Ultraviolet Protection From a Patented Amino Acid Complex Technology.

OBJECTIVE:   This study aimed to investigate the ultraviolet (UV) protection/repair benefits of a patented Amino Acid Complex (AAComplex). METHODS: I) AAComplex was incubated with dermal fibroblasts, with/without UVA, and collagen I was measured with a GlasBoxPlus device. II) A lotion, with/without AAComplex (1%) was applied topically to skin explants, following UVA irradiation, and quantified for health-related biomarkers (TNFalpha, histamine, and MMP-1). III) A broad spectrum sunscreen with SPF 46 and a skincare serum containing AAComplex (2%) were assessed using epidermal equivalents, in the presence of UV irradiation, for effects on IL-1alpha, thymine dimers, Ki-67, filaggrin and Nrf2. RESULTS: I) Collagen I synthesis in dermal fibroblasts was significantly decreased after UVA compared to without UV. The presence of AAComplex prevented this decrease. II) UVA irradiation of skin explants increased histamine, TNFα, and MMP-1. Hydrocortisone aceponate cream significantly decreases all 3 biomarkers. AAComplex contained lotion also significantly decreased all 3 biomarkers, the no AAComplex control lotion only reduced histamine. III) With the regimen of sunscreen + AAComplex contained skincare serum, the significant reduction in IL-1alpha was observed along with a complete recovery of Ki-67 and stimulation of filaggrin and Nrf2T. No thymine dimer positive cell was observed indicating the most positive skin impact from the regiment.  Conclusion: This research using different human skin models demonstrated that AAComplex can provide protection and damage repair caused by UV, at the ingredient level also when formulated in a serum or lotion formula. Skin may be best protected from UV damage when the regimen is used.   J Drugs Dermatol. 2024;23(5):366-375. doi:10.36849/JDD.7916.

In vitro, ex vivo, instrumental and clinical evaluation of a topical cream on the signs of periorbital ageing.

OBJECTIVE: Periorbital skin ageing signs are multidimensional, highly visible and a concern for many. We evaluated the potential efficacy of an eye cream to diminish these signs. METHODS: Biological markers associated with ageing, barrier function and homeostasis were analysed in vitro to determine the effects of topically applied eye cream, compared to those of a placebo using human skin tissue models and/or explants. Collagen IV, elastin and bone morphogenic protein 4 (BMP4) expression was investigated by immunohistochemical labelling, while filaggrin, kallikrein 7 (KLK7) and HB-EGF were evaluated by RT-qPCR. IL-1α and melanin levels in darkly pigmented skin models were also quantified. The protective effect of the cream on glycation was assessed by a non-enzymatic assay. Finally, the benefits of twice-daily applications of the eye cream for 56 days were instrumentally and clinically evaluated on 33 women. RESULTS: Only the eye cream, not the placebo, stimulated collagen IV and BMP4 protein expression, as well as increased elastin fibre length. It also led to higher HB-EGF, filaggrin and KLK7 mRNA levels. The placebo and the eye cream did not induce changes in IL-1α and melanin levels, but both reduced non-enzymatic glycation. When assessing the in vivo effects of the cream, short-term results indicated skin hydration, transepidermal water loss (TEWL) and skin profilometry improvement within 15 min. Instrumental evaluations of wrinkles showed a reduction after 7 days, which was clinically perceivable after 28 or 56 days. The eye-opening angle and eyelid sagging also improved after seven and 28 days, respectively. Finally, dark circles became lighter within 7 days (instrumental measurement) or 28 days (clinical assessment). CONCLUSION: The instrumental and clinical evaluations revealed that the eye cream reduced all periorbital ageing signs evaluated. Its effects are supported by the in vitro and ex vivo analyses of molecular markers.

