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The appearance of new dominant variants of concern (VOC) of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) threatens the global response to the coronavirus disease 2019 (COVID-19) pandemic. Of these, the alpha variant (also known as B.1.1.7), which appeared initially in the United Kingdom, became the dominant variant in much of Europe and North America in the first half of 2021. The spike (S) glycoprotein of alpha acquired seven mutations and two deletions compared to the ancestral virus, including the P681H mutation adjacent to the polybasic cleavage site, which has been suggested to enhance S cleavage. Here, we show that the alpha spike protein confers a level of resistance to beta interferon (IFN-β) in human lung epithelial cells. This correlates with resistance to an entry restriction mediated by interferon-induced transmembrane protein 2 (IFITM2) and a pronounced infection enhancement by IFITM3. Furthermore, the P681H mutation is essential for resistance to IFN-β and context-dependent resistance to IFITMs in the alpha S. P681H reduces dependence on endosomal cathepsins, consistent with enhanced cell surface entry. However, reversion of H681 does not reduce cleaved spike incorporation into particles, indicating that it exerts its effect on entry and IFN-β downstream of furin cleavage. Overall, we suggest that, in addition to adaptive immune escape, mutations associated with VOC may well also confer a replication and/or transmission advantage through adaptation to resist innate immune mechanisms. IMPORTANCE Accumulating evidence suggests that variants of concern (VOC) of SARS-CoV-2 evolve to evade the human immune response, with much interest focused on mutations in the spike protein that escape from antibodies. However, resistance to the innate immune response is essential for efficient viral replication and transmission. Here, we show that the alpha (B.1.1.7) VOC of SARS-CoV-2 is substantially more resistant to type I interferons than the parental Wuhan-like virus. This correlates with resistance to the antiviral protein IFITM2 and enhancement by its paralogue IFITM3. The key determinant of this is a proline-to-histidine change at position 681 in S adjacent to the furin cleavage site, which in the context of the alpha spike modulates cell entry pathways of SARS-CoV-2. Reversion of the mutation is sufficient to restore interferon and IFITM2 sensitivity, highlighting the dynamic nature of the SARS CoV-2 as it adapts to both innate and adaptive immunity in the humans.

Objectives: To analyse nosocomial transmission in the early stages of the coronavirus 2019 (COVID-19) pandemic at a large multisite healthcare institution. Nosocomial incidence is linked with infection control interventions., Methods: Viral genome sequence and epidemiological data were analysed for 574 consecutive patients, including 86 nosocomial cases, with a positive PCR test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first 19 days of the pandemic., Results: Forty-four putative transmission clusters were found through epidemiological analysis; these included 234 cases and all 86 nosocomial cases. SARS-CoV-2 genome sequences were obtained from 168/234 (72%) of these cases in epidemiological clusters, including 77/86 nosocomial cases (90%). Only 75/168 (45%) of epidemiologically linked, sequenced cases were not refuted by applying genomic data, creating 14 final clusters accounting for 59/77 sequenced nosocomial cases (77%). Viral haplotypes from these clusters were enriched 1-14x (median 4x) compared to the community. Three factors implicated unidentified cases in transmission: (a) community-onset or indeterminate cases were absent in 7/14 clusters (50%), (b) four clusters (29%) had additional evidence of cryptic transmission, and (c) in three clusters (21%) diagnosis of the earliest case was delayed, which may have facilitated transmission. Nosocomial cases decreased to low levels (0-2 per day) despite continuing high numbers of admissions of community-onset SARS-CoV-2 cases (40-50 per day) and before the impact of introducing universal face masks and banning hospital visitors., Conclusion: Genomics was necessary to accurately resolve transmission clusters. Our data support unidentified cases-such as healthcare workers or asymptomatic patients-as important vectors of transmission. Evidence is needed to ascertain whether routine screening increases case ascertainment and limits nosocomial transmission., (Copyright © 2021. Published by Elsevier Ltd.)

