Molecular mechanisms of acquired resistance to third-generation EGFR-TKIs in EGFR T790M-mutant lung cancer

Ann Oncol 2018; 29: i28–i37 (doi:10.1093/annonc/mdx705)

Phase II study of nab-paclitaxel in refractory small bowel adenocarcinoma and CpG island methylator phenotype (CIMP)-high colorectal cancer

Ann Oncol 2018; 29: 139–144 (doi:10.1093/annonc/mdx688)

Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium

Ann Oncol 2017; 28: 2517–2525 (doi:10.1093/annonc/mdx352)

Vertebral Compression Fractures in Elderly: How to Recognize and Report

Abstract

Purpose of Review

In elderly patients, when there is no obvious evidence of malignancy on plain radiography, it can be difficult to evaluate benign and malignant vertebral fractures, because these patients are predisposed to senile osteoporosis and malignant disease. The only complaint could be back pain, as both types of fractures have the same symptoms and signs.

Recent Findings

A reliable imaging modality is always required, as appropriate management and early diagnosis of malignant vertebral fractures are important.

Summary

The aim of this study was to highlight the importance of recognizing, through diagnostic techniques, the presence of vertebral fractures, since the majority of vertebral fractures do not come to clinical attention and to determine the parameters that are useful for the early differentiation between benign versus malignant vertebral fractures.

Advanced oxidation of antihypertensives losartan and valsartan by photo-electro-Fenton at near-neutral pH using natural organic acids and a dimensional stable anode-gas diffusion electrode (DSA-GDE) system under light emission diode (LED) lighting

Abstract

In this work photo-electro-Fenton (PEF) processes using a dimensionally stable anode-gas diffusion electrode (DSA-GDE) system under light emission diodes (LED)-type radiation were used in the degradation of the angiotensin-II-receptor antagonists (ARA II), valsartan (VAL), and losartan (LOS), which are used in the treatment of hypertension diseases, and are considered among the emerging contaminants (ECs). Organic acids as citric, tartaric, and oxalic acids were used as complexing agents of iron ions in order to maintain the performance of the Fenton reaction at near-neutral pH value. The results show that at 3.42 mA/cm² after 90 min of electro-Fenton (EF) treatment, degradation of 70% of VAL and 100% of LOS were observed. Total degradation of VAL and LOS was reached with a PEF process at the same time with mineralization of 30%. When citric and tartaric acids were used instead of oxalic acid, similar results were obtained, i.e., total degradation of both compounds, LOS and VAL, after 90 min of treatment. The degradation performance can be attributed to the increase of the initial dissolved iron in the system, facilitating the Fe³⁺/Fe²⁺ turnover in the catalytic photo-Fenton reaction and consequently, hydroxyl radical (^•OH) production. In addition, the increased photo-activity of the complexes can be associated with their high capability to complex Fe³⁺ and to promote ligand-to-metal charge transfer, which is of key importance to feed Fe²⁺ to the Fenton process. The results show that the system evaluated was more efficient to eliminate sartan family compounds using LED lighting in comparison with traditional UV-A lamps used in this kind of work. Moreover, three transformation products of VAL degradation and two transformation products of LOS degradation were identified by high-resolution mass spectrometry (HRMS) using hybrid quadrupole-time-of-flight (QTOF) MS and, at the end of the PEF system, the several organic compounds accumulated and no mineralized were effectively treated in a subsequent aerobic biological system.

Tamarind seed coat extract restores fluoride-induced hematological and biochemical alterations in rats

