Die Umsetzung der EU-Hochwasserrichtlinie (RL 2007/60/EG) in Österreich

Zusammenfassung

Hochwasser haben das Potenzial, zu Todesfällen, zur Umsiedlung von Personen und zu Umweltschäden zu führen, die wirtschaftliche Entwicklung ernsthaft zu gefährden und wirtschaftliche Tätigkeiten in der Gemeinschaft zu behindern. Die Richtlinie 2007/60/EG des Europäischen Parlaments und des Rates vom 23. Oktober 2007 über die Bewertung und das Management von Hochwasserrisiken hat zum Ziel einen Rahmen für die Bewertung und das Management von Hochwasserrisiken zur Verringerung der hochwasserbedingten nachteiligen Folgen auf die menschliche Gesundheit, die Umwelt, das Kulturerbe und wirtschaftliche Tätigkeiten in der Gemeinschaft zu schaffen. Im Rahmen des Beitrags wird dargestellt, wie die einzelnen Arbeitsschritte der Richtlinie auf Basis bundesweit einheitlicher Methoden in Österreich umgesetzt und international koordiniert wurden.

Trends and predictors of syphilis prevalence in the general population: Global pooled analyses of 1103 prevalence measures including 136 million syphilis tests

Abstract

Background

This study assessed levels, trends, and associations of observed syphilis prevalence in the general adult population using global pooled analyses.

Methods

A standardized database of syphilis prevalence was compiled by pooling systematically-gathered data. Random-effects meta-analyses and meta-regressions were conducted using data from 1990–2016 to estimate pooled measures and assess predictors and trends. Countries were classified by World Health Organization regions. Sensitivity analyses were conducted.

Results

The database included 1103 prevalence measures from 136 million syphilis tests across 154 countries (85% from antenatal care women). Global pooled mean prevalence (weighted by region population size) was 1.11% (95% confidence interval [CI]: 0.99–1.22). Prevalence predictors were region, diagnostic assay, sample size, and calendar year interacting with region. Compared to the African Region, the adjusted odds ratio (AOR) was 0.42 (95% CI: 0.33–0.54) for the Americas, 0.13 (95% CI: 0.09–0.19) for Eastern Mediterranean, 0.05 (95% CI: 0.03–0.07) for European, 0.21 (95% CI: 0.16–0.28) for South-East Asia, and 0.41 (95% CI: 0.32–0.53) for Western Pacific. TPHA-only or RPR-only tests, compared to dual RPR/TPHA diagnosis, produced higher prevalence (AOR>1.26), as did smaller sample-size studies (<500 persons) (AOR>2.16). Prevalence declined in all regions; the annual AORs ranged from 0.84 (95% CI: 0.79–0.90) in Eastern Mediterranean to 0.97 (95% CI: 0.97–1.01) in Western Pacific. The pooled mean male-to-female prevalence ratio was 1.00 (95% CI: 0.89–1.13). Sensitivity analyses confirmed robustness of results.

Conclusion

Syphilis prevalence has declined globally over the past three decades. Large differences in prevalence persist among regions, with the African Region consistently the most affected.

Risk of Subsequent Sepsis within 90 Days of a Previous Hospital Stay by Type of Antibiotic Exposure

Abstract

Background

We examined the risk of sepsis within 90 days after discharge from a previous hospital stay by type of antibiotic received during the previous stay.

Methods

We retrospectively identified a cohort of hospitalized patients from the Truven Health MarketScan Hospital Drug Database. We examined the association between the use of certain antibiotics, determined a priori, during the initial hospital stay and risk of post-discharge sepsis controlling for potential confounding factors in a multivariable logistic regression model. Our primary exposure was receipt of antibiotics more strongly associated with clinically important microbiome disruption. Our primary outcome was a hospital stay within 90 days of the index stay that included an ICD-9-CM discharge diagnosis of severe sepsis (995.92) or septic shock (785.52).

Results

Among 516 hospitals, we randomly selected a single stay for eligible patients. Of those, 0.17% developed severe sepsis/septic shock within 90 days after discharge. The risk of sepsis associated with exposure to our high risk antibiotics was 65% higher compared to those without antibiotic exposure.

Conclusions

Our study identified an increased risk of sepsis within 90 days of discharge among patients with exposure to high risk or increased quantities of antibiotics during hospitalization. Given a significant proportion of inpatient antimicrobial use may be unnecessary, this study builds on previous evidence suggesting that increased stewardship efforts in hospitals may not only prevent antimicrobial resistance, CDI and other adverse effects, but also reduce unwanted outcomes potentially related to disruption of the microbiota, including sepsis.

Risks of infection and mortality among patients colonized with KPC-producing Klebsiella pneumoniae : validation of scores and proposal for management.

Abstract

Background

The management and indication of empirical treatment in Klebsiella pneumoniae-carbapenemase producing K. pneumoniae (KPC-Kp) colonized patients should be improved.

Methods

A prospective cohort of 94 patients colonized by KPC-Kp was followed for 90 days to validate: (i) the Giannella risk score (GRS) to predict the development of any type of KPC-Kp infection and (ii) the INCREMENT-CPE score (ICS) to predict 30-day mortality in patients with infection. Both scores were combined in order to recommend appropriate empirical treatment. The predictive ability of the scores was measured by calculating the area under the receiver operating characteristic (AUROC) curve.

Results

The GRS showed an AUROC curve for infection due to KPC-Kp of 0.92 (CI 95%: 0.87–0.98). The optimal cutoff point was fixed at < 7 and ≥ 7 (92.9% sensitivity, 84.8% specificity); infection developed in 6.3% patients in the 0–6 GRS group and in 84.8% patient in the ≥ 7 GRS group. According to the ICS, the severity of the infection was also significantly higher in the ≥ 7 GRS group. The ICS showed an AUROC of 0.78 (95% CI: 0.65–0.91) for 30-day all-cause mortality among patients with infection. A CART analysis confirmed the GRS cutoff point at 7, and selected ≥ 12 points to predict a KPC-Kp infection with a high ICS.

Conclusion

Our results validate the GRS and ICS for indicating empirical therapy in KPC-Kp- colonized patients

Bedaquiline resistance: Its emergence, mechanism and prevention

Abstract

Bedaquiline, a new anti-tuberculosis drug, has already been used in more than 50 countries. The emergence of bedaquiline resistance is alarming, as it may result in the rapid loss of this new drug. This paper aims to review currently identified mechanisms of resistance, the emergence of bedaquiline resistance, and discuss strategies to delay the resistance acquisition. In vitro and clinical studies as well as reports from the compassionate use have identified the threat of bedaquiline resistance and cross-resistance with clofazimine, emphasizing the crucial need for the systematic surveillance of resistance. Currently known mechanisms of resistance include mutations within the atpE, Rv0678 and pepQ genes. The development of standardized drug susceptibility testing (DST) for bedaquiline is urgently needed.Understanding any target and non-target based mechanisms is essential to minimize the resistance development and treatment failure, help to develop appropriate DST for bedaquiline and genetic based resistance screening.

Urinary Tract Infections: Molecular Pathogenesis and Clinical Management, second edition

Edited by MulveyMA, KlumppDJ, StapletonAE.Washington, D.C.: ASM Press, 2017. XX pp. $150.00 (hardcover) ISBN: 9781555817398

Economic evaluations of mass drug administration: The importance of economies of scale and scope

Abstract

It is recognised that changing the current approaches for the control of the neglected tropical diseases will be needed to reach the World Health Organization's (WHO) 2020 goals. Consequently, it is important that economic evaluations of the alternative approaches are conducted. A vital component of such evaluations is the issue of how the intervention's costs should be incorporated. We discuss this issue – focusing on mass drug administration. We argue that the common approach of assuming an intervention's cost per treatment is constant, regardless of the number of individuals treated, is a misleading way to consider the delivery costs of mass drug administration due to the occurrence of economies/diseconomies of scale and scope. Greater care and consideration are required when the costs are incorporated into such analyses. Without this, these economic evaluations could potentially lead to incorrect policy recommendations.

Current Epidemiology and Trends in Meningococcal Disease—United States, 1996-2015

Abstract

Background

In 2005, meningococcal conjugate vaccine (MenACWY) was recommended for routine use among adolescents aged 11–18 years. This report describes the epidemiologic features of meningococcal disease and trends in meningococcal disease incidence following MenACWY introduction in the United States.

Methods

Incidence rates and case-fatality ratios by age group and serogroup during 2006–2015 were calculated using data from the National Notifiable Diseases Surveillance System (NNDSS); changes in incidence during this time were evaluated. Additionally, 20-year trends (1996–2015) in age- and race-standardized incidence were examined using data from Active Bacterial Core surveillance (ABCs).

Results

During the years 2006–2015, 7,924 cases of meningococcal disease were reported to NNDSS, resulting in an average annual incidence of 0.26 cases per 100,000 population; 14.9% of cases were fatal. Among cases with serogroup information, 2,290 (35.8%) were serogroup B, 1,827 (28.5%) were serogroup Y, 1,457 (22.8%) were serogroup C, 436 (6.8%) were serogroup W, and 392 (6.1%) were other serogroups. The incidence of serogroups A, C, W, and Y combined declined 76% among persons aged 11–20 years from 2006–2010 to 2011–2015 (p<.0001). From 1996-2015, the incidence of meningococcal disease declined among all age groups and predominant serogroups.

Conclusions

Declines in meningococcal disease incidence in the United States have been observed among all age groups and predominant serogroups (B, C, and Y). Reductions in the incidence of meningococcal disease due to serogroups A, C, W, and Y among adolescents suggest an impact of the MenACWY vaccine program in this age group.

The Importance of HIV Research for Transgender and Gender Non-Binary Individuals.

Abstract

Transgender and gender non-binary (trans/GNB) individuals are disproportionally affected by HIV, yet they are not adequately represented in HIV research and often underserved in clinical care. By building on community strengths and addressing structural, psychological and biological challenges, we can improve the engagement of trans/GNB people in research and ultimately improve prevention, testing and care for this population. Here, we review the current state of the science related to HIV for trans/GNB people, and we discuss next steps to expand research that aims to improve the lives and well-being of trans/GNB persons.

Poly-L-lactic acid for the Improvement of photodamage and rhytids of the décolletage

Summary

Background

Poly-L-lactic acid (PLLA) is a biostimulatory filler approved for use in HIV lipoatrophy as well as cosmetic improvement in facial folds and wrinkles in immunocompetent patients. Similar to the face and hands, the décolletage is commonly subject to photodamage and the resulting appearance of rhytids and crepiness, which could benefit from PLLA treatment.

Objectives

The objective of the study was to assess the safety and efficacy of injected PLLA for the improvement in rhytids and crepiness of the décolletage.

