Non-invasive evaluation of Secukinumab efficacy in severe plaque psoriasis with confocal microscopy and optical coherence tomography: A case report

Feature analysis of ultrasound elastography image for quantitative assessment of cutaneous carcinoma

Abstract

Background

To evaluate the feasibility of using quantitative texture features computed from high frequency ultrasound and ultrasound elastography (USE) images in the discrimination of benign from malignant skin lesions.

Methods

A commercial ultrasound system with a 14 MHz transducer was used to visualize skin lesions requiring biopsy on clinical evaluation. Patients were enrolled over a 6-month period and imaged prospectively by operators blind to the histopathologic diagnosis. Anatomic ultrasound and USE imaging of the skin lesions was performed using a 2-4 mm gel standoff pad before biopsy and histopathologic evaluation. The ElastoAnalysis software developed for the texture analysis of USE images was provided by Hitachi. The software computes thirteen texture features within a region of interest (ROI), which have demonstrated promise in diagnostic characterization of liver fibrosis staging and in quantitative elastography of breast cancer. This approach has not yet been studied in the quantitative assessment of skin cancer. Results were retrospectively compared to the histopathologic diagnosis and a diagnostic criteria with the goal of maximizing sensitivity was evaluated for each textural feature.

Results

Of the 37 lesions included, among 30 patients who participated, 12 lesions were malignant and 25 were benign. Eleven out of thirteen textural metrics computed by the software were useful in differentiating benign from malignant lesions with 100% sensitivity and specificities ranging from 28% to 85%.

Conclusions

This feasibility study demonstrated that feature analysis of USE may be useful in quantitatively differentiating cancerous from benign primary solitary skin lesions prior to biopsy.

Sensitive skin in Korean population: An epidemiological approach

Abstract

Background/Purpose

Sensitive skin is characterized by uncomfortable sensations in response to multiple factors that do not normally have irritant properties. We used an epidemiological approach to evaluate the prevalence and characteristics of sensitive skin in a Korean population, and compared the results with those of populations from other countries.

Methods

A representative nationwide sample of 1000 Koreans aged ≥15 years was selected. The methodology used in this study (questionnaires) was the same as that used in similar studies conducted in other countries.

Results

Sensitive skin was present in 56.8% of the Koreans. The prevalence of sensitive skin was highest among countries such as the USA (44.6%), Europe (38.4%), Russia (39.7%), Brazil (34.2%), and Japan (54.5%). Participants with sensitive skin were more likely to accompany skin disorders than those with non-sensitive skin (72.3% vs 38.0%; P < .001). Sensitive skin group were 2-3 times more reactive to climatic and environmental factors, cosmetics, and food items than non-sensitive skin group.

Conclusion

The prevalence of sensitive skin in Korea is the highest among countries in which such investigation has been conducted. The sensitive skin group appears more likely to experience dermatological reactions to unexpected factors than the non-sensitive skin group.

Haptic augmented skin surface generation toward telepalpation from a mobile skin image

Abstract

Background/purpose

Very little is known about the methods of integrating palpation techniques to existing mobile teleskin imaging that delivers low quality tactile information (roughness) for telepalpation. However, no study has been reported yet regarding telehaptic palpation using mobile phone images for teledermatology or teleconsultations of skincare.

Methods

This study is therefore aimed at introducing a new algorithm accurately reconstructing a haptic augmented skin surface for telehaptic palpation using a low-cost clip-on microscope simply attached to a mobile phone. Multiple algorithms such as gradient-based image enhancement, roughness-adaptive tactile mask generation, roughness-enhanced 3D tactile map building, and visual and haptic rendering with a three-degrees-of-freedom (DOF) haptic device were developed and integrated as one system.

Results

Evaluation experiments have been conducted to test the performance of 3D roughness reconstruction with/without the tactile mask. The results confirm that reconstructed haptic roughness with the tactile mask is superior to the reconstructed haptic roughness without the tactile mask. Additional experiments demonstrate that the proposed algorithm is robust against varying lighting conditions and blurring. In last, a user study has been designed to see the effect of the haptic modality to the existing visual only interface and the results attest that the haptic skin palpation can significantly improve the skin exam performance.

Conclusion

Mobile image-based telehaptic palpation technology was proposed, and an initial version was developed. The developed technology was tested with several skin images and the experimental results showed the superiority of the proposed scheme in terms of the performance of haptic augmentation of real skin images.

Benefit of early initiation of neuraminidase inhibitor treatment to hospitalized patients with avian influenza A (H7N9) virus

Abstract

Background

The significance of early neuraminidase inhibitor (NAI) therapy for treating influenza A(H7N9) is currently unknown.

Methods

The duration of viral shedding was monitored by RT-PCR after patients with confirmed H7N9 infection were admitted to the First Affiliated Hospital, Zhejiang University during April 2013 to April 2017. Indices such as the length of hospitalization and mortality were collected, and the correlation between the time of administration of NAI and the severity of disease was systematically analyzed.

Results

160 patients with confirmed H7N9 infection were divided into three groups according to NAI starting time. 3 (15%) out of 20 patients for whom NAI was administered within 2 days died compared with 12 (23.1%) out of 52 patients who received treatment within 2–5 days and 33 (37.5%) out of 88 patients who were treated after 5 days (P<0.05). The median durations of viral shedding from NAI therapy initiation was 4.5 days (interquartile range (IQR): 3–9) for patients who took antiviral medication within 2 days, which was significantly different from that for patients who took medication within 2–5 days (7.5 days,IQR: 4.25–12.75) or after 5 days (7days, IQR: 5–10) (P<0.05). We found that the duration of viral shedding from NAI therapy was the shortest of 5.5 days in spring 2013 and the longest of 8.5 days in winter-spring 2016–17 (P<0.05), showing a prolonged trend.

Conclusions

Early NAI therapy within 2 days of illness shorten the duration of viral shedding and improve survival in patients with H7N9 viral infections.

Retreatment with sofosbuvir plus grazoprevir/elbasvir plus ribavirin of patients with hepatitis C virus genotype 1 or 4 who previously failed a NS5A or NS3-containing regimen. ANRS HC34 REVENGE

Abstract

Failure to achieve sustained virological response (SVR) with hepatitis C virus (HCV) direct-acting antiviral-based regimens is commonly associated with emergence of resistance-associated substitutions (RAS). Re-treatment of patients who failed prior direct-acting antivirals remain challenging. The aim of this prospective and randomized study was to evaluate the efficacy (SVR12 primary endpoint) and safety of sofosbuvir + grazoprevir/elbasvir + ribavirin for 16 or 24 weeks in patients who had failed to achieve SVR on previous NS5A or NS3-based therapy and with evidence of RAS at failure. Patients were chronically infected with HCV genotype (GT) 1 or 4. Most of them had advanced fibrosis or compensated cirrhosis (liver stiffness 5.8–48.8 kPa). All patients achieved HCV RNA below lower limit of quantification (either TD[u] or TND) during treatment. SVR12 was achieved by 25/26 patients. The only patient who did not reach SVR was a patient who died but HCV-RNA was negative at this time (5 weeks after stopping treatment). No patient discontinued treatment because of adverse events or virological failure. Globally, treatment was well tolerated. In conclusion, our findings support the concept of retreating with sofosbuvir+ grazoprevir/elbasvir + ribavirin for 16 weeks GT1 or GT4 DAA-experienced patients with proven NS5A or NS3 RAS.

Investigation of a Cluster of Sequence Type 22 Methicillin-Resistant Staphylococcus aureus Transmission in a Community Setting

Abstract

Background

Whole-genome sequencing (WGS) has typically been used to confirm or refute hospital/ward outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) identified through routine practice. However, appropriately targeted WGS strategies that identify routinely "undetectable" transmission remain the ultimate aim.

Methods

WGS of MRSA isolates sent to a regional microbiological laboratory was performed as part of a 12-month prospective observational study. Phylogenetic analyses identified a genetically related cluster of E-MRSA15 isolated from patients registered to the same general practice (GP) surgery. This led to an investigation to identify epidemiological links, find additional cases, and determine potential for ongoing transmission.

Results

We identified 15 MRSA-positive individuals with 27 highly related MRSA isolates who were linked to the GP surgery, 2 of whom died with MRSA bacteremia. Of the 13 cases that were further investigated, 11 had attended a leg ulcer/podiatry clinic. Cases lacked epidemiological links to hospitals, suggesting that transmission occurred elsewhere. Environmental and staff screening at the GP surgery did not identify an ongoing source of infection.

Conclusions

Surveillance in the United Kingdom shows that the proportion of MRSA bacteremias apportioned to hospitals is decreasing, suggesting the need for greater focus on the detection of MRSA outbreaks and transmission in the community. This case study confirms that the typically nosocomial lineage (E-MRSA15) can transmit within community settings. Our study exemplifies the continued importance of WGS in detecting outbreaks, including those which may be missed by routine practice, and suggests that universal WGS of bacteremia isolates may help detect outbreaks in low-surveillance settings.

Vancomycin Ineffective in Eliminating MRSA Colonization of Respiratory Secretions in Ventilated ICU Patients: A Clinical and Pharmacokinetic Perspective

Antibiotic PharmacokineticsAntibiotic secretion penetration

Endocarditis prophylaxis

Reply to Raoult

Trichomonas vaginalis brain abscess in a neonate

Abstract

We describe a case of cerebral trichomoniasis in a neonate who developed seizures and multi-organ failure during treatment for staphylococcal sepsis. Brain abscesses were identified on cranial sonography. Trichomonas vaginalis was isolated from cerebrospinal fluid. There was a fatal outcome despite metronidazole therapy.

