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Background Many reports have documented the relationship between previous traumatic experiences, including childhood trauma, and the development of later life psychopathology, including posttraumatic stress disorder (PTSD). Identification of individuals at greatest risk for the development of PTSD could lead to preventative interventions. The present study examined the developmental course of PTSD after trauma exposure, using histories of previous traumatic experiences and the severity of the reaction to the trauma as predictors. Methods Participants (N = 713) were recruited from Emergency Departments in Miami and Atlanta immediately following a traumatic experience. Histories of previous traumatic experiences and the immediate reaction to the new trauma were examined at baseline. Follow-up assessments of PTSD severity were conducted at 1, 3, and 6 months. Results Histories of child abuse and pre-existing trauma symptoms predicted the immediate response to stress (R2 = .21, p 0.86). Conclusions The current findings suggest that previous traumatic experiences lead to a greater immediate reaction to trauma and combine to predict the development of PTSD, the maintenance of which is not moderated by these earlier experiences. The identification of people likely to develop PTSD may be aided by the assessment of prior experiences and immediate reactions.

Background People who inject drugs (PWID) suffer high morbidity and mortality from injection related infections (IRI). The inpatient setting is an ideal opportunity to treat underlying substance use disorder (SUD), but it is unclear how often this occurs. Objectives To quantify the utilization of behavioral health services for PWID during inpatient admissions for IRI. Methods Data for all hospital admissions in Florida in FY2017 were obtained from the Agency for Healthcare Administration. Hospitalization for IRI were obtained using a validated ICD-10 algorithm and treatment for substance use disorder was quantified using ICD-10-Procedure Coding System (ICD-10-PCS) codes. Result Among the 20,001 IRI admissions, there were 230 patients who received behavioral health services as defined by ICD-10-PCS SAT codes for treatment for SUD. Conclusions In a state with a large number of IRI, only a very small portion of admissions received behavioral health services. Increased efforts should be directed to studying referral patterns among physicians and other providers caring for this population and increasing utilization of behavioral health services.

Background: Arthrodesis of the first metatarsophalangeal (MTP) joint has been shown to be effective in alleviating pain and correcting deformity in hallux rigidus. However, outcomes in specific sports and physical activities remain unclear. The aim of this study was to assess sports and physical activities in young patients following first MTP joint arthrodesis and to compare these results with clinical outcomes. Methods: Patients between ages 18 and 55 years who underwent MTP arthrodesis were identified by review of a prospective registry. Fifty of 73 eligible patients (68%) were reached for follow-up at a mean of 5.1 (range, 2.2-10.2) years with a mean age at surgery of 49.7 (range, 23-55) years. Physical activity was evaluated with a previously developed sports-specific, patient-administered questionnaire. Clinical outcomes were evaluated with the Foot and Ankle Outcome Score (FAOS). Results: Patients participated in 22 different sports and physical activities. The most common were walking, biking, weightlifting, swimming, running, and golf. Compared to preoperatively, patients rated 27.4% of activities as less difficult, 51.2% as the same, and 21.4% as more difficult. Patients returned to 44.6% of preoperative physical activities in less than 6 months and reached their maximal level of participation in 88.6% of physical activities. Ninety-six percent of patients (48/50) were satisfied with the procedure regarding return to sports and physical activities. Improvements in the FAOS Symptoms subscore were associated with increased postoperative running and walking duration, and improvements in FAOS Pain subscores were associated with greater patient satisfaction. Conclusion: Patients were able to participate in a wide variety of sports and physical activities postoperatively. Some patients reported increased difficulty, but were nonetheless satisfied with the procedure regarding physical activity participation. These findings suggest that first MTP joint arthrodesis is a reasonable option in young, active patients, and may be used to guide postoperative expectations. Level of Evidence: Level IV, retrospective case series.

Neuronal activity is a potent extrinsic regulator of oligodendrocyte generation and central nervous system myelination. Clinically, repetitive transcranial magnetic stimulation (rTMS) is delivered to noninvasively modulate neuronal activity; however, the ability of rTMS to facilitate adaptive myelination has not been explored. By performing cre‐lox lineage tracing, to follow the fate of oligodendrocyte progenitor cells in the adult mouse brain, we determined that low intensity rTMS (LI‐rTMS), administered as an intermittent theta burst stimulation, but not as a continuous theta burst or 10 Hz stimulation, increased the number of newborn oligodendrocytes in the adult mouse cortex. LI‐rTMS did not alter oligodendrogenesis per se, but instead increased cell survival and enhanced myelination. These data suggest that LI‐rTMS can be used to noninvasively promote myelin addition to the brain, which has potential implications for the treatment of demyelinating diseases such as multiple sclerosis., Main Points The impact that low intensity repetitive transcranial magnetic stimulation (LI‐rTMS) has on cells of the oligodendrocyte lineage is stimulation frequency and cell‐stage specific.LI‐rTMS does not affect oligodendrocyte progenitor cell proliferation or density.LI‐rTMS, delivered in an intermittent theta burst pattern, promotes the survival of premyelinating oligodendrocytes and enhances myelin internode extension by newly myelinating oligodendrocytes.

