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Τετάρτη 6 Δεκεμβρίου 2017

Histoplasmosis, una micosis endémica emergente

Publication date: Available online 6 December 2017
Source:Actas Dermo-Sifiliográficas
Author(s): A. Pulido Pérez




Granuloma aséptico facial idiopático: hallazgos clínicos y ecográficos de 3 casos

Publication date: Available online 6 December 2017
Source:Actas Dermo-Sifiliográficas
Author(s): A.I. Rodríguez-Bandera, M. Feito-Rodríguez, R. Maseda-Pedrero, R. de Lucas-Laguna
El granuloma aséptico facial idiopático es una entidad propia de la infancia que se caracteriza por la presencia de uno o varios nódulos asintomáticos en la mejilla. Aunque su patogenia no está clara, se ha sugerido que pueda pertenecer al espectro de la rosácea infantil. Resuelve espontáneamente pero puede plantear dudas diagnósticas con otras lesiones que sí requieren tratamiento.Presentamos los hallazgos clínicos y ecográficos y la evolución, tanto clínica y ecográfica, de 3 nuevos casos. En 2 pacientes, la lesión se presentó en el contexto de una rosácea infantil. En ecografía, el granuloma aséptico facial idiopático mostró un patrón característico, con variaciones en función del momento evolutivo.La ecografía de alta frecuencia puede facilitar el diagnóstico diferencial, evitando biopsias o extirpaciones innecesarias.Idiopathic facial aseptic granuloma is a typical childhood disease characterized by the presence of one or more asymptomatic nodules on the cheek. Although pathogenesis remains unclear, the disease is thought to be a type of childhood rosacea. It resolves spontaneously, yet it could be confused with other lesions that require treatment.We present clinical and ultrasound findings and outcome from 3 new cases. In 2 cases, the lesion presented as childhood rosacea. Ultrasound revealed a characteristic pattern, with variations depending on the stage of development.High-frequency ultrasound can facilitate the differential diagnosis and thus obviate unnecessary biopsy or excision.



Mucormicosis cutánea primaria por Rhizopus arrhizus en una niña de 8 años

Publication date: Available online 6 December 2017
Source:Actas Dermo-Sifiliográficas
Author(s): M.F. Albízuri-Prado, A. Sánchez-Orta, A. Rodríguez-Bandera, M. Feito-Rodríguez




Proceso de traducción y adaptación cultural de instrumentos de medición en salud

Publication date: Available online 6 December 2017
Source:Actas Dermo-Sifiliográficas
Author(s): S. Ortiz-Gutiérrez, A. Cruz-Avelar




Búsqueda de nuevas pautas terapéuticas de imiquimod 5% para el tratamiento de las queratosis actínicas

Publication date: Available online 6 December 2017
Source:Actas Dermo-Sifiliográficas
Author(s): R. Salido Vallejo




Pitiriasis liquenoide y varioliforme aguda asociada al virus herpes humano tipo 7

Publication date: Available online 6 December 2017
Source:Actas Dermo-Sifiliográficas
Author(s): M. Costa-Silva, A. Calistru, J. Sobrinho-Simões, C. Lisboa, F. Azevedo
Tanto la pitiriasis liquenoide y varioliforme aguda como la pitiriasis liquenoide crónica representan 2 extremos de un espectro de enfermedad de etiología desconocida. En este trabajo se describen 2 casos de pitiriasis liquenoide y varioliforme aguda, en los que se detectó ADN de virus herpes humano tipo 7 en muestras de piel mediante la metodología de reacción en cadena de la polimerasa, una asociación no descrita previamente. Este manuscrito puede apoyar la participación de la infección viral en la etiopatogenia de esta enfermedad.Pityriasis lichenoides et varioliformis acuta and pityriasis lichenoides chronica represent 2 ends of a disease spectrum of unknown etiology. Herein we describe 2 cases of pityriasis lichenoides et varioliformis acuta, in which human herpesvirus 7 DNA was detected in skin samples by polymerase chain reaction methodology, an association not previously described. This report may support the involvement of viral infection in the etiopathogeny of this disease.



Un caso de poroqueratosis diseminada eruptiva en un paciente oncológico tratado con trastuzumab y exemestano: ¿fenómeno asociado al cáncer o inducido por fármacos?

Publication date: Available online 6 December 2017
Source:Actas Dermo-Sifiliográficas
Author(s): C. Mangas, V. Espeli, R. Blum




La investigación clínica en las secciones territoriales de la Academia Española de Dermatología y Venereología (AEDV)

Publication date: Available online 6 December 2017
Source:Actas Dermo-Sifiliográficas
Author(s): Á. Iglesias-Puzas, A. Batalla, Á. Flórez
IntroducciónLa investigación clínica (IC) se centra en el estudio de los pacientes para mejorar su atención. Nuestro objetivo fue conocer qué porcentaje de las comunicaciones presentadas a las reuniones de tres secciones territoriales de la AEDV cumplen criterios de IC, su nivel de evidencia y su evolución temporal.Material y métodosSe revisaron las comunicaciones científicas de las reuniones territoriales gallega, astur-cántabro-castellano-leonesa (ACL) y andaluza publicadas en los suplementos de la revista Actas Dermosifiliográficas (años 2000-2015). Utilizando una definición de IC previamente validada, se estableció cuáles de los resúmenes se ajustaban a dicha definición, se determinó su nivel de evidencia y la evolución temporal del porcentaje de estudios de investigación.ResultadosDe las 1.188 comunicaciones analizadas, el 29,6% cumplieron criterios de IC. La mayoría correspondían a un nivel de evidencia4 (95,2%), distribuidos en un 44,2% de estudios transversales y un 55,8% de series de casos. La prevalencia de la IC en las secciones gallega, ACL y andaluza fue del 26,6% (94,7%, nivel 4), del 22,7% (97,6%, nivel 4) y del 37,2% (94,3%, nivel 4), respectivamente. El porcentaje de trabajos de IC aumentó significativamente a lo largo de los años.ConclusionesLa IC representa el 29,6% de las comunicaciones en las reuniones evaluadas. La mayoría de los trabajos corresponden a series de casos y estudios transversales. Los territorios estudiados muestran diferencias en cuanto al porcentaje de IC, pero siguen una distribución similar de los niveles de evidencia. En el periodo de tiempo evaluado, el porcentaje de comunicaciones sobre IC se ha incrementado.IntroductionClinical research is the study of patients with the aim of improving care. Our objectives were to calculate the percentage of presentations at territorial section meetings of the Spanish Academy of Dermatology and Venereology (AEDV) that described clinical research, to assess the level of evidence the research provided, and to analyze change in clinical research volume over time.Material and methodsWe reviewed supplements of the journal Actas Dermosifiliográficas for 2000 through 2015 that contained abstracts of presentations given at the AEDV section meetings in Galicia; the area comprising Asturias, Cantabria, and Castile-Leon (ACCL); and Andalusia. We selected abstracts that met a previously validated definition of clinical research and categorized each according to level of evidence. We also analyzed how the weight of clinical research presentations changed over time.ResultsOf the total of 1,188 presentations, 29.6% met the criteria that defined clinical research. Most provided level-4 evidence (95.2%); 44.2% of those presentations reported cross-sectional studies and 55.8% analyzed case series. Clinical research accounted for 26.6% of the presentations in Galicia (94.7% of them, level 4), 22.7% of those at the ACCL meeting (97.6%, level 4), and 37.2% of those in Andalusia (94.3%, level 4). The proportion of clinical research increased significantly over the years studied.ConclusionsClinical research accounted for 29.6% of the communications presented at the meetings we reviewed. Most of these presentations concerned case series or cross-sectional studies. The prevalence of clinical research presentations differed between the 3 territories studied, but the levels of evidence were similar. The proportion of clinical research in the programs of these meetings has increased over time.

Graphical abstract

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Varicella pseudo-Koebner phenomenon associated with vascular access opening



Allergic contact dermatitis caused by topical herbal remedies: importance of patch testing with the patients' own products

Summary

Background

Natural ingredients have variable compositions, so their allergenic potencies may differ.

Objectives

To retrospectively analyse subjects reacting to herbal remedies over the past 27 years, with the aim of (i) evaluating demographic characteristics and lesion locations, (ii) describing the frequencies of positive patch test reactions, (iii) identifing sensitization sources, and (iv) studying concomitant sensitivity.

Patients and Methods

In total, 15980 patients were patch tested between 1990 and 2016 with the European baseline series and/or other series, product(s) used, and, whenever possible, the respective ingredients.

Results

Altogether, 8942 (56%) of 15 980 patients presented with at least one positive reaction. Reactions to topical herbal medicines, most often applied to treat an eczematous condition, leg ulcers, or other wounds, were seen in 125 (0.8%), that is, 1.4% of the contact-allergic subjects. Hands, legs and feet were the most frequently affected body sites. Twenty-one botanical allergens were identified, the commonest being Myroxylon pereirae (balsam of Peru), Compositae plants, and tincture of benzoin. Many patients presented with multiple positive test reactions, and some did not react to the commercial allergens but only to the products used.

Conclusions

Topical herbal remedies should not be applied on damaged skin, as multiple sensitization may develop. Moreover, patch testing with the culprit products is important for the diagnosis.



Potential for plant biocontrol activity of isolated Pseudomonas aeruginosa and Bacillus stratosphericus strains against bacterial pathogens acting through both induced plant resistance and direct antagonism

Abstract
Phytopathogenic bacteria have caused significant damage to agricultural crops in both controlled and open cultivation practices, imposing heavy losses to farmers. Thereby, the goal of this study was to evaluate Pseudomonas aeruginosa and Bacillus stratosphericus isolated from soil has antagonistic activity against bacterial phytopathogens with the potential to control plant diseases. Isolated novel strains of P. aeruginosa and B. stratosphericus showed broad spectrum of antagonistic activity against five bacterial phytopathogens. Antagonistic activity was examined under optimized pH (8 and 7), carbon sources (lactose and starch), nitrogen sources (ammonium chloride, peptone and ammonium nitrate) for P. aeruginosa and B. stratosphericus, respectively, and biocatalyst production (chitinase, protease and amylase) was studied. Additionally, up-regulation of defense-related genes (PR-1a and PAL) was studied in tomato plants treated with P. aeruginosa and B. stratosphericus. The induction of defense-related genes in tomato plant was triggered after 12 h treatment with a cell concentration of 0.20 O.D. for P. aeruginosa and 0.21 O.D. for B. stratosphericus during treatment period. Broad spectrum antagonistic activity was observed due to antibiotic and siderophore production by P. aeruginosa and B. stratosphericus.