Surgical excision of osteochondroma on mandibular condyle via preauricular approach with zygomatic arch osteotomy

Abstract

Background

Osteochondroma is a benign tumor that tends to develop in mandibular condyle and coronoid process in the craniofacial region. If tumor mass has grown from condyle into the infratemporal space with zygomatic arch obstructing the access, there are risks associated with surgical exposure and local resection of these masses.

Case presentation

This study reports on a case of osteochondroma on mandibular condylar head where we treated with surgical excision via preauricular approach with 3D analysis. After the local resection, there were no surgical and post-operative complications until 8-month follow-up period.

Conclusions

In local excision of osteochondroma, our method is a minimally invasive method. It is a good example of osteochondroma treatment.

Evaluation of mandibular lingula and foramen location using 3-dimensional mandible models reconstructed by cone-beam computed tomography

Abstract

Background

The positions of the mandibular lingula and foramen have been set as indexes for inferior alveolar nerve (IAN) block and ramus osteotomies in orthognathic surgery. This study aimed to evaluate the anatomical structures of mandibular ramus, especially the mandibular lingula and foramen, by analyzing the cone-beam computed tomography (CBCT) data of young adults.

Methods

We evaluated 121 sides of hemi-mandibular CBCT model of 106 patients (51 male and 55 female patients; 18 to 36 years old). All the measurements were performed using the 2- and 3-dimensional rulers of OnDemand3D® software.

Results

Statistical analysis of the data revealed that there was no significant difference in the mandibular angle between the genders. The mandibular lingula was found to be located at the center of ramus in males, but a little posterior in relation to the center in females. The mandibular lingula was rarely located below the occlusal plane; however, the position of the mandibular foramen was more variable (84.3% below, 12.4% above, and 3.3% at the level of the occlusal plane).

Conclusions

The results of this study provide a valuable guideline for IAN block anesthesia and orthognathic surgery. CBCT can be considered effective and accurate in evaluating the fine structures of the mandible.

Book Review: Jason Brennan, Against Democracy . Princeton, New Jersey: Princeton University Press, 2016, ix + 288 pp, ISBN 9780691162607 $29.95

Bullous Sweet's syndrome with myositis

Publication date: Available online 24 October 2017
Source:Actas Dermo-Sifiliográficas
Author(s): K. Sato, T. Miura, M. Ohtsuka, T. Yamamoto

Extracellular Hsp70 induces inflammation and modulates LPS/LTA-stimulated inflammatory response in THP-1 cells

Abstract

Extracellular Hsp70 (eHsp70) can act as damage-associated molecular pattern (DAMP) via Toll-like receptors TLR2 and TLR4, and stimulate immune and inflammatory responses leading to sterile inflammation and propagation of already existing inflammation. It was found elevated in the blood of patients with chronic obstructive pulmonary disease (COPD), who might suffer occasional bacterial colonizations and infections. We used a monocytic THP-1 cell line as a cellular model of systemic compartment of COPD to assess inflammatory effects of eHsp70 when present alone or together with bacterial products lypopolysaccharide (LPS) and lypoteichoic acid (LTA). THP-1 cells were differentiated into macrophage-like cells and treated with various concentrations of recombinant human Hsp70 protein (rhHsp70), LPS (TLR4 agonist), LTA (TLR2 agonist), and their combinations for 4, 12, 24, and 48 h. Concentrations of IL-1α, IL-6, IL-8, and TNF-α were determined by ELISA. Cell viability was assessed by MTS assay, and mode of cell death by luminometric measurements of caspases-3/7, -8, and -9 activities. rhHsp70 showed cell protecting effect by suppressing caspases-3/7 activation, while LPS provoked cytotoxicity through caspases-8 and -3/7 pathway. Regarding inflammatory processes, rhHsp70 alone induced secretion of IL-1α and IL-8, but had modulatory effects on release of all four cytokines when applied together with LPS or LTA. Combined effect with LPS was mainly synergistic, and with LTA mainly antagonistic, although it was cytokine- and time-dependent. Our results confirmed pro-inflammatory function of extracellular Hsp70, and suggest its possible implication in COPD exacerbations caused by bacterial infection through desensitization or inappropriate activation of TLR2 and TLR4 receptors.

A Novel and More Aesthetic Injection Pattern for Malar Cheek Volume Restoration

Abstract

The loss of superior midface contour and projection can be corrected with the use of injectable hyaluronic acid (HA) dermal fillers, however, the most frequently used injection pattern employs a technique which was originally designed for malar implant surgery. Here we describe a novel injection pattern for restoring facial contours with a HA dermal filler inspired by traditional make-up artistry, which includes greater superolateral positioning of injection sites. Importantly, this technique helps injectors avoid creating an excess of volume in the anterior portion of the malar complex. Contributing authors/injectors, who now use this technique exclusively, have found that it has so far provided optimal aesthetic results for hundreds of patients with no observables complications. The malar cheek contributes much to the aesthetic curvature of the face and deserves a thoughtful update for injectable HA, as the traditional technique has never actually been aligned with its medium. In the experience of the contributing authors, this technique helps achieve a greater aesthetic outcome in the correction of midface contour deficiencies and has consistently resulted in high patient satisfaction.

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.

The Incidence of Psychiatric Medication Use and Its Effect on Intraoperative Bleeding in Facial Cosmetic Patients

Abstract

Purpose

Psychiatric medications, particularly the selective serotonin reuptake inhibitors, have been associated with increased surgical bleeding. This study aims to compare intraoperative surgical bleeding between cosmetic surgery patients who are and are not taking psychiatric medications.

Methods

The charts of 392 consecutive patients who underwent cosmetic facial surgery at the senior author's practice were reviewed. Independent variables included self-reported psychiatric history, psychiatric diagnoses, and psychiatric medications as documented in the preoperative history and physical examination. The primary endpoint was administration of desmopressin (DDAVP), our proxy for increased surgical bleeding. Significant predictors of these endpoints were determined via Chi-squared testing.

Results

One hundred and seventeen patients had a psychiatric diagnosis (30%), and 129 patients were taking some class of psychiatric medication (33%). Seventy-two patients received DDAVP (18%). A psychiatric diagnosis did not predict DDAVP administration (14.3% for patients with a psychiatric diagnosis vs. 20.88% for those without, p = 0.14). The use of a psychiatric medication was not associated with DDAVP administration (14.7 vs. 21%, p = 0.14). Male gender significantly predicted DDAVP administration (27.8 vs. 16.9% for females, p = 0.04).

Conclusion

The use of psychiatric medications does not predict increased intraoperative surgical bleeding. This is useful given the prevalence of psychiatric medication use among this patient population and obviates the need for discontinuation of these medications, which otherwise could be consequential.

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.

Foeniculum vulgare essential oil ameliorates acetic acid-induced colitis in rats through the inhibition of NF-kB pathway

Abstract

Aim

The aim of the present study is to investigate the protective effects of Foeniculum vulgare essential oil on intestinal inflammation through the inhibition of NF-kB pathway in acetic acid-induced rat colitis.

Methods

Acute colitis was induced by intra-rectal administration of 2 mL of diluted acetic acid (4%) solution. Two hours after the induction of colitis, 0.2% tween 80 in normal saline, dexamethasone (2 mg/kg) and F. vulgare essential oil (100, 200, 400 mg/kg) were administered to the animals by oral gavage and continued for 5 consecutive days. Assessment of macroscopic and microscopic lesions was done. MPO activity was evaluated by biochemical method. Furthermore, TNF-α activity was detected by immunohistochemistry (IHC) and the expression level of p-NF-kB p65 protein was measured by western blot analysis.

Results

Dexamethasone and F. vulgare essential oil (200, 400 mg/kg) reduced the macroscopic and microscopic lesions compared to the acetic acid group (p < 0.01, p < 0.001). In addition, these agents decreased the activity of MPO (p < 0.01, p < 0.001) and the expression of TNF-α positive cells (p < 0.05, p < 0.01, p < 0.001) in the colon tissue compared to acetic acid group. Furthermore, they inhibited acetic acid-induced expression of p-NF-kB p65 protein (p < 0.05, p < 0.001).

Conclusion

It is proposed that the anti-inflammatory activity of F. vulgare essential oil on acetic acid-induced colitis in rats may involve the inhibition of NF-kB pathway.

Bipedicled conchal bowl composite sling flap for reconstruction of the upper third of the ear

Publication date: Available online 24 October 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): S. Alison Basak, Kimberly M. Ken, Nicholas J. Golda

Myxofibrosarcoma of unusual sites

Abstract

Introduction

Myxofibrosarcoma classically presents as a painless mass in the proximal extremities. Cutaneous myxofibrosarcomas arising in the head and neck and distal extremities are extremely uncommon. We present a series of six cases of myxofibrosarcoma presenting in the head and neck and acral locations.

Methods

Archives were searched using the term "myxofibrosarcoma" over a 6-year period (2009–2015). The clinicopathologic features of myxofibrosarcoma were recorded. Cases in the head and neck or acral locations were retrieved. When available, the patient's medical records were reviewed.

Results

Ninety-five cases of myxofibrosarcoma were identified over a 6-year period. Six patients were identified with myxofibrosarcoma arising in the head (n = 4, M:F 3:1), hand (n = 1, F), and foot (n = 1, F). Each had typical features of myxofibrosarcoma. Two of the tumors on the head were high-grade and had multiple recurrences, while the remaining two were intermediate grade. Both acral tumors were intermediate grade and one recurred locally within a year of diagnosis.

Conclusions

Myxofibrosarcoma may rarely involve the head and neck and acral locations, and presentation in these sites is a potential source of diagnostic difficulty. Recognition of the characteristic histologic features of myxofibrosarcoma in conjunction with judicial use of immunohistochemical stains should allow for accurate diagnosis.

