Wearable device for iontophoretic treatment and monitoring of pressure ulcers: Proof-of-concept.

This work demonstrates the feasibility of an all-in-one system for the detection, monitoring and treatment of pressure ulcers using two non-invasive methods, namely impedance spectroscopy and transdermal drug delivery by iontophoresis. The purpose of this device is to detect these chronic skin wounds at an early stage and treat them locally by delivering a vasodilator. The developed wearable flexible electrodes coupled to the compact electronic device used as a controlled current source show an increase in drug penetration by a factor of up to 8 for a current of 250 µA in comparison to passive diffusion.

[Prognostic value of the ELS grading system for assessment of laryngotracheal stenosis in children]. / Prognostische Aussagekraft der ELS-Klassifikation bei der Beurteilung laryngotrachealer Stenosen im Kindesalter.

BACKGROUND: In 2015, the European Laryngological Society (ELS) published a consensus paper in which a new classification system for laryngotracheal stenosis (LTS) was presented. This retrospective analysis investigates the classification's reliability and prognostic value regarding the outcome of surgical airway reconstruction in a pediatric population. MATERIALS AND METHODS: A total of 191 pediatric patients treated with cricotracheal or segmental resection were included. The ELS score was retrospectively calculated using information on the degree of stenosis, number of involved subsites, and presence of significant comorbidity. Reliability and prognostic value for airway restoration, surgical complications, and need of additional treatment were analyzed. RESULTS: Decannulation rate differed with regards to etiology (96% for acquired LTS, 86 and 87% for congenital and posttraumatic LTS, respectively). Decannulation was significantly more likely with 1-2 involved subsites than in LTS with 3-4 subsites (97 vs. 72%). The number of additional interventions after reconstruction was largely dependent on the number of involved subsites and the presence of significant comorbidity. CONCLUSION: The ELS score for LTS permits prognostically reliable classification and is thus a valuable tool for decision making, counseling of patients and relatives, and comparing treatment outcomes.

Androgenic and estrogenic indices in human newborns and infants: the MIREC-ID study.

Prenatal sex steroid exposure plays an important role in determining child development. Yet, measurement of prenatal hormonal exposure has been limited by the paucity of newborn/infant data and the invasiveness of fetal hormonal sampling. Here we provide descriptive data from the MIREC-ID study (n=173 girls; 162 boys) on a range of minimally invasive physical indices thought to reflect prenatal exposure to androgens [anogenital distances (AGDs); penile length/width, scrotal/vulvar pigmentation], to estrogens [vaginal maturation index (VMI) - the degree of maturation of vaginal wall cells] or to both androgens/estrogens [2nd-to-4th digit ratio (2D:4D); areolar pigmentation, triceps/sub-scapular skinfold thickness, arm circumference]. VMI was found to be associated with triceps skinfold thickness (ß=0.265, P=0.005), suggesting that this marker may be sensitive to estrogen levels produced by adipose tissue in girls. Both estrogenic and androgenic markers (VMI: ß=0.338, P=0.031; 2D:4D - right: ß=-0.207, P=0.040; left: ß=-0.276, P=0.006; AGD-fourchette - ß=0.253, P=0.036) were associated with areolar pigmentation in girls, supporting a role for the latter as an index of both androgen and estrogen exposure. We also found AGD-penis (distance from the anus to the penis) to be associated with scrotal pigmentation (ß=0.290, P=0.048), as well as right arm circumference (ß=0.462, P<0.0001), supporting the notion that these indices may be used together as markers of androgen exposure in boys. In sum, these findings support the use of several physical indices at birth to convey a more comprehensive picture of prenatal exposure to sex hormones.

Is maternal periconceptional smoking associated with 2D:4D digit ratio in their children?

