Ocular transmissibility of COVID-19: possibilities and perspectives.

Since the initial outbreak of coronavirus disease 2019 (COVID-19), extensive research has emerged from across the globe to understand the pathophysiology of this novel coronavirus. Transmission of this virus is a subject of particular interest as researchers work to understand which protective and preventative measures are most effective. Despite the well understood model of aerosol-respiratory mediated transmission, the exact mechanism underlying the inoculation, infection and spread of COVID-19 is currently unknown. Given anatomical positioning and near constant exposure to aerosolized pathogens, the eye may be a possible gateway for COVID-19 infection. This critical review explores the possibility of an ocular-systemic or ocular-nasal-pulmonic pathway of COVID-19 infection and includes novel insights into the possible immunological mechanisms leading to cytokine surge.

Similarities and differences in revised reinforcement sensitivities across eating disorder subtypes.

Reinforcement Sensitivity Theory has been used to investigate personality in the development and maintenance of disordered eating. However, the vast majority of research from this perspective has been limited by the use of measures developed to assess the original theory, rather than the significantly revised theory, potentially overlooking key personality differences in eating disorder subtypes. The current study aimed to overcome limitations when using measures based on the original theory by investigating differences and similarities in reinforcement sensitivity across eating disorder subtypes and healthy controls. The measure based on the revised theory assesses i) reward sensitivity [goal-drive persistence; reward interest, reward reactivity], ii) impulsivity, iii) behavioural inhibition, and iv) threat sensitivity. A total of 374 women from the community participated, including those with a past or present AN-R diagnosis (AN-R = 109); those with a past or present binge-type ED (Binge-type = 132); and healthy controls (HC = 133). Participants completed a questionnaire assessing personality, eating disorder symptoms, and past or present eating disorder diagnoses. Results showed that both the AN-R and Binge-type groups were higher in behavioural inhibition and threat sensitivity compared to the HC group. The Binge-type group showed higher impulsivity relative to the AN-R and HC group, and lower Goal-Drive Persistence relative to the HC group. The AN-R group showed lower Reward Interest and Reward Responsiveness relative to the HC group. This study supports and extends previous research with the findings of heightened threat and anxiety sensitivity in those with diagnosed eating disorders. Additionally, among those with a past or present eating disorder, the findings implicate impulsivity in differentiating bingeing versus restricting subtypes.

Long COVID: Complications, Underlying Mechanisms, and Treatment Strategies.

Long Covid is one of the most prevalent and puzzling conditions that arose with the Covid pandemic. Covid-19 infection generally resolves within several weeks but some experience new or lingering symptoms. Though there is no formal definition for such lingering symptoms the CDC boadly describes long Covid as persons having a wide range of new, recurring or sustained health issues four or more weeks after first being infected with SARS-CoV2. The WHO defines long Covid as the manifestation of symptoms from a "probable or confirmed" Covid-19 infection that start approximately 3 months after the onset of the acute infection and last for more than 2 months. Numerous studies have looked at the implications of long Covid on various organs. Many specific mechanisms have been proposed for such changes. In this article, we provide an overview of some of the main mechanisms by which long Covid induces end-organ damage proposed in recent research studies. We also review various treatment options, current clinical trials, and other potential therapeutic avenues to control long Covid followed by the information about the effect of vaccination on long Covid. Lastly, we discuss some of the questions and knowledge gaps in the present understanding of long Covid. We believe more studies of the effects long Covid has on quality of life, future health and life expectancy are required to better understand and eventually prevent or treat the disease. We acknowledge the effects of long Covid are not limited to those in this article but as it may affect the health of future offspring and therefore, we deem it important to identify more prognostic and therapeutic targets to control this condition.

Therapeutic Potential of "Smart" Exosomes in Peripheral Nerve Regeneration.

Peripheral nerve injury results in severe loss of motor and sensory function in the affected limb. The gold standard for peripheral nerve repair is autologous nerve grafts, but their inherent drawbacks limit their use. Satisfactory clinical data are yet to be obtained using tissue engineered nerve grafts with neurotrophic factors introduced in these grafts for nerve repair. Therefore, peripheral nerve regeneration still remains a challenge for clinicians. Exosomes are secreted nanovesicles from the extracellular membrane. They are critical for communication within the cell and play a crucial role in the pathologic process of the peripheral nervous system. Recent research supports the role of exosomes in exhibiting neurotherapeutic effects through axonal growth, Schwann cell activation, and regulating inflammation. Indeed, the use of "smart" exosomes by reprogramming or manipulating the secretome contents and functions are rising as a therapeutic option for treating peripheral nerve defects. This review provides an overview on the promising role of exosomes in the process of peripheral nerve regeneration.