Background: In synergy with the mounting scientific evidence for the capacity of recovery after spinal cord injury (SCI) and training, new evidence-based therapies advancing neuromuscular recovery are emerging. There is a parallel need for outcome instruments that specifically address recovery. The Pediatric Neuromuscular Recovery Scale (Pediatric NRS) is one example with established content validity to assess neuromuscular capacity within task performance. Objective: The objective of this study was to determine interrater reliability of the Pediatric NRS to classify motor capacity in children after SCI. Methods: Pediatric physicians (3), occupational therapists (5), and physical therapists (6) received standardized training in scoring the scale, then rated video assessments of 32 children post SCI, 2–12 years of age, 78% non-ambulatory. Interrater reliability was analyzed using Kendall coefficient of concordance for individual Pediatric NRS items and overall score. Results: The interrater reliability coefficient was determined to be near 1 for the overall Pediatric NRS score (ICC = 0.966; 95% CI, 0.89–0.98). Twelve of 16 individual items exhibited high concordance coefficients (Kendall's W ≥ 0.8) and four items demonstrated concordance coefficients, < 0.8 and > 0.69. Interrater reliability was equivalent among groups defined by age and neurological level, but lower among non-ambulatory individuals. Conclusion: Strong interrater reliability was demonstrated by pediatric clinicians who scored children with SCI using the Pediatric NRS.

Background: Activity-based therapies aim to improve neuromuscular capacity after spinal cord injury (SCI). Objective: The purpose of this prospective study was to report the impact of Activity-based Locomotor Training (AB-LT) on neuromuscular capacity in pediatric patients with SCI. Methods: Participants were enrolled for their first episode of AB-LT for a minimum of 60 daily, 1.5-hour sessions. The Segmental Assessment of Trunk Control (SATCo) and the Pediatric Neuromuscular Recovery Scale (Pediatric NRS) were assessed initially, every 20 sessions, and post 60 sessions. Results: Twenty-six consecutive patients, mean age 5 years (SD = 3), completed a mean 55 sessions (SD = 4) within 63 weekdays (SD = 9). The Pediatric NRS total score improved significantly, adjusted mean 11.4, from initial to post-60 sessions (p < .05) with an average adjusted evaluation-to-evaluation 3.7 change. SATCo scores improved significantly across 60 sessions, mean change 5.2, an estimated 1.7 change between evaluations (p < .05). Age at enrollment and chronicity had no effect; however, initial neuromuscular capacity scores were negatively correlated with change scores (p < .05). Conclusion: Sixty AB-LT sessions significantly improved trunk and neuromuscular capacity in children with SCI, regardless of age or chronicity at enrollment. Patients with lower initial scores made greater improvements than patients with higher initial neuromuscular capacity. Anecdotal parent reports of their child's functional change in the home and community highlight the synergy between quantitative change in neuromuscular capacity and meaningful, improved quality of life and the need for formal investigation of this relationship.

Many reports have documented the relationship between post-traumatic stress disorder (PTSD) and substance use. Substance use is commonly comorbid with PTSD and is a risk factor for trauma exposure. The aim of this study was to prospectively examine how recent substance use, abuse, or dependence influenced the development of PTSD in the context of a prior trauma history, including child abuse, and the severity of initial trauma reactions. Participants (N = 81) were recruited and assessed at the emergency department of a large urban hospital in Miami and serum levels of common drugs of abuse were measured. Although substance use appeared to be a risk factor for trauma exposure, neither self-reported nor blood toxicology influenced the development of PTSD. Positive toxicology screens were more likely to be associated with a diagnosis of substance abuse or dependence, χ2 (1) = 4.11, p = .04. Participants with a history of physical abuse were more likely to have a positive toxicology screen, χ2 (1) = 4.03, p = .05. The majority of our trauma-exposed subjects (66%) were found to be positive for one or more illicit substances at presentation at the ED. The current findings provide support for the “high risk” hypothesis in which substance use is associated with increased trauma exposure.

Central nervous system myelination increases action potential conduction velocity. However, it is unclear how myelination is coordinated to ensure the temporally precise arrival of action potentials and facilitate information processing within cortical and associative circuits. Here, we show that myelin sheaths, supported by mature oligodendrocytes, remain plastic in the adult mouse brain and undergo subtle structural modifications to influence action potential conduction velocity. Repetitive transcranial magnetic stimulation and spatial learning, two stimuli that modify neuronal activity, alter the length of the nodes of Ranvier and the size of the periaxonal space within active brain regions. This change in the axon-glial configuration is independent of oligodendrogenesis and robustly alters action potential conduction velocity. Because aptitude in the spatial learning task was found to correlate with action potential conduction velocity in the fimbria-fornix pathway, modifying the axon-glial configuration may be a mechanism that facilitates learning in the adult mouse brain.

Schizophrenia is a complex severe mental illness with high morbidity and mortality. It is characterized by positive symptoms, negative symptoms, and cognitive impairment. Cognitive impairment is strongly associated with functional impairment and presents a major barrier to recovery. This article reviews some of the most recent research on cognition in schizophrenia and the clinical implications. There have been recent studies related to the genomics of cognition and neural structures involved in cognition. We review recent investigations into the assessment of social cognition and the implications of impaired introspective accuracy. A recent network analysis assessed the relationship of neurocognition and social cognition to functional capacity. We further discuss the role of specific symptoms in functioning, including negative symptoms and symptoms related to autism spectrum disorder. We conclude with a discussion of a novel computerized treatment for social cognition. Recent research has sought to better understand several dimensions of cognition including genomics, brain structure, social cognition, functional capacity, and symptomatology. This recent research brings us closer to understanding the complex clinical picture of schizophrenia and the best treatments to achieve recovery.