The 2nd--4th finger ratio (2D:4D) has been proposed as a potential indicator of greater androgen exposure during fetal development. Maternal periconceptional smoking may alter the homeostasis of fetal androgens, which could in turn result in differential development of 2D:4Ds in utero. The aim of the present study was to assess the effect of maternal periconceptional smoking (i.e. 1 year before through the first trimester of pregnancy) on the 2D:4D of children within The Maternal-Infant Research on Environmental Chemicals (MIREC) study. Maternal smoking history was obtained through questionnaires during the first trimester of pregnancy in 2001 women from 10 cities across Canada. The periconceptional smoking prevalence was 12%. A follow-up study was conducted to measure growth and development up to 5 years of age in a subsample of some 800 MIREC children (MIREC-CD Plus), and digital pictures of the ventral surface of both hands were obtained in mothers and children (2-5 years). The 2D:4D was calculated as the ratio of the 2nd and 4th fingers of each hand. Boys had lower mean 2D:4Ds compared with girls in both hands. Age and maternal 2D:4D were strong determinants of the children's 2D:4D, however, the mean 2D:4D did not differ among children whose mothers had smoked during the periconceptional period compared with those who had not, irrespective of sex. In conclusion, we did not find an association between maternal periconceptional smoking and children's 2D:4D, although the smoking prevalence was low.

Management of severe congenital laryngeal webs - a 12 year review.

OBJECTIVE: The aim of this study was to investigate respiratory and voice outcomes after open surgery for severe congenital laryngeal web. METHODS: Included were all patients treated for severe congenital glottic web (Cohen type 3 and 4) between 2002 and 2014. Demographic data, symptoms, endoscopic findings, type of operation, outcome and complications were analyzed. Open surgery was performed with division of the web and enlargement of the subglottis by a laryngotracheal reconstruction or an extended partial cricotracheal resection. RESULTS: Fourteen patients were included. Information on the pre-operative voice was available in 11 patients. Aphonia was present in 6 patients (55%), dysphonia was severe in 1 (9%), moderate in 2 (18%) and mild in 2 (18%). Median age at operation was 19.3 months. As a first line treatment, laryngotracheal reconstruction was performed in 12 patients, and an extended partial cricotracheal resection in 2. Median follow-up was 9.5 months. All patients were successfully decannulated in a median time of 4 months after first surgery. Voice was improved in 10/11 (91%). Post-operatively, 3 patients (27%) had good voice. Dysphonia was severe in 2 (18%), moderate in 3 (27%) and mild in 3 patients (27%). CONCLUSION: Open surgery for Cohen type 3 and 4 glottic web allowed establishing a patent airway with successful decannulation in all cases. Quality of voice was improved in 91%, however, voice results were variable. In our opinion a delicate operative technique described in the paper is important for optimal voice results.

Female digit length ratio (2D:4D) and time-to-pregnancy.