Methods

In this open-label, prospective, interventional study, 25 healthy female volunteers aged 40-to-70 years with moderate-to-severe crepiness and wrinkling of the décolletage were injected with 1 vial of PLLA at each of three treatments. The Fabi-Bolton 5-point chest wrinkling scale was used by both investigators and subjects to assign pretreatment and post-treatment follow-up scores at 1 month, 3 months, and 6 months. Adverse events were reported at each visit.

Results

All post-treatment mean scores had statistically significant improvement compared to the pretreatment baseline means as rated by both investigators and subjects. At 1 month following the last treatment, compared to baseline, investigators rated 83% of subjects had improved by at least one point on the scale. Subjects rated 74% of subjects improved by at least one point. At 6 months, 90% of subjects, as rated by the investigators, and 57% of subjects, as rated by the subjects, had improvement from baseline.

Conclusion

PLLA is safe and effective for improvement in the rhytids and skin quality of the photodamaged décolletage.

Open access: Is there a predator at the door?

Deposition of absolute and relative airborne metals on eggshells: a field study

Abstract

A biomonitoring field study was conducted to test the deposition of airborne metals on chicken eggshell. The goal was to correlate PM2.5 particle concentration in air, absolute (metals in air) and relative (metals in PM2.5 particles) metals, and metal accumulation on eggshell. The PM2.5 sample was collected for 8 h at different air pollution sites as well as an unpolluted site with glass fiber filters via a fine particulate sampler (with and without addition of eggshell). The PM2.5 particle concentration was high at a cement factory site and low at a sugar factory site. The highest absolute total mass of metal (total mass of all metals in air) was found in the traffic site, and the highest relative total mass of metal (total mass of all metals in PM2.5 particles) was found at the tannery factory. The accumulation of Zn and Pb in eggshell was high at the tannery and sugar factory sites, and Fe was high in the other areas. Three common metals including Cd, As, and Pb were found with significant positive correlation between absolute and relative metals with the metals accumulated in eggshell. The results concluded that the eggshells might be useful tools for monitoring the airborne metals.

Impacto económico de la dermatitis atópica en adultos: estudio de base poblacional (estudio IDEA)

Publication date: Available online 8 November 2017
Source:Actas Dermo-Sifiliográficas
Author(s): A. Sicras-Mainar, R. Navarro-Artieda, J.M. Carrascosa Carrillo
ObjetivoDeterminar el uso de los recursos y los costes de la dermatitis atópica (DA) en adultos según su gravedad y las comorbilidades asociadas en situación de práctica clínica habitual.Pacientes y métodosSe efectuó un diseño observacional retrospectivo realizado a partir de la revisión de registros de pacientes ≥18años que demandaron asistencia durante 2013-2014 en un área geográfica de Cataluña con una población de 215.634 personas. Se constituyeron 3 grupos de gravedad en función del tratamiento prescrito. Las variables evaluadas fueron el conjunto de comorbilidades, la medicación concomitante/específica; y los costes sanitarios directos/indirectos. El análisis estadístico se elaboró mediante modelos de regresión múltiple, p<0,05.ResultadosSe reclutaron 6.186 sujetos con diagnóstico de DA (edad-media: 47,1años; mujeres, 61,6%). En función de la gravedad de la DA se consideraron 3 grupos; el 55,7% leve (n=3.445), el 38,2% moderada (n=2.361) y el 6,1% grave (n=380). La DA grave se asoció a la probabilidad de presentar comorbilidades (β=0,192); específicamente: asma (β=0,138), depresión (β=0,099), eventos cardiovasculares (β=0,087), obesidad (β=0,085) y hábito tabáquico (β=0,025), p<0,001. El coste ascendió a 9,3 millones de euros (costes sanitarios: 75,5%; pérdidas de productividad: 24,5%), con un promedio/unitario de 1.504euros/año. Los promedios/unitarios corregidos (ANCOVA) fueron mayores en la DA grave en comparación con la moderada y la leve (3.397 vs. 2.111 y 885 euros, respectivamente; p<0,001).ConclusionesLa DA grave se asocia a una elevada utilización de recursos sanitarios y costes para el Sistema Nacional de Salud proporcional a la gravedad de la dermatosis. La comorbilidad general y el asma fueron los factores con mayor impacto asociado al coste sanitario.ObjectiveTo determine resource usage and costs associated with atopic dermatitis in adults according to severity and comorbid conditions in daily clinical practice.Patients and methodsWe performed an observational, retrospective study based on a review of registries of patients aged ≥18 years who sought health care in 2013 and 2014 in an area of Catalonia, Spain, with a population of 215,634 persons. We established 3 classes of severity depending on the treatment prescribed. The variables evaluated were total comorbid conditions, concomitant/specific medication, and direct/indirect health care costs. The statistical analysis was based on multiple regression models. Statistical significance was set at P<.05.ResultsWe included 6,186 patients with a diagnosis of atopic dermatitis (mean age, 47.1 years; women, 61.6%). We established 3 groups based on severity, as follows: mild (n=3,445 [55.7%]); moderate (n=2,361 [38.2%]); and severe (n=380 [6.1%]). Severe atopic dermatitis was associated with risk of presenting comorbid conditions (β=0.192), namely, asthma (β=0.138), depression (β=0.099), cardiovascular events (β=0.087), obesity (β=0.085), and smoking (β=0.025); P<.001. Costs reached €9.3 million (health care costs, 75.5%; loss of productivity, 24.5%), with an average unit cost of €1,504 per year. The corrected average unit cost (ANCOVA) was greater in severe atopic dermatitis compared with moderate and mild disease (€3,397 vs. €2,111 vs. €885; P<.001), respectively.ConclusionsSevere atopic dermatitis generates considerable usage of health care resources and high costs for the National Health System. These are in proportion with the severity of the disease. General comorbid conditions and asthma were the factors with the greatest impact on health care costs.

Graphical abstract

Correction to: Apocynin and dimethyl sulfoxide synergistically protect against ischemia-reperfusion injury in a rat hind limb ischemia-reperfusion model

Abstract

Dr. Ozer Sehirli's affiliation needs to be updated as he was transferred from Marmara University Faculty of Pharmacy to Near East University Faculty of Dentistry two years ago. The updated information is provided in the affiliation section below.

Brain amyloid PET interpretation approaches: from visual assessment in the clinic to quantitative pharmacokinetic modeling

Abstract

Purpose

Cerebral β-amyloid burden can be measured by positron emission tomography (PET) tracers, including ¹¹C-Pittsburgh Compound B (¹¹C-PiB) and three fluorinated tracers that have been approved by regulatory agencies. This review focuses on the current clinical use of amyloid PET and the added utility of quantifying β-amyloid deposition.

Methods

Using systematic review methods, a PubMed search identified studies on the added value of standardized uptake value ratio (SUVR) to visual reads. PubMed search was also performed to identify studies that illustrate important factors that cause variability in SUVR results, as well as key papers in the initial development of ¹¹C-PiB.

Results

Among studies comparing visual interpretation and SUVR, there is high concordance between visual reads and SUVR for diagnosis classification, with evidence that SUVR decreases inter-reader variability in visual interpretation and improves accuracy. The variability among results of studies utilizing SUVR is likely multifactorial, including choice of reference regions, choice of target regions, and methods for determining SUVR thresholds. The initial ¹¹C-PiB studies illustrate the importance of rigorous pharmacokinetic modeling and stepwise simpler quantitative methods when translating radiotracers.

Conclusion

There is increasing evidence of the added value of SUVR in the clinic, in particular in borderline cases or for detection of subtle changes. SUVR provides a reasonably accurate measurement of amyloid plaque deposition compared to pharmacokinetic modeling methods.

The interface interaction behavior between E. coli and two kinds of fibrous minerals

Abstract

In the present, studies of interaction between human normal flora and fibrous mineral are still lacking. Batch experiments were performed to deal with the interaction of Escherichia coli and two fibrous minerals (brucite and palygorskite), and the interface and liquid phase characteristics in the short-term interaction processes were discussed. The bacterial concentrations, the remnant glucose (GLU), pyruvic acid, and the activity of β-galactosidase and six elements were measured, and the results show that the promoting effect of brucite on the growth of E. coli was more significant than that of palygorskite. FTIR and XRD analysis results also confirmed E. coli has obviously dissolved on brucite and damage effect on palygorskite silicon structure. SEM results show that the interfacial contact degree between E. coli cells and brucite fibers was higher than that of palygorskite. These may be due to the zeta potential difference between E. coli and palygorskite was 14.57–22.37 mV, while it of brucite was 44.04–64.24 mV. The elements dissolving of two fibrous minerals not only increased regularly to liquid EC but also had a good buffer effect to the decrease of liquid pH. Studies of short-term interaction between E. coli and brucite and palygorskite can help to understand the effect of fibrous minerals on microeubiosis of human normal flora and the contribution of microbial behaviors on the fibrous minerals weathering in the natural environment.

Photolytic degradation of ciprofloxacin in solid and aqueous environments: kinetics, phototransformation pathways, and byproducts

Abstract

Many lipophilic pharmaceuticals may be sorbed in solid phases, leading to different photochemical behaviors. This study investigated the photochemistry of ciprofloxacin in a solid-phase system and compared it to that in a water-phase system. Kaolinite was used as the model solid matrix. The photolysis of ciprofloxacin in kaolinite fits pseudo-first-order kinetics for thicknesses less than 199 μm, and the rate constants k _p decreased from 0.0154 to 0.0016 min⁻¹ as the thickness of the layer increased. Unlike the aqueous phase, two-step degradation processes were observed for all kaolinite layer thicknesses (14–199 μm), and the pseudo-first-order constant at the surface of the kaolinite layer was smaller than that in the water phase. Comparatively, a similar photolysis rate constant of ciprofloxacin in a kaolinite suspension was also observed, and it was an order of magnitude smaller than that of the direct photodegradation (0.035 min⁻¹) in water. The results indicate that ciprofloxacin is likely more stable when it is adsorbed on kaolinite and that the half-lives of ciprofloxacin in kaolinite and a kaolinite suspension are 2–25 times longer than that in deionized water (20 min) under simulated sunlight. Direct photolysis is proposed to be the main photodegradation mechanism for ciprofloxacin in kaolinite, and the cleavage of a piperazine ring is the main degradation pathway. However, the interaction between ciprofloxacin and kaolinite reduces the direct photolysis and leads to a higher light stability. In association with the reduction in photolysis, the yields of norfloxacin and defluorinated byproduct decreased significantly. Consequently, the interaction increases the persistence of ciprofloxacin and thus the ecological risk to the environment.

Liquid chromatography-mass spectrometry method for evaluating the dissipation dynamics of cyromazine and its metabolite in Agaricus bisporus and dietary risk assessment

Abstract

Providing guidance on the reasonable use of pesticide in agricultural production is of particular importance for ensuring food safety. In the present study, a field trial was performed to study the dissipation and accumulative pattern of cyromazine (CA) and its metabolite in Agaricus bisporus (A. bisporus) cultivation. An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was first developed and validated for the determination of CA and melamine (MEL) in the casing soil and fruiting body. During the cultivation period, the dissipation rates of CA in the casing soil were between 51.57 and 63.48% at three dose groups. The fruiting body presented higher accumulation ability for MEL compared with CA. The terminal residues of MEL never exceeded the maximum residue limits (MRLs) in food. In addition, the intake health risk from the CA and MEL residues in the fruiting body were negligible to humans. This study will help to provide valuable guidance on the application strategies of CA in A. bisporus cultivation.

