Borrelia miyamotoi Activates Human Dendritic Cells and Elicits T Cell Responses.

The spirochete Borrelia miyamotoi has recently been shown to cause relapsing fever. Like the Lyme disease agent, Borrelia burgdorferi, B. miyamotoi is transmitted through the bite of infected ticks; however, little is known about the response of the immune system upon infection. Dendritic cells (DCs) play a central role in the early immune response against B. burgdorferi We investigated the response of DCs to two different strains of B. miyamotoi using in vitro and ex vivo models and compared this to the response elicited by B. burgdorferi. Our findings show that B. miyamotoi is phagocytosed by monocyte-derived DCs, causing upregulation of activation markers and production of proinflammatory cytokines in a similar manner to B. burgdorferi. Recognition of B. miyamotoi was demonstrated to be partially mediated by TLR2. DCs migrated out of human skin explants upon inoculation of the skin with B. miyamotoi. Finally, we showed that B. miyamotoi-stimulated DCs induced proliferation of naive CD4+ and CD8+ T cells to a larger extent than B. burgdorferi. In conclusion, we show in this study that DCs respond to and mount an immune response against B. miyamotoi that is similar to the response to B. burgdorferi and is able to induce T cell proliferation.

Emerging therapies for dry eye disease.

INTRODUCTION: Dry Eye Disease (DED) is defined as a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and a vicious cycle of inflammation on the ocular surface. Despite its high prevalence and standing as one of the most common eye conditions seen by practitioners, the current treatment options available to patients have not proven adequate. AREAS COVERED: This review will discuss the burden of DED, its pathophysiology, as well as emerging therapies. These therapies include immunosuppressants, immunomodulators, anti-inflammatory drugs, and corticosteroids. The mechanisms of these drugs will be discussed, as well as their phase of development and results from recent clinical trials. The literature search was performed using PubMed, Cochrane Library, Web of Science, ClinicalTrials.gov, and the Springer AdisInsight database. EXPERT OPINION: The optimal therapy for DED is associated with improved bioavailability, minimal ocular side effects, and effective dosing. The ideal treatment has not yet been established, but this paper outlines a number of promising therapies. Continued development of therapies targeting the inflammation cascade, as well as the establishment of objective markers to quantify DED severity, are important aspects in the progression of treatment.

Effect of Posture Feedback Training on Health.

Collapsed or slouching posture has been associated with negative health outcomes such as pain, depression, and overall stress ratings as well as declines in general health, emotional well-being, and energy/fatigue levels. Currently, wearable devices and accompanying smartphone applications (apps) can provide feedback about shifting posture (e.g., erect vs. collapsed or slouching positions), as well as provide suggestions that support positive posture awareness. This study investigates the effect of a wearable 'UpRight' posture-feedback device on self-reports of pain, mood, and performance in comparison to a non-treatment control group. 56 Student participants filled out the SF-36 RAND Health Survey at the beginning and end of the 4-week study. The treatment group (n = 13) used a wearable device for at least 15 min per day, for 4 weeks, while a matched comparison group (n = 13) participated without the device over the same period. Evaluations before and after the 4 weeks included the SF-36, as well as qualitative descriptions of their experiences. The treatment group significantly improved on the SF-36 measures of physical functioning, emotions, energy/fatigue, confidence and overall stress ratings, as well as on subjective ratings of neck and back posture as compared to the control group. The wearable biofeedback device positively influenced awareness of neck and back posture, as well as key measures on the RAND SF-36 Health Survey. This study provides preliminary support that a wearable posture feedback device is a useful tool to teach posture awareness and improve well-being.

Hepatitis B and C testing strategies in healthcare and community settings in the EU/EEA: A systematic review.