The impact of hoist sling fabrics on interface pressure whilst sitting in healthy volunteers and wheelchair users: A comparative study

Publication date: Available online 6 December 2017
Source:Journal of Tissue Viability
Author(s): J. Webb, M. Twiste, L.A. Walton, P. Hogg
Aim of the studyTo evaluate the effect of three sling fabrics on gluteal interface pressure whilst sitting in a population of wheelchair users and to compare these to data previously collected in a pilot study with a healthy population.Materials and methodsA repeated measures experimental design was used with 32 adult wheelchair users (15 women, 17 men). Healthy population pilot study consisted of 61 participants (51 women, 10 men) recruited from staff and students at The University of Salford.MethodsGluteal pressures at six pressure zones were recorded using the X-sensor PX100 pressure sensor at 30 s intervals for 10 min. Data were collected in 4 conditions with participants seated in a standardised chair, followed by the chair with slings made of three different fabrics.ResultsThe spacer fabric reduced the mean gluteal pressure more effectively than slipfit and polyester (p = 0.014 and p = 0.01 respectively, 95%CI) and reduced peak pressure at the left ischial tuberosity and coccyx when compared to the slipfit (p = 0.003 and p = 0.005) with the wheelchair users. When comparing data with the pilot study, the mean gluteal pressure and peak pressures at the ischial tuberosities and coccyx were significantly higher in the wheelchair user group (p < 0.005).ConclusionThe fabric identified as the most effective in reducing mean and peak pressures in both groups was the spacer fabric, suggesting that a spacer fabric sling is more likely to reduce the risk of pressure ulcer development.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.



Nanoparticle-based lateral flow biosensor combined with multiple cross displacement amplification for rapid, visual and sensitive detection of Vibrio cholerae

Abstract
Vibrio cholerae is an important human pathogen that is responsible for cholera, a severe acute watery diarrhea. In the current study, a multiple cross displacement amplification (MCDA) coupled with amplicon detection by chromatographic lateral flow biosensor (LFB) method (MCDA-LFB) was successfully established and evaluated for the identification of V. cholerae. A set of 10 primers was designed specifically to recognize 10 different regions of the V. cholerae-specific gene ompW. The optimized time and temperature conditions for the MCDA were 30 min and 63°C, respectively. The MCDA-LFB assay correctly identified 31 strains of V. cholerae but did not detect 13 non-cholerae Vibrio strains and 30 non-Vibrio strains. The sensitivity of MCDA-LFB for target pathogen detection in pure culture was 10 fg per reaction. In the case of spiked shrimp samples without enrichment, the limit of detection was 4.1 CFUs per reaction or equivalent to 4.1 × 102 CFU g−1. The whole process, including shrimp homogenates processing (30 min), MCDA reaction (30 min) and results reporting (2 min), could be finished within 65 min. These results show that this assay is suitable for the rapid, sensitive and specific detection of V. cholerae in food, environmental and clinical samples.

Study of mesophilic Aeromonas salmonicida A527 strain sheds light on the species’ lifestyles and taxonomic dilemma

Abstract
The Gram-negative bacterium Aeromonas salmonicida contains five subspecies: salmonicida, smithia, achromogenes, masoucida and pectinolytica. Pectinolytica is a mesophilic subspecies with the ability to thrive at a wide range of temperatures, including 37°C, while the four other subspecies are psychrophilic, restricted to lower temperatures. The psychrophilic subspecies are known to infect a wide range of fishes. However, there is no evidence of pathogenicity for the mesophilic subspecies pectinolytica. Study of the differences between the mesophilic and psychrophilic subspecies is hampered by the lack of completely sequenced and closed genomes from the mesophilic subspecies. A previous study reported that insertion sequences, which can induce genomic rearrangements at temperatures around 25°C, could be one of the determinants explaining the differences in lifestyle (mesophilic or psychrophilic) between the subspecies. In this study, the genome of mesophilic strain A527 of A. salmonicida was sequenced, closed and analyzed to investigate the mesophilic–psychrophilic discrepancy. This reference genome supports the hypothesis that insertion sequences are major determinants of the lifestyle differences between the A. salmonicida subspecies. Moreover, the phylogenetic analysis performed to position strain A527 within the taxonomy raises an issue regarding the intraspecies structure of A. salmonicida.

Overproduction of Sinorhizobium meliloti ArgC ( N -acetyl-gamma-glutamyl phosphate reductase) promotes growth delay and inefficient nodules

Abstract
argC encodes N-acetyl-gamma-glutamyl phosphate reductase, the enzyme that catalyzes the high-energy-consuming third step in the arginine synthesis pathway. A comparative analysis revealed two translation start sites in argC from Sinorhizobium meliloti. To determine whether both protein versions are synthesized in the organism and their functional role, we obtained genetic constructs with one (1S) or two (2S) start sites, with promoters of low (pspeB) or high (plac) transcriptional rate. The constructs were transferred to the S. meliloti 1021 derivative argC mutant strain. Both protein versions were found in the free-living proteomes, but only ArgC 1S showed post-translational modification. Expression levels from argC 1S were five times higher than those of 2S, when transcribed by plac, and in concordance, its protein activity was 3-fold greater. The overexpression of both versions under plac delayed cellular growth. Inoculation of Medicago sativa plants with the S. meliloti strain harboring the argC 1S under plac induced nodulation but not nitrogen fixation. However, the strain with the argC 2S under the same promoter had a positive phenotype. Overproduction of ArgC protein for the synthesis of arginine induced physiological and symbiotic effects.

Packaging of Mycobacterium smegmatis bacteria into fecal pellets by the ciliate Tetrahymena pyriformis

Abstract
Mycobacteria are widespread microorganisms that live in various environments, including man-made water systems where they cohabit with protozoa. Environmental mycobacterial species give rise to many opportunistic human infections and can infect phagocytic protozoa. Protozoa such as amoebae and ciliates feeding on bacteria can sometimes get rid of non-digestible or pathogenic material by packaging it into secreted fecal pellets. Usually, packaged bacteria are still viable and are protected against chemical and physical stresses. We report here that mycobacteria can be packaged into pellets by ciliates. The model bacterium Mycobacterium smegmatis survived digestion in food vacuoles of the ciliate Tetrahymena pyriformis and was included in expelled fecal pellets. LIVE/DEAD® staining confirmed that packaged M. smegmatis cells preserved their viability through the process. Scanning and transmission electron microscopy revealed that bacteria are packaged in undefined filamentous and/or laminar substances and that just a thin layer of material seemed to keep the pellet contents in a spherical shape. These results imply that packaging of bacteria is more common than expected, and merits further study to understand its role in persistence and dissemination of pathogens in the environment.

Methicillin - resistant Staphylococcus aureus in minas frescal cheese: evaluation of classic enterotoxin genes, antimicrobial resistance and clonal diversity

Abstract
This study aimed to investigate classical enterotoxin (sea to see) and mecA genes, by polymerase chain reaction and anitimicrobial susceptibility, by disk diffusion test of Staphylococcus aureus isolated from minas frescal cheese (MFC). All methicillin-resistant S. aureus (MRSA) isolates were investigated for the presence of Panton-Valentine leukocidin (PVL) genes and clonal diversity. Thirty-one S. aureus were isolated from four MFC samples. Seven (22.6%) S. aureus carried mecA gene and two of them carried enterotoxin genes seb/sec and sea/seb. Five (16.1%) S. aureus isolates showed induced resistance to clindamycin and nine (29%) were resistant to multiple –antibiotics (MDR), among these, six were MRSA. No MRSA isolates presented the PVL genes. Four MRSA were grouped into three clones and three isolates were not typable by pulsed field gel electrophoresis. MRSA isolates showed, by multilocus sequence typing, sequence types ST1, ST5, ST72 and ST4304 (new ST) and S. aureus protein A (spa type) t127, t568 and t2703. These data suggest that MFC may constitute a risk to the consumer because of its potential for staphylococcal food poisoning; however it might, also, become one of MRSA and MDR strains disseminator, including clones usually found in the hospital environment.

Antibiotic stewardship: a European perspective

Abstract
Antibiotic stewardship programmes, which are a set of interventions aiming at prescribing antibiotics appropriately and responsibly, are one of the key strategies to tackle the current worldwide bacterial resistance crisis. We will present here some examples of international and national initiatives, with a focus on Europe, discuss the role of clinical microbiologists, and present some perspectives and future developments.

Potential impact of global climate change on benthic deep-sea microbes

Abstract
Benthic deep-sea environments are the largest ecosystem on Earth, covering ∼65% of the Earth surface. Microbes inhabiting this huge biome at all water depths represent the most abundant biological components and a relevant portion of the biomass of the biosphere, and play a crucial role in global biogeochemical cycles. Increasing evidence suggests that global climate changes are affecting also deep-sea ecosystems, both directly (causing shifts in bottom-water temperature, oxygen concentration and pH) and indirectly (through changes in surface oceans' productivity and in the consequent export of organic matter to the seafloor). However, the responses of the benthic deep-sea biota to such shifts remain largely unknown. This applies particularly to deep-sea microbes, which include bacteria, archaea, microeukaryotes and their viruses. Understanding the potential impacts of global change on the benthic deep-sea microbial assemblages and the consequences on the functioning of the ocean interior is a priority to better forecast the potential consequences at global scale. Here we explore the potential changes in the benthic deep-sea microbiology expected in the coming decades using case studies on specific systems used as test models.

Venous thromboembolism events after breast reconstructions with DIEP free flaps in 192 consecutive case

Publication date: Available online 6 December 2017
Source:Annales de Chirurgie Plastique Esthétique
Author(s): A. Modarressi, A.-V. Schettini, E.M. Rüegg, B. Pittet-Cuénod
BackgroundPatient candidates for breast reconstruction with free deep inferior epigastric perforator flap (DIEP) may present several risk factors for venous thromboembolism (VTE). Risk identification is essential for appropriate VTE prophylaxis measures to be put in place. This study aims to investigate VTE incidence after DIEP flap breast reconstruction and to assess the accuracy of the Caprini Risk Assessment Model (RAM), which is the unique score validated to assess the VTE risk for plastic surgery procedures and identify patients at high VTE risk.MethodsA chart review was conducted of 192 consecutive patients who underwent breast reconstruction with a DIEP flap from 1999 to 2016. VTE rate was assessed and the Caprini score was calculated for each patient and correlated with the VTE incidence.ResultsDuring the 90 post-operative days, four patients presented a pulmonary embolism (2.1%) and two patients (1%) had deep venous thrombosis (overall VTE incidence of 3.1%). Most patients (92.2%) were assessed as high-risk (Caprini score >5) and all VTE occurred among this group. Apart from the Caprini score, no specific single risk factor could be identified for VTE.ConclusionsOur data confirm that the Caprini RAM is a valuable assessment tool for VTE risk measurement among all patients undergoing autologous breast reconstruction. As most candidates for DIEP flap belong to the high-risk group, combined anticoagulation prophylaxis methods are required for most cases, particularly chemoprophylaxis up to four weeks postoperatively.