Abstract

Fluoride (F⁻) is becoming an ineluctable environmental pollutant causing deleterious effects in humans. In the present study, we examined whether tamarind seed coat extract (TSCE) is beneficial against the F⁻-induced systemic toxicity and hematological changes. Wistar rats were randomly grouped as follows: group I served as control; group II intoxicated with sodium fluoride (NaF, 300 ppm) in drinking water; group III was administered through oral intubation with TSCE (100 mg/kg bw); group IV was treated with NaF (300 ppm) in association with TSCE (100 mg/kg bw) for 30 days. The results indicated that F⁻ exposure induced oxidative stress as evidenced by elevated levels of reactive oxygen species and lipid peroxidation in the brain, liver, and kidney. F⁻ administration modulates hematological indices—WBC, RBC, and mean corpuscular volume. Moreover, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, acetylcholinesterase, and monoamine oxidase significantly increased on F⁻ exposure. Conversely, δ-aminolevulinic acid dehydratase and glutathione/reduced glutathione ratio were decreased. Activity of antioxidants—superoxide dismutase, catalase, glutathione peroxidase, and vitamin C—was also significantly decreased due to F⁻ administration. Treatment with TSCE effectively mitigated the alterations through its antioxidant potential. The data suggested that the TSCE had beneficial effects in alleviating the F⁻-induced toxicity and hence can serve as a promising neutraceutical agent.

EXTRACAPSULAR DISSECTION AND LIMITED PAROTIDECTOMY

Parotid surgery has evolved over the last century. Many of the long-held principles have been questioned and consequently modified. The basic tenets of parotid surgery for benign disease have been identifying and preserving the facial nerve and complete excision of the tumor with an adequate cuff of normal tissue. This can be safely accomplished by extracapsular dissection or limited/partial parotidectomy. Extracapsular dissection implies no attempt at finding the facial nerve, while limited or partial parotidectomy includes finding one (or more) branch of the facial nerve and then dissecting that branch in a retrograde fashion.

Neck dissection for salivary gland malignancies

Salivary gland carcinomas are diverse, and their biological behavior and surgical management are also variable and somewhat controversial. Cervical lymph node status is an important prognostic variable for salivary gland malignancies. Neck dissection should be undertaken if there is clinical or radiographic evidence of associated nodal metastasis in the neck. However, indications for elective neck dissections in a clinically N0 neck remains a controversial topic. This article describes indications for elective neck dissection in salivary gland malignancies, provides a detailed review of the neck dissection technique, and discusses postoperative management of these patients.

Sublingual Gland

It is infrequent for surgery to be necessary for the sublingual salivary gland. As such the anatomy of the floor of mouth is not well taught or understood to medical graduates and head and neck surgeons. Three diseases or conditions require surgical management: the ranula, neoplasm and sialolithiasis. In the benign conditions, the lingual nerve and submandibular duct must be identified and preserved to avoid patient morbidity. Malignant salivary gland neoplasms are rare, and hence an inaccurate diagnosis frequently delayed commencement of correct treatment.

A Phase 2, Randomized Dose-Finding Study of Tapinarof (GSK2894512 Cream) for the Treatment of Atopic Dermatitis

Safe and efficacious topical treatments are needed for atopic dermatitis (AD).

Apremilast for moderate hidradenitis suppurativa: results of a randomized controlled trial

Effective anti-inflammatory treatments for hidradenitis suppurativa (HS) are limited.

A Comparison of Skin Cancer Screening and Treatment Costs at a Massachusetts Cancer Center, 2008 versus 2013

Temporal analyses of skin cancer costs are needed to examine how expenditure differences between diagnoses are changing.

Chronic Non-Melanoma Skin Cancers and Health Related Impairment: A Case-Control Study

Kinetics, mechanism, and global warming potentials of HFO-1234yf initiated by O 3 molecules and NO 3 radicals: insights from quantum study

Abstract

In the present investigation, the oxidation of HFO-1234yf (2,3,3,3-tetrafluoropropene) with O₃ molecule and NO₃ radical is studied by quantum chemical methods. The possible reaction pathways of the titled molecule with O₃ molecule and NO₃ radical are analyzed using M06-2X meta-hybrid density functional with the 6-311++G(d,p) basis set. We have further employed a series of single-point energy calculations by using a potentially high-level couple cluster method with single and double excitations, including perturbative corrections ((CCSD(T)) at the same basis set. The addition reaction of HFO-1234yf with O₃ molecule is initiated by the formation of primary ozonide complex, which leads to the formation of various carbonyl compounds and Criegee intermediates. The calculated energy barriers and thermochemical parameters inferred that decomposition of C˙H₂OO˙ and CF₃CFO is slightly more preferred over the formation of CF₃C˙FOO˙ and CH₂O. Further, the NO₃ radical addition at α- and β-sits of CF₃CF〓CH₂ molecule is analyzed in details. The individual and overall rate constants for each reaction pathways are calculated by using canonical transition state theory over the temperature range of 250–450 K. We have observed that the computed rate constants are in good agreement with the available experimental data. Atmospheric lifetimes and global warming potentials of the HFO-1234yf are also reported in this manuscript.

