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Background: Potentiating current antidepressant treatment is much needed. Based on animal studies, caffeine may augment the effects of currently available antidepressants. Objective: Here, we tested whether habitual caffeine consumption moderates the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) using intermittent theta-burst stimulation (iTBS). Methods: Forty patients with current depressive episodes were randomized to active iTBS ( n = 19) or sham treatment ( n = 21; shielded side of the coil and weak transcutaneous electrical stimulation) delivered two times per day for 10–15 weekdays. Neuronavigated stimulation was applied to the dorsomedial prefrontal cortex. Symptom improvement was measured using change in self-reported Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Pretreatment habitual caffeine consumption was quantified using self-reports of number of cups of coffee and energy drinks consumed the 2 days before the treatment starts. Results: Habitual caffeine consumption was associated with symptom improvement following active iTBS ( r = 0.51, 95% confidence interval (CI): 0.08–0.78, p = 0.025) but not following sham treatment ( r = −0.02, 95% CI: −0.45 to 0.42, p = 0.938). A multiple regression analysis corroborated the findings by showing a significant caffeine consumption × treatment group interaction (β = 0.62, p = 0.043), but no main effects of treatment group (β = 0.22, p = 0.140) or caffeine consumption (β = −0.01, p = 0.948). No group differences in pretreatment symptom scores or caffeine consumption were detected ( p values > 0.86). Conclusion: Habitual caffeine consumption moderated the antidepressant effect of dorsomedial iTBS, consistent with caffeine improving antidepressant pharmacological treatments in animals. Caffeine is an antagonist of adenosine receptors and may enhance antidepressant effects through downstream dopaminergic targets.

Background: In recent years, there has been significant research on the mental health effects of classic psychedelic use, but there is very little evidence on how classic psychedelics might influence physical health. Aims: The purpose of the present study was to investigate the associations between lifetime classic psychedelic use and markers of physical health. Methods: Using data from the National Survey on Drug Use and Health (2015-2018) with 171,766 (unweighted) adults aged 18 or above in the United States, the current study examined the associations between lifetime classic psychedelic use and three markers of physical health (self-reported overall health, body mass index, and heart condition and/or cancer in the past 12 months) while controlling for a range of covariates. Results: Respondents who reported having tried a classic psychedelic at least once in their lifetime had significantly higher odds of greater self-reported overall health and significantly lower odds of being overweight or obese versus having a normal weight. The association between lifetime classic psychedelic use and having a heart condition and/or cancer in the past 12 months approached conventional levels of significance, with lower odds of having a heart condition and/or cancer in the past 12 months for respondents who had tried a classic psychedelic at least once. Conclusion: The results of the present study suggest that classic psychedelics may be beneficial to physical health. Future research should investigate the causal effects of classic psychedelics on physical health and evaluate possible mechanisms.

The recent increase of migration to Europe represents a risk of increased the prevalence of multidrug-resistant (MDR) bacteria. We conducted a cross-sectional study among asylum seekers admitted at two hospitals in Switzerland. Of the 59 patients included, 9 (14%) were colonised by a MDR bacteria, including 5 (8.5%) methicilin-resistant Staphylococcus aureus (MRSA) and 4 (6.8%) extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. No patient carried both ESBL-producing bacteria and MRSA. None of the patients carried a vancomycin-resistant Enterococcus (VRE) or a carbapenem-resistant Enterobacteriaceae (CRE). Colonisation with MDR bacteria was not associated with hospitalisation abroad or recent arrival in Switzerland. Whole genome sequencing analysis allowed us to exclude transmission between patients. The prevalence of MDR bacteria carriage is moderate among asylum seekers in western Switzerland. Further surveillance studies are necessary to determine if there is a risk of dissemination of pathogens into the local population.

Status migrainosus (SM) is a subtype of migraine defined by migraine lasting >72 hours and is difficult to treat in clinical practice. Magnesium is commonly used in the treatment of migraine. We conducted a retrospective cohort study to determine if length of admission was associated with IV magnesium therapy in patients with SM. We reviewed the charts of all patients admitted to a large military treatment facility from October 2013 to December 2018 with the admission diagnosis of migraine. There were 333 patients that were reviewed and 141 met the inclusion criteria. Nearly half of patients received IV magnesium therapy with routine care (46.8%, n = 66). IV magnesium therapy was not associated with length of admission (58 hours (IQR 25.5, 86) compared to 42 hours (IQR 25.5, 80.5) respectively, p = 0.47). Of the cases without Neurology consultation, patients who received magnesium therapy (n = 5) had numerically shorter admission but this difference did not meet statistical significance (n = 12) (17 hours (IQR 13.75, 31.25) versus 24.5 hours (IQR 15.25, 58.75), p = 0.0534). This study contributes to the limited pool of available data on the treatment of SM. Prospective research is needed to study magnesium therapy in patients with prolonged migraine.

Reversible cerebral vasoconstriction syndrome (RCVS) is a condition characterized by thunderclap headache and associated vasospasm of the cerebral vasculature. A multitude of factors are considered to potentially predispose to the development of RCVS. These potential precipitants include numerous illicit drugs. In this study, we investigated the role of illicit drugs as a precipitating factor for RCVS, through systematic review of the relevant literature. We found the strongest evidence for cannabis, but a relative lack of evidence to support other illicit drugs, particularly as individual precipitating factors. We also identified a lack of the consistent application of diagnostic criteria for RCVS, which undoubtedly hampers advancement of knowledge in this field. Consistent adherence to diagnostic criteria will be important for future studies. Ultimately, a prospective registry of RCVS cases would be advantageous to advance understanding of the condition and its underlying causes.

Background: A project was designed to improve decontamination procedures in our hospitals. This included: improving skills with training provided within clinical areas, simplifying procedures to reduce variation and increasing access to decontamination products. Aim: To make it easy for healthcare workers (HCWs) to do the right thing and for HCWs to be confident that they were doing the right thing. Methods: A pre-intervention survey of 120 HCWs in 10 wards on three hospital sites identified variations in the products used, variations in precautions taken and deficits in HCWs’ capabilities due to unmet training needs. Intervention: We streamlined the available products, provided an education programme and then undertook a second survey involving 133 HCWs in 12 wards. Results: Significant improvements were attained in the reported time taken to clean and disinfect ( P < 0.0001) and in HCW capability ( P < 0.0001) (reported training received); other improvements in the use of appropriate products and the use of personal protective equipment were evident. The key finding was that a large, previously unrecognised, unmet training need existed; only 44% of HCWs in the pre-intervention survey reported having received training on the topic. Conclusion: The utility of a pre-intervention survey is critical to knowing whether any change becomes improvement and to set the priorities for change. By focusing on the process rather than the outcomes, greater improvements can be attained. The assumption that all nurses know how to clean is erroneous.

