparations.

Concussion and Brain Injury in Contact Sport: Legal Implications

A concussed participant leaving the field of play is one of the most worrying sights in sport. It is also one that might have serious legal implications for sports governing bodies. Over the past number of years, a major class action suit has rumbled through the US courts as taken against that country's biggest professional sport, the National Football League. The NFL is at present attempting to settle the lawsuit from more than 4,500 retired players who claim that the NFL knew for decades about the chronic health risks associated with cumulative concussions in American football but failed to warn players or take preventative steps. Testimony from retired NFL players has revealed stories of chronic headaches, Alzheimer-like forgetfulness, altered personalities and sometimes a downward spiral into depression, violence and suicide. Medical research is suggesting that professional American football players are three times more likely to die as a result of certain neurodegenerative diseases than the general population. This paper notes that the concerns about concussion are not confined to the NFL and extend to contact sport more widely and notably rugby union. This paper also assesses the reaction of leading sports governing bodies globally to the recorded medical risks and accompanying legal vulnerabilities.

Acute skin GVHD following syngeneic BMT for CLL

A 41-year-old woman received a syngeneic BMT for CLL and subsequently developed acute skin GVHD. Transfusion-related allogeneic GVHD was excluded on the basis of an unchanged HLA type in circulating lymphocytes. Short tandem repeat PCR was used to confirm syngeneicity between donor and recipient. The patient had a personal and family history of autoimmune disease which may have made her particularly susceptible to development of syngeneic GVHD. The distinction between allogeneic and syngeneic or autologous GVHD is important because of therapeutic implications.

Wing Panel Design with Novel Skin-Buckling Containment Features

The impact of buckling containment features on the stability of thin-gauge fuselage, metallic stiffened panels has previously been demonstrated. With the continuing developments in manufacturing technology, such as welding, extrusion, machining, and additive layer manufacture, understanding the benefits of additional panel design features on heavier applications, such as wing panels, is timely. This compression testing of thick-gauge panels with and without buckling containment features has been undertaken to verify buckling and collapse behaviors and validate sizing methods. The experimental results demonstrated individual panel mass savings on the order of 9%, and wing cover design studies demonstrated mass savings on the order of 4 to 13%, dependent on aircraft size and material choice.

Spinal cord injury reveals multilineage differentiation of ependymal cells

Spinal cord injury often results in permanent functional impairment. Neural stem cells present in the adult spinal cord can be expanded in vitro and improve recovery when transplanted to the injured spinal cord, demonstrating the presence of cells that can promote regeneration but that normally fail to do so efficiently. Using genetic fate mapping, we show that close to all in vitro neural stem cell potential in the adult spinal cord resides within the population of ependymal cells lining the central canal. These cells are recruited by spinal cord injury and produce not only scar-forming glial cells, but also, to a lesser degree, oligodendrocytes. Modulating the fate of ependymal progeny after spinal cord injury may offer an alternative to cell transplantation for cell replacement therapies in spinal cord injury.

Assessment of the double-skin façade passive thermal buffer effect.

Double Skin Façades (DSFs) are becoming increasingly popular architecture for commercial office buildings. Although DSFs are widely accepted to have the capacity to offer significant passive benefits and enable low energy building performance, there remains a paucity of knowledge with regard to their operation. Identification of the most determinant architectural parameters of DSFs is the focus of ongoing research. This paper presents an experimental and simulation study of a DSF installed on a commercial building in Dublin, Ireland. The DSF is south facing and acts to buffer the building from winter heat losses, but risks enhancing over-heating on sunny days. The façade is extensively monitored during winter months. Computational Fluid Dynamic (CFD) models are used to simulate the convective operation of the DSF. This research concludes DSFs as suited for passive, low energy architecture in temperature climates such as Ireland but identifies issues requiring attention in DSF design.

Technological aids for the rehabilitation of memory and executive functioning in children and adolescents with acquired brain injury (Review).