BRAF Mutation Status Concordance Between Primary Cutaneous Melanomas and Corresponding Metastases: A Review of the Latest Evidence

Publication date: Available online 8 November 2017
Source:Actas Dermo-Sifiliográficas (English Edition)
Author(s): E. Godoy-Gijón, M. Yuste-Chaves, Á. Santos-Briz
The identification of B-Raf proto-oncongene (BRAF) mutation and the emergence of targeted therapy marked a turning point in the treatment of melanoma. The study of mutation status concordance between primary tumors and metastases in this cancer has major treatment implications as it facilitates the selection of candidates for targeted therapy. This review analyzes the evidence on the level of mutation status concordance between primary tumors and different types of metastases in cutaneous melanoma and provides an overview of the advantages and disadvantages of the various methods used to detect BRAF mutations.

Schnitzler Syndrome With Response to Anakinra Monotherapy: 7 Years of Follow-up

Publication date: Available online 8 November 2017
Source:Actas Dermo-Sifiliográficas (English Edition)
Author(s): Y. Hidalgo-García, E. García-Fernández, L. Palacio-Aller, P. Gonzalvo

Writing a better research paper: Advice for young authors

Correcting the literature

We make important therapeutic decisions based on the best available evidence and it is important to correct the literature when results are in question. Appropriate actions may include publication of a correction, links to previously cited data to avoid double counting of outcomes, expressions of concern about study methods or integrity, and retraction of a published article. Corrections should be published as soon as possible, appear in a prominent position on a numbered page in the journal that originally published the article, and include the complete original citation to help ensure that an appropriate reference to the published erratum will be added to the MEDLINE citation.

Duplicate publication

Authorship

Common reasons why manuscripts are rejected: Advice for young investigators

Ethics and fairness during the review and publication process

Planning better research projects: Advice for young researchers

Presentation of data

Advice for reviewers (and authors and readers)

Getting the most out of on-line literature searches – More on Boolean logic

Psoriasis and the Risk of Diabetes: A Prospective Population-Based Cohort Study.

Data evaluating the impact of objectively measured psoriasis severity on type 2 diabetes mellitus (T2DM) risk are lacking.

Sample size

Study design and statistical analysis

Misclassification of Study Designs in the Dermatology Literature

The appropriate classification of study designs is important for review and assessment of the relevant scientific literature as a basis for decision-making. However, little is known about whether study designs have been appropriately reported in the dermatology literature.

Objective Outcome Measures: Collecting Meaningful Data on Alopecia Areata

Although alopecia areata is a common disorder, it has no FDA approved treatment and evidence-based therapeutic data is lacking.

Successful treatment of moderate-to-severe alopecia areata improves health-related quality of life

An extemporaneous approach for optimizing acitretin dosing in pediatric patients

Getting the most out of on-line literature searches Tips for advanced searches

Thorough and efficient literature searches are important to authors and practicing physicians alike, and modern search engines have many tools to expedite the process. In databases such as PubMed, new logic, or natural language, is set up to answer questions by simply typing them in.

Vasculitis and IgA monoclonal gammopathy of cutaneous significance

Abstract

IgA vasculitis (Henoch-Schonlein purpura) is a small vessel systemic vasculitis involving IgA immunoglobulin polyclonal activation¹. Monoclonal gammopathy of cutaneous significance is a subgroup of monoclonal gammopathy with skin disease, without myeloma or lymphoproliferative disorder². We report 3 patients with vasculitis and IgA monoclonal gammopathy of cutaneous significance. Three men, 38, 37 and 50 years old, had a vascular purpura for more than 10 years with partial remission and frequent necrotic flares (Figure 1).

This article is protected by copyright. All rights reserved.

Actinic keratosis area and severity index (AKASI) is associated with the incidence of squamous cell carcinoma

Abstract

Background

Actinic keratoses (AKs) are commonly diagnosed clinically. Actinic keratosis area and severity index (AKASI) is a new easy-to-use tool to assess the severity of AK on the head.

Objective

To determine the association between chronically UV-induced tumours such as basal cell carcinomas (BCC) or squamous cell carcinomas (SCC) and AKASI.

Methods

We performed a retrospective analysis of patients who had undergone oncological surgery due to UV-induced tumours and who were assessed for AKASI and Physician's Global Assessment (PGA) prior to surgery. Statistical analysis was performed to evaluate correlation between AKASI, PGA and invasive carcinomas.

Results

Of the 210 patients included, 26 patients had histologically diagnosed SCCs and presented with a median (range) AKASI of 6.9 (0 – 13.0) and PGA of 2 (0 - 4). In contrast, the 82 patients with BCCs showed a median (range) AKASI of 3.3 (0 -15.2) and PGA of 1 (0 - 4). The Mann-Whitney U test showed significant differences (p= 0.0018) between AKASI of patients with SCC and BCC. In addition, we found a significantly higher AKASI in patients with SCC compared to patients with non-invasive lesions like AK and Bowen disease (BD) (p= 0.0275). Spearman's coefficient of rank correlation between AKASI and PGA indicates that these measures of AK severity were strongly correlated (p< 0.0001; r = 0.90; 95%CI 0,865 to 0,920).

Conclusions

Patients with SCC show significantly higher AKASI than patients with BCC or patients without invasive tumours. Hence, AKASI may be used to stratify risk for developing invasive SCC.

This article is protected by copyright. All rights reserved.

Biological False Positive Venereal Disease Research Laboratory Test in Cerebrospinal Fluid in the Diagnosis of Neurosyphilis – A Case-Control Study

Abstract

Background

There is no clear consensus on the diagnosis of neurosyphilis. The Venereal Disease Research Laboratory (VDRL) test from cerebrospinal fluid (CSF) has traditionally been considered the gold standard for diagnosing neurosyphilis, but is widely known to be insensitive.

Objective

In this study, we compared the clinical and laboratory characteristics of true positive VDRL-CSF cases with biological false positive VDRL-CSF cases.

Methods

We retrospectively identified cases of true and false positive VDRL-CSF across a 3-year period received by the Immunology and Serology Laboratory, Singapore General Hospital. A biological false positive VDRL-CSF is defined as a reactive VDRL-CSF with a non-reactive Treponema pallidum particle agglutination (TPPA)-CSF and/or negative Line Immuno Assay (LIA)-CSF IgG. A true positive VDRL-CSF is a reactive VDRL-CSF with a concordant reactive TPPA-CSF and/or positive LIA-CSF IgG.

Results

During the study period, a total of 1,254 specimens underwent VDRL-CSF examination. Among these, 60 specimens from 53 patients tested positive for VDRL-CSF. Of the 53 patients, 42 (79.2%) were true positive cases and 11 (20.8%) were false positive cases. In our setting, a positive non-treponemal serology has 97.6% sensitivity, 100% specificity, 100% positive predictive value, and 91.7% negative predictive value for a true positive VDRL-CSF based on our laboratory definition. HIV seropositivity was an independent predictor of a true positive VDRL-CSF.

Conclusion

Biological false positive VDRL-CSF is common in a setting where patients are tested without first establishing a serological diagnosis of syphilis. Serological testing should be performed prior to CSF evaluation for neurosyphilis.

This article is protected by copyright. All rights reserved.

Penetration of Gold Nanoparticles Across the Stratum Corneum Layer of Thick-Skin

A major hurdle for transdermal drug delivery, is the passage of drugs across the stratum corneum (SC) layer of the epidermis. The SC comprises of thick keratinized epithelium that blocks entry of most hydrophobic and hydrophilic drugs [1]. Of special interest is the skin over the palmar and plantar areas, where the overall thickness of skin, along with the SC is much higher than other anatomical sites [2,3]. Further, the epidermis in the plantar and palmar areas is 3–4 fold thicker, thus making topical drug absorption highly dependent on the site of application [4].

The anterolateral thigh flap with kiss technique for microsurgical reconstruction of oncological scalp defects

Publication date: Available online 7 November 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Lingyun Xiong, Nengqiang Guo, Emre Gazyakan, Ulrich Kneser, Christoph Hirche

Segmentale Neurofibromatose

Zusammenfassung

Bei einem nun 48-jährigen Patienten entwickelten sich 13 Jahre zuvor zahlreiche Neurofibrome in einem umschriebenen Areal thorakal rechts. Zeitgleich wurde ein beidseitig vorliegendes Seminom diagnostiziert und behandelt. Aktuelle Untersuchungen ergaben keine Hinweise für weitere Begleiterkrankungen einer Neurofibromatose. Die Familienanamnese war unauffällig. Die bei dem Patienten vorliegende segmentale Neurofibromatose (SN) ist Ausdruck einer Mosaikbildung infolge einer Mutation des NF1-Gens, einem Tumorsuppressorgen. Begleiterkrankungen, wie sie für die Neurofibromatosis generalisata (NFG) typisch sind und zu denen auch maligne Neoplasien gezählt werden, stellen bei der SN die Ausnahme dar.

Error in End Matter

In the Editorial titled "Industry Influence in Dermatology Clinical Practice Guideline Development" by Katz, the end matter has been corrected by adding "Additional Information: Dr Katz is a member of the AAD and is co-chair of the AAD's Expert Resource Group on LGBT/Sexual and Gender Minority Health, and a member of the AAD's Bylaws Committee."

Topical Timolol for Paronychia and Pseudopyogenic Granuloma

This study evaluated the efficacy and tolerability of topical timolol, 0.5%, gel as a treatment of paronychia and pseudopyogenic granuloma induced by antineoplastic agents.

Interdisciplinary Perspectives on Sun Safety

This article describes efforts to harness interdisciplinary perspectives to enhance understanding of sun exposure risk and improve sun protection interventions.

Confirmed Gadolinium Presence Within Cutaneous Sclerotic Bodies

This case report describes the confirmation of gadolinium presence within cutaneous sclerotic bodies via laser ablation inductively coupled plasma mass spectrometry

Probiotic Strains for Children With Moderate Atopic Dermatitis

This randomized clinical trial investigates whether a mixture of oral probiotics is safe and effective in the treatment of atopic dermatitis symptoms and evaluates its influence on the use of topical steroids in children.

Resilience and Depression in Patients With Hidradenitis Suppurativa

This survey study uses clinical data from a set of self-administered, self-graded questionnaires to examine the correlation among resilience, depression, and health-related quality of life for patients with hidradenitis suppurativa.

