NLC-Based Sunscreen Formulations with Optimized Proportion of Encapsulated and Free Filters Exhibit Enhanced UVA and UVB Photoprotection.

The topical use of sunscreens is recommended for avoiding the damaging effects of UV radiation. However, improvements are still needed in the existing products to enhance their photoprotection effectiveness and safety. This involves minimizing the use of chemical UV filters while providing enhanced and prolonged photoprotection. This work investigated novel sunscreen formulations and their UV protection effects by encapsulating Uvinul® A, Tinosorb® S, and Uvinul® T150 into nanostructured lipid carriers (NLCs) based on bacuri butter and raspberry seed oil. First, the impact of critical formulation and process parameters on NLCs' particle size was evaluated using a 22 Face Centered Central Composite Design. Then, formulations were evaluated in terms of critical quality factors, in vitro skin permeation, and in vitro and in vivo photoprotection activities. The developed NLCs-containing formulations exhibited appropriate size (122-135 nm), PdI (<0.3), encapsulation efficiency (>90%), and drug content (>80%), which were preserved for at least 90 days under different stability conditions. Moreover, these NLCs-based formulations had equivalent skin permeation to emulsion-based controls, and the addition of NLCs into sunscreen cream bases in the optimum proportion of 20% (w/w) resulted in enhanced UVA and UVB photoprotection levels, despite a 10% reduction in the total filters content. Altogether, these results describe the application of nanoencapsulated organic UV filters in innovative sunscreen formulations to achieve superior photoprotection and cosmeceutical properties.

An app with brief behavioural support to promote physical activity after a cancer diagnosis (APPROACH): study protocol for a pilot randomised controlled trial.

BACKGROUND: There are multiple health benefits from participating in physical activity after a cancer diagnosis, but many people living with and beyond cancer (LWBC) are not meeting physical activity guidelines. App-based interventions offer a promising platform for intervention delivery. This trial aims to pilot a theory-driven, app-based intervention that promotes brisk walking among people living with and beyond cancer. The primary aim is to investigate the feasibility and acceptability of study procedures before conducting a larger randomised controlled trial (RCT). METHODS: This is an individually randomised, two-armed pilot RCT. Patients with localised or metastatic breast, prostate, or colorectal cancer, who are aged 16 years or over, will be recruited from a single hospital site in South Yorkshire in the UK. The intervention includes an app designed to encourage brisk walking (Active 10) supplemented with habit-based behavioural support in the form of two brief telephone/video calls, an information leaflet, and walking planners. The primary outcomes will be feasibility and acceptability of the study procedures. Demographic and medical characteristics will be collected at baseline, through self-report and hospital records. Secondary outcomes for the pilot (assessed at 0 and 3 months) will be accelerometer measured and self-reported physical activity, body mass index (BMI) and waist circumference, and patient-reported outcomes of quality of life, fatigue, sleep, anxiety, depression, self-efficacy, and habit strength for walking. Qualitative interviews will explore experiences of participating or reasons for declining to participate. Parameters for the intended primary outcome measure (accelerometer measured average daily minutes of brisk walking (≥ 100 steps/min)) will inform a sample size calculation for the future RCT and a preliminary economic evaluation will be conducted. DISCUSSION: This pilot study will inform the design of a larger RCT to investigate the efficacy and cost-effectiveness of this intervention in people LWBC. TRIAL REGISTRATION: ISRCTN registry, ISRCTN18063498 . Registered 16 April 2021.

Informing patient choice and service planning in surgical voice restoration: valve usage over three years in a UK head and neck cancer unit.

OBJECTIVE: This study aimed to determine the number, reasons and costs of surgical voice restoration related tracheoesophageal valve attendances over 36 months at a head and neck oncology unit. METHOD: Demographic, medical and valve related details from all patient contacts were recorded, including self-change information, urgent appointment information, modifications required and costs of prostheses. RESULTS: Over 3 years, 99 patients underwent 970 valve changes. The main reasons for changes were central leakage, prophylactic change and self-change at home. Changes were significantly more frequent in the first 12 months (mean, 42 days) compared with longstanding patients (mean, 109.96). Intervals between changes were unpredictable; no predictive factors reached statistical significance. Mean expenditure on valves was £966.63 per week (including value added tax and in-house customisation). CONCLUSION: Valve lifespan is comparable with outcomes in similar units despite more pre-emptive and patient-led changes and more comprehensive data inclusion. Investigation into how patient satisfaction and costs relate to valve selection and units' service delivery models is needed.