OBJECTIF: Les signes de vieillissement de la peau périorbitaire sont nombreux, très visibles et préoccupent de nombreuses personnes. Nous avons évalué l'efficacité potentielle d'une crème pour les yeux pour atténuer ces signes. MÉTHODES: Les marqueurs biologiques associés au vieillissement, à la fonction barrière et à l'homéostasie de la peau ont été analysés in vitro pour évaluer l'efficacité d'une crème pour les yeux appliquée localement. Ces effets ont été comparés à ceux d'un placebo, sur des modèles et/ou des explants de tissus cutanés humains. L'expression du collagène IV, de l'élastine et de la protéine morphogénique osseuse 4 (BMP4) a été étudiée par marquage immunohistochimique. Celle de la filaggrine, de la kallikréine 7 (KLK7), et du HB­EGF par RT­qPCR. Les niveaux d'IL­1α et de mélanine dans un modèle de peau pigmentée ont également été quantifiés. L'effet protecteur de la crème sur la glycation a été évalué par un test non enzymatique. Enfin, les bénéfices d'une application biquotidienne de la crème pour les yeux ont été évalués instrumentalement et cliniquement sur 33 femmes pendant 56 jours. RÉSULTATS: Seule la crème pour les yeux a stimulé l'expression du collagène IV et de BMP4 en comparaison avec le placebo. La crème est aussi la seule à augmenter la longueur des fibres d'élastine. Elle a également entraîné une augmentation des niveaux d'ARNm de HB­EGF, de la filaggrine et de KLK7. Le placebo et la crème pour les yeux n'ont pas modifié les niveaux d'IL­1α et de la mélanine, mais ont tous deux réduit la glycation non enzymatique. Lors de l'évaluation des effets in vivo, les résultats à court terme ont montré une amélioration de l'hydratation de la peau, de la Perte Insensible en Eau (PIE) et du profil de la peau en 15 min. Les évaluations instrumentales de la profondeur des rides ont indiqué une réduction après 7 jours d'application, réduction cliniquement perceptible après 28 ou 56 jours. La crème périorbitale induit également une amélioration de l'angle d'ouverture des yeux et de l'affaissement des paupières respectivement après 7 et 28 jours. Enfin, les cernes sont devenus plus clairs après 7 jours (mesure instrumentale) ou 28 jours (évaluation clinique). CONCLUSION: Les évaluations instrumentales et cliniques ont révélé que la crème pour les yeux réduisait tous les signes de vieillissement périorbitaires évalués. Ses effets sont confirmés par les analyses in vitro et ex vivo des marqueurs moléculaires.

Illness-related communication between siblings and parents of children with chronic illness and life-limiting conditions: A qualitative analysis.

BACKGROUND: Having a brother or sister who has a chronic illness (lasting >6 months and requiring long-term care) or life-limiting condition (LLC; where cure is highly unlikely and the child is expected to die) has major impacts on siblings. Parent-sibling illness-related communication may contribute to siblings' capacity to cope. OBJECTIVES: In this study, we aimed to explore parent-sibling illness-related communication, from the perspectives of parents and siblings. We also aimed to qualitatively compare participants' responses according to illness group (chronic illness vs. LLCs). METHODS: We collected qualitative data from siblings (32 with a brother/sister with a chronic illness, 37 with a brother/sister with an LLC) and parents of a child with a chronic illness (n = 86) or LLC (n = 38) using purpose-designed, open-ended survey questions regarding illness-related communication. We used an inductive qualitative content analysis and matrix coding to explore themes and compare across illness groups. RESULTS: Two-thirds of siblings expressed satisfaction with their family's illness-related communication. Siblings typically reported satisfaction with communication when it was open and age-appropriate, and reported dissatisfaction when information was withheld or they felt overwhelmed with more information than they could manage. Parents generally favored an open communication style with the siblings, though this was more common among parents of children with an LLC than chronic illness. SIGNIFICANCE OF RESULTS: Our findings show that while many siblings shared that they felt satisfied with familial illness-related communication, parents should enquire with the siblings about their communication preferences in order to tailor illness-related information to the child's maturity level, distress, and age.

Unraveling a century of global change impacts on winter bird distributions in the eastern United States.

One of the most pressing questions in ecology and conservation centers on disentangling the relative impacts of concurrent global change drivers, climate and land-use/land-cover (LULC), on biodiversity. Yet studies that evaluate the effects of both drivers on species' winter distributions remain scarce, hampering our ability to develop full-annual-cycle conservation strategies. Additionally, understanding how groups of species differentially respond to climate versus LULC change is vital for efforts to enhance bird community resilience to future environmental change. We analyzed long-term changes in winter occurrence of 89 species across nine bird groups over a 90-year period within the eastern United States using Audubon Christmas Bird Count (CBC) data. We estimated variation in occurrence probability of each group as a function of spatial and temporal variation in winter climate (minimum temperature, cumulative precipitation) and LULC (proportion of group-specific and anthropogenic habitats within CBC circle). We reveal that spatial variation in bird occurrence probability was consistently explained by climate across all nine species groups. Conversely, LULC change explained more than twice the temporal variation (i.e., decadal changes) in bird occurrence probability than climate change on average across groups. This pattern was largely driven by habitat-constrained species (e.g., grassland birds, waterbirds), whereas decadal changes in occurrence probabilities of habitat-unconstrained species (e.g., forest passerines, mixed habitat birds) were equally explained by both climate and LULC changes over the last century. We conclude that climate has generally governed the winter occurrence of avifauna in space and time, while LULC change has played a pivotal role in driving distributional dynamics of species with limited and declining habitat availability. Effective land management will be critical for improving species' resilience to climate change, especially during a season of relative resource scarcity and critical energetic trade-offs.