STUDY QUESTION: Is the female 2th- to 4th-finger ratio (2D:4D) associated with fecundity as measured by time-to-pregnancy (TTP)? SUMMARY ANSWER: Our study does not support an association between female 2D:4D and TTP. WHAT IS KNOWN ALREADY: The 2th- to 4th-finger ratio (2D:4D) has been proposed as a potential indicator of greater androgen exposure during fetal development. Women exposed in utero to unbalanced steroid hormones may have impaired fecundity in the adulthood. Fecundity is often measured by TTP, an epidemiological tool commonly used to assess the impact of environmental factors in human conception. STUDY DESIGN, SIZE, DURATION: The Maternal-Infant Research on Environmental Chemicals (MIREC) Study is a pregnancy and birth cohort of 2001 women recruited before 14 weeks of gestation in 10 cities across Canada between 2008 and 2011. The present analysis is part of MIREC-CD Plus, a follow-up study in a subsample of some 800 MIREC mothers and their children from 2012 to 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: TTP and maternal characteristics were collected from questionnaires administered during the first trimester of pregnancy as part of the MIREC study. Digital pictures of the ventral surface of both hands were obtained in the MIREC mothers at the MIREC-CD Plus follow-up study. The 2D:4D was calculated as the ratio of the second and fourth fingers of each hand. The exposure of interest was the 2D:4D of the women categorized by tertiles, or dichotomized as ≥1 (index finger longer than the ring finger) or <1 (ring finger longer than the index finger, implying greater androgen exposure during fetal development). The final sample included 696 mothers. Statistical analyses included discrete-time Cox proportional hazard models, allowing adjustment for potential confounding factors. MAIN RESULTS AND THE ROLE OF CHANCE: There was no evidence of diminished/increased fecundability according to the 2D:4D, neither on the right nor on the left hand. In our analysis by tertiles, the smallest 2D:4D (i.e. higher androgen exposure during fetal life) resulted in FORs higher than 1 (i.e. shorter TTP) in both hands, although this was not statistically significant (FOR 1.19 [95% CI 0.93, 1.51] in the right hand and 1.16 [95% CI 0.91, 1.47] in the left hand). In the dichotomous analysis, 2D:4D <1 resulted in FORs higher than 1 (i.e. shorter TTP), but this was also not statistically significant (FOR 1.08 [95% CI 0.88, 1.33] in the right hand and 1.14 [95% CI 0.92, 1.42] in the left hand). Our large sample size resulted in a high statistical power to exclude an association between female 2D:4D and TTP. LIMITATIONS, REASONS FOR CAUTION: The MIREC Study is a cohort of pregnant women, and therefore, women with infertility were excluded by design from our study. WIDER IMPLICATIONS OF THE FINDINGS: Our data do not provide evidence for an association between female 2D:4D and fecundity as measured by TTP. Whether the female 2D:4D is a marker of in utero androgen exposure and whether it is associated with fecundity have yet to be determined. STUDY FUNDING/COMPETING INTEREST: The MIREC Study was funded by Health Canada's Chemicals Management Plan, the Canadian Institute of Health Research (CIHR grant # MOP - 81285), and the Ontario Ministry of the Environment. MIREC-CD Plus was funded by Health Canada's Chemicals Management Plan Research Fund. The 2D:4D component was funded by a research grant from the CIHR-Quebec Training Network in Perinatal Research (QTNPR). M.P. Vélez was supported by a CIHR Fellowship Award, and a QTNPR scholarship. P. Monnier is supported by the Research Institute of the McGill University Health Centre. W.D Fraser is supported by a CIHR Canada Research Chair. There are no conflicts of interest to declare.

Ultra-compact III‒V-on-Si photonic crystal memory for flip-flop operation at 5 Gb/s.

We report on a photonic crystal (PhC) nanolaser based on the heterogeneous integration of a III-V PhC nanocavity on SOI, configured to operate as a Set-Reset Flip-Flop (SR-FF). The active layer is a nanobeam cavity made of a 650 nm × 285 nm InP-based wire waveguide evanescently coupled to 500 nm × 220 nm SOI wire waveguides, demonstrating a record-low footprint of only 6.2 µm2. Injection locking enables optical bistability allowing for memory operation with only 6.4 fJ/bit switching energies and <50 ps response times. Bit-level SR-FF memory operation was evaluated at 5 Gb/s with PRBS-resembling data patterns, revealing error free operation with a negative power penalty.

ϒ-secretase and LARG mediate distinct RGMa activities to control appropriate layer targeting within the optic tectum.

While a great deal of progress has been made in understanding the molecular mechanisms that regulate retino-tectal mapping, the determinants that target retinal projections to specific layers of the optic tectum remain elusive. Here we show that two independent RGMa-peptides, C- and N-RGMa, activate two distinct intracellular pathways to regulate axonal growth. C-RGMa utilizes a Leukemia-associated RhoGEF (LARG)/Rho/Rock pathway to inhibit axonal growth. N-RGMa on the other hand relies on ϒ-secretase cleavage of the intracellular portion of Neogenin to generate an intracellular domain (NeICD) that uses LIM-only protein 4 (LMO4) to block growth. In the developing tectum (E18), overexpression of C-RGMa and dominant-negative LARG (LARG-PDZ) induced overshoots in the superficial tectal layer but not in deeper tectal layers. In younger embryos (E12), C-RGMa and LARG-PDZ prevented ectopic projections toward deeper tectal layers, indicating that C-RGMa may act as a barrier to descending axons. In contrast both N-RGMa and NeICD overexpression resulted in aberrant axonal-paths, all of which suggests that it is a repulsive guidance molecule. Thus, two RGMa fragments activate distinct pathways resulting in different axonal responses. These data reveal how retinal projections are targeted to the appropriate layer in their target tissue.