Caffeine in the management of patients with headache

Caffeinated headache medications, either alone or in combination with other treatments, are widely used by patients with headache. Clinicians should be familiar with their use as well as the chemistry, pharmac...

Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Prevented Weight Regain in Obese Women with Polycystic Ovary Syndrome Previously Treated with Liraglutide: A Pilot Randomized Study

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.

Low levels of PSMA expression limit the utility of 18 F-DCFPyL PET/CT for imaging urothelial carcinoma

Abstract

Objective

To explore the clinical utility of PSMA-targeted ¹⁸F-DCFPyL PET/CT in patients with metastatic urothelial carcinoma.

Methods

Three patients with metastatic urothelial carcinoma were imaged with ¹⁸F-DCFPyL PET/CT. All lesions with perceptible radiotracer uptake above background were considered positive. Maximum standardized uptake values were recorded for each detected lesion and findings on ¹⁸F-DCFPyL PET/CT were compared to those on conventional imaging studies. To further explore PSMA as a molecular target of urothelial carcinoma, RNA-sequencing data from The Cancer Genome Atlas were used to compare the relative expression of PSMA among cases of bladder cancer, prostate cancer, and clear cell renal cell carcinoma. Additionally, immunohistochemical staining for PSMA was performed on a biopsy specimen from one of the imaged patients.

Results

¹⁸F-DCFPyL PET/CT allowed for the detection of sites of urothelial carcinoma, albeit with low levels of radiotracer uptake. Analysis of RNA-sequencing data revealed that bladder cancer had significantly lower levels of PSMA expression than both prostate cancer and clear cell renal cell carcinoma. Consistent with this observation, immunohistochemical staining of tissue from one of the imaged patients demonstrated a low level of neovascularization and nearly absent PSMA expression.

Conclusion

The relatively scant expression of PSMA by urothelial carcinoma likely limits the utility of PSMA-targeted PET imaging of this malignancy. Future research efforts should focus on the development of other molecularly targeted imaging agents for urothelial carcinoma.

29th Annual Meeting of the Wound Healing Society, SAWC-Spring/WHS Joint Meeting: San Diego Convention Center, San Diego, California, USA, April 5–9, 2017

Impact of hypoxia in head and neck cancer radiotherapy

Abstract

Background

Radiotherapy plays an important role in the treatment of pharyngo-laryngeal and oral cavity head and neck squamous cell carcinoma (HNSCC) either as single modality, in combination with concomitant chemotherapy or epithermal growth factor inhibitor, or as adjuvant treatment after curative surgery. Various biological factors have been shown to impact on tumour response to radiotherapy, and among them tumour hypoxia.

Aim

This article reviews the clinical data on measurement of tumour hypoxia and summarizes the various options to counteract it, with a special emphasis on the use of hypoxic cell radiosensitizers, radiation dose escalation, and the proper selection of patients who may benefit from such therapeutic interventions.

Results

It has been shown that up to 25% of HNSCC express pO₂ value below 2.5 mm Hg, and modification of tumour hypoxia has been demonstrated to improve loco-regional control and overall survival. In particular, the concomitant use of nimorazole, a hypoxic cell radiosensitizer, has been demonstrated in a seminal DAHANCA trial to significantly improve outcome in patients with head and neck SCC. More recently, among the patients included into this trial, a 15-gene hypoxia classifier indicated that only those patients with hypoxic tumours benefited from the combined radiotherapy and nimorazole treatment.

Conclusions

An ongoing trial is validating both the use of nimorazole and the gene classifier for patients treated with concomitant chemo-radiotherapy.

Off-label prescriptions and decisions on reimbursement requests in Germany – a retrospective analysis

Summary

Background and objectives

"Off-label use" is defined as the prescription of pharmaceutical products outside their approved indications. Rare diseases frequently lack "on-label" treatment options. In order to avoid reimbursement claims following the prescription of off-label drugs, physicians in Germany can – on a case-by-case basis – file an application for cost coverage with the competent health insurance prior to treatment initiation.

Patients and methods

We conducted a chart review for cost coverage requests submitted by two outpatient clinics at a university-affiliated dermatology department between 2010 and 2012 (clinic for autoimmune diseases and urticaria clinic). Insurance providers, acceptance rates, reasons for rejection, and processing times were analyzed.

Results

The analysis showed that 56.8 % of applications for off-label use (n = 44) were approved during the first round. The rate increased to 75.0 % when including approvals granted after up to two rejections. The time between initial application and the response of health insurers was 49 days (median). In case of cost coverage approval, treatments were initiated 92 days (median) after the initial request.

Conclusions

The present case series shows that, in the majority of cases, health insurers in Germany have agreed to reimburse the costs of proposed off-label therapies. A prospective study is required in order to evaluate whether current changes to legal regulations (GKV-Versorgungsstrukturgesetz, Patientenrechtegesetz) adequately address the problems identified.

Enhancement of the photokilling effect of TiO2 in photodynamic therapy by conjugating with reduced graphene oxide and its mechanism exploration

Publication date: Available online 24 October 2017
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Hongyuan Shang, Dong Han, Min Ma, Sha Li, Wenting Xue, Aiping Zhang
As a promising next-generation photodynamic therapy (PDT) photosensitizer, TiO2 nanoparticles (NPs) has gained great attention due to its higher efficiency. Yet, its application in PDT is strongly limited by its UV light response range. In this work, TiO2 NPs conjugated with reduced graphene oxide (RGO-TiO2) composites were successfully prepared by hydrothermal reduction method. They were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Transmission electron microscope (TEM), Brunauer-Emmett-Teller (BET), UV–vis spectroscopy and X-ray photoelectron spectroscopy (XPS). Superior adsorption and killing efficiency under UV-A light or visible light were achieved in the presence of the RGO rather than that of unmodified TiO2. The optimal photocatalytic activity was obtained when modified proportion was 0.2 (RGO:TiO2). Dark cytotoxicity was observed using 0–500μgmL⁻¹ RGO-TiO2 during long incubation time. In parallel, following exposure of human hepatocellular carcinoma cell line (HepG2 cells) to RGO-TiO2 and UV-A or visible light irradiation, a marked decrease in the ratio of the super-coiled DNA, mitochondrial membrane potential (MMP), and the oxidative damage effects, as well as increased the apoptosis rate and intracellular calcium concentration were observed. Moreover, photocatalytic RGO-TiO2 composites killed the HepG2 cells by apoptosis pathway. The results suggested that RGO-TiO2 composites were an excellent candidate as a PDT photosensitizer in the near future.

Graphical abstract

Functional role of DNA methylation at the FLO1 promoter in budding yeast

Abstract

We have previously reported that the transformation of the budding yeast with plasmids encoding the human DNA methyltransferases DNMT1 and DNMT3B cDNAs induce the mRNA of flocculin gene FLO1 and the flocculation phenotype. In the present study, we evaluated the effect of DNMT inhibitor in the transformed yeasts using a FLO1 promoter-based green fluorescent protein (GFP) reporter gene assay. The DNMT inhibitor, 5-aza-2'-deoxycytidine (5AZ), decreased GFP fluorescence driven by FLO1 promoter in DNMT-genes transformed yeast (DNMT yeast). Surprisingly, the GFP activity driven by cytosine–phosphate–guanine (CpG) motif-reduced FLO1 promoter decreased both in DNMTs gene-transformed as well as control strains. Yeast cells transformed with expression vector encoding a maintenance enzyme DNMT1 cDNA showed a flocculation phenotype which was associated with enhanced mRNA level of FLO1. Bisulfite sequencing revealed methylated CpG sites at the FLO1 promoter in a control strain not expressing any DNMT transgenes and no detectable methylation at the sites was observed in cells treated with 5AZ. These results suggest that the FLO1 promoter is endogenously de novo methylated leading to the activation of FLO1 gene transcription. Furthermore, the methylation level at the FLO1 promoter is responsible for the significant differences in FLO1 promoter-driven expression of GFP in DNMT yeast.

Improvement of a yeast self-excising integrative vector by prevention of expression leakage of the intronated Cre recombinase gene during plasmid maintenance in Escherichia coli .

Abstract

The use of plasmids possessing a regulatable gene coding for a site-specific recombinase together with its recognition sequences significantly facilitates genome manipulations since it allows self-excision of the portion of the genetic construct integrated into the host genome. Stable maintenance of such plasmids in Escherichia coli, which is used for plasmid preparation, requires prevention of recombinase synthesis in this host, which can be achieved by interrupting the recombinase gene with an intron. Based on this approach, Saccharomyces cerevisiae and Hansenula polymorpha self-excising vectors possessing intronated gene for Cre recombinase and its recognition sites (LoxP) were previously constructed. However, this work shows instability of the H. polymorpha vectors during plasmid maintenance in E. coli cells. This could be due to recombination between the loxP sites caused by residual expression of the cre gene. Prevention of translation reinitiation on an internal methionine codon completely solved this problem. A similar modification was made in a self-excising vector designed for S. cerevisiae. Apart from substantial improvement of yeast self-excising vectors, the obtained results also narrow down the essential part of Cre sequence.

