Aerosol delivery and spatiotemporal tissue distribution of hydroxychloroquine in rat lung.

Inhalation enables the delivery of drugs directly to the lung, increasing the retention for prolonged exposure and maximizing the therapeutic index. However, the differential regional lung exposure kinetics and systemic pharmacokinetics are not fully known, and their estimation is critical for pulmonary drug delivery. The study evaluates the pharmacokinetics of hydroxychloroquine in different regions of the respiratory tract for multiple routes of administration. We also evaluated the influence of different inhaled formulations on systemic and lung pharmacokinetics by identifying suitable nebulizers followed by early characterization of emitted aerosol physicochemical properties. The salt- and freebase-based formulations required different nebulizers and generated aerosol with different physicochemical properties. An administration of hydroxychloroquine by different routes resulted in varied systemic and lung pharmacokinetics, with oral administration resulting in low tissue concentrations in all regions of the respiratory tract. A nose-only inhalation exposure resulted in higher and sustained lung concentrations of hydroxychloroquine with a lung parenchyma-to-blood ratio of 386 after 1440 min post-exposure. The concentrations of hydroxychloroquine in different regions of the respiratory tract (i.e., nasal epithelium, larynx, trachea, bronchi, and lung parenchyma) varied over time, indicating different retention kinetics. The spatiotemporal distribution of hydroxychloroquine in the lung is different due to the heterogeneity of cell types, varying blood perfusion rate, clearance mechanisms, and deposition of inhaled aerosol along the respiratory tract. In addition to highlighting the varied lung physiology, these results demonstrate the ability of the lung to retain increased levels of inhaled lysosomotropic drugs. Such findings are critical for the development of future inhalation-based therapeutics, aiming to optimize target site exposure, enable precision medicine, and ultimately enhance clinical outcomes.

Precision-activated T-cell engagers targeting HER2 or EGFR and CD3 mitigate on-target, off-tumor toxicity for immunotherapy in solid tumors.

To enhance the therapeutic index of T-cell engagers (TCEs), we engineered masked, precision-activated TCEs (XPAT proteins), targeting a tumor antigen (human epidermal growth factor receptor 2 (HER2) or epidermal growth factor receptor (EGFR)) and CD3. Unstructured XTEN polypeptide masks flank the N and C termini of the TCE and are designed to be released by proteases in the tumor microenvironment. In vitro, unmasked HER2-XPAT (uTCE) demonstrates potent cytotoxicity, with XTEN polypeptide masking providing up to 4-log-fold protection. In vivo, HER2-XPAT protein induces protease-dependent antitumor activity and is proteolytically stable in healthy tissues. In non-human primates, HER2-XPAT protein demonstrates a strong safety margin (>400-fold increase in tolerated maximum concentration versus uTCE). HER2-XPAT protein cleavage is low and similar in plasma samples from healthy and diseased humans and non-human primates, supporting translatability of stability to patients. EGFR-XPAT protein confirmed the utility of XPAT technology for tumor targets more widely expressed in healthy tissues.

Pharmacists' Satisfaction with Work and Working Conditions in New Zealand-An Updated Survey and a Comparison to Canada.

BACKGROUND: As roles have evolved over time, changes in workplace environments have created higher patient expectations creating stressful conditions for pharmacists. AIM: To evaluate pharmacists' perceptions of their working conditions, work dissatisfaction, and psychological distress; determine their predictors in New Zealand (NZ); and compare results with Canadian studies and historic NZ data. METHODS: A cross-sectional online survey was distributed to registered pharmacists in NZ. The survey included demographics, work satisfaction, psychological distress, and perceptions of their working conditions (six statements with agreement rated on a 5-point Likert scale). Comparisons were made with surveys from Canada and NZ. Chi-square, t-tests, and non-parametric statistics were used to make comparisons. RESULTS: The response rate was 24.7% (694/2815) with 73.1% practicing in a community pharmacy (45.8% independent, 27.3% chains). Pharmacists disagreed on having adequate time for breaks and tasks, while the majority contemplated leaving the profession and/or not repeating their careers again if given the choice. Working longer hours and processing more prescriptions per day were predictive factors for poorer job satisfaction. More NZ pharmacists perceived their work environment to be conducive to safe and effective primary care (57% vs. 47%, p < 0.001) and reported that they had enough staff (45% vs. 32%, p = 0.002) as compared to Canadian pharmacists. Pharmacists' job satisfaction and psychological distress have not improved compared to the assessment 20 years prior. CONCLUSIONS: NZ pharmacists perceive working conditions to be sub-optimal yet had higher satisfaction than their Canadian counterparts. Work dissatisfaction and psychological distress are high and have not improved over the last two decades.

