Lichen Planus triggered by infliximab biosimilar CT-P13 and recurred during secukinumab treatment

Abstract

we read with interest the manuscript published by Gonzales et al,¹ highlighting lichenoid reactions as an emerging side effect of biologics, with special regard to infliximab-biosimilar. We recently observed a 50-year-old male patient with a long-standing history of moderate-to-severe psoriasis, who developed oral lichen planus (LP) triggered by infliximab biosimilar CT-P13. Interestingly the same patient experienced cutaneous and oral LP when treated with IL-17A blocker, secukinumab. The patient suffered for hypertension, in treatment with valsartan, and anxiety. He previously failed to respond to phototherapy, methotrexate, etanercept and adalimumab.

This article is protected by copyright. All rights reserved.

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Irradiance, as well as body site and timing of readings, is important in determining ultraviolet A minimal erythemal dose

Abstract

Irradiance, as well as body site and timing of readings, is important in determining ultraviolet A minimal erythemal dose. (Response to Gambichler et al. July BJD)

Gambichler et al. demonstrated that, in their population, using a 25 mWcm⁻² ultraviolet A-1 (UVA-1) source the median 24-hour delayed minimal erythema dose (MED) on the inner forearm was > 130 Jcm⁻².¹ This differs from the 20 Jcm⁻² to 28 Jcm⁻² median MED reported from our centre.²

This article is protected by copyright. All rights reserved.

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Risk of malignancies associated with ustekinumab

Abstract

A recently published report by Florek et al.¹ associates malignancies with ustekinumab (STELARA^®) treatment. Janssen emphasizes patient safety and welcomes rigorous safety analyses from other parties. However, it is unclear how this report adds to the understanding of ustekinumab's safety profile.

This article is protected by copyright. All rights reserved.

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Low-dose valganciclovir prophylaxis for cytomegalovirus in intermediate-risk (R+) renal transplant recipients: single center experience

Abstract

Renal transplant recipients (RTR) who are seropositive for CMV (R+) are considered to be at intermediate-risk for CMV disease. Current guidelines recommend high-dose valganciclovir (VGCV) prophylaxis because of limited data on the efficacy of low-dose VGCV. We describe our experience with using low-dose VGCV in R+ RTR. We retrospectively reviewed a cohort of 316 R+ RTR at our institution between 2002 and 2006. The primary endpoint was CMV disease at 1 year post transplant. The incidence of CMV disease at 12 months after transplantation was only 3% (6/221) in the D+R+ and 4% (4/95) in the D-R+ RTR. Low-dose VGCV was effective at preventing CMV disease in intermediate-risk (R+) RTR.

This article is protected by copyright. All rights reserved.

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Biochars derived from giant reed ( Arundo donax L.) with different treatment: characterization and ammonium adsorption potential

Abstract

The adsorption characteristics of Arundo donax L.(AD) biochars for ammonium(NH₄⁺-N) were investigated. Absorbents were characterized through scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy analyses. AD-500 and AD-800 were produced from raw AD and pyrolyzed from room temperature to 500 and 800 °C, respectively. PD-500 was prepared by impregnating AD with a mild alkali solution and pyrolyzing from room temperature to 500 °C. The feasibility of the use of AD-500, AD-800, and PD-500 removing NH₄⁺-N from an aqueous solution was examined. The adsorption system followed the pseudo-first-order model. Results showed that the adsorption capacities of AD-biochars for NH₄⁺-N were enhanced after the final pyrolysis; temperature was increased or the mild alkali pretreatment was administered. When the initial NH₄⁺-N concentration was changed from 4 to 8 mM, the NH₄⁺-N sorption capacity of the biochar increased from 23 to 51%, with the final pyrolysis temperature increasing from 500 to 800 °C. The improved ratios were 12 to 33% when the biochar was prepared at 500 °C after the mild alkali pretreatment, and NH₄⁺-N sorption was enhanced due to ion exchange in the PD biochar.

Graphical abstract

Biochars derived from giant reed (Arundo donax L.) with different treatment :characterization and ammonium adsorption potential.

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Source apportionment of polycyclic aromatic carbons (PAHs) in sediment core from Honghu Lake, central China: comparison study of three receptor models

Abstract

The spatial distribution of polycyclic aromatic hydrocarbons (PAHs) and their source contributions employing receptor models has been widely reported. However, the temporal distribution of PAH source contributions is less studied. Thus, in this paper, three receptor models including principle component analysis-multiple linear regression (PCA-MLR), positive matrix factorization (PMF), and Unmix were used to PAH source apportionment study in a sediment core from Honghu Lake, China. Sixteen USEPA priority PAHs in 37 sliced sediment layers (1-cm interval) were measured, with the concentrations of ∑₁₆PAH (sum of 16 PAHs) ranging from 93.0 to 431 ng g⁻¹. The source apportionment results derived from three receptor models were similar, with three common sources: mixed sources of biomass burning and coal combustion (31.0–41.4% on average), petroleum combustion (31.8–45.5%), and oil leakage (13.1–21.3%). The PMF model segregated an additional source: domestic coal combustion (contributed 20.9% to the ∑₁₆PAHs). Four aspects including intra-comparison, inter-comparison, source numbers and compositions, and source contributions were considered in comparison study. The results indicated that the PMF model was most reasonable in PAH source apportionment research in this study.

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Dental hygiene classes for children have launched in Battersea

Yolo Teeth aims to 'empower children to look after their teeth', with their classes designed and taught only by dentists which are said to be informative, memorable and fun as they are equipped with hygiene skills for life. All of Yolo Teeth's dentists are said to be fully qualified, DBS checked and experienced with children and classes are currently available for toddlers and 12-year-olds.

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Diffuse peritoneal mesothelioma: A case series of 62 patients including paraoccupational exposures to chrysotile asbestos

Background

Diffuse peritoneal malignant mesothelioma (DPM) is caused by exposure to asbestos. The medical literature has linked DPM primarily to high levels of asbestos exposure, in particular amosite. Controversy persists as to whether chrysotile is capable of causing DPM, especially when exposures are paraoccupational.

Methods

Sixty-two subjects (51 men, 11 women) with DPM were reviewed in medical-legal consultation with deposition and product identification evidence.

Results

All had pathologically confirmed DPM. Most were exposed to both amphibole and chrysotile, but chrysotile alone was documented in 14/62 (26%) cases. A total of 7/14 (50%) cases of the paraoccupational exposures were to chrysotile alone. Women were younger than men as were those with paraoccupational versus those with occupational exposure. The mean duration of exposure for all cases was 17.9 ± 10 years and latency from time of first exposure was 45.9 + 11.6 years.

Conclusions

DPM occurs with both occupational and paraoccupational exposures to asbestos and may be seen in paraoccupational exposures to chrysotile asbestos.

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Occupational noise exposure and risk of hypertension in an industrial workforce

Background

Community noise exposure has been shown to increase the risk of hypertension; however, the relationship between occupational noise exposure and hypertension is less clear.

Methods

Using an inception cohort of workers in a specialty metals manufacturing company, we retrospectively assessed occupational noise exposure, hearing acuity, and incident hypertension diagnoses using administrative datasets. Time-weighted average noise exposure levels were assigned to employees based on their job histories. Cox proportional hazards models were performed to determine the association of noise exposure with risk of incident hypertension.

Results

The adjusted hazard ratio (HR) of incident hypertension did not significantly differ between groups by cumulative continuous or categorized noise exposure metric.

Conclusion

We found no increased risk of incident hypertension with exposure to occupational noise among workers. Further assessment examining workers' use of hearing protection devices is warranted.

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Human mesenchymal factors induce rat hippocampal- and human neural stem cell dependent oligodendrogenesis

Abstract

The generation of new oligodendrocytes is essential for adult brain repair in diseases such as multiple sclerosis. We previously identified the multifunctional p57kip2 protein as a negative regulator of myelinating glial cell differentiation and as an intrinsic switch of glial fate decision in adult neural stem cells (aNSCs). In oligodendroglial precursor cells (OPCs), p57kip2 protein nuclear exclusion was recently found to be rate limiting for differentiation to proceed. Furthermore, stimulation with mesenchymal stem cell (MSC)-derived factors enhanced oligodendrogenesis by yet unknown mechanisms. To elucidate this instructive interaction, we investigated to what degree MSC secreted factors are species dependent, whether hippocampal aNSCs respond equally well to such stimuli, whether apart from oligodendroglial differentiation also tissue integration and axonal wrapping can be promoted and whether the oligodendrogenic effect involved subcellular translocation of p57kip2. We found that CC1 positive oligodendrocytes within the hilus express nuclear p57kip2 protein and that MSC dependent stimulation of cultured hippocampal aNSCs was not accompanied by nuclear p57kip2 exclusion as observed for parenchymal OPCs after spontaneous differentiation. Stimulation with human MSC factors was observed to equally promote rat stem cell oligodendrogenesis, axonal wrapping and tissue integration. As forced nuclear shuttling of p57kip2 led to decreased CNPase- but elevated GFAP expression levels, this indicates heterogenic oligodendroglial mechanisms occurring between OPCs and aNSCs. We also show for the first time that dominant pro-oligodendroglial factors derived from human fetal MSCs can instruct human induced pluripotent stem cell-derived NSCs to differentiate into O4 positive oligodendrocytes.

Main Points

• Human fetal MSCs potently instruct oligodendrogenesis from adult rat hippocampal- and hIPSC-derived neural stem cells.
• Oligodendrocyte generation does not depend on nuclear p57kip2 protein shuttling as opposed to parenchymal OPC differentiation.