XdhR negatively regulates actinorhodin biosynthesis in Streptomyces coelicolor M145

Abstract

The xdhR gene encodes a TetR-family regulator in Streptomyces coelicolor. However, little is known about the function of XdhR in regulating actinorhodin production. Here, we report that XdhR negatively regulates actinorhodin biosynthesis in S. coelicolor. Deletion of xdhR resulted in overproduction of actinorhodin by approximately 2.5-fold compared to the wild-type strain. Complementation of the xdhR deletion strain restored actinorhodin production to normal levels. In addition, the relative expression levels of actinorhodin cluster genes were all significantly increased in the xdhR deletion strain compared to the wild-type strain. XdhR can specifically bind the promoters of actII-4 and actII-1, two pathway-specific regulators of actinorhodin biosynthesis. These results suggest that xdhR negatively controls actinorhodin biosynthesis by directly regulating actII-4 and actII-1 in S. coelicolor.

The secreted polyketide boydone A is responsible for the anti- Staphylococcus aureus activity of Scedosporium boydii

Abstract

Usually living as a soil saprophyte, the filamentous fungus Scedosporium boydii may also cause various infections in human. Particularly, it is one of the major causative agents of fungal colonization of the airways in patients with cystic fibrosis (CF). To compete with other microorganisms in the environment, fungi have evolved sophisticated strategies, including the production of secondary metabolites with antimicrobial activity which may also help them to establish successfully within the respiratory tract of receptive hosts. Here, the culture filtrate from a human pathogenic strain of S. boydii was investigated searching for an antibacterial activity, mainly against the major CF bacterial pathogens. A high antibacterial activity against Staphylococcus aureus, including methicillin-resistant strains of this species, was observed. Bio-guided fractionation and analysis of the active fractions by nuclear magnetic resonance or by high performance—liquid chromatography and high resolution—electrospray ionization—mass spectrometry allowed us to identify boydone A as responsible for this antibacterial activity. Together these results suggest that this 6-membered cyclic polyketide could be one of the virulence factors of the fungus. Genes involved in the synthesis of this secreted metabolite are currently being identified in order to confirm the role of this polyketide in pathogenesis.

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.

UV-based evaluation of ergosterol for monitoring the fungal exposure in Italian buffalo farms

Abstract

This study provided a reliable way to identify and estimate the ergosterol in farm environments, since it is renowned that is a specific indicator for the occurrence of molds and yeasts. The quickly valuation of exposure to airborne microorganisms is essential to assess the risk to which the health of employees are subjected in working places characterized by great humidity. From this view, it is worth estimating the total biomass of molds and yeast, including viable and non-viable forms, which may cause respiratory concerns to human. Air samples were collected with passive method and the microbial growth was evaluated with traditional counting method. At the same time, the ergosterol was quantified from yeasts and molds. In this way, the aerosol concentrations of molds and yeasts were compared by using the two methods, the cultivation on plates, as well as through ergosterol measurement by means of UV spectroscopy. Results showed, for the first time, a positive correlation between the amount of ergosterol and the yeast cells. Based on these outcomes, the ergosterol is a statistically significant biomarker to be used in the control of the air quality of indoor and outdoor farm spaces, by means of a simple and direct UV procedure.

Molecular markers of DNA damage and repair in cervical cancer patients treated with cisplatin neoadjuvant chemotherapy: an exploratory study

Abstract

Neoadjuvant (or induction) chemotherapy can be used for cervical cancer patients with locally advanced disease; this treatment is followed by radical surgery and/or radiation therapy. Cisplatin is considered to be the most active platinum agent drug for this cancer, with a response rate of 20%. In order to understand how the cisplatin treatment affects the stress response, in this work, we performed an exploratory study to analyze a number of stress proteins before and after cisplatin neoadjuvant chemotherapy. The study involved 14 patients; the pre- and post-chemotherapy paired biopsies were examined by hematoxylin and eosin staining and by immunohistochemistry. The proteins evaluated were p53, P16/INK4A, MSH2, nuclear protein transcriptional regulator 1 (NUPR1), and HSPB1 (total: HSPB1/t and phosphorylated: HSPB1/p). These proteins were selected because there is previous evidence of their relationship with drug resistance. The formation of platinum-DNA adducts was also studied. There was a great variation in the expression levels of the mentioned proteins in the pre-chemotherapy biopsies. After chemotherapy, p53 was not significantly affected by cisplatin, as well as P16/INK4A and MSH2 while nuclear NUPR1 content tended to decrease (p = 0.056). Cytoplasmic HSPB1/t expression levels decreased significantly following cisplatin therapy while nuclear HSPB1/t and HSPB1/p tended to increase. Since the most significant changes following chemotherapy appeared in the HSPB1 expression levels, the changes were confirmed by Western blot. The platinum-DNA adducts were observed in HeLa cell in apoptosis; however, in the tumor samples, the platinum-DNA adducts were observed in morphologically healthy tumor cells; these cells displayed nuclear HSPB1/p. Further mechanistic studies should be performed to reveal how HSPB1/p is related with drug resistance. When the correlations of the markers with the response to neoadjuvant chemotherapy were examined, only high pre-chemotherapy levels of cytoplasmic HSPB1/p correlated with a poor clinical and pathological response to neoadjuvant cisplatin chemotherapy (p = 0.056) suggesting that this marker could be useful opening its study in a larger number of cases.

The reality of scientific research in Latin America; an insider’s perspective

Abstract

There is tremendous disparity in scientific productivity among nations, particularly in Latin America. At first sight, this could be linked to the relative economic health of the different countries of the region, but even large and relatively rich Latin American countries do not produce a good level of science. Although Latin America has increased the number of its scientists and research institutions in recent years, the gap between developed countries and Latin American countries is startling. The prime importance of science and technology to the development of a nation remains unacknowledged. The major factors contributing to low scientific productivity are the limited access to grant opportunities, inadequate budgets, substandard levels of laboratory infrastructure and equipment, the high cost and limited supply of reagents, and inadequate salaries and personal insecurity of scientists. The political and economic instability in several Latin America countries results in a lack of long-term goals that are essential to the development of science. In Latin America, science is not an engine of the economy. Most equipment and supplies are imported, and national industries are not given the incentives to produce these goods at home. It is a pity that Latin American society has become accustomed to expect new science and technological developments to come from developed countries rather than from their own scientists. In this article, we present a critical view of the Latin American investigator's daily life, particularly in the area of biomedicine. Too many bright young minds continue to leave Latin America for developed countries, where they are very successful. However, we still have many enthusiastic young graduates who want to make a career in science and contribute to society. Governments need to improve the status of science for the sake of these young graduates who represent the intellectual and economic future of their countries.

Protective effects of Nebivolol against interleukin-1β (IL-1β)-induced type II collagen destruction mediated by matrix metalloproteinase-13 (MMP-13)

Abstract

The pathological progression of osteoarthritis (OA) involves degradation of articular cartilage matrix. Type II collagen is the main component of cartilage matrix, which is degraded by pro-inflammatory cytokines such as IL-1β mediated by MMP-13. Nebivolol, a licensed drug used for the treatment of hypertension in clinics, displays its anti-inflammatory capacity in various conditions. However, whether Nebivolol has a protective effect on cartilage matrix degradation has not been reported before. In this study, we investigated the effects of Nebivolol on regulating the expression of MMP-13 and degradation of type II collagen. Our results indicate that Nebivolol alleviated the increase in gene expression, protein expression, and activity of MMP-13 induced by IL-1β. Importantly, IL-1β strikingly reduced the levels of type II collagen in cell culture supernatants, which was reversed by treatment with Nebivolol in a dose-dependent manner. Mechanistically, Nebivolol was found to alleviate the increased levels of phosphorylated IκBα and reduced levels of total IκBα induced by IL-1β, which subsequently mitigated p65 nuclear translocation and the transcriptional activity of NF-κB. Furthermore, our results indicated that IL-1β treatment resulted in a significant increase in expression of the transcriptional factor interferon regulatory factor-1 (IRF-1) at both the mRNA and protein levels, which was significantly ameliorated by treatment with Nebivolol. The combination of these findings suggests that Nebivolol can potentially be applied in human OA treatment.

Proteasome properties of hemocytes differ between the whiteleg shrimp Penaeus vannamei and the brown shrimp Crangon crangon (Crustacea, Decapoda)

Abstract

Crustaceans are intensively farmed in aquaculture facilities where they are vulnerable to parasites, bacteria, or viruses, often severely compromising the rearing success. The ubiquitin-proteasome system (UPS) is crucial for the maintenance of cellular integrity. Analogous to higher vertebrates, the UPS of crustaceans may also play an important role in stress resistance and pathogen defense. We studied the general properties of the proteasome system in the hemocytes of the whiteleg shrimp, Penaeus vannamei, and the European brown shrimp Crangon crangon. The 20S proteasome was the predominant proteasome population in the hemocytes of both species. The specific activities of the trypsin-like (Try-like), chymotrypsin-like (Chy-like), and caspase-like (Cas-like) enzymes of the shrimp proteasome differed between species. P. vannamei exhibited a higher ratio of Try-like to Chy-like activities and Cas-like to Chy-like activities than C. crangon. Notably, the Chy-like activity of P. vannamei showed substrate or product inhibition at concentrations of more than 25 mmol L⁻¹. The K _M values ranged from 0.072 mmol L⁻¹ for the Try-like activity of P. vannamei to 0.309 mmol L⁻¹ for the Cas-like activity of C. crangon. Inhibition of the proteasome of P. vannamei by proteasome inhibitors was stronger than in C. crangon. The pH profiles were similar in both species. The Try-like, Chy-like, and Cas-like sites showed the highest activities between pH 7.5 and 8.5. The proteasomes of both species were sensitive against repeated freezing and thawing losing ~80–90% of activity. This study forms the basis for future investigations on the shrimp response against infectious diseases, and the role of the UPS therein.