Subventricular zone neural precursor cell responses after traumatic brain injury and binge alcohol in male rats.

Traumatic brain injury (TBI) is a major cause of disability worldwide. Additionally, many TBI patients are intoxicated with alcohol at the time of injury, but the impact of acute intoxication on recovery from brain injury is not well understood. We have previously found that binge alcohol prior to TBI impairs spontaneous functional sensorimotor recovery. However, whether alcohol administration in this setting affects reactive neurogenesis after TBI is not known. This study, therefore, sought to determine the short- and long-term effects of pre-TBI binge alcohol on neural precursor cell responses in the subventricular zone (SVZ) following brain injury in male rats. We found that TBI alone significantly increased proliferation in the SVZ as early as 24 hr after injury. Surprisingly, binge alcohol alone also significantly increased proliferation in the SVZ after 24 hr. However, a combined binge alcohol and TBI regimen resulted in decreased TBI-induced proliferation in the SVZ at 24 hr and 1 week post-TBI. Furthermore, at 6 weeks after TBI, binge alcohol administered at the time of TBI significantly decreased the TBI-induced neuroblast response in the SVZ and the rostral migratory stream (RMS). The results from this study suggest that pre-TBI binge alcohol negatively impacts reparative processes in the brain by decreasing short-term neural precursor cell proliferative responses as well as long-term neuroblasts in the SVZ and RMS.

Targeted gene mutation of E2F1 evokes age-dependent synaptic disruption and behavioral deficits.

Aberrant expression and activation of the cell cycle protein E2F1 in neurons has been implicated in many neurodegenerative diseases. As a transcription factor regulating G1 to S phase progression in proliferative cells, E2F1 is often up-regulated and activated in models of neuronal death. However, despite its well-studied functions in neuronal death, little is known regarding the role of E2F1 in the mature brain. In this study, we used a combined approach to study the effect of E2F1 gene disruption on mouse behavior and brain biochemistry. We identified significant age-dependent olfactory and memory-related deficits in E2f1 mutant mice. In addition, we found that E2F1 exhibits punctated staining and localizes closely to the synapse. Furthermore, we found a mirroring age-dependent loss of post-synaptic protein-95 in the hippocampus and olfactory bulb as well as a global loss of several other synaptic proteins. Coincidently, E2F1 expression is significantly elevated at the ages, in which behavioral and synaptic perturbations were observed. Finally, we show that deficits in adult neurogenesis persist late in aged E2f1 mutant mice which may partially contribute to the behavior phenotypes. Taken together, our data suggest that the disruption of E2F1 function leads to specific age-dependent behavioral deficits and synaptic perturbations. E2F1 is a transcription factor regulating cell cycle progression and apoptosis. Although E2F1 dysregulation under toxic conditions can lead to neuronal death, little is known about its physiologic activity in the healthy brain. Here, we report significant age-dependent olfactory and memory deficits in mice with dysfunctional E2F1. Coincident with these behavioral changes, we also found age-matched synaptic disruption and persisting reduction in adult neurogenesis. Our study demonstrates that E2F1 contributes to physiologic brain structure and function.

Microbiome and lipidomic analysis reveal the interplay between skin bacteria and lipids in a cohort study.