After The Demonstration: What States Sustained After the End of Federal Grants to Improve Children’s Health Care Quality

Abstract

Introduction Under the CHIPRA Quality Demonstration Grant Program, CMS awarded $100 million through 10 grants that 18 state Medicaid agencies implemented between 2010 and 2015. The program's legislatively-mandated purpose was to evaluate promising ideas for improving the quality of children's health care provided through Medicaid and CHIP. As part of the program's multifaceted evaluation, this study examined the extent to which states sustained key program activities after the demonstration ended. Methods We identified 115 potentially sustainable elements within states' CHIPRA demonstrations and analyzed data from grantee reports and key informant interviews to assess sustainment outcomes and key influential factors. We also assessed sustainment of the projects' intellectual capital. Results 56% of potentially sustainable elements were sustained. Sustainment varied by topic area: Elements related to quality measure reporting and practice facilitation were more likely to be sustained than others, such as parent advisors. Broad contextual factors, the state's Medicaid environment, implementation partners' resources, and characteristics of the demonstration itself all shaped sustainment outcomes. Discussion Assessing sustainment of key elements of states' CHIPRA quality demonstration projects provides insight into the fates of the "promising ideas" that the grant program was designed to examine. As a result of the federal government's investment in this grant program, many demonstration states are in a strong position to extend and spread specific strategies for improving the quality of care for children in Medicaid and CHIP. Our findings provide insights for policymakers and providers working to improve the quality of health care for low income children.

The fragmentary model of temporal experience and the mirroring constraint

Abstract

A central debate in the current philosophical literature on temporal experience is over the following question: do temporal experiences themselves have a temporal structure that mirrors their temporal contents? Extensionalists argue that experiences do have a temporal structure that mirrors their temporal contents. Atomists insist that experiences don't have a temporal structure that mirrors their contents. In this paper, I argue that this debate is misguided. Both atomism and extensionalism, considered as general theories of temporal experience, are false, since temporal experience is not a single undifferentiated phenomena as both theories require. I argue for this conclusion in two steps. First, I show that introspection cannot settle the debate. Second, I argue that the neuroscientific evidence is best read as revealing a host of mechanisms involved in temporal perception - some admitting of an extensionalist interpretation while others admitting only of an atomistic interpretation. As a result, neither side of the debate wins.

On being difficult: towards an account of the nature of difficulty

Abstract

This paper critically assesses existing accounts of the nature of difficulty, finds them wanting, and proposes a new account. The concept of difficulty is routinely invoked in debates regarding degrees of moral responsibility, and the value of achievement. Until recently, however, there has not been any sustained attempt to provide an account of the nature of difficulty itself. This has changed with Gwen Bradford's Achievement, which argues that difficulty is a matter of how much intense effort is expended. But while this account captures something important about the relationship between difficulty and achievement, it fails to account for the fact that part of what makes achievements great is that they are difficult in a moderately agent-neutral kind of way. Nor is this thought captured by any other extant account. I argue that to fill this gap we should think of (one kind of) difficulty in terms of low probability of success.

Euler’s Königsberg: the explanatory power of mathematics

Abstract

The present paper provides an analysis of Euler's solutions to the Königsberg bridges problem. Euler proposes three different solutions to the problem, addressing their strengths and weaknesses along the way. I put the analysis of Euler's paper to work in the philosophical discussion on mathematical explanations. I propose that the key ingredient to a good explanation is the degree to which it provides relevant information. Providing relevant information is based on knowledge of the structure in question, graphs in the present case. I also propose computational complexity and logical strength as measures of relevant information.

Suppression and Contrast Normalization in Motion Processing

Sensory neurons are activated by a range of stimuli to which they are said to be tuned. Usually, they are also suppressed by another set of stimuli that have little effect when presented in isolation. The interactions between preferred and suppressive stimuli are often quite complex and vary across neurons, even within a single area, making it difficult to infer their collective effect on behavioral responses mediated by activity across populations of neurons. Here, we investigated this issue by measuring, in human subjects (three males), the suppressive effect of static masks on the ocular following responses induced by moving stimuli. We found a wide range of effects, which depend in a nonlinear and nonseparable manner on the spatial frequency, contrast, and spatial location of both stimulus and mask. Under some conditions, the presence of the mask can be seen as scaling the contrast of the driving stimulus. Under other conditions, the effect is more complex, involving also a direct scaling of the behavioral response. All of this complexity at the behavioral level can be captured by a simple model in which stimulus and mask interact nonlinearly at two stages, one monocular and one binocular. The nature of the interactions is compatible with those observed at the level of single neurons in primates, usually broadly described as divisive normalization, without having to invoke any scaling mechanism.

SIGNIFICANCE STATEMENT The response of sensory neurons to their preferred stimulus is often modulated by stimuli that are not effective when presented alone. Individual neurons can exhibit multiple modulatory effects, with considerable variability across neurons even in a single area. Such diversity has made it difficult to infer the impact of these modulatory mechanisms on behavioral responses. Here, we report the effects of a stationary mask on the reflexive eye movements induced by a moving stimulus. A model with two stages, each incorporating a divisive modulatory mechanism, reproduces our experimental results and suggests that qualitative variability of masking effects in cortical neurons might arise from differences in the extent to which such effects are inherited from earlier stages.

Dynamic Trial-by-Trial Recoding of Task-Set Representations in the Frontoparietal Cortex Mediates Behavioral Flexibility

Cognitive flexibility forms the core of the extraordinary ability of humans to adapt, but the precise neural mechanisms underlying our ability to nimbly shift between task sets remain poorly understood. Recent functional magnetic resonance imaging (fMRI) studies employing multivoxel pattern analysis (MVPA) have shown that a currently relevant task set can be decoded from activity patterns in the frontoparietal cortex, but whether these regions support the dynamic transformation of task sets from trial to trial is not clear. Here, we combined a cued task-switching protocol with human (both sexes) fMRI, and harnessed representational similarity analysis (RSA) to facilitate a novel assessment of trial-by-trial changes in neural task-set representations. We first used MVPA to define task-sensitive frontoparietal and visual regions and found that neural task-set representations on switch trials are less stably encoded than on repeat trials. We then exploited RSA to show that the neural representational pattern dissimilarity across consecutive trials is greater for switch trials than for repeat trials, and that the degree of this pattern dissimilarity predicts behavior. Moreover, the overall neural pattern of representational dissimilarities followed from the assumption that repeating sets, compared with switching sets, results in stronger neural task representations. Finally, when moving from cue to target phase within a trial, pattern dissimilarities tracked the transformation from previous-trial task representations to the currently relevant set. These results provide neural evidence for the longstanding assumptions of an effortful task-set reconfiguration process hampered by task-set inertia, and they demonstrate that frontoparietal and stimulus processing regions support "dynamic adaptive coding," flexibly representing changing task sets in a trial-by-trial fashion.

SIGNIFICANCE STATEMENT Humans can fluently switch between different tasks, reflecting an ability to dynamically configure "task sets," rule representations that link stimuli to appropriate responses. Recent studies show that neural signals in frontal and parietal brain regions can tell us which of two tasks a person is currently performing. However, it is not known whether these regions are also involved in dynamically reconfiguring task-set representations when switching between tasks. Here we measured human brain activity during task switching and tracked the similarity of neural task-set representations from trial to trial. We show that frontal and parietal brain regions flexibly recode changing task sets in a trial-by-trial fashion, and that task-set similarity over consecutive trials predicts behavior.

Correction: Melo-Carrillo et al., "Selective Inhibition of Trigeminovascular Neurons by Fremanezumab: A Humanized Monoclonal Anti-CGRP Antibody"

Hebbian Learning in a Random Network Captures Selectivity Properties of the Prefrontal Cortex

Complex cognitive behaviors, such as context-switching and rule-following, are thought to be supported by the prefrontal cortex (PFC). Neural activity in the PFC must thus be specialized to specific tasks while retaining flexibility. Nonlinear "mixed" selectivity is an important neurophysiological trait for enabling complex and context-dependent behaviors. Here we investigate (1) the extent to which the PFC exhibits computationally relevant properties, such as mixed selectivity, and (2) how such properties could arise via circuit mechanisms. We show that PFC cells recorded from male and female rhesus macaques during a complex task show a moderate level of specialization and structure that is not replicated by a model wherein cells receive random feedforward inputs. While random connectivity can be effective at generating mixed selectivity, the data show significantly more mixed selectivity than predicted by a model with otherwise matched parameters. A simple Hebbian learning rule applied to the random connectivity, however, increases mixed selectivity and enables the model to match the data more accurately. To explain how learning achieves this, we provide analysis along with a clear geometric interpretation of the impact of learning on selectivity. After learning, the model also matches the data on measures of noise, response density, clustering, and the distribution of selectivities. Of two styles of Hebbian learning tested, the simpler and more biologically plausible option better matches the data. These modeling results provide clues about how neural properties important for cognition can arise in a circuit and make clear experimental predictions regarding how various measures of selectivity would evolve during animal training.

SIGNIFICANCE STATEMENT The prefrontal cortex is a brain region believed to support the ability of animals to engage in complex behavior. How neurons in this area respond to stimuli—and in particular, to combinations of stimuli ("mixed selectivity")—is a topic of interest. Even though models with random feedforward connectivity are capable of creating computationally relevant mixed selectivity, such a model does not match the levels of mixed selectivity seen in the data analyzed in this study. Adding simple Hebbian learning to the model increases mixed selectivity to the correct level and makes the model match the data on several other relevant measures. This study thus offers predictions on how mixed selectivity and other properties evolve with training.

A Role of Endogenous Progesterone in Stroke Cerebroprotection Revealed by the Neural-Specific Deletion of Its Intracellular Receptors

Treatment with progesterone protects the male and female brain against damage after middle cerebral artery occlusion (MCAO). However, in both sexes, the brain contains significant amounts of endogenous progesterone. It is not known whether endogenously produced progesterone enhances the resistance of the brain to ischemic insult. Here, we used steroid profiling by gas chromatography-tandem mass spectrometry (GC-MS/MS) for exploring adaptive and sex-specific changes in brain levels of progesterone and its metabolites after MCAO. We show that, in the male mouse brain, progesterone is mainly metabolized via 5α-reduction leading to 5α-dihydroprogesterone (5α-DHP), also a progesterone receptor (PR) agonist ligand in neural cells, then to 3α,5α-tetrahydroprogesterone (3α,5α-THP). In the female mouse brain, levels of 5α-DHP and 3α,5α-THP are lower and levels of 20α-DHP are higher than in males. After MCAO, levels of progesterone and 5α-DHP are upregulated rapidly to pregnancy-like levels in the male but not in the female brain. To assess whether endogenous progesterone and 5α-DHP contribute to the resistance of neural cells to ischemic damage, we inactivated PR selectively in the CNS. Deletion of PR in the brain reduced its resistance to MCAO, resulting in increased infarct volumes and neurological deficits in both sexes. Importantly, endogenous PR ligands continue to protect the brain of aging mice. These results uncover the unexpected importance of endogenous progesterone and its metabolites in cerebroprotection. They also reveal that the female reproductive hormone progesterone is an endogenous cerebroprotective neurosteroid in both sexes.