Background: Patients hospitalised with COVID-19 have increased morbidity and mortality, which requires extensive involvement of specialist Hospital Palliative Care Teams. Evaluating the response to the surge in demand for effective symptom management can enhance provision of Palliative Care in this patient population. Aim: To characterise the symptom profile, symptom management requirements and outcomes of hospitalised COVID-19 positive patients referred for Palliative Care, and to contextualise Palliative Care demands from COVID-19 against a ‘typical’ caseload from 2019. Design: Service evaluation based on a retrospective cohort review of patient records. Setting/participants: One large health board in Scotland. Demographic data, patient symptoms, drugs/doses for symptom control, and patient outcomes were captured for all COVID-19 positive patients referred to Hospital Palliative Care Teams between 30th March and 26th April 2020. Results: Our COVID-19 cohort included 186 patients (46% of all referrals). Dyspnoea and agitation were the most prevalent symptoms (median 2 symptoms per patient). 75% of patients were prescribed continuous subcutaneous infusion for symptom control, which was effective in 78.6% of patients. Compared to a ‘typical’ caseload, the COVID-19 cohort were on caseload for less time (median 2 vs 5 days; p Conclusions: Hospitalised COVID-19 positive patients referred for Palliative Care may have a short prognosis, differ from ‘typical’ caseload, and predominantly suffer from dyspnoea and agitation. Such symptoms can be effectively controlled with standard doses of opioids and benzodiazepines.

Background: Coronavirus disease 2019 (COVID-19) has a substantial mortality risk with increased rates in the elderly. We hypothesized that age is not sufficient, and that frailty measured by preadmission Palliative Performance Scale would be a predictor of outcomes. Improved ability to identify high-risk patients will improve clinicians’ ability to provide appropriate palliative care, including engaging in shared decision-making about life-sustaining therapies. Aim: To evaluate whether preadmission Palliative Performance Scale predicts mortality in hospitalized patients with COVID-19. Design: Retrospective observational cohort study of patients admitted with COVID-19. Palliative Performance Scale was calculated from the chart. Using logistic regression, Palliative Performance Scale was assessed as a predictor of mortality controlling for demographics, comorbidities, palliative care measures and socioeconomic status. Setting/participants: Patients older than 18 years of age admitted with COVID-19 to a single urban public hospital in New Jersey, USA. Results: Of 443 admitted patients, we determined the Palliative Performance Scale score for 374. Overall mortality was 31% and 81% in intubated patients. In all, 36% (134) of patients had a low Palliative Performance Scale score. Compared with patients with a high score, patients with a low score were more likely to die, have do not intubate orders and be discharged to a facility. Palliative Performance Scale independently predicts mortality (odds ratio 2.89; 95% confidence interval 1.42–5.85). Conclusions: Preadmission Palliative Performance Scale independently predicts mortality in patients hospitalized with COVID-19. Improved predictors of mortality can help clinicians caring for patients with COVID-19 to discuss prognosis and provide appropriate palliative care including decisions about life-sustaining therapy.

High-touch surfaces contributing to infection transmission are particularly concerning in the ophthalmology clinic where frequent contact exists between ophthalmologists and various ophthalmic instruments. Areas of surface contamination from an ophthalmologist’s contact with the slit lamp environment were identified using ultraviolet fluorescence as a surrogate for pathogen contamination. Ultraviolet fluorescent product was applied on the ophthalmologist’s hands after thorough hand washing to indicate the contamination that may be derived from multiple sources in the ophthalmology clinic, such as touching the patient or the patient’s folder during eye examinations and transfers. The ophthalmology clinic was run normally, with the ophthalmologist wiping down patient-contact surfaces on the slit lamp and performing thorough hand hygiene after every patient. Using ultraviolet black light, persistence of surface contamination in the slit lamp environment was identified and evaluated across five days. High-touch surfaces of suboptimal disinfection were inclined towards those touched only by the ophthalmologist, for example: joystick and chin-rest adjustment knob, as compared to patient-contact surfaces. Persistent contamination on the same surfaces revealed inefficacy of current hand hygiene and clinical disinfection practices. This poses a significant risk for pathogen transmission and underscores the importance of including these specific clinician high-touch surfaces in existing cleaning protocols.

Microbial contamination of hematopoietic stem cells (HSC), used for autologous and allogenic transplantations, is rare but could cause serious blood stream infection in transplanted patients. These infections occur immediately, or later following the formation of biofilm on the catheter lumen. The present study describes an intermittent B. cepacia HSC contamination associated with nosocomial bacteremia: from October 2011 to April 2015, 17 B. cepacia strains were isolated in HSC bags ( n = 14) and blood cultures ( n = 3) in patients hospitalized in the National Bone Marrow Transplant Center. Two epidemiologic investigations in the National Blood Transfusion Center, allowing the isolation of three strains in hygiene samples, and four interventions in this institution were done. To identify the source of this contamination, a molecular investigation was done on 23 B. cepacia strains isolated in our center from 2007 to 2015. PFGE analysis revealed five clusters. The major cluster included 18 strains isolated from HSC bags ( n = 14), blood culture ( n = 1), and water cans and bath ( n = 3). The second cluster (B) including only two and the remaining clusters (C, D, and E) contained single strains isolated before the epidemic period. These findings confirmed that the origin of the outbreak was the contaminated water used in the water bath during the thawing step of HSC bags. Based on this result, new sterile water was used for every defrosting, but HSC bags contamination persisted. In May 2015, the water bath was replaced with a dry bath and no B. cepacia strain was isolated from that date to April 2020.

