La e-dermatología en la formación del residente

Publication date: May 2018
Source:Actas Dermo-Sifiliográficas, Volume 109, Issue 4
Author(s): Lara Ferrándiz, David Moreno-Ramírez

Metástasis digital acral: presentación de 2casos clínicos

Publication date: Available online 1 May 2018
Source:Actas Dermo-Sifiliográficas
Author(s): A.J. Baños-Arévalo, N. López-Navarro, E. Gallego-Domínguez, E. Herrera
Las metástasis cutáneas aparecen en el 0,6-10,4% de los pacientes con tumores malignos y representan hasta el 2% de los tumores cutáneos. En algunos casos representan la primera manifestación de una neoplasia no conocida. Además pueden poner de manifiesto la progresión metastásica del tumor primario. Las metástasis de localización acral son particularmente raras. En la mayoría de los casos aparecen secundariamente a afectación ósea. Aunque la clínica es variable, generalmente se confunden con un proceso infeccioso o inflamatorio, retrasándose el diagnóstico. Cuando se localizan en los dedos de la mano la causa más frecuente es el carcinoma de pulmón, mientras que las localizadas en los dedos de los pies suelen deberse a tumores del tracto genitourinario. El estudio dermatopatológico en estos casos es fundamental para establecer el diagnóstico y orientar hacia el origen del tumor primario.Presentamos 2casos clínicos de metástasis digital acral. El primero de ellos representa el primer caso de la literatura de metástasis acral de mioepitelioma maligno (carcinoma mioepitelial) de mama y el otro una metástasis acral como manifestación inicial de carcinoma de pulmón.Cutaneous metastases appear in 0.6% to 10.4% of malignant tumors and account for 2% of all cutaneous tumors. Metastasis to the skin may arise from progression of a known primary tumor or provide the first sign of an unsuspected one. Acral metastases are particularly unusual. Most derive from bone tumors. Clinical signs vary and the lesions generally resemble infection or inflammation, leading to diagnostic delays. When metástasis involves the fingers, the primary tumor is usually lung carcinoma. In contrast, toe involvement usually derives from a tumor in the genitourinary tract. A pathologic diagnosis in these cases is necessary and will suggest the location of the primary tumor.We report 2 cases of metástasis to the fingers. One is the first report of acral metástasis of a myoepithelial carcinoma of the breast. The other concerns acral metástasis as the first sign of lung carcinoma.

Graphical abstract

Antineoplastic influence of nimesulide in chemically induced hepatocellular carcinoma by inhibition of DNA synthesis

Abstract

Hepatocellular carcinoma is emerging as one of the most common forms of cancer resulting in thousands of death worldwide. The purpose of this study was to screen nimesulide for anticancer activity in chemically induced hepatocellular carcinoma in Wistar rats as well as in BEL 7402 and HEP G2 cell lines. HCC in rats was induced by administering a single dose of diethyl nitrosamine (150 mg/kg) intraperitoneally. Duration of the in vivo study was 12 weeks and the anticancer potential was further confirmed by in vitro cell line study. Administration of DENA in Wistar rats significantly elevated the levels of serum biochemical parameters and α-feto protein. Treatment with different dose of nimesulide significantly decreased the markedly raised serum levels of biochemical parameters as well as maintained the histology of the liver tissues nearly similar to the normal. Further study of hepatocytes enzymes showed that treatment with nimesulide also improved the antioxidant enzyme levels. Our study also examined the cytotoxicity and DNA synthesis inhibition by nimesulide in BEL 7402 and Hep G2 cell lines. Cell viability was assessed by [³H]-thymidine uptake procedure. The results obtained by in vitro cell line study, histopathological and biochemical data concluded that nimesulide, a preferential COX-2 inhibitor, has anticancer activity, which is by first reducing the formation of reactive oxygen species and second by inhibiting the PGE₂ effect via Wnt signaling pathway (cell invasion, angiogenesis, and cell proliferation).

Editorial board

The Editor's Choice

Mitochondrial damage and cytoskeleton reorganization in human dermal fibroblasts exposed to artificial visible light similar to screen-emitted light

Human skin is the tissue most responsive to sunlight, which may impair its integrity and regeneration. Although the visible spectrum (400–700 nm) constitutes roughly 44% of sunlight [1], it was considered to have minimal impact on the skin because of its low energy. In recent decades, the visible part of the sunlight spectrum therefore received a little attention concerning its possible contribution to skin damage. However, observations of immediate skin pigmentation following exposure to visible light [2] sparked increased interest.