Deadliness of Traumatic Subdural Hematomas in the First Quarter of the Year: A Measurement by the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP).

Background Traumatic acute subdural hematoma (ASDH) is a surgical emergency and has been associated with high morbidity and mortality. However, it is not known whether mortality from ASDH occurs more frequently in a particular season. Methodology We queried the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) from 2016 to 2019. They were identified in the NSQIP using the International Classification of Diseases (ICD-10) code S06.5 to capture all admissions with a primary diagnosis of traumatic subdural hematoma. Mortality rates were reviewed per season, defined as three consecutive months in the year. Demographics such as age, race, ethnicity, height, and weight were reviewed. Comorbidities such as diabetes, risk factors, including smoking history, and hospitalization characteristics, such as admission year, operation year, and inpatient/outpatient treatment type, were also reviewed. Results A total of 1,656 patients were included in this study. The mean age of all participants was 70.6 years, with 37% (604/1,656) being female. The mortality rate was highest in January, February, and March at 24.5% (104/425, P = 0.045) of admitted patients compared to mortality rates of 18.8% (70/373) in April to June, 18.4% (81/441) in July to September, and 17.5% (73/417) in October to December. Conclusions Mortality is significantly greater during the winter months of January, February, and March among patients with ASDH. Despite better survival rates of ASDH over the past two decades, postoperative mortality rates still remain high.

Lived experience of dietary change among Chinese colorectal cancer survivors in Hong Kong: A qualitative study.

OBJECTIVES: This is a qualitative study which aims to understand the lived experience of dietary changes among Chinese survivors of colorectal cancer who participated in a dietary intervention. SETTING: The surgical and oncological departments of four public hospitals in Hong Kong. PARTICIPANTS: Fifty-five Chinese colorectal cancer survivors who were aged 18 years or above and had received potentially curative treatment in the surgical and oncological departments in Hong Kong were examined. Participants' mean age was 64 years, with 29 (53%) males. INTERVENTION: A 12-month dietary intervention delivered via face-to-face motivational interviews, fortnightly motivational phone calls, monthly electronic pamphlets, quarterly newsletters and quarterly group meeting. OUTCOME MEASURE: We adopted the qualitative approach to capture participants' perspectives and to apply the understanding pragmatically in everyday life. Content analysis was conducted. RESULTS: We identified themes of motives to changes of dietary practices including (1) individual commitment to dietary change; (2) adaptive strategies in interpersonal contexts and (3) working with healthcare professionals during the journey. CONCLUSIONS: The findings demonstrated how Chinese custom and culture posing unique challenges to colorectal cancer survivors and the need of having dietary advice from healthcare professionals. Participants were motivated to change their eating habits by support from family, friends and healthcare professionals. Our findings could help healthcare professionals provide specific dietary advice and guidance to Chinese colorectal cancer survivors. TRIAL REGISTRATION NUMBER: NCT01708824.

Sterile Leukocytosis Predicts Hemorrhagic Transformation in Arterial Ischemic Stroke: A National Inpatient Sample Study.