Génioplasties d’augmentation prothétiques et osseuses, à visée esthétique : revue de littérature et actualisation des connaissances

Publication date: Available online 6 December 2017
Source:Annales de Chirurgie Plastique Esthétique
Author(s): A. Baus, K. Rem, M. Revol, S. Cristofari
La génioplastie d'augmentation est un geste chirurgical couramment pratiqué, que ce soit dans le traitement des microgénies, dans le cadre d'une chirurgie orthognatique ou à visée esthétique. Le choix de la technique diffère selon les spécialités chirurgicales qui la pratiquent. Il existe un grand nombre de publications sur le sujet, permettant de comparer les différentes méthodes chirurgicales, leurs indications et leurs complications. Le but de cette étude était de réaliser une revue de littérature avec actualisation des connaissances, ainsi qu'une synthèse des indications préférentielles de génioplasties osseuses et prothétiques à visée esthétique.ConclusionMalgré la généralisation des implants « modernes » en France, la génioplastie prothétique reste plus fréquemment pourvoyeuse de complications graves (infections, extrusions, érosions osseuses). De même, cette technique possède des indications bien plus limitées que la génioplastie osseuse, qui a l'avantage d'une meilleure longévité. Dans une logique d'augmentation mentonnière à visée esthétique, la génioplastie osseuse devrait donc être réalisée plus facilement et plus fréquemment par les chirurgiens, toutes spécialités confondues.Chin augmentation is commonly practiced, whether in microgenia treatment, in cases of orthognathic or cosmetic surgery. Located at the crossroads of many specialties, the technique choice still differs according to the surgeon specialiy. A large number of publications on the subject are available. A comparaison between different surgical methods is therefore possible concerning their indications and their complication. The purpose of this study was to carry out a literature review, with updating knowledge, as well as a synthesis indication regarding aesthetic osseous and alloplastic genioplasty. Despite the generalization of "modern" implants in France, prosthetic genioplasty remains more frequently the source of serious complications (infections, extrusions, bone erosions). Similarly, this technique has much more limited indications than osseous genioplasty, which has the advantage of a better longevity. In order to increase the aesthetic appearance of the chin, osseous genioplasty should be performed more easily and more frequently by surgeons on all sides.



Le lambeau médial sural perforant : bases anatomiques, technique chirurgicale et indications en reconstruction cervicofaciale

Publication date: Available online 6 December 2017
Source:Annales de Chirurgie Plastique Esthétique
Author(s): S. Struk, J.-B. Schaff, Q. Qassemyar
IntroductionLe lambeau médial sural perforant (medial sural artery perforator [MSAP] flap) est un lambeau cutanéo-graisseux, fin et malléable, prélevé aux dépens de la face médiale de la jambe. Ce lambeau est encore peu utilisé en France. L'objectif de ce travail, effectué à partir de dissections sur sujets anatomiques, est de rappeler les bases anatomiques et la technique chirurgicale de ce lambeau, et de proposer des indications en reconstruction cervicofaciale.Matériel et méthodesNous avons disséqué 10 lambeaux MSAP sur 5 sujets anatomiques différents. Dans chaque cas, le nombre et la localisation des perforantes issues de l'artère surale médiale étaient enregistrés. Pour chaque lambeau, nous avons rapporté la longueur du pédicule, le calibre des vaisseaux à l'origine du pédicule ainsi que l'épaisseur du lambeau. Enfin, nous avons réalisé un cas clinique pour un trismus post-thérapeutique.RésultatsUn total de 23 perforantes de calibre supérieur à 1mm a été identifié sur les 10 jambes disséquées. L'artère surale médiale donnait 1 à 4 perforantes musculocutanées. Les perforantes étaient localisées en moyenne à 10,3cm±2cm du creux poplité et à 3,6cm±1cm de la ligne médiane du mollet. La longueur moyenne du pédicule était de 12,1cm±2,5cm. À l'origine du pédicule, l'artère mesurait en moyenne 1,8mm±0,25mm et les veines mesuraient en moyenne 2,45mm±0,9mm. Le cas clinique s'est déroulé sans complication avec le prélèvement d'un lambeau perforant sural médial droit.DiscussionCette étude confirme la constance de l'anatomie du lambeau médial sural perforant. Le lambeau MSAP est fin, malléable et particulièrement adaptée à la reconstruction des pertes de substance muqueuses de la cavité orale ou pour le « resurfaçage » de la face ou des extrémités. Les séquelles au niveau du site donneur sont moindres qu'avec le lambeau antébrachial radial pour des résultats fonctionnels équivalents en reconstruction cervicofaciale.IntroductionThe medial sural artery perforator (MSAP) flap is defined as a thin cutaneo-adipose perforator flap harvested on the medial aspect of the leg. The aims of this study were to describe the anatomical basis as well as the surgical technique and discuss the indications in head and neck reconstructive surgery.Material and methodsWe harvested 10 MSAP flap on 5 fresh cadavers. For each case, the number and the location of the perforators were recorded. For each flap, the length of pedicle, the diameter of source vessels and the thickness of the flap were studied. Finally, we performed a clinical application of a MSAP flap.ResultsA total of 23 perforators with a diameter superior than 1mm were dissected on 10 legs. The medial sural artery provided between 1 and 4 musculocutaneous perforators. Perforators were located in average at 10.3cm±2cm from the popliteal fossa and at 3.6cm±1cm from the median line of the calf. The mean pedicle length was 12.1cm±2.5cm. At its origin, the source artery diameter was 1.8mm±0.25mm and source veins diameters were 2.45mm±0.9mm in average. There was no complication in our clinical application.DiscussionThis study confirms the reliability of previous anatomical descriptions of the medial sural artery perforator flap. This flap was reported as thin and particularly adapted for oral cavity reconstruction and for facial or limb resurfacing. Sequelae might be reduced as compared to those of the radial forearm flap with comparable results.



Cutometric assessment of elasticity of skin with striae distensae following carboxytherapy

Summary

Objective

The aim of the study was to evaluate the effectiveness of carboxytherapy in the treatment of striae distensae. Additionally, discomfort and side effects associated with the treatment were assessed.

Materials and methods

This study involved 15 women aged 22-40 years. They underwent 3 sessions of carboxytherapy at one-week intervals. Treatment was performed in skin area within stretch marks located on stomach, buttocks, and thighs. Cutometric probe was used to evaluate skin elasticity. Four measurements were performed—immediately before each treatment and one month after the last session. Photographic documentation was made before and after a series of treatment to perform clinical evaluation of changes in skin condition.

Results

Statistical analysis of results obtained with the use of Cutometer (R2 and R8 parameters) demonstrated that carboxytherapy significantly improved skin elasticity within stretch marks (P < .05). The analysis of photographic documentation revealed 58% improvement in stretch mark visibility. The width and length of stretch marks decreased, and their color became more like the natural color of the skin. Carboxytherapy is associated with moderate pain/discomfort. The occurrence of hematoma is the main side effect of this procedure.

Conclusions

Carboxytherapy seems to be an effective method of reducing stretch marks. This procedure is safe, and it can be performed without the risk of complications. Moreover, it does not require special postoperative convalescence. Photographic documentation is a method of assessment of aesthetic procedures effectiveness, which is complementary to other objective methods (eg, the use of MPA probes).



Environmental levels of triclosan and male fertility

Abstract

Triclosan is a synthetic chemical with broad antimicrobial activity that has been used extensively in consumer products, including personal care products, textiles, and plastic kitchenware, although the exposure which is widespread evidence from human studies is scarce. Our study aims to investigate the relationship between triclosan exposure and male fertility. Triclosan (TCS) urinary concentrations were measured using gas chromatography coupled with tandem mass spectrometry in 315 men recruited from a male reproductive health clinic with normal sperm concentration (≥ 15 mln/ml) (WHO 2010) under 45 years of age. Participants were interviewed and provided a semen sample. TCS was detected in 84.13% of urine samples, with a median concentration of 2.83 μg/l (2.57 μg/g creatinine). A multiple linear regression analysis showed a positive association between the urinary concentrations of triclosan 50th–75th percentile and ≥ 50 percentile and percentage of sperm with abnormal morphology (p = 0.016 and p = 0.002, respectively). The study provides evidence that exposure to triclosan is associated with poorer semen quality. Future studies are needed to confirm these findings.



Characteristics of different molecular weight EPS fractions from mixed culture dominated by AnAOB and their role in binding metal ions

Abstract

Ultraviolet-visible (UV-Vis) absorbance spectra were adopted to quantify the binding of metal ions (e.g., Fe(III), Cu(II), Pb(II), and Cd(II)) on three MW fractions (> 100, 10~100, and < 10 k Da) of extracellular polymeric substances (EPS) extracted from mixed cultures dominated by anaerobic ammonium-oxidizing bacteria (AnAOB). The results showed that the AnAOB EPS with different MW size ranges all had strongest binding capability of Fe(III), and the lowest binding capability of Cd(II). The complexation ability of metal ions for the EPS of AnAOB with molecular weight < 10 kDa was stronger than EPS with >100 and 10~100 kDa, very likely because of the contribution of the tyrosine-, tryptophan-, and aromatic protein-like components. It was obvious that the different size fractions of EPS affect the metal binding ability. Essentially, the content of proteins, polysaccharides, TOC, and UVA254 distributed within various MW fractions of EPS from AnAOB were different, as well as the different fluorescent components and total functional groups.



Amicarbazone degradation promoted by ZVI-activated persulfate: study of relevant variables for practical application

Abstract

Alarming amounts of organic pollutants are being detected in waterbodies due to their ineffective removal by conventional treatment techniques, which warn of the urgent need of developing new technologies for their remediation. In this context, advanced oxidation processes (AOPs), especially those based on Fenton reactions, have proved to be suitable alternatives, due to their efficacy of removing persistent organic compounds. However, the use of ferrous iron in these processes has several operational constraints; to avoid this, an alternative iron source was here investigated: zero-valent-iron (ZVI). A Fenton-like process based on the activation of a recently explored oxidant-persulfate (PS)—with ZVI was applied to degrade an emerging contaminant: Amicarbazone (AMZ). The influence of ZVI size and source, PS/ZVI ratio, pH, UVA radiation, dissolved O2, and inorganic ions was evaluated in terms of AMZ removal efficiency. So far, this is the first time these parameters are simultaneously investigated, in the same study, to evaluate a ZVI-activated PS process. The radical mechanism was also explored and two radical scavengers were used to determine the identity of major active species taking part in the degradation of AMZ. The degradation efficiency was found to be strongly affected by the ZVI dosage, while positively affected by the PS concentration. The PS/ZVI system enabled AMZ degradation in a wide range of pH, although with a lower efficiency under slightly alkaline conditions. Dissolved O2 revealed to play an important role in reaction kinetics as well as the presence of inorganic ions. UVA radiation seems to improve the degradation kinetics only in the presence of extra O2 content. Radicals quenching experiments indicated that both sulfate (SO4•−) and hydroxyl (OH) radicals contributed to the overall oxidation performance, but SO4•− was the dominant oxidative species.