Underuse of the Sentinel Lymph Node Biopsy for High-Risk SCC of the Skin—Reply

In Reply We read with interest the response by Glazer et al regarding our study on the underuse of sentinel lymph node biopsy (SLNB) for high-risk cutaneous squamous cell carcinoma (cSCC) and noted several important inquiries and comments.

Onychomadesis Following a Fish Pedicure

This case reports describe the occurrence of onychomadesis in a patient following a fish pedicure.

An Annular Eruption in a Young Child

A young child had a 6-month history of an asymptomatic expanding erythematous eruption on the lower legs, abdomen, and buttocks; clinical examination was significant for faint, nonscaling annular serpiginous, erythematous plaques. What is your diagnosis?

Prescription to OTC Switch of Metronidazole and Azelaic Acid for Rosacea

This Viewpoint considers the advantages and disadvantages of topical treatments for rosacea, specifically metronidazole and azelaic acid, undergoing review to switch from prescription to over-the-counter availability.

The Future of JAMA Dermatology

I am deeply humbled to be selected to serve as Editor in Chief of JAMA Dermatology. The fundamental role of an editor in chief is to review, select, and publish the articles that best help clinicians practice more safely and effectively. The opportunity to illuminate the aspects of our field that deserve spotlight is a task both daunting and delightful. I am committed to do a deep dive into dermatology to identify what is most significant, what is most fascinating, what is most problematic, and to find opportunities to improve and elevate the practice of dermatologists. My ultimate goal is to ensure that dermatologists deliver the best patient care possible, and I consider it an incredible honor to be able to contribute to the specialty through this work.

Dupilumab Treatment of Very Severe Refractory Atopic Hand Eczema

This case report describes the use of dupilumab to treat a patient with very severe refractory atopic hand eczema.

Underuse of the Sentinel Lymph Node Biopsy for High-Risk SCC of the Skin

To the Editor We read with interest the article by Ahadiat et al regarding the potential underuse of sentinel lymph node biopsy (SLNB) in patients with high-risk cutaneous squamous cell carcinoma (cSCC). Although SLNB may be underused in these patients, we have some inquiries regarding the research methods and generalizability of the data.

Human Papillomavirus Vaccine to Treat Cutaneous Basaloid Squamous Cell Carcinomas

This case report describes a woman with multiple, inoperable cutaneous basaloid squamous cell carcinomas who was treated with 9-valent human papillomavirus vaccine.

Association of Inadequately Controlled Disease With Patient-Reported Disease Burden in Atopic Dermatitis

This cross-sectional study examines the association of atopic dermatitis severity and disease control with the patient-reported disease burden in clinical practice.

Assessment of arsenic removal efficiency by an iron oxide-coated sand filter process

Abstract

Arsenic is among the most dangerous contaminants which can limit groundwater use for drinking water consumption. Among the most diffused As-removal technologies around the world, adsorptive media systems are usually favored for relatively low cost and simplicity of operation. This study examines the performance of a laboratory-scale iron oxide-coated sand (IOCS) column filter, to remove arsenic (arsenate (As[V]) and arsenite (As[III])) from groundwater. This technology could be adopted in small communities, as it showed consistent removal rates of 99% with an easy-to-operate process. Some considerations about the possible introduction of such technology in developing countries are provided, highlighting the general impacts to human health related to high arsenic concentrations in groundwater. This, among other adsorption processes, could be recommended as a sustainable mean of ensuring good drinking water quality in developing regions, reducing human health impacts.