OBJECTIVE: Hemorrhage transformation (HT) is a known complication of arterial ischemic stroke (AIS). In addition, it is known that the increase of proinflammatory immune cells in the brain tissue after AIS predict worse outcomes. However, it is not clear whether inflammation due to preceding or post-stroke infections affect outcomes and moreover, if systemic inflammatory markers could be useful as a clinical prediction tool for HT post-stroke. Therefore, our objective was to assess the association between systemic pro-inflammatory profile in AIS patients with HT and in-hospital mortality that did not course with acute infections during hospitalization. METHODS: This study was conducted using the 2016 and 2017 National Inpatient Sample (NIS) with International Classification of Diseases (ICD-10) codes. Multivariate logistic regression was used to examine the association between HT and in-hospital mortality with pro-inflammatory anomalies of white blood cells (WBCs) in AIS patients. Exclusion criteria comprised patients with under 18 years old, and with a diagnosis of gastrointestinal, urogenital, respiratory infection, bacteremia, viral infection, sepsis, or fever. RESULTS: A total of 212,356 patients with AIS were included in the analysis. 422 (0.2%) patients had a HT and 10,230 (4.8%) patients died during hospitalization. The most common WBC pro-inflammatory marker was leukocytosis with 6.9% (n=29/422) of HT and 5.5% (n=560/10,230) of patients that died during hospitalization. After adjusting for socio-demographic, comorbidities and treatment factors, leukocytosis was found to be an independent risk factor for both outcomes, HT [OR = 1.5, 95% CI: 1-2.3, p=0.024] and, in-hospital mortality [OR = 1.5, 95% CI: 1.3-1.6, p < 0.001]. CONCLUSION: Sterile leukocytosis is a potential clinical prediction tool to determine which patients are at higher risk of developing HT and die during hospitalization.

White matter hyperintensities and cognition across different Alzheimer's biomarker profiles.

BACKGROUND/OBJECTIVES: To examine the association between white matter hyperintensities (WMH) and cognitive domains such as memory and executive function (EF) across different clinical and biomarker categories of Alzheimer's disease (AD). DESIGN: Cross-sectional study. SETTING: Alzheimer's Disease Neuroimaging Initiative. PARTICIPANTS: A total of 216 cognitively normal (CN) participants and 407 participants with mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) at baseline. MEASUREMENTS: Based on the 2018 research framework, participants were classified using AT(N) (amyloid-ß deposition [A], pathologic tau [T], and neurodegeneration [(N)]) biomarkers into one of three categories: biomarker negative [A - T- (N)-], amyloid negative but other biomarker positive [A - T ± (N)+ or A - T + (N)±] or amyloid positive [A + T ± (N)±]. Linear regression models were then used to examine the association between WMH and memory composite scores and EF composite scores. RESULTS: Higher WMH burden was associated with worse EF in both CN and MCI subgroups while a significant association between WMH and memory was only found in the MCI subgroup. Furthermore, WMH was associated with EF in the group with A - T ± (N)+ or A - T + (N)± biomarker category, but not for A - T - (N)- (normal biomarker) and A + T ± (N) ± (AD pathology). The association between higher WMH and worse memory was independent of amyloid levels in individuals with MCI with evidence of AD pathology. CONCLUSION: Vascular disease, as indexed by WMH, independent of AD pathology affects cognitive function in both CN and MCI subgroups. Future studies using the AT(N) research framework should consider white matter lesions as a key biomarker contributing to the clinical presentation of AD.

Medical Malpractice and Trigeminal Neuralgia: An Analysis of 49 Cases.

PURPOSE: Our study fills the vacancy of litigation research related to trigeminal neuralgia management, giving health care providers the information needed to understand the potential litigious outcomes that follow treatment methods. METHODS: We queried the Westlaw database to identify litigation cases related to trigeminal neuralgia management. Key variables extracted included medical complaints, trial outcomes, and demographics. Continuous variables were compared between cases in favor of defendant and cases in favor of plaintiff using t-test or Wilcoxon rank sum test. Categorial variables were compared using χ2 or Fisher exact test. RESULTS: About 49 cases met the inclusion criteria-for those cases surgical complications (42.9%) were cited as the most common reasons for malpractice claims. Cranial nerve deficits (34.7%) were the most frequent postoperative complaints. Verdicts ruled in favor of the plaintiff in 26.5% of cases with a mean payout of $1,982,428.46. Dentists were included in the most cases, 63.3%, and the average payout was $415,908, whereas neurosurgeons were involved in 20.4% of cases with an average payout of $618,775. Cases with verdicts in favor of the plaintiff were more likely to be older than cases with verdicts in favor of the defendant (P = .03). CONCLUSIONS: Over one-half of cases resulted in verdicts in favor of the defendant with surgical complications cited as the most common reason for litigation. Dentistry was the most common individual clinical specialty for defendants, whereas neurosurgery contributed to the largest average payout based on specialty (for n > 1). Cranial nerve deficits were the most common plaintiff postoperative complaints. These analyses may help doctor teams involved in management of trigeminal neuralgia to have a more informed discussion with the patient at every visit so that such litigations may be avoided.