Upregulation of heat-shock proteins in larvae, but not adults, of the flesh fly during hot summer days

Abstract

Heat-shock proteins (HSPs) are highly expressed when organisms are exposed to thermal stresses. The HSPs are considered to play significant roles in thermal adaptation because they function as molecular chaperones facilitating proper protein synthesis. The expression of HSPs under field conditions, however, has not been evaluated much, and their importance, based on the ecological contexts in nature, is still unclear. We investigated this aspect in the larvae and adults of the flesh fly, Sarcophaga similis. These larvae spend their larval life in the carrion or faeces of vertebrates; therefore, they are less mobile and are occasionally exposed to high temperature. In contrast, the adults of this species can fly and, therefore, they are highly mobile. Massive transcription of Hsps was detected both in the larvae and adults in a laboratory heat-shock experiment. The larvae in the field showed no or less Hsp production on thermally mild days, whereas considerable upregulation of Hsp expression was detected on days with high temperature. The adults can also be exposed to thermal stress as high as 40 °C or higher in the field. However, most of the flies showed no or less Hsp expression. The observations in the experimental cage under field conditions revealed behavioural thermoregulation of adults through microhabitat selection. The present study demonstrates ontogenetic alteration of the strategy to overcome thermal stress in an insect; in the field, less mobile larvae use physiological protection against heat (HSP production), whereas highly mobile adults avoid the stress behaviourally (through microhabitat selection).

Thermal treatment of luteolin-7-O-β-glucoside improves its immunomodulatory and antioxidant potencies

Abstract

Phytochemicals extracted from flowers, roots and bark, leaves, and other plant sources have been used extensively throughout human history with varying levels of efficacy in prevention and treatment of disease. Recently, advanced methods for characterization and clinical use of these materials have allowed modern understanding of their properties to be used as immunomodulatory agents that act by enhancement of endogenous cytoprotective mechanisms, avoiding interference with normal physiologic signaling and highly effective medical treatment with minimal adverse side effects. Simple methods have been identified for improving their biological effects, such as thermal conditioning by heating or freezing—prominent example being heat treatment of lycopene and tetrahydrocannabinol. The present investigation shows improvement of the ability of heat to augment splenocyte proliferation, natural killer (NK) cell activities, and antioxidant capacity of the flavonoid luteolin-7-O-β-glucoside (L7G) in comparison with the native (non heat-treated) molecule, while further demonstrating that both the native and the heat-treated variants exhibit comparable antioxidant properties, as evidenced by their effects in macrophages by inhibition of nitric oxide production and lysosomal enzyme activity in experiments that strengthen lysosomal membrane integrity. Outcomes of these studies suggest that heat-treated L7G shows promise for use in immunotherapy, including anti-cancer regimens, as shown by its improvement of NK cell cytotoxicity.

On the role, ecology, phylogeny, and structure of dual-family immunophilins

Abstract

The novel class of dual-family immunophilins (henceforth abbreviated as DFI) represents naturally occurring chimera of classical FK506-binding protein (FKBP) and cyclophilin (CYN), connected by a flexible linker that may include a three-unit tetratricopeptide (TPR) repeat. Here, I report a comprehensive analysis of all current DFI sequences and their host organisms. DFIs are of two kinds: CFBP (cyclosporin- and FK506-binding protein) and FCBP (FK506- and cyclosporin-binding protein), found in eukaryotes. The CFBP type occurs in select bacteria that are mostly extremophiles, such as psychrophilic, thermophilic, halophilic, and sulfur-reducing. Essentially all DFI organisms are unicellular. I suggest that DFIs are specialized bifunctional chaperones that use their flexible interdomain linker to associate with large polypeptides or multisubunit megacomplexes to promote simultaneous folding or renaturation of two clients in proximity, essential in stressful and denaturing environments. Analysis of sequence homology and predicted 3D structures of the FKBP and CYN domains as well as the TPR linkers upheld the modular nature of the DFIs and revealed the uniqueness of their TPR domain. The CFBP and FCBP genes appear to have evolved in parallel pathways with no obvious single common ancestor. The occurrence of both types of DFI in multiple unrelated phylogenetic clades supported their selection in metabolic and environmental niche roles rather than a traditional taxonomic relationship. Nonetheless, organisms with these rare immunophilins may define an operational taxonomic unit (OTU) bound by the commonality of chaperone function.

Serum histones as biomarkers of the severity of heatstroke in dogs

Abstract

Heatstroke is associated with systemic inflammatory response syndrome, leading to multiple organ dysfunction and death. Currently, there is no specific treatment decreasing hyperthermia-induced inflammatory/hemostatic derangements. Emerging studies indicate that histones leaking from damaged cells into the extracellular space are toxic, pro-inflammatory, and pro-thrombotic. We therefore hypothesize that serum histones (sHs) are elevated during heatstroke and are associated with the severity of the disease. Sixteen dogs with heatstroke and seven healthy controls were included in the study. Median serum histones (sHs) upon admission in dogs with heatstroke were significantly higher (P = 0.043) compared to that in seven controls (13.2 vs. 7.3 ng/mL, respectively). sHs level was significantly higher among non-survivors and among dogs with severe hemostatic derangement (P = 0.049, median 21.4 ng/mL vs. median 8.16 ng/mL and P = 0.038, 19.0 vs. 7.0 ng/mL, respectively). There were significant positive correlation between sHs and urea (r = 0.8, P = 0.02); total CO2 (r = 0.661, P = 0.05); CK (r = 0.678, P = 0.04); and prothrombin time (PT) 12 h post presentation (r = 0.888, P = 0.04). The significant positive correlation between sHs and other heatstroke severity biomarkers, and significant increase among severely affected dogs, implies its role in inflammation/oxidation/coagulation during heatstroke. sHs, unlike other prognostic and severity biomarkers in heatstroke, can be pharmacologically manipulated, offering a potential therapeutic target.

Addition of exogenous SOD1 aggregates causes TDP-43 mislocalisation and aggregation

Abstract

ALS is characterised by a focal onset of motor neuron loss, followed by contiguous outward spreading of pathology throughout the nervous system, resulting in paralysis and death generally within a few years after diagnosis. The aberrant release and uptake of toxic proteins including SOD1 and TDP-43 and their subsequent propagation, accumulation and deposition in motor neurons may explain such a pattern of pathology. Previous work has suggested that the internalization of aggregates triggers stress granule formation. Given the close association of stress granules and TDP-43, we wondered whether internalisation of SOD1 aggregates stimulated TDP-43 cytosolic aggregate structures. Addition of recombinant mutant G93A SOD1 aggregates to NSC-34 cells was found to trigger a rapid shift of TDP-43 to the cytoplasm where it was still accumulated after 48 h. In addition, SOD1 aggregates also triggered cleavage of TDP-43 into fragments including a 25 kDa fragment. Collectively, this study suggests a role for protein aggregate uptake in TDP-43 pathology.

SG2NA is a regulator of endoplasmic reticulum (ER) homeostasis as its depletion leads to ER stress

Abstract

SG2NA belongs to a three-member striatin subfamily of WD40 repeat superfamily of proteins. It has multiple protein-protein interaction domains involved in assembling supramolecular signaling complexes. Earlier, we had demonstrated that there are at least five variants of SG2NA generated by alternative splicing, intron retention, and RNA editing. Such versatile and dynamic mode of regulation implicates it in tissue development. In order to shed light on its role in cell physiology, total proteome analysis was performed in NIH3T3 cells depleted of 78 kDa SG2NA, the only isoform expressing therein. A number of ER stress markers were among those modulated after knockdown of SG2NA. In cells treated with the ER stressors thapsigargin and tunicamycin, expression of SG2NA was increased at both mRNA and protein levels. The increased level of SG2NA was primarily in the mitochondria and the microsomes. A mouse injected with thapsigargin also had an increase in SG2NA in the liver but not in the brain. Cell cycle analysis suggested that while loss of SG2NA reduces the level of cyclin D1 and retains a population of cells in the G1 phase, concurrent ER stress facilitates their exit from G1 and traverse through subsequent phases with concomitant cell death. Thus, SG2NA is a component of intrinsic regulatory pathways that maintains ER homeostasis.

Identification of the acclimation genes in transcriptomic responses to heat stress of White Pekin duck

Abstract

White Pekin duck is an important meat resource in the livestock industries. However, the temperature increase due to global warming has become a serious environmental factor in duck production, because of hyperthermia. Therefore, identifying the gene regulations and understanding the molecular mechanism for adaptation to the warmer environment will provide insightful information on the acclimation system of ducks. This study examined transcriptomic responses to heat stress treatments (3 and 6 h at 35 °C) and control (C, 25 °C) using RNA-sequencing analysis of genes from the breast muscle tissue. Based on three distinct differentially expressed gene (DEG) sets (3H/C, 6H/C, and 6H/3H), the expression patterns of significant DEGs (absolute log2 > 1.0 and false discovery rate < 0.05) were clustered into three responsive gene groups divided into upregulated and downregulated genes. Next, we analyzed the clusters that showed relatively higher expression levels in 3H/C and lower levels in 6H/C with much lower or opposite levels in 6H/3H; we referred to these clusters as the adaptable responsive gene group. These genes were significantly enriched in the ErbB signaling pathway, neuroactive ligand-receptor interaction and type II diabetes mellitus in the KEGG pathways (P < 0.01). From the functional enrichment analysis and significantly regulated genes observed in the enriched pathways, we think that the adaptable responsive genes are responsible for the acclimation mechanism of ducks and suggest that the regulation of phosphoinositide 3-kinase genes including PIK3R6, PIK3R5, and PIK3C2B has an important relationship with the mechanisms of adaptation to heat stress in ducks.