Gulf War Illness (GWI) is a multisymptom disorder including widespread chronic pain, fatigue and gastrointestinal problems. The objective of this study was to examine the low glutamate diet as a treatment for GWI. Forty veterans with GWI were recruited from across the US. Outcomes included symptom score, myalgic score, tender point count, dolorimetry and the Chalder Fatigue Scale. Subjects were randomized to the low glutamate diet or a wait-listed control group, with symptom score being compared after one month. Subjects then went onto a double-blind, placebo-controlled crossover challenge with monosodium glutamate (MSG)/placebo to test for return of symptoms. Symptom score was compared between diet intervention and wait-listed controls with an independent t-test and effect size was calculated with Cohen&rsquo, s d. Change scores were analyzed with Wilcoxon Signed Rank tests. Crossover challenge results were analyzed with General Linear Models and cluster analysis. The diet intervention group reported significantly less symptoms (p = 0.0009) than wait-listed controls, with a very large effect size, d = 1.16. Significant improvements in average dolorimetry (p = 0.0006), symptom score, tender point number, myalgic score and the Chalder Fatigue Scale (all p &lt, 0.0001) were observed after the 1-month diet. Challenge with MSG/placebo resulted in significant variability in individual response. These results suggest that the low glutamate diet can effectively reduce overall symptoms, pain and fatigue in GWI, but differential results upon challenge suggest that other aspects of the diet, or underlying differences within the population, may be driving these changes. Future research is needed to identify potential nutrient effects, biomarkers, and underlying metabolic differences between responders and non-responders.

While antipsychotics have been generally successful in treating psychosis in schizophrenia, there is a major treatment gap for negative symptoms and cognitive deficits. Given that these aspects of the disease contribute to poor functional outcomes independently of positive symptoms, treatments would have profound implications for quality of life. The 5-HTRitanserin and volinanserin, are historically important compounds in this area, while pimavanserin, roluperidone, and lumateperone are either newly approved, in late stages of development, or currently being tested for efficacy in schizophrenia-related features. The focus will be on their efficacy in the treatment of negative symptoms, with a limited secondary discussion of cognition.In addition to their efficacy in treating negative symptoms and cognition, these compounds may also have a role in modulating antipsychotic-induced dopamine super-sensitivity and preventing relapse. They may also show efficacy in treating patients with milder symptoms such as patients with schizotypal personality disorder and attenuated psychosis syndrome. Their utility may also expand outside the spectrum of schizophrenia to encompass Parkinson's Disease psychosis, major depression, bipolar depression, and dementia-associated apathy.

Objectives: Removing artificial food coloring (AFC) is a common dietary intervention for children with Attention-Deficit/Hyperactivity Disorder (ADHD), but has not been tested in young adults. This...

Cuba, the Dominican Republic, and Puerto Rico, otherwise known as the Spanish Insular Caribbean, comprise a subgroup of insular territories that have similar cultural, historical, and colonial backgrounds. The Spanish Insular Caribbean population faces a particularly high risk for dementia, and only steadily emerging, albeit unique behavioral and psychological approaches for treatment. Comprehensive efforts to provide adequate and culturally congruent treatment are complex and characterized by social, economic, political, and public health influences. This chapter begins contextualizing the treatment of dementia by describing the cultural and historical landscape of the Spanish-speaking islands in the Caribbean. Prevalence rates of dementia in these regions are also discussed along with the current strategic, national guidelines for comprehensive care and the systems of healthcare provision in each country. Furthermore, cultural considerations for dementia management are discussed, including a summary of the psychological strengths exemplified within the Cuban, Dominican, and Puerto Rican communities. The chapter concludes with a review of treatment practices and interventions for individuals with dementia and their caregivers.

Background: While metatarsus primus elevatus (MPE) has been implicated in the development of hallux rigidus, previous studies have presented conflicting findings regarding the relationship between MPE and arthritis. This may be due to the variety of definitions for MPE and the radiographic measurement techniques that are used to assess it. Additionally, previous studies have only assessed elevation of the first metatarsal with respect to the floor or the second metatarsal, and not with respect to the proximal phalanx. The aim of this study was to examine the reliability of new radiographic measurements that consider the elevation of the first metatarsal in relation to the proximal phalanx, rather than in relation to the second metatarsal as previously described, to assess for MPE. In addition, we aimed to determine whether the elevation of the first metatarsal was significantly different in patients with hallux rigidus than in a control population. Methods: A retrospective chart review was conducted from prospectively collected registry data at the investigators’ institution to identify patients with hallux rigidus ( n = 65). A size-matched control cohort of patients without evidence for first metatarsophalangeal (MTP) joint arthritis was identified ( n = 65). Patients with a previous history of foot surgery, rheumatoid arthritis, or hallux valgus were excluded. Five blinded raters of varying levels of training, including 2 research assistants, 1 senior orthopedic resident, 1 foot and ankle fellowship-trained orthopedic surgeon, and 1 attending musculoskeletal fellowship-trained radiologist, evaluated 7 radiographic measurements for their reliability in assessing for MPE in hallux rigidus and control groups. Four of the 7 were newly designed measurements that include the relationship of the first MTP joint. Inter- and intrarater reliability were calculated using intraclass correlation coefficients (ICCs) and categorized by Landis and Koch reliability thresholds. The measurements between the hallux rigidus and control populations were compared using an independent t test. Results: Six of the 7 radiographic measurements were found to have substantial to almost perfect interrater reliability (ICC, 0.800-0.953) between all levels of training, except for the proximal phalanx–first metatarsal angle, which showed moderate reliability (ICC, 0.527). Substantial to almost perfect intrarater reliability (ICC, 0.710-0.982) was demonstrated by the measurements performed by research assistants. All 7 of the measurements taken by the musculoskeletal fellowship-trained radiologist demonstrated significant differences in first metatarsal elevation between the hallux rigidus and control populations, with the hallux rigidus group showing increased elevation ( P < .001-.019). Conclusion: This study confirmed the reliability of 7 radiographic measurements used to assess for MPE, including 3 previously established and 4 newly described measurements. Observers across all levels of training were able to demonstrate reliable measurements. In addition, the measurements were used to show that patients with hallux rigidus were more likely to have MPE compared with patients without radiographic evidence for first MTP arthritis. These measurements could be used in future work to examine how the presence of MPE relates to the etiology and progression of hallux rigidus, and how it affects the results of operative treatment. Level of Evidence: Level III, retrospective comparative study.