Distinct kinetics of two pathologies induced in mice by topical treatment with imiquimod cream: psoriasis-like inflammation and systemic autoimmunity

Perturbations of the immune system by a variety of microorganisms or endogenous molecules such as self-nucleic acids or antimicrobial peptides result in the activation of innate immunity through pattern recognition receptors (PRPs) and subsequent adaptive immunity to maintain the homeostasis of the body. However, abnormal responses of PRPs, including Toll-like receptors, can lead to the development of inflammatory diseases. It has been demonstrated that the TLR7 signaling pathway is involved in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE) in humans as well as in mouse models [1–3].

The Pedicled Anterolateral Thigh Phalloplasty

The anterolateral thigh (ALT) flap is a viable and reliable option for phalloplasty. The primary advantages of the ALT flap remain an inconspicuous donor site and flexibility in phallus length. The disadvantages of the ALT flap are a higher incidence of both flap and urethral complications compared with a radial forearm phalloplasty. Although the ALT phalloplasty can achieve the primary goals of standing micturition, penetrative intercourse, and an aesthetic phallus, multiple stages and revisions are often necessary. Careful patient selection is paramount in attaining acceptable results with the ALT phalloplasty technique.

Introduction to Phalloplasty

Phalloplasty represents the most complete genitoperineal transformation. Because it requires complex, staged procedures as well as the use of tissue from remote sites, patients must be well informed as to the nature of surgery. Surgical techniques for phalloplasty continue to evolve. Although many surgeons prefer the radial forearm free flap technique, a visible flap donor site makes this procedure less desirable for some patients. Other surgical options are available and include the anterolateral thigh flap, sometimes in conjunction with secondary flaps, and the musculocutaneous latissimus dorsi flap.

Penile Prostheses

Phalloplasty represents the most complete genitoperineal transformation for trans men. Although voiding while standing is a priority for most trans men, most patients want to use the neophallus for sexual experience after they are accustomed to their new voiding abilities. Different techniques have been used to obtain rigidity in the neophallus, often resulting in complications and failure. Implantation of an erectile prosthesis remains the best option for achieving sexual intercourse in trans men. This article discusses the current state of art of penile prostheses in trans men, including a description of the prostheses, techniques for implantation, and complications.

Radial Forearm

The radial forearm free flap phalloplasty provides a thin, potentially sensate, minimally hair-bearing cutaneous flap. Since its initial description, several modifications of the technique have emerged. The earliest dimensions described needed to be increased because of the increase amount of subcutaneous fat in the Western population. Incorporating a centrally placed neo-urethra with a distal extension that gets folded over to create a semblance of a neoglans eliminates the distal/meatal stenosis. Performing a urethral extension at a preliminary surgery and extending the neourethra proximally has improved the position of the neophallus and minimized proximal urethral strictures and fistulas in transgender men.

Male-to-Female Gender Reassignment Surgery

The major steps in vaginoplasty are orchiectomy, penile amputation, creation of the neovaginal cavity with lining, and reconstruction of urethral meatus, labia, and clitoris. During pedicled intestinal transfer, an intestinal segment is transferred in a dissected cavity between the bladder and rectum. The bowel harvest is performed by a total laparoscopic technique. It is imperative to create the labia majora and minora, the clitoris, and a clitoral hood to achieve the physiologic and aesthetic equivalent of female external genitalia. Intestinal vaginoplasty seems to be associated with a low rate of adverse events. Life-long vaginal hygiene and dilatation is recommended.

Hormone Therapy for Transgender Men

This article provides an account of the current understanding of hormone therapy options for transgender men and emphasizes the importance of continued physician-supervised monitoring for long-term care.

Primary Care for the Transgender and Gender Nonconforming Patient

All physicians are likely to encounter gender diverse patients, and some of these patients require medically necessary surgical procedures. It is optimal for surgeons to collaborate with other providers who interact with this patient population. Primary care physicians initiate treatment with consultation from mental health professionals and refer to surgeons when necessary. Best practices consist of preventative care, hormone therapy induction when indicated, monitoring of all health parameters, and continuing care medically and postoperatively.