An estimated 9 million individuals are chronically infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) across the European Union/European Economic Area (EU/EEA), many of which are yet to be diagnosed. We performed a systematic review to identify interventions effective at improving testing offer and uptake in the EU/EEA. Original research articles published between 1 January 2008 and 1 September 2017 were retrieved from PubMed and EMBASE. Search strings combined terms for HBV/HCV, intervention, testing and geographic terms (EU/EEA). Out of 8331 records retrieved, 93 studies were selected. Included studies reported on testing initiatives in primary health care (9), hospital (12), other healthcare settings (31) and community settings (41). Testing initiatives targeted population groups such as migrants, drug users, prisoners, pregnant women and the general population. Testing targeted to populations at higher risk yielded high coverage rates in many settings. Implementation of novel testing approaches, including dried blood spot (DBS) testing, was associated with increased coverage in several settings including drug services, pharmacies and STI clinics. Community-based testing services were effective in reaching populations at higher risk for infection, vulnerable and hard-to-reach populations. In conclusion, our review identified several successful testing approaches implemented in healthcare and community settings, including testing approaches targeting groups at higher risk, community-based testing services and DBS testing. Combining a diverse set of testing opportunities within national testing strategies may lead to higher impact both in terms of testing coverage and in terms of reduction, on the undiagnosed fraction.

Hepatitis B and C prevalence and incidence in key population groups with multiple risk factors in the EU/EEA: a systematic review.

BackgroundPeople living with HIV (PLHIV) and people in prison are population groups with a potentially high risk and/or prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection.AimWe conducted a systematic review in order to find prevalence and incidence estimates in these populations in the European Union/European Economic Area (EU/EEA).MethodsOriginal research articles published between January 2005 and February 2017 were retrieved from PubMed and Embase in February 2017.ResultsFifty-two articles were included, providing 97 estimates of HBV/HCV infection prevalence or incidence. Estimates of HBV infection prevalence ranged between 2.9% and43.4% in PLHIV and 0.0% and 25.2% in people in prison. Estimates of HCV infection prevalence ranged from 2.9% to 43.4% in PLHIV and 0.0% to 25.2% in people in prison. Incidence estimates ranged between 0.0 and 2.5 cases per 100 person-years for HBV infection in PLHIV. No such data was available for people in prison. HCV infection incidence ranged between 0.3 and 0.9 cases per 100 person-years in PLHIV and between 1 and 1.2 cases per 100 person-years in people in prison. Prevalence estimates were generally higher than in the general population, especially for HCV infection and among groups with multiple risk factors.ConclusionsPLHIV, people in prison and groups with multiple risk factors, have a high prevalence of HBV and HCV and may be at ongoing risk of infection. These groups should be among the populations prioritised and targeted for active case finding and prevention programmes in the EU/EEA.

Vitrectomy and Vitrector Port Needle Biopsy of Choroidal Melanoma for Gene Expression Profile Testing Immediately before Brachytherapy.

PURPOSE: Transvitreal and transscleral needle biopsy can result in complications including vitreous hemorrhage and retinal detachment. This study evaluated a technique using 25-gauge vitrectomy as an adjunct to needle biopsy immediately before brachytherapy to minimize these complications and preserve good visual acuity. DESIGN: Retrospective, observational case series. PARTICIPANTS: Fifty-seven consecutive eyes of 57 patients with treatment-naïve medium choroidal melanomas without extraocular extension from July 2012 through September 2015. METHODS: Fifty-seven consecutive eyes of 57 patients with a clinically diagnosed choroidal melanoma underwent complete 25-gauge posterior vitrectomy followed by transvitrector port fine-needle aspiration biopsy of the tumor immediately before implantation of a radioactive iodine 125 plaque as treatment for the tumor. Cytopathologic analysis was not performed on the tumor aspirates in this study. MAIN OUTCOME MEASURES: Best-corrected postoperative visual acuity, postoperative complications of the reported technique, implantation tumor development, local tumor recurrence, presence of metastatic disease after surgery, and sufficiency of the tumor aspirates obtained by the reported technique for successful gene expression profile testing and prognostic classification. RESULTS: Mean preoperative and postoperative visual acuities were similar (20/60 vs. 20/80, respectively). Mean tumor thickness was 5.0 mm (range, 2.5-10 mm) and mean tumor basal diameter was 13.1 mm (range, 7-22 mm). Only 1 of 57 eyes (1.8%) showed a transient vitreous hemorrhage, biopsy yield was 100% for genetic analysis, and no patients showed recurrence or implantation tumor at the vitrector site. CONCLUSIONS: Combined 25-gauge posterior vitrectomy and 25-gauge trans-vitrector port needle aspiration biopsy immediately before brachytherapy is excellent for obtaining tumor aspirate for gene expression profiling while controlling for hemostasis, resulting in few complications.