Medical malpractice and meningiomas: an analysis of 47 cases.

OBJECTIVE: Among medical practices, surgical fields, including neurosurgery, are at a high risk for medical malpractice litigation. With meningiomas contributing to 10% of the total neurosurgery litigation cases, the aim of this study was to identify demographic characteristics, reasons for litigation, and surgical complications commonly reported in these cases. This analysis serves to increase neurosurgeons' awareness of factors associated with medical malpractice litigation. METHODS: The online legal database Westlaw was utilized to query public litigation cases related to the medical management of meningiomas between December 1985 and May 2020. Variables extracted included the following: plaintiff and defendant demographics, litigation category, plaintiff medical complaints, and trial outcomes. The authors compared these characteristics between cases with decisions in favor of the defendant and those with decisions in favor of the plaintiff. RESULTS: A total of 47 cases met the inclusion criteria. Failure to diagnose (68.1%) was the most common type of malpractice claim, and surgical complications (19.1%), motor weakness (33%), and financial loss (33%) were cited as the most common postoperative complaints. Individual specialties that most often required defense due to malpractice claims were radiology (21.7%) and neurosurgery (19.6%). The jury verdict was in favor of the defense in 51.1% of cases and in favor of the plaintiff in 27.7% of cases. A settlement was reached in 19.1% of cases. The mean payout for a verdict in favor of the plaintiff was $3,409,650.22, while the mean payout for settlements was $867,555.56. The greatest average payout for specialties was in neurosurgery at $3,414,400, followed by radiology at $3,192,960. Cases with a verdict in favor of the plaintiff were more likely to involve an internal medicine physician as a defendant (p = 0.007). CONCLUSIONS: Over one-half of the cases resulted in a defendant's verdict with failure to diagnose cited as the most common reason for litigation. Radiology and neurosurgery were the most common specialties for legal cases and also had some of the largest average payouts based on specialty. Motor weakness and financial loss were the most common plaintiff postoperative complaints. These findings may inform surgeons on active measures to take, such as increasing focus on diagnostic accuracy and reducing specific postoperative complaints, such as motor weakness, through risk management and prophylactic measures, to reduce unfavorable legal outcomes.

Urban Trees and Human Health: A Scoping Review.

The urban forest is a green infrastructure system that delivers multiple environmental, economic, social and health services, and functions in cities. Environmental benefits of urban trees are well understood, but no review to date has examined how urban trees affect human health. This review provides a comprehensive summary of existing literature on the health impacts of urban trees that can inform future research, policy, and nature-based public health interventions. A systematic search used keywords representing human health, environmental health, and urban forestry. Following screening and appraisal of several thousand articles, 201 studies were conceptually sorted into a three-part framework. Reducing Harm, representing 41% of studies, includes topics such as air pollution, ultraviolet radiation, heat exposure, and pollen. Restoring Capacities, at 31%, includes attention restoration, mental health, stress reduction, and clinical outcomes. Building Capacities, at 28%, includes topics such as birth outcomes, active living, and weight status. The studies that were reviewed show substantial heterogeneity in purpose and method yet indicate important health outcomes associated with people's exposure to trees. This review will help inform future research and practice, and demonstrates why urban forest planning and management should strategically promote trees as a social determinant of public health.

Effects of dietary and physical activity interventions on generic and cancer-specific health-related quality of life, anxiety, and depression in colorectal cancer survivors: a randomized controlled trial.