SIGNIFICANCE STATEMENT The brain responds to injury with protective signaling and has a remarkable capacity to protect itself. We show here that, in response to ischemic stroke, levels of progesterone and its neuroactive metabolite 5α-dihydroprogesterone are upregulated rapidly in the male mouse brain but not in the female brain. An important role of endogenous progesterone in cerebroprotection was demonstrated by the conditional inactivation of its receptor in neural cells. These results show the importance of endogenous progesterone, its metabolites, and neural progesterone receptors in acute cerebroprotection after stroke. This new concept could be exploited therapeutically by taking into account the progesterone status of patients and by supplementing and reinforcing endogenous progesterone signaling for attaining its full cerebroprotective potential.

In Vivo Imaging of CNS Injury and Disease

In vivo optical imaging has emerged as a powerful tool with which to study cellular responses to injury and disease in the mammalian CNS. Important new insights have emerged regarding axonal degeneration and regeneration, glial responses and neuroinflammation, changes in the neurovascular unit, and, more recently, neural transplantations. Accompanying a 2017 SfN Mini-Symposium, here, we discuss selected recent advances in understanding the neuronal, glial, and other cellular responses to CNS injury and disease with in vivo imaging of the rodent brain or spinal cord. We anticipate that in vivo optical imaging will continue to be at the forefront of breakthrough discoveries of fundamental mechanisms and therapies for CNS injury and disease.

Illuminating Neural Circuits: From Molecules to MRI

Neurological disease drives symptoms through pathological changes to circuit functions. Therefore, understanding circuit mechanisms that drive behavioral dysfunction is of critical importance for quantitative diagnosis and systematic treatment of neurological disease. Here, we describe key technologies that enable measurement and manipulation of neural activity and neural circuits. Applying these approaches led to the discovery of circuit mechanisms underlying pathological motor behavior, arousal regulation, and protein accumulation. Finally, we discuss how optogenetic functional magnetic resonance imaging reveals global scale circuit mechanisms, and how circuit manipulations could lead to new treatments of neurological diseases.

CB1-Dependent Long-Term Depression in Ventral Tegmental Area GABA Neurons: A Novel Target for Marijuana

The VTA is necessary for reward behavior with dopamine cells critically involved in reward signaling. Dopamine cells in turn are innervated and regulated by neighboring inhibitory GABA cells. Using whole-cell electrophysiology in juvenile-adolescent GAD67-GFP male mice, we examined excitatory plasticity in fluorescent VTA GABA cells. A novel CB1-dependent LTD was induced in GABA cells that was dependent on metabotropic glutamate receptor 5, and cannabinoid receptor 1 (CB1). LTD was absent in CB1 knock-out mice but preserved in heterozygous littermates. Bath applied ⁹-tetrahydrocannabinol depressed GABA cell activity, therefore downstream dopamine cells will be disinhibited; and thus, this could potentially result in increased reward. Chronic injections of ⁹-tetrahydrocannabinol occluded LTD compared with vehicle injections; however, a single exposure was insufficient to do so. As synaptic modifications by drugs of abuse are often tied to addiction, these data suggest a possible mechanism for the addictive effects of ⁹-tetrahydrocannabinol in juvenile-adolescents, by potentially altering reward behavioral outcomes.

SIGNIFICANCE STATEMENT The present study identifies a novel form of glutamatergic synaptic plasticity in VTA GABA neurons, a currently understudied cell type that is critical for the brain's reward circuit, and how ⁹-tetrahydrocannabinol occludes this plasticity. This study specifically addresses a potential unifying mechanism whereby marijuana could exert rewarding and addictive/withdrawal effects. Marijuana use and legalization are a pressing issue for many states in the United States. Although marijuana is the most commonly abused illicit drug, the implications of legalized, widespread, or continued usage are speculative. This study in juvenile-adolescent aged mice identifies a novel form of synaptic plasticity in VTA GABA cells, and the synaptic remodeling that can occur after ⁹-tetrahydrocannabinol use.

Unconventional NMDA Receptor Signaling

In the classical view, NMDA receptors (NMDARs) are stably expressed at the postsynaptic membrane, where they act via Ca²⁺ to signal coincidence detection in Hebbian plasticity. More recently, it has been established that NMDAR-mediated transmission can be dynamically regulated by neural activity. In addition, NMDARs have been found presynaptically, where they cannot act as conventional coincidence detectors. Unexpectedly, NMDARs have also been shown to signal metabotropically, without the need for Ca²⁺. This review highlights novel findings concerning these unconventional modes of NMDAR action.

Foxp1 in Forebrain Pyramidal Neurons Controls Gene Expression Required for Spatial Learning and Synaptic Plasticity

Genetic perturbations of the transcription factor Forkhead Box P1 (FOXP1) are causative for severe forms of autism spectrum disorder that are often comorbid with intellectual disability. Recent work has begun to reveal an important role for FoxP1 in brain development, but the brain-region-specific contributions of Foxp1 to autism and intellectual disability phenotypes have yet to be determined fully. Here, we describe Foxp1 conditional knock-out (Foxp1^cKO) male and female mice with loss of Foxp1 in the pyramidal neurons of the neocortex and the CA1/CA2 subfields of the hippocampus. Foxp1^cKO mice exhibit behavioral phenotypes that are of potential relevance to autism spectrum disorder, including hyperactivity, increased anxiety, communication impairments, and decreased sociability. In addition, Foxp1^cKO mice have gross deficits in learning and memory tasks of relevance to intellectual disability. Using a genome-wide approach, we identified differentially expressed genes in the hippocampus of Foxp1^cKO mice associated with synaptic function and development. Furthermore, using magnetic resonance imaging, we uncovered a significant reduction in the volumes of both the entire hippocampus as well as individual hippocampal subfields of Foxp1^cKO mice. Finally, we observed reduced maintenance of LTP in area CA1 of the hippocampus in these mutant mice. Together, these data suggest that proper expression of Foxp1 in the pyramidal neurons of the forebrain is important for regulating gene expression pathways that contribute to specific behaviors reminiscent of those seen in autism and intellectual disability. In particular, Foxp1 regulation of gene expression appears to be crucial for normal hippocampal development, CA1 plasticity, and spatial learning.

SIGNIFICANCE STATEMENT Loss-of-function mutations in the transcription factor Forkhead Box P1 (FOXP1) lead to autism spectrum disorder and intellectual disability. Understanding the potential brain-region-specific contributions of FOXP1 to disease-relevant phenotypes could be a critical first step in the management of patients with these mutations. Here, we report that Foxp1 conditional knock-out (Foxp1^cKO) mice with loss of Foxp1 in the neocortex and hippocampus display autism and intellectual-disability-relevant behaviors. We also show that these phenotypes correlate with changes in both the genomic and physiological profiles of the hippocampus in Foxp1^cKO mice. Our work demonstrates that brain-region-specific FOXP1 expression may relate to distinct, clinically relevant phenotypes.

Nonhuman Primate Optogenetics: Recent Advances and Future Directions

Optogenetics is the use of genetically coded, light-gated ion channels or pumps (opsins) for millisecond resolution control of neural activity. By targeting opsin expression to specific cell types and neuronal pathways, optogenetics can expand our understanding of the neural basis of normal and pathological behavior. To maximize the potential of optogenetics to study human cognition and behavior, optogenetics should be applied to the study of nonhuman primates (NHPs). The homology between NHPs and humans makes these animals the best experimental model for understanding human brain function and dysfunction. Moreover, for genetic tools to have translational promise, their use must be demonstrated effectively in large, wild-type animals such as Rhesus macaques. Here, we review recent advances in primate optogenetics. We highlight the technical hurdles that have been cleared, challenges that remain, and summarize how optogenetic experiments are expanding our understanding of primate brain function.

Dendritic and Axonal L-Type Calcium Channels Cooperate to Enhance Motoneuron Firing Output during Drosophila Larval Locomotion

Behaviorally adequate neuronal firing patterns are critically dependent on the specific types of ion channel expressed and on their subcellular localization. This study combines in situ electrophysiology with genetic and pharmacological intervention in larval Drosophila melanogaster of both sexes to address localization and function of L-type like calcium channels in motoneurons. We demonstrate that Dmca1D (Ca_v1 homolog) L-type like calcium channels localize to both the somatodendritic and the axonal compartment of larval crawling motoneurons. In situ patch-clamp recordings in genetic mosaics reveal that Dmca1D channels increase burst duration and maximum intraburst firing frequencies during crawling-like motor patterns in semi-intact animals. Genetic and acute pharmacological manipulations suggest that prolonged burst durations are caused by dendritically localized Dmca1D channels, which activate upon cholinergic synaptic input and amplify EPSPs, thus indicating a conserved function of dendritic L-type channels from Drosophila to vertebrates. By contrast, maximum intraburst firing rates require axonal calcium influx through Dmca1D channels, likely to enhance sodium channel de-inactivation via a fast afterhyperpolarization through BK channel activation. Therefore, in unmyelinated Drosophila motoneurons different functions of axonal and dendritic L-type like calcium channels likely operate synergistically to maximize firing output during locomotion.

SIGNIFICANCE STATEMENT Nervous system function depends on the specific excitabilities of different types of neurons. Excitability is largely shaped by different combinations of voltage-dependent ion channels. Despite a high degree of conservation, the huge diversity of ion channel types and their differential localization pose challenges in assigning distinct functions to specific channels across species. We find a conserved role, from fruit flies to mammals, for L-type calcium channels in augmenting motoneuron excitability. As in spinal cord, dendritic L-type channels amplify excitatory synaptic input. In contrast to spinal motoneurons, axonal L-type channels enhance firing rates in unmyelinated Drosophila motoraxons. Therefore, enhancing motoneuron excitability by L-type channels seems an old strategy, but localization and interactions with other channels are tuned to species-specific requirements.

Sensation during Active Behaviors

A substantial portion of our sensory experience happens during active behaviors such as walking around or paying attention. How do sensory systems work during such behaviors? Neural processing in sensory systems can be shaped by behavior in multiple ways ranging from a modulation of responsiveness or sharpening of tuning to a dynamic change of response properties or functional connectivity. Here, we review recent findings on the modulation of sensory processing during active behaviors in different systems: insect vision, rodent thalamus, and rodent sensory cortices. We discuss the circuit-level mechanisms that might lead to these modulations and their potential role in sensory function. Finally, we highlight the open questions and future perspectives of this exciting new field.