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Lineage tracing reveals dynamic changes in oligodendrocyte precursor cells following cuprizone-induced demyelination

Abstract

The regeneration of oligodendrocytes is a crucial step in recovery from demyelination, as surviving oligodendrocytes exhibit limited structural plasticity and rarely form additional myelin sheaths. New oligodendrocytes arise through the differentiation of platelet-derived growth factor receptor α (PDGFRα) expressing oligodendrocyte progenitor cells (OPCs) that are widely distributed throughout the CNS. Although there has been detailed investigation of the behavior of these progenitors in white matter, recent studies suggest that disease burden in multiple sclerosis (MS) is more strongly correlated with gray matter atrophy. The timing and efficiency of remyelination in gray matter is distinct from white matter, but the dynamics of OPCs that contribute to these differences have not been defined. Here, we used in vivo genetic fate tracing to determine the behavior of OPCs in gray and white matter regions in response to cuprizone-induced demyelination. Our studies indicate that the temporal dynamics of OPC differentiation varies significantly between white and gray matter. While OPCs rapidly repopulate the corpus callosum and mature into CC1 expressing mature oligodendrocytes, OPC differentiation in the cingulate cortex and hippocampus occurs much more slowly, resulting in a delay in remyelination relative to the corpus callosum. The protracted maturation of OPCs in gray matter may contribute to greater axonal pathology and disease burden in MS.

Main Points

• The timing and efficiency of remyelination in gray matter is distinct from white matter.
• Our studies indicate that the temporal dynamics of OPC differentiation varies significantly between white and gray matter.

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Adaptation of the 2015 American College of Rheumatology treatment guideline for rheumatoid arthritis for the Eastern Mediterranean Region: an exemplar of the GRADE Adolopment

It has been hypothesized that adaptation of health practice guidelines to the local setting is expected to improve their uptake and implementation while cutting on required resources. We recently adapted the p...

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Sleep bruxism: risk factors

This review of risk factors for sleep bruxism identified 9 studies involving a total of 12,454 patients. Strong associations were found for sleep bruxism, GERD and a gene related to serotonergic neurotransmission.

The post Sleep bruxism: risk factors appeared first on National Elf Service.

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Double-Layer Surface Modification of Polyamide Denture Base Material by Functionalized Sol-Gel Based Silica for Adhesion Improvement

Abstract

Purpose

Limited surface treatments have been proposed to improve the bond strength between autopolymerizing resin and polyamide denture base materials. Still, the bond strength of autopolymerizing resins to nylon polymer is not strong enough to repair the fractured denture effectively. This study aimed to introduce a novel method to improve the adhesion of autopolymerizing resin to polyamide polymer by a double layer deposition of sol-gel silica and N-2-(aminoethyl)-3-aminopropyltrimethoxysilane (AE-APTMS).

Materials and Methods

The silica sol was synthesized by acid-catalyzed hydrolysis of tetraethylorthosilicate (TEOS) as silica precursors. Polyamide specimens were dipped in TEOS-derived sol (TS group, n = 28), and exposed to ultraviolet (UV) light under O₂ flow for 30 minutes. UV-treated specimens were immersed in AE-APTMS solution and left for 24 hours at room temperature. The other specimens were either immersed in AE-APTMS solution (AP group, n = 28) or left untreated (NT group, n = 28). Surface characterization was investigated by fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). Two autopolymerizing resins (subgroups G and T, n = 14) were bonded to the specimens, thermocycled, and then tested for shear bond strength with a universal testing machine. Data were analyzed with one-way ANOVA followed by Tukey's HSD (α = 0.05).

Results

FTIR spectra of treated surfaces confirmed the chemical modification and appearance of functional groups on the polymer. One-way ANOVA revealed significant differences in shear bond strength among the study groups. Tukey's HSD showed that TS_T and TS_G groups had significantly higher shear bond strength than control groups (p = 0.001 and p < 0.001, respectively). Moreover, bond strength values of AP_T were statistically significant compared to controls (p = 0.017).

Conclusion

Amino functionalized TEOS-derived silica coating is a simple and cost-effective method for improving the bond strength between the autopolymerizing resin and polyamide denture base. Clinical implications: Amino-functionalized silica coating could represent a more applicable and convenient option for improving the repair strength of autopolymerizing resin to polyamide polymer.

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Osteonecrosis of the jaw and survival of patients with cancer: a nationwide cohort study in Denmark

Abstract

Osteonecrosis of the jaw (ONJ) is an adverse effect of bone-targeted therapies, which are used to prevent symptomatic skeletal events following bone malignancy. We examined the association between ONJ and survival among cancer patients treated with bone-targeted agents. Using nationwide registries and databases in Denmark, we identified 184 cancer patients with incident ONJ between 2010 and 2015, and a comparison cohort of 1067 cancer patients without ONJ and with a history of hospital-administered treatment with bisphosphonates or denosumab initiating from cancer diagnosis. At the date of confirmed ONJ diagnosis, the comparison cohort was matched to the ONJ patients on age, cancer site, year of cancer diagnosis, and stage at diagnosis. The patients were followed up for survival until emigration or 15 June 2016. We computed overall survival and estimated mortality rate ratios adjusted for sex, and for the presence of distant metastases and other comorbidity at start of follow-up. A match was found for 149 of the 184 ONJ patients. The 1- and 3-year survival among all 184 cancer patients with ONJ was 70% (95% confidence interval [CI]: 63%–76%) and 42% (95% CI: 34%–51%), respectively. Among the matched patients, ONJ was associated with an adjusted mortality rate ratio of 1.31 (95% CI: 1.01–1.71). ONJ was associated with reduced survival among cancer patients treated with bone-targeted agents. ONJ may be a marker of advanced disease or of survival-related lifestyle characteristics.

In this nationwide cohort study, the authors examined the association between osteonecrosis of the jaw (ONJ) and survival among cancer patients treated with bone-targeted agents. ONJ was associated with reduced survival. The reason for the association is likely ONJ being a marker of advanced disease or of survival-related lifestyle characteristics.

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Editorial Board

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CE Registry

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Associate Registry

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Call for 2019 Award Nominations

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Table of Contents

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Health and well-being management in the military: a systematic review of genetic studies

Background

Genetic research may have therapeutic value for mental and physical disorders and could have an indicative or preventative capacity. Little is known about the extent, form and utility of military-specific genetic research.

Method

A systematic review was conducted to evaluate existing genetic well-being studies of service personnel. The review specifically aimed to ascertain the current state of knowledge and feasibility of using genetics to aid recruitment and health management within military populations. Databases searched included MEDLINE, Embase, PsycINFO and Web of Science for relevant studies. Papers were rated using a genetics-specific quality assessment framework.

Results

Ten papers were included within the final review, with seven mental-health-focused and three physical-health-focused genetic studies found within military populations. Eight papers considered candidate genes, one gene expression and one study was an outline of a future study of significant interest. Genetic commonalties were derived to yield shared physiological pathways. The 10 reviewed papers revealed moderate quality based on quality assessment.

Conclusions

Current genetic research within military populations is limited. Further studies on genetics, cost effectiveness, ethics and continual monitoring need to be explored before considering any movement toward clinical translation.

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Low-intensity pulsed ultrasound activates ERK1/2 and PI3K-Akt signalling pathways and promotes the proliferation of human amnion-derived mesenchymal stem cells

Abstract

Objectives

This study was to investigate the effect and mechanism of low-intensity pulsed ultrasound (LIPUS) on the proliferation of human amnion-derived mesenchymal stem cells (hAD-MSCs).

Methods

Human amnion-derived mesenchymal stem cells were isolated from the amnion of term placentas and identified by flow cytometry and differentiation culture. Proliferation of hAD-MSCs was investigated by Cell Counting Kit-8, cell cycle and EdU assays. Western blotting was used to determine the protein expression levels.

Results

Human amnion-derived mesenchymal stem cells were successfully isolated from the amnion and identified as multipotent mesenchymal stem cells. Low-intensity pulsed ultrasound promoted the proliferation of hAD-MSCs. Cell cycle analysis showed that LIPUS promoted cells to enter S and G2/M phases from G0/G1 phase. Western blot results showed that LIPUS promoted the phosphorylation and activation of ERK1/2 and Akt and significantly upregulated expression of cyclin D1, cyclin E1, cyclin A2 and cyclin B1. ERK1/2 inhibitor (U0126) and PI3K inhibitor (LY294002) significantly reduced LIPUS-induced phosphorylation of ERK1/2 and Akt, respectively, which in turn reduced the LIPUS-induced proliferation of hAD-MSCs.

Conclusions

Low-intensity pulsed ultrasound can promote the proliferation of hAD-MSCs, and ERK1/2 and PI3K-Akt signalling pathways may play important roles in this process.

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Long non-coding RNA CRNDE sponges miR-384 to promote proliferation and metastasis of pancreatic cancer cells through upregulating IRS1

Abstract

Objective

Colorectal neoplasia differentially expressed (CRNDE), a vital cancer-related long non-coding RNA (lncRNA), has been brought to reports for playing quintessential functions in the growth and progression of several human malignancies. Nevertheless, the expression as well as the functional mechanisms of CRNDE in pancreatic cancer is not known so for. This study aimed at investigating the biological and clinical importance of CRNDE in human pancreatic cancer.

Materials and methods

The expression levels of CRNDE in pancreatic cancer tissues as well as cell lines were identified with the help of quantitative real-time PCR (qRT-PCR). Furthermore, the analysis of the relationship between CRNDE expression and clinicopathologic characteristics of patients with pancreatic cancer was also performed. Novel target of CRNDE was identified with the use of bioinformatics analysis and confirmed by a dual-luciferase reporter assay. Colorectal neoplasia differentially expressed was knocked down using siRNA in pancreatic cancer cells. Thereafter, cell proliferation, migration and invasion were examined. Tumour xenograft was created to explore the function of CRNDE in tumorigenesis in vivo.

Results

Upregulation of the expression of CRNDE was found in pancreatic cancer tissues as well as cell lines, in comparison with the adjacent non-tumour tissues and human pancreatic duct epithelial cells. High expression of CRNDE was correlated with poor clinicpathological characteristics and shorter overall survival. We identified miR-384 as a direct target for CRNDE. Moreover, the CRNDE knockdown considerably inhibited pancreatic cancer cell proliferation, migration and invasion not only in vitro but also in vivo. In addition, CRNDE positively regulated IRS1 expression through sponging miR-384.