Targeting caspase-6 and caspase-8 to promote neuronal survival following ischemic stroke.

Previous studies show that caspase-6 and caspase-8 are involved in neuronal apoptosis and regenerative failure after trauma of the adult central nervous system (CNS). In this study, we evaluated whether caspase-6 or -8 inhibitors can reduce cerebral or retinal injury after ischemia. Cerebral infarct volume, relative to appropriate controls, was significantly reduced in groups treated with caspase-6 or -8 inhibitors. Concomitantly, these treatments also reduced neurological deficits, reduced edema, increased cell proliferation, and increased neurofilament levels in the injured cerebrum. Caspase-6 and -8 inhibitors, or siRNAs, also increased retinal ganglion cell survival at 14 days after ischemic injury. Caspase-6 or -8 inhibition also decreased caspase-3, -6, and caspase-8 cleavage when assayed by western blot and reduced caspase-3 and -6 activities in colorimetric assays. We have shown that caspase-6 or caspase-8 inhibition decreases the neuropathological consequences of cerebral or retinal infarction, thereby emphasizing their importance in ischemic neuronal degeneration. As such, caspase-6 and -8 are potential targets for future therapies aimed at attenuating the devastating functional losses that result from retinal or cerebral stroke.

Long-term outcomes following functional endoscopic sinus surgery in Samter's triad.

OBJECTIVE: This study aimed to assess the long-term outcome of functional endoscopic sinus surgery for Samter's triad patients using an objective visual analogue scale and nasal endoscopy. METHOD: Using a retrospective database, 33 Samter's triad patients who underwent functional endoscopic sinus surgery were evaluated pre- and post-operatively between 1987 and 2007 in Hospital of La Chaux-de-Fonds, Switzerland. RESULTS: A total of 33 patients participated in the study, and the mean follow-up period was 11.6 years (range 1.2-20 years). Patients were divided into two groups based on visual analogue scale scores of the five parameters with the greatest difference in intensity of symptoms between the beginning and end of follow up. Group 1 included patients with a mean visual analogue scale score of 6 and below at the end of follow up and group 2 included patients with a mean visual analogue scale score of more than 6. The only statistically significant difference noted between the two groups was the endonasal findings: stage III-IV polyposis was present in 1 out of 24 patients (4 per cent) in group 1 and in 5 out of 9 patients (56 per cent) in group 2. CONCLUSION: The results of our study indicate that functional endoscopic sinus surgery helps stabilise disease progression. Stage III-IV polyposis had a significant adverse effect on long-term outcome.

Exposure to phthalates, bisphenol A and metals in pregnancy and the association with impaired glucose tolerance and gestational diabetes mellitus: The MIREC study.

BACKGROUND: Studies from several countries report increases in rates of gestational diabetes mellitus (GDM) over recent decades. Exposure to environmental chemicals could contribute to this trend. OBJECTIVES: To determine the associations between plasticisers and metals measured in early pregnancy with impaired glucose tolerance (IGT) and GDM in a Canadian pregnancy cohort. METHODS: Women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study were included if they had a singleton delivery and did not have pre-existing diabetes. Eleven phthalate metabolites and total bisphenol A (BPA) were measured in first-trimester urine samples, and four metals (lead, cadmium, mercury and arsenic) were measured in first-trimester blood samples. IGT and GDM were assessed in accordance with standard guidelines by chart review. Chemical concentrations were grouped by quartiles, and associations with outcomes were examined using logistic regression with adjustment for maternal age, race, pre-pregnancy BMI, and education. Restricted cubic spline analysis was performed to help assess linearity and nature of any dose-response relationships. RESULTS: Of 2001 women recruited into the MIREC cohort, 1274 met the inclusion criteria and had outcome data and biomonitoring data measured for at least one of the chemicals we examined. Elevated odds of GDM were observed in the highest quartile of arsenic exposure (OR = 3.7, 95% CI = 1.4-9.6) in the adjusted analyses. A significant dose-response relationship was observed in a cubic spline model between arsenic and odds of GDM (p < 0.01). No statistically significant associations were observed between phthalates or BPA or other metals with IGT or GDM. CONCLUSIONS: Our findings add to the growing body of evidence supporting the role of maternal arsenic exposure as a risk factor for gestational diabetes.