Molecular identification of Leishmania spp. isolates causes cutaneous leishmaniasis (CL) in Sanliurfa Province, Turkey, where CL is highly endemic

Abstract

Cutaneous leishmaniasis (CL) is an important public health problem in Turkey. CL has been most frequently seen in Sanliurfa. There is an expectation of increase in the population of leishmaniasis cases with the influence of Syrian refugees arriving in Turkey. In this study we aimed to diagnosis of CL and identifying of parasite from Leishmania isolates by using ITS 1 PCR RFLP. Samples were collected from 135 CL patients in Sanliurfa. After the specimens were inoculated in medium NNN, the ones which were cultures positive were cultivated in RPMI 1640 followed by PCR-RFLP. Genomic DNA was extracted phenol-chloroform procedure. Samples were examined by using ITS 1 PCR followed by RFLP analysis. Our results indicated that two species, L. tropica (132 samples) and L. major (3 samples), are responsible for cutaneous leishmaniasis in Sanlıurfa. Our study is the first scientific study in which it is reported molecular analyses of cutaneous leishmaniasis cases caused by L. major in Sanliurfa in Southestern Anatolia Region. Because CL cases caused by L.major are detected in our study, it is considered that genotyping is important for diagnosis of Leishmania and following change of epidemiology.



Lipoid proteinosis: towards predictive clinical clues



Cigarette butts abundance and association of mercury and lead along the Persian Gulf beach: an initial investigation

Abstract

The toxic metal contents of cigarette butts and distribution of cigarette butts have not been studied well in maritime environment. In the present study, cigarette butts distribution and the associations of Hg and Pb from cigarette butts were monitored along the Persian Gulf with 10 days interval sampling time. The number of cigarette butts, and Hg and Pb associations of butts were found to vary widely between 2 and 38 items per square meter, 2.5 and 86.32 ng/g cigarette butt (CB), as well as 650 and 8630 ng/g CB, respectively. Wilcoxon signed-rank test showed that there were no significant differences between the number of butts, and Hg and Pb contents of the butts at different sampling times. Considering amount of cigarette butts littered yearly, this study demonstrates that remarkable toxic metals of Hg and Pb may enter maritime environment each year and may introduce critical hazards to aquatic organisms, enter food chain, and finally human body.



Cities of the future—bionic systems of new urban environment

Abstract

The concepts of the cities we know nowadays, and which we are accustomed to, change at a very rapid pace. The philosophy of their design is also changing. It will base on new standards, entering a completely different, futuristic dimension. This stage is related to changes in the perception of space, location and lack of belonging to definite, national or cultural structures. Cities of the future are cities primarily intelligent, zero-energetic, zero-waste, environmentally sustainable, self-sufficient in terms of both organic food production and symbiosis between the environment and industry. New cities will be able to have new organisational structures—either city states, or, apolitical, jigsaw-like structures that can change their position—like in the case of the city of Artisanopolis, designed as a floating city, close to the land, reminiscent of the legendary Atlantis. This paper is focused on the main issues connected with problems of the contemporary city planning. The purpose of the research was to identify existing technological solutions, whose aim is to use solar energy and urban greenery. The studies were based on literature related to future city development issues and futuristic projects of the architects and city planners. In the paper, the following issues have been verified: futuristic cities and districts, and original bionic buildings, both residential and industrial. The results of the analysis have been presented in a tabular form.



Robert acland (1941-2016) innovator, microsurgeon, anatomist and teacher

Publication date: Available online 5 December 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Duncan McGrouther
The breadth and depth of Robert (Bob) Acland's contribution to Plastic and Reconstructive Surgery merits communication to younger generations. From early days at boarding school Bob took a great interest in acquiring precision skills in metalwork and carpentry which were to prepare him for later innovations in the design and manufacture of prototype microsurgical instruments. He then worked with suppliers and manufacturers to market the microsurgical instrumentation which is in international use today. Bob was particularly proud of the fine needles which revolutionized microvascular repair as described in letters of a correspondence with Harry J Buncke Jr over a 6 year period. Ultimately Bob performed the first UK series of 6 free flaps at Canniesburn Hospital with 100% success demonstrating to a conservative specialty that free flaps were to become a standard treatment at the top of the ladder of reconstruction. Moving to Luisville USA as microsurgical teacher and research worker, Bob's craftsmanship was to be expressed later in anatomical dissections dynamically illustrated from numerous aspects through his manufacture of moving stages. All his innovative works in microsurgery and anatomy were characterized by a meticulous attention to detail.



How Acne Bumps Cause the Blues: The Influence of Acne Vulgaris on Self-Esteem

Acne vulgaris is one of the most common dermatologic complaints. Although dermatologists are skilled at treating acne, invisible psychological scars can be left by the disease. We review 13 articles that examined the effect of acne vulgaris on patients' self-esteem. Overall, these studies demonstrated that acne has a negative effect on self-esteem among patients of all age groups. These effects most strongly affect women and those with severe acne (both subjectively and objectively). Despite the impact on self-esteem, only a minority of patients seek medical treatment, and even fewer seek treatment from a dermatologist.

Commentary: Mastopexy on Reconstructed Breast Following Massive Weight Loss: An Innovative Technique Using Dermo-Capsular Flaps



The Efficacy and Safety of Early Postoperative Botulinum Toxin A Injection for Facial Scars

Abstract

Background

Scars widen when the underlying musculature pulls apart suture lines, and scars oriented against relaxed skin tension lines are especially susceptible to these distraction forces. Because botulinum toxin A (BTA) induces complete muscle paralysis, the purpose of the current study was to evaluate the effects of BTA using both observer-dependent qualitative assessments and quantitative measurements to verify its beneficial effects on facial scarring.

Methods

Patients with vertical forehead lacerations, treated by primary closure, were randomly assigned to two groups: one (n = 15) received BTA injections within 5 days of primary closure and the other (n = 15) received no further treatment. Vancouver scar scale (VSS) scores and wound width were determined at the 1-month and 6-month follow-up visits. Quantitative color differences between the scar and surrounding normal skin, using the Commission International d'Eclairage L*a*b* color coordinates, were measured and compared by analyzing photographs.

Result

Improved VSS scores, less increase in wound width, and less scar discoloration were noted among patients treated with BTA injections compared with the control group. These differences were observed at the 6-month visit, but not at the 1-month visit.

Conclusion

BTA injection improves scar quality when injected during the early postoperative days.

Level of Evidence I

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.



Using Four-Layer Sculpted Rib Cartilage Framework to Increase Transverse Height of the Reconstructive Ear in One Operative Stage for Microtia Patients

Abstract

Purpose

This case study improves an operative method of ear reconstruction for microtia patients by using a four-layer rib cartilage framework to increase transverse height of the reconstructive ear to a natural level in one operative stage.

Materials and Methods

The procedures of ear reconstruction were conducted from February 2014 to May 2016. The ear framework used in the procedures was fabricated from autologous rib cartilage into a four-layer spliced sculpture. Totally 23 patients with unilateral microtia were willing to be enrolled in this study.

Results

After the operation, 23 patients achieved 2.3–2.8 cm transverse height of reconstructed ears, which was basically the same as the normal side. Both patients and their families felt satisfied with the results. Follow-up was performed at 6–16 months after the procedures. Only one case showed significantly lowered transverse height of the reconstructed ear, compared to the normal one. It was due to the sleeping position of the patient (10-year-old boy), which put the reconstructed ear under pressure and reduced the transverse height of the ear.

Conclusions

The method of four-layer sculpted autologous rib cartilage ear reconstruction has good clinical effect. It can provide a reconstructed ear that reaches normal transverse height and avoids a third operation to increase the transverse height by rib cartilage transplantation.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.



Prevalence of occult hepatitis C virus among hemodialysis patients in Tanta university hospitals: a single-center study

Abstract

Occult hepatitis C virus infection (OCI) is a newly defined type of infection by the chronic hepatitis virus (HCV) distinguished by the existence of HCV RNA in liver tissue and/or peripheral blood mononuclear cells (PBMCs) in patients whose plasma are devoid of both positive serology and RNA. Patients on maintenance hemodialysis evince a higher HCV prevalence than the general population due to high nosocomial transmission by the dialysis units. We investigated the prevalence of occult HCV infection in patients attending our university hemodialysis centers for maintenance hemodialysis. Sixty-two CHD patients negative for serum HCV tests were enrolled in the study. PMNCs were tested by real-time PCR for the presence of HCV RNA. For the 62 patients, the average duration since starting dialysis was 32.7 months and the mean (SD) alanine transaminase and aspartate transaminase were 25.74 ± 9.75 and 28.81 ± 11.32 IU/l, respectively. Out of the 62 CHD patients negative for serum anti-HCV and HCV RNA patients, only three (4.84%) were shown to have HCV RNA in their PBMCs implying the diagnosis of OCI; their viral load range was 1.24–4.15 IU/ml. All three OCI-proven patients gave no history of hepatic disease. In this study, we found that patients considered to be free of HCV can have HCV replicating in their PBMCs. This awareness points to the possibility of HCV being transmitted from apparently uninfected persons. A positive HCV RNA detection in PBMCs is dependable in determining OCI among high-risk subjects particularly when a liver biopsy is not an option. HCV transmission can occur through hemodialysis units signaling incorrect application of infection control measures in our Egyptian dialysis units. Additional studies on hemodialysis patients are necessary to realize the true magnitude of OCI among this patient group and to highlight the importance of incorporating HCV viral assays in PBMCs into the diagnostic algorithm.