N-methyl-d-aspartate receptors (NMDARs) dysfunction in the nucleus accumbens (NAc) participates in regulating many neurological and psychiatric disorders such as drug addiction, chronic pain, and depression. NMDARs are heterotetrameric complexes generally composed of two NR1 and two NR2 subunits (NR2A, NR2B, NR2C and NR2D). Much attention has been focused on the role of NR2A and NR2B-containing NMDARs in a variety of neurological disorders; however, the function of NR2C/2D subunits at NAc in chronic pain remains unknown. In this study, spinal nerve ligation (SNL) induced a persistent sensory abnormity and depressive-like behavior. The whole-cell patch clamp recording on medium spiny neurons (MSNs) in the NAc showed that the amplitude of NMDAR-mediated excitatory postsynaptic currents (EPSCs) was significantly increased when membrane potential held at −40 to 0 mV in mice after 14 days of SNL operation. In addition, selective inhibition of NR2C/2D-containing NMDARs with PPDA caused a larger decrease on peak amplitude of NMDAR-EPSCs in SNL than that in sham-operated mice. Appling of selective potentiator of NR2C/2D, CIQ, markedly enhanced the evoked NMDAR-EPSCs in SNL-operated mice, but no change in sham-operated mice. Finally, intra-NAc injection of PPDA significantly attenuated SNL-induced mechanical allodynia and depressive-like behavior. These results for the first time showed that the functional change of NR2C/2D subunits-containing NMDARs in the NAc might contribute to the sensory and affective components in neuropathic pain.

Multilocus Sequence Typing (MLST) is a precise microbial typing approach at the intra-species level for epidemiologic and evolutionary purposes. It operates by assigning a sequence type (ST) identifier to each specimen, based on a combination of alleles of multiple housekeeping genes included in a defined scheme. The use of MLST has multiplied due to the availability of large numbers of genomic sequences and epidemiologic data in public repositories. However, data processing speed has become problematic due to the massive size of modern datasets. Here, we present FastMLST, a tool that is designed to perform PubMLST searches using BLASTn and a divide-and-conquer approach that processes each genome assembly in parallel. The output offered by FastMLST includes a table with the ST, allelic profile, and clonal complex or clade (when available), detected for a query, as well as a multi-FASTA file or a series of FASTA files with the concatenated or single allele sequences detected, respectively. FastMLST was validated with 91 different species, with a wide range of guanine-cytosine content (%GC), genome sizes, and fragmentation levels, and a speed test was performed on 3 datasets with varying genome sizes. Compared with other tools such as mlst, CGE/MLST, MLSTar, and PubMLST, FastMLST takes advantage of multiple processors to simultaneously type up to 28 000 genomes in less than 10 minutes, reducing processing times by at least 3-fold with 100% concordance to PubMLST, if contaminated genomes are excluded from the analysis. The source code, installation instructions, and documentation of FastMLST are available at https://github.com/EnzoAndree/FastMLST

Interferons (IFNs) are cytokines secreted by infected cells that can interfere with viral replication. Besides activating antiviral defenses, type I IFNs also exhibit diverse biological functions. IFN-β has been shown to have a protective effect against neurotoxic and inflammatory insults on neurons. Therefore, we aimed to investigate the possible role of IFN-β in reducing mechanical allodynia caused by Complete Freund’s Adjuvant (CFA) injection in rats. We assessed the antinociceptive effect of intrathecal IFN-β in naïve rats and the rats with CFA–induced inflammatory pain. After the behavioral test, the spinal cords of the rats were harvested for western blot and immunohistochemical double staining. We found that intrathecal administration of IFN-β in naïve rats can significantly increase the paw withdrawal threshold and paw withdrawal latency. Further, the intrathecal injection of a neutralizing IFN-β antibody can reduce the paw withdrawal threshold and paw withdrawal latency, suggesting that IFN-β is produced in the spinal cord in normal conditions and serves as a tonic inhibitor of pain. In addition, intrathecal injection of IFN-β at dosages from 1000 U to 10000 U demonstrates a significant transient dose-dependent inhibition of CFA-induced inflammatory pain. This analgesic effect is reversed by intrathecal naloxone, suggesting that IFN-β produces an analgesic effect through central opioid receptor-mediated signaling. Increased expression of phospho-µ-opioid receptors after IFN-β injection was observed on western blot, and immunohistochemical staining showed that µ-opioids co-localized with IFN-α/βR in the dorsal horn of the spinal cord. The findings of this study demonstrate that the analgesic effect of IFN-β is through µ-opioid receptors activation in spial cord.

Conventional microbiological investigations, including pathogen detection, antibiotic susceptibility testing and molecular epidemiological testing, are valuable tools in helping to manage nosocomial outbreaks. However, the microbiology laboratory, by using other techniques, can investigate additional microbiological aspects of outbreaks, which are often overlooked. Bacterial isolates (n=6) from an outbreak of Pseudomonas aeruginosa bacteraemia in a neonatal intensive care unit (NICU) in Belfast were examined. Enhanced microbiology testing included: (1) susceptibility of outbreak strains to biocides in common use in the unit; (2) effect of organic soils relevant to the area of the outbreak and their effect on the efficacy of biocide; and (3) the persistence of outbreak strains in organic soils. By emulating bespoke conditions of the outbreak, these methods were able to demonstrate that: (1) biocides were effective against the outbreak strains; (2) the critical concentration of soil which rendered biocide ineffective; and (3) how long the outbreak strains could persist. Enhanced microbiological analysis outside the conventional repertoire of testing may therefore offer valuable data that may help guide outbreak management teams.

Considerable evidence for contextual effects in emotion perception has been reported, but little is known about how contexts influence the perception of smiles, a rich source of social information. We investigated whether the perceived genuineness of a smile depends on the valence of the situation accompanying the smile, and whether such contextual effects depend on culture. Seventy-two North Americans and 83 mainland Chinese rated the genuineness of smiles displayed by Caucasians and East Asians in three situational contexts (positive, negative, and in isolation). Smiles in a negative situation were considered less genuine than the same smiles rated in isolation; this effect was observed for both groups of observers but stronger for North Americans, a finding at odds with the notion that East Asians are more likely to engage in holistic perceptual processes. Our study demonstrates contextual effects in assessment of smile genuineness, contributing new insights into the perception of affective information.