Partitioning of absorbed light energy within photosystem II in barley can be affected by chloroplast movement

Publication date: Available online 2 July 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): J. Semer, M. Štroch, V. Špunda, M. Navrátil
Plants have developed many ways to protect reaction centres of photosystems against overexcitation. One of the mechanisms involves reduction of the leaf absorption cross-section by light-induced chloroplast avoidance reaction. Decrease in the probability of photon absorption by the pigments bound within photosystem II (PSII) complexes leads to the increase in quantum yield of PSII photochemistry (ΦPSII). On the other hand, the decrease of PSII excitation probability causes reduction of chlorophyll a fluorescence intensity which is manifested as the apparent increase of determined quantum yield of regulated light induced non-photochemical quenching (ΦNPQ). Absorption of different light intensity by phototropins led to the different chloroplast distribution within barley leaves, estimated by measurement of the leaf transmittance. Due to a weak blue light used for transmittance measurements, leaves exposed to actinic light with wavelengths longer than 520 nm undergo chloroplast accumulation reaction, in contrast with leaves exposed to light with shorter wavelengths, that showed a different extent of chloroplast avoidance reaction. Based on the ΦNPQ action spectra measured simultaneously with the transmittance, the influence of different chloroplast distribution on ΦNPQ was assessed. The analysis of results showed that decrease in the leaf absorption cross-section due to increasing part of chloroplasts reaching profile position significantly affected the partitioning of excitation energy within PSII and such rearrangement also distorted measured ΦNPQ and cannot be neglected in its interpretation. When the majority of chloroplasts reached profile position the photoprotective effect appeared to be the most prominent for strong blue light that has the highest absorption in the upper leaf layers in comparison with green or red ones.

Tuning the chain length of new pyrene derivatives for site-selective photocleavage of avidin

Publication date: Available online 2 July 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Sudarat Yenjai, Challa V. Kumar, Mayuso Kuno, Teerayuth Liwporncharoenvong, Siritron Samosorn, Apinya Buranaprapuk
Rational design of photoreagents with systematic modifications of their structures can provide valuable information for a better understanding of the protein photocleavage mechanism by these reagents. Variation of the length of the linker connecting the photoactive moiety with the protein anchoring-group allowed us to investigate the control of the protein photocleavage site. A series of new photochemical reagents (PMA-1A, PMA-2A and PMA-3A) with increasing chain lengths is examined in the current study. Using avidin as a model system, we examined the interaction of these probes by UV–Vis, fluorescence spectroscopic methods, photocleavage and computational docking studies. Hypochromism of the absorption spectrum was observed for the binding of these new photochemical reagents with estimated binding constants (Kb) of 6.2 × 10⁵, 6.7 × 10⁵ and 4.6 × 10⁵ M⁻¹, respectively. No significant changes of Stern-Volmer quenching constant (Ksv) with Co(NH3)6Cl3 has been noted and the data indicated that the probes bind near the surface of the protein with sufficient exposure to the solvent. Photoexcitation of the probe-avidin complex, in the presence of Co(NH3)6Cl3, resulted in protein fragmentation, and the cleavage yield decreased with the increase in the linker length, and paralleled with the observed Ksv values. Amino acid sequencing of the photofragments indicated that avidin is cleaved between Thr77 and Val78, as a major cleavage site for all the three photoreagents. This site is proximate to the biotin binding site on avidin, and molecular docking studies indicated that the H-bonding interactions between the polar end-group of the photoreagents and hydrophilic amino acids of avidin were important in positioning the reagent on the protein. The major cleavage site, at residues 77–78, was within 5 Å of the pyrenyl moiety of the probe, and hence, molecular tuning of the linker provided a simple approach to position the photoreagent along the potential photocleavage site.

Graphical abstract

The percentage of patients achieving complete remission of urticaria increases with repeated courses of treatment

Publication date: Available online 2 July 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Andrea Matucci, Francesca Nencini, Oliviero Rossi, Sara Pratesi, Paola Parronchi, Enrico Maggi, Alessandra Vultaggio

Environmental Endocrinology: Insights Into the Diversity of Regulatory Mechanisms in Life Cycles