During the first wave of the global COVID-19 pandemic the clinical utility and indications for SARS-CoV-2 serological testing were not clearly defined. The urgency to deploy serological assays required rapid evaluation of their performance characteristics. We undertook an internal validation of a CE marked lateral flow immunoassay (LFIA) (SureScreen Diagnostics) using serum from SARS-CoV-2 RNA positive individuals and pre-pandemic samples. This was followed by the delivery of a same-day named patient SARS-CoV-2 serology service using LFIA on vetted referrals at central London teaching hospital with clinical interpretation of result provided to the direct care team. Assay performance, source and nature of referrals, feasibility and clinical utility of the service, particularly benefit in clinical decision-making, were recorded. Sensitivity and specificity of LFIA were 96.1% and 99.3% respectively. 113 tests were performed on 108 participants during three-week pilot. 44% participants (n = 48) had detectable antibodies. Three main indications were identified for serological testing; new acute presentations potentially triggered by recent COVID-19 e.g. pulmonary embolism (n = 5), potential missed diagnoses in context of a recent COVID-19 compatible illness (n = 40), and making infection control or immunosuppression management decisions in persistently SARS-CoV-2 RNA PCR positive individuals (n = 6). We demonstrate acceptable performance characteristics, feasibility and clinical utility of using a LFIA that detects anti-spike antibodies to deliver SARS-CoV-2 serology service in adults and children. Greatest benefit was seen where there is reasonable pre-test probability and results can be linked with clinical advice or intervention. Experience from this pilot can help inform practicalities and benefits of rapidly implementing new tests such as LFIAs into clinical service as the pandemic evolves., Competing Interests: One of the co-authors (JR) is employed by Viapath LLP. This commercial affiliation with Viapath LLP does not alter our adherence to all PLOS ONE policies on sharing data and materials. Viapath LLP did not have any role in study design, data collection and analysis, decision to publish, or preparation of this manuscript.

There is a clear requirement for an accurate SARS-CoV-2 antibody test, both as a complement to existing diagnostic capabilities and for determining community seroprevalence. We therefore evaluated the performance of a variety of antibody testing technologies and their potential use as diagnostic tools. Highly specific in-house ELISAs were developed for the detection of anti-spike (S), -receptor binding domain (RBD) and -nucleocapsid (N) antibodies and used for the cross-comparison of ten commercial serological assays-a chemiluminescence-based platform, two ELISAs and seven colloidal gold lateral flow immunoassays (LFIAs)-on an identical panel of 110 SARS-CoV-2-positive samples and 50 pre-pandemic negatives. There was a wide variation in the performance of the different platforms, with specificity ranging from 82% to 100%, and overall sensitivity from 60.9% to 87.3%. However, the head-to-head comparison of multiple sero-diagnostic assays on identical sample sets revealed that performance is highly dependent on the time of sampling, with sensitivities of over 95% seen in several tests when assessing samples from more than 20 days post onset of symptoms. Furthermore, these analyses identified clear outlying samples that were negative in all tests, but were later shown to be from individuals with mildest disease presentation. Rigorous comparison of antibody testing platforms will inform the deployment of point-of-care technologies in healthcare settings and their use in the monitoring of SARS-CoV-2 infections., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate the measurement properties of the Psoriasis Symptom Inventory (PSI) in psoriatic arthritis (PsA)., Methods: The PSI is an 8-item, patient-reported outcome measure of the severity of psoriasis signs and symptoms. This was a secondary analysis of pooled data from a phase II study evaluating the efficacy of brodalumab in patients with PsA. Unidimensionality and item evaluation were assessed using factor and Rasch analyses. Reliability was assessed using Cronbach's alpha (internal consistency) and intraclass correlation coefficients (ICCs) for PSI scores in patients with stable disease (test-retest). Construct validity was evaluated by correlations between PSI scores and body surface area (BSA) affected by psoriasis and selected Short Form 36 (SF-36) health survey domains. Known-groups validity was evaluated based on BSA severity categories, and the ability to detect change was evaluated based on improvement in the subject's global assessment (SGA)., Results: The analysis sample (n = 154) was 93.5% white and 63.0% female. The mean ± SD baseline affected BSA was 10.4% ± 15.6%, and age was 52.2 ± 11.5 years. The PSI demonstrated unidimensionality, with good item fit and correctly ordered categories, excellent internal consistency (α = 0.95), good test-retest reliability (total score ICC 0.70; item ICCs range 0.67-0.81), convergent validity based on moderate correlations with BSA (r = 0.50), discriminant validity based on small baseline correlations (r <-0.3) with the SF-36 domains (role-physical, role-emotional, vitality), known groups validity based on significant differences between BSA groups, and responsiveness based on SGA improvements (P < 0.05)., Conclusion: The PSI demonstrated excellent test-retest and internal consistency reliability and good construct validity in measuring psoriasis signs and symptoms severity in PsA., (© 2015, American College of Rheumatology.)