VITREORETINAL SURGICAL OUTCOMES PERFORMED BY SUPERVISED RETINAL FELLOWS VERSUS ATTENDING FACULTY SURGEONS.

PURPOSE: To evaluate common vitreoretinal surgeries performed by retinal fellows under direct faculty supervision, compared with experienced faculty members. METHODS: Retrospective study analyzing 592 consecutive eyes undergoing retinal surgery from 2009 to 2011 at Retina Consultants of Alabama/University of Alabama at Birmingham, Department of Ophthalmology. Vitreoretinal surgeries included macular hole, macular pucker, retinal detachment, diabetic vitreous hemorrhage, and diabetic tractional retinal detachment. Three fellows performed 390 cases (divided into first or second year fellows), while 4 faculty members performed 202 cases. All 390 fellow-performed cases were under direct supervision. Chi-square analysis was used to compare outcomes. RESULTS: There were no baseline differences between the groups. The mean postoperative visual improvement was statistically significant and equal in all groups, as well as between each physician (P ≤ 0.0001). Complications occurred in 29/592 cases (4.8%), whereas reoperations occurred in 21/592 cases (3.5%) and were equally distributed across groups. There were no differences in complications and reoperations when comparing first-year with second-year fellows. CONCLUSION: With proper supervision, vitreoretinal fellows can achieve an equally high visual improvement with low complication and reoperation rates compared with experienced faculty. The year of fellowship does not significantly influence outcomes or complications. Quality outcomes after vitreoretinal surgery can be obtained throughout fellowship training.

Metacognitive judgment formation during map learning: Evidence for global monitoring.

Street maps are sometimes complex. They may show landmark names, locations, routes between landmarks, and where landmarks are relative to one another. Map learners may aim to learn one map component, like landmark locations, but later must remember a different component, such as routes. In other words, congruency between learning goals and tests may contribute to map memory. Further, research demonstrates that complex knowledge acquisition may be improved when metacognitive processes are congruent with tested material. The present work examined the relationship between learning goals, a type of metacognitive monitoring judgment referred to as judgments of learning (JOLs), and tests of map learning to determine whether congruency between goals and JOL prompts (Exp 1) and JOL prompts and tests (Exp 2) influenced memory and metacognitive accuracy. Congruency between learning goals and JOL prompts contributed to metacognitive accuracy, particularly when map components were highly complex. Contrary to our hypotheses, congruency between JOL prompts and tests did not contribute to memory or metacognitive accuracy. Our results suggest learners could accurately predict their memory, and cues such as map complexity and information accumulation across learning trials influenced rating magnitude.

Penta- and hexavalent vaccination of extremely and very-to-moderate preterm infants born at less than 34 weeks and/or under 1500 g: A systematic literature review.

Debate regarding vaccinating high-risk infants with penta- and hexavalent vaccines persists, despite their good immunogenicity and acceptable safety profile in healthy full-term infants. We report the findings of a systematic literature search that aimed to present data on the immunogenicity, efficacy, effectiveness, safety, impact, compliance and completion of penta- and hexavalent vaccination in high-risk infants, including premature newborns. Data from the 14 studies included in the review showed that the immunogenicity and the safety profile of penta- and hexavalent vaccines in preterm infants was generally similar to those seen in full-term infants, with the exception of an increase in cardiorespiratory adverse events such as apnea, bradycardia and desaturation following vaccination in preterm infants. Despite recommendations of vaccinating preterm infants according to their actual age, and the relatively high completion rate of the primary immunization schedule, vaccination was often delayed, increasing the vulnerability of this high-risk population to vaccine-preventable diseases.