PURPOSE: To assess the effects of dietary and physical activity (PA) interventions on generic and cancer-specific quality of life (QoL), anxiety, and depression levels among adult Chinese colorectal cancer (CRC) survivors. METHODS: Two-hundred twenty-three adult CRC survivors within 1 year of completion of primary cancer treatment were randomized to receive dietary, PA or combined intervention, or usual care for a 12 monthduration, under a 2 (diet vs usual care) × 2 (PA vs usual care) factorial design. Generic and cancer-specific QoL was assessed using a Chinese version 12-Item Short Form Health Survey (SF-12) and the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) scale, respectively. Anxiety and depression was assessed using the Hospital Anxiety and Depression Scale at baseline, 6, 12, 18, and 24 months. Linear mixed models were used for examining the intervention effects. RESULTS: Participants receiving dietary intervention experienced a significant improvement in the generic measure of QoL (SF-6D utility scores, mean difference 0.042, 95%CI 0.03 to 0.081) at 12 months, the cancer-specific QoL scores (mean difference 3.09, 95%CI 0.13 to 6.04), and levels of depression (P = 0.015) at both 12 and 24 months follow-up. Participants receiving PA intervention only demonstrated a significant improvement in SF-6D utility index (mean difference 0.039, 95%CI 0.002 to 0.077) and physical functioning (mean difference 2.85, 95%CI 1.00 to 4.70) at 6 months. CONCLUSIONS: Dietary intervention improved the generic and cancer-specific QoL and depression in CRC survivors. TRIAL REGISTRATION: The study was prospectively registered on 17 October 2012 at ClinicalTrials.gov (NCT01708824). IMPLICATIONS FOR CANCER SURVIVORS: CRC survivors can benefit from dietary interventions in alleviating depression and improving overall health-related QoL.

Wnt5a induces ROR1 to recruit cortactin to promote breast-cancer migration and metastasis.

ROR1 is a conserved oncoembryonic surface protein expressed in breast cancer. Here we report that ROR1 associates with cortactin in primary breast-cancer cells or in MCF7 transfected to express ROR1. Wnt5a also induced ROR1-dependent tyrosine phosphorylation of cortactin (Y421), which recruited ARHGEF1 to activate RhoA and promote breast-cancer-cell migration; such effects could be inhibited by cirmtuzumab, a humanized mAb specific for ROR1. Furthermore, treatment of mice bearing breast-cancer xenograft with cirmtuzumab inhibited cortactin phosphorylation in vivo and impaired metastatic development. We established that the proline at 841 of ROR1 was required for it to recruit cortactin and ARHGEF1, activate RhoA, and enhance breast-cancer-cell migration in vitro or development of metastases in vivo. Collectively, these studies demonstrate that the interaction of ROR1 with cortactin plays an important role in breast-cancer-cell migration and metastasis.

Mucopenetration and biocompatibility of polydopamine surfaces for delivery in an Ex Vivo porcine bladder.

Urine voiding and the presence of a mucus layer on the apical surface of the urothelium are two major challenges towards an effective intravesical drug delivery for bladder malignancies. Improved bioavailability to the underlying bladder tissue could be achieved with delivery vectors that diffuse efficiently through the bladder mucus. Pegylation of delivery vectors remains the existing "gold standard" to enhance mucosal delivery despite known poor cell uptake and reported PEG sensitivity. Here, we showed improved mucopenetration of carboxylated polystyrene (PS) nanoparticles (NPs) passivated with a polydopamine (PDA) surface, at similar level as PEG. While the diffusion of PS NPs in mucus was retarded by ~1000-fold, PS-PDA diffused only 6-fold slower in mucus than water. This enabled faster and deeper penetration of PS-PDA into porcine bladder tissue beneath the mucus layer. The same PDA surface also conferred biocompatibility and enabled photothermal therapy (PTT) with significant surface disruption on an ex vivo porcine bladder model upon localized laser irradiation, which was not possible with PEG. Our outcomes suggested the facile and versatile PDA surface passivation of nanoparticles as an enabler for dual purposes of enhancing mucopenetration and allowing photothermal therapy on bladder tissue, which has not been demonstrated to date.

Inhibition of chemotherapy resistant breast cancer stem cells by a ROR1 specific antibody.