Fluorine (19F) NMR has emerged as a useful tool for characterization of slow dynamics in 19F-labeled proteins. One-dimensional (1D) 19F NMR spectra of proteins can be broad, irregular and complex, due to exchange of probe nuclei between distinct electrostatic environments; and therefore cannot be deconvoluted and analyzed in an objective way using currently available software. We have developed a Python-based deconvolution program, decon1d, which uses Bayesian information criteria (BIC) to objectively determine which model (number of peaks) would most likely produce the experimentally obtained data. The method also allows for fitting of intermediate exchange spectra, which is not supported by current software in the absence of a specific kinetic model. In current methods, determination of the deconvolution model best supported by the data is done manually through comparison of residual error values, which can be time consuming and requires model selection by the user. In contrast, the BIC method used by decond1d provides a quantitative method for model comparison that penalizes for model complexity helping to prevent over-fitting of the data and allows identification of the most parsimonious model. The decon1d program is freely available as a downloadable Python script at the project website (https://github.com/hughests/decon1d/).

Unlabelled: Pain intensity assessments are used widely in human pain research, and their transparent reporting is crucial to interpreting study results. In this systematic review, we examined reporting of human pain intensity assessments and related elements (eg, administration frequency, time period assessed, type of pain) in all empirical pain studies with adult participants in 3 major pain journals (ie, European Journal of Pain, Journal of Pain, and Pain) between January 2011 and July 2012. Of the 262 articles identified, close to one-quarter (24%) ambiguously reported the pain intensity assessment. Elements related to the pain intensity assessment were frequently not reported: 31% did not identify the time period participants were asked to rate, 43% failed to report the type of pain intensity rated, and 58% did not report the specific location or pain condition rated. No differences were observed between randomized clinical trials and experimental (eg, studies involving experimental manipulation without random group assignment and blinding) and observational studies in reporting quality. The ability to understand study results, and to compare results between studies, is compromised when pain intensity assessments are not fully reported. Recommendations are presented regarding key details for investigators to consider when conducting and reporting pain intensity assessments in human adults., Perspective: This systematic review demonstrates that publications of pain research often incompletely report pain intensity assessments and their details (eg, administration frequency, type of pain). Failure to fully report details of pain intensity assessments creates ambiguity in interpreting research results. Recommendations are proposed to increase transparent reporting., (Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Cell entry of severe acute respiratory coronavirus-2 (SARS-CoV-2) and other CoVs can occur via two distinct routes. Following receptor binding by the spike glycoprotein, membrane fusion can be triggered by spike cleavage either at the cell surface in a transmembrane serine protease 2 (TMPRSS2)-dependent manner or within endosomes in a cathepsin-dependent manner. Cellular sialoglycans have been proposed to aid in CoV attachment and entry, although their functional contributions to each entry pathway are unknown. In this study, we used genetic and enzymatic approaches to deplete sialic acid from cell surfaces and compared the requirement for sialoglycans during endosomal and cell-surface CoV entry using lentiviral particles pseudotyped with the spike proteins of different sarbecoviruses. We show that entry of SARS-CoV-1, WIV1-CoV and WIV16-CoV, like the SARS-CoV-2 omicron variant, depends on endosomal cathepsins and requires cellular sialoglycans for entry. Ancestral SARS-CoV-2 and the delta variant can use either pathway for entry, but only require sialic acid for endosomal entry in cells lacking TMPRSS2. Binding of SARS-CoV-2 spike protein to cells did not require sialic acid, nor was sialic acid required for SARS-CoV-2 entry in TMRPSS2-expressing cells. These findings suggest that cellular sialoglycans are not strictly required for SARS-CoV-2 attachment, receptor binding or fusion, but rather promote endocytic entry of SARS-CoV-2 and related sarbecoviruses. In contrast, the requirement for sialic acid during entry of MERS-CoV pseudoparticles and authentic HCoV-OC43 was not affected by TMPRSS2 expression, consistent with a described role for sialic acid in merbecovirus and embecovirus cell attachment. Overall, these findings clarify the role of sialoglycans in SARS-CoV-2 entry and suggest that cellular sialoglycans mediate endosomal, but not cell-surface, SARS-CoV-2 entry. Author summary: The COVID-19 pandemic, caused by SARS-CoV-2, has resulted in over 700 million infections and 7 million deaths so far, demonstrating the threat posed by emerging CoVs. In humans, SARS-CoV-2 and related coronaviruses cause respiratory tract infections, such as the common cold, as well as more severe disease in some individuals. To prepare for future outbreaks, conserved steps in the CoV replication could be considered for antiviral prophylactic or therapeutic approaches. One such process is CoV cell entry, which occurs via two main routes: At the cell surface or within endosomes. Cellular receptors, proteases and complex sugars, known as glycans, mediate CoV entry steps. In this study, we compared the role of a specific glycan subset, sialoglycans, in endosomal and cell surface CoV entry. We show that sialoglycans are required for entry of various CoVs that are mainly dependent on the endosomal route, but in the case of SARS-CoV-2, sialoglycans were not required when the cell-surface entry route was available. Our findings contribute to understanding the mechanisms of CoV entry, which could inform development of pan-CoV antivirals that target CoV entry steps. [ABSTRACT FROM AUTHOR]

