Clinical response to PD-1 blockade correlates with a sub-fraction of peripheral central memory CD4+ T cells in patients with malignant melanoma

Abstract

Cancer immunotherapy that blocks immune checkpoint molecules, such as PD-1/PD-L1, unleashes dysfunctional antitumor T-cell responses and has durable clinical benefits in various types of cancers. Yet its clinical efficacy is limited to a small proportion of patients, highlighting the need for identifying biomarkers that can predict the clinical response by exploring antitumor responses crucial for tumor regression. Here we explored T-cell responses associated with clinical benefits using peripheral blood mononuclear cells (PBMCs) from patients with malignant melanoma treated with anti-PD-1 monoclonal antibody (mAb). Pre- and post-treatment samples were collected from two different cohorts (discovery set and validation set) and subjected to mass cytometry assays that measured the expression levels of 35 proteins. Screening by high dimensional clustering in the discovery set identified increases in three micro-clusters of CD4⁺ T cells, a subset of central memory CD4⁺ T cells harboring CD27⁺FAS^-CD45RA^-CCR7⁺ phenotype, after treatment in long-term survivors, but not in non-responders. The same increase was also observed in clinical responders in the validation set. We propose that increases in this subset of central memory CD4⁺ T cells in peripheral blood can be potentially used as a predictor of clinical response to PD-1 blockade therapy in patients with malignant melanoma.

Implementation of a Regional Perinatal Data Repository from Clinical and Billing Records

Abstract

Objectives To describe the implementation of the first phase of a regional perinatal data repository and to provide a roadmap for others to navigate technical, privacy, and data governance concerns in implementing similar resources. Methods Our implementation integrated regional physician billing records with maternal and infant electronic health records from an academic delivery hospital. These records, representing births during 2013–2015, constituted a data core supporting linkage to additional ancillary data sets. Measures obtained from pediatric follow-up, urgent care, emergency, and inpatient encounters were linked at the individual level as were measures obtained by home visitors during pre- and postnatal encounters. Residential addresses were geocoded supporting linkage to area-level measures. Results Integrated data contained regional billing records for 69,290 newborns representing approximately 81% of all regional live births and nearly 95% of live births in the region's most populous county. Billing records linked to 7293 infant delivery hospital records and 7107 corresponding maternal hospital records. Manual review demonstrated 100% validity of matches among audited records. Additionally, 2430 home visiting records were linked to the data core as were pediatric primary care, urgent care, emergency department, and inpatient visits representing 42,541 children. More than 99% of the newborn billing records were geocoded and assigned a census tract identifier. Conclusions for Practice Our approach to methodological and regulatory challenges affords opportunities for expansion of systems to integrate electronic health records originating from additional medical centers as well as individual- and area-level linkage to additional data sets relevant to perinatal health.

Decision support tool for accidental pollution management

Abstract

Accidental river pollution can cause damage to the environment, put at risk the health of people that use the water for domestic purposes, and, not lastly, compromise dependent economic activities (e.g., agriculture). The reduction of the concentration of pollutant on any river following an accidental pollution can be achieved using dilution, by opening for certain duration the bottom gates of the reservoirs placed on the river's tributaries and releasing a significant volume of clean water in the main river. The hydraulic simulation and the pollutant transport are executed, firstly considering there is no dilution and secondly for the dilution scenario (bottom gates of the reservoirs open). A database was created, containing the results of simulations of pollutant transport for various values of the pollution characteristics in both diluted/undiluted scenarios. The database served for the implementation of a web decision support tool that presents an intuitive and easy to use GUI that allows the user to input details of the accidental pollution. Straightforward actions to be taken are presented to the end-user (e.g., "Open the bottom gates of the reservoir X at time T1 and close it at time T2") and synchronized charts show the effect of the dilution in respect to the concentration of pollutant at certain locations on the river. Using the described approach, a reduction of pollutant concentration in the river with up to 90% can be obtained.