The Genomic Grade Index predicts post-operative clinical outcome in patients with soft tissue sarcoma

Abstract

Background

Soft-tissue sarcomas (STS) are a group of rare, heterogeneous and aggressive tumors, with high metastatic risk and relatively few efficient systemic therapies. We hypothesized that the Genomic Grade Index (GGI), a 108-gene signature previously developed in early-stage breast cancer, might improve the prognostic assessment of patients with early-stage STS.

Patients and methods

We collected gene expression and clinicopathological data of 678 operated STS, and searched for correlations between the GGI-based classification and clinicopathological variables, including the metastasis-free survival (MFS).

Results

Based on GGI, 275 samples (41%) were classified as "GGI-low" and 403 (59%) as "GGI-high". The "GGI-high" class was more associated with poor-prognosis features than the "GGI-low" class: pathological grade 3 (p=9.50E-11), undifferentiated sarcomas and leiomyosarcomas (p<1.00E-06), location in extremities (p<1.00E-06), and complex genetic profile (p=2.1E-20). The 5-year MFS was 53% (95%CI 47-59) in the "GGI-high" class vs. 78% (95%CI 72-85) in the "GGI-low" class (p=3.02E-11), with a corresponding Hazard Ratio for metastatic relapse equal to 2.92 (95%CI 2.10-4.07; p=2.23E-10). In multivariate analysis, the GGI-based classification remained significant, whereas the pathological grade did not. In fact, the GGI-based classification stratified the patients with pathological grade 1-2 and those with pathological grade 3 in two classes with different 5-year MFS. Comparison of the GGI and CINSARC multigene signatures revealed similar correlations with clinicopathological variables, which were however stronger with GGI than with CINSARC, a strong concordance (71%) in term of low-risk or high-risk classifications, and independent prognostic value for MFS in multivariate analysis, suggesting complementary prognostic information.

Conclusion

GGI refines the prediction of MFS in operated STS and might improve the tailoring of adjuvant chemotherapy. Further clinical validation is warranted in larger retrospective, then prospective series, as well as the functional validation of relevant genes that could provide new therapeutic targets.

Mechanistic overview of immune checkpoints to support the rational design of their combinations in cancer immunotherapy

Abstract

Checkpoint receptor blockers, known to act by blocking the pathways that inhibit immune cell activation and stimulate immune responses against tumor cells, have been immensely successful in the treatment of cancer. Among several checkpoint receptors of immune cells, cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), T-cell immunoglobulin and ITIM domain (TIGIT), T-cell immunoglobulin-3 (TIM-3) and lymphocyte activation gene 3 (LAG-3) are the most commonly targeted checkpoints for cancer immunotherapy. Six drugs including one CTLA-4 blocker (ipilimumab), two PD-1 blockers (nivolumab and pembrolizumab), and three PD-L1 blockers (atezolizumab, avelumab and durvalumab) are approved for the treatment of different types of cancers including both solid tumors such as melanoma, lung cancer, head and neck cancer, bladder cancer and Merkel cell cancer as well as hematological tumors such as classic Hogdkins lymphoma. The main problem with checkpoint blockers is that only a fraction of patients respond to the therapy. Insufficient immune activation is considered as one of the main reason for low response rates and combination of checkpoint blockers has been proposed to increase the response rates. The combination of checkpoint blockers was successful in melanoma but had significant adverse events. A combination that is selected based on the mechanistic differences between checkpoints and the differences in expression of checkpoints and their ligands in the tumor microenvironment (TME) could have a synergistic effect in a given cancer subtype and also have a manageable safety profile. This review aims to help in design of optimal checkpoint blocker combinations by discussing the mechanistic details and outlining the subtle differences between major checkpoints targeted for cancer immunotherapy.

Ten-year Results of Intense Dose-dense chemotherapy show superior survival compared to a conventional schedule in High-risk Primary Breast Cancer: Final results of AGO Phase III iddEPC trial.

Abstract

Background

Primary breast cancer patients with extensive axillary lymph-node involvement have a limited prognosis. The AGO (Arbeitsgemeinschaft fuer Gynaekologische Onkologie) trial compared intense dose-dense adjuvant chemotherapy with conventionally scheduled chemotherapy in high-risk breast cancer patients. Here we report the final, 10-year follow-up analysis.

Patients and methods

Enrolment took place between December 1998 until April 2003. 1284 patients with four or more involved axillary lymph nodes were randomly assigned to receive three courses each of intense dose-dense sequential epirubicin, paclitaxel and cyclophosphamide (iddEPC) q2w or standard epirubicin/cyclophosphamide followed by paclitaxel (EC&cenveo_unknown_entity_wingdings_F0E0;P) q3w. Event-free survival (EFS) was the primary endpoint.

Results

658 patients were assigned to receive iddEPC and 626 patients were assigned to receive EC&cenveo_unknown_entity_wingdings_F0E0;P. The median duration of follow-up was 122 months. EFS was 47% (95% CI 43%-52%) in the standard group and 56% (95% CI 52%-60%) in the iddEPC group (hazard ratio [HR] 0.74, 95% CI 0.63-0.87; log-rank P=0.00014, one sided). This benefit was independent of menopausal, hormone receptor or HER2 status. 10-year overall survival (OS) was 59% (95% CI 55%-63%) for patients in the standard group and 69% (95% CI 65%-73%) for patients in the iddEPC group (HR = 0.72, 95% CI 0.60-0.87; log-rank P=0.0007, two sided). Nine vs. two cases of secondary myeloid leukaemia/MDS were observed in the iddEPC and the EC&cenveo_unknown_entity_wingdings_F0E0;P arm, respectively.

Conclusion

The previously reported OS benefit of intense dose-dense EPC in comparison to conventionally dosed EC&cenveo_unknown_entity_wingdings_F0E0;P has been further increased and achieved an absolute difference of 10% after 10 years of follow-up.

Use of CSP typing for genotyping of azole-resistant and -susceptible Aspergillus fumigatus isolates in Iran

Summary

Aspergillus fumigatus is the leading cause of mortality in severely immunocompromised individuals. Understanding pathogen dispersion and relatedness is essential for determining the epidemiology of nosocomial infections. Therefore, the aim of this study was to investigate the diversity and putative origins of clinical and environmental azole-susceptible and -resistant A. fumigatus isolates from Iran. Seventy-nine isolates, including 64 azole-susceptible and 15 azole-resistant isolates, were genotyped using the cell surface protein (CSP) gene. Seven distinct repeat types (r01, r02, r03, r04, r05, r06 and r07) and 11 different CSP variants (t01, t02, t03, t04A, t06A, t06B, t08, t10, t18A, t18B and t22) were observed. Interestingly t06B, t18A and t18B were exclusively present in azole-resistant isolates. The Simpson's index of diversity (D) was calculated at 0.78. Resistant isolates were genetically less diverse than azole-susceptible isolates. However, azole-resistant A. fumigatus without TR₃₄/L98H were more diverse than with TR₃₄/L98H. The limited CSP type diversity of the TR₃₄/L98H isolates versus azole- susceptible isolates suggests that repeated independent emergence of the TR₃₄/L98H mechanism is unlikely. It has been suggested that CSP types might have a common ancestor that developed locally and subsequently migrated worldwide.

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Inflammation and oxidative stress in corneal tissue in experimental keratitis due to Fusarium solani: amelioration following topical therapy with voriconazole and epigallocatechin gallate

Summary

Combined antifungal and antioxidant therapy may help to reduce oxidative stress in fungal keratitis. Experimental Fusarium solani keratitis was induced by application of F. solani conidia to scarified cornea (right eye) of 16 rabbits (another 4 rabbits were negative controls [Group I]). Five days later, F. solani-infected animals began receiving hourly topical saline alone (Group II), voriconazole (10 mg/ml) alone (Group III), epigallocatechingallate (EGCG, 10 mg/ml) alone (Group IV) or voriconazole and EGCG (Group V). Twenty days post-inoculation, corneal lesions were graded. After animal sacrifice, excised corneas underwent histopathological and microbiological investigations. Corneal tissue levels/activities of interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) gene mRNA transcripts, matrix metalloproteinase(MMP) 2 and 9 proteins, malondialdehyde(MDA) and reduced glutathione(GSH), and superoxide dismutase(SOD), catalase(CAT) and glutathione peroxidise(GPx), were also measured. Clinical and histopathological scores (severity of corneal lesions; [P<0.05]) and mean levels (P<0.05) of IL-1ß and TNF-α mRNA transcripts, MMP 2, MMP 9 and MDA were Group II > Groups IV and III >groups V and I. Mean SOD, CAT, GPx and GSH levels (P<0.05) were Group II < Groups IV and III <groups V and I. Topical voriconazole with EGCG apparently reduces inflammation in experimental F. solani keratitis, as manifested by improved clinical, histological, microbiological and molecular parameters.

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In vitro antifungal activity of amphotericin B and eleven comparators against Aspergillus terreus species complex

Summary

Aspergillus terreus infections are difficult to treat because of the intrinsic resistance to amphotericin B, and higher mortality compared to infections caused by other Aspergillus species. The aim of the present study was to determine the in vitro antifungal activity of amphotericin B and eleven comparators against clinical (n = 36) and environmental (n = 45) A. terreus isolates. In vitro antifungal susceptibility was performed using the CLSI M38-A2 procedure. Amphotericin B exhibited the highest MICs (MIC range, 0.125 to 4 μg/ml; MIC90, 2 μg/ml), followed by terbinafine (MIC range, 0.002 to 1 μg/ml; MIC90, 1 μg/ml). Only one isolate (1/81) showed amphotericin B MIC above the epidemiologic cutoff value (ECV; 4 μg/ml). None of the isolates had a MIC of ≥ ECV for voriconazole, itraconazole and posaconazole. The reasons for the difference in amphotericin B susceptibility patterns between studies remain unknown. The genetic and species diversity, clinical, environmental and ecological factors in Terrei section on various amphotericin B susceptibility profiles in different countries should be considered more as the main reasons associated with these differences.