Combined vaccines such as penta- and hexavalent vaccines against multiple childhood diseases are widely used in healthy babies born at term. However, it is still debated whether these vaccines act the same way in babies considered to be high-risk: babies born prematurely at <34 weeks of pregnancy, those with a birthweight of <1500 g or babies with chronic diseases. We did a systematic literature search to find studies on such high-risk babies vaccinated with penta- or hexavalent vaccines; we focused on their antibody levels following vaccination, side effects, and protection from the diseases against which they were vaccinated. We also analyzed whether they were vaccinated on time and with all the doses recommended for healthy full-term babies. We found 14 studies that included premature babies. The results of these studies suggest that premature babies' immune systems respond to penta- and hexavalent vaccines in largely the same way as those of full-term babies; side effects of penta- and hexavalent vaccines are also mostly similar to those seen in full-term babies. However, side effects like pauses in breathing, slow heart rate or low blood oxygen levels seem to be more common in preterm babies; for safety, these babies should be monitored closely after vaccination. Preterm babies are often vaccinated with a delay compared to the recommended schedule. No studies reported data on protection from the diseases covered by penta- and hexavalent vaccinations in preterm babies. More research is needed on penta- and hexavalent vaccination of other high-risk babies besides those born prematurely.

Chronic almond nut snacking alleviates perceived muscle soreness following downhill running but does not improve indices of cardiometabolic health in mildly overweight, middle-aged, adults.

Introduction: As a popular food snack rich in protein, fiber, unsaturated fatty acids, antioxidants and phytonutrients, almond nut consumption is widely associated with improvements in cardiometabolic health. However, limited data exists regarding the role of almond consumption in improving exercise recovery. Accordingly, we aimed to investigate the impact of chronic almond snacking on muscle damage and cardiometabolic health outcomes during acute eccentric exercise recovery in mildly overweight, middle-aged, adults. Methods: Using a randomized cross-over design, 25 mildly overweight (BMI: 25.8 ± 3.6 kg/m2), middle-aged (35.1 ± 4.7 y) males (n = 11) and females (n = 14) performed a 30-min downhill treadmill run after 8-weeks of consuming either 57 g/day of whole almonds (ALMOND) or an isocaloric amount (86 g/day) of unsalted pretzels (CONTROL). Muscle soreness (visual analogue scale), muscle function (vertical jump and maximal isokinetic torque) and blood markers of muscle damage (creatine kinase (CK) concentration) and inflammation (c-reactive protein concentration) were measured pre and post (24, 48, and 72 h) exercise. Blood biomarkers of cardiometabolic health (total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol), body composition and psycho-social assessments of mood (POMS-2 inventory), appetite and well-being were measured pre and post intervention. Results: Downhill running successfully elicited muscle damage, as evidenced by a significant increase in plasma CK concentration, increased perception of muscle soreness, and impaired vertical jump performance (all p < 0.05) during acute recovery. No effect of trial order was observed for any outcome measurement. However, expressed as AUC over the cumulative 72 h recovery period, muscle soreness measured during a physical task (vertical jump) was reduced by ~24% in ALMOND vs. CONTROL (p < 0.05) and translated to an improved maintenance of vertical jump performance (p < 0.05). However, ALMOND did not ameliorate the CK response to exercise or isokinetic torque during leg extension and leg flexion (p > 0.05). No pre-post intervention changes in assessments of cardiometabolic health, body composition, mood state or appetite were observed in ALMOND or CONTROL (all p > 0.05). Conclusion: Chronic almond supplementation alleviates task-specific perceived feelings of muscle soreness during acute recovery from muscle damaging exercise, resulting in the better maintenance of muscle functional capacity. These data suggest that almonds represent a functional food snack to improve exercise tolerance in mildly overweight, middle-aged adults.

On the proposed role of metacognition in environment learning: recommendations for research.