Human skin acts as a protective barrier between the body and the external environment. Skin microbiome and intercellular lipids in the stratum corneum (SC) are essential for maintaining skin barrier function. However, the interplay between skin bacteria and the lipids is not fully understood. In this study, we characterized the skin microbiome and SC lipid profiles from the forearm and face in a cohort of 57 healthy participants. 16S rRNA gene sequencing showed the skin microbial composition is significantly different between body locations and genders. Female forearm samples have the highest microbial diversity. The relative abundance of Staphylococcus hominis, Micrococcus luteus, Corynebacterium tuberculostearicum, Finegoldia magna, and Moraxellaceae sp. are significantly higher in the forearm than the face. The predictive functional analysis of 16S rRNA gene sequencing by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) and ANCOM-BC showed different bacterial metabolic pathway profiles between body locations or genders, and identified 271 differential pathways, including arginine and polyamine biosynthesis, chorismate biosynthesis pathways, which are more abundant in the female forearm, and sulfur oxidation pathway, which is more abundant in the male face. The SC lipid profiles differ between the body locations as well. Total free fatty acids (FFA), cholesterol sulfate and sphingosine are more abundant in the face. Dihydro-/6-hydroxy/phyto-ceramides are more abundant in the forearm. The correlation analysis of 16S rRNA gene sequencing and lipids revealed novel interplay between the bacteria and skin lipids. Shannon entropy and S. hominis negatively correlated with FFA, cholesterol sulfate and sphingosine; while positively correlated with dihydro-/6-hydroxy/phyto-ceramides. The correlation of predictive pathway profiles and lipids identified pathways involved in amino acids metabolism, carbohydrates degradation, aromatic compounds metabolism and fatty acid degradation metabolism are positively correlated with dihydro-/6-hydroxy/phyto-ceramides and negatively correlated with FFA, cholesterol sulfate and sphingosine. This study provides insights on the potential correlation between skin microbiome and lipids.

Traits shaping urban tolerance in birds differ around the world.

As human density increases, biodiversity must increasingly co-exist with urbanization or face local extinction. Tolerance of urban areas has been linked to numerous functional traits, yet few globally consistent patterns have emerged to explain variation in urban tolerance, which stymies attempts at a generalizable predictive framework. Here, we calculate an Urban Association Index (UAI) for 3,768 bird species in 137 cities across all permanently inhabited continents. We then assess how this UAI varies as a function of ten species-specific traits and further test whether the strength of trait relationships vary as a function of three city-specific variables. Of the ten species traits, nine were significantly associated with urban tolerance. Urban-associated species tend to be smaller, less territorial, have greater dispersal ability, broader dietary and habitat niches, larger clutch sizes, greater longevity, and lower elevational limits. Only bill shape showed no global association with urban tolerance. Additionally, the strength of several trait relationships varied across cities as a function of latitude and/or human population density. For example, the associations of body mass and diet breadth were more pronounced at higher latitudes, while the associations of territoriality and longevity were reduced in cities with higher population density. Thus, the importance of trait filters in birds varies predictably across cities, indicating biogeographic variation in selection for urban tolerance that could explain prior challenges in the search for global patterns. A globally informed framework that predicts urban tolerance will be integral to conservation as increasing proportions of the world's biodiversity are impacted by urbanization.

Amino acid complex (AAComplex) benefits in cosmetic products: In vitro and in vivo clinical studies.

BACKGROUND: Amino acids are major components of skin's natural moisturizing factors and play a role in regulating skin hydration and skin pH. OBJECTIVE: This research examines a proprietary amino acid complex technology (AAComplex) designed to help reduce skin irritation and repair skin damage. METHODS: In- vitro Scratch Assay HaCaT cells are scratched, and the wounds are imaged at different time points until the closure of the scratch wound is detected. In-vitro 3D Reconstructed Human Tissue Evaluation The concentration of heat shock protein 27 (HSP-27) extracted from 3D reconstructed human skin equivalent tissues and IL-1a released to the media was determined using enzyme-linked immunosorbent assays. In Vivo Clinical Study 37 subjects were enrolled in a split-face study design. On test days 1, 2, 4, and 8, subjects visited the test facility to have their face assessed by facial swabbing and bio-instrumentation measurements. RESULTS: In- vitro Scratch Assay The AAComplex demonstrated a strong cell renewal benefit in the HaCaT (human) cells scratch assay. In Vitro 3D Reconstructed Human Tissue Evaluation AAComplex demonstrated a significant skin repair benefit by quantifying Heat Shock Protein, HSP-27. Induced skin irritation was significantly reduced by quantifying interleukin-1 alpha biomarker, IL-1a. In Vivo Clinical Study The test products delivered skin benefits by reducing visual redness and skin irritation while increasing moisturization. CONCLUSION: The in vitro and in vivo clinical studies demonstrated that the AAComplex technology formulated in the commercially available Skin Recovery System effectively reduced skin irritation and redness as well as accelerating the skin repair process.