Degradation reaction of Diazo reactive black 5 dye with copper (II) sulfate catalyst in thermolysis treatment

Abstract

The theme of present research demonstrates performance of copper (II) sulfate (CuSO₄) as catalyst in thermolysis process to treat reactive black 5 (RB 5) dye. During thermolysis without presence of catalyst, heat was converted to thermal energy to break the enthalpy of chemical structure bonding and only 31.62% of color removal. With CuSO₄ support as auxiliary agent, the thermally cleaved molecular structure was further destabilized and reacted with CuSO₄. Copper ions functioned to delocalize the coordination of π of the lone paired electron in azo bond, C=C bond of the sp² carbon to form C-C of the sp³ amorphous carbon in benzene and naphthalene. Further, the radicals of unpaired electrons were stabilized and RB 5 was thermally decomposed to methyl group. Zeta potential measurement was carried out to analyze the mechanism of RB 5 degradation and measurement at 0 mV verified the critical chemical concentration (CCC) (0.7 g/L copper (II) sulfate), as the maximum 92.30% color removal. The presence of copper (II) sulfate catalyst has remarkably increase the RB 5 dye degradation as the degradation rate constant without catalyst, k₁ is 6.5224 whereas the degradation rate constant with catalyst, k₂ is 25.6810. This revealed the correlation of conversion of thermal energy from heat to break the chemical bond strength, subsequent fragmentation of RB 5 dye molecular mediated by copper (II) sulfate catalyst. The novel framework on thermolysis degradation of molecular structure of RB 5 with respect to the bond enthalpy and interfacial intermediates decomposition with catalyst reaction were determined.

Measuring heavy metal stress in ryegrass using helium-cadmium excitation-based photoluminescence

Abstract

As the chemical analysis of heavy metal uptake and toxicity in plants is time-consuming, expensive, and destructive, a simple and reliable method for detecting heavy metal transfer from the soil to plants is thus necessary. We aimed to measure copper (Cu), lead (Pb), and cadmium (Cd) stress in ryegrass in vivo using plant photoluminescence based on a helium (He)-cadmium excitation source (wavelength 325 nm). The soils were combined with Cu, Pb and Cd, respectively. Fifteen ryegrass seedlings (Lolium multiflorum) were planted in each pot. After 30 days, leaves from seedlings at the fourth-leaf stage were collected and the fluorescence excitation spectra were detected using a He-Cd laser at an excitation wavelength of 325 nm. Three emission peaks that constitute known chlorophyll wavelengths, namely 450, 690, and 735 nm, were detected. These three peaks were strongly influenced by Cu, Pb, and Cd concentrations in the soil. Higher peak heights at 450 nm were observed with increasing Cu, Pb, and Cd concentrations in the soil, whereas no changes were noted at 690 and 735 nm. The P450/P690 and P450/P735 ratios were positively correlated with Cu, Pb, and Cd soil concentrations, ryegrass uptake, and DTPA-extractable Cu, Pb, and Cd in the soil. The related coefficients were all greater than 0.9. However, no correlation between the P690/P735 ratio, Cu, Pb, and Cd ryegrass uptake, and DTPA-extractable Cu, Pb, and Cd in the soil was observed. The measurement of plant photoluminescence in vivo using a He-Cd excitation source (wavelength 325 nm) may be utilized as an approach for monitoring the response of plants to specific stressors.

Potato tubers contamination with nitrate under the influence of nitrogen fertilizers and spray with molybdenum and salicylic acid

Abstract

A field trial was conducted through 2015 and 2016 growing seasons to study the effect of nitrogen fertilizer sources and foliar spray with molybdenum (Mo), salicylic acid (SA) and their combination on tubers yield, some chemical constituents, nutrients uptake, nitrate accumulation and nitrate reductase activity in potato tubers. N source was added at a rate of 350 kg N ha⁻¹in five equal doses as two different forms, the first is urea and the second is ammonium sulfate plus calcium nitrate equally. SA was sprayed with three rates of 0, 75 and 150 mg l⁻¹. Also, Mo as ammonium molybdate was sprayed using three rates 0, 50 and 100 mg l⁻¹Mo. Both treatments of SA and Mo were applied separately as well as with each other, at three successive times 30, 50 and 70 days after planting of potato plants. Results indicated that the addition of 350 kg N ha⁻¹ as ammonium sulfate and calcium nitrate equally caused a significant elevation (P > 0.05) in fresh weight, chlorophyll b, carotenoids, chlorophyll a, nitrate reductase activity, dry weight and NPK uptake by potato tubers compared with the same amount of nitrogen in the form of urea only. All the aforementioned characteristics were improved with increasing concentration of Mo and/or SA. The highest accumulation of nitrate was recorded under the addition of 350 kg N ha⁻¹ as urea alone. The highest average of all the aforementioned characteristics was observed at the treatment of 350 kg N ha⁻¹ as ammonium sulfate and calcium nitrate equally plus spraying with 100 mg l⁻¹Mo and 150 mg l⁻¹ SA. In contrast, this treatment gave the lowest accumulation of nitrates in potato tubers.