Oncostatin M, Serpins, and Oxidative Stress in Extracellular Matrix Remodeling and Arteriovenous Fistula Maturation.

End-stage renal disease is a crippling diagnosis that generally requires dialysis to prolong life. To facilitate filtration of patient's blood in dialysis, surgical formation of an arteriovenous fistula (AVF) is commonly performed. Maturation of the AVF is required to allow for successful dialysis. However, AVFs commonly fail to mature, leading to the fistula closure, the necessity for another fistula site, and markedly increased morbidity and mortality. The current literature concerning molecular mechanisms associated with AVF maturation failure supports the role of inflammatory mediators involving immune cells and inflammatory cytokines. However, the role of oncostatin M (OSM), an inflammatory cytokine, and its downstream targets are not well investigated. Through inflammation, oxidative stress, and hypoxic conditions, the vascular tissue surrounding the AVF undergoes fibrosis, stenosis, and wall thickening, leading to complete occlusion and nonfunctional. In this report, first we critically review the existing literature on the role of OSM in the most common causes of early AVF failure - vascular inflammation, thrombosis, and stenosis. We next consider the potential of using OSM as a therapeutic target, and finally discuss therapeutic agents targeting inflammatory mediators involved in OSM signaling to potentiate successful maturation of the AVF.

Longitudinal study of inflammation and relapse in schizophrenia.

INTRODUCTION: The clinical course of schizophrenia is often characterized by recurrent relapses. Blood inflammatory markers are altered in acute psychosis, and may be state markers for illness relapse in schizophrenia. Few studies have investigated longitudinal, intra-individual changes in inflammatory markers as a predictor of relapse. In the present study, we explored this association in a relapse prevention trial in patients with schizophrenia. METHODS: We analyzed blood inflammatory markers in 200 subjects, with a mean 11 samples per subject, during the 30 month Preventing Relapse in schizophrenia: Oral Antipsychotics Compared to Injectable: eValuating Efficacy (PROACTIVE) trial. Associations between longitudinal changes in inflammatory markers and relapse were analyzed using a within-subjects design. RESULTS: 70 (35 %) of subjects relapsed during the study period. There were no significant differences in mean inflammatory marker levels based on relapse status (yes/no). Baseline levels of inflammatory markers did not predict incident relapse. Among subjects who relapsed, there was a significant decrease in mean blood IL-6 (n = 38, p = 0.019) and IFN-γ (n = 44, p = 0.012) levels from the visit before the relapse to the visit after relapse. CONCLUSION: Although there was some evidence for inflammation as a potential state marker for acute psychosis, we did not find significant evidence for its utility as a relapse-predictive marker.

From BIS to binge: The role of negative affect in the pathway between personality and binge eating.

Recent research has highlighted the utility of using revised Reinforcement Sensitivity Theory (RST) to further understand the individual differences that influence binge eating behaviours. The current study draws on both RST and theoretical models that implicate negative affect in binge eating, with the aim of identifying indirect pathways between individual differences in RST systems and binge eating as mediated through negative affect. Undergraduate students (n = 229, M = 22.67 years of age, SD = 8.95, 76% female) completed self-report measures of revised reinforcement sensitivities, negative affect and binge eating symptoms. Bootstrapped tests of indirect effects showed that negative affect mediated the pathway between the Behavioural Inhibition System (BIS) and binge eating symptoms. Additionally, negative affect mediated the pathway between rash impulsivity and binge eating symptoms. This study supports and extends previous research by highlighting the experience of negative affect as a possible mechanism through which heightened BIS and rash impulsivity leads to binge eating.

The influence of depositional environment on the abundance of microplastic pollution on beaches in the Bristol Channel, UK.

Microplastic is a ubiquitous environmental contaminant, but large gaps still exist in our knowledge of its distribution. We conducted a detailed assessment of the extent and variability of microplastic pollution in the Bristol Channel, UK. Sand samples were collected between the 5th and 30th August 2017, with microplastic recovered from 15 of the 16 beaches sampled along a coastal extent of ~230 km. In total, 1446 particles of suspected microplastic were extracted using a cascade of sieves and visual identification. The most common microplastics recovered were fragments (74%) and industrial plastic pellets (13%). We used Fourier-Transform Infrared (FTIR) spectroscopy to analyse 25% of recovered particles, 96.5% of which were confirmed as plastic, with polyethylene (61%) and polypropylene (26%) the most common polymers. Our analysis of local beach environments indicates microplastic burdens were higher on lower energy beaches with finer sediments, highlighting the importance of depositional environment in determining microplastic abundance.