Over the course of the COVID-19 pandemic, variants have emerged with increased mutations and immune evasive capabilities. This has led to breakthrough infections (BTI) in vaccinated individuals, with a large proportion of the neutralizing antibody response targeting the receptor binding domain (RBD) of the SARS-CoV-2 Spike glycoprotein. Immune imprinting, where prior exposure of the immune system to an antigen can influence the response to subsequent exposures, and its role in a population with heterogenous exposure histories has important implications in future vaccine design. Here, we develop an accessible approach to map epitope immunodominance of the neutralizing antibody response in sera. By using a panel of mutant Spike proteins in a pseudotyped virus neutralization assay, we observed distinct epitope usage in convalescent donors infected during wave 1, or infected with the Delta, or BA.1 variants, highlighting the antigenic diversity of the variant Spikes. Analysis of longitudinal serum samples taken spanning 3 doses of COVID-19 vaccine and subsequent breakthrough infection, showed the influence of immune imprinting from the ancestral-based vaccine, where reactivation of existing B cells elicited by the vaccine resulted in the enrichment of the pre-existing epitope immunodominance. However, subtle shifts in epitope usage in sera were observed following BTI by Omicron sub-lineage variants. Antigenic distance of Spike, time after last exposure, and number of vaccine boosters may play a role in the persistence of imprinting from the vaccine. This study provides insight into RBD neutralizing epitope usage in individuals with varying exposure histories and has implications for design of future SARS-CoV-2 vaccines. Author summary: Throughout the COVID-19 pandemic, the continued emergence of new SARS-CoV-2 variants has resulted in a rise in breakthrough infections (BTIs). Infection with different variants has led to varying exposure histories in the general population. Although the neutralizing response to Spike has been thoroughly characterized, with several key epitopes identified, there is a lack of knowledge of the proportion each epitope contributes to the neutralizing response in sera and how this is affected by exposure history. Here, we use a panel of mutant Spike pseudotyped viruses to screen epitope usage and immunodominance in polyclonal sera. In a cohort of unvaccinated donors infected with different variants, distinct epitope usage was observed, highlighting the antigenic diversity between the variant Spikes. Furthermore, samples collected spanning multiple vaccine doses and BTI showed the influence of prior immunity from the vaccine on epitope usage. Although a large proportion of the immune response following BTI could be attributed to enrichment of pre-existing immunodominance from the vaccine, subtle shifts in epitope usage were observed with infection by more mutated variants. This work gives more detailed insight into differences in the neutralizing response of individuals with varying exposure histories that may inform next generation SARS-CoV-2 vaccines. [ABSTRACT FROM AUTHOR]