Migration of epoxidized soybean oil from polyvinyl chloride/polyvinylidene chloride food packaging wraps into food simulants

Abstract

Epoxidized soybean oil (ESBO) has been used in polyvinyl chloride (PVC)/polyvinylidene chloride (PVDC) food packaging cling film as a plasticizer and stabilizer. The aim of this study was to investigate the migration of ESBO from PVC/PVDC cling film, based on gas chromatography mass spectrometry (GC-MS). The specific migration of ESBO was evaluated using various food simulants (water, 4% acetic acid, 50% ethanol and n-heptane) for PVC and PVDC wrap products. ESBO did not migrate into water and 4% acetic acid for all the tested samples. However, it was released into 50% ethanol and n-heptane in several PVC/PVDC wraps, with maximum migration levels of 38.4 ± 0.7 and 37.4 ± 0.8 μg/mL, respectively. These results demonstrate that ESBO is capable of being released from PVC/PVDC wrap into amphiphilic/oily food and its migration should be regularly monitored.

Effects of low-level engineered nanoparticles on the quorum sensing of Pseudomonas aeruginosa PAO1

Abstract

The toxicity of engineered nanoparticles (ENPs) on bacteria has aroused much interest. However, few studies have focused on the effects of low-level ENPs on bacterial group behaviors that are regulated by quorum sensing (QS). Herein, we investigated the effects of nine ENPs (Ag, Fe, ZnO, TiO₂, SiO₂, Fe₂O₃, single-wall carbon nanotubes (SWCNTs), graphene oxide (GO), and C₆₀) on QS in Pseudomonas aeruginosa PAOl. An ENP concentration of 100 μg L⁻¹ did not impair bacterial growth. However, concentrations of 100 μg L⁻¹ of Ag and GO ENPs induced significant increases in 3OC₁₂–HSL in the culture and significantly promoted protease production and biofilm formation of PAO1. C₄–HSL synthase and its transcription factors were less sensitive to 100 μg L⁻¹ Ag and GO ENPs compared with 3OC₁₂-HSL. Fe ENPs induced a significant increase in the 3OC₁₂–HSL concentration, similar to Ag and GO ENPs. However, Fe ENPs did not induce any significant increase in protease production or biofilm formation. Different size distributions, chemical compositions, and aggregation states of the ENPs had different effects on bacterial QS. These whole circuit indicators could clarify the effects of ENPs on bacterial QS. This study furthers our understanding of the effects of low-level ENPs on bacterial social behaviors.

Epstein–Barr virus exanthem in an adult patient with myelodysplastic syndrome

Ischaemic ulcers on the toes secondary to Raynaud phenomenon in a patient with systemic sclerosis successfully treated with botulinum toxin

2018, Forward, Going Online and all that...

Issue Information

SMR Congress 2017 abstracts

Improved Photophysical and Photochemical Properties of Thiopheneethoxy Substituted Metallophthalocyanines on Immobilization onto Gold-speckled Silica Nanoparticles

Abstract

This work reports on the synthesis of tetrakis–[(thiophineethoxy) phthalocyaninato] indium(II) chloride (3). The photophysical behaviour of complex 3 was compared to that of the Zn derivative (tetrakis–[(thiophineethoxy) phthalocyaninato] zinc(II) (complex 2)). The compounds were interacted with gold–speckled silica (GSS) nanoparticles via Au–S self assembly to afford the conjugates (2–GSS and 3–GSS). The photophysicochemical behaviour of the compounds and their conjugates were assessed. The conjugates afforded a decrease in fluorescence quantum yields and lifetimes with improved triplet and singlet oxygen quantum yields in comparison to complexes 2 and 3 alone. The complexes and their conjugates could serve as good candidates for photodynamic therapy.