The role of complex emotions in inconsistent diagnoses of schizophrenia.

In the case of large-scale epidemiological studies, there is evidence of substantial disagreement when lay diagnoses of schizophrenia based on structured interviews are compared with expert diagnoses of the same patients. Reasons for this level of disagreement are investigated in the current study, which made use of advances in text-mining techniques and associated structural representations of language expressions. Specifically, the current study examined whether content analyses of transcribed diagnostic interviews obtained from 150 persons with serious psychiatric disorders yielded any discernable patterns that correlated with diagnostic inconsistencies of schizophrenia. In summary, it was found that the patterning or structure of spontaneous self-reports of emotion states in the diagnostic interview was associated with diagnostic inconsistencies of schizophrenia, irrespective of confounders; i.e., age of patient, gender, or ethnicity. In particular, complex emotion patterns were associated with greater disagreement between experts and trained lay interviewers than were simpler patterns.

Evolutionary perspectives on human behavior during the coronavirus pandemic: Insights from game theory.

The coronavirus pandemic constitutes a global challenge to society and medicine. Here, we review evolutionary insights that are relevant for the understanding of how people respond to the pandemic and what to expect in the aftermath of the crisis. Specifically, we argue that the behavioral immune system (BIS) and sickness behavior (SB) comprise two adaptive responses to impending and actual infection, respectively, and that individuals activating their BIS differ from those showing SB in important ways that may have implications for the prevention and treatment of COVID-19. Moreover, we reframe some of the behavioral health issues associated with the pandemic in a game-theoretical scenario, illustrating the difficulties that arise when public health is treated as a 'public good'. Lay summary: The coronavirus pandemic constitutes a global challenge to society and medicine. In this article, we employ evolutionary theory to improve our understanding of how people respond to the pandemic. Specifically, we argue that human behavior is guided by ancient mechanisms involving either the avoidance of infection or defense against attacks in times of enhanced vulnerability. Moreover, we reframe some of the behavioral health issues associated with the pandemic in a game-theoretical scenario. This helps understand why most people comply with rules of social distancing, while a minority fails to do so for very different reasons. The evolutionary perspective also allows making some predictions for the course of the pandemic.

Neuropeptides: relevance in treatment of depression and anxiety disorders.

The etiology and pathophysiology of both depression and anxiety remain unclear, but involve dysfunctional monoaminergic neurotransmission and function. The currently available antidepressant medications that work through optimizing the monoaminergic system are often limited by their lack of efficacy or their adverse effects. There is increasing evidence that some neuropeptides, including substance P, corticotropin-releasing factor, neuropeptide Y, vasopressin and galanin, may have relevance in both depression and anxiety. Integration of anatomical, physiological and clinical evidence suggests that modulation of monoaminergic transmission is the most likely mechanism by which neuropeptides may work in these disorders. These neuropeptides and their receptors may serve not only as potential therapeutic targets for treatment of depression and anxiety, but may also help enhance our understanding of the psychopathology of these two major psychiatric disorders.

Standard and higher dose of olanzapine in patients with schizophrenia or schizoaffective disorder: a randomized, double-blind, fixed-dose study.

The objective of this study was to assess the dose-response relationship of standard and higher doses of olanzapine in a randomized, double-blind, 8-week, fixed-dose study comparing olanzapine 10 (n = 199), 20 (n = 200), and 40 mg/d (n = 200) for patients with schizophrenia or schizoaffective disorder and suboptimal response to current treatment. Patients meeting criteria for antipsychotic treatment resistance were excluded. Dose-response relationship was assessed by linear regression analysis with log-transformed dose (independent variable) and Positive and Negative Syndrome Scale (PANSS) total score (dependent variable). There were no significant dose group differences in patients completing the study (overall, 67.8%). All dose groups showed statistically significant improvement in PANSS total scores from baseline to end point without significant dose-response relationship (P = 0.295). Post hoc analysis of response showed significant interaction between baseline PANSS and dose (P = 0.023), indicating better response at higher doses for patients with higher baseline PANSS. There was a significant dose response for mean change in weight (P = 0.003) with significant difference between the 10- and 40-mg-dose groups (P = 0.002; 1.9 [10 mg/d], 2.3 [20 mg/d], and 3.0 kg [40 mg/d]). There was a significant dose response for change in prolactin (P < 0.001) with a significant difference between each group (-10.5 [10 mg/d], -1.7 [20 mg/d], and 4.9 ng/mL [40 mg/d]; P < or = 0.018). Over 8 weeks, non-treatment-resistant patients with schizophrenia or schizoaffective disorder responded to all 3 doses of olanzapine, without a statistically significant dose-response relationship, suggesting that for many patients with schizophrenia or schizoaffective disorder, particularly those who are mildly or moderately ill, 10 mg/d should be the initial dose of choice.