Metacognition plays a role in environment learning (EL). When navigating, we monitor environment information to judge our likelihood to remember our way, and we engage in control by using tools to prevent getting lost. Yet, the relationship between metacognition and EL is understudied. In this paper, we examine the possibility of leveraging metacognition to support EL. However, traditional metacognitive theories and methodologies were not developed with EL in mind. Here, we use traditional metacognitive theories and approaches as a foundation for a new examination of metacognition in EL. We highlight three critical considerations about EL. Namely: (1) EL is a complex process that unfolds sequentially and is thereby enriched with multiple different types of cues, (2) EL is inherently driven by a series of ecologically relevant motivations and constraints, and (3) monitoring and control interact to support EL. In doing so, we describe how task demands and learning motivations inherent to EL should shape how metacognition is explored. With these considerations, we provide three methodological recommendations for investigating metacognition during EL. Specifically, researchers should: (1) instantiate EL goals to impact learning, metacognition, and retrieval processes, (2) prompt learners to make frequent metacognitive judgments and consider metacognitive accuracy as a primary performance metric, and (3) incorporate insights from both transfer appropriate processing and monitoring hypotheses when designing EL assessments. In summary, to effectively investigate how metacognition impacts EL, both ecological and methodological considerations need to be weighed.

Predictions about the Cognitive Consequences of Language Switching on Executive Functioning Inspired by the Adaptive Control Hypothesis Fail More Often than Not.

The adaptive control hypothesis developed by Green and Abutalebi is the most influential theory of bilingual language control. The focus of this article is on the predictions that other researchers have derived based on the three different modes of interactional context described by the hypothesis. Foremost, that dual-language contexts should enhance domain-general executive functions more than single-language contexts. Several recent and ambitious behavioral tests of these predictions are reviewed. Although there was some evidence that dual-language contexts are associated with smaller switch costs, the evidence is inconsistent and there were no similar advantages for inhibitory control. The hypothesis also predicts neuroanatomical adaptations to the three types of interactional context. A careful evaluation of the relevant fMRI and ERP studies that take into account whether behavioral differences align with neuroscience differences and resolves valence ambiguities led to the conclusion that the neuroscience evidence for the hypothesis is, at best, inconsistent. The study also includes new analyses of two large-sample studies that enable the identification of relatively pure cases of single-language bilinguals, dual-language bilinguals, and dense-code switchers. Across nine different measures of executive functioning, the predicted advantage of the dual-language context never materialized. The hypotheses derived from the adaptive control hypothesis do not accurately predict behavioral performance on tests of executive functioning and do not advance our understanding as to what dimensions of bilingualism may lead to enhancements in specific components of executive functioning.

Unilateral Distribution of Lichen Planus Pigmentosus-Inversus Unresponsive to Clobetasol and Hydroquinone.

Lichen planus pigmentosus-inversus (LPP-inversus) is a rare, pigmented variant of lichen planus of unknown etiology. This skin condition typically affects the intertriginous and flexural regions of the body bilaterally. We report an unusual case presentation with unilateral distribution of LPP-inversus in a woman originally from Nepal. The lesions developed rapidly over a three-month period and were recalcitrant to therapy with topical clobetasol and hydroquinone.

Autism Traits Predict Self-reported Executive Functioning Deficits in Everyday Life and an Aversion to Exercise.

Are Autism Quotient (AQ) scores related to executive functioning (EF)? We sampled 200 students of normal intelligence and examined the relationship between AQ scores and: (a) 5 self-ratings of EF, (b) 5 performance-based measures of EF, and (c) 5 types of activities or experiences that are assumed to recruit EF and sometimes enhance EF. Our findings reveal that as AQ scores increase, self-rated EF ability decreases. AQ scores and self-reported EF measures do not correlate with objective EF task performance. Furthermore, AQ scores were shown to be negatively associated with many specific types of physical activity. As AQ scores increase, individuals report fewer positive reasons for exercise and more rationalizations for not engaging in more exercise.

Comparison of Genicular Nerve Block in Combination With Adductor Canal Block in Both Primary and Revision Total Knee Arthroplasty: A Retrospective Case Series.