Clinicopathological and prognostic significance of programmed cell death ligand 1 expression in patients diagnosed with breast cancer: meta-analysis.

BACKGROUND: Uncertainty exists regarding the clinical relevance of programmed cell death ligand 1 (PD-L1) expression in breast cancer. METHODS: A systematic review was performed in accordance with PRISMA guidelines. Observational studies that compared high versus low expression of PD-L1 on breast cancer cells were identified. Log hazard ratios (HRs) for disease-free and overall survival and their standard errors were calculated from Kaplan-Meier curves or Cox regression analyses, and pooled using the inverse-variance method. Dichotomous variables were pooled as odds ratios (ORs) using the Mantel-Haenszel method. RESULTS: Sixty-five studies with 19 870 patients were included; 14 404 patients were classified as having low and 4975 high PD-L1 expression. High PD-L1 was associated with achieving a pathological complete response following neoadjuvant chemotherapy (OR 3.30, 95 per cent confidence interval 1.19 to 9.16; P < 0.01; I2 = 85 per cent). Low PD-L1 expression was associated with human epidermal growth factor receptor 2 (OR 3.98, 1.81 to 8.75; P < 0.001; I2 = 96 per cent) and luminal (OR 14.93, 6.46 to 34.51; P < 0.001; I2 = 99 per cent) breast cancer subtypes. Those with low PD-L1 had favourable overall survival rates (HR 1.30, 1.05 to 1.61; P = 0.02; I2 = 85 per cent). CONCLUSION: Breast cancers with high PD-L1 expression are associated with aggressive clinicopathological and immunohistochemical characteristics and are more likely to achieve a pathological complete response following neoadjuvant chemotherapy. These breast cancers are, however, associated with worse overall survival outcomes.

Co-Infection with SARS-COV-2 and Parainfluenza in a young adult patient with pneumonia: Case Report.

Coronavirus 2 (SARS-CoV-2) is now considered a pandemic causing Coronavirus disease (COVID-19), multiple fatalities and morbidities which have been associated with it worldwide. We report a severe pneumonia causing acute respiratory distress syndrome due to a coinfection with SARS-COV-2 and Parainfluenza 4 virus in a Hispanic 21 year old male in Florida, USA. The case represents the importance of prompt diagnosis and awareness of the potential co-infection with other respiratory viruses and this novel deadly virus.

Whole-genome analysis of extraintestinal Escherichia coli sequence type 73 from a single hospital over a 2 year period identified different circulating clonal groups.

Sequence type (ST)73 has emerged as one of the most frequently isolated extraintestinal pathogenic Escherichia coli. To examine the localized diversity of ST73 clonal groups, including their mobile genetic element profile, we sequenced the genomes of 16 multiple-drug resistant ST73 isolates from patients with urinary tract infection from a single hospital in Sydney, Australia, between 2009 and 2011. Genome sequences were used to generate a SNP-based phylogenetic tree to determine the relationship of these isolates in a global context with ST73 sequences (n=210) from public databases. There was no evidence of a dominant outbreak strain of ST73 in patients from this hospital, rather we identified at least eight separate groups, several of which reoccurred, over a 2 year period. The inferred phylogeny of all ST73 strains (n=226) including the ST73 clone D i2 reference genome shows high bootstrap support and clusters into four major groups that correlate with serotype. The Sydney ST73 strains carry a wide variety of virulence-associated genes, but the presence of iss, pic and several iron-acquisition operons was notable.

The real penalty: number of OMFS patients presenting to the emergency department at Sunderland Royal Hospital after England fixtures before and during the 2018 FIFA Football World Cup.