Conclusions

Colorectal neoplasia differentially expressed performed an oncogenic function in cell proliferation as well as metastasis of pancreatic cancer. Our results suggest that CRNDE is likely to serve as an efficient therapeutic approach in respect of pancreatic cancer treatment.

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Production, partial optimization and characterization of keratinase enzyme by Arthrobacter sp. NFH5 isolated from soil samples

The study was conducted to select the best promising keratinolytic bacterial strain. A good keratinase positive bacterium isolated from the soil samples of Hazaribagh tannery industrial zone, Dhaka was identif...

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Nutrigenomics and Nutrigenetics: New Insight in Disease Prevention and Cure

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Balanitis

Balanitis: Inflammation of the rounded head (the glans) of the penis. Inflammation of the foreskin is called posthitis. In the uncircumcised male, balanitis and posthitis generally occur together as balanoposthitis: inflammation of both the glans and foreskin.

MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
We Bring Doctors' Knowledge To You

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Posteriorly dislocated capsular tension ring leading to rhegmatogenous retinal detachment

Description

A 54-year-old woman presented with sudden diminution of vision in her left eye 4 months before. Medical history revealed that she underwent a phacoemulsification 1 year before in the left eye and 4 years before in the right eye. Snellen visual acuity in the right eye was 20/20 while she was just able to count fingers at 1 m in the left eye. She had a divergent squint of 30 prism dioptres in the left eye. The right eye had a well-centred foldable posterior chamber intraocular lens (PCIOL) in the capsular bag, while the left eye had a rigid polymethyl methacrylate (PMMA) PCIOL in the sulcus with a large posterior capsular defect (figure 1A). On fundus examination of the left eye, we found a total rhegmatogenous retinal detachment with a large punched-out toxoplasma scar at the macula, three retinal horseshoe tears superonasally at the equator (figure 2B) and a...

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Splenic calcification in systemic lupus erythematosus

Description

A 39-year-old woman with known systemic lupus erythematosus (SLE) nephropathy, antiphospholipid syndrome and chronic renal failure was evaluated for renal transplant. She was asymptomatic; nevertheless, the abdominal ultrasonogram showed splenic calcification (figure 1). The chest radiograph showed faint lesions suggestive of (L) hypochondrial calcification (figure 2). The tuberculin skin test result revealed induration of 3 mm. She had no history of treatment for tuberculosis or brucellosis. The angiotensin-converting enzyme was normal at 19 U/L (normal range 29–112 U/L). A CT scan of the abdomen and pelvis showed a bulky spleen that contained numerous small and differently sized smooth calcific foci probably related to granulomatous disease. No calcification was seen in the liver (figure 3A, B). There were no definite or suspicious pulmonary nodules seen on a whole body fluorodeoxyglucose positron-emission tomography (PET) scan. Similarly, numerous tiny splenic calcifications with no abnormal metabolic activity were detected...

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Diaphyseal tuberculosis - a rare manifestation

DESCRIPTION

A 2 year old child presented with low-grade fever, progressive pain and swelling of right leg for the past 3 months. There was no history of injury, chronic cough, respiratory symptoms, weight loss or arthritis. Child's father had been treated for pulmonary tuberculosis 1 year back. On examination, there was a firm, diffuse, tender swelling over the medial aspect of middle one-third of right tibia and matted inguinal lymphadenopathy. Rest of the systemic examination was not contributory. A clinical diagnosis of diaphyseal bone tumour or chronic infective osteomyelitis was considered.

Investigations showed erythrocyte sedimentation rate 46 mm in first hour, haemoglobin 96 g/L and 20 mm induration after Mantoux test and normal chest radiograph. Radiograph of the right tibia showed a lytic intramedullary bone lesion (Figure 1A–B). MRI confirmed an intramedullary lytic lesion with cortical breach and thickening (figure 1C). Histopathology showed caseous necrosis, granuloma formation, Langhans giant cells...

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Cholesterol embolism: its always a good idea to look into the eye

Description

Atheroembolism is a rare but feared complication of arteriography, causing a myriad of signs and symptoms including livedo reticularis, abdominal pain, cyanosis of the toes and renal injury. The main cause is a rupture of atherosclerotic plaque in vessel walls and its embolisation to small diameter vessels affecting more frequently skin and kidneys.1 Here, we present a 69-year-old Hispanic male with medical history of hypertension, type 2 diabetes mellitus and unstable angina status post drug-eluting stent in the left anterior descending coronary artery placement 10 days prior to admission, who arrived to the emergency department with intense diffuse sharp abdominal pain, nausea, vomiting, oliguria and lower extremity pain. Physical examination disclosed livedo reticularis in lower extremities (figure 1), tender abdomen with decreased bowel sounds and funduscopy positive for a Hollenhorst crystal observed in right inferotemporal quadrant (figure 2) and increased creatinine and...

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Infected enteric duplication cyst

Description

An 8-month-old female infant presented with a 2-day history of vomiting, diarrhoea and fever. Physical examination revealed a painful right abdomen. Laboratory tests showed a C-reactive protein of 140 mg/L (normal: <6 mg/L) and a white blood cell count of 12.8x10⁹/L (normal: 4–15x10⁹/L). Ultrasound of the abdomen revealed a paracolic cystic mass of 1.4x5 cm with septations from the lower part of the liver into the right fossa with no signs of volvulus or intussusception (figure 1). Abdominal CT confirmed the cystic mass and revealed signs of infection. MRI of the abdomen suggested an enteric duplication cyst as the most likely diagnosis (figure 2).

Figure 1

Ultrasound: encapsulated tubular mass with predominant hypoechoic heterogeneous echogenicity under the right lobe of the liver.

Figure 2

MRI coronal T1-weighted image with intravenous contrast: tubular cystic mass with thick wall ventral and lateral...

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An airway traffic jam: a plastic traffic cone masquerading as bronchial carcinoma

Tracheobronchial foreign body (TFB) aspiration is a common occurrence in children compared with adults. Long-standing cases of TFB aspiration during childhood presenting in an adult have rarely been reported. We report the unique case of an endobronchial Playmobil traffic cone that went undetected for 40 years and presented as a suspected bronchogenic carcinoma. This was subsequently removed successfully with flexible bronchoscopy. To our knowledge this is the first case of a TFB that was overlooked this length of time.

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Help-seeking behaviours, opportunistic treatment and psychological implications of adolescent acne: cross-sectional studies in schools and hospital outpatient departments in the UK

Background

Acne vulgaris (acne) is a common adolescent skin condition. It is associated with negative psychological impacts and sufferers do not easily seek help, hence is undertreated.

Objectives

We investigated the self-reported prevalence, severity and psychological sequelae of acne, together with assessing help-seeking behaviour and its barriers, in separate school and hospital samples. We explored opportunistic treatment by paediatricians.

Methods

Self-reported survey with participants drawn from: (1) 120 adolescents aged 13–18 in a London tertiary paediatric outpatient department and (2) 482 adolescents from two London schools, aged 11–18. Adolescents confidentially and anonymously completed a questionnaire (paper or online) and those with acne completed the Cardiff Acne Disability Index (CADI) questionnaire.

Outcome measures

To explore if acne is being addressed opportunistically in outpatient appointments and the behaviours associated with seeking help and psychological implications of acne.

Results

Acne prevalence was reported as 58.3% in the clinic and 42.3% in schools, with 34.3% and 20.6% of participants having moderate acne (MA) or severe acne (SA), respectively. The correlation between acne severity and CADI was significant (regression coefficient=4.86, p<0.005 (MA) and 9.08, p<0.005 (SA) in the hospital; 1.92, p<0.001 (MA) and 7.41, p<0.005 (SA) in schools). Severity of acne was associated with increased likelihood of seeing a doctor in both samples (OR=8.95, 2.79–28.70 (MA) in the clinic and 1.31, 1.30–2.90 (MA) and 3.89, 0.66–22.98 (SA) in the community). Barriers to help seeking included embarrassment and believing doctors were unapproachable. Doctors addressed acne opportunistically in 2.9% of the sample, although 16.7% of those with MA and SA wished their doctor had raised it.

Conclusion

Acne is common and has negative psychological implications, correlating with severity. Young people often forego seeking help and hospital clinicians rarely address acne opportunistically. Further work is needed to investigate how to reduce barriers to help seeking for acne.

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Urine cytology screening of French workers exposed to occupational urinary tract carcinogens: a prospective cohort study over a 20-year period

Objectives

To demonstrate that urine cytology screening can provide relevant epidemiological data for earlier detection of urothelial cancer caused by occupational exposure.

Design

Prospective cohort study.

Setting

Industries using urothelial carcinogens in France. Urine samples were collected on site, after a work week and were analysed at the University Hospital of Clermont-Ferrand, France.

Participants

Participants were workers exposed to urothelial carcinogens. Women and current smokers at time of study recruitment were exclusion criteria.

Outcomes

Urine cells atypia were ranged into three classes: negative/normal, atypical/suspicious/dysplasia or positive/malignant.