Race as a Predictor of Patient Preferences for Biopsy Result Communication



Generational Influence on Patient Learning Preferences in Dermatology



Prospective Analysis Comparing Arthroplasty with HD-Flex versus Trapezial Resection Alone in Basilar Joint Arthritis

imageNo abstract available

Dynamic Model of Applied Facial Anatomy with Emphasis on Teaching of Botulinum Toxin A

imageBackground: The use of botulinum toxin type A is considered one of the most revolutionary and promising face rejuvenation methods. Although rare, most of the complications secondary to the use of botulinum toxin A are technician dependent. Among the major shortcomings identified in the toxin administration education is unfamiliarity with applied anatomy. This article proposes the use of body painting as an innovative method of teaching the application of botulinum toxin A. Methods: Using the body painting technique, facial anatomy was represented on the face of a model showing the major muscle groups of botulinum toxin A targets. Photographic records and films were made for documentation of represented muscles at rest and contraction. Results: Using the body painting technique, each of the muscles involved in facial expression and generation of hyperkinetic wrinkles can be faithfully reproduced on the model's face. The documentation of the exact position of the points of application, the distribution of the feature points in the muscular area, the proper angulation and syringe grip, as well as the correlation of the points of application with the presence of hyperkinetic wrinkles, could be properly registered, providing professional training with information of great practical importance, development of highly effective treatments, and low complication rates. Conclusion: By making it possible to interrelate anatomy of a function, body painting is proposed in the present study as an innovative method, which in a demonstrative and highly didactic manner presents great potential as a teaching tool in the application of botulinum toxin A.

Negative-Pressure Wound Therapy for Ludwig’s Angina: A Case Series

imageSummary: Negative-pressure wound therapy (NPWT) is a well-established therapeutic approach for various complex wound classes. There is currently limited information on the use of NPWT for the scope of head and neck wounds. However, NPWT has been used successfully in some cases, including malignancy, infection, and trauma. In West Virginia, the incidence of dental-related infections leading to Ludwig's Angina is high due to lack of access to dental care. Our case series describes the application of vacuum-based therapy in conjunction with antibiotic therapy for quick, effective closure of deep tissue infections before definitive complex wound repair via graft and flap reconstructions. Over a period of 3 months, 2 patients with submental infections extending to the lateral neck demonstrated clean, efficient wound closure with NPWT for less than 14 days while hospitalized at West Virginia University Medicine. Outpatient follow-up with these patients demonstrated excellent cosmetic outcomes with minimal contracture or hypertrophy of healing tissue. NPWT promotes wound healing through decreased edema, improved perfusion, and increased granulation of tissue based on our findings. Our series encourages the use of NPWT for initial closure of complex wounds secondary to deep neck infections.

Risk Factors for Complications in Expander-Based Breast Reconstruction: Multivariate Analysis in Asian Patients

imageBackground: There have been many studies examining risk factors for complications in expander-based breast reconstruction after mastectomy, and some patient factors have been identified as risk factors. However, most of the previous studies were based on Caucasian patients. Methods: Asian patients who had a tissue expander placed for immediate breast reconstruction between January 2006 and December 2015 (363 patients and 371 expanders) were analyzed retrospectively. Univariate and multivariate analyses were performed to elucidate risk factors for complications. Results: The rate of skin necrosis was significantly higher in nipple-sparing mastectomy than in other types of mastectomies (12 patients among 107 patients, P = 0.001). The weight of the resected specimen was significantly higher in the group with complications than in the group without complications (444 g compared with 363 g, P = 0.027). Other factors (age, body mass index, smoking, expander type, preoperative chemotherapy, axillary dissection) had no significant effect on complications. Multivariate analysis with a logistic regression showed that a large breast (over 500 g) was the only significant risk factor for complications, with an odds ratio of 3.20 and a 95% confidence interval of 1.33–7.54 (P = 0.010). Conclusion: In this series of Asian patients, breast size, rather than body mass index, is the most important predictor for complications in expander-based breast reconstruction.

Minimally Invasive Genioplasty Procedure

imageSummary: In this technical note, we present a new surgical approach for genioplasty in which a minimally invasive procedure is used to perform the chin osteotomy. The main goal was to reduce postoperative functional recovery time and possible complications, especially reduction of lip incompetence, chin ptosis, and muscle dysfunction, by retaining the intactness of the mentalis muscles.

Stakeholders’ Perspectives on Postmastectomy Breast Reconstruction: Recognizing Ways to Improve Shared Decision Making

imageBackground: Postmastectomy breast reconstruction (PMBR) is an elective, preference-sensitive decision made during a stressful, time-pressured period after a cancer diagnosis. Shared decision making (SDM) can improve decision quality about preference-sensitive choices. Stakeholders' perspectives on ways to support PMBR decision-making were explored. Methods: Forty semi-structured interviews with stakeholders (20 postmastectomy patients, 10 PMBR surgeons, 10 PMBR nurses) were conducted. Clinicians were recruited from diverse practices across the United States. Patients were recruited using purposive sampling with varying PMBR experiences, including no reconstruction. The interview guide was based on an implementation research framework. Themes were identified using grounded theory approach, based on frequency and emotive force conveyed. Results: Engagement in SDM was variable. Some patients wanted more information about PMBR from clinicians, particularly about risks. Some clinicians acknowledged highlighting benefits and downplaying risks. Many patients felt pressured to make a choice by their clinicians. Clinicians who successfully engaged patients through decisions often used outside resources to supplement conversations. Conclusions: Patient–clinician trust was critical to high-quality decisions, and many patients expressed decision regret when they were not engaged in PMBR discussions. Patients often perceived a race- or age-related bias in clinician information sharing. Interventions to support SDM may enhance decision quality and reduce decision regret about PMBR, ultimately improving patient-centered care for women with breast cancer.

Central Mound Mastopexy for the Correction of Tuberous/Tubular Breast Deformity

imageSummary: Tuberous and tubular breast deformity are well-recognized abnormalities in the plastic surgery community that incur severe physical and psychological consequences in affected patients. Current reconstructive options for the tuberous and tubular breasts favor the use of prosthetic implants and soft-tissue manipulation. We present a case of tuberous and tubular breast deformity treated with a central mound reduction technique and mastopexy with imbricating sutures without the use of prosthetic implants. The patient remained extremely pleased with her results at long-term follow-up. This represents a unique case of successful reconstruction in a patient with a tuberous and tubular breast deformity using a central mound reduction technique with mastopexy and without a prosthetic device.

Synchronous Premaxillary Osteotomy with Primary Cheiloplasty for BCLP Patients with Protrusion of the Premaxillae

imageBackground: In bilateral cleft lip and palate (BCLP) patients with protrusion and/or torsion of the premaxillae, it is difficult to achieve a good outcome. We have developed a series of procedures of premaxillary osteotomy with primary cheiloplasty for BCLP patients who did not respond well to presurgical orthodontics (PSO). Methods: A total of 27 BCLP patients with protrusion and/or torsion of the premaxillae underwent PSO. For 3 BCLP patients in whom the protruded premaxillae could not be returned to a good position, a primary premaxillary osteotomy and gingivoperiosteoplasty (GPP) with cheiloplasty were performed simultaneously. Subsequently, Furlow palatoplasty was performed by one and a half years of age. Maxillary growth was evaluated by dental occlusion at 4 years of age. Results: A premaxillary osteotomy and GPP with cheiloplasty were performed at 6 months. The patients' facial structures improved, their premaxillae were positioned more superiorly, and normal inclination of the incisors was achieved. They had edge-to-edge occlusions or cross bites at 4 years of age. Conclusions: As advantages, the patients' facial structures improved, and the alveolar bones were formed by GPP. As a disadvantage, premaxillary necrosis might occur because of poor blood circulation. It is important to secure the following 2 blood supplies: from the periosteum and soft-tissue of the anterior premaxillae and from the periosteum and mucosa of the nasal septum. Synchronous premaxillary osteotomy and GPP with primary cheiloplasty are appropriate when the premaxillae cannot be properly repositioned by PSO or PSO cannot be done.

Combining Follicular Unit Extraction and Scalp Micropigmentation for the Cosmetic Treatment of Alopecias

imageTwo relatively new modalities, follicular unit extraction (FUE) and scalp micropigmentation have changed the treatment of hair loss, to reduce the number of procedures and the total costs of the hair restoration process. These 2 modalities augment each other when treating patients with thinning hair and balding. The explosion of FUE procedures (which reflected 52.6% of the hair transplant procedures performed in 2016, up from 48.5%) and the appearance of more and more new physicians offering hair restoration technologies employing FUE have caused a 20% annual growth in this industry over the past few years. This article reviews the use of FUE and scalp micropigmentation when used in combination.

Open Cancellous Bone Grafting for Recalcitrant Palatal Fistula: Repurposing the Papineau Technique

imageSummary: Cleft palate fistula is defined as a breakdown in the primary surgical repair of the palate resulting in oronasal communication, which can create symptomatic regurgitation for fluids/solids and affect speech, manifested by airflow escape during phonation. With the reported postoperative occurrence rate of 33–37% postfistula repair, it remains a challenging problem. The primary aim of this study was to describe our experience in the management of 7 consecutive cases of recalcitrant palatal fistula, all secondary to primary cleft palate repair. Pure cancellous bone graft was harvested in a standard fashion in sufficient quantity based on size of fistula from the iliac crest and was morselized and was kept mixed with the patient's blood. After flap turnover for nasal closure, the graft was packed over the raw surface on the oral aspect and was secured by placing an oxidized regenerated cellulose sheet fixed to the surrounding mucosa. As per the Papineau technique, no oral closure was performed. Six-month follow-up showed complete epithelization of the oral raw surface in 6 of the 7 patients. In the diverse spectra of cleft surgeries, management of recalcitrant cleft palate fistula remains a surgical challenge. Repurposing Papineau's concept of open cancellous bone grafting in cleft palate fistula is a novel attempt with a sound scientific basis. In our experience, this technique has proved to be very effective in managing recalcitrant palatal fistulae.

Strategy for Nasal Reconstruction in Atypical Facial Clefts

imageSummary: It is difficult to put forward a strategy for the treatment of nasal clefts due to the rarity and diversity of anatomical aberrations of these cases contrary to the common nasal affection in cleft lip and palate patients, which differ in severity rather than differing in the morbid anatomy. This simple strategy for correction of these nasal clefts will hopefully help surgeons to achieve better results. In the mean time I intended to describe the morbid anatomy of these cases by choosing examples of each morbid anatomy.