The Modified Intracerebral Hemorrhage (MICH) score is a simple tool created to provide prognostication in basal ganglia hemorrhages. Current prognostic scores, including the MICH, are based on the assessment of baseline patient characteristics, failing to account for significant developments, such as intraventricular extension and clinical deterioration, which may occur over the first 72 hours. We propose to validate the MICH in all hemorrhage locations and hypothesize that its calculation at 72 hours will outperform its baseline counterpart with respect to predicting mortality and functional outcome. We performed a retrospective analysis of collated data from the Virtual International Stroke Trials Archive database. Primary outcome was 90-day mortality. Secondary outcome was poor outcome (modified Rankin Scale 4-6) at 90 days. Receiver operating characteristic curves were generated looking at the predictive ability of the MICH score for mortality and poor outcome, at baseline and at 72 hours. Competing curves were assessed with nonparametric methods. A total of 226 patients were included, with a 90-day mortality of 22.5%. The MICH scores calculated at 72 hours were more predictive of mortality than at baseline (area under the curve [AUC]: 0.89 [95% confidence interval [CI]: 0.83-0.94] vs 0.78 [95% CI: 0.70-0.85]), P < .01. The MICH scores at 72 hours similarly better predicted functional outcome (AUC: 0.78 [95% CI: 0.72-0.84] vs AUC: 0.72 [95% CI: 0.66-0.78]), P = .047. The MICH score has positive prognostic value for mortality and poor functional outcome in all hemorrhage locations. Delaying its calculation resulted in higher predictive values for both and suggests that delaying discussions around withdrawal of care may result in more accurate prognostication in acute intracerebral hemorrhage.

Background: Patients in a high secure hospital are a high-risk population for exposure to blood-borne viruses (BBV) because of previous lifestyles. Objective: This service improvement study intends to improve patients care by the Infection Prevention and Control Team (IPCT) coordinating the BBV screening and vaccination programme within the hospital. Methods: A retrospective review of patients’ notes in 2007 and 2016 was used. Results: The results show an increase in screening offered and screening undertaken from 2007 to 2016. It also identifies an increase in hepatitis B vaccination programmes completed. Discussion: The expansion of the IPC and Physical Healthcare Team appear to be associated with the increase of screening and vaccination rates.

Studies have shown that individuals’ choice of a life partner predicts their life outcomes, from their relationship satisfaction to their career success. The present study examined whether the reach of one’s spouse extends even further, to the ultimate life outcome: mortality. A dyadic survival analysis using a representative sample of elderly couples ( N = 4,374) followed for up to 8 years showed that a 1-standard-deviation-higher level of spousal life satisfaction was associated with a 13% lower mortality risk. This effect was robust to controlling for couples’ socioeconomic situation (e.g., household income), both partners’ sociodemographic characteristics, and baseline health. Exploratory mediation analyses pointed toward partner and actor physical activity as sequential mediators. These findings suggest that life satisfaction has not only intrapersonal but also interpersonal associations with longevity and contribute to the fields of epidemiology, positive psychology, and relationship research.

This communication reports the effect of alphaxalone on motor somatosensory evoked potential (SEPs) in a rhesus macaque. The animal was deeply anaesthetised with an infusion of ketamine, medetomidine, midazolam and alfentanil. The median nerve was stimulated, and SEPs were recorded from the motor cortex. The successive administration of three doses of alphaxalone (0.5, 1 and 2 mg/kg) induced an increase of the latency time and a decrease of the amplitude of the SEPs. However, the structure of the waveforms was conserved, and hence alphaxalone might represent a suitable general anaesthetic option in neuroscience research as well as veterinary or human medicine.

Background: Digital health interventions are becoming increasingly important and may be particularly relevant for paediatric palliative care. In line with the aims of palliative care, digital health interventions should aim to maintain, if not improve, psychological wellbeing. However, the extent to which the psychological outcomes of digital health interventions are assessed is currently unknown. Aim: To identify and synthesise the literature exploring the impact of all digital health interventions on the psychological outcomes of patients and families receiving paediatric palliative care. Design: Systematic review and narrative synthesis. Data sources: MEDLINE, EMBASE, Health Management Information Consortium, PsycINFO, Cumulative Index to Nursing and Allied Health Literature and the Midwives Information & Resource Service were searched on the 27th July 2020, in addition to the first five pages of Google Scholar. To be included in the review, papers must have contained: quantitative or qualitative data on psychosocial outcomes, data from patients aged 0–18 receiving palliative care or their families, a digital health intervention, and been written in English. Results: Three studies were included in the review. All looked at the psychological impact of telehealth interventions. Papers demonstrated fair or good quality reporting but had small sample sizes and varied designs. Conclusions: Despite the design and development of digital health interventions that span the technological landscape, little research has assessed their psychosocial impact in the paediatric palliative care community. Whilst the evidence base around the role of these interventions continues to grow, their impact on children and their families must not be overlooked.

Calpain I is a calcium-dependent cysteine protease which has dual effects on tissue inflammation depending on its cellular location. Intracellularly, calpain I has pro-inflammatory properties but becomes anti-inflammatory when exteriorised into the extracellular space. In this study, the effect of calpain I on joint pain was investigated using the kaolin/carrageenan model of acute synovitis. Evoked pain behaviour was determined by von Frey hair algesiometry and non-evoked pain was measured using dynamic hindlimb weight bearing. Local administration of calpain I reduced secondary allodynia in the acute inflammation model and this effect was blocked by the cell impermeable calpain inhibitor E-64c. Calpain I also blocked the algesic effect of the protease activated receptor-2 (PAR-2) cleaving enzyme mast cell tryptase. The cell permeable calpain blocker E-64d also produced analgesia in arthritic joints. These data suggest that calpain I produces disparate effects on joint pain viz. analgesia when present extracellularly by disarming PAR-2, and pro-algesic when the enzyme is inside the cell.

Bangladesh is one of the most densely populated countries in the world struggling to prevent COVID-19 (coronavirus disease 2019). This study employed correlation, cluster analysis, and multiple linear regression analyses using district-wise COVID-19 infection and socioeconomic data. It is observed that there is a strong positive correlation ( r = 0.876, P < .001) between population density and COVID-19, explaining a 60% variation in Bangladesh. The relationship between urbanization and COVID-19 is also positively strong ( r = 0.802, P < .001). Urban settlements have a higher risk of spreading diseases due to the enormous population density. For future planning to prevent COVID-19 and other related infectious diseases, population density should be considered a risk factor.