This study explored health-seeking practices and utilization of ethnomedical therapies for chronic pain management among people who use drugs (PWUD) in Nigeria. Data were generated through in-depth interviews with PWUD who lived with chronic pain (n = 26). Participants were recruited through snowball sampling in Uyo, Nigeria. Interviews were recorded, transcribed verbatim, coded and analysed thematically. Participants reported challenges with biomedical pain management, including a lack of cure for pain and low adherence to medications due to financial constraints and restrictions on dispensing of pharmaceutical opioids. These challenges contributed to inadequate biomedical management of chronic pain and encouraged utilization of herbal remedies, including those originating from other ethno-linguistic settings. While some preferred herbal remedies to biomedical care, others used these remedies due to inability to access biomedical pain management. Further, while some found herbal remedies to be helpful in relieving pain, others experienced adverse reactions and sought emergency medical services for this reason. As a result, they disavowed ethnomedical therapies and reaffirmed trust in biomedicine. Participants choose between biomedicine and ethnomedical therapies in managing chronic pain, and these choices were often shaped by structural inequality and the wider context of medical pluralism. Findings indicate a need to promote diversity and choice in healthcare and ensure access to safe, equitable and culturally-appropriate care through health insurance coverage and formal regulation of ethnomedical providers. [ABSTRACT FROM AUTHOR]

The lac repressor protein (LacI) efficiently represses transcription of the lac operon in Escherichia coli by binding to two distant operator sites on the bacterial DNA and causing the intervening DNA to form a loop. We employed single-molecule tethered particle motion to observe LacI-mediated loop formation and breakdown in DNA constructs that incorporate optimized operator binding sites and intrinsic curvature favorable to loop formation. Previous bulk competition assays indirectly measured the loop lifetimes in these optimized DNA constructs as being on the order of days; however, we measured these same lifetimes to be on the order of minutes for both looped and unlooped states. In a range of single-molecule DNA competition experiments, we found that the resistance of the LacI-DNA complex to competitive binding is a function of both the operator strength and the interoperator sequence. To explain these findings, we present what we believe to be a new kinetic model of loop formation and DNA competition. In this proposed new model, we hypothesize a new unlooped state in which the unbound DNA-binding domain of the LacI protein interacts nonspecifically with nonoperator DNA adjacent to the operator site at which the second LacI DNA-binding domain is bound., (Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Beliefs surrounding the use of opioids for chronic noncancer pain have vacillated over time. Concerns regarding long-term efficacy and adverse effects of opioids, along with increases in opioid prescribing, have contributed to many political, regulatory, and clinical responses. The present study was designed to (1) develop a reliable and valid measure (Clinicians' Attitudes about Opioids Scale [CAOS]) to assess current and evolving beliefs regarding opioids and opioid use in patients with chronic pain; and (2) survey these beliefs in a nationally representative sample of providers from multiple medical specialties throughout the United States. We developed the questionnaire in 3 phases: (1) focus groups and content development; (2) pilot testing and subsequent revisions; and (3) formal survey (N = 1,535) and assessment of stability (N = 251). The resulting 38-item measure assessed 5 domains: (1) Impediments and Concerns; (2) Perceived Effectiveness; (3) Schedule II versus III Opioids; (4) Medical Education; and (5) Tamper Resistant Formulations. No significant differences were identified among geographical regions; however, several differences were observed among medical specialties. Orthopedists were most troubled by impediments/concerns from long-term opioid use and had the least confidence in opioid efficacy, whereas Pain Medicine specialists and Physical Medicine and Rehabilitation specialists were the most confident in efficacy., Perspective: This article presents the psychometric properties of a new measure of clinicians' beliefs surrounding opioid use for chronic pain. Using this measure, beliefs and behaviors of physicians across medical specialties and geographic regions using a nationally representative sample are presented, updating findings from a similar survey conducted 20 years ago., (Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Objective: People with fibromyalgia (FM) report a number of physical, cognitive, and psychological symptoms. The purpose of the current study was to determine whether people with FM differed based on the type and severity of symptoms, and if so, whether subgroups differ with respect to health care utilization, functional ability, and work status., Methods: Symptom, health care utilization, work, and physical data were available for 2,182 female responders to an Internet survey. Factor analysis was conducted on the physical and cognitive/psychological symptoms, and resulting factor scores were utilized in a cluster analysis to identify subgroups based on symptoms. Cluster groups were compared on a set of variables (e.g., health care utilization, coping)., Results: Factor analyses resulted in 3 symptom factor scores: musculoskeletal, non-musculoskeletal, and cognitive/psychological symptoms. The optimal cluster solution to the cluster analysis revealed 4 clusters. Group 1 was high on all 3 symptom domains, group 2 was moderate on the 2 physical symptom domains and high on cognitive/psychological symptoms, group 3 was moderate on the 2 physical symptom domains and low on cognitive/psychological symptoms, and group 4 was low on all symptom domains. The more symptomatic groups reported the greatest amount of health care utilization and difficulty in coping with symptoms., Conclusion: The FM population is heterogeneous with regard to symptom reporting. Additional research is needed to better understand differential symptom experience among people with FM. Clarification of these differences may increase understanding of the mechanisms involved in FM and provide guidance for treatment decisions.