Myelination of central nervous system axons increases action potential conduction velocity and increases the speed of information transfer. However, it is unclear whether myelination optimizes action potential conduction to achieve synchronicity and facilitate information processing within cortical and associative circuits. Here we show that myelin sheaths remain plastic in the adult mouse and undergo subtle structural modifications to influence action potential conduction. Repetitive transcranial magnetic stimulation and spatial learning, two stimuli that modify neuronal activity, alter the length of the nodes of Ranvier and the size of the periaxonal space within active brain regions. This change in the axon-glial configuration, which is independent of oligodendrogenesis, tunes conduction velocity to increase the synchronicity of action potential conduction. One Sentence Summary The activity-dependent modulation of nodes of Ranvier and the periaxonal space allows central conduction to be tuned to achieve synchronicity.

Aggressive and violent behavior, including both verbal and physical aggression, have considerable adverse consequences for people with schizophrenia. There are several potential causes of violent behavior on the part of people with severe mental illness, which include intellectual impairments, cognitive and social-cognitive deficits, skills deficits, substance abuse, antisocial features, and specific psychotic features. This review explores the interventions that have been tested to this date. Computerized Cognitive Training (CCT) or Computerized Social-Cognitive Training (CSCT) have been associated with reductions in violence. Combined CCT and CSCT have been found to improve social cognition and neurocognition, as well as everyday functioning when combined with rehabilitation interventions. These interventions have been shown to reduce violence in schizophrenia patients across multiple environments, including forensic settings. The reductions in violence and aggression have manifested in various ways, including reduced violent thinking and behavior, reduced physical and violent assaults, and reduced disruptive and aggressive behaviors. Effects of cognitive training may be associated with improvements in problem-solving and the increased ability to deploy alternative strategies. The effect of social cognition training on violence reduction appears to be direct, with improvements in violence related to the extent of improvement in social cognition. There are still remaining issues to be addressed in the use of CCT and CSCT, and the benefits should not be overstated; however, the results of these interventions are very promising.

Autistic traits are a feature of schizophrenia and has been found to impair social functioning and social cognition. Other influences on social outcomes in schizophrenia include depression and social avoidance. However, challenges in self-assessment of abilities and functioning (i.e., introspective accuracy) and self-assessment bias also contribute to disability. Depression has been studied for its association with introspective accuracy and bias, but autistic traits have not. Participants were 177 patients with schizophrenia who self-reported their everyday functioning and social cognitive ability as well as their depression. All were rated with the PANSS and a separate rater generated all-sources ratings of everyday functioning and social cognitive ability. Correlations between self-reported everyday functioning and social cognitive ability, ratings of everyday functioning and social cognitive ability, and the discrepancies between those ratings were examined for correlations with depression, autistic features and social avoidance. Accuracy was defined by the absolute value of the difference between self-reports and all-sources ratings and bias was defined by the direction of discrepancy (positive vs. negative). There was a statistically significant difference between sources on every measure. Bias was not directional on average, but patients with the lowest levels of depression overestimated their abilities on every measure and those with the highest depression underestimated. Autistic traits were associated with impairments in everyday functioning and underestimation of those impairments, while social avoidance was associated with impaired social functioning and accurate self-assessment. Features of schizophrenia have differential implications for impaired functioning and self-assessment, with autistic features and low levels of depression associated with consistent self-assessment biases.

Cell-penetrating peptides (CPPs) are a class of small peptides that are able to cross cell membranes via direct translocation or endocytosis. They have been widely used to deliver tethered bioactive molecules to cells, but recombinantly producing CPPs as fusions to protein cargo leads to low yields. We used Escherichia coli cells to recombinantly produce genetic fusions of NPFSD (derived from a yeast endocytosis signal) and pVEC (derived from a murine vascular endothelium cadherin) to the N-terminus of green fluorescent protein (GFP) with and without a flexible glycine-serine linker between the CPP and GFP. The flexible linker improved the expression of the NPFSD construct and the pVEC construct, resulting in a 24.5 % improvement in yield for the NPFSD fusion and a 50.0 % improvement in yield for the pVEC fusion. The linker did not diminish the ability of the fusions to translocate into the fungal pathogen Candida albicans, and the translocation of the NPFSD constructs actually increased by 58 % at 10 min. Moreover, the toxicity of the fusions towards C. albicans was not affected by the incorporation of the linker. These results illustrate the utility of including a linker for CPP-cargo fusions and the potential of NPFSD and pVEC fusions for use in delivering protein cargo to C. albicans.