Breast cancers enduring treatment with chemotherapy may be enriched for cancer stem cells or tumor-initiating cells, which have an enhanced capacity for self-renewal, tumor initiation, and/or metastasis. Breast cancer cells that express the type I tyrosine kinaselike orphan receptor ROR1 also may have such features. Here we find that the expression of ROR1 increased in breast cancer cells following treatment with chemotherapy, which also enhanced expression of genes induced by the activation of Rho-GTPases, Hippo-YAP/TAZ, or B lymphoma Mo-MLV insertion region 1 homolog (BMI1). Expression of ROR1 also enhanced the capacity of breast cancer cells to invade Matrigel, form spheroids, engraft in Rag2-/-[Formula: see text] mice, or survive treatment with paclitaxel. Treatment of mice bearing breast cancer patient-derived xenografts (PDXs) with the humanized anti-ROR1 monoclonal antibody cirmtuzumab repressed expression of genes associated with breast cancer stemness, reduced activation of Rho-GTPases, Hippo-YAP/TAZ, or BMI1, and impaired the capacity of breast cancer PDXs to metastasize or reengraft Rag2-/-[Formula: see text] mice. Finally, treatment of PDX-bearing mice with cirmtuzumab and paclitaxel was more effective than treatment with either alone in eradicating breast cancer PDXs. These results indicate that targeting ROR1 may improve the response to chemotherapy of patients with breast cancer.

Refractive error magnitude and variability: Relation to age.

PURPOSE: To investigate mean ocular refraction (MOR) and astigmatism, over the human age range and compare severity of refractive error to earlier studies from clinical populations having large age ranges. METHODS: For this descriptive study patient age, refractive error and history of surgery affecting refraction were abstracted from the Waterloo Eye Study database (WatES). Average MOR, standard deviation of MOR and astigmatism were assessed in relation to age. Refractive distributions for developmental age groups were determined. MOR standard deviation relative to average MOR was evaluated. Data from earlier clinically based studies with similar age ranges were compared to WatES. RESULTS: Right eye refractive errors were available for 5933 patients with no history of surgery affecting refraction. Average MOR varied with age. Children <1 yr of age were the most hyperopic (+1.79D) and the highest magnitude of myopia was found at 27yrs (-2.86D). MOR distributions were leptokurtic, and negatively skewed. The mode varied with age group. MOR variability increased with increasing myopia. Average astigmatism increased gradually to age 60 after which it increased at a faster rate. By 85+ years it was 1.25D. J0 power vector became increasingly negative with age. J45 power vector values remained close to zero but variability increased at approximately 70 years. In relation to comparable earlier studies, WatES data were most myopic. CONCLUSIONS: Mean ocular refraction and refractive error distribution vary with age. The highest magnitude of myopia is found in young adults. Similar to prevalence, the severity of myopia also appears to have increased since 1931.

Dietary and Physical Activity Interventions for Colorectal Cancer Survivors: A Randomized Controlled Trial.

There has been evidence on the protective effects of diets high in fiber and low in red and processed meat (RPM), and physical activity (PA) against colorectal cancer (CRC) development, but that against CRC recurrence has been limited. This study evaluated the efficacy of a behavioral program comprising dietary and PA interventions in improving Chinese CRC survivors' lifestyle. A 2 × 2 factorial randomized controlled trial of 223 CRC patients (82 females, mean age 65), randomly assigned to receive dietary, PA or both interventions, or usual care for 12 months, and assessed every 6 months for 24 months. Primary outcomes included two dietary and two PA targets. Secondary outcomes included changes in dietary consumptions and PA levels. Dietary interventions significantly increased the odds of achieving the targets of consuming less RPM at all time-points (OR 3.22-4.57, all p < 0.01) and refined grain (RG) at months 6 (OR 3.13, p = 0.002) and 24 (OR 2.19, p = 0.039), and reduced RPM (2.49-3.48 servings/week, all p < 0.01) and RG (0.31-0.5 servings/day, all p < 0.01) consumptions. Patients receiving PA interventions potentially spent more time on moderate-to-vigorous PA. This study demonstrated the efficacy of a behavioral program in improving dietary habits of Chinese CRC survivors.

Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3.