Predicting relapse in schizophrenia: Is BDNF a plausible biological marker?

Understanding the biological processes that underlie why patients relapse is an issue of fundamental importance to the detection and prevention of relapse in schizophrenia. Brain Derived Neurotrophic Factor (BDNF), a facilitator of brain plasticity, is reduced in patients with schizophrenia. In the present study, we examined whether decreases in plasma BDNF levels could be used as a biological predictor of relapse in schizophrenia. A total of 221 patients were prospectively evaluated for relapse over 30months in the Preventing Relapse in Schizophrenia: Oral Antipsychotics Compared to Injectables: eValuating Efficacy (PROACTIVE) study. Serial blood samples were collected at a maximum of 23 time points during the 30-month trial and BDNF levels were measured in plasma samples by ELISA. Receiver Operating Characteristic (ROC) curve analysis indicated that BDNF was not a significant predictor of relapse, hospitalization or exacerbation. Regardless of treatment group (oral second generation antipsychotic vs. long-acting injectable risperidone microspheres), baseline BDNF value did not differ significantly between those who experienced any of the adverse outcomes and those who did not. While contrary to the study hypothesis, these robust results offer little support for the use of plasma BDNF alone as a biomarker to predict relapse in schizophrenia.

Risperidone monotherapy for post-traumatic stress disorder related to sexual assault and domestic abuse in women.

Post-traumatic stress disorder is a common, chronic, and often disabling mental illness. Selective serotonin reuptake inhibitors are the usual first-line treatment for post-traumatic stress disorder, but many patients fail to respond adequately. Thus, other treatment options, including the atypical antipsychotics such as risperidone, need to be tested. Women between the ages of 19 and 64 years with post-traumatic stress disorder were enrolled. Symptom severity was rated at baseline using the Treatment Outcomes Post-traumatic Stress Disorder Scale-8, Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Clinician Administered Post-traumatic Stress Disorder Scale. After washout from other psychotropic medications, 20 participants were randomized to either risperidone or placebo. Total score on the Treatment Outcomes Post-traumatic Stress Disorder Scale-8 served as the primary outcome measure. Repeated-measures analysis of variance was followed by Newman-Keuls tests. A significant main effect exists for visits using the Treatment Outcomes Post-traumatic Stress Disorder Scale-8 raw score. For the treatment group, the difference between baseline Treatment Outcomes Post-traumatic Stress Disorder Scale-8 scores and treatment visit scores was significant beginning at visit 6 and continued through visit 11. No significant difference observed between baseline and any treatment visit for the placebo group. The Clinician Administered Post-traumatic Stress Disorder Scale, Hamilton Rating Scale for Anxiety, and Hamilton Rating Scale for Depression data revealed a similar pattern. In this small pilot study, risperidone monotherapy was more effective than placebo in the treatment of post-traumatic stress disorder.

Comparison of Injectable and Oral Antipsychotics in Relapse Rates in a Pragmatic 30-Month Schizophrenia Relapse Prevention Study.

OBJECTIVE: In a pragmatic clinical trial, this study sought to compare relapses among patients receiving either long-acting injectable or oral second-generation antipsychotics. METHODS: PROACTIVE (Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy), a prior 30-month relapse prevention study, compared use of a long-acting injectable second-generation antipsychotic with use of an oral second-generation antipsychotic by 305 patients with schizophrenia or schizoaffective disorder and found similar rates of first relapse between groups (42% with injectable medication, 32% with oral medication). This study examined subsequent relapses among patients who had relapsed in PROACTIVE and who continued in treatment, follow-up, or both. RESULTS: Thirty-two patients (11%) experienced two relapses, and 13 patients (4%) had three relapses. Neither rate of relapse nor time to successive relapses differed between treatment groups. CONCLUSIONS: There was an impressively low rate of subsequent relapses in this pragmatic clinical trial. Because all patients had a clinic visit according to the biweekly long-acting injectable medication administration schedule, frequent contact may have contributed to low relapse rates. Maintaining frequent clinical contact may be a valid psychosocial relapse prevention treatment.