Background: Out-of-pocket costs are a serious barrier to care and drive suboptimal medical therapy. Understanding of these costs can lead to care oriented around the limits they generate. Despite this, there is minimal attention paid to these costs in post-graduate education. Objective: To define a potential knowledge gap regarding costs experienced by patients by surveying Internal Medicine residents at our large academic institution. Methods: We surveyed Internal Medicine residents in spring 2019 about knowledge and practices surrounding patient out-of-pocket costs. Participants answered questions considering their most recent inpatient panel and their clinic patient panel. Familiarity was ranked on a 5-point Likert scale, and for the purposes of presentation, was divided into “Poor” and “Moderate or Better.” Non-parametric analysis was used to test differences between outpatients and inpatients and by year of training. Results: Of 159 residents, 109 (67%) responded. Familiarity with patient insurance status was moderate or better in 85%. Reported understanding of costs associated with medications, testing, and clinic visits was less common. Respondents had higher familiarity with out-of-pocket costs for clinic patients compared with inpatients. Knowledge of cost of care was not an often-considered factor in decision making. There was no significant difference in response by year of training. Conclusion: Patient out-of-pocket costs are an important dimension of patient care which Internal Medicine Trainees at our institution do not confidently understand or utilize. Improvements in education around this topic may enable more patient-centered care.

We report the case of a healthcare worker who presented with a large vessel acute ischemic stroke in setting of a mild SARS-CoV-2 infection and provide a review of the emerging literature on COVID-related stroke. A 43-year-old female presented with right-sided hemiparesis, aphasia and dysarthria. She had a nonproductive of cough for 1 week without fever, fatigue or dyspnea. A CT Head, CT angiography and CT perfusion imaging revealed a M1 segment occlusion of the left middle cerebral artery requiring transfer from a primary to a comprehensive stroke center. A nasopharyngeal swab confirmed SARS-CoV-2 infection prior to arrival at the accepting center. During the thrombectomy a 3 cm thrombus was removed. Thrombus was also evident in the 8 French short sheath during closure device placement so a hypercoagulable state was suspected. Stroke work-up revealed a glycosylated hemoglobin of 8.7%, elevation of inflammatory markers and an indeterminate level of lupus anticoagulant IgM. On discharge home, she had near complete neurological recovery. This case highlights suspected mechanisms of hypercoagulability in SARS-CoV-2 infection and the importance of optimizing stroke care systems during the COVID-19 pandemic.

The Rotating Snakes illusion is a motion illusion based on repeating, asymmetric luminance patterns. Recently, we found certain gray-value conditions where a weak illusory motion occurs in the opposite direction. Of the four models for explaining the illusion, one also explains the unexpected perceived opposite direction.We here present a simple new model, without free parameters, based on an array of standard correlation-type motion detectors with a subsequent nonlinearity (e.g., saturation) before summing the detector outputs. The model predicts (a) the pattern-appearance motion illusion for steady fixation, (b) an illusion under the real-world situation of saccades across or near the pattern (pattern shift), (c) a relative maximum of illusory motion for the same gray values where it is found psychophysically, and (d) the opposite illusion for certain luminance values. We submit that the new model’s sparseness of assumptions justifies adding a fifth model to explain this illusion.

Background: Advances in technology provide opportunities for communication using electronic mediums. Sexting is one form of electronic communication and includes the sending of explicit sexual content (e.g., photos, text) through electronic mediums. Previous research demonstrated a positive association between sexting and behaviors such as substance use. Moreover, substance use increases the risk for intimate partner violence and is also associated with risky behaviors. Objectives: The aim of the present study was to examine the prevalence of sexting in a sample of 84 women mandated to attend batterer intervention programs following arrest for domestic violence. The associations between sexting, substance use, and intimate partner violence were also examined. Method: Participants completed self-report questionnaires that assessed sexting, intimate partner violence, and alcohol and drug use symptoms. Results: Fifty-four percent of participants reported being asked to send a sext, 35.1% reported sending a sext, and 32.0% reported requesting a sext. Drug use symptoms were positively associated with some forms of sexting and intimate partner violence. There was a significant difference in drug use symptoms, such that women who received a request to send a sext had significantly more symptoms relative to women who had not received a request to send a sext. Conclusion: This is the first examination of sexting in a sample of women arrested for domestic violence. Findings indicate an association between drug use symptoms, sexting, and intimate partner violence, warranting continued research in this domain.

Objective To prospectively assess anti-JCV antibody index (AI) and its relationship to immunoglobulin levels in ocrelizumab-treated MS patients. Methods Monocentric prospective observational study over 24 months assessing anti-JCV AI and immunoglobulin levels in MS patients before and after initiation of ocrelizumab. Results No significant change in anti-JCV AI titers was observed 458 ± 300 days after initiation of ocrelizumab (n = 45, 0.7 ± 2.21 vs. 0.6 ± 2.06, p = 0.8). Seroconversion occurred in 1/20 initially anti-JCV seronegative patients. There was no correlation between changes in anti-JCV AI and immunoglobulins. Conclusion Treatment with ocrelizumab is not associated with an increase in anti-JCV AI titers.

The ketamine metabolite (2 R,6 R)-hydroxynorketamine has been proposed to have rapid and persistent antidepressant actions in rodents, but its mechanism of action is controversial. We have compared the ability of ( R,S)-ketamine with the (2 S,6 S)- and (2 R,6 R)-isomers of hydroxynorketamine to affect the induction of N-methyl-d-aspartate receptor–dependent long-term potentiation in the mouse hippocampus. Following pre-incubation of these compounds, we observed a concentration-dependent (1–10 μM) inhibition of long-term potentiation by ketamine and a similar effect of (2 S,6 S)-hydroxynorketamine. At a concentration of 10 μM, (2 R,6 R)-hydroxynorketamine also inhibited the induction of long-term potentiation. These findings raise the possibility that inhibition of N-methyl-d-aspartate receptor–mediated synaptic plasticity is a site of action of the hydroxynorketamine metabolites with respect to their rapid and long-lasting antidepressant-like effects.

There is a lack of literature documenting the use of alemtuzumab in pediatric multiple sclerosis (MS) patients. Here we describe a 16-year-old and a 17-year-old patient receiving alemtuzumab and being followed for 37 months and 20 months, respectively. Both patients experienced a 1.0 decrease in Expanded Disability Status Scale since initial alemtuzumab infusion and had stable disease. No serious infusion reactions, infections, or definite relapses were recorded on follow-up. Alemtuzumab has been relatively well-tolerated and effective; however, larger, longer-term studies are necessary to understand the specific risks and benefits of alemtuzumab in pediatric MS.