Mental Health Evaluation for Gender Confirmation Surgery

The requests for medically necessary surgical interventions for transgender individuals have steadily increased over the past several years. So too has the recognition of the diverse nature of this population. The surgeon relies heavily on the mental health provider to assess the readiness and eligibility of the patient to undergo surgery, which the mental health provider documents in a referral letter to the surgeon. The mental health provider explores the individual's preparedness for surgery, expectations, and surgical goals and communicates with the surgeon and other providers to promote positive outcomes and inform multidisciplinary care.

Metoidioplasty

Transmasculine gender confirmation surgery remains challenging and demanding. As there is no perfect or standard procedure for creating male genitalia, practitioners continue to strive for better solutions. There are 2 goals in the surgical treatment of transgender persons: removal of the native genitalia and secondary sexual characteristics and creation of the desired genitalia and secondary sexual characteristics. In transmen, this often means removal of the uterus, fallopian tubes, ovaries, and vagina and creation of the external genitalia. This article highlights metoidioplasty. Metoidioplasty with simultaneous removal of the internal genitalia may be performed in a single procedure.

Dermoscopy of the Hair and Nails, Second Edition, Antonella Tosti. CRC Press, Taylor & Francis Group, Boca Raton, FL (2016)

Publication date: March–April 2018
Source:Clinics in Dermatology, Volume 36, Issue 2
Author(s): Mark Juhl

Clinical Significance of Autoantibodies in Dermatomyositis and Systemic Sclerosis

Publication date: Available online 12 April 2018
Source:Clinics in Dermatology
Author(s): Danielle M. Tartar, Lorinda Chung, David F. Fiorentino
Autoimmune connective tissue diseases (AI-CTD), including dermatomyositis and systemic sclerosis, have a heterogeneous clinical presentation and prognosis; moreover, their clinical features are often incomplete and overlap with other rheumatic disorders, which can make diagnosis and prognostic stratification challenging. Specific autoantibodies have been associated with certain clinical findings as well as prognostic implications, and many new associations have been made over the last decade. While patient populations manifest considerable heterogeneity, autoantibodies can be used to help predict clinical features, prognosis, and response to therapy. In this review, the clinical and prognostic implications associated with disease-specific autoantibodies in dermatomyositis and scleroderma are summarized with an emphasis on how the clinician can use this information for patient care.

Systemic sclerosis - current concepts of skin and systemic manifestations

Publication date: Available online 12 April 2018
Source:Clinics in Dermatology
Author(s): David R. Pearson, Victoria P. Werth, Lisa Pappas-Taffer
Systemic sclerosis is an uncommon autoimmune connective tissue disease with multi-organ system involvement and significant associated morbidity and mortality. Cutaneous signs and symptoms are of particular importance as they may be recognized before systemic manifestations, allowing earlier risk stratification into the limited and diffuse cutaneous subtypes, as well as earlier initiation of treatment. Important cutaneous manifestations include Raynaud's phenomenon, digital ulcers, cutaneous sclerosis, calcinosis cutis, telangiectasias, pruritus, and dyspigmentation. Despite investigation of a wide variety of treatments, no FDA-approved pharmacologic therapies exist for systemic sclerosis, and data from high quality studies are limited. In the following review, we will discuss skin-directed therapies. While there is evidence to support specific treatments for Raynaud's phenomenon, digital ulcers, and cutaneous sclerosis, there are limited rigorous studies evaluating the treatment of other cutaneous signs and symptoms. Additional randomized-controlled trials and large observational studies are necessary to develop future evidence-based treatment options.

Editorial Board

Publication date: March–April 2018
Source:Clinics in Dermatology, Volume 36, Issue 2

Cutaneous Vasculitis in Rheumatologic Disease: - current concepts of skin and systemic manifestations

Publication date: Available online 10 April 2018
Source:Clinics in Dermatology
Author(s): Robert G. Micheletti
Cutaneous vasculitis may be limited to the skin, a manifestation of systemic vasculitis, or a sign of an important underlying disease state. A thorough and systematic approach is required for accurate diagnosis and evaluation of such patients in order to enable appropriate management of the vasculitis and any associated condition. Occasionally, cutaneous vasculitis is a manifestation or presenting sign of connective tissue disease, such as systemic lupus erythematosus, Sjögren syndrome, or another condition. Such patients are at risk for poor outcomes related to systemic manifestations of vasculitis, as well as increased severity of the underlying disease. Recognition of this important subset of patients with skin vasculitis enables appropriate work-up and successful management.