Projected changes in bird assemblages due to climate change in a Canadian system of protected areas.

National parks often serve as a cornerstone for a country's species and ecosystem conservation efforts. However, despite the protection these sites afford, climate change is expected to drive a substantial change in their bird assemblages. We used species distribution models to predict the change in environmental suitability (i.e., how well environmental conditions explain the presence of a species) of 49 Canadian national parks during summer and winter for 434 bird species under a 2°C warming scenario, anticipated to occur in Canada around the mid-21st century. We compared these to existing species distributions in the 2010s, and classified suitability projections for each species at each park as potential extirpation, worsening, stable, improving, or potential colonisation. Across all parks, and both seasons, 70% of the projections indicate change, including a 25% turnover in summer assemblages and 30% turnover in winter assemblages. The majority of parks are projected to have increases in species richness and functional traits in winter, compared to a mix of increases and decreases in both in summer. However, some changes are expected to vary by region, such as Arctic region parks being likely to experience the most potential colonisation, while some of the Mixedwood Plains and Atlantic Maritime region parks may experience the greatest turnover and potential extirpation in summer if management actions are not taken to mitigate some of these losses. Although uncertainty exists around the precise rate and impacts of climate change, our results indicate that conservation practices that assume stationarity of environmental conditions will become untenable. We propose general guidance to help managers adapt their conservation actions to consider the potentially substantive changes in bird assemblages that are projected, including managing for persistence and change.

Efficacy Evaluation of a Topical Hyaluronic Acid Serum in Facial Photoaging.

INTRODUCTION: Hyaluronic acid (HA) acts as a biologic humectant, thus retaining water in the skin, making HA useful as a topical moisturizing ingredient. The goal of the research was to evaluate the ability of a HA facial serum to deliver skin benefits. METHODS: Forty females 30-65 years of age with Fitzpatrick skin types I-VI who exhibited photoaging used the HA facial serum twice daily with sunscreen. The dermatologist investigator evaluated smoothness, plumping, hydration, fine lines/wrinkles, and global appearance issues on a 5-point ordinal scale. The subjects assessed product tolerability in terms of stinging, itching, and burning. Corneometry was undertaken, with assessments performed at baseline, immediately after application, and at weeks 2, 4, and 6. Facial swabbing and photography were performed at the same intervals on a subset of 15 subjects. RESULTS: The HA serum demonstrated excellent tolerability and produced an increase in skin hydration (as measured by corneometry) immediately after application of 134% (p < 0.001), with a sustained increase of 55% (p < 0.001) at week 6. At week 6, there was also improvement (p ≤ 0.001) in all evaluated attributes: smoothness (64%), plumping (60%), hydration (63%), fine lines (31%), wrinkles (14%), and overall global assessment (43%). Facial swabbing confirmed an increase in topical HA at week 6 (p = 0.04), accounting for the enhanced skin appearance, but there was no statistically significant increase in IL-1a, indicating no product irritation. CONCLUSION: Topical HA in a serum formulation provides excellent skin hydration, as demonstrated through clinical, photographic, chemical, and instrumental assessments.

Improved Functional Outcome After Peripheral Nerve Stimulation of the Impaired Forelimb Post-stroke.

Lack of blood flow to the brain, i.e., ischemic stroke, results in loss of nerve cells and therefore loss of function in the effected brain regions. There is no effective treatment to improve lost function except restoring blood flow within the first several hours. Rehabilitation strategies are widely used with limited success. The purpose of this study was to examine the effect of electrical stimulation on the impaired upper extremity to improve functional recovery after stroke. We developed a rodent model using an electrode cuff implant onto a single peripheral nerve (median nerve) of the paretic forelimb and applied daily electrical stimulation. The skilled forelimb reaching test was used to evaluate functional outcome after stroke and electrical stimulation. Anterograde axonal tracing from layer V pyramidal neurons with biotinylated dextran amine was done to evaluate the formation of new neuronal connections from the contralesional cortex to the deafferented spinal cord. Rats receiving electrical stimulation on the median nerve showed significant improvement in the skilled forelimb reaching test in comparison with stroke only and stroke with sham stimulation. Rats that received electrical stimulation also exhibited significant improvement in the latency to initiate adhesive removal from the impaired forelimb, indicating better sensory recovery. Furthermore, axonal tracing analysis showed a significant higher midline fiber crossing index in the cervical spinal cord of rats receiving electrical stimulation. Our results indicate that direct peripheral nerve stimulation leads to improved sensorimotor recovery in the stroke-impaired forelimb, and may be a useful approach to improve post-stroke deficits in human patients.