Background: Active participation in patients’ own care is essential for success after Lapidus procedure. Poor health literacy, comprehension, and retention of patient instructions may be correlated with patient participation. Currently, there is no objective measure of how well patients internalize and retain instructions before and after a Lapidus procedure. We performed this study to assess how much of the information given to patients preoperatively was able to be recalled at the first postoperative visit. Methods: All patients between ages 18 and 88 years undergoing a Lapidus procedure for hallux valgus by the senior author between June 2016 and July 2018 were considered eligible for inclusion. Patients were excluded if they had a history of previous bunion surgery or if the procedure was part of a flatfoot reconstruction. Patients were given written and verbal instructions at the preoperative visit. Demographic and comprehension surveys were administered at their first visit approximately 2 weeks postoperatively. A total of 50 patients, of which 42 (84%) were female and 43 (86%) had a bachelor’s degree or higher, were enrolled. Results: Mean overall score on the comprehension survey was 6.2/8 (±1.2), mean procedure subscore was 1.8/3 (±0.64), and mean postoperative protocol subscore was 4.4/5 (±0.8). The most frequently missed question asked patients to identify the joint fused in the procedure. Conclusion: Although comprehension and retention of instructions given preoperatively was quite high in our well-educated cohort, our findings highlight the importance of delivering clear instructions preoperatively and reinforcing these instructions often. Level of Evidence: Level II, prospective cohort study.

Impairments in self-assessment in schizophrenia have been shown to have functional and clinical implications. Prior studies have suggested that overconfidence can be associated with poorer cognitive performance in people with schizophrenia, and that reduced awareness of performance may be associated with disability. However, overconfidence is common in healthy individuals as well. This study examines the correlations between performance on a social cognitive test, confidence in performance, effort allocated to the task, and correlates of confidence in patients with schizophrenia and healthy controls (HC). Measures included self-reports of depression, social cognitive ability, and social functioning. A performance-based emotion recognition test assessed social cognitive performance and provided the basis for confidence judgments. Although schizophrenia patients had reduced levels of overall confidence, there was a substantial subset of schizophrenic patients who manifested extreme overconfidence and these people had the poorest performance and reported the least depression. Further, a substantial number of HC over-estimated their performance as well. Patients with schizophrenia, in contrast to HC, did not adjust their effort to match task difficulty. Confidence was minimally related to task performance in patients but was associated with more rapid decisions in HC, across both correct and incorrect responses. Performance on social cognitive measures was minimally related to self-reports of social functioning in both samples. These data suggest global self-assessments are based on multiple factors, with confidence affecting self-assessments in the absence of feedback about performance. Keywords: Social cognition, Self-assessment, Social functioning, Schizophrenia, Confidence

The purpose of this study was to assess the sensitivity and responsiveness of the Segmental Assessment of Trunk Control (SATCo) for evaluating trunk control in children with spinal cord injury (SCI) receiving activity-based locomotor training (AB-LT).Prospective study of nine outcomes for consecutively enrolled children in outpatient AB-LT. To evaluate sensitivity to change, linear-mixed models were constructed and adjusted for covariates: age at and time since SCI. To evaluate responsiveness, standardized response means and 95% confidence intervals were estimated per outcome.SATCo scores increased significantly (p 0.05) regardless of chronicity, initial score, and injury level. The SATCo was the most responsive measure and the only outcome demonstrating a large effect size after 3 months of therapy.Children with SCI receiving AB-LT improved trunk control regardless of chronicity, initial impairment, or prior experience. SATCo sensitivity and responsiveness support its usefulness in measuring trunk control in children with SCI.

Background: Reconstruction of the stage II adult-acquired flatfoot deformity (AAFD) often requires the use of multiple osteotomies and soft tissue procedures that may not heal well in older patients. The purpose of our study was to determine whether patients older than 65 years with stage II AAFD had inferior clinical outcomes or an increased number of subsequent surgical procedures after flatfoot reconstruction when compared with younger patients. Methods: One-hundred forty consecutive feet (70 right, 70 left) with stage II AAFD in 137 patients were divided into 3 groups based on age: younger than 45 years (young; n = 21), 45 to 65 years (middle-aged; n = 87), and 65 years and older (older; n = 32). Preoperative and postoperative Foot and Ankle Outcome Scores (FAOSs) at a minimum of 2 years were compared. Hospital records were reviewed to determine if patients underwent a subsequent procedure postoperatively. Results: Patients in the older group did not demonstrate any differences in changes in FAOS subscales compared with patients in the young and middle-aged groups (all P > .15). The older group had significant preoperative to postoperative improvements in all the FAOS subgroups ( P < .01). In addition, patients in the older group were not more likely to undergo a subsequent surgery than were the younger patients (all P > .10). Conclusions: Our study found that patients older than 65 years with stage II AAFD have improvements in patient-reported outcomes and rates of revision surgery after surgical reconstruction that were not significantly different than those of younger patients. Level of Evidence: Therapeutic Level III, comparative series.

Background:The number of opioids prescribed and used has increased precipitously over the past 2 decades for a number of reasons and has led to increases in long-term dependency, opioid-related deaths, and diversion. Most studies examining the role of prescribing habits have investigated nonoperative providers, although there is some literature describing perioperative opioid prescription and use. There are no studies looking at the number of pills consumed after outpatient foot and ankle surgeries, nor are there guidelines for how many pills providers should prescribe. The purpose of this study was to quantify the number of narcotic pills taken by opioid-naïve patients undergoing outpatient foot and ankle surgeries with regional anesthesia.Methods:Eighty-four patients underwent outpatient foot and ankle surgeries under spinal blockade and long-acting popliteal blocks. Patients were given 40 or 60 narcotic pills, a 3-day supply of ibuprofen, deep vein thrombosis prophylaxis, and antiemetics. Patients received surveys at postoperative day (POD) 3, 7, 14, and 56 documenting if they were still taking narcotics, the quantity of pills consumed, whether refills were obtained, their pain level, and their reason for stopping opioids.Results:Patients consumed a mean of 22.5 pills, with a 95% confidence interval from 18 to 27 pills. Numerical Rating Scale pain scores started at 4 on POD 3 and decreased to 1.8 by POD 56. The percentage of patients still taking narcotics decreased from 55% on POD 3 to 2.8% by POD 56. Five new prescriptions were given during the study, with 3 being due to side effects from the original medication.Conclusions:Patients receiving regional anesthesia for outpatient foot and ankle surgeries reported progressively lower pain scores with low narcotic use up to 56 days postoperatively. We suggest that providers consider prescribing 30 pills as the benchmark for this patient population.Level of Evidence:Level II, prospective comparative study.