Results

We included 2020 workers over a period of 20 years from 1993 to 2013: 606 worked in rubber manufacturing, 692 from metal processing, 245 in chemical industry and 477 in roadwork and building industry. Workers had a mean exposure of 15.2±10.4 years before their first urine cytology screening. There was a mean of 3.4±4.3 urine cytology screenings per worker between 1993 and 2013. 6478 cytology were normal, 462 suspicious and 13 malignant. Suspicious and malignant cytology occurred in 4.8% of workers exposed for 1–10 years, 6.2% for 11–20 years of exposure, 7.6% for 21–30 years and 8.6% for >30 years (p<0.001). Using exposure for 1–10 years as reference, the adjusted OR of receiving a suspicious or malignant diagnosis increased with duration of exposure: OR=1.50 (95% CI 1.10 to 2.05, p=0.01) for 21–30 years and OR=1.78 (95% CI 1.23 to 2.56, p=0.002) for >30 years of exposure. Using metal processing as reference, the risk of pathological urine cytology results increased for rubber manufacturing (OR=1.32, 95% CI 1.05 to 1.65, p=0.02), with a trend for roadwork and building industry (OR=1.39, 95% CI 0.98 to 1.97, p=0.07) and for chemical industry (OR=1.34, 95% CI 0.94 to 1.93, p=0.11).

Conclusions

Urine cytology is a useful tool in occupational medicine. We promote new guidelines with an early screening of urothelial cancer by cytology, starting with beginning of exposure.

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Household and familial resemblance in risk factors for type 2 diabetes and related cardiometabolic diseases in rural Uganda: a cross-sectional community sample

Objectives

Prevention of type 2 diabetes (T2D) has been successfully established in randomised clinical trials. However, the best methods for the translation of this evidence into effective population-wide interventions remain unclear. To assess whether households could be a target for T2D prevention and screening, we investigated the resemblance of T2D risk factors at household level and by type of familial dyadic relationship in a rural Ugandan community.

Methods

This cross-sectional household-based study included 437 individuals ≥13 years of age from 90 rural households in south-western Uganda. Resemblance in glycosylated haemoglobin (HbA1c), anthropometry, blood pressure, fitness status and sitting time were analysed using a general mixed model with random effects (by household or dyad) to calculate household intraclass correlation coefficients (ICCs) and dyadic regression coefficients. Logistic regression with household as a random effect was used to calculate the ORs for individuals having a condition or risk factor if another household member had the same condition.

Results

The strongest degree of household member resemblances in T2D risk factors was seen in relation to fitness status (ICC=0.24), HbA1c (ICC=0.18) and systolic blood pressure (ICC=0.11). Regarding dyadic resemblance, the highest standardised regression coefficient was seen in fitness status for spouses (0.54, 95% CI 0.32 to 0.76), parent–offspring (0.41, 95% CI 0.28 0.54) and siblings (0.41, 95% CI 0.25 to 0.57). Overall, parent–offspring and sibling pairs were the dyads with strongest resemblance, followed by spouses.

Conclusions

The marked degree of resemblance in T2D risk factors at household level and between spouses, parent–offspring and sibling dyads suggest that shared behavioural and environmental factors may influence risk factor levels among cohabiting individuals, which point to the potential of the household setting for screening and prevention of T2D.

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Does psychedelic drug use reduce risk of suicidality? Evidence from a longitudinal community-based cohort of marginalised women in a Canadian setting

Objective

This study aimed to longitudinally investigate whether ever having used a psychedelic drug can have a protective effect on incidence of suicidality among marginalised women.

Design

Longitudinal community-based cohort study.

Setting

Data were drawn from a prospective, community-based cohort of marginalised women in Metro Vancouver, Canada.

Participants

766 women completed the baseline questionnaire between January 2010 and August 2014. Participants who did not report suicidality at baseline and who completed at least one follow-up visit were included.

Main outcome measure

Extended Cox regression was used to model predictors of new suicidality (suicide ideation or attempts) over 54-month follow-up.

Results

Nearly half (46%; n=355) of participants reported prior suicidality and were thus excluded from the present analyses. Of 290 women eligible at baseline, 11% (n=31) reported recent suicidality during follow-up, with an incidence density of 4.42 per 100 person-years (95% CI 3.10 to 6.30). In multivariable analysis, reported lifetime psychedelic drug use was associated with a 60% reduced hazard for suicidality (adjusted HR (AHR) 0.40; 95% CI 0.17 to 0.94). Crystal methamphetamine use (AHR 3.25; 95% CI 1.47 to 7.21) and childhood abuse (AHR 3.54; 95% CI 1.49 to 8.40) remained independent predictors of suicidality.

Conclusion

The high rate of suicidality identified in this study is of major concern. Alongside emerging evidence on the potential of psychedelic-assisted therapy to treat some mental illness and addiction issues, our findings demonstrate that naturalistic psychedelic drug use is independently associated with reduced suicidality, while other illicit drug use and childhood trauma predispose women to suicidality. While observational, this study supports calls for further investigation of the therapeutic utility of psychedelic drugs in treating poor mental health and promoting mental wellness.

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Association between gender and short-term outcome in patients with ST elevation myocardial infraction participating in the international, prospective, randomised Administration of Ticagrelor in the catheterisation Laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery (ATLANTIC) trial: a prespecified analysis

Objectives

To evaluate gender differences in outcomes in patents with ST-segment elevation myocardial infarction (STEMI) planned for primary percutaneous coronary intervention (PPCI).

Settings

A prespecified gender analysis of the multicentre, randomised, double-blind Administration of Ticagrelor in the catheterisation Laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery.

Participants

Between September 2011 and October 2013, 1862 patients with STEMI and symptom duration <6 hours were included.

Interventions

Patients were assigned to prehospital versus in-hospital administration of 180 mg ticagrelor.

Outcomes

The main objective was to study the association between gender and primary and secondary outcomes of the main study with a focus on the clinical efficacy and safety outcomes. Primary outcome: the proportion of patients who did not have 70% resolution of ST-segment elevation and did not meet the criteria for Thrombolysis In Myocardial Infarction (TIMI) flow 3 at initial angiography. Secondary outcome: the composite of death, MI, stent thrombosis, stroke or urgent revascularisation and major or minor bleeding at 30 days.

Results

Women were older, had higher TIMI risk score, longer prehospital delays and better TIMI flow in the infarct-related artery. Women had a threefold higher risk for all-cause mortality compared with men (5.7% vs 1.9%, HR 3.13, 95% CI 1.78 to 5.51). After adjustment, the difference was attenuated but remained statistically significant (HR 2.08, 95% CI 1.03 to 4.20). The incidence of major bleeding events was twofold to threefold higher in women compared with men. In the multivariable model, female gender was not an independent predictor of bleeding (Platelet Inhibition and Patient Outcomes major HR 1.45, 95% CI 0.73 to 2.86, TIMI major HR 1.28, 95% CI 0.47 to 3.48, Bleeding Academic Research Consortium type 3–5 HR 1.45, 95% CI 0.72 to 2.91). There was no interaction between gender and efficacy or safety of randomised treatment.

Conclusion

In patients with STEMI planned for PPCI and treated with modern antiplatelet therapy, female gender was an independent predictor of short-term mortality. In contrast, the higher incidence of bleeding complications in women could mainly be explained by older age and clustering of comorbidities.

Clinical trial registration

NCT01347580;Post-results.

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Usage of purchased self-tests for HIV and sexually transmitted infections in Amsterdam, the Netherlands: results of population-based and serial cross-sectional studies among the general population and sexual risk groups

Objectives

There are limited data on the usage of commercially bought self-tests for HIV and other sexually transmitted infections (STIs). Therefore, we studied HIV/STI self-test usage and its determinants among the general population and sexual risk groups between 2007 and 2015 in Amsterdam, the Netherlands.

Setting

Data were collected in four different studies among the general population (S1–2) and sexual risk groups (S3–4).

Participants

S1–Amsterdam residents participating in representative population-based surveys (2008 and 2012; n=6044) drawn from the municipality register; S2–Participants of a population-based study stratified by ethnicity drawn from the municipality register of Amsterdam (2011–2015; n=17 603); S3–Men having sex with men (MSM) participating in an HIV observational cohort study (2008 and 2013; n=597) and S4–STI clinic clients participating in a cross-sectional survey (2007–2012; n=5655).

Primary and secondary outcome measures

Prevalence of HIV/STI self-test usage and its determinants.

Results

The prevalence of HIV/STI self-test usage in the preceding 6–12 months varied between 1% and 2% across studies. Chlamydia self-tests were most commonly used, except among MSM in S3. Chlamydia and syphilis self-test usage increased over time among the representative sample of Amsterdam residents (S1) and chlamydia self-test usage increased over time among STI clinic clients (S4). Self-test usage was associated with African Surinamese or Ghanaian ethnic origin (S2), being woman or MSM (S1 and 4) and having had a higher number of sexual partners (S1–2). Among those in the general population who tested for HIV/STI in the preceding 12 months, 5–9% used a self-test.

Conclusions

Despite low HIV/STI self-test usage, we observed increases over time in chlamydia and syphilis self-test usage. Furthermore, self-test usage was higher among high-risk individuals in the general population. It is important to continue monitoring self-test usage and informing the public about the unknown quality of available self-tests in the Netherlands and about the pros and cons of self-testing.

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Protocol for a realist review of complex interventions to prevent adolescents from engaging in multiple risk behaviours

Objectives

Adolescent risk behaviours are a key health concern. The purpose of this research is to gaina deeper understanding of how, why, for whom, and inwhat circumstances complex adolescent risk behaviourprevention programmes are most successful.

Methods and analysis

To understand how adolescent risk behaviour prevention programmes work in a reallife context, a realist synthesis will be undertaken, operationalised in four phases.

Phase one Developing a framework to map the theoretical and conceptual landscape of adolescent risk behaviour prevention. Guided by stakeholder consultation.

Phase two Formulating initial programme theories through exploration of the literature, along with primary data from professional stakeholder interviews.

Phase three Refining programme theories through more purposeful, in depth screening of the literature, along with primary qualitative data, from young people and professionals. Data will be collected through semi structured focus groups, to explore specific elements of the emerging programme theories.

Phase four Testing programme theories through interviews with youth workers, following consultation with young people, using vignettes to explore the relationship between specific programme theories. This relatively novel method of primary and secondary data integration within a realist synthesis will provide deeper insight in to young peoples lived experience of risk behaviour prevention programmes, while maintaining transparency in the process of programme theory development.