Delineating the Diversity of Spinal Interneurons in Locomotor Circuits

Locomotion is common to all animals and is essential for survival. Neural circuits located in the spinal cord have been shown to be necessary and sufficient for the generation and control of the basic locomotor rhythm by activating muscles on either side of the body in a specific sequence. Activity in these neural circuits determines the speed, gait pattern, and direction of movement, so the specific locomotor pattern generated relies on the diversity of the neurons within spinal locomotor circuits. Here, we review findings demonstrating that developmental genetics can be used to identify populations of neurons that comprise these circuits and focus on recent work indicating that many of these populations can be further subdivided into distinct subtypes, with each likely to play complementary functions during locomotion. Finally, we discuss data describing the manner in which these populations interact with each other to produce efficient, task-dependent locomotion.

Distinct Laterality in Forelimb-Movement Representations of Rat Primary and Secondary Motor Cortical Neurons with Intratelencephalic and Pyramidal Tract Projections

Two distinct motor areas, the primary and secondary motor cortices (M1 and M2), play crucial roles in voluntary movement in rodents. The aim of this study was to characterize the laterality in motor cortical representations of right and left forelimb movements. To achieve this goal, we developed a novel behavioral task, the Right-Left Pedal task, in which a head-restrained male rat manipulates a right or left pedal with the corresponding forelimb. This task enabled us to monitor independent movements of both forelimbs with high spatiotemporal resolution. We observed phasic movement-related neuronal activity (Go-type) and tonic hold-related activity (Hold-type) in isolated unilateral movements. In both M1 and M2, Go-type neurons exhibited bias toward contralateral preference, whereas Hold-type neurons exhibited no bias. The contralateral bias was weaker in M2 than M1. Moreover, we differentiated between intratelencephalic (IT) and pyramidal tract (PT) neurons using optogenetically evoked spike collision in rats expressing channelrhodopsin-2. Even in identified PT and IT neurons, Hold-type neurons exhibited no lateral bias. Go-type PT neurons exhibited bias toward contralateral preference, whereas IT neurons exhibited no bias. Our findings suggest a different laterality of movement representations of M1 and M2, in each of which IT neurons are involved in cooperation of bilateral movements, whereas PT neurons control contralateral movements.

SIGNIFICANCE STATEMENT In rodents, the primary and secondary motor cortices (M1 and M2) are involved in voluntary movements via distinct projection neurons: intratelencephalic (IT) neurons and pyramidal tract (PT) neurons. However, it remains unclear whether the two motor cortices (M1 vs M2) and the two classes of projection neurons (IT vs PT) have different laterality of movement representations. We optogenetically identified these neurons and analyzed their functional activity using a novel behavioral task to monitor movements of the right and left forelimbs separately. We found that contralateral bias was reduced in M2 relative to M1, and in IT relative to PT neurons. Our findings suggest that the motor information processing that controls forelimb movement is coordinated by a distinct cell population.

Consciousness Regained: Disentangling Mechanisms, Brain Systems, and Behavioral Responses

How consciousness (experience) arises from and relates to material brain processes (the "mind-body problem") has been pondered by thinkers for centuries, and is regarded as among the deepest unsolved problems in science, with wide-ranging theoretical, clinical, and ethical implications. Until the last few decades, this was largely seen as a philosophical topic, but not widely accepted in mainstream neuroscience. Since the 1980s, however, novel methods and theoretical advances have yielded remarkable results, opening up the field for scientific and clinical progress. Since a seminal paper by Crick and Koch (1998) claimed that a science of consciousness should first search for its neural correlates (NCC), a variety of correlates have been suggested, including both content-specific NCCs, determining particular phenomenal components within an experience, and the full NCC, the neural substrates supporting entire conscious experiences. In this review, we present recent progress on theoretical, experimental, and clinical issues. Specifically, we (1) review methodological advances that are important for dissociating conscious experience from related enabling and executive functions, (2) suggest how critically reconsidering the role of the frontal cortex may further delineate NCCs, (3) advocate the need for general, objective, brain-based measures of the capacity for consciousness that are independent of sensory processing and executive functions, and (4) show how animal studies can reveal population and network phenomena of relevance for understanding mechanisms of consciousness.

Volition and Action in the Human Brain: Processes, Pathologies, and Reasons

Humans seem to decide for themselves what to do, and when to do it. This distinctive capacity may emerge from an ability, shared with other animals, to make decisions for action that are related to future goals, or at least free from the constraints of immediate environmental inputs. Studying such volitional acts proves a major challenge for neuroscience. This review highlights key mechanisms in the generation of voluntary, as opposed to stimulus-driven actions, and highlights three issues. The first part focuses on the apparent spontaneity of voluntary action. The second part focuses on one of the most distinctive, but elusive, features of volition, namely, its link to conscious experience, and reviews stimulation and patient studies of the cortical basis of conscious volition down to the single-neuron level. Finally, we consider the goal-directedness of voluntary action, and discuss how internal generation of action can be linked to goals and reasons.

Central Network Dynamics Regulating Visceral and Humoral Functions

The brain processes information from the periphery and regulates visceral and immune activity to maintain internal homeostasis, optimally respond to a dynamic external environment, and integrate these functions with ongoing behavior. In addition to its relevance for survival, this integration underlies pathology as evidenced by diseases exhibiting comorbid visceral and psychiatric symptoms. Advances in neuroanatomical mapping, genetically specific neuronal manipulation, and neural network recording are overcoming the challenges of dissecting complex circuits that underlie this integration and deciphering their function. Here we focus on reciprocal communication between the brain and urological, gastrointestinal, and immune systems. These studies are revealing how autonomic activity becomes integrated into behavior as part of a social strategy, how the brain regulates innate immunity in response to stress, and how drugs impact emotion and gastrointestinal function. These examples highlight the power of the functional organization of circuits at the interface of the brain and periphery.

The Lateral Habenula and Its Input to the Rostromedial Tegmental Nucleus Mediates Outcome-Specific Conditioned Inhibition

Animals can readily learn that stimuli predict the absence of specific appetitive outcomes; however, the neural substrates underlying such outcome-specific conditioned inhibition remain largely unexplored. Here, using female and male rats as subjects, we examined the involvement of the lateral habenula (LHb) and of its inputs onto the rostromedial tegmental nucleus (RMTg) in inhibitory learning. In these experiments, we used backward conditioning and contingency reversal to establish outcome-specific conditioned inhibitors for two distinct appetitive outcomes. Then, using the Pavlovian-instrumental transfer paradigm, we assessed the effects of manipulations of the LHb and the LHb–RMTg pathway on that inhibitory encoding. In control animals, we found that an outcome-specific conditioned inhibitor biased choice away from actions delivering that outcome and toward actions earning other outcomes. Importantly, this bias was abolished by both electrolytic lesions of the LHb and selective ablation of LHb neurons using Cre-dependent Caspase3 expression in Cre-expressing neurons projecting to the RMTg. This deficit was specific to conditioned inhibition; an excitatory predictor of a specific outcome-biased choice toward actions delivering the same outcome to a similar degree whether the LHb or the LHb–RMTg network was intact or not. LHb lesions also disrupted the ability of animals to inhibit previously encoded stimulus–outcome contingencies after their reversal, pointing to a critical role of the LHb and of its inputs onto the RMTg in outcome-specific conditioned inhibition in appetitive settings. These findings are consistent with the developing view that the LHb promotes a negative reward prediction error in Pavlovian conditioning.

SIGNIFICANCE STATEMENT Stimuli that positively or negatively predict rewarding outcomes influence choice between actions that deliver those outcomes. Previous studies have found that a positive predictor of a specific outcome biases choice toward actions delivering that outcome. In contrast, a negative predictor of an outcome biases choice away from actions earning that outcome and toward other actions. Here we reveal that the lateral habenula is critical for negative predictors, but not positive predictors, to affect choice. Furthermore, these effects were found to require activation of lateral habenula inputs to the rostromedial tegmental nucleus. These results are consistent with the view that the lateral habenula establishes inhibitory relationships between stimuli and food outcomes and computes a negative prediction error in Pavlovian conditioning.

Adolescence and Reward: Making Sense of Neural and Behavioral Changes Amid the Chaos

Adolescence is a time of significant neural and behavioral change with remarkable development in social, emotional, and cognitive skills. It is also a time of increased exploration and risk-taking (e.g., drug use). Many of these changes are thought to be the result of increased reward-value coupled with an underdeveloped inhibitory control, and thus a hypersensitivity to reward. Perturbations during adolescence can alter the developmental trajectory of the brain, resulting in long-term alterations in reward-associated behaviors. This review highlights recent developments in our understanding of how neural circuits, pubertal hormones, and environmental factors contribute to adolescent-typical reward-associated behaviors with a particular focus on sex differences, the medial prefrontal cortex, social reward, social isolation, and drug use. We then introduce a new approach that makes use of natural adaptations of seasonally breeding species to investigate the role of pubertal hormones in adolescent development. This research has only begun to parse out contributions of the many neural, endocrine, and environmental changes to the heightened reward sensitivity and increased vulnerability to mental health disorders that characterize this life stage.

Descriptive Error in the Text

In the Original Investigation titled "Prevalence of Pubic Hair Grooming–Related Injuries and Identification of High-Risk Individuals in the United States," published online August 16, 2017, there was a descriptive error in the text. The term vagina was used rather than the more accurate labia majora in 4 instances. This article has been corrected online.

Patient Perceptions of Primary Care–Based Skin Cancer Screening

This analysis of a series of interviews seeks to better understand patient perceptions of primary care–based skin cancer screening.

Prior Authorizations for Diagnostic Skin Biopsies

This Viewpoint outlines how managed care policies on prior authorization for diagnostic skin biopsies are affecting costs, access to care, and quality of care for patients.

November 2017 Issue Highlights

Attempting to Define “Hypoallergenic”

The North American Contact Dermatitis Group (NACDG) commends Xu et al for bringing attention to challenges facing dermatologists and consumers. Their original approach of using sales data provides a snapshot of what consumers are actually using (lotions!), and their assessment of commonly used marketing terms and their connection to cost and product composition are innovative.

Purpura Annularis Telangiectodes of Majocchi Associated With Apremilast

This case report describes a patient with purpura annularis telangiectodes of Majocchi associated with the initiation and rechallenge of apremilast for psoriasis vulgaris

Delay and Disparity in Time to Surgical Treatment for Melanoma

The relationship between patient health insurance status, health care use, and outcomes has been explored in great depth and detail over decades for myriad diseases in the United States. Likewise, health services research has become increasingly relevant within the specialty of dermatology, especially as the emergence of "big data" and advanced analytics continue to transform overall health care delivery.

Robert Chesebrough and the Dermatologic Wonder of Petroleum Jelly

Robert Chesebrough (1837-1933) was an American chemist whose serendipitous discovery and scientific tenacity led to one of the most common and enduring treatments in dermatology. He began his career in Brooklyn isolating kerosene from whale oil, but in 1858, his business's viability was threatened by the first successful American oil well, located in Titusville, Pennsylvania.

Performance Characteristics of and Allergens in Best-selling Moisturizers

This cohort study examines the product performance characteristics and ingredients of best-selling moisturizers.