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Sentinel lymph node biopsy status is not the most powerful predictor of prognosis in cutaneous melanoma

Abstract

Sentinel lymph node (SLN) status has been advocated in several recently published articles as the single most valuable prognostic marker for melanoma, and of greater prognostic importance than more established parameters such as Breslow thickness. A careful examination of the evidence for these claims, however, indicates that they are not substantiated by the available data, are somewhat misleading and suggest misinterpretation of the statistical analysis of the papers to which they refer. We will examine the basis for these claims and show why they are invalid.

Chemical peels: A review of current practice

Abstract

Chemical peels belong to a group of cutaneous resurfacing procedures that are used in the treatment of photoageing, inflammatory dermatoses, epidermal proliferations, pigmentary disorders and scarring. This review describes best current practice, highlights recent advances in chemical peel technology and discusses the recommended uses for different peel types. It also presents the results of a survey of the chemical peeling practices of 30 Australian dermatologists.

High-risk squamous cell carcinoma masquerading as dense inflammation on Mohs frozen sections

Abstract

High-risk squamous cell carcinoma (SCC) can present a unique challenge in Mohs surgery. This case report describes how high-risk SCC may masquerade as only a dense inflammation on frozen sections. This feature should raise the index of suspicion for hidden SCC and be a routine indication for further processing by paraffin sections and immunohistochemistry.

UK multicentre audit of the management of eczema in children

Zielgruppe Mann in der ästhetischen Chirurgie

Zusammenfassung

Wer Männer als Zielgruppe für sich gewinnen will, muss das Marketing auch darauf ausrichten. Ob sich ein männlicher Patient tatsächlich für ein Beratungsgespräch entscheidet, hängt davon ab, ob dieser bei seiner Recherche das Empfinden entwickelt, bei einer auch auf Männer spezialisierten Praxis oder Klinik zu sein. Die dafür verantwortlichen Botschaften wie Vertrauen, Kompetenz und Sympathie werden nicht nur durch Text, sondern auch durch Bilder transportiert – der Text untermauert nur noch die Meinung. Um bei einer Suchmaschine wie Google tatsächlich angeklickt zu werden, muss diese Internetseite bei den Treffern oben stehen, idealerweise auf der ersten Seite, und das ist eine Aufgabe von SEO („search engine optimization"). Wer Männer als Zielgruppe so gewinnen will, muss also auch seine SEO-Arbeit genau darauf ausrichten – sonst stehen zu Themen wie „Haartransplantation" andere Anbieter auf den begehrten vorderen Trefferseiten. Jede positive Bewertung ist eine Empfehlung, und eine positive Bewertung eines männlichen Patienten ist somit eine glaubwürdige, hervorragende Empfehlung ästhetischer Eingriffe für Männer. Facebook ist schnell und unkompliziert und quasi eine Suchmaschine. Mit den richtigen Hashtags und Posts kann die Zielgruppe Mann hervorragend gefunden und angesprochen werden. Bei einem Durchschnittsalter der deutschen Facebook-Nutzer von über 40 Jahren stellt Facebook also eine hervorragende Marketingmöglichkeit dar. Instagram muss sich noch beweisen, doch hier gilt: Wer nun Instagram erfolgreich nutzt, ist später vorn dabei. Nicht jeder Patient wählt zur anonymen Information das eher unpersönliche Internet – viele bevorzugen das Gespräch, möglichst anonym, und dafür sind Patientenveranstaltungen bestens geeignet.

Targeted antibody therapy and relevant novel biomarkers for precision medicine for rheumatoid arthritis

Abstract

Over the past two decades, the management of rheumatoid arthritis has progressed remarkably, encompassing the development of new diagnostic tools and efficacious biological agents, such as monoclonal antibodies against inflammatory cytokines and surface markers on immune cells. In addition to the significant efficacy of these biological agents, biomarkers for rheumatoid arthritis are under consideration for their potential to classify heterogeneous patients into several groups based on clinical and immunological phenotypes for the prediction of clinical course and prognosis and the facilitation of appropriate and precise treatment with the appropriate therapeutic monoclonal antibodies. Biomarkers, particularly those for the prediction and monitoring of the responses to therapeutic monoclonal antibodies for rheumatoid arthritis, are in demand, with many approaches examined in recent years. In this article, we have summarized the background research on biomarkers and introduced recent topics in the field that enable the possible clinical applications of biomarkers, especially those related to pathogenic cytokines, to guide the treatment of rheumatoid arthritis.

Sweet SIGNs: IgG glycosylation leads the way in IVIG-mediated resolution of inflammation

Abstract

A hallmark of many chronic inflammatory and autoimmune diseases is that there is an impaired resolution of inflammation and return to the steady state. The infusion of high doses of pooled serum IgG preparations from thousands of donors [intravenous immunoglobulin (IVIG) therapy] has been shown to induce resolution of inflammation in a variety of chronic inflammatory and autoimmune diseases, suggesting that IgG molecules can instruct the immune system to stop inflammatory processes and initiate the return to the steady state. The aim of this review is to discuss how insights into the mechanism of IVIG activity may help to understand the molecular and cellular pathways underlying resolution of inflammation. We will put a special emphasis on pathways dependent on the IgG F_C-domain and IgG sialylation, as several recent studies have provided new insights into how this glycosylation-dependent pathway modulates innate and adaptive immune responses through different sets of C-type or I-type lectins.

Single-stage reconstruction of combined hypopharyngeal and anterior neck skin defects with the dual-paddle anterolateral thigh flap

Abstract

Background

The 'dual-paddle' anterolateral thigh (dpALT) flap has recently emerged as a single-stage reconstructive option for complex defects arising in the setting of pharyngolaryngectomy. We describe our technique, reflect on our initial experience and review this with reference to outcomes reported in the literature for the dpALT flap.

Methods

A single surgeon, multi-site retrospective study was performed for patients managed with a dpALT for combined hypopharyngeal and anterior neck defects. A standardised approach was devised for preoperative flap planning, harvest and inset. Peri-operative details were appraised and key outcome measures were assessed with particular reference to long-term anatomical and functional endpoints such as fistula and stricture formation, diet tolerability and speech intelligibility. A systematic review of the literature was also performed to identify all studies previously reporting outcomes for the dpALT in hypopharyngeal reconstruction.

Results

Seven patients received dpALT reconstruction for combined defects of the hypopharynx and anterior neck between 2009 and 2016. All flaps survived and five patients received the dpALT for a tubular reconstruction of the hypopharynx with two patches performed. Median follow-up was 27.4 months with no reported fistulas and a single case of stricture formation. Regular oral diet was achieved in six patients and alaryngeal speech was intelligible in all seven patients.

Conclusions

We report a high success rate with the dpALT flap for extensive hypopharyngeal defects that include an anterior neck skin component. The dpALT adds further to the armamentarium available to the reconstructive surgeon for complicated defects within the head and neck.

Level of Evidence: Level IV, therapeutic study.

Effect of menstrual cycle phase and hormonal treatments on evaluation of tubal patency in baboons

Abstract

Background

We evaluated whether menstrual cycle phase influences the assessment of tubal patency by hysterosalpingography (HSG) in baboons.

Methods

Retrospective analysis of baseline tubal patency studies and serum estradiol (E₂) and progesterone (P4) values obtained from female baboons used as models for development of non-surgical permanent contraception in women. The main outcome measure was bilateral tubal patency (BTP) in relationship with estradiol level.

Results

Female baboons (n = 110) underwent a single (n = 81), two (n = 26), or three (n = 3) HSG examinations. In 33/142 (23%) HSG examinations, one or both tubes showed functional occlusion (FO). The median E₂ in studies with BTP (49 pg/mL) was significantly higher than in those studies with FO (32 pg/mL, P = .005). Among 18 animals with repeat examinations where serum E₂ changed from <60 to ≥ 60 pg/mL, 13 results changed from FO to BTP (P = .0001). No sets showed a change from BTP to FO with an increase in estradiol.

Conclusion

In baboons, functional occlusion of the fallopian tube is associated with low estradiol levels, supporting a role for estrogen-mediated relaxation of the utero-tubal junction.

Recurrent heat shock impairs the proliferation and differentiation of C2C12 myoblasts

Abstract

Heat-related illness and injury are becoming a growing safety concern for the farmers, construction workers, miners, firefighters, manufacturing workers, and other outdoor workforces who are exposed to heat stress in their routine lives. A primary response by a cell to an acute heat shock (HS) exposure is the induction of heat-shock proteins (HSPs), which chaperone and facilitate cellular protein folding and remodeling processes. While acute HS is well studied, the effect of repeated bouts of hyperthermia and the sustained production of HSPs in the myoblast-myotube model system of C2C12 cells are poorly characterized. In C2C12 myoblasts, we found that robust HS (43 °C, dose/time) significantly decreased the proliferation by 50% as early as on day 1 and maintained at the same level on days 2 and 3 of HS. This was accompanied by an accumulation of cells at G2 phase with reduced cell number in G1 phase indicating cell cycle arrest. FACS analysis indicates that there was no apparent change in apoptosis (markers) and cell death upon repeated HS. Immunoblot analysis and qPCR demonstrated a significant increase in the baseline expression of HSP25, 70, and 90 (among others) in cells after a single HS (43 °C) for 60 min as a typical HS response. Importantly, the repeated HS for 60 min each on days 2 and 3 maintained the elevated levels of HSPs compared to the control cells. Further, the continuous HS exposure resulted in significant inhibition of the differentiation of C2C12 myocytes to myotubes and only 1/10th of the cells underwent differentiation in HS relative to control. This was associated with significantly higher levels of HSPs and reduced expression of myogenin and Myh2 (P < 0.05), the genes involved in the differentiation process. Finally, the cell migration (scratch) assay indicated that the wound closure was significantly delayed in HS cells relative to the control cells. Overall, these results suggest that a repeated HS may perturb the active process of proliferation, motility, and differentiation processes in an in vitro murine myoblast-myotube model.