Data analysis

A realist logic of analysis will be used to align data from each phase with context mechanism outcome configurations or specific elements thereof. Substantive theory will then be sought to understand and explain the findings.

Ethics and dissemination

This study has been approved by the Ethics committee at Northumbria University, UK. Findings will be disseminated through knowledge exchange with stakeholders, publications in peer-reviewed journals, conference presentations, and formal and informal reports.

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Protocol of a randomised controlled trial characterising the immune responses induced by varicella-zoster virus (VZV) vaccination in healthy Kenyan women: setting the stage for a potential VZV-based HIV vaccine

Introduction

A protective HIV vaccine would be expected to induce durable effector immune responses at the mucosa, restricting HIV infection at its portal of entry. We hypothesise that use of varicella-zoster virus (VZV) as an HIV delivery vector could generate sustained and robust tissue-based immunity against HIV antigens to provide long-term protection against HIV. Given that HIV uniquely targets immune-activated T cells, the development of human vaccines against HIV must also involve a specific examination of the safety of the vector. Thus, we aim to evaluate the effects of VZV vaccination on the recipients' immune activation state, and on VZV-specific circulating humoral and cellular responses in addition to those at the cervical and rectal mucosa.

Methods and analysis

This open-label, randomised, longitudinal crossover study includes healthy Kenyan VZV-seropositive women at low risk for HIV infection. Participants receive a single dose of a commercial live-attenuated VZV_Oka vaccine at either week 0 (n=22) or at week 12 (n=22) of the study and are followed for 48 and 36 weeks postvaccination, respectively. The primary outcome is the change on cervical CD4⁺ T-cell immune activation measured by the coexpression of CD38 and HLA-DR 12 weeks postvaccination compared with the baseline (prevaccination). Secondary analyses include postvaccination changes in VZV-specific mucosal and systemic humoral and cellular immune responses, changes in cytokine and chemokine measures, study acceptability and feasibility of mucosal sampling and a longitudinal assessment of the bacterial community composition of the mucosa.

Ethics and dissemination

The study has ethical approval from Kenyatta National Hospital/University of Nairobi Ethics and Research Committee, the University of Toronto Research Ethics Board and by Kenyan Pharmacy and Poisons Board. Results will be presented at conferences, disseminated to participants and stakeholders as well as published in peer-reviewed journals.

Trial registration number

NCT02514018. Pre-results.

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Recording a diagnosis of stroke, transient ischaemic attack or myocardial infarction in primary healthcare and the association with dispensation of secondary preventive medication: a registry-based prospective cohort study

Objectives

The aim of this study was to explore whether recording in primary care of a previously recorded hospital diagnosis was associated with increased patient utilisation of recommended medications.

Design

Registry-based prospective cohort study.

Setting and participants

19 072 patients with a hospital discharge diagnosis of transient ischaemic attack (TIA), stroke or acute coronary syndrome from hospitals in Stockholm County 2010–2013 were included in the study.

Main outcome measure

The outcome of the study was medication dispensation as a marker of adherence to recommended medications. Adherence was defined as having had at least two filled prescriptions in the third year following hospital discharge.

Results

Recording a diagnosis was associated with higher utilisation of all recommended medications with the exception of antihypertensives in patients with TIA. The differences between the groups with and without a recorded diagnosis remained after adjusting for age, sex, index year and visits to private practitioners. Dispensation of antithrombotics was high overall, 80%–90% in patients without a recorded diagnosis and 90%–94% for those with a diagnosis. Women with recorded ischaemic stroke/TIA/acute coronary syndrome were dispensed more statins (56%–71%) than those with no recorded diagnosis (46%–59%). Similarly, 68%–83% of men with a recorded diagnosis were dispensed statins (57%–77% in men with no recorded diagnosis). The rate of diagnosis recording spanned from 15% to 47% and was especially low in TIA (men 15%, women 16%).

Conclusion

Recording a diagnosis of TIA/stroke or acute coronary syndrome in primary care was found to be associated with higher dispensation of recommended secondary preventive medications. Further study is necessary in order to determine the mechanisms underlying our results and to establish the utility of our findings.

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Publication of interventional phase 3 and 4 clinical trials in radiation oncology: an observational study

Objectives

Clinical trials produce the best data available for decision-making in modern evidence-based medicine. We aimed to determine the rate of non-publication of interventional phase 3 and 4 clinical trials involving patients with cancer undergoing radiotherapy.

Setting

The ClinicalTrials.gov database was searched for interventional phase 3 and 4 trials in radiotherapy with a primary completion date before 1 January 2013. We determined how many of these registry entries have not published the compulsory deposition of their results in the database and performed a systematic search for published studies in peer-reviewed journals.

Results

Of 576 trials, 484 (84.0%) did not deposit a summary result in the registry. In addition, 44.9% of them did not publish their results in a peer-reviewed journal. Similar percentages were found for most cancer subtypes: brain (41%), breast (38%), cervical (66%), colorectal (38%), lung (48%), prostate (45%), bladder (56%), head and neck (56%) and lymphoma (33%).

Conclusion

Our results show that most trials in radiation oncology did not report the results in the registry. Almost half of these trials have not been published in the biomedical literature. This means that a large number of study participants were exposed to the risks of trial participation without the supposed benefits that sharing and publishing of results would offer to future generations of patients.

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Perceptions of parents and paediatricians on pain induced by bone marrow aspiration and lumbar puncture among children with acute leukaemia: a qualitative study in China

Objective

To obtain in-depth insight into the perceptions of parents and paediatricians in China regarding current procedural pain management on bone marrow aspirations and lumbar punctures in paediatric haemato-oncology department.

Design, setting and participants

This qualitative study was conducted in a 4500-bed university hospital in northwest China. To collect data, in-depth semistructured interviews were conducted with parents of children with acute leukaemia (n=12) and haemato-oncology paediatricians (n=11) using purposive sampling. Interviews were audiotaped and transcribed and subjected to thematic analysis.

Results

The suffering of procedural pain among paediatric patients was not adequately recognised and properly treated at the paediatric haemato-oncology department. The current paediatric procedural pain management is inadequate for paediatric patients. Crucial factors were identified including lack of awareness about the damage of uncontrolled pain in children, parents' low supportive ability, the limited capacity to provide general analgesia by anaesthetists, inadequate knowledge in the usage of analgesia and sedation and lack of efficient analgesic for children's procedural pain. The participants strongly expected optimal interventions to improve paediatric procedural pain management.

Conclusions

The result suggested a perceived and actual poor management of paediatric procedural pain in haemato-oncology department in northwest China. A relevant pain management education programme for paediatricians and parents as well as an effective pain medication are urgently needed in northwest China.

Trial registration

Chinese Clinical Trial Registry. Identifier: ChiCTR-INR-16007989.

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Is increasing urbanicity associated with changes in breastfeeding duration in rural India? An analysis of cross-sectional household data from the Andhra Pradesh children and parents study

Objective

To investigate whether village-level urbanicity and lower level socioeconomic factors are associated with breastfeeding practices in transitioning rural communities in India.

Setting

29 villages in Ranga Reddy district, southern India between 2011 and 2014.

Participants

7848 children under 6 years identified via a cross-sectional household survey conducted as part of the Andhra Pradesh Children and Parents Study.

Outcome measures

Two key indicators of optimal breastfeeding: termination of exclusive breastfeeding before 6 months and discontinuation of breastfeeding by 24 months. Village urbanicity was classified as low, medium or high according to satellite assessed night-light intensity.

Results

Breastfeeding initiation was almost universal, and approximately two in three children were exclusively breastfed to 6 months and a similar proportion breastfed to 24 months. Using multilevel logistic regression, increasing urbanicity was associated with breastfeeding discontinuation before 24 months (medium urbanicity OR 1.45, 95% CI 0.71 to 2.96; high urbanicity OR 2.96, 95% CI 1.45 to 6.05) but not with early (<6 months) termination of exclusive breastfeeding. Increased maternal education was independently associated with both measures of suboptimal breastfeeding, and higher household socioeconomic position was associated with early termination of exclusive breastfeeding.

Conclusion

In this transitional Indian rural community, early stage urbanicity was associated with a shorter duration of breastfeeding. Closer surveillance of changes in breastfeeding practices alongside appropriate intervention strategies are recommended for emerging economies.

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Determinants of community pharmacists quality of care: a population-based cohort study using pharmacy administrative claims data

Objective

To determine if a prototype pharmacists' services evaluation programme that uses linked community pharmacy claims and health administrative data to measure pharmacists' performance can be used to identify characteristics of pharmacies providing higher quality of care.

Design

Population-based cohort study using community pharmacy claims from 1 November 2009 to 30 June 2010.

Setting

All community pharmacies in Quebec, Canada.

Participants

1742 pharmacies dispensing 8 655 348 antihypertensive prescriptions to 760 700 patients.

Primary outcome measure

Patient adherence to antihypertensive medications.

Predictors

Pharmacy level: dispensing workload, volume of pharmacist-provided professional services (eg, refusals to dispense, pharmacotherapy recommendations), pharmacy location, banner/chain, pharmacist overlap and within-pharmacy continuity of care. Patient level: sex, age, income, patient prescription cost, new/chronic therapy, single/multiple antihypertensive medications, single/multiple prescribers and single/multiple dispensing pharmacies. Dispensing level: prescription duration, time of day dispensed and antihypertensive class. Multivariate alternating logistic regression estimated predictors of the primary outcome, accounting for patient and pharmacy clustering.

Results

9.2% of dispensings of antihypertensive medications were provided to non-adherent patients. Male sex, decreasing age, new treatment, multiple prescribers and multiple dispensing pharmacies were risk factors for increased non-adherence. Pharmacies that provided more professional services were less likely to dispense to non-adherent hypertensive patients (OR: 0.60; 95% CI: 0.57 to 0.62) as were those with better scores on the Within-Pharmacy Continuity of Care Index. Neither increased pharmacists' services for improving antihypertensive adherence per se nor increased pharmacist overlap impacted the odds of non-adherence. However, pharmacist overlap was strongly correlated with dispensing workload. There was significant unexplained variability among pharmacies belonging to different banners and chains.