Unlabelled: Approximately 1 in 5 adults in the United States are affected by the pain, disability, and decreased quality of life associated with arthritis. The primary focus of treatment is on reducing joint inflammation and pain through a variety of pharmacotherapies, each of which is associated with various side effects. Hyperbaric oxygen therapy is an alternative treatment that has been recommended to treat a variety of inflammatory diseases, ranging from chronic brain injury to exercise induced muscle soreness. The purpose of this set of experiments was to explore the effect of hyperbaric oxygen therapy on joint inflammation and mechanical hyperalgesia in an animal model of arthritis, and compare these effects to treatment with aspirin. Hyperbaric oxygen therapy significantly reduced both joint inflammation and hyperalgesia. As compared with aspirin treatment, hyperbaric treatment was equally as effective in decreasing joint inflammation and hyperalgesia., Perspective: This article reports that hyperbaric oxygen treatment decreases pain and inflammation in an animal model of arthritis. The effect of hyperbaric oxygen treatment is very similar in magnitude to the effect of acetylsalicylic acid treatment. Potentially, hyperbaric oxygen could be used to treat pain and inflammation in patients with arthritis.

Interferons (IFNs) play a crucial role in the regulation and evolution of host–virus interactions. Here, we conducted a genome-wide arrayed CRISPR knockout screen in the presence and absence of IFN to identify human genes that influence Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. We then performed an integrated analysis of genes interacting with SARS-CoV-2, drawing from a selection of 67 large-scale studies, including our own. We identified 28 genes of high relevance in both human genetic studies of Coronavirus Disease 2019 (COVID-19) patients and functional genetic screens in cell culture, with many related to the IFN pathway. Among these was the IFN-stimulated gene PLSCR1. PLSCR1 did not require IFN induction to restrict SARS-CoV-2 and did not contribute to IFN signaling. Instead, PLSCR1 specifically restricted spike-mediated SARS-CoV-2 entry. The PLSCR1-mediated restriction was alleviated by TMPRSS2 overexpression, suggesting that PLSCR1 primarily restricts the endocytic entry route. In addition, recent SARS-CoV-2 variants have adapted to circumvent the PLSCR1 barrier via currently undetermined mechanisms. Finally, we investigate the functional effects of PLSCR1 variants present in humans and discuss an association between PLSCR1 and severe COVID-19 reported recently. Interferons (IFNs) have a role in the regulation of virus-host interactions. This study uses genome-wide CRISPR knockout screen data to identify 28 genes that impact SARS-CoV-2 infection, including PLSCR1, which restricts spike-mediated SARS-CoV-2 entry independently of its IFN-related role. [ABSTRACT FROM AUTHOR]