C-tactile afferents are hypothesized to form a distinct peripheral channel that encodes the affective nature of touch. Prevailing views indicate they project, as with other unmyelinated afferents, in lamina I-spinothalamic pathways that relay homeostatically relevant information from the body toward cortical regions involved in interoceptive processing. However, in a recent study, we found that spinothalamic ablation in humans, while profoundly impairing the canonical spinothalamic modalities of pain, temperature, and itch, had no effect on benchmark psychophysical affective touch metrics. These novel findings appear to indicate that perceptual judgments about the affective nature of touch pleasantness do not depend on the integrity of the lamina I-spinothalamic tract. In this commentary, we further discuss the implications of these unexpected findings. Intuitively, they suggest that signaling of emotionally relevant C-tactile mediated touch occurs in an alternative ascending pathway. However, we also argue that the deficits seen following interruption of a putative C-tactile lamina I-spinothalamic relay might be barely perceptible—a feature that would underline the importance of the C-tactile afferent in neurodevelopment.

A ring of points that is rotated so rapidly is perceived as a stationary outline circle that can induce an illusory rotation with the same spin direction in a subsequently presented ring of stationary points. This motion bridging effect (MBE) demonstrates that motion information can be conveyed by temporal frequencies generally thought to exceed the processing capabilities of the human visual system. It was first described in displays shown with an analog oscilloscope, but the rapid rotation rates needed to produce the MBE have heretofore prevented it from being investigated with conventional raster scan monitors. Here, we demonstrate the MBE can be reliably generated using the new generation of 240 Hz LCD gaming monitors, and exhibits basic characteristics similar to those reported previously. These monitors therefore provide a readily available resource for research on the MBE and the studies of the visual processing rapid motions in general. Open-Access-Publikationsfonds 2020 peerReviewed

Background: Healthcare professionals and researchers in the field of palliative care often have difficulties finding relevant articles in online databases. Standardized search filters may help improve the efficiency and quality of such searches, but prior developed filters showed only moderate performance. Aim: To develop and validate a specific search filter and a sensitive search filter for the field of palliative care. Design: We used a novel, objective method for search filter development. First, we created a gold standard set. This set was split into three groups: term identification, filter development, and filter validation set. After creating the filters in PubMed, we translated the filters into search filters for Ovid MEDLINE, Embase, CINAHL, PsychINFO, and Cochrane Library. We calculated specificity, sensitivity and precision of both filters. Results: The specific filter had a specificity of 97.4%, a sensitivity of 93.7%, and a precision of 45%. The sensitive filter had a sensitivity of 99.6%, a specificity of 92.5%, and a precision of 5%. Conclusion: Our search filters can support literature searches in the field of palliative care. Our specific filter retrieves 93.7% of relevant articles, while 45% of the retrieved articles are relevant. This filter can be used to find answers to questions when time is limited. Our sensitive filter finds 99.6% of all relevant articles and may, for instance, help conducting systematic reviews. Both filters perform better than prior developed search filters in the field of palliative care.

Synonymous mutations do not change the amino acid but do change the synonymous codon usage. In genomes of different organisms, the gene conversion process is biased toward GC, which is irrespective of mutation bias. In the coding region, this trend is especially obvious and it is possibly caused by the preference on G/C-ending codons over the A/T-ending ones. If the G/C-ending codons are advantageous, then the synonymous mutations that change A/T to G/C would be “optimal” compared to the opposite ones. In theory, one should observe signals of positive selection on these optimal synonymous mutations. The recently released single-nucleotide polymorphism (SNP) data from the 1001 genome project of Arabidopsis thaliana provided researchers with an unprecedented opportunity to verify this assumption. I fully take advantage of the SNP data from 1,135 A thaliana lines and came to the conclusion that synonymous mutations in natural populations are not strictly neutral: the synonymous mutations that increase GC content (from A/T to G/C) tend to have higher derived allele frequencies (DAFs) and, therefore, are likely to be positively selected. My current study broadens our knowledge of the selection patterns of synonymous mutations and should be appealing to evolutionary biologists. One sentence summary: In 1135 genomes of Arabidopsis thaliana, the synonymous mutations that increase the GC content tend to have higher derived allele frequencies (DAFs) and are likely to be positively selected.

Following acute West Nile virus (WNV) infection in humans, there is upregulation of pro-inflammatory molecules that promote neuroinflammation, including S100 calcium binding protein B (S100B), high-mobility group box-1 (HMGB1), and osteopontin (OPN). The effects of S100B and HMGB1 are transduced by the receptor for advanced glycation end products (RAGE). Interestingly, the same immunoregulatory proteins that fuel neuroinflammation can also promote tumorigenesis. We present 2 cases of glial neuronal tumors, a glioblastoma multiforme and dysembryoplastic neuroepithelial tumor, in patients with severe West Nile neuroinvasive disease (WNND). In these cases, the viral infection was a precursor to the development of the aggressive brain tumors. We describe a potential mechanism where the presence of tumorigenic proteins in the microenvironment induced by WNV, and subsequent RAGE and OPN signaling, may contribute to development or aggressive growth of these tumors. Although it is certainly possible that the occurrence of primary brain tumors following WNND is coincidental, the ability of WNV to alter cellular signaling and increase expression of pro-inflammatory and tumorigenic molecules merits further investigations to determine whether there is an association between these disease processes or implications for brain tumor patients who develop WNV infection.

A cluster of dots such as lotus seed pods evokes extremely strong disgust when it is placed on human and animal skins. However, few empirical studies have examined the role of the background image, such as skin, in the generation of disgust. In this study, we investigated whether the orientation of background faces influences the disgust evoked by the dot pattern. The participants were asked to evaluate disgust to an upright, inverted, or phase-scrambled face image with or without a cluster of dots on it and then complete a questionnaire measuring trypophobia proneness (Trypophobia Questionnaire). The results suggested that disgust was intensified by the background faces, especially by the upright faces. The intensification of disgust in the upright face was correlated positively with the Trypophobia Questionnaire scores. The results indicated a face-inversion effect on the disgust to the dot pattern, suggesting a significant role of the background image.