Conclusions

Pharmacy administrative claims data can be used to calculate pharmacy-level characteristics associated with improved quality of care. This study supports the importance of pharmacist's professional services and continuity of pharmacist's care.

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Erratum to: Activations in gray and white matter are modulated by uni-manual responses during within and inter-hemispheric transfer: effects of response hand and right-handedness

Abstract

The original version of this article unfortunately contained a mistake. The family name of Paolo Brambilla was incorrectly spelled as Bambilla.

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Erratum to: Activations in gray and white matter are modulated by uni-manual responses during within and inter-hemispheric transfer: effects of response hand and right-handedness

Abstract

The original version of this article unfortunately contained a mistake. The family name of Paolo Brambilla was incorrectly spelled as Bambilla.

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Squamous-Cell Carcinoma of the Mouth

Figure 1.

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Metformin as a repurposed therapy in advanced non-small cell lung cancer (NSCLC): results of a phase II trial

Summary

Background Metformin has been shown to have anti-neoplastic activity in non-small cell lung cancer (NSCLC) in both preclinical and observational studies, however this has never been prospectively evaluated. This single-arm phase II trial, while not fully accrued, is the first known prospective study evaluating the use of metformin with chemotherapy in advanced NSCLC. Methods Patients received carboplatin AUC 5 + pemetrexed 500 mg/m2 IV every 21 days for 4 cycles. For patients who achieved at least stable disease, maintenance pemetrexed was administered until progression or toxicity. Metformin was initiated at 1000 mg/day for week 1, 1500 mg/day for week 2, then 2000 mg/day thereafter, in divided doses. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and adverse events (AE). Tumor tissue was tested for LKB1/STK11 mutations, and non-fasting serum insulin levels were longitudinally assessed. Results Of a planned 50 patients, 14 were enrolled. ORR was 23% and median PFS was 3.9 months. Median OS was 11.7 months. No LKB1/STK11 mutations were identified. The most common AE were fatigue (42.9%), anemia, and nausea (28.6% each). The most common grade III AE was nausea (14.3%). No grade IV AE occurred. Mean duration of metformin treatment was 5.6 months. Conclusion Adding metformin to chemotherapy for advanced NSCLC was safe but did not significantly improve clinical outcomes compared to historical phase III controls. These results are limited by the small sample size; larger trials are needed.

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Treatment-related serious adverse events and fatal adverse events with regorafenib in cancer patients: a meta-analysis of phase 3 randomized controlled trials

Summary

Regorafenib (Stivarga) is an oral small-molecule multikinase inhibitor commonly used against a variety of cancers. We performed a meta-analysis of all phase 3 randomized controlled trials (RCTs) of regorafenib to quantify the increased risk of SAEs and FAEs. We carried out a systematic search of electronic databases for studies published from inception to February 2017 without any restrictions. Eligibility criteria included phase 3 RCTs of tumors comparing regorafenib, alone or in combination with non-targeted chemotherapy (regorafenib arm) versus placebo or non-targeted chemotherapy (control arm). Data on SAEs and FAEs were extracted from each study and pooled to determine the overall incidence, relative risks (RRs) and 95% confidence intervals (CIs). A total of four phase 3 RCTs involving 1736 cancer patients met the eligibility criteria and were included. The overall incidence of SAEs and FAEs with regorafenib were 0.23 (95%CI, 0.05–0.40) and 0.02 (95%CI, 0.01–0.03), respectively. Compared with control, the summary RR of developing a regorafenib-related SAE was 1.60 (95%CI, 0.95–2.68, P=0.07), the summary RR of developing a regorafenib-related FAE was 1.71 (95%CI, 0.69–4.24, P=0.25). No evidence was found for the association between regorafenib and higher risk of SAEs and FAEs. This association varied significantly with cancer types (P=0.02) for SAEs but no evidence of heterogeneity was found for FAEs. This meta-analysis demonstrates no evidence for the association between regorafenib and higher risk of SAEs and FAEs. This analysis will be important when considering the trade-off of regorafenib treatment during clinical decision-making.

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Predicted burden could replace predicted risk in preventive strategies for cardiovascular disease

Publication date: Available online 21 September 2017
Source:Journal of Clinical Epidemiology
Author(s): G.R. Lagerweij, G.A. de Wit, K.G.M. Moons, W.M.M. Verschuren, J. Boer, H. Koffijberg
ObjectivesTo explore the extent of the differences in definitions of composite endpoints and assess how these differences influence estimates of CVD burden.Study Design and Settings: Data from a Dutch cohort study (n=19484) were used to calculate 10-year risks according to four CVD risk prediction models: ATP-III, Framingham (FRS), Pooled Cohort Equations (PCE) and SCORE. Health loss was estimated based on the impact of event types included in the corresponding composite endpoints. Finally, each prediction model was used to estimate the expected CVD burden in high-risk individuals, expressed as Quality-Adjusted Life Years (QALYs) lost.ResultsThe definition of the composite endpoints varied widely across the four models. FRS predicted the highest CVD risks and the composite endpoint used in SCORE was associated with the highest health burden. The predicted CVD burden in high-risk individuals was 0.23, 0.74, 0.43, and 0.39 QALYs lost per individual when using ATP, FRS, PCE and SCORE, respectively.ConclusionThe investigated CVD risk prediction models showed huge variation in definition of composite endpoints and associated health burden. Therefore, health consequences related to predicted risks cannot be readily compared across prediction models, and estimates of burden of disease depend crucially on the prediction model used.



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Investigating Heterogeneity of Effects and Associations Using Interaction Terms

Publication date: Available online 21 September 2017
Source:Journal of Clinical Epidemiology
Author(s): Evangelos Kontopantelis, Matthew Sperrin, Mamas Mamas, Iain Buchan
Effect heterogeneity, the variability of an association or exposure across subgroups, usually warrants further investigation. The aim of this deeper analysis is to identify effect modifiers (or moderators) and quantify their relationship with the exposure. We explain why it is better to harness interaction effects within a single analytic model than to use separate models to analyse each subgroup. Using examples, we demonstrate a practical approach to modelling and interpretation with interaction terms from various measurement scales (categorical by categorical; categorical by continuous; and continuous by continuous).



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Interpretation of epidemiological studies very often lacked adequate consideration of confounding

Publication date: Available online 21 September 2017
Source:Journal of Clinical Epidemiology
Author(s): Lars G. Hemkens, Hannah Ewald, Florian Naudet, Aviv Ladanie, Jonathan G. Shaw, Gautam Sajeev, John P.A. Ioannidis
BackgroundConfounding bias is a most pervasive threat to validity of observational epidemiological research.MethodsWe assessed whether authors of observational epidemiological studies consider confounding bias when interpreting the findings. We randomly selected 120 cohort or case-control studies published in 2011 and 2012 by the general medical, epidemiological, and specialty journals with the highest impact factors. We used Web of Science to assess citation metrics through January 2017.Results68 studies (56.7%, 95% confidence interval 47.8% to 65.5%) mentioned "confounding" in the Abstract or Discussion sections, another 20 (16.7%; 10.0% to 23.3%) alluded to it, and there was no mention or allusion at all in 32 studies (26.7%; 18.8% to 34.6%). Authors often acknowledged that for specific confounders there was no adjustment (34 studies; 28.3%) or deem it possible or likely that confounding affected their main findings (29 studies; 24.2%). However, only 2 studies (1.7%; 0% to 4.0%) specifically used the words "caution" or "cautious" for the interpretation due to confounding-related reasons and eventually only 4 studies (3.3%; 0.1% to 6.5%) had limitations related to confounding or any other bias in their Conclusions. Studies mentioning that the findings were possibly or likely affected by confounding were more frequently cited than studies with a statement that findings were unlikely affected (median 6.3 vs. 4.0 citations per year, p=0.04).ConclusionsMany observational studies lack satisfactory discussion of confounding bias. Even when confounding bias is mentioned, authors are typically confident that it is rather irrelevant to their findings and they rarely call for cautious interpretation. More careful acknowledgement of possible impact of confounding is not associated with lower citation impact.



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Curcusone C induces telomeric DNA-damage response in cancer cells through inhibition of telomeric repeat factor 2

Publication date: Available online 21 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Author(s): Mingxue Wang, Jiaojiao Cao, Jian-Yong Zhu, Jun Qiu, Yan Zhang, Bing Shu, Tian-Miao Ou, Jia-Heng Tan, Lian-Quan Gu, Zhi-Shu Huang, Sheng Yin, Ding Li
Telomeric repeat factor 2 (known as TRF2 or TERF2) is a key component of telomere protection protein complex named as Shelterin. TRF2 helps the folding of telomere to form T-loop structure and the suppression of ATM-dependent DNA damage response activation. TRF2 has been recognized as a potentially new therapeutic target for cancer treatment. In our routine screening of small molecule libraries, we found that Curcusone C had significant effect in disrupting the binding between TRF2 and telomeric DNA, with potent antitumor activity against cancer cells. Our result showed that Curcusone C could bind with TRF2 without binding interaction with TRF1 (telomeric repeat factor 1) although these two proteins share high sequence homology, indicating that their binding conformations and biological functions in telomere could be different. Our mechanistic studies showed that Curcusone C bound with TRF2 possibly through its DNA binding site causing blockage of its interaction with telomeric DNA. Further in cellular studies indicated that the interaction of TRF2 with Curcusone C could activate DNA-damage response, inhibit tumor cell proliferation, and cause cell cycle arrest, resulting in tumor cell apoptosis. Our studies showed that Curcusone C could become a promising lead compound for further development for cancer treatment. Here, TRF2 was firstly identified as a target of Curcusone C. It is likely that the anti-cancer activity of some other terpenes and terpenoids are related with their possible effect for telomere protection proteins.