Background: Electroencephalography (EEG) is a promising tool for identifying the physiological biomarkers of fibromyalgia (FM). Evidence suggests differences in power band and density between individuals with FM and healthy controls. EEG changes appear to be associated with pain intensity; however, their relationship with the quality of pain has not been examined. We aimed to investigate whether abnormal EEG in the frontal and central points of the 10–20 EEG system in individuals with FM is associated with pain's sensory-discriminative and affective-motivational dimensions. The association between EEG and the two dimensions of emotional disorders (depression and anxiety) was also investigated. Methods: In this cross-sectional pilot study, pain experience (pain rating index [PRI]) and two dimensions of emotional disorders (depression and anxiety) were assessed using the McGill Pain Questionnaire (PRI-sensory and PRI-affective) and Hospital Anxiety and Depression Scale (HADS), respectively. In quantitative EEG analysis, the relative spectral power of each frequency band (delta, theta, alpha, and beta) was identified in the frontal and central points during rest. Results: A negative correlation was found between the relative spectral power for the delta bands in the frontal (r= -0.656; p = 0.028) and central points (r= -0.624; p = 0.040) and the PRI-affective scores. A positive correlation was found between the alpha bands in the frontal (r = 0.642; p = 0.033) and central points (r = 0.642; p = 0.033) and the PRI-affective scores. A negative correlation between the delta bands in the central points and the anxiety subscale of the HADS (r = -0.648; p = 0.031) was detected. Conclusion: The affective-motivational dimension of pain and mood disorders may be related to abnormal patterns of electrical activity in patients with FM. Trial registration: Retrospectively registered on ClinicalTrials.gov (NCT05962658). [ABSTRACT FROM AUTHOR]

Proteus mirabilis is a very common gram-negative facultative anaerobe seen in urinary tract infections. This rod-shaped bacterium tends to cause urolithiasis via its ability to alkalinize the urine. However, in some cases, this bacterium has been shown to cause bacteremia as well as other complicated infections. Here we would like to present a rare case of Proteus mirabilis that has invaded the brain in a patient that has a ventriculoperitoneal (VP) shunt placed due to coccidioidal meningitis causing hydrocephalus. We would also like to discuss the importance of the monitoring of VP shunt and discuss their likelihood of infections and the medical as well as surgical management. [ABSTRACT FROM AUTHOR]

Background: Overdose prevention sites (OPS) are a harm reduction strategy that offer people who use drugs a variety of resources including but not limited to sterile supplies, linkage to healthcare resources, and intervention if an overdose occurs. OPS operate in over 120 countries and evidence has demonstrated they are an effective harm reduction strategy. Despite their success elsewhere, OPS remain federally illegal in the United States and thus there is limited research on their implementation and outcomes in the United States. This study aimed to identify Colorado healthcare providers' knowledge and attitudes about OPS and determine if there is a correlation between healthcare providers with more knowledge about OPS having a more positive attitude about OPS. Methods: An electronic survey was distributed to healthcare providers in Colorado. Responses were collected in early 2022 and recorded on a 5-point Likert scale. Mean scores between 1 and 5 were calculated for each participant and analysis of variance methods were used to determine correlating demographic factors. A p value of ≤ 0.05 was used to determine statistical significance of all findings. Results: This study included 698 participants. A Pearson correlation analysis revealed a strong positive relationship (r = 0.76, p < 0.0001) between provider knowledge and attitudes about OPS. Emergency medicine providers scored the highest in mean knowledge and attitude scores in comparison to all other specialties. Respondents affiliated with a harm reduction center exhibited the highest mean knowledge and attitude scores. Mean knowledge and attitude scores generally rose with respondents' increasing encounters with people who inject drugs in a typical workday, except when reaching nine or more encounters, where a sharp decline occurred. Conclusions: Our study highlights the importance of education, exposure to harm reduction strategies, and inter-specialty collaboration in shaping healthcare providers' knowledge and attitudes about OPS. The positive correlation between providers' knowledge and attitudes about OPS suggests that educating healthcare providers on harm reduction strategies, specifically OPS, may lead to reduced stigmatization of OPS among healthcare professionals. [ABSTRACT FROM AUTHOR]