Reconstruction of Congenital Sternal Clefts: Surgical Experience and Literature Review

imageBackground: Sternal cleft is a rare anomaly with a reported incidence of 1:100,000 cases per live births. Surgical intervention represents a crucial factor altering the overall patient prognosis, since they are at high risk of impaired oxygenation, as well as multiple chest infections. Herein, we are reporting our experience of surgical management of such rare cases, alerting plastic surgeons to their possibly crucial role in the reconstructive team. Methods: A retrospective chart review of 2 cases presenting with chest wall defects. All perioperative data were collected and presented. Results: Two patients with sternal clefts of variable degrees were managed. The first was an 18-month-old boy with partial inferior sternal cleft, who was otherwise asymptomatic. The patient underwent reconstruction at the same age using autologous rib graft and pectoralis major flaps due to ectopia cordis that was putting the patient at higher risk for cardiac trauma. The second patient was a 3-month-old girl having a V-shaped partial superior cleft with lung herniation. Surgical reconstruction was applied due to difficulty in weaning the patient off of ventilator support. Initially, reconstruction was applied with SurgiMend dermal matrix, but this was complicated by chest retraction and high oxygen requirement. Definitive reconstruction was later applied with allogeneic bone graft and pectoralis major flaps. Conclusions: Meticulous patient assessment and screening for associated anomalies are crucial. Surgical intervention is warranted at an early age. The use of acellular dermal matrix products in the reconstruction is of interest, but should be approached with caution.

Laparoscopic Harvest of the Rectus Abdominis for Perineal Reconstruction

imageSummary: The rectus abdominis is a workhorse flap for perineal reconstruction, in particular after abdominoperineal resection (APR). Laparoscopic and robotic techniques for abdominoperineal surgery are becoming more common. The open harvest of the rectus abdominis negates the advantages of these minimally invasive approaches. (Sentence relating to advantages of laparoscopic rectus deleted here.) We present our early experience with laparoscopic harvest of the rectus muscle for perineal reconstruction. Three laparoscopic unilateral rectus abdominis muscle harvests were performed for perineal reconstruction following minimally invasive colorectal and urological procedures. The 2 patients who underwent APR also had planned external perineal skin reconstruction with local flaps. (Sentence deleted here to shorten abstract.) All rectus muscle harvests were performed laparoscopically. Two were for perineal reconstruction following laparoscopic APR, and 1 was for anterior vaginal wall reconstruction. This was done with 4 ports positioned on the contralateral abdomen. The average laparoscopic harvest time was 60–90 minutes. The rectus muscle remained viable in all cases. One patient developed partial necrosis of a posterior thigh fasciocutaneous flap after cancer recurrence. There were no pelvic abscesses, or abdominal wall hernias. Laparoscopic harvest of the rectus appears to be a cost-effective, reliable, and reproducible procedure for perineal with minimal donor-site morbidity. Larger clinical studies are needed to further establish the efficacy and advantages of the laparoscopic rectus for perineal reconstruction.

Genetic Overview of Syndactyly and Polydactyly

imageSummary: Syndactyly and polydactyly—respectively characterized by fused and supernumerary digits—are among the most common congenital limb malformations, with syndactyly presenting at an estimated incidence of 1 in 2,000–3,000 live births and polydactyly at a frequency of 1 in approximately 700–1,000 live births. Despite their relatively regular manifestation in the clinic, the etiologies of syndactyly and polydactyly remain poorly understood because of their phenotypic and genetic diversity. Further, even though concrete knowledge of genotypic links has been established for some variants of syndactyly and polydactyly, there appears to be no single comprehensive published summary of all syndromic and nonsyndromic syndactyly and polydactyly presentations, and there is decidedly no resource that maps all syndromic and nonsyndromic syndactylies and polydactylies to their genetic bases. This gap in the literature problematizes comprehensive carrier screening and prenatal diagnosis and complicates novel diagnostic attempts. This review thus attempts to collect all that is known about the genetic bases of syndromic and nonsyndromic syndactylies and polydactylies, as well as to highlight the dactyly manifestations for which no genetic bases are as yet known. Then, having established a summation of existing and missing knowledge, this work briefly outlines the diagnostic techniques that a genetics-reinforced understanding of syndactyly and polydactyly could inform.

The Boomerang-shaped Pectoralis Major Musculocutaneous Flap for Reconstruction of Circular Defect of Cervical Skin

imageSummary: We report on a patient with a recurrence of oral cancer involving a cervical lymph node. The patient's postexcision cervical skin defect was nearly circular in shape, and the size was about 12 cm in diameter. The defect was successfully reconstructed with a boomerang-shaped pectoralis major musculocutaneous flap whose skin paddle included multiple intercostal perforators of the internal mammary vessels. This flap design is effective for reconstructing an extensive neck skin defect and enables primary closure of the donor site with minimal deformity.

The Fine Wire Technique for Flexor Tenolysis

imageBackground: Flexor tenolysis surgery for flexor digitorum profundus and superficialis adhesions is a common procedure performed by hand surgeons. Releasing these adhered tendons can greatly improve hand function and improve quality of life. Recent evidence, however, has shown that the outcomes of tenolysis surgeries are often suboptimal and can result in relapsing adhesions or even tendon ruptures. Methods: This article describes a new technique with potential for reduced complication rates: The Fine Wire Technique for Flexor Tenolysis (FWT). Results: Following FWT, the patient detailed in this article had an excellent recovery of function and no complications: including tendon rupture, infection, hematomas, or any other complications. She reported a major improvement from her preoperative functionality and continues to have this level of success. The wire's thinness allows for a swift tenolysis. Conclusions: The FWT is a new option available to the hand surgeon associated with good functional results. The wire is readily available to the clinician and is also inexpensive.

STRATAFIX for Abdominal Wall Repair following Abdominal Flap Harvest

imageNo abstract available

Hemi-Intravascular Stenting for Supermicrosurgical Anastomosis

imageBackground: Although supermicrosurgical anastomosis is a widely known reconstructive microsurgical technique, it is difficult to perform. To expand the clinical use of supermicrosurgery, we used hemi-intravascular stenting (hemi-IVaS), which is performed by inserting an intravascular stent into one side of the vessel. We conducted lymphaticovenular anastomosis, free perforator flap transfer, and fingertip replantation with supermicrosurgical anastomosis using hemi-IVaS technique and examined its usefulness. Methods: Between January 2013 and February 2015, 11 anastomoses in 11 cases of lymphaticovenular anastomosis for lymphedema patients, 14 anastomoses in 7 cases of free perforator flap transfer with supermicrosurgical perforator-to-perforator anastomosis, and 9 anastomoses in 5 cases of fingertip replantation were performed using hemi-IVaS. Time required for anastomosis and complications were examined. Flap survival rate was also examined in free perforator flap transfer cases and fingertip replantation cases. Results: In all cases, anastomoses were performed without complications such as inadvertent catching of the back wall of the vessel during the procedure or the need for reanastomoses. The average time required to complete the anastomosis was 16.4 ± 3.20 minutes using the hemi IVaS technique. All flaps survived in the supermicrosurgical perforator-to-perforator anastomosis as well as fingertip replantation cases. Conclusions: Hemi-IVaS could be a useful alternative to conventional intravascular stenting techniques and is also effective for supermicrosurgical perforator-to-perforator anastomosis. Further studies are needed to improve the success rate and to explore its other possible utilizations in supermicrosurgery.

Vaginoplasty and Perineoplasty

imageNo abstract available

Superficial Soft-Tissue Sarcomas Rarely Require Advanced Soft-Tissue Reconstruction following Resection

imageObjective: Soft-tissue sarcomas are most frequently located deep within myofascial compartments. Superficial soft-tissue sarcomas (S-STS) are relatively less common and may be managed differently than deep sarcomas because generous resection margins are often possible without sacrificing critical structures. We sought to investigate the frequency and types of soft-tissue reconstructive procedures that are required following excision of S-STS. Methods: We reviewed 457 consecutively treated patients with S-STS with a minimum 2-year follow-up from our prospectively maintained database between 1989 and 2009. Results: Mean follow-up was 10.5 years (range, 2–23). Four hundred twenty-one tumors (91%) were excised with negative margins, 38 (8.3%) had microscopically positive margins, and three (0.7%) had grossly positive margins. One patient required an amputation. In 271 (58%) patients, the wounds were closed primarily. In comparison, 93 patients (20%) required a rotation flap, 70 (15%) required a split-thickness skin graft, and 23 (5%) underwent a free tissue transfer (ie, advanced reconstructive procedure). The overall complication rate was 12%, although 43% of patients undergoing free tissue transfer developed complications (P = 0.04). An unplanned excision before referral to our center was a risk factor for local recurrence (P = 0.03) when residual tumor was recovered in the reexcision specimen pathologically. Conclusions: Although concern about the morbidity associated with a free tissue transfer (ie, advanced reconstructive procedure) may potentially limit the adequacy of resection in some patients with S-STS, the results of this study showed that the majority of patients had complete excisions with negative margins and primary closure. Obtaining a negative margin when excising a known or suspected S-STS rarely requires an advanced reconstructive procedure and almost never results in loss of limb.

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

imageNo abstract available

Optical Coherence Tomography Features of Dermatophytoma

This case report illustrates the optical coherence tomography features of dermatophytoma.

Practicing Safe Dermatology—Screening Out Liability

The article "Characteristics of Medical Liability Claims Against Dermatologists From 1991 Through 2015" by Kornmehl and colleagues is a welcome addition in our quest to understand how to reduce dermatology practice risk. The study confirms much of what we already knew or suspected but also provides some new interesting insights. It is reassuring to see that most malpractice cases against dermatologists are "abandoned, withdrawn or dismissed." Similarly, it is comforting to know that there has been a net reduction of 29.2% in paid claims for dermatologists. Is this secondary to improved patient care? The changing landscape of tort reform? Or both?

Knowledge to Detect Scalp and Neck Melanoma

This study tests the association between a video intervention and hairdresser knowledge of melanoma and self-confidence in skin lesion detection.

Trends in Medical Liability Claims Against Dermatologists

This study analyzes 24 years of data through 2015 from a nationally representative liability claims registry to compare the medical liability claims against dermatologists vs nondermatologists.

Immunotherapy and Overall Survival in Elderly Patients With Melanoma

This cohort study evaluates if age influences clinical outcome and immune adverse events in patients treated by immunotherapy for `metastatic melanoma.

Effect of Tannic acid on skin barrier function

Abstract

In this study, we investigated how tannic acid (TA) protects the skin from inflammation caused by external irritation. The effects of TA were evaluated by using a mouse 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced skin inflammation model and a reconstructed human epidermal model (RHEM). We then used Lucifer Yellow for visual confirmation of TA's suppression effect at the SC surface. TA treatment of the skin prevented Lucifer Yellow from permeating the skin. This result suggests that TA acts as a barrier against external stimulants such as TPA and artificial sweat on the SC surface.