Raynaud's Phenomenon: current concepts of skin and systemic manifestations

Publication date: Available online 10 April 2018
Source:Clinics in Dermatology
Author(s): Thomas Stringer, Alisa N. Femia
Raynaud's phenomenon (RP) is a transient, acral, vasospastic phenomenon that manifests with characteristic color changes. This vasospasm, classically triggered by cold temperatures, may also be driven by shifts in temperature, climate, or emotional state. Primary RP (PRP) is a common condition without severe sequelae. Secondary RP (SRP), which may be driven by vascular, autoimmune, hematologic, or endocrine etiologies, can result in digital ulceration, irreversible ischemia and necrosis, and secondary infection. This review delineates the clinical manifestations of both primary and secondary RP as well as current understanding of RP epidemiology and pathogenesis. Proper examination, including nailfold capillary microscopy, and laboratory workup for secondary causes of RP are also discussed. The traditional armamentarium of therapies used for RP as well as newer medical and surgical options are also summarized with particular regard to the clinical evidence for their efficacy.

Eosinophilic Fasciitis: Current concepts of skin and systemic manifestations

Publication date: Available online 10 April 2018
Source:Clinics in Dermatology
Author(s): Nicole Fett, Megan Arthur
Eosinophilic fasciitis (EF) is an uncommon connective tissue disease characterized by abrupt onset of edema, followed by progressive induration of primarily the distal extremities. Patients may exhibit inflammatory arthritis, joint contractures, decreased mobility, and nerve entrapment. Almost half of patients with EF may have coexisting morphea plaques. Classic laboratory studies display peripheral eosinophilia, hypergammaglobulinemia, and elevated inflammatory markers. EF is included in the spectrum of scleroderma-like disorders and may be difficult to distinguish from other sclerosing skin disorders. Full thickness biopsy containing muscle and fascia is considered the gold standard for diagnosis and reveals sclerosis of the mid-deep dermis, subcutaneous fat, and thickening of the fascia. MRI has been increasingly utilized to augment diagnostic capabilities. Ultimately, the diagnosis of EF relies upon the combination of characteristic clinical, laboratory, imaging, and histologic findings. While some patients experience spontaneous remission, systemic corticosteroids (SCS) are the mainstay of treatment. Patients who fail to improve with SCS alone require the addition of a second immunosuppressive drug. Additionally, although data are limited, there is evidence to suggest that initial combination therapy with SCS, and methotrexate may be most beneficial.

Dermatomyositis – Current Concepts of Skin and Systemic Manifestations

Publication date: Available online 12 April 2018
Source:Clinics in Dermatology
Author(s): Ivan Bogdanov, Jana Kazandjieva, Razvigor Darlenski, Nikolai Tsankov
Dermatomyositis (DM) is a multifactorial chronic autoimmune disorder with characteristic skin changes and involvement of different organ systems including the muscles, blood vessels, joints, esophagus, and lungs. In terms of epidemiology, DM affects both children and adults—it is most often observed beyond the age of 40, but there is also a peak of incidence between 5 and 12 years of age. The current paradigm describing the pathophysiology of DM is an autoimmune attack on affected organs that is triggered by environmental factors such as UV exposure, drugs, infection, and lifestyle decisions in genetically susceptible individuals. Importantly, DM is also regarded as a paraneoplastic phenomenon, as cancer may precede, occur concurrently with, or follow the development of the clinical signs of DM. The cutaneous manifestations of DM can be categorized as pathognomonic, characteristic, compatible, less common, rare, recent, and non-specific. The treatment of DM is a difficult task due to its rarity, its multiple phenotypes, and the fact that the disease may affect multiple organs and is commonly treatment-refractory. The lack of randomized, controlled intervention trials and, until recently, the insufficiency of validated, clinically meaningful outcome instruments in part contribute to the lack of approved treatments.

Morphea: current concepts of skin and systemic manifestations

Publication date: Available online 10 April 2018
Source:Clinics in Dermatology
Author(s): Stephanie Florez-Pollack, Elaine Kunzler, Heidi T. Jacobe
Morphea is an inflammatory, sclerosing skin disorder that can involve the underlying soft tissues. Although the cause of morphea remains poorly investigated, genetic predisposition, immune dysregulation, and environmental factors have been implicated. Morphea is associated with cosmetic and functional sequelae, while internal organ involvement is rare. Early diagnosis and treatment are imperative to minimize damage such as limitation of range of motion. This review summarizes advances in diagnosis and treatment of morphea, allowing clinicians to better serve patients with this condition.