Background: It is critical for patients seeking foot and ankle care to have access to quality online resources, as the treatment of their conditions may involve the use of a variety of diagnostic and therapeutic modalities with which they are unfamiliar. This study was performed to enhance our understanding of if and why patients use Internet-based educational materials, to identify trends in utilization, and to delineate the patient-perceived attributes of quality resources. Methods: Questionnaires were distributed to 150 adult foot and ankle patients. The questionnaire consisted of demographic and Internet utilization questions. Statistical analysis was performed to determine the frequency of responses for each question and the relationship between demographics and Internet usage. Results: Younger patients were more likely to use the Internet ( P= .006). However, there were no other significant differences in demographic attributes between patients who did (76%) and did not (24%) utilize the Internet ( P Conclusion: Although physician and medical society endorsement positively shape patients’ opinions of online education materials, patients often struggle in remembering the site they visited and if it was sponsored by a certain society. Despite this, patients are generally satisfied with online foot and ankle education resources. Future works must assess whether patient and physician perceptions of quality Internet resources are correlated. Level of Evidence: Level IV, case series.

The schizophrenia spectrum has been a long-time concept and includes conditions that are related genetically and phenomenologically to schizophrenia, such as schizoaffective disorder, schizotypal personality disorder (SPD), and attenuated psychosis syndrome (APS). The spectrum, now officially recognized within Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), also reflects the genetic and neurobiological relationships between schizophrenia, schizoaffective disorder, and SPD (Clark et al., 2017). APS, although not currently recognized as part of the spectrum within DSM-5 (Tsuang et al., 2013), has been shown to predict conversion to full-scale schizophrenia spectrum disorders (Zuschlag et al., 2016), potentially warranting its inclusion. Often referred to by a variety of terms such as the prodrome, at-risk mental state, or ultra-high-risk, APS is characterized by subthreshold levels of psychosis, negative symptoms, and social, productive, and cognitive deficits (Glenthoj et al., 2016; Lam et al., 2018; Piskulic et al., 2012; Tsuang et al., 2013). Importantly, patients diagnosed with APS do not uniformly either convert to psychosis or recover; rather, many of these individuals go on to develop other conditions, which may include SPD. A central feature of the spectrum, noted since its earliest description, is cognitive impairment; this is seen in schizophrenia and in other conditions of the spectrum including SPD. Impaired cognition is also observed in individuals who eventually develop schizophrenia when they are seen during their premorbid or prodromal periods, and in unaffected first-degree relatives of people with spectrum conditions, including children who are potentially vulnerable (Harvey et al., 1981) and those who have likely already passed the age of highest risk for developing schizophrenia (Keefe et al., 1994). Impairments in the ability to perform everyday functions are a central feature of schizophrenia and, more recently, have been studied in the spectrum. Since the first descriptions of schizophrenia, the pervasive inability to sustain employment, social relationships, and functional independence has been reported (Harvey et al., 2007). Cognitive impairments are central determinants of these aspects of disability (Green, 1996), and in the last 15 years, it has been proposed that the influence of cognitive deficits on disability is largely mediated by their impact on functional capacity (i.e., the ability to perform critical, cognitively demanding functional skills). These include social and vocational skills, and everyday functions, such as medication management and activities of daily living (Harvey et al., 2007). Across the spectrum, a number of studies have linked cognitive impairment, functional capacity, and everyday functioning. Recently, attempts have been made to intervene with spectrum members who do not meet the criteria for schizophrenia by using rehabilitation-focused interventions including cognitive remediation. Such efforts are longstanding in schizophrenia (but are a new development in other spectrum conditions), and the results of meta-analyses support their efficacy (McGurk et al., 2007; Wykes et al., 2011). Interestingly, in the context of relatively poor results for pharmacological interventions aimed at cognition in schizophrenia, there have been several successful interventions using pharmacological approaches in SPD (McClure et al., 2007; McClure et al., 2010; Rosell et al., 2015). This paper reviews cognitive impairments, functional capacity deficits, and impairments in everyday functioning of people in the schizophrenia spectrum who do not meet the criteria for schizophrenia, with a focus on characteristics and recent treatment approaches. This will include both cognitive remediation and pharmacological-focused efforts and will address improvements in cognition and functional capacity using these interventions. 1.1. Specific features of attenuated psychosis syndrome Prodromal features of schizophrenia have been described for many decades and have typically included deterioration in social and functional competence prior to the onset of psychotic symptoms. Furthermore, cognitive functioning appears to change over the lifetime of psychotic symptom development. As noted by Seidman et al. (2016), “there is ample evidence of significant but milder impairments during the premorbid phase, greater deficits during the prodromal or clinical high-risk (CHR) period [of psychosis], culminating in relatively severe deficits in the first episode and chronic phases (Seidman et al., 2016).” Several large-scale studies have focused on cognition in prodromal cases, including the North American Prodrome Longitudinal Study Phase 1 (NAPLS-1) (Seidman et al., 2010) and 2 (NAPLS-2) (Seidman et al., 2016), the Longitudinal Youth at-Risk Study (LYRIKS) in Singapore (Lam et al., 2018), and several other studies conducted in Europe and Australia (Dickson et al., 2018; McDonald et al., 2018; Mollon et al., 2018; Nelson et al., 2018a; Nelson et al., 2018b). Analyses of data from NAPLS-2 revealed that among 609 patients at CHR, 74 (12%) converted to psychosis, 242 (40%) did not convert, and 293 (48%) went on to develop other outcomes (McLaughlin et al., 2016). As of 2018, 10% of patients in the LYRIKS study were converters; of the 90% who did not convert, 54% were found to remit and the other 46% remained impaired over the entire follow-up period (Lam et al., 2018). Longer-term studies with up to 10 years of follow-up suggest that those who are stably impaired at 2 years do not show marked changes toward conversion to psychosis (Klosterkotter et al., 2001; Nelson et al., 2013) or remission of symptoms (Klosterkotter et al., 2001). Thus, a substantial proportion of individuals within NAPLS, and other similar studies, are not converted/recovered and may potentially represent the earliest stages of SPD. Indeed, non-remitting patients with APS have been suggested to demonstrate similar cognitive and functional deficits to those observed in SPD populations (Harvey, 2018). In fact, SPD was used as one of the potential entry criteria for adolescent patients (age