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The Reduction of Ventrolateral Prefrontal Cortex Gray Matter Volume Correlates with Loss of Economic Rationality in Aging

The population of people above 65 years old continues to grow, and there is mounting evidence that as humans age they are more likely to make errors. However, the specific effect of neuroanatomical aging on the efficiency of economic decision-making is poorly understood. We used whole-brain voxel-based morphometry analysis to determine where reduction of gray matter volume in healthy female and male adults over the age of 65 years correlates with a classic measure of economic irrationality: violations of the Generalized Axiom of Revealed Preference. All participants were functionally normal with Mini-Mental State Examination scores ranging between 26 and 30. While our elders showed the previously reported decline in rationality compared with younger subjects, chronological age per se did not correlate with rationality measures within our population of elders. Instead, reduction of gray matter density in ventrolateral prefrontal cortex correlates tightly with irrational behavior. Interestingly, using a large fMRI sample and meta-analytic tool with Neurosynth, we found that this brain area shows strong coactivation patterns with nearly all of the value-associated regions identified in previous studies. These findings point toward a neuroanatomic locus for economic rationality in the aging brain and highlight the importance of understanding both anatomy and function in the study of aging, cognition, and decision-making.

SIGNIFICANCE STATEMENT Age is a crucial factor in decision-making, with older individuals making more errors in choices. Using whole-brain voxel-based morphometry analysis, we found that reduction of gray matter density in ventrolateral prefrontal cortex correlates with economic irrationality: reduced gray matter volume in this area correlates with the frequency and severity of violations of the Generalized Axiom of Revealed Preference. Furthermore, this brain area strongly coactivates with other reward-associated regions identified with Neurosynth. These findings point toward a role for neuroscientific discoveries in shaping long-standing economic views of decision-making.



Assessing the Role of Inhibition in Stabilizing Neocortical Networks Requires Large-Scale Perturbation of the Inhibitory Population

Neurons within cortical microcircuits are interconnected with recurrent excitatory synaptic connections that are thought to amplify signals (Douglas and Martin, 2007), form selective subnetworks (Ko et al., 2011), and aid feature discrimination. Strong inhibition (Haider et al., 2013) counterbalances excitation, enabling sensory features to be sharpened and represented by sparse codes (Willmore et al., 2011). This balance between excitation and inhibition makes it difficult to assess the strength, or gain, of recurrent excitatory connections within cortical networks, which is key to understanding their operational regime and the computations that they perform. Networks that combine an unstable high-gain excitatory population with stabilizing inhibitory feedback are known as inhibition-stabilized networks (ISNs) (Tsodyks et al., 1997). Theoretical studies using reduced network models predict that ISNs produce paradoxical responses to perturbation, but experimental perturbations failed to find evidence for ISNs in cortex (Atallah et al., 2012). Here, we reexamined this question by investigating how cortical network models consisting of many neurons behave after perturbations and found that results obtained from reduced network models fail to predict responses to perturbations in more realistic networks. Our models predict that a large proportion of the inhibitory network must be perturbed to reliably detect an ISN regime robustly in cortex. We propose that wide-field optogenetic suppression of inhibition under promoters targeting a large fraction of inhibitory neurons may provide a perturbation of sufficient strength to reveal the operating regime of cortex. Our results suggest that detailed computational models of optogenetic perturbations are necessary to interpret the results of experimental paradigms.

SIGNIFICANCE STATEMENT Many useful computational mechanisms proposed for cortex require local excitatory recurrence to be very strong, such that local inhibitory feedback is necessary to avoid epileptiform runaway activity (an "inhibition-stabilized network" or "ISN" regime). However, recent experimental results suggest that this regime may not exist in cortex. We simulated activity perturbations in cortical networks of increasing realism and found that, to detect ISN-like properties in cortex, large proportions of the inhibitory population must be perturbed. Current experimental methods for inhibitory perturbation are unlikely to satisfy this requirement, implying that existing experimental observations are inconclusive about the computational regime of cortex. Our results suggest that new experimental designs targeting a majority of inhibitory neurons may be able to resolve this question.



Phencyclidine Discoordinates Hippocampal Network Activity But Not Place Fields

We used the psychotomimetic phencyclidine (PCP) to investigate the relationships among cognitive behavior, coordinated neural network function, and information processing within the hippocampus place cell system. We report in rats that PCP (5 mg/kg, i.p.) impairs a well learned, hippocampus-dependent place avoidance behavior in rats that requires cognitive control even when PCP is injected directly into dorsal hippocampus. PCP increases 60–100 Hz medium-freguency gamma oscillations in hippocampus CA1 and these increases correlate with the cognitive impairment caused by systemic PCP administration. PCP discoordinates theta-modulated medium-frequency and slow gamma oscillations in CA1 LFPs such that medium-frequency gamma oscillations become more theta-organized than slow gamma oscillations. CA1 place cell firing fields are preserved under PCP, but the drug discoordinates the subsecond temporal organization of discharge among place cells. This discoordination causes place cell ensemble representations of a familiar space to cease resembling pre-PCP representations despite preserved place fields. These findings point to the cognitive impairments caused by PCP arising from neural discoordination. PCP disrupts the timing of discharge with respect to the subsecond timescales of theta and gamma oscillations in the LFP. Because these oscillations arise from local inhibitory synaptic activity, these findings point to excitation–inhibition discoordination as the root of PCP-induced cognitive impairment.

SIGNIFICANCE STATEMENT Hippocampal neural discharge is temporally coordinated on timescales of theta and gamma oscillations in the LFP and the discharge of a subset of pyramidal neurons called "place cells" is spatially organized such that discharge is restricted to locations called a cell's "place field." Because this temporal coordination and spatial discharge organization is thought to represent spatial knowledge, we used the psychotomimetic phencyclidine (PCP) to disrupt cognitive behavior and assess the importance of neural coordination and place fields for spatial cognition. PCP impaired the judicious use of spatial information and discoordinated hippocampal discharge without disrupting firing fields. These findings dissociate place fields from spatial cognitive behavior and suggest that hippocampus discharge coordination is crucial to spatial cognition.



History-Dependent Odor Processing in the Mouse Olfactory Bulb

In nature, animals normally perceive sensory information on top of backgrounds. Thus, the neural substrate to perceive under background conditions is inherent in all sensory systems. Where and how sensory systems process backgrounds is not fully understood. In olfaction, just a few studies have addressed the issue of odor coding on top of continuous odorous backgrounds. Here, we tested how background odors are encoded by mitral cells (MCs) in the olfactory bulb (OB) of male mice. Using in vivo two-photon calcium imaging, we studied how MCs responded to odors in isolation versus their responses to the same odors on top of continuous backgrounds. We show that MCs adapt to continuous odor presentation and that mixture responses are different when preceded by background. In a subset of odor combinations, this history-dependent processing was useful in helping to identify target odors over background. Other odorous backgrounds were highly dominant such that target odors were completely masked by their presence. Our data are consistent in both low and high odor concentrations and in anesthetized and awake mice. Thus, odor processing in the OB is strongly influenced by the recent history of activity, which could have a powerful impact on how odors are perceived.

SIGNIFICANCE STATEMENT We examined a basic feature of sensory processing in the olfactory bulb. Specifically, we measured how mitral cells adapt to continuous background odors and how target odors are encoded on top of such background. Our results show clear differences in odor coding based on the immediate history of the stimulus. Our results support the argument that odor coding in the olfactory bulb depends on the recent history of the sensory environment.



Familiar But Unexpected: Effects of Sound Context Statistics on Auditory Responses in the Songbird Forebrain

Rapid discrimination of salient acoustic signals in the noisy natural environment may depend, not only on specific stimulus features, but also on previous experience that generates expectations about upcoming events. We studied the neural correlates of expectation in the songbird forebrain by using natural vocalizations as stimuli and manipulating the category and familiarity of context sounds. In our paradigm, we recorded bilaterally from auditory neurons in awake adult male zebra finches with multiple microelectrodes during repeated playback of a conspecific song, followed by further playback of this test song in different interleaved sequences with other conspecific or heterospecific songs. Significant enhancement in the auditory response to the test song was seen when its acoustic features differed from the statistical distribution of context song features, but not when it shared the same distribution. Enhancement was also seen when the time of occurrence of the test song was uncertain. These results show that auditory forebrain responses in awake animals in the passive hearing state are modulated dynamically by previous auditory experience and imply that the auditory system can identify the category of a sound based on the global features of the acoustic context. Furthermore, this probability-dependent enhancement in responses to surprising stimuli is independent of stimulus-specific adaptation, which tracks familiarity, suggesting that the two processes could coexist in auditory processing. These findings establish the songbird as a model system for studying these phenomena and contribute to our understanding of statistical learning and the origin of human ERP phenomena to unexpected stimuli.

SIGNIFICANCE STATEMENT Traditional auditory neurophysiology has mapped acoustic features of sounds to the response properties of neurons; however, growing evidence suggests that neurons can also encode the probability of sounds. We recorded responses of songbird auditory neurons in a novel paradigm that presented a familiar test stimulus in a sequence with similar or dissimilar sounds. The responses encode, not only stimulus familiarity, but also the expectation for a class of sounds based on the recent statistics of varying sounds in the acoustic context. Our approach thus provides a model system that uses a controlled stimulus paradigm to understand the mechanisms by which top-down processes (expectation and memory) and bottom-up processes (based on stimulus features) interact in sensory coding.



Cellular Functions of the Autism Risk Factor PTCHD1 in Mice

The gene patched domain containing 1 (PTCHD1) is mutated in patients with autism spectrum disorders and intellectual disabilities and has been hypothesized to contribute to Sonic hedgehog (Shh) signaling and synapse formation. We identify a panel of Ptchd1-interacting proteins that include postsynaptic density proteins and the retromer complex, revealing a link to critical regulators of dendritic and postsynaptic trafficking. Ptchd1 knock-out (KO) male mice exhibit cognitive alterations, including defects in a novel object recognition task. To test whether Ptchd1 is required for Shh-dependent signaling, we examined two Shh-dependent cell populations that express high levels of Ptchd1 mRNA: cerebellar granule cell precursors and dentate granule cells in the hippocampus. We found that proliferation of these neuronal precursors was not altered significantly in Ptchd1 KO male mice. We used whole-cell electrophysiology and anatomical methods to assess synaptic function in Ptchd1-deficient dentate granule cells. In the absence of Ptchd1, we observed profound disruption in excitatory/inhibitory balance despite normal dendritic spine density on dentate granule cells. These findings support a critical role of the Ptchd1 protein in the dentate gyrus, but indicate that it is not required for structural synapse formation in dentate granule cells or for Shh-dependent neuronal precursor proliferation.

SIGNIFICANCE STATEMENT The mechanisms underlying neuronal and cellular alterations resulting from patched domain containing 1 (Ptchd1) gene mutations are unknown. The results from this study support an association with dendritic trafficking complexes of Ptchd1. Loss-of-function experiments do not support a role in sonic hedgehog-dependent signaling, but reveal a disruption of synaptic transmission in the mouse dentate gyrus. The findings will help to guide ongoing efforts to understand the etiology of neurodevelopmental disorders arising from Ptchd1 deficiency.