Cutaneous lupus erythematosus - reflecting on practice changing observations over the past 50years

Publication date: Available online 10 April 2018
Source:Clinics in Dermatology
Author(s): Jeffrey P. Callen
I discuss some of the historical observations that have led to our current understanding of the diagnosis, evaluation, and management of patients with cutaneous lupus erythematosus. In addition, I examine the relationship of skin lesions to systemic disease and highlight what I consider to be seminal advances in our knowledge including the development of a classification system for cutaneous lupus, the use of a validated scoring system to assess patients' disease activity and damage, expansion of our knowledge of the action spectrum of this disease, observations about drugs as causes of subacute cutaneous lupus erythematosus, the risk of progression from 'pure' cutaneous disease to systemic disease, and some new observations about traditional therapies as well as some of the newer therapies that might be used.

Less common rheumatologic disorders: - current concepts of skin and systemic manifestations

Publication date: Available online 10 April 2018
Source:Clinics in Dermatology
Author(s): Taraneh Paravar
The cutaneous manifestations of the common rheumatologic disorders, such as systemic lupus erythematosus, dermatomyositis, and systemic sclerosis, are well known. In contrast, the dermatologic findings of less common rheumatologic disorders, including Sjögren syndrome, mixed connective tissue disease, and relapsing polychondritis, are less widely known. The cutaneous manifestations of these connective tissue disorders are reviewed.

Dual protective effect of ginger and rosemary extracts against CCl 4 -induced hepatotoxicity in rats

Abstract

The present study aimed to investigate the protective effect of aqueous extracts of ginger (GE) and rosemary (RE), both individually and in combination, on carbon tetrachloride (CCl₄)-induced liver injury in adult male rats. CCl₄ induced significant increase in liver enzymes, bilirubin, triglycerides, and total cholesterol while total protein, albumin, and globulin were significantly decreased. Also, the activity of cytochrome P₄₅₀ (CYP) and oxidative stress markers were found to be elevated with a concomitant decrease in the activity of antioxidant enzymes in hepatic tissue. Supplementation with extracts of ginger or rosemary effectively relieved most of the CCl₄-induced alterations when administered singly. The joint therapy of the two extracts was more effective. The histological investigation strongly confirmed the highly protective effect of the two plant extracts in the hepatocytes. These findings suggest that rosemary and ginger extracts are effective in improving both the function and structure of the hepatocytes through their potent antioxidant effect and point out to the possibility of using a combination of both as an adjunct therapy in liver diseases.

Bioaccumulation of As, Hg, and Se in tunas Thunnus albacares and Katsuwonus pelamis from the Eastern Pacific: tissue distribution and As speciation

Abstract

With the aim of knowing the distribution of As, Hg, and Se in skipjack (Katsuwonus pelamis, Linnaeus, 1758) and yellowfin tuna (Thunnus albacares, Bonnaterre, 1788) from the Eastern Pacific, elemental concentrations were determined in the muscle and liver; As species were also analyzed in the stomach content. Additionally, health risk for consumers was assessed. For both tunas, levels of As and Se were significantly higher (p < 0.05) in the liver than in the muscle. In K. pelamis, Hg concentrations in the muscle were significantly higher (p < 0.05) than those in the liver. In T. albacares, As, Hg, and Se showed a trend to increase with fish dimensions. Arsenic extractability was better in the muscle than in the liver of both species; in K. pelamis, As species were better extracted than in T. albacares. In both tuna species, the most extractable arsenic was arsenobetaine (AsB) and a minor part was dimethylarsinic acid (DMA). The liver contained mainly AsB with some DMA and arsenocholine (AsC). Hazard indexes (HI) indicated no risk from Hg and Se intake through these tuna species. Considering the individual contribution to the HI, Hg contributed more (80 to 86%) than Se. In the context of health risk, none of the As and Hg values were above the permissible limits; however, two samples of T. albacares (9%) and three samples of K. pelamis (12%) had Se concentrations over the limits. If Hg and Se in the edible portion of tuna are considered under the approach of the HBV_Se, tuna consumption is beneficial.