Liquid-liquid phase separation plays a key role in the assembly of diverse intracellular structures. However, the biophysical principles by which phase separation can be precisely localized within subregions of the cell are still largely unclear, particularly for low-abundance proteins. Here, we introduce an oligomerizing biomimetic system, "Corelets," and utilize its rapid and quantitative light-controlled tunability to map full intracellular phase diagrams, which dictate the concentrations at which phase separation occurs and the transition mechanism, in a protein sequence dependent manner. Surprisingly, both experiments and simulations show that while intracellular concentrations may be insufficient for global phase separation, sequestering protein ligands to slowly diffusing nucleation centers can move the cell into a different region of the phase diagram, resulting in localized phase separation. This diffusive capture mechanism liberates the cell from the constraints of global protein abundance and is likely exploited to pattern condensates associated with diverse biological processes. VIDEO ABSTRACT.

Cell and tissue degeneration, and the development of degenerative diseases, are influenced by genetic and environmental factors that affect protein misfolding and proteotoxicity. To better understand the role of the environment in degeneration, we developed a genetic model for heat shock (HS)-stress-induced degeneration in Drosophila. This model exhibits a unique combination of features that enhance genetic analysis of degeneration and protection mechanisms involving environmental stress. These include cell-type-specific failure of proteostasis and degeneration in response to global stress, cell-nonautonomous interactions within a simple and accessible network of susceptible cell types, and precise temporal control over the induction of degeneration. In wild-type flies, HS stress causes selective loss of the flight ability and degeneration of three susceptible cell types comprising the flight motor: muscle, motor neurons and associated glia. Other motor behaviors persist and, accordingly, the corresponding cell types controlling leg motor function are resistant to degeneration. Flight motor degeneration was preceded by a failure of muscle proteostasis characterized by diffuse ubiquitinated protein aggregates. Moreover, muscle-specific overexpression of a small heat shock protein (HSP), HSP23, promoted proteostasis and protected muscle from HS stress. Notably, neurons and glia were protected as well, indicating that a small HSP can mediate cell-nonautonomous protection. Cell-autonomous protection of muscle was characterized by a distinct distribution of ubiquitinated proteins, including perinuclear localization and clearance of protein aggregates associated with the perinuclear microtubule network. This network was severely disrupted in wild-type preparations prior to degeneration, suggesting that it serves an important role in muscle proteostasis and protection. Finally, studies of resistant leg muscles revealed that they sustain proteostasis and the microtubule cytoskeleton after HS stress. These findings establish a model for genetic analysis of degeneration and protection mechanisms involving contributions of environmental factors, and advance our understanding of the protective functions and therapeutic potential of small HSPs., Summary: A Drosophila model for environmental-stress-induced degeneration exhibits key features for genetic analysis of degenerative disease mechanisms and reveals new forms of protection mediated by small heat shock proteins.

Category: Midfoot/Forefoot Introduction/Purpose: While Metatarsus Primus Elevatus (MPE) has been implicated in the development of hallux rigidus, previous studies have presented conflicting findings regarding the relationship between an elevated first metatarsal and arthritis. This may be due to the variety of definitions for MPE and the radiographic measurement techniques that are used to assess it. The aim of this study was to examine the reliability of new radiographic measurements that take into account the elevation of the first metatarsal in relation to the proximal phalanx, rather than in relation to the second metatarsal as previously described, to assess for MPE. In addition, we aimed to determine whether the elevation of the first metatarsal was significantly different in hallux rigidus patients than in a control population. Methods: A retrospective chart review was conducted from prospectively collected registry data at the investigators’ institution to identify patients with hallux rigidus (n=65). A size matched control cohort of patients without evidence for first metatarsophalangeal (MTP) joint arthritis were identified (n=65). Patients with a previous history of foot surgery, rheumatoid arthritis, or hallux valgus were excluded. Five blinded raters of varying levels of training, including two research assistants, a senior orthopedic resident, a foot & ankle fellow, and an attending radiologist, evaluated seven radiographic measurements for their reliability in assessing for MPE in hallux rigidus and control groups. Four of the seven measurements were newly designed taking into account the relationship of the first MTP joint. Inter- and intrarater reliability were calculated using Intraclass Correlation Coefficients (ICC) and categorized by Landis and Koch reliability thresholds. The measurements between the hallux rigidus and control populations were compared using an independent t-test. Results: Six of the seven radiographic measurements were found to have substantial to almost perfect interrater reliability (ICC=0.800 to 0.953) between all levels of training, except for the Proximal Phalanx-First Metatarsal Angle which showed moderate reliability (ICC=0.527) (Table). Substantial to almost perfect intrarater reliability (ICC=0.710-0.980) was demonstrated by the research assistants. Six of the seven measurements taken by the attending radiologist demonstrated significant differences in first metatarsal elevation between the hallux rigidus and control populations with the hallux rigidus group showing increased elevation (p=0.000-0.020). Only the First Metatarsal Elevation Angle failed to show a significant difference between the populations (p=0.368). However, the First Metatarsal Elevation Angle measurements of the research assistant and the senior orthopedic resident did show a significant difference between the two populations (pConclusion: This study confirmed the reliability of seven radiographic measurements used to assess for MPE, including three previously established and four newly described measurements. Observers across all levels of training were able to demonstrate reliable measurements. In addition, the measurements were used to show that hallux rigidus patients are more likely to have an elevated first metatarsal compared to patients without radiographic evidence for first MTP arthritis. These measurements could be used in future work to examine how the presence of MPE relates to the etiology and progression of hallux rigidus, and how it affects the results of operative treatment.