Emerging evidence indicates that the pathogenesis of Parkinson's disease (PD) may be due to cell-to-cell transmission of misfolded preformed fibrils (PFF) of α-synuclein (α-syn). The mechanism by which α-syn PFF spreads from neuron to neuron is not known. Here, we show that LAG3 (lymphocyte-activation gene 3) binds α-syn PFF with high affinity (dissociation constant = 77 nanomolar), whereas the α-syn monomer exhibited minimal binding. α-Syn-biotin PFF binding to LAG3 initiated α-syn PFF endocytosis, transmission, and toxicity. Lack of LAG3 substantially delayed α-syn PFF-induced loss of dopamine neurons, as well as biochemical and behavioral deficits in vivo. The identification of LAG3 as a receptor that binds α-syn PFF provides a target for developing therapeutics designed to slow the progression of PD and related α-synucleinopathies.

The effect of topical anti blister products on the risk of friction blister formation on the foot.

INTRODUCTION: Foot blisters are a common injury, which can impact on activity and lead to infection. Increased skin surface hydration has been identified as a risk factor for blister formation, indicating that a reduction in hydration could reduce the risk of blister. METHOD: Thirty healthy adults were randomised into 3 groups, each receiving a preventative foot blister treatment (2Toms(®) Blister Shield(®); Flexitol(®) Blistop and Boots Anti-Perspirant Foot Spray). Cycles of compression and shear loads where applied to heel skin using a mechanism driven by compressed air. Temperature changes were measured during load application using a thermal imaging camera (FLIR Systems Inc. and Therm CAM™ Quick Report). Near surface hydration of the skin was measured using a Corneometer(®) (C & K, Germany). RESULTS: There was no significant difference in the rate of temperature change of the skin between the three groups compared to not using products (p = 0.767, p = 0.767, p = 0.515) or when comparing each product (p = 0.551). There was a significant decrease in near surface skin hydration, compared to baseline, after the application of powder (-8.53 AU, p = 0.01). There was no significant difference in hydration after the application of film former and antiperspirant (-1.47 AU, p = 0.26; -1.00 AU, p = 0.80, respectively). CONCLUSION: With the application of external load we found no significant difference in the effect of the three products on temperature change. The powder product demonstrated an effect on reducing the risk of blister. It is postulated that powder may have a barrier effect.

The evaluation of three treatments for plantar callus: a three-armed randomised, comparative trial using biophysical outcome measures.

BACKGROUND: Callus is one of the most common foot skin complaints experienced by people of all ages. These painful and unsightly lesions often result in disability. The 'gold standard' of treatment is scalpel debridement by a trained specialist; however, people also seek over-the-counter remedies. There is a lack of clinical evidence for the efficacy of such products, which makes selection by patients and practitioners difficult. METHODS: This randomised, three-armed, parallel, comparative trial aimed to test the efficacy of two home treatments for plantar callus using novel, objective outcome measures (skin hydration using the capacitance method; elasticity using negative pressure application; and surface texture using imaging). Additional outcome measures were: size of callus, quality of life (Foot Health Status Questionnaire) and self-reported participant satisfaction and compliance. The results were compared to a podiatry treatment. Participants were randomly allocated to one of three groups: potassium hydroxide (KOH, 40 %); trichloroacetic acid (TCA); and podiatry treatment. Participants were followed for 3 weeks after their initial intervention appointment (days 7, 14 and 21). The primary outcomes were the change from baseline in callus hydration, elasticity, texture, and size at each of the three time points. The secondary outcomes where: change in quality of life 21 days after treatment; resolution of calluses via visual inspection; and participant compliance and perception. RESULTS: Forty-six participants (61 ft) with plantar calluses were recruited. The podiatry treatment showed immediate and significant changes in all objective outcomes, associated foot pain and function (p <0.01). Lesser changes in skin quality and perceived pain and functional benefits occurred with TCA and KOH over 21 days. CONCLUSIONS: This is the first study where objective outcome measures have been used to measure changes in the nature of skin in response to callus treatments. We found significant differences in plantar callus in response to podiatry and two home treatments. The podiatry treatment showed immediate and significant changes in skin and associated foot pain and function. Lesser, but sometimes comparable, changes in skin and perceived pain and functional benefits occurred with TCA and KOH over 21 days. TRIAL REGISTRATION: ISRCTN14751843 : date of registration: 30 April 2015.