The aim of this study was to establish a link between a large televised sporting event and the incidence of patients presenting to the emergency department with oral and maxillofacial injuries. When compared with daily attendances throughout the year, the mean (SD) number rose from 2.53 (1.69) to 4.00 (1.53) (p=0.005) between 1 November 2017 and 31 July 2018 on the day after an England fixture, an increase of 58%. These data show the need for workforce planning during large-scale national sporting events because of the rise in the number of patients presenting. They show that the increase in workload is caused by a higher number of both traumatic and non-traumatic injuries.

Development of AD-Like Pathology in Skeletal Muscle.

Effective therapeutic strategy against Alzheimer's disease (AD) requires early detection of AD; however, clinical diagnosis of Alzheimer's disease (AD) is not precise and a definitive diagnosis of AD is only possible via postmortem examination for AD pathological hallmarks including senile plaques composed of Aß and neuro fibrillary tangles composed of phosphorylated tau. Although a variety of biomarker has been developed and used in clinical setting, none of them robustly predicts subsequent clinical course of AD. Thus, it is essential to identify new biomarkers that may facilitate the diagnosis of early stages of AD, prediction of subsequent clinical course, and development of new therapeutic strategies. Given that pathological hallmarks of AD including Aßaccumulation and the presence of phosphorylated tau are also detected in peripheral tissues, AD is considered a systemic disease. Without the protection of blood-brain barrier, systemic factors can affect peripheral tissues much earlier than neurons in brain. Here, we will discuss the development of AD-like pathology in skeletal muscle and the potential use of skeletal muscle biopsy (examination for Aßaccumulation and phosphorylated tau) as a biomarker for AD.

A review of question prompt lists used in the oncology setting with comparison to the Patient Concerns Inventory.

A question prompt list (QPL) is a simple and inexpensive communication tool used to facilitate patient participation in medical consultations. The QPL is composed of a structured list of questions and has been shown to be an effective way of helping ensure patients' individual information needs are appropriately met. This intervention has been investigated in a variety of settings but not specifically head and neck cancer (HNC). The aim of this paper was to perform a narrative review of literature reporting the use of a QPL for oncology patients and to draw comparison to the Patient Concerns Inventory (PCI-HN). The databases Scopus, PubMed and MEDLINE were searched using the key terms 'question prompt list', 'question prompt sheet', 'cancer' and 'oncology'. Of 98 articles hand searched, 30 of which were found to meet all inclusion criteria, and described in a tabulated summary. The studies concluded that the QPL was an effective intervention, enabling active patient participation in medical consultations. The PCI-HN is specific for HNC and differs from many QPLs, which are more general cancer tools. The QPL approach should prove to be a useful intervention for HNC sufferers, however further research into the clinical utility is required.

Carotid-cavernous fistula: current concepts in aetiology, investigation, and management.

A carotid-cavernous fistula (CCF) is an abnormal communication between arteries and veins within the cavernous sinus and may be classified as either direct or dural. Direct CCFs are characterized by a direct connection between the internal carotid artery (ICA) and the cavernous sinus, whereas dural CCFs result from an indirect connection involving cavernous arterial branches and the cavernous sinus. Direct CCFs frequently are traumatic in origin and also may be caused by rupture of an ICA aneurysm within the cavernous sinus, Ehlers-Danlos syndrome type IV, or iatrogenic intervention. Causes of dural CCFs include hypertension, fibromuscular dysplasia, Ehlers-Danlos type IV, and dissection of the ICA. Evaluation of a suspected CCF often involves non-invasive imaging techniques, including standard tonometry, pneumotonometry, ultrasound, computed tomographic scanning and angiography, and/or magnetic resonance imaging and angiography, but the gold standard for classification and diagnosis remains digital subtraction angiography. When a direct CCF is confirmed, first-line treatment is endovascular intervention, which may be accomplished using detachable balloons, coils, liquid embolic agents, or a combination of these tools. As dural CCFs often resolve spontaneously, low-risk cases may be managed conservatively. When invasive treatment is warranted, endovascular intervention or stereotactic radiosurgery may be performed. Modern endovascular techniques offer the ability to successfully treat CCFs with a low morbidity and virtually no mortality.