Low-income countries' orthopaedic information needs: challenges and opportunities.

BACKGROUND: The Internet should, in theory, facilitate access to peer-reviewed scientific articles for orthopaedic surgeons in low-income countries (LIC). However, there are major barriers to access, and most full-text journal articles are available only on a subscription basis, which many in LIC cannot afford. Various models exist to remove such barriers. We set out to examine the potential, and reality, of journal article access for surgeons in LIC by studying readership patterns and journal access through a number of Internet-based initiatives, including an open access journal ("PLoS Medicine"), and programs from the University of Toronto (The Ptolemy Project) and World Health Organization (WHO) (Health InterNetwork Access to Research Initiative [HINARI]). QUESTIONS/PURPOSES: Do Internet-based initiatives that focus on peer-reviewed journal articles deliver clinically relevant information to those who need it? More specifically: (1) Can the WHO's program meet the information needs of practicing surgeons in Africa? (2) Are healthcare workers across the globe aware of, and using, open access journals in a manner that reflects global burden of disease (GBD)? METHODS: We compared actual Ptolemy use to HINARI holdings. We also compared "PLoS Medicine" readership patterns among low-, middle-, and high-income regions. RESULTS: Many of the electronic resources used through Ptolemy are not available through HINARI. In contrast to higher-income regions, "PLoS Medicine" readership in Africa is proportional to both the density of healthcare workers and the GBD there. CONCLUSIONS: Free or low-cost Internet-based initiatives can improve access to the medical literature in LIC. Open access journals are a key component to providing clinically relevant literature to the regions and healthcare workers who need it most.

Dentate Gyrus Proliferative Responses After Traumatic Brain Injury and Binge Alcohol in Adult Rats.

BACKGROUND: Traumatic brain injury is a significant public health issue that results in serious disability in survivors. Traumatic brain injury patients are often intoxicated with alcohol when admitted to the hospital; however, it is not clear how acute intoxication affects recovery from a traumatic brain injury. Our group has previously shown that binge alcohol prior to traumatic brain injury resulted in long-term impairment in a fine sensorimotor task that was correlated with a decreased proliferative and neuroblast response from the subventricular zone. However, whether binge alcohol prior to traumatic brain injury affects the proliferative response in the hippocampal dentate gyrus is not yet known. METHODS: Male rats underwent binge alcohol (3 g/kg/day) by gastric gavage for 3 days prior to traumatic brain injury. Cell proliferation was labeled by BrdU injections following traumatic brain injury. Stereological quantification and immunofluorescence confocal analysis of BrdU+ cells in the hippocampal dorsal dentate gyrus was performed at 24 hours, 1 week and 6 weeks post traumatic brain injury. RESULTS: We found that either traumatic brain injury alone or binge alcohol alone significantly increased dentate gyrus proliferation at 24 hours and 1 week. However, a combined binge alcohol and traumatic brain injury regimen resulted in decreased dentate gyrus proliferation at 24 hours post-traumatic brain injury. At the 6 week time point, binge alcohol overall reduced the number of BrdU+ cells. Furthermore, more BrdU+ cells were found in the dentate hilar region of alcohol traumatic brain injury compared to vehicle traumatic brain injury groups. The location and double-labeling of these mismigrated BrdU+ cells was consistent with hilar ectopic granule cells. CONCLUSION: The results from this study showed that pre-traumatic brain injury binge alcohol impacts the injury-induced proliferative response in the dentate gyrus in the short-term and may affect the distribution of newly generated cells in the dentate gyrus in the long-term.

Air Particulate Matter Induces Skin Barrier Dysfunction and Water Transport Alteration on a Reconstructed Human Epidermis Model.