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Folliculotropism in pigmented facial macules: Differential diagnosis with Reflectance confocal microscopy

Abstract

Pigmented facial macules are common on sun damage skin. The diagnosis of early stage lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging. Reflectance confocal microscopy (RCM) has been proven to increase diagnostic accuracy of facial lesions.

A total 154 pigmented facial macules, retrospectively collected, were evaluate for the presence of already described RCM features and new parameters depicting aspects of the follicle .

Melanocytic nests, roundish pagetoid cells, follicular infiltration, bulgings from the follicles and many bright dendrites, and infiltration of the hair follicle (i.e. folliculotropism) were found to be indicative of LM/LMM compared to non-melanocytic skin neoplasms, with an overall sensitivity of 96% and specificity of 83%. Concerning non-melanocytic skin neoplasms, solar lentigo and lichen planus-like keratosis resulted better distinguishable from LM/LMM because usually lacking malignant features and presenting characteristic diagnostic parameters, such as cepidermal cobblestone pattern and polycyclic papillary contours. On the other hand, distinction of pigmented actinic keratosis (PAK) resulted more difficult, and needing evaluation of hair follicle infiltration and bulging structures, due to the frequent observation of few bright dendrites in the epidermis, but predominantly not infiltrating the hair follicle (estimated specificity for PAK 53%). .

A detailed evaluation of the components of the folliculotropism may help to improve the diagnostic accuracy. The classification of the type, distribution and amount of cells, and the presence of bulging around the follicles seem to represent important tools for the differentiation between PAK and LM/LMM at RCM analysis.

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Reply to: “An exploratory study using framework analysis to investigate health-seeking behaviour in patients with psoriasis”

Abstract

We recently read with interest "An exploratory study using framework analysis to investigate health-seeking behaviour in patients with psoriasis" by Simpson et al. This interview based-study added to the understanding of obstacles patients face when seeking psoriasis treatment. Given the recent advances in effective systemic treatment options for psoriasis, we were similarly interested in exploring the discordance between available therapies and patient satisfaction and outcomes using a survey in a larger series of patients.

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Novel POFUT1 mutation associated with hidradenitis suppurativa-Dowling Degos Disease firm up a role for Notch signalling in the pathogenesis of this disorder: reply from authors

Abstract

We thank González-Villanueva et al. for their comments and commend them for their intriguing results. They report on a single patient with clinical and histopathological evidence for Dowling-Degos disease. In addition, the patient developed hidradenitis suppurativa. The patient was found to carry a mutation in POFUT1, a gene previously known to be associated with Dowling-Degos disease.

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Preface

Surgery for thyroid disease encompasses a broad spectrum of procedures involving multiple disease entities. Thyroid surgery may range from simple isthmusectomy/lobectomy to expansive procedures which involves bilateral cervical lymphadenectomy, resection of upper aerodigestive tract elements and mediastinal dissection. Accordingly, these procedures are accompanied by varying degrees of difficulty in the execution of many of the surgical maneuvers involved in performing a safe and successful operative procedure.

Substernal thyroidectomy: the trans-cervical approach

Substernal thyroid goiters that require surgery may pose unique challenges to thyroid surgeons based on the size and inferior extent of the disease. Consequently, there are multiple variations to the approach and additional considerations in operative planning and technique that are often required. While there is some debate on the precise definition of substernal thyroid, for the purposes of this manuscript it is considered to be thyroid tissue below the sternal notch or clavicle. This article aims to provide thyroid surgeons who encounter the challenges of substernal thyroid a straightforward algorithm for planning and operative techniques that have proven successful in the safe and effective management of this condition.

Techniques for thyroid cancer involving extreme superior thyroid pole

Standard operative techniques for thyroidectomy have become well refined and widely disseminated. However, special circumstances, such as superior pole thyroid cancers, can present unique difficulties for the unprepared surgeon. Appropriate workup and appreciation of the unique anatomic relationships in the superior-most extent of the thyroid gland is vital in surgical planning. The ability to anticipate and manage a variety of contingencies such as superior laryngeal nerve sacrifice, vascular isolation / repair, laryngectomy, and repair of pharyngeal defects are essential for safe surgery for cancers of the extreme superior thyroid pole.