Application of feature selection and regression models for chlorophyll-a prediction in a shallow lake

Abstract

As a representative index of the algal bloom, the concentration of chlorophyll-a (Chl-a) is a key parameter of concern for environmental managers. The relationships between environmental variables and Chl-a are complex and difficult to establish. Two machine learning methods, including support vector machine for regression (SVR) and random forest (RF), were used in this study to predict Chl-a concentration based on multiple variables. To improve the model accuracy and reduce the input number, two feature selection methods, including minimum redundancy and maximum relevance method (mRMR) and RF, were integrated with regression models. The results showed that the RF model had a higher predictive ability than the SVR model. Furthermore, the less computational time cost and unnecessary prior data transformation also indicated a better applicability of the RF model. The comparison between ensemble models of mRMR-RF and RF-RF showed that the RF-RF yielded a better performance with fewer variables. Seven variables selected from the candidate predictors could interpret most information, and their potential implications to Chl-a were discussed based on the level of importance. Overall, the RF-RF ensemble model can be considered as a useful approach to determine the significant stressors and achieve satisfactory prediction of Chl-a concentration.

Le lambeau fasciocutané fibulaire en ilôt

Publication date: Available online 4 May 2018
Source:Annales de Chirurgie Plastique Esthétique
Author(s): A.-C. Masquelet, J. Gaillard, A. Cambon-Binder, R. Mauprivez
L'artère fibulaire émet le long de son parcours de nombreuses perforantes cutanées qui irriguent la face postéro-latérale de jambe. Ces perforantes sont reliées entre elle par des arcs anastomotiques qui constituent un véritable réseau supra-fascial. Nous présentons une courte série clinique de cinq cas de lambeau fascio cutané fibulaire en ilôt dont la palette cutanée et le pédicule adipo-fascial ont été prélevés en regard de l'axe fibulaire. Quatre lambeaux à point de pivot distal ont été réalisés pour des pertes de substance du tiers inférieur de jambe (3 cas) et de la face latérale du talon (1 cas). Un lambeau à point de pivot proximal a permis de réparer une perte de substance de la région du genou. Tous les lambeaux ont cicatrisé en totalité sans congestion veineuse. Le lambeau fascio cutané fibulaire offre de nombreux avantages : position opératoire de prélèvement qui permet un accès aisé à la face antéro-médiale de jambe, préservation du nerf sural et de la veine petite saphène, point de pivot du pédicule qui peut être choisi sur la projection du trajet de l'artère fibulaire. Sous réserve de placer au tiers moyen de jambe le point de pivot distal du pédicule adipo-fascial, il est possible d'associer un lambeau sural distal. En pratique, le lambeau fibulaire en ilôt nous paraît particulièrement indiqué pour les pertes de substance du tiers distal de jambe.The perforators of the fibular artery provide a well vascularised supra fascial network which allows to raise a proximally or a distally based island fascio cutaneous flap with an adipo-fascial pedicle. We present a short series of five cases of this flap for coverage of soft tissue defects involving the region of the knee, the distal third of the leg and the lateral aspect of the heel. All flaps healed entirely without venous congestion. The advantages of the fascio cutaneous fibular island flap are the supine operative position, the preservation of the sural nerve and the lesser saphenous vein and a pivot point which can be located at the middle third of the leg. According to our experience, the fascio cutaneous fibular island flap is especially indicated for repairing defects of the distal leg.

A novel strategy for water disinfection with a AgNPs/gelatin sponge filter

Abstract

Disinfection of bacteria in water with sustainable and energy-efficient methods is still a great challenge. Herein, a novel gelatin sponge with embedded AgNPs is fabricated via freeze-drying using gelatin as the reducing agent to synthesize AgNPs in situ. UV-vis spectroscopy, HRTEM, XRD, and XPS characterization prove the formation of AgNPs with an average size of 8.55 ± 0.35 nm. TEM and SEM images confirm the even distribution of AgNPs throughout the AgNPs/gelatin sponges. The composite sponge has a low bulk density of 20 ± 3.5 mg/cm³ and a pore size of 6.2 ± 1.5 μm. The AgNPs/gelatin sponges exhibit excellent antibacterial performance to E. coli in water, probably by destroying their cell membranes. The porous AgNPs/gelatin composite sponges are promising filter materials for water disinfection. The removal rate of AgNPs/gelatin composite sponges on E. coli reached almost 100%.

Graphical abstract

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Impact of Mono‐Fluorination on the Photophysics of the Flavin Chromophore

Photochemistry and Photobiology, EarlyView.