Knowing the damage that particulate matter (PM) can cause in skin is important for tightly controlling the release of air pollutants and preventing more serious diseases. This study investigates if such alterations are present in reconstructed human epidermis exposed to coarse air PM. Exposure of reconstructed human epidermis to increasing concentrations (2.2, 8.9, and 17.9 µg/cm2) of standard urban PM over time led to decreased cell viability at 48 hours. The barrier function was shown to be compromised by 24 hours of exposure to high doses (17.9 µg/cm2). Morphological alterations included cytoplasm vacuolization and partial loss of epidermal stratification. Cytokeratin 10, involucrin, loricrin, and filaggrin protein levels were significantly decreased. We confirmed an inflammatory process by IL-1α release and found a significant increase in AQP3 expression. We also demonstrated changes in NOTCH1 and AhR expression of epidermis treated with coarse air PM. The use of hydrogen peroxide altered AQP3 and NOTCH1 expression, and the use of N-acetyl-L-cysteine altered NOTCH1 expression, suggesting that this is a redox-dependent process. These results demonstrate that coarse air PM induces dose-dependent inflammatory response and alterations in protein markers of differentiation and water transport in the epidermis that could ultimately compromise the structural integrity of the skin, promoting or exacerbating various skin diseases.

Projected avifaunal responses to climate change across the U.S. National Park System.

Birds in U.S. national parks find strong protection from many longstanding and pervasive threats, but remain highly exposed to effects of ongoing climate change. To understand how climate change is likely to alter bird communities in parks, we used species distribution models relating North American Breeding Bird Survey (summer) and Audubon Christmas Bird Count (winter) observations to climate data from the early 2000s and projected to 2041-2070 (hereafter, mid-century) under high and low greenhouse gas concentration trajectories, RCP8.5 and RCP2.6. We analyzed climate suitability projections over time for 513 species across 274 national parks, classifying them as improving, worsening, stable, potential colonization, and potential extirpation. U.S. national parks are projected to become increasingly important for birds in the coming decades as potential colonizations exceed extirpations in 62-100% of parks, with an average ratio of potential colonizations to extirpations of 4.1 in winter and 1.4 in summer under RCP8.5. Average species turnover is 23% in both summer and winter under RCP8.5. Species turnover (Bray-Curtis) and potential colonization and extirpation rates are positively correlated with latitude in the contiguous 48 states. Parks in the Midwest and Northeast are expected to see particularly high rates of change. All patterns are more extreme under RCP8.5 than under RCP2.6. Based on the ratio of potential colonization and extirpation, parks were classified into overall trend groups associated with specific climate-informed conservation strategies. Substantial change to bird and ecological communities is anticipated in coming decades, and current thinking suggests managing towards a forward-looking concept of ecological integrity that accepts change and novel ecological conditions, rather than focusing management goals exclusively on maintaining or restoring a static set of historical conditions.

Staphylococcus aureus Bacteremia in Patients not Meeting Sepsis Criteria: Clinical Features, Host Immune Response and Outcomes.

BACKGROUND: Limitations regarding the sensitivity and specificity of the systemic inflammatory response (SIRS) criteria prompted the recent revision in consensus definitions of sepsis and septic shock. We evaluated patients with Staphylococcus aureus bacteremia (SAB) who did not meet SIRS criteria for sepsis (SIRS-negative, SIRS-N) to compare host immune response and outcomes with SIRS-positive (P) patients. METHODS: A prospective observational study of patients hospitalized for SAB during 2012-2015 was conducted. Pro- (TNFα, IL6, IL8) and anti-inflammatory (IL10) cytokine levels (pg/mL) were compared between SIRS-N and SIRS-P patients. Outcome endpoints were day 4 persistence and 30-day mortality. RESULTS: Of the 353 study patients, 23% were SIRS-N. A similar proportion of SIRS-N and SIRS-P patients had an infection-related admitting diagnosis (70% vs. 66%, p=0.5946), and both groups received timely antibiotic administration. Less than 1/3 of SIRS-N group had abnormal WBC count, tachycardia, or tachypnea while <15% had fever/hypothermia or hypotension. Initial proand anti-inflammatory cytokine levels were significantly lower and in balance as indicated by IL10/TNF ratio in SIRS-N compared to SIRS-P patients. IL10/TNF ratio increased progressively in patients with increasing sepsis severity and mortality. CONCLUSIONS: Clinical management of patients with SAB seemed driven largely by clinician assessment rather than SIRS criteria alone, with one in 4 patients not meeting SIRS criteria. Importantly, the severity of presentation and outcomes of SAB correspond well to the magnitude of underlying imbalance in pro- and anti-inflammatory cytokine levels, supporting the updated sepsis definition as "life-threatening organ dysfunction caused by a dysregulated host response to infection". KEY POINTS: In a prospective observational study of 353 patients with Staphylococcus aureus bacteremia, 23% did not meet SIRS criteria for sepsis. Severity of sepsis and risk of death is supported by a dysregulated host cytokine response with progressively increasing IL10/TNF ratio.

