pH drives electron density fluctuations that enhance electric field-induced liquid flow.

Liquid flow along a charged interface is commonly described by classical continuum theory, which represents the electric double layer by uniformly distributed point charges. The electrophoretic mobility of hydrophobic nanodroplets in water doubles in magnitude when the pH is varied from neutral to mildly basic (pH 7 → 11). Classical continuum theory predicts that this increase in mobility is due to an increased surface charge. Here, by combining all-optical measurements of surface charge and molecular structure, as well as electronic structure calculations, we show that surface charge and molecular structure at the nanodroplet surface are identical at neutral and mildly basic pH. We propose that the force that propels the droplets originates from two factors: Negative charge on the droplet surface due to charge transfer from and within water, and anisotropic gradients in the fluctuating polarization induced by the electric field. Both charge density fluctuations couple with the external electric field, and lead to droplet flow. Replacing chloride by hydroxide doubles both the charge conductivity via the Grotthuss mechanism, and the droplet mobility. This general mechanism deeply impacts a plethora of processes in biology, chemistry, and nanotechnology and provides an explanation of how pH influences hydrodynamic phenomena and the limitations of classical continuum theory currently used to rationalize these effects.

Ustekinumab treatment for moderate-to-severe plaque psoriasis: eight-year real-life experience.

Background: Limited information is available from real-life studies evaluating the long-term efficacy and drug retention of ustekinumab.Research design and methods: Data from 378 patients with moderate-severe psoriasis were retrospectively analyzed. Over 8 years, disease severity and treatment response were evaluated using the PASI score. Predictors of PASI response were evaluated by logistic regression. Ustekinumab retention rate was calculated by the Kaplan-Meier method.Results: Over the 8 years, >80% of patients achieved a PASI score of <3 and PASI 75, 90 and 100 response was achieved in 76.2%, 61.9% and 57.1% of patients, respectively. Predictor variables for improved PASI response (after 2 years) were HLA-C*06-POS patients, female gender and BMI <30 Kg/M2. The 2-year retention rate was 81% and 59% after 8 years with mean retention rate of 5.4 years. Improved retention rate was observed in patients positive for the HLA-C*06 allele (3.7 vs. 2.5 years, p = 0.005) and female gender (3.7 vs. 3.3 years, p = 0.06), with no significant difference observed in other patient groups. Ustekinumab was generally well tolerated without evidence of cumulative toxicity or organ toxicity.Conclusion: The long-term use of ustekinumab was observed to be effective and safe in patients with moderate-severe chronic psoriasis in a real world-setting.

Sex-related differences of clinical features in hidradenitis suppurativa: analysis of an Italian-based cohort.

The clinical characteristics associated with hidradenitis suppurativa (HS) severity are poorly understood. In this study, 124 patients with HS from 6 Italian dermatology centres participated in this study. Disease severity was assessed using the Hidradenitis Suppurativa Physician's Global Assessment score (HS-PGA) and Hurley score. The impact of clinical characteristics on disease severity was assessed by logistic regression. Clinical characteristics were similar between men (n = 53) and women (n = 71). Disease severity was also similar; 75% of the patients had Hurley stage II or III disease, and > 60% had moderate, severe or very severe HS as judged by HS-PGA. Lesions were more frequent in the gluteal region in men (32.3% in men vs. 8.7% in women, P < 0.001) and more frequent on the breast in women (16.3% in women vs. 4.6% in men, P = 0.02). Obesity was associated with increased disease severity as measured by HS-PGA (OR: 3.28, 95% CI 1.55-6.95, P < 0.01) and Hurley classification (OR: 3.22, 95% CI 1.34-7.31, P < 0.01). Although severity of HS is similar between the sexes, the localization of lesions is different.

Slipped Upper Femoral Epiphysis: Are We Missing the Point?

Slipped upper femoral epiphysis (SUFE) is one of the most common orthopaedic conditions in adolescents. SUFE typically presents as hip pain and limping, but it may present deceptively as knee pain or contralateral hip pain. We discuss a case of a child with a deceptive presentation of SUFE resulting in delayed diagnosis.

Psoriasis Area and Severity Index response in moderate-severe psoriatic patients switched to adalimumab: results from the OPPSA study.