Investigating the association of rs2910164 with cancer predisposition in an Irish cohort.

INTRODUCTION: MicroRNAs (miRNAs) are small noncoding RNA molecules that exert post-transcriptional effects on gene expression by binding with cis-regulatory regions in target messenger RNA (mRNA). Polymorphisms in genes encoding miRNAs or in miRNA-mRNA binding sites confer deleterious epigenetic effects on cancer risk. miR-146a has a role in inflammation and may have a role as a tumour suppressor. The polymorphism rs2910164 in the MIR146A gene encoding pre-miR-146a has been implicated in several inflammatory pathologies, including cancers of the breast and thyroid, although evidence for the associations has been conflicting in different populations. We aimed to further investigate the association of this variant with these two cancers in an Irish cohort. METHODS: The study group comprised patients with breast cancer (BC), patients with differentiated thyroid cancer (DTC) and unaffected controls. Germline DNA was extracted from blood or from saliva collected using the DNA Genotek Oragene 575 collection kit, using crystallisation precipitation, and genotyped using TaqMan-based PCR. Data were analysed using SPSS, v22. RESULTS: The total study group included 1516 participants. This comprised 1386 Irish participants; 724 unaffected individuals (controls), 523 patients with breast cancer (BC), 136 patients with differentiated thyroid cancer (DTC) and three patients with dual primary breast and thyroid cancer. An additional cohort of 130 patients with DTC from the South of France was also genotyped for the variant. The variant was detected with a minor allele frequency (MAF) of 0.19 in controls, 0.22 in BC and 0.27 and 0.26 in DTC cases from Ireland and France, respectively. The variant was not significantly associated with BC (per allele odds ratio = 1.20 (0.98-1.46), P = 0.07), but was associated with DTC in Irish patients (per allele OR = 1.59 (1.18-2.14), P = 0.002). CONCLUSION: The rs2910164 variant in MIR146A is significantly associated with DTC, but is not significantly associated with BC in this cohort.

Neurodegeneration in equine grass sickness is not attributable to niacin deficiency.

BACKGROUND: The aetiology of equine grass sickness (EGS) is currently unknown. We hypothesised that an acute deficiency of niacin (vitamin B3), which plays a key role in neural homeostasis, may contribute to neurodegeneration in EGS. Niacin deficiency can potentially result from ingestion of niacin antagonists produced by pasture mycotoxigenic fungi. OBJECTIVES: To compare the niacin status of EGS and control grazing horses. A secondary objective was to compare blood concentrations of vitamins B1, B2 and B6 in EGS and control grazing horses to determine if the status of these vitamins was altered in EGS. STUDY DESIGN: Case-control study. METHODS: Indices of niacin status, namely the erythrocyte nicotinamide adenine dinucleotide:nicotinamide adenine dinucleotide phosphate ratio (NAD:NADP ratio) and erythrocyte concentrations of NAD and NADP, were compared in blood collected from EGS and healthy control grazing horses. Blood concentrations of vitamins B1, B2 and B6 were also compared. RESULTS: There was no significant intergroup difference in the NAD:NADP ratio, the main index of functional niacin status (control group: median 2.1, interquartile range [IQR] 1.8-2.6; EGS group: median 2.1, IQR 1.9-2.6). EGS horses had significantly higher (median value increased by 25%) concentrations of NADP. There were no intergroup differences in blood concentrations of vitamins B1, B2 and B6. MAIN LIMITATIONS: The interpretation of data was limited by the lack of previously defined equine reference ranges for many of the analytes. Sample size was low. CONCLUSIONS: Niacin deficiency does not contribute to EGS neurodegeneration.

Intracytoplasmic morphologically selected sperm injection and congenital birth defects: a retrospective cohort study.