Invasive squamous cell carcinoma: comparison of differentiation grade and tumour depth by anatomical site in 1666 tumours

Summary

Background

Invasive squamous cell carcinomas (SCCs) presents with different grades of differentiation and depths of invasion.

Aim

To compare the grade of differentiation, tumour diameter and tumour depth by anatomical site in invasive SCC.

Methods

Retrospective clinical and histopathological data on consecutive cases of SCC came from a clinic in Sydney, Australia were assessed. A multinomial logistic regression model was applied to compare grades of differentiation by age, sex, anatomical sites, and histological tumour maximum diameter and depth.

Results

In total, 1666 SCCs were identified, including 82.1% (n = 1367) well-differentiated, 13.3% (n = 222), moderately differentiated and 4.6% (n = 77) poorly differentiated SCCs. Patients with poorly differentiated tumours were more likely to be older and male (both P < 0.001). The most common site for poor differentiation was the scalp in men (n = 12; 15.6%) and the cheek or chin in women (n = 7; 9.1%). In the multivariate model, compared with well-differentiated SCC, older age was significantly associated with poorly and moderately differentiated SCC (P < 0.01 and P = 0.02, respectively). Larger tumour diameters were related to poor differentiation (P = 0.03). Ear, forehead and chest sites had increased tumour depth and poor differentiation.

Conclusions

This study found increased rates of poorly differentiated SCC on the forehead and cheek for both sexes, while men displayed increased rates of poorly differentiated SCC on the bald scalp and the ears. Tumour diameter and depth increased as tumours varied from well-differentiated to moderately differentiated and from moderately differentiated to poorly differentiated. An increase in depth and increased prevalence of poorly differentiated tumours were found on the ears for men and on various facial sites for both sexes.

In chronic spontaneous urticaria, high numbers of dermal endothelial cells, but not mast cells, are linked to recurrent angio-oedema

Summary

Background

Chronic spontaneous urticaria (CSU) is an inflammatory skin disorder characterized by recurrent weals, angio-oedema or both. Recent studies have shown that the number of endothelial cells is increased in the skin of patients with CSU, but the underlying mechanisms and clinical implications of this are unclear.

Aim

To evaluate whether mast cell (MC) or endothelial cell (EC) numbers correlate with CSU and whether they are relevant for disease duration, disease activity or the presence of clinical features.

Methods

We determined the numbers of CD31+ ECs and MCs in nonlesional skin of 30 patients with CSU using quantitative histomorphometry, and assessed their correlation with each other and with clinical features such as disease duration, disease activity and occurrence of angio-oedema.

Results

The numbers of MCs and ECs were high in the nonlesional skin of patients with CSU, but did not correlate with each other. Neither MC number nor EC number correlated with disease duration or disease activity. Interestingly, patients with high numbers of cutaneous CD31+ ECs had higher rates of recurrent angio-oedema and vice versa.

Conclusions

Based on these findings, we speculate that vascular remodelling and MC hyperplasia in patients with CSU occurs independently and via different mechanisms. Targeting of the mechanisms that drive neoangiogenesis in CSU may result in novel therapeutic strategies for the management of patients with angio-oedema.

Mehr Sicherheit in der geführten Implantologie

Zusammenfassung

Vor oraler Rehabilitation durch implantatgetragenen Zahnersatz wird inzwischen regelhaft ein digitales Volumentomogramm (DVT) angefertigt, anhand dessen das Knochenangebot dreidimensional bewertet werden kann. Nach dem Konzept des „backward planning" werden, ausgehend von der angestrebten Versorgung, die notwendigen präprothetischen Maßnahmen gezielt geplant. Prinzipiell gibt es unterschiedliche Vorgehensweisen, eine virtuelle Planung in die Realität umzusetzen. Die Navigation ist ein Verfahren, bei dem in Echtzeit die 3‑D-Position des Bohrers durch meist optische Systeme permanent überprüft wird und die korrekte Position und Achsneigung „chair-side" auf einem Bildschirm kontrolliert werden kann. Neben der navigationsgestützten kann die schablonengeführte Implantologie angewandt werden, bei der die Informationen über vorab geplante 3‑D-Positionierung eines Implantats in Bohrhülsen, die sich in einer Bohrschablone befinden, enthalten sind und durch starre Führung der Bohrer und Implantatinsertion umgesetzt werden. Die virtuell festgelegte Position wird dadurch reproduzierbar auf den Patienten übertragen. Zu unterscheiden sind bei der Anfertigung die separate Erstellung von Röntgen- und Bohrschablonen sowie die Herstellung der Bohrschablonen mit moderner 3‑D-Drucktechnik. Die geführte Implantologie gilt insbesondere bei limitiertem Knochenangebot als sicheres und präzises Verfahren. Sowohl die navigierte als auch die schablonengeführte Implantologie dienen dem Ziel, vitale Strukturen zu schonen, postoperative Komplikationen zu verringern und zu einem funktionell und ästhetisch optimalen Ergebnis zu gelangen. Eine präzise Planung, unter Einbeziehung chirurgischer und prothetischer Aspekte, beeinflusst in der Implantologie die Langzeitprognose wesentlich.

Correction to: Biochars mitigate greenhouse gas emissions and bioaccumulation of potentially toxic elements and arsenic speciation in Phaseolus vulgaris L.

Abstract

The original version of this article unfortunately contained a mistake. One affiliation and one author were missing. The corrected affiliations and authors are given here.

Repeated ultraviolet irradiation induces the expression of Toll-like receptor 4, IL-6, and IL-10 in neonatal human melanocytes

Summary

Background

Human melanocytes express Toll-like receptor 4 (TLR4), which regulates ultraviolet (UV)-induced cutaneous immunosuppression in Langerhans cells. Lipopolysaccharide (LPS) stimulation increases melanocyte pigmentation and TLR4 expression, while inducing local innate inflammatory responses.

Aims

We investigated whether UV radiation induces TLR4 expression in neonatal human melanocytes (NHMs) and how this affects the immune system.

Methods

We cultured NHMs with LPS treatment or with one-time or repeated UVA or UVB exposure, and investigated and compared the effects on TLR4 expression, melanin contents, and cytokine production.

Results

NHMs in the resting state did not express TLR4. LPS stimulation induced TLR4 expression and increased pigmentation. TLR4 expression was not detected after single-dose UVA or UVB treatment, but pigmentation increased. Repeated UV treatment induced TLR4 expression and increased pigmentation. LPS stimulation and repeated UV treatment increased IL-6 secretion, and repeated UVB treatment increased IL-10 secretion.

Conclusion

These results suggest that human melanocytes may actively participate in UV-induced immune modulation.

This article is protected by copyright. All rights reserved.

Occupational contact dermatitis caused by hydrogenated formaldehyde–benzenamine polymer (FBAP) in epoxy hardeners

In search of a better patch test concentration for povidone-iodine

Erythema multiforme-like reaction resulting from vitamin K1 oxide (phytomenadione epoxide)

Intractable pruritus with chronic eczema in an elderly patient caused by long-term intake of calcium channel blocker

Skin contact with a stinging tree requiring intensive care unit admission

Concomitant immediate and delayed sensitization by philodendron (Philodendron scandens) in a plant keeper

Occupational allergic contact dermatitis caused by isothiazolinones in ultrasound gel: 2 cases

Active sensitization to cadmium, tin, and indium

Editorial

Hand dermatitis: hand hygiene consequences among healthcare workers

Linear eczema on the amputation stump as a clinical clue to the diagnosis

Airborne contact dermatitis in a patient with type I and IV sensitivity to chicory

Erythema multiforme-like eruption induced by risedronate

A new application for epoxy resins resulting in occupational allergic contact dermatitis: the three-dimensional printing industry

Allergic contact stomatitis caused Salvadora persica in toothpaste

Septic Shock following Prostate Biopsy: Aggressive Limb Salvage for Extremities after Pressor-Induced Ischemic Gangrene

Summary: Vasopressors used to treat patients with septic shock can cause ischemic necrosis of appendages such as the ears and nose, as well as the extremities. Cases of quadruple-extremity necrosis have high morbidity and mortality, and a profound negative impact on quality of life. This case report details the successful limb salvage and return to function using free tissue transfer as a means to salvage bilateral lower extremities in a patient who suffered vasopressor-induced ischemia of upper and lower extremities after prostate biopsy–induced septic shock. Septic shock following transrectal ultrasound–guided prostate biopsy is a rare, yet life-threatening complication. Successful treatment included thorough planning and staging of therapies such as awaiting tissue demarcation and serial surgical debridement to adequately prepare the tissue bed for free tissue transfer. Adjunctive treatments such as hyperbaric oxygen therapy, negative-pressure wound therapy, and meticulous wound care played a crucial role in wound healing. This vigilant planning and coordinated care resulted in the successful lower extremity salvage, consisting of bilateral transmetatarsal amputations and free tissue transfer to both limbs. We present our long-term follow-up of a functional ambulatory patient after catastrophic, life-threatening infection and appropriate multidisciplinary care.