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X-linked ichthyosis associated with psychosis and behavioral abnormalities: a case report

X-linked ichthyosis is a dermatological condition caused by deficiency for the enzyme steroid sulfatase. Previously, X-linked ichthyosis/steroid sulfatase deficiency has been associated with developmental and ...

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Breast cancer metastases to the thyroid gland – an uncommon sentinel for diffuse metastatic disease: a case report and review of the literature

Metastases to the thyroid are rare. The most common primary cancer to metastasize to the thyroid is renal cell carcinoma, followed by malignancies of the gastrointestinal tract, lungs, and skin, with breast ca...

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Computed tomography in children with community-acquired pneumonia

Abstract

Diagnostic imaging plays a significant role in both the diagnosis and treatment of complications of pneumonia in children and chest radiography is the imaging modality of choice. Computed tomography (CT) on the other hand, is not currently a first-line imaging tool for children with suspected uncomplicated community-acquired pneumonia and is largely reserved for when complications of pneumonia are suspected or there is difficulty in differentiating pneumonia from other pathology. This review outlines the situations where CT needs to be considered in children with pneumonia, describes the imaging features of the parenchymal and pleural complications of pneumonia, discusses how CT may have a wider role in developing countries where human immunodeficiency virus (HIV) and tuberculosis are prevalent, makes note of the role of CT scanning for identifying missed foreign body aspiration and, lastly, addresses radiation concerns.

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Proteomic analysis of Phytophthora infestans reveals the importance of cell wall proteins in pathogenicity [Research]

The oomycete Phytophthora infestans is the most harmful pathogen of potato. It causes the disease late blight, which generates increased yearly costs of up to one billion euro in the EU alone and is difficult to control. We have performed a large-scale quantitative proteomics study of six P. infestans life stages with the aim to identify proteins that change in abundance during development, with a focus on pre-infectious life stages. Over 10 000 peptides from 2061 proteins were analysed. We identified a number of abundance profiles of proteins that were up- or downregulated in different combinations of life stages. One of these profiles contained 59 proteins that were more abundant in germinated cysts and appressoria. A large majority of these proteins were not previously recognized as being appressorial proteins or involved in the infection process. Among those are proteins with putative roles in transport, amino acid metabolism, pathogenicity (including one RXLR effector) and cell wall structure modification. We analysed the expression of the genes encoding nine of these proteins using RT-qPCR and found an increase in transcript levels during disease progression, in agreement with the hypothesis that these proteins are important in early infection. Among the nine proteins was a group involved in cell wall structure modification and adhesion, including three closely related, uncharacterized proteins encoded by PITG_01131, PITG_01132, and PITG_16135, here denoted Piacwp1-3. Transient silencing of these genes resulted in reduced severity of infection, indicating that these proteins are important for pathogenicity. Our results contribute to further insight into P. infestans biology, and indicate processes that might be relevant for the pathogen while preparing for host cell penetration and during infection. The mass spectrometry data have been deposited to ProteomeXchange via the PRIDE partner repository with the dataset identifier PXD002446.

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Isolation of five proanthocyanidins from pear ( Pyrus pyrifolia Nakai) fruit peels

Abstract

Five proanthocyanidins, two B-type dimers and three A-type trimers, were purified and isolated from the fruit peels of Pyrus pyrifolia Nakai cv. Chuhwangbae. The isolated compounds were identified as (–)-epicatechin gallate-(4β → 8)-(–)-epicatechin (Hahashi et al. in Ann Biol Res 3:3200–3207, 2012), (–)-epicatechin-(4β → 8)-(–)-epicatechin (procyanidin B2) (Tanrioven and Eksi in Food Chem 93:89–93, 2005), (–)-epicatechin-(4β → 8, 2β → O-7)-(–)-epicatechin-(4β → 8)-(–)-epicatechin (cinnamtannins B1) (Salta et al. in J. Fun. Food 2: 153–157, 2010), (–)-epicatechin-(4β → 8)-(–)-epicatechin-(4β → 8, 2β → O-7)-(–)-epicatechin (aesculitannin A) (Challice and Westwood in Phytochemistry 11: 37–44, 1972), and (–)-epicatechin-(4β → 6)-(–)-epicatechin-(4β → 8, 2β → O→7)-(–)-epicatechin (Es-Safi et al. in J Agric Food Chem 54: 6969–6977, 2006). Their structures were determined by nuclear magnetic resonance and mass spectrometry. The three A-type proanthocyanidin trimers were identified for the first time from pear.

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Properties of two laccases from the Trametes hirsuta 072 multigene family: Twins with different faces

Publication date: Available online 21 September 2017
Source:Biochimie
Author(s): Olga S. Savinova, Konstantin V. Moiseenko, Ekaterina A. Vavilova, Tatiana V. Tyazhelova, Daria V. Vasina
Utilization of laccases in biotechnology and bioremediation has created a strong demand for the characterization of new enzymes and an increase in production of known laccases. Thus, additional research into these enzymes is critically needed.In this study, we report a comparative study of the biochemical and transcriptional properties of two different laccase isozymes from Trametes hirsuta 072 – the constitutive and inducible forms. A recombinant LacC enzyme was expressed in Penicillium canescens to characterize its properties. LacC is single-purpose enzyme, unlike LacA, which can operate efficiently under a wide range of temperatures and pHs (55–70 °C and pH 3–5, respectively). LacC has a lower RedOx potential than LacA and does not oxidize substrates containing amine groups. Expression of the lacC gene was selective compared to that of the lacA gene and increased significantly in the presence of complex synthetic compounds such as dyes and xenobiotics.This study shows that laccases from the multigene families of basidiomycetes differ significantly in their properties, thus providing a complementary effect during lignin degradation.

Graphical abstract

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Lack of serum- and glucocorticoid-inducible kinase 3 leads to podocyte dysfunction [Research]

Serum- and glucocorticoid-inducible kinase 3 (SGK3) is a downstream mediator of PI3K, which is essential for maintaining the functional integrity of podocytes. However, little is known about the role of SGK3 in podocyte function. Herein, we demonstrated that SGK3 contributes to the maintenance of podocyte integrity. Conditionally immortalized mouse podocyte cells (MPCs) were treated with puromycin aminonucleoside (PAN). PAN treatment inhibited the activity of SGK3 and the expression of podocin. Short hairpin RNA (shRNA)–mediated knockdown of SGK3 also reduced podocin expression in the absence of PAN. Adriamycin (ADR)-treated mice developed proteinuria and had decreased renal glomerular SGK3 expression in comparison to control mice. Consistent with a role for SGK3 in the ADR effect, SGK3 knockout (KO) mice had markedly reduced kidney podocin expression and significantly elevated proteinuria compared with wild-type mice. Electron microscopy revealed that SGK3 KO mice displayed partial effacement of podocyte foot processes. Further, a SGK3 target protein, glycogen synthase kinase-3 (GSK3), was discovered to be dramatically activated in PAN and SGK3 shRNA-treated MPCs and in SGK3 KO mice. Taken together, these data strongly suggest that SGK3 plays a significant role in regulating podocyte function, likely by controlling the expression and activity of GSK3.—Peng, L.-Q., Zhao, H., Liu, S., Yuan, Y.-P., Yuan, C.-Y., Mwamunyi, M.-J., Pearce, D., Yao, L.-J. Lack of serum- and glucocorticoid-inducible kinase 3 leads to podocyte dysfunction.

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Identification of truncated form of NosP as a transcription factor to regulate the biosynthesis of nosiheptide [Research]

Nosiheptide (NOS), a typical member of the thiopeptides, possesses strong activities against multidrug-resistant, gram-positive bacterial pathogens. Similar to other thiopeptides, the biosynthetic pathway of NOS belongs to a ribosomally synthesized and posttranslationally modified peptide system. Bioinformatics analysis of the NOS gene cluster suggests that nosP gene encodes a homologous protein of Streptomyces antibiotic regulatory protein (SARP) family. In the present study, the actual initiation codon of nosP was identified by comparison of potential initiation codons GUG and AUG. In contrast to previous predictions of starting with GUG, AUG, corresponding to methionine residue as the 53rd residue in the original sequence, is actually the initiation codon of nosP, indicating that a truncated form of NosP (NosP_53–323) is a functional protein. For better understanding of the transcriptional regulation for NOS biosynthesis, the binding region was subsequently investigated with NosP_53–323, demonstrating that NosP_53–323 specifically binds the bidirectional nosL-nosM promoter region. Additionally, NosP_53–323 was confirmed to serve as a transcription factor to activate the transcription of all 15 structural genes in the gene cluster. The present study provides new insights into pathway-specific regulation of the biosynthesis of NOS, which would be beneficial to the investigation of the regulatory function of similar SARP proteins in the gene clusters of other thiopeptides.—Wu, X., Jin, L., Zhang, H., Tong, R., Ma, M., Chen, Y. Identification of truncated form of NosP as a transcription factor to regulate the biosynthesis of nosiheptide.

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Germany's Greens: “I don’t want the last car made in Germany to end up in a museum”

Main image:  LAST week I caught up with Cem Özdemir, lead candidate of Germany's Green Party, to talk about his country's future. The latest polls put his party on about 8%. Mr Özdemir's perspective matters, for two reasons.First, the polls suggest that Angela Merkel may have to choose between another "grand coalition" with the Social Democrats (SPD)—who are fed up with governing with her—and a three-way coalition with the centre-left Greens and the right-liberal Free Democrats (FDP). In the latter scenario (called "Jamaica" as the colours of the parties match those of country's flag) Mr Özdemir might well become Germany's foreign minister. That would make him the second Green to hold that job after Joschka Fischer and the first Turkish-German to hold any major government rank (his father moved to Germany from Tokat, north-east of Ankara).Second, Mr Özdemir is actually willing to discuss the big challenges facing Germany. Whether or not you agree with him, this is welcome in an election campaign marked and marred by the big parties' inability to talk what Germans call Klartext, or frank sense, about the big issues. How should the Euro zone advance? What are Germany's international responsibilities? How can the country's business model be made fit for the future? How can the country's car industry get ...