There were 211,000 Indonesian Hajj pilgrims going to Mecca through 11 main airports in 2015 who were at risk of contracting the Middle East respiratory syndrome coronavirus (MERS-CoV). We aimed to find out whether there was any occurrence of MERS-CoV by performing screening on 28,197 returning pilgrims. Those with a body temperature of > 38 °C and respiratory symptoms were sent to the airport clinic to have an oropharyngeal swab and a bacterial culture. Fifteen pilgrims had fever (> 38 °C) accompanied by respiratory symptoms; of these, 12 patients were diagnosed with upper and lower respiratory tract infections and three patients with pneumonia. However, none of them were found to be infected with MERS-CoV. The bacterial cultures showed evidence of normal flora growth.

A “weekend effect” resulting in higher mortality rates for patients with stroke admitted on weekends has been reported. We examine this phenomenon for patients with acute ischemic stroke (AIS) presenting to telestroke (TS) sites to determine its effect on stroke alert process times and outcomes. From October 2015 to June 2017, we reviewed patients with AIS receiving intravenous alteplase within our TS network. We compared patients presenting to TS sites on weekdays (Monday 07:00 to Friday 18:59) to those presenting on weekends (Friday 19:00 to Monday 06:59). We analyzed door-to-alert activation, alert activation-to-TS evaluation, door-to-imaging, and door-to-needle times. Rates of favorable outcome (modified Rankin Scale score ≤2) and death at 90 days were compared. We identified 89 (54 weekday and 35 weekend) patients (mean age: 71.8 ± 13.3 years, 47.2% women) during the study period. Median door-to-alert activation ( P = .01) and door-to-needle ( P = .004) times were significantly longer for patients presenting on weekends compared to weekdays. There were no significant differences in median door-to-imaging ( P = .1) and alert activation-to-TS evaluation ( P = .07) times. Rates of favorable outcome ( P = .19) and death ( P = .56) at 90 days did not differ. While there were no significant differences in outcomes, patients presenting on weekends had longer door-to-alert activation and door-to-needle times. Efforts to improve methods in efficiency of care on weekends should be considered.

Background: In a recent study, we documented that partially unstable Weber B/SER4a fracture types reach union with preserved normal ankle congruence after treatment with a functional orthosis and weightbearing allowed. In the present article, we present a case series of weightbearing stable bimalleolar fractures treated nonoperatively that extends our previously published research. Methods: We included 5 patients with primarily nondisplaced bimalleolar ankle fractures that were stable on weightbearing radiographs. Participants were treated with a walking boot or cast with weightbearing allowed. We also provide a qualitative anatomical analysis of fracture morphology on computed tomographic scans. Results: Median medial clear space (MCS) of fractured ankles after union were 2.4 mm (range, 1.5-3.1). Qualitative descriptions of fracture morphology showed that all fractures were oblique starting at the intercollicular groove of the medial malleolus and extended anteriorly and proximally. Conclusion: MCS measurements after fracture union of nonoperatively treated weightbearing stable bimalleolar fractures seemed consistent with normative data of ankle congruence in our previous study. We consistently recorded oblique fracture patterns involving the anterior colliculus, leaving the origin of posterior deep deltoid ligament intact. We present our material as an argument for the existence of a bony (bimalleolar) equivalent to the ligamentous SER4a fracture. Level of Evidence: Level IV, prospective case series.

The visual system represents textural image regions as simple statistics that are useful for the rapid perception of scenes and surfaces. What images ‘textures’ are, however, has so far mostly been subjectively defined. The present study investigated the empirical conditions under which natural images are processed as texture. We first show that ‘texturality’ – i.e., whether or not an image is perceived as a texture – is strongly correlated with the perceived similarity between an original image and its Portilla-Simoncelli (PS) synthesized image. We found that both judgments are highly correlated with specific PS statistics of the image. We also demonstrate that a discriminant model based on a small set of image statistics could discriminate whether a given image was perceived as a texture with over 90% accuracy. The results provide a method to determine whether a given image region is represented statistically by the human visual system.

Serial dependence effects have been observed using a variety of stimuli and tasks, revealing that the recent past can bias current percepts, leading to increased similarity between two. The aim of this study is to determine whether this temporal integration occurs in egocentric or allocentric coordinates. We ask participants to perform an orientation reproduction task using grating stimuli while the head is kept at a fixed position throughout the whole session or while alternating position from one trial to the next, from left (−20°) to right (+20°), putting the egocentric and allocentric cues in conflict. Under these conditions, allocentric cues prevail.

Partial ornithine transcarbamylase deficiency (pOTCD), an enzymatic defect within the urea cycle, is an increasingly recognized etiology for hyperammonemia of unclear source following a stressor within female adults. Here we present a case of newly diagnosed pOTCD following a systemic stressor and prolonged hospitalization course. From a neurological perspective, prompt recognition provided the patient with a swift and near complete recovery. We briefly review the pertinent literature pertaining to this genetically based condition including historical context and current therapeutic approaches. Given the potential morbidity of prolonged hyperammonemia, neurohospitalists need to be aware of partial ornithine transcarbamylase as an entity.

Background: Children and infants with impaired swallow or compromised enteral absorption require alternative routes for administration of analgesia. Recent clinical guidance and practice for paediatric palliative care teams, who often treat such children, supports buccal morphine sulphate as a fast acting, effective and easily administered agent for pain relief. However, a consideration of the physicochemical properties and potency of morphine would suggest that it is not a suitable candidate for delivery via the transmucosal route, raising questions about its use in children and infants. Aim: To explore the permeability of buccal morphine sulphate in an established ex vivo porcine buccal mucosa as a necessary step in examining efficacy for use in children with life-limiting conditions and life-threatening illnesses. Design: A permeation study conducted with morphine sulphate in an ex vivo porcine buccal tissue model. Flux values and pharmacokinetic data were used to calculate the plasma values of morphine that would result following buccal administration in a 20kg child. Results: Results show that the estimated steady state plasma values of morphine sulphate following buccal administration in this model do not achieve minimum therapeutic concentration. Conclusion: These data strongly suggest that morphine sulphate is not suitable for buccal administration and that further research is needed to establish its efficacy in relief of pain in children with life-limiting conditions and life-threatening illnesses.