Coverage of IVIG for Autoimmune Blistering Diseases by US Insurers

In this study, the authors examine coverage for IVIG to treat autoimmune blistering diseases by public and private insurers in the United States.

Association of Delays in Surgery for Melanoma With Insurance Type

This cohort study investigates whether patients with Medicaid are more likely than patients with Medicare or private insurance to experience delays in surgery for melanoma.

Secukinumab-Induced Psoriasiform Eruption

This case report describes a patient with secukinumab-induced psoriasiform eruption.

Pubic Hair Grooming Injuries and Identification of High-Risk Individuals

This cross-sectional study of US adults identifies demographic and behavioral risk factors associated with pubic hair grooming–related injuries to characterize individuals at high risk for injury and develop recommendations for safe grooming practices.

The Treatment of Actinic Keratoses—The Rule Rather Than the Exception

To the Editor We read with great interest the article by Berry et al entitled "Influence of Information Framing on Patient Decisions to Treat Actinic Keratosis." This work highlights a critical aspect of the physician-patient relationship—communication. As expected, the findings suggest that the verbiage used to describe actinic keratoses (AKs) can affect the patient's decision to pursue treatment. Interestingly, regardless of how the question was framed, most patients preferred to treat these lesions.

Improvement of Genetic Testing for Cutaneous Melanoma

This study evaluates the efficiency of using the "rule of 3" vs the widely accepted "rule of 2" for the detection of melanoma-prone mutations in France, a country with low to moderate melanoma incidence.

The Black Panther, From Politics to Popular Culture

Although the black panther is not a true animal species, the term is used to describe black pigmentation in a number of large feline species, including jaguars and leopards. Studies show that their dark pigmentation patterns are linked to polymorphisms in 2 genes, the melanocortin-1 receptor (MC1R) and the agouti-signaling protein (ASIP). The melanocortin-1 receptor is activated by binding of α-melanocyte–stimulating hormone, leading to the production of eumelanin, which is responsible for dark pigmentation. Conversely, the melanocortin-1 receptor is inhibited by the antagonist ASIP, leading to the production of pheomelanin, which is responsible for light pigmentation. Therefore, activating mutations in MC1R and inactivating mutations in ASIP are thought to underlie the melanization of the captivating black panther. In 1966, these striking animals became a symbol for one of the most influential civil rights groups, as well as the inspiration for Marvel Comics' first black superhero.

Risk Factors for Melanoma in Renal Transplant Recipients

This cohort study uses data from the United States Renal Data System to investigate risk factors and characteristics of renal transplant recipients who develop melanoma.

Nathaniel Hawthorne’s “The Birthmark”

A short story titled "The Birthmark," written by Nathaniel Hawthorne in 1843, revolves around none other than a prominent birthmark. The main character, Aylmer, is an intelligent, retired scientist whose love of science is only matched by his love for his spectacularly beautiful new wife, Georgiana. But soon after the two wed, Aylmer becomes obsessed with a crimson, hand-shaped mark on his bride's left cheek, a mark Georgiana had considered a "charm" prior to Aylmer's mention. Georgiana's perception of her mark turns to disgust with each passing day of her husband's obsession. Aylmer believes he can liberate his wife from this mark, her only flaw, and he spends the length of the story seeking a method to do so.

Pneumocystis Pneumonia in Patients With Autoimmune Blistering Diseases

This analysis assesses the incidence of Pneumocystis pneumonia in patients with autoimmune blistering diseases receiving no routine prophylaxis.

Erythema With Nonscarring, Tense Blisters and No Anti-BP180 Antibodies

A woman in her 80s had scaly erythematous plaques with nonscarring, tense blister formation without circulating anti-BP180 antibodies. What is your diagnosis?

Pedicle-to-Perforator Bypass Using Supermicrosurgical Technique for Deep Inferior Epigastric Artery Perforator Flap Salvage

No abstract available

Psychometric Validation of the BODY-Q in Danish Patients Undergoing Weight Loss and Body Contouring Surgery

Background: A well-developed patient-reported outcome instrument is needed for use in Danish bariatric and body contouring patients. The BODY-Q is designed to measure changes in important patient outcomes over the entire patient journey, from obesity to post-body contouring surgery. The current study aims to psychometrically validate the BODY-Q for use in Danish patients. Methods: The process consisted of 3 stages: translation and linguistic validation, field-test, and data analysis. The translation was performed in accordance with the International Society for Pharmacoeconomics and Outcomes Research and World Health Organization guidelines, and field-test data were collected in 4 departments in 2 different hospitals. Field-test data were analyzed using Rasch Measurement Theory. Results: A total of 495 patients completed the Danish BODY-Q field-test 1–4 times, leading to a total of 681 assessments with an overall response rate at 76%. Cronbach α values were ≥ 0.90, and person separation index values were in general high. The Rasch Measurement Theory analysis provided broad support for the reliability and validity of the Danish version of the BODY-Q scales. Item fit was outside the criteria for 34 of 138 items, and of these, 21 had a significant chi-square P value after Bonferroni adjustment. Most items (128 of 138) had ordered thresholds, indicating that response options worked as intended. Conclusion: The Danish version of the BODY-Q is a reliable and valid patient-reported outcome instrument for use in Danish bariatric and body contouring patients.

Facial Contouring Surgery—Mandibuloplasty: Genioplasty and Mandible Angle Correction

No abstract available

Preliminary Study of PGA Fabric for Seromas at Latissimus Dorsi Flap Donor Sites

Background: Seroma formation is a major complication following latissimus dorsi (LD) flap transfer for breast reconstruction. We implanted a nonwoven polyglycolic acid (PGA) fabric—a biodegradable polymer—in the LD flap donor site and examined its effect on postoperative seroma formation and resolution in a comparative study on 38 patients undergoing primary 1-stage breast reconstruction by LD flap. Method: A PGA treatment group had a PGA fabric placed in the donor wound (PGA group, n = 20), whereas a second group was treated with standard donor site closure (control group, n = 18). The incidence of seromas was comparable between the groups. Result: There was a significant reduction in aspiration volume by needle aspiration after drain removal (P

Can Friedberg’s Triad Solve Persistent Anesthesia Problems? Over-Medication, Pain Management, Postoperative Nausea and Vomiting

Summary: Friedberg's Triad is (1) measure the brain; (2) preempt the pain; (3) emetic drugs abstain. Persistent anesthesia problems include over- and under-medication, postoperative pain management, and postoperative nausea and vomiting. Inspired by Vinnik's diazepam-ketamine paradigm, Friedberg's propofol ketamine paradigm was first published in 1993. The 1997 addition of the bispectral (BIS) index brain monitor made the propofol ketamine paradigm numerically reproducible. The 1998 addition of the frontalis electromyogram (EMG) as a secondary trend to the BIS transformed the time-delayed BIS monitor into a real-time, extremely useful device. Before BIS monitoring, anesthesiologists only had heart rate (HR) and blood pressure (BP) changes to guide depth of anesthesia. Not surprisingly, the American Society of Anesthesiologists' Awareness study showed no HR or BP changes in half of the patients experiencing awareness with recall. HR and BP changes may only reflect brain stem signs while consciousness and pain are processed at higher, cortical brain levels. BIS/electromyogram measurement can accurately reflect propofol effect on the cerebral cortex in real time. Although propofol requirements can vary as much as a hundred-fold, titrating propofol to 60

DIEP Flap Breast Reconstruction in Patients with Breast Ptosis: 2-Stage Reconstruction Using 3-Dimensional Surface Imaging and a Printed Mold

Background: Autologous breast reconstruction can be performed for breasts with ptosis to a certain extent, but if patients desire to correct ptosis, mastopexy of the contralateral breast is indicated. However, accurate prediction of post-mastopexy breast shape is difficult to make, and symmetrical breast reconstruction requires certain experience. We have previously reported the use of three-dimensional (3D) imaging and printing technologies in deep inferior epigastric artery perforator (DIEP) flap breast reconstruction. In the present study, these technologies were applied to the reconstruction of breasts with ptosis. Methods: Eight breast cancer patients with ptotic breasts underwent two-stage unilateral DIEP flap breast reconstruction. In the initial surgery, tissue expander (TE) placement and contralateral mastopexy are performed simultaneously. Four to six months later, 3D bilateral breast imaging is performed after confirming that the shape of the contralateral breast (post-mastopexy) is somewhat stabilized, and a 3D-printed breast mold is created based on the mirror image of the shape of the contralateral breast acquired using analytical software. Then, DIEP flap surgery is performed, where the breast mold is used to determine the required flap volume and to shape the breast mound. Results: All flaps were engrafted without any major perioperative complications during both the initial and DIEP flap surgeries. Objective assessment of cosmetic outcome revealed that good breast symmetry was achieved in all cases. Conclusions: The method described here may allow even inexperienced surgeons to achieve reconstruction of symmetrical, non-ptotic breasts with ease and in a short time. While the requirement of two surgeries is a potential disadvantage, our method will be particularly useful in cases involving TEs, i.e., delayed reconstruction or immediate reconstruction involving significant skin resection.

Infectious Complications following Breast Reconstruction Using Tissue Expanders in Patients with Atopic Dermatitis

Summary: Infectious complications represent one of the most prominent factors contributing to tissue expander (TE) loss in breast reconstruction procedures. Several patient characteristics that increase the risk for surgical-site infection or TE infection have been reported, but no study has focused on the relationship between atopic dermatitis (AD) and TE infection or surgical-site infection. Recently, we investigated 203 cases of breast reconstruction surgeries performed using TEs and noted that all 3 patients who had AD developed infectious complications that ultimately led to TE removal. Considering its pathophysiology, it is likely that patients with AD relatively easily develop infectious complications due to barrier dysfunction, abnormalities in innate immune responses, or colony formation by Staphylococcus aureus. Particular caution should be exercised for breast reconstruction using man-made materials in cases complicated by AD.

Outcomes Comparison for Microsurgical Breast Reconstruction in Specialty Surgery Hospitals Versus Tertiary Care Facilities

Background: Postoperative monitoring is crucial in the care of free flap breast reconstruction patients. Tertiary care facilities (TCFs) provide postoperative monitoring in an ICU after surgery. Specialty surgery hospitals (SSHs) do not have ICUs, but these facilities perform free flap breast reconstruction as well. Are outcomes comparable between the 2 facilities in terms of flap reexploration times and overall success? Methods: Retrospective study including 163 SSH and 157 TCF patients. Primary predictor was facility in which the procedure was performed. Secondary predictors included operative, demographic, and comorbidity data. Primary outcomes were flap take back rate and flap failures. Secondary outcomes were total time from adverse event noticed in the flap to returning to the operating room (OR) and total time from decision made to return to the OR to returning to the OR (decision made). Tertiary outcomes were length of stay, operative times, and blood loss. Results: Patients at the TCF were generally less healthy than SSH patients. Salvage rates and failure rates were similar between the 2 institutions. Adverse event noticed and decision made times did not differ between the 2 facilities. Overall flap success rate was 98.22% at SSH and 98.81% at TCF. No primary or secondary predictors had a significant correlation with increased odds for flap failure. Conclusion: SSHs can offer similar outcomes in free flap breast reconstruction with just as effective clinical response times to endangered flaps as found in a TCF. However, surgery at an SSH may best be reserved for healthier patients.