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Climate change: There is still no room for complacency in matters climatic

Print section Print Rubric:  Changed estimates of how much carbon dioxide can still be emitted to meet climate targets leave no room for complacency Print Headline:  Breathing space Print Fly Title:  Carbon budgets UK Only Article:  standard article Issue:  Jeremy Corbyn: Britain's most likely next prime minister Fly Title:  Climate change Main image:  20170923_STD001_0.jpg IN JUNE Christiana Figueres, the UN's former climate chief who helped broker the Paris agreement in 2015, warned that the world has "three years to safeguard our climate". It was a hyperbolic claim, even then. New research makes it seem even more of one today. An analysis published in Nature Geoscience on September 18th, by Richard Millar of Oxford University and his colleagues, suggests that climate researchers have been underestimating the carbon "budget" compatible with the ambitions ...

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Isolation and characterization of endothelial-to-mesenchymal transition-cells in pulmonary arterial hypertension

Endothelial-to-mesenchymal transition (EndMT) is a process in which endothelial cells lose polarity and cell-to-cell contacts, and undergo a dramatic remodeling of the cytoskeleton. It has been implicated in initiation and progression of pulmonary arterial hypertension (PAH). However, the characteristics of cells which have undergone EndMT-cells in vivo have not been reported and so remain unclear. To study this, sugen5416 and hypoxia (SuHx)-induced PAH was established in Cdh5-Cre / Gt(ROSA)26Sor^{tm4(ACTB-tdTomato,-EGFP)Luo}/J double-transgenic mice, in which GFP was stably expressed in pan-endothelial cells. After 3 weeks of SuHx, flow cytometry and immunohistochemistry demonstrated CD144-negative and GFP-positive cells (complete EndMT-cells) possessed higher proliferative and migratory activity compared to other mesenchymal cells. While CD144-positive and α-SMA-positive cells (partial EndMT-cells) continued to express endothelial progenitor cell markers, complete EndMT-cells were Sca-1-rich mesenchymal cells with high proliferative and migratory ability. When transferred in fibronectin-coated chamber slides containing smooth muscle media, α-SMA robustly expressed in these cells compared to cEndMT-cells that were grown in maintenance media. Demonstrating additional paracrine effects, conditioned medium from isolated complete EndMT-cells induced enhanced mesenchymal proliferation and migration, and increased angiogenesis as compared to conditioned medium from resident mesenchymal cells. Overall, these findings show that EndMT-cells could contribute to the pathogenesis of PAH both directly by transformation into smooth muscle-like cells with higher proliferative and migratory potency, as well as indirectly, through paracrine effects on vascular intimal and medial proliferation.

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Attenuation of pulmonary ACE2 activity impairs inactivation of des-Arg9 bradykinin/BKB1R axis and facilitates LPS-induced neutrophil infiltration

Angiotensin converting enzyme 2 (ACE2) is a terminal carboxypeptidase with important functions in the renin angiotensin system and plays a critical role in inflammatory lung diseases. ACE2 cleaves single terminal residues from several bioactive peptides such as angiotensin II. However, few of its substrates in the respiratory tract have been identified and the mechanism underlying the role of ACE2 in inflammatory lung disease has not been fully characterized. In an effort to identify biological targets of ACE2 in the lung, we tested its effects on des-arg9 bradykinin (DABK) in airway epithelial cells based upon a hypothesis that DABK is a biological substrate of ACE2 in the lung and ACE2 plays an important role in the pathogenesis of acute lung inflammation partly through modulating DABK/BKB1R axis signaling. We found that loss of ACE2 function in mouse lung in the setting of endotoxin inhalation led to activation of the DABK/BKB1R (bradykinin receptor B1) axis, release of the proinflammatory chemokines such as CXCL5，MIP2, KC and TNF- MIP2 and TNF-a from airway epithelia, increased neutrophil infiltration and exaggerated lung inflammation and injury. These results indicate that a reduction in pulmonary ACE2 activity contributes to the pathogenesis of lung inflammation, in part due to an impaired ability to inhibit DABK/BKB1R axis mediated signaling, resulting in more prompt onset of neutrophil infiltration and more severe inflammation in the lung. Our study identifies a biological substrate of ACE2 within the airways, as well as a potential new therapeutic target for inflammatory diseases.

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Phagocytosis of microparticles by alveolar macrophages during acute lung injury requires MerTK.

Microparticles are a newly recognized class of mediators in the pathophysiology of lung inflammation and injury, but little is known about the factors that regulate their accumulation and clearance. The primary objective of our study was to determine whether alveolar macrophages engulf microparticles and to elucidate the mechanisms by which this occurs. Alveolar microparticles were quantified in bronchoalveolar fluid of mice with lung injury induced by LPS and hydrochloric acid. Microparticle numbers were greatest at the peak of inflammation and declined as inflammation resolved. Isolated, fluorescently labeled particles were placed in culture with macrophages to evaluate ingestion in the presence of endocytosis inhibitors. Ingestion was blocked with cytochalasin D and wortmannin, consistent with a phagocytic process. In separate experiments, mice were treated intratracheally with labeled microparticles and their uptake was assessed though microscopy and flow cytometry. Resident alveolar macrophages, not recruited macrophages, were the primary cell ingesting microparticles in the alveolus during lung injury. In vitro, microparticles promoted inflammatory signaling in LPS primed epithelial cells, signifying the importance of microparticle clearance in resolving lung injury. Microparticles were found to have phosphatidylserine exposed on their surfaces. Accordingly, we measured expression of phosphatidylserine receptors on macrophages and found high expression of MerTK and Axl on the resident macrophage population. Endocytosis of microparticles was markedly reduced in MerTK-deficient macrophages in vitro and in vivo. In conclusion, microparticles are released during acute lung injury and peak in number at the height of inflammation. Resident alveolar macrophages efficiently clear these microparticles through MerTK mediated phagocytosis.

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Greenbrae dentist fights tooth decay while her dog fights nerves

TV host Leslie Sbrocco, left, and Michelle Martinez, of Greenbrae, on the set of "Check, Please! Bay Area." There's a worrisome spike in tooth decay among U.S. preschoolers in the past decade, with dentists reporting a marked increase of 2- to 5-year-olds needing extensive dental work. Too antsy or scared to sit through long procedures of multiple fillings, even crowns and root canals, many end up undergoing general anesthesia.

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Treatment of oesophageal cancer – Stressing the patient perspective

Publication date: October 2017
Source:European Journal of Cancer, Volume 84
Author(s): Florian Lordick




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First-line treatment in metastatic colorectal cancer: Important or crucial?

Publication date: October 2017
Source:European Journal of Cancer, Volume 84
Author(s): David Malka, Federico Rotolo, Valérie Boige




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Post-market outcome of an extract of traditional Cretan herbs on upper respiratory tract infections: a pragmatic, prospective observational study

The beneficial effects of traditional herbs of Crete, Greece for the treatment of upper respiratory tract infections have been reported in observational and laboratory studies. Following a published, double bl...

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Effectiveness of acupuncture for breast cancer related lymphedema: protocol for a single-blind, sham-controlled, randomized, multicenter trial

Although various treatments for breast cancer related lymphedema exist, there is still a need for a more effective and convenient approach. Pilot studies and our clinical observations suggested that acupunctur...

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Nanoparticles of a polyaspartamide-based brush copolymer for modified release of sorafenib: In vitro and in vivo evaluation

Publication date: 28 November 2017
Source:Journal of Controlled Release, Volume 266
Author(s): Melchiorre Cervello, Giovanna Pitarresi, Antonella Bavuso Volpe, Barbara Porsio, Daniele Balasus, Maria Rita Emma, Antonina Azzolina, Roberto Puleio, Guido Ruggero Loria, Stefano Puleo, Gaetano Giammona
In this paper, we describe the preparation of polymeric nanoparticles (NPs) loaded with sorafenib for the treatment of hepatocellular carcinoma (HCC). A synthetic brush copolymer, named PHEA-BIB-ButMA (PBB), was synthesized by Atom Trasnfer Radical Polymerization (ATRP) starting from the α-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) and poly butyl methacrylate (ButMA). Empty and sorafenib loaded PBB NPs were, then, produced by using a dialysis method and showed spherical morphology, colloidal size, negative ζ potential and the ability to allow a sustained sorafenib release in physiological environment.Sorafenib loaded PBB NPs were tested in vitro on HCC cells in order to evaluate their cytocompatibility and anticancer efficacy if compared to free drug. Furthermore, the enhanced anticancer effect of sorafenib loaded PBB NPs was demonstrated in vivo by using a xenograft model, by first allowing Hep3B cells to grow subcutaneously into nude mice and then administering sorafenib as free drug or incorporated into NPs via intraperitoneal injection. Finally, in vivo biodistribution studies were performed, showing the ability of the produced drug delivery system to accumulate in a significant manner in the solid tumor by passive targeting, thanks to the enhanced permeability and retention effect.

Graphical abstract

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Knowledge, attitude, and practices on intestinal schistosomiasis among primary schoolchildren in the Lake Victoria basin, Rorya District, north-western Tanzania

Globally school-age children, adolescents and young adults bear the highest burden of schistosomiasis. When developing a specific intervention to improve community's knowledge, attitudes, and practices (KAPs),...

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Physical activity and overweight/obesity among Malaysian adults: findings from the 2015 National Health and morbidity survey (NHMS)

Overweight and obesity are growing health problems both worldwide and in Malaysia due to such lifestyle changes as decreased physical activity (PA), increased sedentary behavior and unhealthy eating habits. Th...

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