Gene therapy knockdown of VEGFR2 in retinal endothelial cells to treat retinopathy

Abstract

Inhibition of vascular endothelial growth factor (VEGF) in retinopathy of prematurity (ROP) raises concerns for premature infants because VEGF is essential for retinovascular development as well as neuronal and glial health. This study tested the hypothesis that endothelial cell-specific knockdown of VEGF receptor 2 (VEGFR2), or downstream STAT3, would inhibit VEGF-induced retinopathy without delaying physiologic retinal vascular development. We developed an endothelial cell-specific lentiviral vector that delivered shRNAs to VEGFR2 or STAT3 and a green fluorescent protein reporter under control of the VE-cadherin promoter. The specificity and efficacy of the lentiviral vector-driven shRNAs were validated in vitro and in vivo. In the rat oxygen-induced retinopathy model highly representative of human ROP, the effects of endothelial cell knockdown of VEGFR2 or STAT3 were determined on intravitreal neovascularization (IVNV), physiologic retinal vascular development [assessed as area of peripheral avascular/total retina (AVA)], retinal structure, and retinal function. Targeted knockdown of VEGFR2 or STAT3 specifically in retinal endothelial cells by subretinal injection of lentiviral vectors into postnatal day 8 rat pup eyes efficiently inhibited IVNV, and knockdown of VEGFR2 also reduced AVA and increased retinal thickness without altering retinal function. Taken together, our results support specific knockdown of VEGFR2 in retinal endothelial cells as a novel therapeutic method to treat retinopathy.

Current trends in needle-free jet injection: an update

Response to: Can patch test sensitization with gold sodium thiosulfate be ruled out?—A case report

Contact Dermatitis, EarlyView.

Eyelid allergic contact dermatitis after intravitreal injections of anti‐vascular endothelial growth factor: What is the culprit? A report of 3 cases

Contact Dermatitis, EarlyView.

Allergic contact dermatitis and diabetes medical devices: 2 clinical cases

Contact Dermatitis, EarlyView.

Allergic contact dermatitis caused by Irganox 1076 used as antioxidant in non‐woven fabric

Contact Dermatitis, EarlyView.

A case of allergic contact dermatitis caused by goalkeeper gloves

Contact Dermatitis, EarlyView.

Ramadan Exposure In utero and Child Mortality in Burkina Faso: Analysis of a Population-Based Cohort Including 41,025 Children

Abstract

Ramadan exposure in utero can be regarded as a natural experiment to study how nutritional conditions in utero influence susceptibility to disease later in life. We analyzed data from rural Burkina Faso on 41,025 children born between 1993 and 2012, of which 25,093 to Muslim mothers. Ramadan exposure was assigned based on overlap between Ramadan dates and gestation, creating seven exclusive categories. We used proportional hazards regression with difference-in-differences to estimate the association between Ramadan exposure at different gestational ages and under-five mortality. Under-five mortality was 32 deaths per 1,000 child-years. Under-five mortality among Muslims was 15% higher than among non-Muslims (P < 0.001). In the difference-in-differences analysis, Ramadan occurrence during conception, first, or second trimester was associated with higher under-five mortality rates, only among Muslims. The mortality rates of children born to Muslim mothers were 33%, 29% and 22% higher when Ramadan occurred during conception, first and second trimester, respectively, than among children of non-Muslim mothers born at the same time (P = 0.01, P < 0.001 and P = 0.007). Having a Muslim mother was not associated with mortality when not exposed to Ramadan, born during Ramadan or exposed during the third trimester. Observance of Ramadan during early pregnancy can have detrimental consequences for the future health of the unborn child.

Ramadan, Pregnancy, Nutrition, and Epidemiology

Abstract

Ramadan is observed by 1.6 billion Muslims. In a paper published this month that uses data from the Nouna Health and Demographic Surveillance System site in Burkina Faso, it is found that experiencing Ramadan in early pregnancy is associated with an increased risk of child mortality. Ramadan exposes observant individuals to a specific pattern of nutrition and other behaviors, including changes in sleep patterns. How these behaviors might result in child mortality is not yet understood, and the findings reported in the paper should be replicated in other settings.