Uncoupling Neogenin association with lipid rafts promotes neuronal survival and functional recovery after stroke.

The dependence receptor Neogenin and its ligand, the repulsive guidance molecule a (RGMa), regulate apoptosis and axonal growth in the developing and the adult central nervous system (CNS). Here, we show that this pathway has also a critical role in neuronal death following stroke, and that providing RGMa to neurons blocks Neogenin-induced death. Interestingly, the Neogenin pro-death function following ischemic insult depends on Neogenin association with lipid rafts. Thus, a peptide that prevents Neogenin association with lipid rafts increased neuronal survival in several in vitro stroke models. In rats, a pro-survival effect was also observed in a model of ocular ischemia, as well as after middle cerebral artery occlusion (MCAO). Treatments that prevented Neogenin association with lipid rafts improved neuronal survival and the complexity of the neuronal network following occlusion of the middle artery. Toward the development of a treatment for stroke, we developed a human anti-RGMa antibody that also prevents Neogenin association with lipid rafts. We show that this antibody also protected CNS tissue from ischemic damage and that its application resulted in a significant functional improvement even when administrated 6 h after artery occlusion. Thus, our results draw attention to the role of Neogenin and lipid rafts as potential targets following stroke.

Temporal ringdown of silicon-on-insulator racetrack resonators.

Ring-down temporal measurements of silicon-on-insulator wire racetrack resonators are performed with 150 fs input pulses using a parametric process in a nonlinear crystal to gate and amplify the weak output pulses. We measure the cavity round trip time and the quality factor of these all-pass filters and find excellent agreement with continuous wave spectroscopic measurements as well as with an analytic model built using numerical solutions for the fully vectorial waveguide modes.

Uniformity of the lasing wavelength of heterogeneously integrated InP microdisk lasers on SOI.

We report a high lasing wavelength uniformity of optically pumped InP-based microdisk lasers processed with electron-beam lithography, heterogeneously integrated with adhesive bonding on silicon-on-insulator (SOI) waveguide circuits and evanescently coupled to an underlying waveguide. We study the continuous wave laser emission coupling out of the SOI via a grating coupler etched at one side of the waveguide, and demonstrate a standard deviation in lasing wavelength of nominally identical devices on the same chip lower than 500 pm. The deviation in the diameter of the microdisks as low as a few nanometers makes all-optical signal processing applications requiring cascadability possible.

Evidence for synergism between cell death mechanisms in a cellular model of neurodegeneration in Parkinson's disease.

Delineation of how cell death mechanisms associated with Parkinson's disease (PD) interact and whether they converge would help identify targets for neuroprotective therapies. The purpose of this study was to use a cellular model to address these issues. Catecholaminergic SH-SY5Y neuroblastoma cells were exposed to a range of compounds (dopamine, rotenone, 5,8-dihydroxy-1,4-naphtho-107 quinone [naphthazarin], and Z-Ile-Glu(OBut)-Ala-Leu-al [PSI]) that are neurotoxic when applied to these cells for extended periods of times at specific concentrations. At the concentrations used, these compounds cause cellular stress via mechanisms that mimic those associated with causing neurodegeneration in PD, namely oxidative stress (dopamine), mitochondrial dysfunction (rotenone), lysosomal dysfunction (naphthazarin), and proteasomal dysfunction (PSI). The compounds were applied to the SH-SY5Y cells either alone or in pairs. When applied separately, the compounds produced a significant decrease in cell viability confirming that oxidative stress, mitochondrial, proteosomal, or lysosomal dysfunction can individually result in catecholaminergic cell death. When the compounds were applied in pairs, some of the combinations produced synergistic effects. Analysis of these interactions indicates that proteasomal, lysosomal, and mitochondrial dysfunction is exacerbated by dopamine-induced oxidative stress. Furthermore, inhibition of the proteasome or lysosome or increasing oxidative stress has a synergistic effect on cell viability when combined with mitochondrial dysfunction, suggesting that all cell death mechanisms impair mitochondrial function. Finally, we show that there are reciprocal relationships between oxidative stress, proteasomal dysfunction, and mitochondrial dysfunction, whereas lysosome dysfunction appears to mediate cell death via an independent pathway. Given the highly interactive nature of the various cell death mechanisms linked with PD, we predict that effective neuroprotective strategies should target multiple sites in these pathways, for example oxidative stress and mitochondria.