Abstract

All organisms must time their life cycles appropriately and organize life history stages into temporal sequences that enhance fitness in a changing environment. The endocrine system plays a major regulatory role in transducing information from the environment into morphological, physiological and behavioral responses appropriate for the time of year. The perception, transduction, response pathways via neural and endocrine mechanisms are beginning to be explored and underscore the critical regulatory roles they play. Whereas many conserved mechanisms (evolutionary constraints hypothesis) are emerging, there is a growing realization that there may be alternate pathways unique to populations and individuals (evolutionary flexibility hypothesis). Field investigations (field endocrinology) over the past 45 years have revealed patterns of hormonal responses to environmental changes, physical and social, that could not have been anticipated from laboratory investigations alone. These patterns include differences at population and individual levels that have enabled new insights into acclimation and adaptation to environmental transitions. The number of species studied under natural conditions has grown exponentially in recent years to include all vertebrate classes and some invertebrates as well. These data are now driving evolutionary perspectives and with the advent of comparative genomics a new and exciting era of evolutionary/ecological endocrinology is developing. This paper gives a brief overview of where the field stands now and where it is likely to go in the future especially in relation to the networks of regulatory pathways and how they can be modulated to enable acclimation of individuals as well as populations. One illustrative example, mechanisms underlying modulation of the adrenocortical responses to environmental stress, is the focus of this communication. These "coping" mechanisms will be key for acclimation and adaptation to global change.

Application of Box–Behnken design and desirability function in the optimization of Cd(II) removal from aqueous solution using poly(o-phenylenediamine)/hydrous zirconium oxide composite: equilibrium modeling, kinetic and thermodynamic studies

Abstract

In this research work, poly(o-phenylenediamine) was incorporated into the hydrous zirconium oxide matrix to form poly(o-phenylenediamine)/hydrous zirconium oxide composite which is used for the removal of Cd(II) from aqueous solution. The characterization of the material was done based on FTIR, XRD, SEM, and TGA-DTA. The effects of contact time, pH, adsorbent dose, and initial concentration of Cd(II) on the removal of Cd(II) were studied by performing 29 sets of sorption runs using Box–Behnken design combined with response surface methodology (RSM). Various isotherm models were tested to describe the adsorption equilibrium. The adsorption equilibrium data fitted well with Freundlich isotherm model. The maximum adsorption capacity of 66.66 mg g⁻¹ was obtained from Langmuir isotherm. The pseudo-second-order kinetic model described the adsorption kinetics more accurately. Diffusion-based kinetics such as intraparticle diffusion and Bangham's model suggested that both film and intraparticle pore diffusion were involved in the adsorption process. The Elovich model pointed towards the chemisorption. The investigation of desorption and regeneration suggested that the material can be used as an effective sorbent for removal of Cd(II) from aqueous system.

Microbial fuel cell and membrane bioreactor coupling system: recent trends

Abstract

Membrane bioreactor (MBR) and microbial fuel cell (MFC) are new technologies based on microbial process. MBR takes separation process as the core to achieve the high efficient separation and enrichment the beneficiation of microbes during the biological treatment. MFC is a novel technology based on electrochemical process to realize the mutual conversion between biomass energy and electric energy, in order to solve the problems of serious membrane fouling and low efficiency of denitrification in membrane bioreactor, the low power generation efficiency, and unavailability of bioelectric energy of MFC. In recent years, MFC-MBR coupling system emerged. It can effectively mitigate the membrane fouling and reduce the excess sludge production. Simultaneously, the electricity can be used effectively. The new coupling system has good prospects for development. In this paper, we summarized the research progresses of the two kinds of coupling systems in recent years and analyzed the coupling structure and forms. Based on the above, the future development fields of the MFC-MBR coupling system were prospected.

Fate of PAHs in the vicinity of aluminum smelter

Abstract

Investigation has been carried out in the vicinity of an aluminum smelter located in the industrialized town of Konin. Concentrations of 14 polycyclic aromatic hydrocarbons (PAHs) were determined in grass, spruce needles, and soil collected in the period of the smelter operation and several years after its closing. Significant changes in the quantity of PAHs and their profiles observed in the two measuring periods, stressing the importance of aluminum production with regard to PAH emission. It was confirmed by very high values of the carcinogenic potential (CP) found for PAHs accumulated in grass and soil when compared to the values found in urban and remote sites. PAH ratio rates used as a tool for identifying emission sources showed a pyrogenic origin of PAHs in both periods; the ratios in the period of the smelter running activity were similar to those found in other studies carried out near aluminum smelters. Grass turned out to be a good biomonitor of PAHs similarly to commonly used leaves of various tree species. The use of four age classes of spruce needles, some of which were subjected to emission from the smelter, showed that such approach could serve as an analysis tool for describing retrospective pollution.