Sleep Deprivation Promotes Habitual Control over Goal-Directed Control: Behavioral and Neuroimaging Evidence

Sleep is one of the most fundamental processes of life, playing an important role in the regulation of brain function. The long-term lack of sleep can cause memory impairments, declines in learning ability, and executive dysfunction. In the present study, we evaluated the effects of sleep deprivation on instrumental learning behavior, particularly goal-directed and habitual actions in humans, and investigated the underlying neural mechanisms. Healthy college students of either gender were enrolled and randomly divided into sleep deprivation group and sleep control group. fMRI data were collected. We found that one night of sleep deprivation led to greater responsiveness to stimuli that were associated with devalued outcomes in the slips-of-action test, indicating a deficit in the formation of goal-directed control and an overreliance on habits. Furthermore, sleep deprivation had no effect on the expression of acquired goal-directed action. The level of goal-directed action after sleep deprivation was positively correlated with baseline working memory capacity. The neuroimaging data indicated that goal-directed learning mainly recruited the ventromedial PFC (vmPFC), the activation of which was less pronounced during goal-directed learning after sleep deprivation. Activation of the vmPFC during goal-directed learning during training was positively correlated with the level of goal-directed action performance. The present study suggests that people rely predominantly on habits at the expense of goal-directed control after sleep deprivation, and this process involves the vmPFC. These results contribute to a better understanding of the effects of sleep loss on decision-making.

SIGNIFICANCE STATEMENT Understanding the cognitive consequences of sleep deprivation has become extremely important over the past half century, given the continued decline in sleep duration in industrialized societies. Our results provide novel evidence that goal-directed action may be particularly vulnerable to sleep loss, and the brain mechanism underlying this effect was explored. Elucidation of the effects of sleep deprivation on decision-making will deepen our understanding of the function of sleep, emphasizing the role of sleep in cognitive impairments and mental health.



Abrogated Freud-1/Cc2d1a Repression of 5-HT1A Autoreceptors Induces Fluoxetine-Resistant Anxiety/Depression-Like Behavior

Freud-1/Cc2d1a represses the gene transcription of serotonin-1A (5-HT1A) autoreceptors, which negatively regulate 5-HT tone. To test the role of Freud-1 in vivo, we generated mice with adulthood conditional knock-out of Freud-1 in 5-HT neurons (cF1ko). In cF1ko mice, 5-HT1A autoreceptor protein, binding and hypothermia response were increased, with reduced 5-HT content and neuronal activity in the dorsal raphe. The cF1ko mice displayed increased anxiety- and depression-like behavior that was resistant to chronic antidepressant (fluoxetine) treatment. Using conditional Freud-1/5-HT1A double knock-out (cF1/1A dko) to disrupt both Freud-1 and 5-HT1A genes in 5-HT neurons, no increase in anxiety- or depression-like behavior was seen upon knock-out of Freud-1 on the 5-HT1A autoreceptor-negative background; rather, a reduction in depression-like behavior emerged. These studies implicate transcriptional dysregulation of 5-HT1A autoreceptors by the repressor Freud-1 in anxiety and depression and provide a clinically relevant genetic model of antidepressant resistance. Targeting specific transcription factors, such as Freud-1, to restore transcriptional balance may augment response to antidepressant treatment.

SIGNIFICANCE STATEMENT Altered regulation of the 5-HT1A autoreceptor has been implicated in human anxiety, major depression, suicide, and resistance to antidepressants. This study uniquely identifies a single transcription factor, Freud-1, as crucial for 5-HT1A autoreceptor expression in vivo. Disruption of Freud-1 in serotonin neurons in mice links upregulation of 5-HT1A autoreceptors to anxiety/depression-like behavior and provides a new model of antidepressant resistance. Treatment strategies to reestablish transcriptional regulation of 5-HT1A autoreceptors could provide a more robust and sustained antidepressant response.



Presynaptic Regulation of Leptin in a Defined Lateral Hypothalamus-Ventral Tegmental Area Neurocircuitry Depends on Energy State

Synaptic transmission controls brain activity and behaviors, including food intake. Leptin, an adipocyte-derived hormone, acts on neurons located in the lateral hypothalamic area (LHA) to maintain energy homeostasis and regulate food intake behavior. The specific synaptic mechanisms, cell types, and neural projections mediating this effect remain unclear. In male mice, using pathway-specific retrograde tracing, whole-cell patch-clamp recordings and post hoc cell type identification, we found that leptin reduces excitatory synaptic strength onto both melanin-concentrating hormone- and orexin-expressing neurons projecting from the LHA to the ventral tegmental area (VTA), which may affect dopamine signaling and motivation for feeding. A presynaptic mechanism mediated by distinct intracellular signaling mechanisms may account for this regulation by leptin. The regulatory effects of leptin depend on intact leptin receptor signaling. Interestingly, the synaptic regulatory function of leptin in the LHA-to-VTA neuronal pathway is highly sensitive to energy states: both energy deficiency (acute fasting) and excessive energy storage (high-fat diet-induced obesity) blunt the effect of leptin. These data revealed that leptin may regulate synaptic transmission in the LHA-to-VTA neurocircuitry in an inverted "U-shape" fashion dependent on plasma glucose levels and related to metabolic states.

SIGNIFICANCE STATEMENT The lateral hypothalamic area (LHA) to ventral tegmental area (VTA) projection is an important neural pathway involved in balancing whole-body energy states and reward. We found that the excitatory synaptic inputs to both orexin- and melanin-concentrating hormone expressing LHA neurons projecting to the VTA were suppressed by leptin, a peptide hormone derived from adipocytes that signals peripheral energy status to the brain. Interestingly, energy states seem to affect how leptin regulates synaptic transmission since both the depletion of energy induced by acute food deprivation and excessive storage of energy by high-fat diet feeding dampen the suppressive effect of leptin on synaptic transmission. Together, these data show that leptin regulates synaptic transmission and might be important for maintaining energy homeostasis.



Area-Specific Regulation of Quiescent Neural Stem Cells by Notch3 in the Adult Mouse Subependymal Zone

In the adult mammalian brain, neural stem cells (NSCs) generate new neurons throughout the mammal's lifetime. The balance between quiescence and active cell division among NSCs is crucial in producing appropriate numbers of neurons while maintaining the stem cell pool for a long period. The Notch signaling pathway plays a central role in both maintaining quiescent NSCs (qNSCs) and promoting cell division of active NSCs (aNSCs), although no one knows how this pathway regulates these apparently opposite functions. Notch1 has been shown to promote proliferation of aNSCs without affecting qNSCs in the adult mouse subependymal zone (SEZ). In this study, we found that Notch3 is expressed to a higher extent in qNSCs than in aNSCs while Notch1 is preferentially expressed in aNSCs and transit-amplifying progenitors in the adult mouse SEZ. Furthermore, Notch3 is selectively expressed in the lateral and ventral walls of the SEZ. Knockdown of Notch3 in the lateral wall of the adult SEZ increased the division of NSCs. Moreover, deletion of the Notch3 gene resulted in significant reduction of qNSCs specifically in the lateral and ventral walls, compared with the medial and dorsal walls, of the lateral ventricles. Notch3 deletion also reduced the number of qNSCs activated after antimitotic cytosine β-D-arabinofuranoside (Ara-C) treatment. Importantly, Notch3 deletion preferentially reduced specific subtypes of newborn neurons in the olfactory bulb derived from the lateral walls of the SEZ. These results indicate that Notch isoforms differentially control the quiescent and proliferative steps of adult SEZ NSCs in a domain-specific manner.

SIGNIFICANCE STATEMENT In the adult mammalian brain, the subependymal zone (SEZ) of the lateral ventricles is the largest neurogenic niche, where neural stem cells (NSCs) generate neurons. In this study, we found that Notch3 plays an important role in the maintenance of quiescent NSCs (qNSCs), while Notch1 has been reported to act as a regulator of actively cycling NSCs. Furthermore, we found that Notch3 is specifically expressed in qNSCs located in the lateral and ventral walls of the lateral ventricles and regulates neuronal production of NSCs in a region-specific manner. Our results indicate that Notch3, by maintaining the quiescence of a subpopulation of NSCs, confers a region-specific heterogeneity among NSCs in the adult SEZ.



CK2 Oppositely Modulates L-DOPA-Induced Dyskinesia via Striatal Projection Neurons Expressing D1 or D2 Receptors

We have previously shown that casein kinase 2 (CK2) negatively regulates dopamine D1 and adenosine A2A receptor signaling in the striatum. Ablation of CK2 in D1 receptor-positive striatal neurons caused enhanced locomotion and exploration at baseline, whereas CK2 ablation in D2 receptor-positive neurons caused increased locomotion after treatment with A2A antagonist, caffeine. Because both, D1 and A2A receptors, play major roles in the cellular responses to l-DOPA in the striatum, these findings prompted us to examine the impact of CK2 ablation on the effects of l-DOPA treatment in the unilateral 6-OHDA lesioned mouse model of Parkinson's disease. We report here that knock-out of CK2 in striatonigral neurons reduces the severity of l-DOPA-induced dyskinesia (LID), a finding that correlates with lowered pERK but unchanged pPKA substrate levels in D1 medium spiny neurons as well as in cholinergic interneurons. In contrast, lack of CK2 in striatopallidal neurons enhances LID and ERK phosphorylation. Coadministration of caffeine with a low dose of l-DOPA reduces dyskinesia in animals with striatopallidal knock-out to wild-type levels, suggesting a dependence on adenosine receptor activity. We also detect reduced Golf levels in the striatonigral but not in the striatopallidal knock-out in response to l-DOPA treatment.

Our work shows, in a rodent model of PD, that treatment-induced dyskinesia and striatal ERK activation are bidirectionally modulated by ablating CK2 in D1- or D2-positive projection neurons, in male and female mice. The results reveal that CK2 regulates signaling events critical to LID in each of the two main populations of striatal neurons.

SIGNIFICANCE STATEMENT To date, l-DOPA is the most effective treatment for PD. Over time, however, its efficacy decreases, and side effects including l-DOPA-induced dyskinesia (LID) increase, affecting up to 78% of patients within 10 years of therapy (Hauser et al., 2007). It is understood that supersensitivity of the striatonigral pathway underlies LID, however, D2 agonists were also shown to induce LID (Bezard et al., 2001; Delfino et al., 2004). Our work implicates a novel player in the expression of LID, the kinase CK2: knock-out of CK2 in striatonigral and striatopallidal neurons has opposing effects on LID. The bidirectional modulation of dyskinesia reveals a central role for CK2 in striatal physiology and indicates that both pathways contribute to LID.