A Matter of Survival: The Detrimental Consequences of Adverse Early Life Conditions

Abstract

Studies across different species have shown that moderate dietary restriction is associated with longer lifespan. Surprisingly however, when diet is restricted in prenatal life, the effect is completely the opposite. Animal work and human epidemiologic data have shown that undernutrition in utero negatively affects health in later life and reduces lifespan considerably. In this issue of the American Journal of Epidemiology, Schoeps et al. provide new evidence that variations in nutritional conditions during pregnancy relate to the future health of the unborn child (1). In a detailed analysis of data from Muslim and non-Muslim pregnant women in Burkina Faso, they showed that the occurrence of Ramadan in early life was strongly associated with under-five mortality rates. Mortality rates were highest when Ramadan had occurred in the pre-conception period or during the first trimester. That nutritional conditions in early life can have such profound consequences for child mortality is both astonishing and extremely relevant from a public health perspective.

Authors’ Response to Commentaries

Prospective Feasibility and Safety Assessment of Surgical Biopsy for Patients with Newly Diagnosed Diffuse Intrinsic Pontine Glioma

Abstract

Background

Diagnosis of diffuse intrinsic pontine gliomas (DIPG) has relied on imaging studies since the appearance is pathognomonic, and surgical risk was felt to be high and unlikely to affect therapy. The DIPG Biology and Treatment Study (DIPG-BATS) reported here incorporated a surgical biopsy at presentation and stratified subjects to receive FDA-approved agents chosen on the basis of specific biologic targets.

Methods

Subjects were eligible for the trial if the clinical features and imaging appearance of a newly diagnosed tumor were consistent with a DIPG. Surgical biopsies were performed after enrollment and prior to definitive treatment. All subjects were treated with conventional external beam radiotherapy with bevacizumab, and then stratified to receive bevacizumab with erlotinib or temozolomide, both agents, or neither agent, based on MGMT and EGFR status. Whole-genome sequencing and RNA-sequencing were performed but not used for treatment assignment.

Results

Fifty-three patients were enrolled at 23 institutions, and 50 underwent biopsy. The median age was 6.4 years, with 24 male and 29 female subjects. Surgical biopsies were performed a specified technique and no deaths were attributed to the procedure. Two subjects experienced grade 3 toxicities during the procedure (apnea (n=1) and hypertension (n=1)). One subject experienced a neurologic deficit (left hemiparesis) that did not fully recover. Of the 50 tumors biopsied, 46 provided sufficient tissue to perform the study assays (92%, two-stage exact binomial 90% confidence interval 83-97%).

Conclusions

Surgical biopsy of DIPGs is technically feasible, associated with acceptable risks and can provide biologic data that informs treatment decisions.

Assessing the predictability of IDH mutation and MGMT methylation status in glioma patients using relaxation-compensated multi-pool CEST MRI at 7.0 Tesla

Abstract

Background

Early identification of prognostic superior characteristics in glioma patients such as Isocitrate dehydrogenase(IDH)-mutation and O6-methylguanine-DNA-methyltransferase (MGMT) promotor methylation status is of great clinical importance. The study purpose was to investigate the non-invasive predictability of IDH-mutation status, MGMT promotor methylation, and differentiation of lower versus higher grade glioma (LGG vs. HGG) in newly-diagnosed patients employing relaxation-compensated multi-pool Chemical Exchange Saturation Transfer (CEST) magnetic resonance imaging (MRI) at 7.0 Tesla (7T).

Methods

Thirty-one newly-diagnosed glioma patients were included in this prospective study. CEST MRI was performed at a 7T whole-body scanner. Nuclear Overhauser Effect (NOE) and isolated amide proton transfer (APT, downfield NOE-suppressed APT=dns-APT) CEST signals (mean value and 90^th signal percentile) were quantitatively investigated in the whole tumor area with regard to predictability of IDH-mutation, MGMT promotor methylation status, and differentiation of LGG vs. HGG. Statistics were performed using receiver operating characteristic (ROC) and area under the curve (AUC) analysis. Results were compared to advanced MRI methods (apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) ROC/AUC analysis) obtained at 3T.

Results

dns-APT CEST contrasts yielded highest AUCs in IDH-mutation status prediction (dns-APT_mean=91.84%, p<0.01; dns-APT₉₀=97.96%, p<0.001). Furthermore, dns-APT metrics enabled significant differentiation of LGG vs. HGG (AUC: dns-APT_mean=0.78, p<0.05; dns-APT₉₀=0.83, p<0.05). There was no significant difference regarding MGMT promotor methylation status at any contrast (p>0.05).

Conclusions

Relaxation-compensated multi-pool CEST MRI, particularly dns-APT imaging, enabled prediction of IDH-mutation status and differentiation of LGG vs. HGG and should therefore be considered as non-invasive MR biomarker in the diagnostic workup.

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