BACKGROUND: Few studies have compared the efficacy of switching to adalimumab in the real-life setting in plaque psoriasis patients. OBJECTIVE: To evaluate the effect of adalimumab in psoriasis patients previously treated with other biologics. METHODS: In this multicentre study, psoriasis patients (N = 262) treated with an anti-TNF-alpha agent, ustekinumab or naïve to biologics then switched to adalimumab were included. Disease severity was assessed by the Psoriasis Area and Severity Index (PASI) at baseline and after 3, 6, 12, 24 and 36 months. The association between clinical risk factors and achievement of PASI response was evaluated by logistic regression. RESULTS: Adalimumab treatment resulted in a decrease in PASI (15.1 ± 6.2 at baseline vs. 2.7 ± 4.8 at 6 months, P < 0.0001), regardless of previous biologic treatment. Furthermore, adalimumab allowed 92.5%, 79% and 56% of patients to achieve PASI response (PASI 50, 75 and 90, respectively) and complete remission (PASI 100 response) in 48.4% of patients, by 6 months and maintained over 3 years, independent of prior biologic treatment. The absence of metabolic syndrome, dyslipidemia, hypertension and lower PASI and lower age at baseline was associated with achievement of PASI response at 3, 6 and 12 months, whereas at later time points (24 and 36 months), PASI 90 and PASI 100 response was associated with diagnosis of psoriasis/psoriatic arthritis. CONCLUSION: Adalimumab was effective at reducing PASI score over 3 years, irrespective of whether patients were biologic naïve or previously treated with a TNF-alpha or IL-12/23 inhibitor.

Effect of biophysical therapy on articular pain in a primary care setting compared to ibuprofen and placebo: a randomized controlled trial.

Articular pain is one of the most frequent complaints practitioners face in their daily work. With an aging population, many patients have multiple comorbidities that are associated with the presence of chronic diseases, while others experience allergies, side effects or do not respond to standard medications or procedures. Therefore, there is an urgent need for new effective and safe strategies to manage articular pain, especially in its chronic manifestations. This randomized controlled trial was designed to assess the efficacy of a single therapy session using a biophysical procedure matched with a common non-steroidal anti-inflammatory drug (ibuprofen) and placebo. Biophysical therapy was performed using a Med Select 729 device. One hundred fifty patients (mean age 56±15.6 years) diagnosed with acute or chronic articular pain at different locations were randomized into 3 groups and the Numeric Pain Rating Score (NPRS) was used to measure pain at baseline, after one week, one month, and three months. While no difference in NPRS was observed at baseline among the 3 groups, a statistically significant difference was observed at all subsequent time points, respectively, after one week (p less than 0.05), one month (p less than 0.001), and three months (p less than 0.01), for both ibuprofen and biophysical groups vs placebo. Biophysical treatment of articular pain was shown to be as effective as a conventional non-steroidal anti-inflammatory treatment over a period of 3 months compared to placebo and could, therefore, represent an integrative, safe and long-lasting therapy to be considered for the management of acute and particularly chronic articular pain in current medical practice.

Public health response to an imported case of canine melioidosis.

Melioidosis in humans presents variably as fulminant sepsis, pneumonia, skin infection and solid organ abscesses. It is caused by Burkholderia pseudomallei, which in the United States is classified as a select agent, with "potential to pose a severe threat to both human and animal health, to plant health or to animal and plant products" (Federal Select Agent Program, http://www.selectagents.gov/, accessed 22 September 2016). Burkholderia pseudomallei is found in soil and surface water in the tropics, especially South-East Asia and northern Australia, where melioidosis is endemic. Human cases are rare in the United States and are usually associated with travel to endemic areas. Burkholderia pseudomallei can also infect animals. We describe a multijurisdictional public health response to a case of subclinical urinary B. pseudomallei infection in a dog that had been adopted into upstate New York from a shelter in Thailand. Investigation disclosed three human contacts with single, low-risk exposures to the dog's urine at his residence, and 16 human contacts with possible exposure to his urine or culture isolates at a veterinary hospital. Contacts were offered various combinations of symptom/fever monitoring, baseline and repeat B. pseudomallei serologic testing, and antibiotic post-exposure prophylaxis, depending on the nature of their exposure and their personal medical histories. The dog's owner accepted recommendations from public health authorities and veterinary clinicians for humane euthanasia. A number of animal rescue organizations actively facilitate adoptions into the United States of shelter dogs from South-East Asia. This may result in importation of B. pseudomallei into almost any community, with implications for human and animal health.

Diagnostic exome sequencing in children: A survey of parental understanding, experience and psychological impact.