Filling the Spectrum Expander with Air—A New Alternative

Summary: The Spectrum adjustable saline implant is optimal for prepectoral breast reconstruction as it can be placed virtually empty and thus flat, applying no pressure on the overlying skin flap. However, when saline is added, it tends to pool at the bottom of the implant resulting in its uneven surface and rippling. Air filling results in the uniform distribution within the implant shell and smooth even implant surface, which facilitates acellular dermal matrix adhesion. Pressure to the skin flap is averted, patients are more comfortable, and rippling is not seen.

Review of 494 Consecutive Breast Augmentation Patients: System to Improve Patient Outcomes and Satisfaction

Background: Breast augmentation continues to be one of the most common surgical procedures performed by plastic surgeons. As implant options expand, controlling the numerous variables required for a successful result will prove increasingly challenging. The purpose of this study was to outline specific steps that can be taken during the patient consultation and during surgery to decrease complications and improve overall patient satisfaction and patient outcomes. Methods: A retrospective review of 494 consecutive patients who underwent primary augmentation mammaplasty performed by a single surgeon was undertaken. Surgical outcomes were recorded and compared with previously published results. Patient satisfaction was measured using the BREAST-Q Augmentation Module. Results: Patients were followed for an average of 6 months (range, 0–45 months). Of the 494 patients, 1.3% developed capsular contracture. Other complications included 0.6% asymmetry, 0.4% malposition, 0.2% hematoma, and 0.2% rippling. The median BREAST Q score for the patient's overall satisfaction with outcome was 86%. The median BREAST Q score for patient's satisfaction with the plastic surgeon, medical team, and office staff was 100% in each case. The median score for psychological well-being, physical well-being, and sexual well-being was 100%, 90%, and 88%, respectively. Conclusions: The system outlined in this study showed very low rates of complications and high scores for patient satisfaction. Following a system like this will become increasingly important as breast augmentation continues to become more popular, implant options continue to expand, and social media continues to be used by patients to share surgical experiences.

A New Modified Method of Correcting Cryptotia with a Subcutaneous Pedicled Flap

Summary: We developed a surgical technique to correct cryptotia using a subcutaneous pedicled flap raised from the retroauricular region. A skin paddle over the caudal part of the auricular sulcus is designed and transferred to the skin defect of the upper posterior surface of the auricle. This procedure has been performed on 17 ears in 14 patients with cryptotia since 1992. There were no postoperative complications, such as necrosis of the flaps or deformities, and cryptotia did not recur in any patient. A satisfactory auricular contour with a sufficiently deep auriculotemporal sulcus was preserved in all cases. The intraoperative procedure to correct cryptotia and outcomes obtained are presented herein and compared with other procedures.

Nasal Duplication Combined with Cleft Lip and Palate: Surgical Correction and Long-Term Follow-Up

Background: Diprosopus dirrhinus, or nasal duplication, is a rare entity of partial craniofacial duplication. Methods: The case we present is the first report of diprosopus dirrhinus associated with complete cleft lip and palate. The baby was born in Cambodia at full term by normal vaginal delivery with no significant perinatal and family history. Physical examination revealed significant facial deformity due to the duplicated nose and the left complete cleft lip/palate on the right subset. Results: There were 4 nostrils; both medial apertures including the cleft site were found to be 10–15 mm deep cul-de-sac structures without communication to the nasopharynx. The upper third of the face was notable for hypertelorism with a duplication of the soft-tissue nasion and glabella. Between the 2 nasal dorsums, there was a small cutaneous depression with a lacrimal fistula in the midline. Surgical treatment included the first stage of primary lip and nose repair and the second stage of palatoplasty. Conclusions: The patient was followed up at the age of 10 years showing satisfactory results for both aesthetic and functional aspects. Further management in the future will be required for the hypertelorism and nasal deformity.

Solving Hand/Finger Pain Problems with the Pencil Test and Relative Motion Splinting

No abstract available

Multidirectional Cranial Distraction Osteogenesis with Simplified Modifications for Treating Sagittal Synostosis

Background: Multidirectional cranial distraction osteogenesis (MCDO) is a procedure of ours developed earlier for treating craniosynostosis. However, the numerous bone flaps led to prolonged operative time and occasional bone detachment from dura. We have since simplified the osteotomy design. In treating sagittal synostosis, required bone flaps have been reduced to 11 (from ~20). Methods: In a 2-year period (2014–2015), 5 boys with sagittal synostosis underwent MCDO using our simplified and fixed-form osteotomy. Mean age at surgery was 9.4 months (range, 8–11 months). Pre- and postoperative cranial morphology was assessed by cephalic index and by mid-sagittal vector analysis. Results: Improved cranial shape was confirmed by 3-dimensional CT scans and by mid-sagittal vector index. Mean preoperative cephalic index (68.7) progressively increased to means of 78.5 immediately after distraction device removal, 75.2 at postoperative month 6, and 75.1 at 1 year postoperatively. There were no major complications, although transient cerebrospinal fluid leakage and loosening of anchor pins occurred in 1 patient. Conclusions: Simplified MCDO has a number of advantages over conventional distraction procedures such as discretionary reshaping/expansion of cranium and predictable osteogenesis and is a valid treatment option for patients with sagittal synostosis.

Combined Tongue Flap and Deepithelialized Advancement Flap for Thick Lower Lip Reconstruction

Summary: We repaired a long horizontal defect in the lower lip caused by the resection of squamous cell carcinoma by reconstructing the white lip with a V-Y advancement flap and vermilion with a tongue flap. During this procedure, we deepithelialized the V-Y flap, lifted the upper margin of the flap and sutured it to the remaining upper margin of the lip, and then covered it with the tongue flap, resulting in the successful reconstruction of a thick lip. There were no postoperative complications in articulation or swallowing. This novel procedure is a simple method to aesthetically and functionally reconstruct a thick lower lip.

An Algorithmic Approach to Operative Management of Complex Pediatric Dog Bites: 3-Year Review of a Level I Regional Referral Pediatric Trauma Hospital

Background: Incidence of dog bites continues to rise among the pediatric population and serves as a public health threat for the well-being of children. Plastic surgeons are at the forefront of initial management and eventual outcome of these devastating injuries. This study set out to determine the nature of dog bite injuries treated over a 3-year period at a large level 1 pediatric trauma center. Methods: A retrospective review of emergency room records of all pediatric patients (age, 0–18 years old) who sustained dog bites between January 2012 and December 2014 were gathered. All details about age of patient, location and severity of dog bites, type of dog breed, antibiotics given, and emergency versus operative treatment were recorded and analyzed. Results: One hundred eight patients aged 5 months to 18 years old were treated in the emergency department after suffering dog bite injuries during the study period. The highest incidence of dog bites occurred in preschool children. The mean age for patients who required operative repair was lower than the mean age for patients who underwent primary closure in the emergency department. The location of injury was most commonly isolated to the head/neck region. Of the 56 cases that had an identified dog breed, pit bulls accounted for 48.2% of the dog bites, and 47.8% of pit bull bites required intervention in the operating room. Conclusion: Children with large dog bite injuries require more immediate care in a level 1 pediatric trauma hospitals in order to optimize their hospitalization course and eventual outcome.

Patient-Reported Outcomes following Split-Face Injection of 2 Volumizing Fillers in the Upper Cheeks

Background: Patient-reported outcomes are important measures when assessing the efficacy of aesthetic procedures. Objective: To compare outcomes between 2 volumizing hyaluronic acid fillers. Materials and Methods: Subjects with moderate-to-severe volume loss in the cheeks were randomized in a split-face design to malar enhancement with Cohesive Polydensified Matrix 26 mg/ml HA (CPM-26) and Vycross 20 mg/ml HA (VYC-20). The same injection technique and injection volume were applied for both sides of the face. Anesthetics, overcorrection, and touch-ups were not permitted. Blinded subjects assessed aesthetic improvements using the Global Aesthetic Improvement Scale and treatment satisfaction by confirming their willingness to repeat treatment or recommend it to friends. Follow-up was 18 months. Results: A total of 45 subjects received a single 2 mL injection of CPM-26 on one side and VYC-20 on the contralateral side of the face. The proportion of subjects reporting improvement on the Global Aesthetic Improvement Scale compared with baseline for CPM-26 and VYC-20 was 97.7% and 88.6%, respectively, at 3 months, 73.8% and 71.1% at 12 months, and 61.0% and 56.7% at 18 months. Treatment satisfaction was high, with the majority of subjects stating that they would repeat treatment and recommend it to friends, but at each time point, a higher proportion of subjects was more satisfied with the CPM-26-treated side of the face. Conclusions: In this first direct comparison of CPM-26 and VYC-20, the majority of subjects were satisfied with both treatments throughout the study. Patient-reported outcome measures identified a trend in favor of CPM-26.

Intravenous Access in Infants Undergoing Bilateral Sural Nerve Grafts for Primary Brachial Plexus Exploration

Background: Intravenous access (IVA) in infants undergoing primary brachial plexus exploration may be difficult. Both lower limbs are prepared and draped for sural nerve graft harvesting. The injured upper limb is also prepared and draped and is not available for IVA. In difficult IVA from the remaining upper limb, we have been using one of the feet for IVA. The infection rate and problems of intravenous infusions in this setting have never been studied in the literature. This study documents the infection rate and problems of intravenous infusions in these infants when a foot (within the sterile field) is used for IVA. Methods: This is a retrospective study of 63 consecutive infants undergoing primary brachial plexus exploration, and in whom IVA was obtained from one of the feet. Infection rate and problems of intravenous infusions were recorded. Results: No surgical wound infection and no infection of the IVA site were noted. There were no instances of accidental dislodgement of the intravenous cannula and no instances of extravasation. Conclusion: The use of one of the feet (within the sterile filed) for IVA is safe and acceptable in infants undergoing primary brachial plexus exploration and bilateral sural nerve grafting.

The Idea of Beauty and Its Biases: Critical Notes on the Aesthetics of Plastic Surgery

Summary: Two biases affect the idea of beauty often embodied in aesthetic surgery. The first one is that the living body is the sum of different parts; the second one claims that beauty results from the sum of beautiful elements. Taken together, these 2 biases explain most of the aesthetic surgery procedures, in which a localized improvement is supposed to impact on the whole body image. In this article, I put into question these 2 problematic assumptions, showing that Western and Eastern aesthetics, on one side, and philosophical reflections, on the other side, support a different conception of beauty. In particular, an alternative idea that opens to authenticity and imperfection and focuses on the living body rather than on the mere anatomical surface is proposed here as a more adequate concept of beauty for aesthetic surgery.