One in 3 adults report using complementary and alternative medicine (CAM) and as many as 7 in 10 Hispanic patients report CAM use. Pharmacists often encounter patients who use CAM products and therefore college of pharmacy curricular standards require both CAM and cultural competence training; however, there is little guidance for colleges on how to best deliver this material. In Fall 2017, Larkin University College of Pharmacy implemented a curricular change wherein first professional (P1) year pharmacy students selected, researched, and presented on a CAM product from Latin America. Pre-post surveys were administered to the students to measure their attitudes and behaviors toward CAM before and after completing their project. Survey results showed that student attitudes and behaviors toward CAM were largely unchanged; however, post-survey results showed that students agreed that they knew where to search for Latin American CAM information ( P

Pain is known to disrupt sleep patterns, and disturbances in sleep can further worsen pain symptoms. Sleep spindles occur during slow wave sleep and have established effects on sensory and affective processing in mammals. A number of chronic neuropsychiatric conditions, meanwhile, are known to alter sleep spindle density. The effect of persistent pain on sleep spindle waves, however, remains unknown, and studies of sleep spindles are challenging due to long period of monitoring and data analysis. Utilizing automated sleep spindle detection algorithms built on deep learning, we can monitor the effect of pain states on sleep spindle activity. In this study, we show that in a chronic pain model in rodents, there is a significant decrease in sleep spindle activity compared to controls. Meanwhile, methods to restore sleep spindles are associated with decreased pain symptoms. These results suggest that sleep spindle density correlates with chronic pain and may be both a potential biomarker for chronic pain and a target for neuromodulation therapy.

Systemic inflammation has been associated with negative mood states and human sickness behaviour. Previous studies have shown an association between systemic inflammation and changes in task-related blood-oxygen-level-dependent activity and functional connectivity within large-scale networks. However, no study has examined the effect of inflammation on the magnitude of blood-oxygen-level-dependent low-frequency fluctuations at rest. We used a double-blind placebo-controlled crossover design to randomise 20 male subjects (aged 20–50 years) to receive either a Salmonella typhi vaccine or a placebo saline injection at two separate sessions. All participants underwent a resting-state functional magnetic resonance scan and a measure of inflammation (interleukin 6) and mood (Profile of Mood States) 3 h after injection. We compared the whole brain amplitude of low-frequency fluctuations between the vaccine and placebo conditions using a repeated measures design. Vaccine condition was associated with greater interleukin 6 levels (p

Objectives: Pleomorphic adenomas are benign tumors that rarely involve nonsalivary glands. We report an uncommon case of ala nasi pleomorphic adenoma. We discuss the clinical and histopathologic characteristics, and review the literature on nasal pleomorphic adenoma. Method: A 20-year-old man presented with a painless slow growing lobulated mass located on the right ala nasi extending into the nasal vestibule. Results: Complete surgical excision was performed. Histologic examination found a mixed cellular component: epithelial and myoepithelial cells with chondromyxoid stroma. This was consistent with the diagnosis of a typical pleomorphic adenoma. There was no evidence of recurrence at 18 months after the surgery. Conclusions: Pleomorphic adenomas located in the external nose are extremely rare. In such case, pleomorphic adenoma could originate from ectopic minor salivary gland. Complete surgical excision with long-term follow-up is recommended due to the potential risk of recurrence and malignant transformation.

In this study, we examined the operation of first- and second-order motion mechanisms with respect to object tracking using dichoptic presentation. A bistable apparent motion stimulus composed of four rectangles arranged in square- and diamond-shapes in every other frame was presented binocularly, monocularly, or dichoptically using a stereoscope. Since past motion studies showed that the first-order motion mechanism cannot function under dichoptic stimulation, we evaluated the upper temporal frequency limits of object tracking with dichoptic presentation and compared these results with those obtained with ordinary binocular or monocular (nondichoptic) presentation. We found that the temporal limits were 4 -5 Hz, regardless of the viewing conditions. These limits are similar to those for within-attribute (first- and second-order) object tracking (4 -5 Hz) obtained in our previous study. Thus, this putative mechanism may be responsible for object tracking, based only on second-order components, even in the case of first-order stimuli.

We propose a novel neural network approach for the classification of abnormal mammographic images into benign or malignant based on their texture representations. The proposed framework has the capability of mapping high dimensional feature space into a lower-dimension, in a supervised way. The main contribution of the proposed classifier is to introduce a new neuron structure for map representation and adopt a supervised learning technique for feature classification. This is achieved by making the weight updating procedure dependent on the class reliability of the neuron. We showed high accuracy (95.2%) for our proposed approach in the classification of abnormal real mammographic images when compared to other related methods.

Does the moment when an event is perceived depends on where it is presented? To measure when participants perceived events, they were first familiarized with trial duration, by watching the hand of a clock rotating. Then, the hand was removed, and stimuli were presented at a random time from the trial onset. Participants indicated the location where the hand would have been when the stimulus was presented. The stimuli’s eccentricity, the appearance, and location of the spatial features of the clock were varied. The targets were reported earlier if they were presented in spatial proximity to the clock outline, even when it was not presented during the trial. The effect was replicated with stimuli presented at the same distance from fixation but at different distances from the spatial features. In summary, the time of an event is perceived earlier if it is presented near attended features in the visual scene.

Aim: Following soft tissue ankle injury, patients are often referred for out-patient physiotherapy and present symptoms including pain, reduced range of movement and function, and oedema. In this study, we assess the use of a neuromuscular electrical stimulation (NMES) device as an adjunctive therapy to reduce oedema in patients recovering from grade I and II ankle sprains. Methods: This was a single-centre, pilot randomised controlled study, recruiting patients referred to physiotherapy following an ankle sprain. Participants presenting with oedema were randomised to one of two treatment groups: (1) the current standard of care and (2) the current standard of care plus NMES use. Participants were identified in an emergency department and referred to a physiotherapy department for treatment 1 to 5 days following the injury and returned to clinic 7 days later. Results: Twenty-two participants completed the study and had full data sets for analysis (11 in each group). Mean volumetric displacement was reduced in the intervention group in comparison to the standard care group ( P = .011); however, there were no between-group differences in figure of eight measurements, function or pain scores. The device was well tolerated, with no device-related adverse events recorded. Conclusions: In this pilot, randomised controlled trial, NMES was well tolerated by patients following ankle sprain and demonstrated statistically significant improvements in oedema reduction as measured by fluid displacement. No other changes were observed. Further work will need to confirm the clinical significance and effect on longer term recovery post-ankle sprain.