Hybrid III-V semiconductor/silicon nanolaser.

Heterogeneous integration of III-V compound semiconductors on Silicon on Insulator is one the key technology for next-generation on-chip optical interconnects. In this context, the use of photonic crystals lasers represents a disruptive solution in terms of footprint, activation energy and ultrafast response. In this work, we propose and fabricate very compact laser sources integrated with a passive silicon waveguide circuitry. Using a subjacent Silicon-On-Insulator waveguide, the emitted light from a photonic crystal based cavity laser is efficiently captured. We study experimentally the evanescent wave coupling responsible for the funneling of the emitted light into the silicon waveguide mode as a function of the hybrid structure parameters, showing that 90% of coupling efficiency is possible.

Slow light propagation in a ring erbium-doped fiber.

Slow light propagation is demonstrated by implementing Coherent Population Oscillations in a silica fiber doped with erbium ions in a ring surrounding the single mode core. Though only the wings of the mode interact with erbium ions, group velocities around 1360 m/s are obtained without any spatial distortion of the propagating mode.

The repulsive guidance molecule, RGMa, promotes retinal ganglion cell survival in vitro and in vivo.

The repulsive guidance molecule, RGMa, and its receptor Neogenin, regulate neuronal cell death during development, but little is known about their expression and roles in the adult CNS. Here, we show that Neogenin is expressed in the adult rodent retina, particularly on retinal ganglion cells. To determine whether the Neogenin/RGMa pathway is important in the fully developed retina, we examined its contribution to damage-induced neurodegeneration. The effects of RGMa on survival of retinal ganglion cells (RGCs) were examined in vitro and in vivo. Using cultured whole-mount retinal explants, we showed that the addition of RGMa increased RGC survival and that this effect was mediated by the Neogenin receptor. Immunohistochemical analysis indicated that the inhibition of cell death by RGMa resulted from reduced caspase-3 activation. Then, using an in vivo model of RGC apoptosis after optic nerve transection, we demonstrated that intraocular injection of RGMa at 3 and 7 days after axotomy greatly reduced RGC death 14 days postaxotomy. This study provides the first evidence that RGMa is a molecular target for neuroprotection in retinal pathologies, and suggests that targeting "dependence receptors" such as Neogenin has therapeutic potential for the treatment of neuropathologies in the adult CNS.

Small volume excitation and enhancement of dye fluorescence on a 2D photonic crystal surface.

We demonstrate an easy-to-implement scheme for fluorescence enhancement and observation volume reduction using photonic crystals (PhCs) as substrates for microscopy. By normal incidence coupling to slow 2D-PhC guided modes, a 65 fold enhancement in the excitation is achieved in the near field region (100 nm deep and 1 microm wide) of the resonant mode. Such large enhancement together with the high spatial resolution makes this device an excellent substrate for fluorescence microscopies.

Primary meningioma of the middle ear: case report.

OBJECTIVE: To report a rare case of primary meningioma of the middle ear. METHOD: We describe the case of a 55-year-old woman who presented with decreased hearing and fullness in the left ear, with a middle-ear mass. We also review the world literature regarding primary extracranial meningioma of the middle ear and its management. RESULTS: Primary middle-ear meningioma, a rare clinical entity, was diagnosed in this patient based on an initial transmastoid biopsy. Magnetic resonance imaging with gadolinium enhancement excluded the presence of an intracranial component. Complete excision of the tumour was achieved using a combined approach tympanoplasty. The patient had an uneventful post-operative course. CONCLUSION: Meningiomas, although rare in the middle ear, need to be included in the differential diagnosis of middle-ear lesions presenting to the otolaryngologist. This case emphasises the management strategy required when dealing with a middle-ear mass.