Sustained parental involvement in diabetes management has been generally advised to counteract the deteriorating adherence and glycemic control often seen during adolescence, yet until recently, little attention has been given to the optimal amount, type, and quality of parental involvement to promote the best health outcomes for adolescents with type 1 diabetes (T1D). This review synthesizes research regarding the involvement of caregivers-primarily mothers and fathers-of youth with T1D, with a focus on biopsychosocial outcomes. The recent literature on parental involvement in diabetes management highlights a shift in focus from not only amount but also the types (e.g., monitoring, problem-solving) and quality (e.g., warm, critical) of involvement in both mothers and fathers. We provide recommendations for ways that both parents can remain involved to facilitate greater collaboration in shared direct and indirect responsibility for diabetes care and improve outcomes in youth with T1D.

Objective: The purpose of this study was to explore the self-reported hand hygiene practices and the predictors of hand hygiene among physicians in a midsize Canadian city. Methods: A descriptive cross-sectional survey using self-report questionnaire administered to a complete list of 354 local physicians. Perception of proper compliance was defined in a participant if he/she indicated performance of hand hygiene before and after every patient contact at least 80% of the time. Results: One hundred fifty-four physicians completed the questionnaire, yielding a 44.9% response rate. Only 45.3% of our sample reported performing preprocedure and postprocedure hand hygiene at least 80% of the time. Stepwise logistic regression results suggested that the variables "presence of hand hygiene auditing" (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.47-6.91), "being too busy" (OR, 0.43; 95% CI, 0.20-0.90), "forgetfulness" (OR, 0.27; 95%, CI, 0.13-0.56), and "the perception that hand hygiene products are damaging to the skin" (OR, 0.31;95% CI, 0.11-0.88) were the only independent predictors of physician hand hygiene compliance. Conclusions: Hand hygiene compliance among physicians remains an issue. The findings emphasize the need of health-care institutions to prioritize hand hygiene by ensuring proper promotion and enforcement of current policies to all practicing HCPs. © 2013 by Lippincott Williams and Wilkins.

Selenium is an essential element required for activity of several antioxidant enzymes, including glutathione peroxidase. Because of the critical role of the antioxidant system in responding to traumatic events, we hypothesized that dietary selenium supplementation would enhance neuroprotection in a rodent model of spinal cord injury. Rats were maintained on either a control or selenium-enriched diet prior to, and following, injury. Dietary selenium supplementation, provided as selenized yeast added to normal rat chow, resulted in a doubling of selenium levels in the spinal cord. Dietary selenium reduced the time required for recovery of bladder function following thoracic spinal cord injury. However, this was not accompanied by improvement in locomotor function or tissue sparing.

Background The multi-morbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse COVID-19 outcomes but data are limited. Objective Characterize the course of COVID-19 in psoriasis and identify factors associated with hospitalization. Methods Clinicians reported psoriasis patients with confirmed/suspected COVID-19 via an international registry, PsoProtect. Multiple logistic regression assessed the association between clinical/demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviours. Results Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% a non-biologic and 10% no systemic treatment for psoriasis. 348 (93%) fully recovered from COVID-19, 77 (21%) were hospitalized and nine (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted OR 1.59 per 10 years, 95% CI 1.19-2.13), male sex (OR 2.51, 95% CI 1.23-5.12), non-white ethnicity (OR 3.15, 95% CI 1.24-8.03) and comorbid chronic lung disease (OR 3.87, 95% CI 1.52-9.83). Hospitalization was more frequent in patients using non-biologic systemic therapy than biologics (OR 2.84, 95% CI 1.31-6.18). No significant differences were found between biologic classes. Independent patient-reported data (n=1,626 across 48 countries) suggested lower levels of social isolation in individuals receiving non-biologic systemic therapy compared to biologics (OR 0.68, 95% CI 0.50-0.94). Conclusion In this international moderate-severe psoriasis case series, biologics use was associated with lower risk of COVID-19-related hospitalization than non-biologic systemic therapies, however further investigation is warranted due to potential selection bias and unmeasured confounding. Established risk factors (being older, male, non-white ethnicity, comorbidities) were associated with higher hospitalization rates. Clinical Implications We identify risk factors for COVID-19-related hospitalization in psoriasis patients, including older age, male sex, non-white ethnicity and comorbidities. Use of biologics was associated with lower hospitalization risk than non-biologic systemic therapies., Capsule summary: In this global registry-based study, risk factors for COVID-19-related hospitalization in psoriasis patients were older age, male sex, non-white ethnicity and comorbidities. Use of biologics was associated with lower hospitalization risk than non-biologic systemic treatment.