Our objective was to study the birth defect rates in intracytoplasmic morphologically selected sperm injection (IMSI) pregnancies. A cohort of couples presenting male factor infertility between January 2006 and January 2014 was retrospectively analyzed. Discharge letters and a telephone interview were performed for assessing pregnancy outcome. All clinical data were reviewed by a board certified medical geneticist. Main outcomes were fetal/birth defect and chromosomal abnormality rates. Two thousand two hundred and fifty-eight pregnancies were available for analysis, of them, 1669 (73.9%) resulting from ICSI and 2258 (26.1%) achieved by IMSI. Pregnancy outcome distribution did not show a significant difference. For the fresh embryo transfer cohort, fetal/birth defect rate was 4.5%, chromosomal aberration rate was 1.0%, and structural malformation rate was 3.5%. IMSI vs. ICSI pregnancies were less likely to involve a fetal/birth defect: 3.5% vs. 4.8%, respectively, but did not reach a statistical significance OR 0.71 (95% CI 0.39-1.22). Split by multiplicity, this trend existed only for singleton pregnancies; 1.4% structural malformations rate vs. 3.8%, respectively, OR 0.35 (95% CI 0.11-0.9). The frozen cohort demonstrated a significantly lower birth defect rate (OR 0.25, 95% CI 0.09-0.58). We conclude that IMSI procedure does not involve an increased malformation rate and may offer a reduced anomaly incidence. Further studies are required.

[Artificial Feedback for Invasive Brain-Computer Interfaces].

During the last two decades, considerable progress has been made in the studies of brain-computer interfaces (BCIs)--devices in which motor signals from the brain are registered by multi-electrode arrays and transformed into commands for articial actuators such as cursors and robotic devices. This review is focused on one problem. Voluntary motor control is based on neurophysiological processes which depend heavily on the afferent innervation of skin, muscles and joints. Thus, invasive BCI has to be based on a bidirectional system in which motor control signals are registered by multi-channel micro-electrodes implanted in motor areas, while tactile, proprioceptive and other useful signals are transported back to the brain through spatial-temporal patterns of intracortical microstimulation (ICMS) delivered to sensory areas. In general, the studies of invasive BCIs have advanced in several directions. The progress of BCIs with articial sensory feedback will not only help patients, but will also expand knowledge base in the field of human cortical functions.

Breast Cancer in the Bahamas in 2009-2011.

BACKGROUND: Breast cancer is the most common form of cancer affecting women in the Bahamas, which consists of many islands. This is the first attempt to identify which island has the highest occurrence of breast cancer. OBJECTIVE: The aim of this study was to describe the sociodemographical and spatial features of breast cancer in the Bahamas in 2009-2011. METHODS: A review of the medical records of all women with a confirmed diagnosis of breast cancer during the period January 1, 2009-December 31, 2011, was undertaken. Data were first obtained from the National Oncology Board of the Bahamas and validated by a review of the medical records. The patient address was geocoded and mapped using ArcGIS 10.0 Environmental Systems Research Institute (ESRI) to satellite images obtained from The Nature Conservancy in the Bahamas. RESULTS: We recruited 270 patients who satisfied the entry criteria. The cumulative incidences of breast cancer for the years 2009-2011 were 51.4, 45.4, and 51.4, respectively. Breast cancer occurred most often in women of African origin with a mean age at diagnosis of 56.6 ± 13.8 years. Ductal carcinoma was the most common histological type observed with most cancers occurring in Grade II or higher and presenting as late stage (≥ Stage II). Surgery was the preferred method of treatment with modified radical mastectomy being the procedure of choice. Spatial distribution of cases across the Bahamas revealed one cluster, which is present on the island of New Providence. Further analysis of New Providence showed a consistently skewed kernel density in the central and eastern regions, compared with a scattered distribution in the southern and western regions. CONCLUSION: The island of New Providence had the highest occurrence of breast cancer among all the islands of the Bahamas. The increasing incidence of breast cancer in young women is likely to impose a significant burden on the future of Bahamian health care.

NCOA3 coactivator is a transcriptional target of XBP1 and regulates PERK-eIF2α-ATF4 signalling in breast cancer.