Should MD-PhD programs encourage graduate training in disciplines beyond conventional biomedical or clinical sciences?

The goal of MD-PhD training programs is to produce physician-scientists with unique capacities to lead the future biomedical research workforce. The current dearth of physician-scientists with expertise outside conventional biomedical or clinical sciences raises the question of whether MD-PhD training programs should allow or even encourage scholars to pursue doctoral studies in disciplines that are deemed nontraditional, yet are intrinsically germane to major influences on health. This question is especially relevant because the central value and ultimate goal of the academic medicine community is to help attain the highest level of health and health equity for all people. Advances in medical science and practice, along with improvements in health care access and delivery, are steps toward health equity, but alone they will not come close to eliminating health inequalities. Addressing the complex health issues in our communities and society as a whole requires a biomedical research workforce with knowledge, practice, and research skills well beyond conventional biomedical or clinical sciences. To make real progress in advancing health equity, educational pathways must prepare physician-scientists to treat both micro and macro determinants of health. The authors argue that MD-PhD programs should allow and encourage their scholars to cross boundaries into less traditional disciplines such as epidemiology, statistics, anthropology, sociology, ethics, public policy, management, economics, education, social work, informatics, communications, and marketing. To fulfill current and coming health care needs, nontraditional MD-PhD students should be welcomed and supported as valuable members of our biomedical research workforce.

Comparison of SGA oral medications and a long-acting injectable SGA: the PROACTIVE study.

Until relatively recently, long-acting injectable (LAI) formulations were only available for first-generation antipsychotics and their utilization decreased as use of oral second-generation antipsychotics (SGA) increased. Although registry-based naturalistic studies show LAIs reduce rehospitalization more than oral medications in clinical practice, this is not seen in recent randomized clinical trials. PROACTIVE (Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy) relapse prevention study incorporated efficacy and effectiveness features. At 8 US academic centers, 305 patients with schizophrenia or schizoaffective disorder were randomly assigned to LAI risperidone (LAI-R) or physician's choice oral SGAs. Patients were evaluated during the 30-month study by masked, centralized assessors using 2-way video, and monitored biweekly by on-site clinicians and assessors who knew treatment assignment. Relapse was evaluated by a masked Relapse Monitoring Board. Differences between LAI-R and oral SGA treatment in time to first relapse and hospitalization were not significant. Psychotic symptoms and Brief Psychiatric Rating Scale total score improved more in the LAI-R group. In contrast, the LAI group had higher Scale for Assessment of Negative Symptoms Alogia scale scores. There were no other between-group differences in symptoms or functional improvement. Despite the advantage for psychotic symptoms, LAI-R did not confer an advantage over oral SGAs for relapse or rehospitalization. Biweekly monitoring, not focusing specifically on patients with demonstrated nonadherence to treatment and greater flexibility in changing medication in the oral treatment arm, may contribute to the inability to detect differences between LAI and oral SGA treatment in clinical trials.

New-onset diabetes and ketoacidosis with atypical antipsychotics.

Information from the Ohio Department of Mental Health (ODMH) database was reviewed retrospectively to identify patients at the Cincinnati center treated with an atypical antipsychotic and who had also been evaluated or treated for diabetes mellitus. Blood glucose levels, glucose tolerance, or other evaluations of diabetes had been conducted in 14 of the 126 patients treated with atypical antipsychotics. In 11 of the 14, new-onset, acute, and marked glucose intolerance developed after treatment with clozapine, olanzapine or quetiapine. Of these, six patients required insulin therapy (four only transiently) and five patients developed diabetic ketoacidosis (DKA). Also, glucose metabolism was labile in all cases, and was transient in two cases with subsequent resolution despite on-going antipsychotic therapy. Certain atypical antipsychotics may be associated with new-onset glucose intolerance, including acute diabetes and ketoacidosis. Monitoring for changes in blood glucose levels in patients taking atypical antipsychotics may be indicated. More systematic study data are clearly needed.