The management of pain in patients undergoing total knee arthroplasty (TKA) for chronic knee osteoarthritis (OA) has remained a challenge for the anesthesiologist regarding regional anesthesia as no single regional technique is adequate with regard to balancing effective analgesia with minimal muscle weakness. Severe postoperative pain following TKA has been shown to negatively impact patient outcomes and mortality. The genicular nerve block has recently been demonstrated to provide effective analgesia to the anterior and posterior knee capsule in recent studies. In this retrospective case series, we compare the efficacy of combined genicular nerve block (GNB) and adductor canal block (ACB) to only ACB in both primary and revision TKA patients. This combined novel approach for TKA patients can be utilized to improve patient pain scores and early ambulation, limiting the use of opioids and early discharge.

Fears, Depression, and Anxieties of Patients With Diabetic Retinopathy and Implications for Education and Treatment.

Objective: This study investigates undiagnosed depression and anxiety related to diabetes in patients with diabetic retinopathy and identifies commonly feared complications that these patients experience. Methods: The 74 consecutive individuals with diabetes were recruited for this investigation from the office of a retina specialist, and data were obtained from the participants through a self-report survey given to the patients before their appointment. Results: The most feared complication reported by patients surveyed was blindness (38.36%). When asked about depression and anxiety related to their diabetes, 20.27% of patients stated they have depression related to their diabetes, whereas 18.92% had anxiety related to their diabetes. Only 17.57% of the patients said they were being treated for their depression and/or anxiety at the time of the survey. Conclusions: This study demonstrates that many patients with diabetic retinopathy have coexisting fears and mental health concerns. Because most retina specialists treat a high number of patients with diabetes, it is crucial to understand the barriers and comorbidities related to this patient population. Retina specialists may play a role in identifying the hidden and underlying fears, depression, and anxieties in patients with diabetes so that these patients can get the necessary help and counseling they need.

Interference scores have inadequate concurrent and convergent validity: Should we stop using the flanker, Simon, and spatial Stroop tasks?

BACKGROUND: Two-hundred one college undergraduates completed four nonverbal interference tasks (Simon, spatial Stroop, vertical Stroop, and flanker) and trait scales of self-control and impulsivity. Regression analyses tested 11 predictors of the composite interference scores derived from three of the four tasks and each task separately. The purpose of the study was to examine the relationships between laboratory measures of self-control, self-report measures, and the degree to which control might be related to extensive experience in activities that logically require self-control. RESULTS: Fluid intelligence and sex were significant predictors of the composite measure, but bilingualism, music training, video gaming, mindfulness/meditation, self-control, impulsivity, SES, and physical exercise were not. CONCLUSIONS: Common laboratory measures of inhibitory control do not correlate with self-reported measures of self-control or impulsivity and consequently appear to be measuring different constructs. Bilingualism, mindfulness/meditation, playing action video games, and music training or performance provide weak and inconsistent improvements to laboratory measures of interference control. Flanker, Simon, and spatial Stroop effects should not be used or interpreted as measures of domain-general inhibitory control.

The alchemy of confirmation bias transmutes expectations into bilingual advantages: A tale of two new meta-analyses.

Five recent meta-analyses of the bilingual advantage in executive functioning hypothesis have converged on the outcome that the mean effect size is very small and that the incidence of statistically significant bilingual advantages is very low (about 15% of all comparisons). Those analyses that used the PET-PEESE method to correct for publication bias show mean effect sizes that are not different from zero and sometimes negative. In contrast, van den Noort and colleagues provide a sixth review of 46 studies published before October 31, 2018, that appears to produce a very different outcome, namely that more than half the studies yield clear support for the bilingual advantage hypothesis. We show that the deviance is due in part to search terms that yielded far fewer relevant studies, but more importantly to a subjective method of evaluating the results of each study that enables confirmation biases on the part of study authors and meta-analysts to substantially distort the objective pattern of results. A seventh meta-analysis, by Armstrong and colleagues, reports significant bilingual advantages of g = 0.48 for 32 samples using Simon and Stroop colour-word interference tasks that tested older adults. However, all effects were entered into the funnel plots as positive even though many were negative (bilingual disadvantages). This and other striking anomalies are consistent with the view that confirmation bias can suspend critical judgement and promulgate errors. Meta-analyses that use preregistration and a many-labs collaboration can better control for both publication and experimenter biases.