XBP1 is a multitasking transcription factor and a key component of the unfolded protein response (UPR). Despite the wealth of knowledge about the role of XBP1 in luminal/ER-positive breast cancer, not much is known about the effectors of XBP1 in this context. Here we show that NCOA3 is a transcriptional target of XBP1. We observed increased expression of NCOA3 during conditions of UPR and oestrogen (E2) stimulation. Further investigations revealed a role for the IRE1-XBP1 axis in the induction of NCOA3 during UPR and oestrogen signalling. We identify a novel role for NCOA3 in activation of PERK-ATF4 axis during UPR where knockdown of NCOA3 compromised the optimal activation of the PERK-ATF4 pathway. We found that NCOA3 is required for induction of XBP1 during E2 stimulation and uncover a positive feedback regulatory loop that maintains high levels of NCOA3 and XBP1 in breast cancer. Furthermore, upregulated NCOA3 was required for XBP1-mediated resistance to antihormonal agents. Increased expression of NCOA3 was associated with poor prognosis and higher levels of XBP1-S in breast cancer tissues. Our results uncover a novel steroid hormone-independent role for NCOA3 in UPR signalling. Further we identify a positive feedback regulatory loop consisting of XBP1 and NCOA3 that maintains high levels of NCOA3 and XBP1 expression in breast cancer tissues. Taken together our data identify XBP1-NCOA3 axis that regulates cell fate decisions in ER-positive breast cancer cells.

Quantitative trait locus mapping and functional genomics of an organophosphate resistance trait in the western corn rootworm, Diabrotica virgifera virgifera.

The western corn rootworm, Diabrotica virgifera virgifera, is an insect pest of corn and population suppression with chemical insecticides is an important management tool. Traits conferring organophosphate insecticide resistance have increased in frequency amongst D. v. virgifera populations, resulting in the reduced efficacy in many corn-growing regions of the USA. We used comparative functional genomic and quantitative trait locus (QTL) mapping approaches to investigate the genetic basis of D. v. virgifera resistance to the organophosphate methyl-parathion. RNA from adult methyl-parathion resistant and susceptible adults was hybridized to 8331 microarray probes. The results predicted that 11 transcripts were significantly up-regulated in resistant phenotypes, with the most significant (fold increases ≥ 2.43) being an α-esterase-like transcript. Differential expression was validated only for the α-esterase (ST020027A20C03), with 11- to 13-fold greater expression in methyl-parathion resistant adults (P < 0.05). Progeny with a segregating methyl-parathion resistance trait were obtained from a reciprocal backcross design. QTL analyses of high-throughput single nucleotide polymorphism genotype data predicted involvement of a single genome interval. These data suggest that a specific carboyxesterase may function in field-evolved corn rootworm resistance to organophosphates, even though direct linkage between the QTL and this locus could not be established.

Investigation of In Vivo skin stiffness anisotropy in breast cancer related lymphoedema.

There is a limited range of suitable measurement techniques for detecting and assessing breast cancer related lymphoedema (BCRL). This study investigated the suitability of using skin stiffness measurements, with a particular focus on the variation in stiffness with measurement direction (known as anisotropy). In addition to comparing affected tissue with the unaffected tissue on the corresponding site on the opposite limb, volunteers without BCRL were tested to establish the normal variability in stiffness anisotropy between these two corresponding regions of skin on each opposite limb. Multi-directional stiffness was measured with an Extensometer, within the higher stiffness region that skin typically displays at high applied strains, using a previously established protocol developed by the authors. Healthy volunteers showed no significant difference in anisotropy between regions of skin on opposite limbs (mean decrease of 4.7 +/-2.5% between non-dominant and dominant arms), whereas BCRL sufferers showed a significant difference between limbs (mean decrease of 51.0+/-16.3% between unaffected and affected arms). A large difference in anisotropy was apparent even for those with recent onset of the condition, indicating that the technique may have potential to be useful for early detection. This difference also appeared to increase with duration since onset. Therefore, measurement of stiffness anisotropy has potential value for the clinical assessment and diagnosis of skin conditions such as BCRL. The promising results justify a larger study with a larger number of participants.

Prevention of infectious complications of percutaneous nephrolithotomy.

Infection and sepsis is a complication of percutaneous nephrolithotomy that can lead to morbidity, mortality, and increased costs. Herein we review the current relevant literature on the topic of prevention of sepsis after percutaneous nephrolithotomy.