Background The use of technology in healthcare settings is on the increase and may represent a cost-effective means of delivering rehabilitation. Reductions in treatment time, and delivery in the home, are also thought to be benefits of this approach. Children and adolescents with brain injury often experience deficits in memory and executive functioning that can negatively affect their school work, social lives, and future occupations. Effective interventions that can be delivered at home, without the need for high-cost clinical involvement, could provide a means to address a current lack of provision. We have systematically reviewed studies examining the effects of technology-based interventions for the rehabilitation of deficits in memory and executive functioning in children and adolescents with acquired brain injury. Objectives To assess the effects of technology-based interventions compared to placebo intervention, no treatment, or other types of intervention, on the executive functioning and memory of children and adolescents with acquired brain injury. Search methods We ran the search on the 30 September 2015. We searched the Cochrane Injuries Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), EMBASE Classic + EMBASE (OvidSP), ISI Web of Science (SCI-EXPANDED, SSCI, CPCI-S, and CPSI-SSH), CINAHL Plus (EBSCO), two other databases, and clinical trials registers. We also searched the internet, screened reference lists, and contacted authors of included studies. Selection criteria Randomised controlled trials comparing the use of a technological aid for the rehabilitation of children and adolescents with memory or executive-functioning deficits with placebo, no treatment, or another intervention. Data collection and analysis Two review authors independently reviewed titles and abstracts identified by the search strategy. Following retrieval of full-text manuscripts, two review authors independently performed data extraction and assessed the risk of bias. Main results Four studies (involving 206 participants) met the inclusion criteria for this review. Three studies, involving 194 participants, assessed the effects of online interventions to target executive functioning (that is monitoring and changing behaviour, problem solving, planning, etc.). These studies, which were all conducted by the same research team, compared online interventions against a 'placebo' (participants were given internet resources on brain injury). The interventions were delivered in the family home with additional support or training, or both, from a psychologist or doctoral student. The fourth study investigated the use of a computer program to target memory in addition to components of executive functioning (that is attention, organisation, and problem solving). No information on the study setting was provided, however a speech-language pathologist, teacher, or occupational therapist accompanied participants. Two studies assessed adolescents and young adults with mild to severe traumatic brain injury (TBI), while the remaining two studies assessed children and adolescents with moderate to severe TBI. Risk of bias We assessed the risk of selection bias as low for three studies and unclear for one study. Allocation bias was high in two studies, unclear in one study, and low in one study. Only one study (n = 120) was able to conceal allocation from participants, therefore overall selection bias was assessed as high. One study took steps to conceal assessors from allocation (low risk of detection bias), while the other three did not do so (high risk of detection bias). Primary outcome 1: Executive functioning: Technology-based intervention versus placebo Results from meta-analysis of three studies (n = 194) comparing online interventions with a placebo for children and adolescents with TBI, favoured the intervention immediately post-treatment (standardised mean difference (SMD) -0.37, 95% confidence interval (CI) -0.66 to -0.09; P = 0.62; I2 = 0%). (As there is no 'gold standard' measure in the field, we have not translated the SMD back to any particular scale.) This result is thought to represent only a small to medium effect size (using Cohen’s rule of thumb, where 0.2 is a small effect, 0.5 a medium one, and 0.8 or above is a large effect); this is unlikely to have a clinically important effect on the participant. The fourth study (n = 12) reported differences between the intervention and control groups on problem solving (an important component of executive functioning). No means or standard deviations were presented for this outcome, therefore an effect size could not be calculated. The quality of evidence for this outcome according to GRADE was very low. This means future research is highly likely to change the estimate of effect. Primary outcome 2: Memory One small study (n = 12) reported a statistically significant difference in improvement in sentence recall between the intervention and control group following an eight-week remediation programme. No means or standard deviations were presented for this outcome, therefore an effect size could not be calculated. Secondary outcomes Two studies (n = 158) reported on anxiety/depression as measured by the Child Behavior Checklist (CBCL) and were included in a meta-analysis. We found no evidence of an effect with the intervention (mean difference -5.59, 95% CI -11.46 to 0.28; I2 = 53%). The GRADE quality of evidence for this outcome was very low, meaning future research is likely to change the estimate of effect. A single study sought to record adverse events and reported none. Two studies reported on use of the intervention (range 0 to 13 and 1 to 24 sessions). One study reported on social functioning/social competence and found no effect. The included studies reported no data for other secondary outcomes (that is quality of life and academic achievement). Authors' conclusions This review provides low-quality evidence for the use of technology-based interventions in the rehabilitation of executive functions and memory for children and adolescents with TBI. As all of the included studies contained relatively small numbers of participants (12 to 120), our findings should be interpreted with caution. The involvement of a clinician or therapist, rather than use of the technology, may have led to the success of these interventions. Future research should seek to replicate these findings with larger samples, in other regions, using ecologically valid outcome measures, and reduced clinician involvement.

Experimental analysis of air flow profiles in a double skin facade in a maritime climate

Glazed Double Skin Facades (DSF) offer the potential to improve the performance of all-glass building skins, common to commercial office buildings in which full facade glazing has almost become the standard. Single skin glazing results in increased heating and cooling costs over opaque walls, due to lower thermal resistance of glass, and the increased impact of solar gain through it. However, the performance benefit of DSF technology continues to be questioned and its operation poorly understood, particularly the nature of airflow through the cavity. This paper deals specifically with the experimental analysis of the air flow characteristics in an automated double skin façade. The benefit of the DSF as a thermal buffer, and to limit overheating is evaluated through analysis of an extensive set of parameters including air and surface temperatures at each level in the DSF, airflow readings in the cavity and at the inlet and outlet, solar and wind data, and analytically derived pressure differentials. The temperature and air-flow are monitored in the cavity of a DSF using wireless sensors and hot wire anemometers respectively. Automated louvre operation and building set-points are monitored via the BMS. Thermal stratification and air flow variation during changing weather conditions are shown to effect the performance of the DSF considerably and hence the energy performance of the building. The relative pressure effects due to buoyancy and wind are analysed and quantified. This research aims to developed and validate models of DSFs in the maritime climate, using multi-season data from experimental monitoring. This extensive experimental study provides data for training and validation of models.

Towards a Mobile Assistive Technology for Monitoring and Assessing Cognitive Fatigue in Individuals with Acquired Brain Injury

Those living with an acquired brain injury often have issues with fatigue due to factors resulting from the injury. Cognitive impairments such as lack of memory, concentration and planning have a great impact on an individual’s ability to carry out general everyday tasks, which subsequently has the effect of inducing cognitive fatigue. Moreover, there is difficulty in assessing cognitive fatigue, as there are no real biological markers that can be measured. Rather, it is a very subjective effect that can only be diagnosed by the individual. Consequently, the traditional way of assessing cognitive fatigue is to use a self-assessment questionnaire that is able to determine contributing factors. State of the art methods to evaluate cognitive! fa tigue employ cognitive tests in order to analyse performance on predefined tasks. However, one primary issue with such tests is that they are typically carried out in a clinical environment, therefore do not have the ability to be utilized in situ within everyday life. This paper presents a smartphone application for the evaluation of fatigue, which can be used daily to track cognitive performance in order to assess the influence of fatigue.