Clinical exome sequencing (CES) is increasingly being used as an effective diagnostic tool in the field of pediatric genetics. We sought to evaluate the parental experience, understanding and psychological impact of CES by conducting a survey study of English-speaking parents of children who had diagnostic CES. Parents of 192 unique patients participated. The parent's interpretation of the child's result agreed with the clinician's interpretation in 79% of cases, with more frequent discordance when the clinician's interpretation was uncertain. The majority (79%) reported no regret with the decision to have CES. Most (65%) reported complete satisfaction with the genetic counseling experience, and satisfaction was positively associated with years of genetic counselor (GC) experience. The psychological impact of CES was greatest for parents of children with positive results and for parents with anxiety or depression. The results of this study are important for helping clinicians to prepare families for the possible results and variable psychological impact of CES. The frequency of parental misinterpretation of test results indicates the need for additional clarity in the communication of results. Finally, while the majority of patients were satisfied with their genetic counseling, satisfaction was lower for new GCs, suggesting a need for targeted GC training for genomic testing.

Black patients sustain vision loss while White and South Asian patients gain vision following delamination or segmentation surgery for tractional complications associated with proliferative diabetic retinopathy.

PurposeThis retrospective comparative case series aims to determine whether patient ethnicity (White versus South Asian versus Black) is related to the outcome of surgical treatment for traction complications of severe proliferative diabetic retinopathy (PDR).SettingMoorfields Eye Hospital London, UK.MethodsAll patients who underwent vitrectomy with, delamination and/or segmentation for PDR over a 5-year period (2009-2014) were reviewed retrospectively. Patients were divided into White, South Asian or Black groups, and their age, gender, HbA1C and type of diabetes were recorded. A total of 484 patients (253 White, 117 South Asian, 114 Black) were included. Twenty-one patients were excluded due to inadequate documentation.OutcomesLogMAR Visual acuity (converted from Snellen) (VA), was recorded pre-operatively and ~6 months post surgery (range 5-8 months). Surgical outcome was classified according to the type and duration of tamponade required post-operatively.ResultsPre-operative VA and HbA1C values were similar across all three ethnic groups (P=0.64 and 0.569, respectively). Change in VA (mean±SD) was 0.41±0.78, 0.14±0.76 and -0.26±0.57 in White, South Asian and Black patient groups respectively (P<0.001). Multiple regression analysis showed that post-op VA was significantly related to race and pre-op VA only (both P<0.001). The Black patient group were more likely to require silicone oil tamponade (P<0.001) and long-term retention of silicone oil (P<0.001) than the White and South Asian patient groups.ConclusionsThis study demonstrates that Black patients on average lose vision following delamination surgery for traction complications of PDR while White and South Asian patients gain vision. The same group is also at higher risk of retaining silicone more than 6 months after surgery. This difference remains even when corrected for glycaemic control. The higher risk of visual loss and long-term retention of silicone oil in black patients requires further investigation. If these results are confirmed, surgeons should consider their patients' ethnicity before proceeding with surgical treatment of diabetic tractional detachment.

Improving Management of Paediatric Buckle Fracture in Orthopaedic Outpatients: A Completed Audit Loop.

Introduction Paediatric patient bone fractures are the source of a large number of orthopaedic outpatient visits, especially for fracture clinics. The National Institute for Health and Care Excellence (NICE) guideline NG38 provides guidance on assessing and managing non-complex fractures, such as buckle (i.e., torus) fractures in paediatric patients. Objective We retrospectively audited outpatient records of children younger than 12 years presenting with distal radius buckle fractures for May and June 2017. We compared our practice against the NICE guideline standards. We made certain changes in our practice and then repeated the exercise prospectively for two months from July 15 to September 15, 2017. Material and Methods We identified 31 patients who fit our inclusion criteria. After instituting changes based on the NICE guidelines, the number of children included in the prospective data collection was 33 patients. Results For the 31 children treated according to our older protocol, we had 59 outpatient visits, with an average of 1.90 visits for every child. After the NICE-driven changes were made to our management, 33 patients were treated in 39 visits with an average of 1.2 visits per child. Conclusion Introducing NICE guidelines allowed for considerable improvement in the management and treatment of paediatric patient bone fractures. It is important to fully implement the NICE guidelines not only in fracture clinics but also in other departments, such as accident and emergency departments.

The UK Neovascular AMD Database Report 3: inter-centre variation in visual acuity outcomes and establishing real-world measures of care.