Evaluation of psychiatric hospital wastewater toxicity: what is its impact on aquatic organisms?

Abstract

The primary source of pharmaceuticals to the aquatic environment is the discharge of wastewater effluents. Pharmaceuticals are a large and diverse group of compounds. Among them, psychotropic substances are particularly interesting to study due to their specific known mode of action. The present study was performed to investigate the effects of wastewater effluents from a psychiatric hospital wastewater treatment plant (WWTP) on several aquatic organisms. All the analyzed pharmaceuticals (10 compounds) were detected in WWTP effluents as well as in the receiving river. Although the environmental concentrations were generally at trace levels (ng L⁻¹ to μg L⁻¹), induce toxic effects were observed. This study showed the effects of the WWTP effluents on the oogenesis and/or embryogenesis of amphipod crustacean Gammarus fossarum, Japanese fish medaka Oryzias latipes, mollusk Radix peregra, and planarian Schmidtea polychroa. A decrease of the number of oocytes and produced embryos was observed for G. fossarum and S. polychroa. Similarly, the hatching rate of R. peregra was affected by effluents. In the receiving river, the macroinvertebrate community was affected by the wastewater effluents discharge.

Vertebroplasty in Elderly Patients: A Clinical Effectiveness Analysis

Abstract

Purpose of Review

Minimally invasive vertebral augmentation procedures (VAP) have been first introduced to provide pain relief in patients with osteoporotic vertebral fractures (VF). However, in the last decade scientific literature revealed to be quite controversial about their efficacy. The aim of this review was to analyze clinical evidences from current literature, supported by our own experience.

Recent Findings

Compared to conservative therapies, VAP represent an effective treatment for recent VF and, in elderly patients, reduce mortality and morbidity. Advances in technology have widened the fields of application towards other spine pathologies typical of elderly, such as primary and metastatic tumors.

Summary

In patients with severe pain for recent or un-healed vertebral fracture, VAP are clinically more effective than conservative treatment. Accurate pain assessment and pre-procedural Magnetic Resonance Imaging are highly recommended to obtain optimal patient selection and best treatment results.

Peer Review to Peer Learning in Radiology: Where Have We Been, What Have We Learned and Where Are We Headed?

Abstract

Purpose of review

To review and contrast varying methods of peer assessment driven practice quality improvement programs in radiology with an emphasis on peer review and peer learning.

Recent findings

Review of the literature revealed that the current consensus is that a shift away from the original peer review system toward a peer learning process has the most beneficial effects for organizations seeking to maximally improve performance. This requires altering perceptions towards the peer review process itself, and significant time, effort, and resources.

Summary

The transition to a peer learning process is a necessity to advance the field of radiology into an era of delivering near faultless quality health care.

PET/CT and Bone Scintigraphy: Metabolic Results in Musculoskeletal Lesions

Abstract

Purpose

This review aimed to provide an overview on findings from metabolic imaging modalities such as bone scintigraphy and positron emission tomography–computed tomography (PET/CT) in musculoskeletal lesions. It is conceivable that methods assessing metabolism of bone tumors, combined with the morphological assessment, could enhance the possibility for a personalized therapy with particular emphasis to malignant neoplasms.

Recent Findings

The assessment of bone tumors by conventional scintigaphic and morphological imaging has been recently integrated with the morpho-metabolic appraisal obtained by PET/CT systems. Increasing availability of this diagnostic modality has been shown to stratify properly the patients and the findings correlate well with outcome. Moreover, new tracers are being implemented in the study of musculoskeletal lesions by PET/CT while the new volumetric parameters used to identify the lesions hold great promise.

Summary

Results from PET/CT are associated with tumor grading and histopathology in bone malignant lesions and they could be of value for implementing treatment strategy. Additionally, the metabolic assessment has been demonstrated useful for predicting surgical response and patients' outcome.