The Subventricular Zone Response to Stroke Is Not a Therapeutic Target of Anti-Nogo-A Immunotherapy.

Ischemic stroke is a leading cause of adult disability with no pharmacological treatments to promote the recovery of lost function. Neutralizing antibodies against the neurite outgrowth inhibitor Nogo-A have emerged as a promising treatment for subacute and chronic stroke in animal models; however, whether anti-Nogo-A treatment affects poststroke neurogenesis remains poorly understood. In this study, we confirmed expression of Nogo-A by neuroblasts in the adult rat subventricular zone (SVZ), a major neurogenic niche; however, we found no evidence that Nogo-A was expressed at the surface of these cells. In vitro migration assays demonstrated that Nogo-A signaling induced a modest reduction in neuroblast migration speed, while anti-Nogo-A antibodies had no effect on motility properties. Using a permanent distal middle cerebral artery occlusion model of cortical stroke, we found that the number of proliferating cells in the SVZ was unaffected in response to stroke, while neuroblast mobilization from the SVZ toward the stroke lesion correlated positively with lesion size. However, we found no evidence that proliferation or neuroblast mobilization were affected by anti-Nogo-A antibody treatment. Our results suggest that the SVZ is not a therapeutic target of anti-Nogo-A immunotherapy, and contribute to our understanding of the SVZ response to cortical stroke.

A randomized trial of one-day vs. three-day buprenorphine inpatient detoxification protocols for heroin dependence.

Detoxification from opioids remains an important first step in the treatment of many patients with opioid dependence. Several pharmacologic regimens have been used for opioid detoxification. In the United States, the partial mu-opioid agonist, buprenorphine (BUP) is the most recently approved pharmacotherapy for opioid detoxification and replacement. The literature in recent years has described detoxification protocols using a single high dose of BUP and a three-day BUP regimen. In many settings, such as drug-free programs, a single-dose detoxification protocol would be of significant benefit. There have been no prior studies comparing one-day and three-day BUP-assisted opioid withdrawal. In this pilot study, we conducted an open-label, randomized trial of one-day vs. three-day BUP/naloxone sublingual tablet-assisted opioid withdrawal. Twenty patients from a therapeutic community treatment program were randomly assigned to receive either 32 mg sublingual BUP over one hour (one-day group), or 32 mg sublingual BUP over three days (three-day group). Nine of 10 subjects (90 percent) in each group completed seven days in the detoxification protocol. There was no statistically significant difference between the two groups in all other outcome variables, including retention in the treatment program, intensity of withdrawal signs and symptoms, amounts of adjunct medications used, and ability to produce opiate-free urine. This study further validates the feasibility of the single high dose of BUP as a rapid detoxification method.

A Tensioned Human Skin Explant Model Used for Preliminary Assessment of Chemexfoliant-Stimulated Bioeffects.

A tensioned ex vivo full-thickness human skin explant platform was used to assess the bioeffects arising from application of several commercial chemexfoliation agents. Although such treatments are well-established, and improved understanding of the underlying mechanistic processes continues to emerge, research into the optimum treatments for specific skin types/conditions is still needed for enhanced efficacy while minimizing recovery time. The 3 commercial chemexfoliation agents employed all contained trichloroacetic acid at well-defined concentrations (6, 10, and 20%) and were applied to the explants' stratum corneum. Subsequently, measurements of dermal remodeling factors (COL1A1, ELN, HAS2, HAS3, and procollagen type I) and inflammatory marker (IL-1b) were undertaken using qPCR and immunofluorescent analyses. Statistical analysis of these data facilitated the establishment of benchmarking biological responses to these trichloroacetic acid-containing agents against untreated controls. The performance of an innovative trichloroacetic acid-free chemexfoliation agent was then measured and, upon comparison with the previous benchmarking data, indicated that dermal remodeling factors could be upregulated in fashion comparable with that of the trichloroacetic acid-containing agents but with significant suppression of inflammatory response. Our measurements thus underscore the promise of the tensioned explant over prolonged study periods and also that potentially valuable insights to guide preclinical strategies may be forthcoming from the protocol developed.