PurposeInternational variations in visual acuity (VA) outcomes of eyes treated for neovascular age-related macular degeneration (nAMD) are well-documented, but intra-country inter-centre regional variations are not known. These data are important for national quality outcome indicators. We aimed to determine intra-country and inter-centre regional variations in outcomes for treatment of nAMD.Patients and methodsProspective multicentre national database study of 13 UK centres that treated patients according to a set protocol (three loading doses, followed by Pro-Re-Nata retreatment). A total of 5811 treatment naive eyes of 5205 patients received a total of 36 206 ranibizumab injections over 12 months.ResultsMean starting VA between centres varied from 48.9 to 59.9 ETDRS letters. Mean inter-centre VA change from baseline to 12 months varied from +6.9 letters to -0.6 letters (mean of +2.5 letters). The proportion of eyes achieving VA of 70 letters or more varied between 21.9 and 48.7% at 12 months. Median number of injections (visits) at each centre varied from 5 to 8 (9 to 12), with an overall median of 6 (11). Age, starting VA, number of injections, and visits, but not gender were significantly associated with variation in these VA outcomes (P<0.01). Significant variation between centres persisted even after adjusting for these factors.ConclusionThere are modest differences in VA outcomes between centres in the UK. These differences are influenced, but not completely explained, by factors such as patient age, starting VA, number of injections, and visits. These data provide an indication of the VA outcomes that are achievable in real-world settings.

Does delay in referral of proliferative diabetic retinopathy from the diabetic eye screening programme lead to visual loss?

AimsTo ascertain the effect on visual acuity (VA) of a delay in Hospital Eye Service (HES) consultation for patients referred with proliferative diabetic retinopathy (PDR; R3) from the Diabetic Eye Screening Programme (DESP).MethodsAll patients referred to Moorfields Eye Hospital from DESP between April and December 2013 with a referral diagnosis of PDR in at least one eye were eligible. Screening programme VA was compared with VA at first HES appointment and final follow-up appointment. Reasons for any VA loss were noted.ResultsA total of 86 patients were included. Of these, 28 (33%) were seen in more than 4 weeks after their DESP referral. At first HES appointment, 39 (45%) patients were graded as having active PDR in at least one eye. Delay in referral did not significantly predict the likelihood of vision loss in all patients referred (χ(2), P=0.49) or in just those patients with a definitive HES diagnosis of active PDR (χ(2), P=1.00). In only 3 patients with active PDR was a delay in presentation thought to have led directly to VA loss.ConclusionsThere may be minimal short-term visual consequence in several weeks of delayed referral for many patients with a diagnosis of R3. However, the national guidance remains important. This is due to the occasional patient at very high risk of vision loss and the many gains for the patients in terms of time to properly assess medical and ocular conditions and counsel and consent them for treatment where necessary.

Clinical, ultrasound, and videodermatoscopy monitoring of psoriatic patients following biological treatment.

BACKGROUND AND PURPOSE: Effective non-invasive techniques to monitor plaque psoriasis progression and treatment are desirable. The aim of the study was to evaluate changes in vascular pattern using videodermatoscopy (VD) and in skin thickness by ultrasound (US), along with clinical observation, during treatment with biologicals. METHODS: Forty-two patients with moderate-to-severe plaque psoriasis treated with adalimumab, etanercept, or ustekinumab were evaluated. Following the identification of a 'target' plaque at baseline, lesion changes were monitored at 15, 30 and 60 days by clinical observation using a Target Lesion Score (TLS), and by VD and US. RESULTS: After 60 days, a significant improvement in all three parameters was observed. In adalimumab-treated patients mean values of TLS, VD, and US were reduced by 83.9%, 73.5%, and 90%, respectively; in etanercept-treated patients by 67.9%, 49.7%, and 79.3%; in ustekinumab-treated patients by 80.9%, 66.4%, and 80.1%. Skin thickness was the first parameter to improve. Vascular improvement was slower compared to clinical and US responses. CONCLUSION: VD and US may be useful to monitor psoriasis treatment. Further investigations are warranted to assess if the persistence of an altered vascular pattern despite clinical and US normalization, as observed in 22% of patients, may influence disease progression and/or correlate with rate and severity degree of relapse.

3D chemical imaging in the laboratory by hyperspectral X-ray computed tomography.

We report the development of laboratory based hyperspectral X-ray computed tomography which allows the internal elemental chemistry of an object to be reconstructed and visualised in three dimensions. The method employs a spectroscopic X-ray imaging detector with sufficient energy resolution to distinguish individual elemental absorption edges. Elemental distributions can then be made by K-edge subtraction, or alternatively by voxel-wise spectral fitting to give relative atomic concentrations. We demonstrate its application to two material systems: studying the distribution of catalyst material on porous substrates for industrial scale chemical processing; and mapping of minerals and inclusion phases inside a mineralised ore sample. The method makes use of a standard laboratory X-ray source with measurement times similar to that required for conventional computed tomography.

Real time chemical imaging of a working catalytic membrane reactor during oxidative coupling of methane.

We report the results from an operando XRD-CT study of a working catalytic membrane reactor for the oxidative coupling of methane. These results reveal the importance of the evolving solid state chemistry during catalytic reaction, particularly the chemical interaction between the catalyst and the oxygen transport membrane.