Background: Swyer–James–MacLeod syndrome (SJMS) is a rare lung condition characterized by a unilateral lung hyperlucency and reduction in the pulmonary vasculature, with or without the presence of bronchiectasis. In the 1950s, Swyer, James, and Macleod simultaneously characterized the syndrome for the first time. It is typically diagnosed in childhood. Adult-onset cases are extremely rare, with little literature available on its clinical presentation and diagnostic challenges. Swyer–James–MacLeod syndrome can mimic other lung disorders, resulting in misdiagnosis and improper treatment. Case presentation: A 49- year-old woman from Debre Berhan, Ethiopia, presented to the emergency department of Hakim Gizaw Teaching Hospital with symptoms and radiographic findings mimicking acute pulmonary embolism. On the basis of the clinical presentation and radiographic findings, the patient was first treated as a probable case of pulmonary embolism. Anticoagulant therapy and oxygen support were initiated. Nevertheless, additional testing using a chest computed tomography angiography revealed left lung hyperlucency, decreased vascularity, bronchiectasis, and a negative result for pulmonary embolism. As a result, Swyer–James–MacLeod syndrome was diagnosed. Conclusion: The symptoms of Swyer–James–MacLeod syndrome can be mistaken for pulmonary embolism, which could lead to ineffective treatment and needless expenses. In individuals presenting with symptoms suggestive of pulmonary embolism, this case emphasizes the significance of considering Swyer–James–MacLeod syndrome as a differential diagnosis, especially in the absence of established risk factors for pulmonary embolism. [ABSTRACT FROM AUTHOR]

Background: Post-acute COVID-19 syndrome (long COVID) refers to the persistence of COVID-19 symptoms or exceptional symptoms following recovery. Even without conferring fatality, it represents a significant global public health burden. Despite many reports on long COVID, the prevalence and data on associated biological factors remain unclear and limited. This research aimed to determine the prevalence of long COVID during the two distinct epidemic periods in Thailand, due to the Delta and Omicron variants of SARS-CoV-2, and to investigate the biological factors associated with long COVID. In addition, the spike protein amino acid sequences of the Delta and Omicron variants were compared to determine the frequency of mutations and their potential biological implications. Methods: A retrospective cross-sectional study was established to recruit confirmed COVID-19 participants at Maharat Nakhon Ratchasima Hospital who had recovered for at least three months and were infected between June 2021 and August 2022. The demographic data and long COVID experience were collected via telephone interview. The biological factors were analyzed through binary logistic regression. The datasets of the SARS-CoV-2 spike protein amino acid sequence of the Delta and Omicron variants in Thailand were retrieved from GIDSAID to determine mutation frequencies and to identify possible roles of the mutations based on published data. Results: Data was collected from a total of 247 participants comprising 106 and 141 participants of the Delta and Omicron epidemic periods, respectively. Apart from the COVID-19 severity and health status, the baseline participant data of the two time periods were remarkably similar. The prevalence of long COVID observed in the Omicron period was higher than in the Delta period (74.5% vs. 66.0%). The biological factors associated with long COVID were epidemic variant, age, treatment with symptomatic medicines, and vaccination status. When the spike protein sequence data of the two variants were compared, it was observed that the Omicron variant exhibited a greater quantity of amino acid changes in its receptor-binding domain (RBD) and receptor-binding motif (RBM). The critical changes of the Omicron variant within these regions had a significant function in enhancing virus transmissibility and host immune response resistance. Conclusion: This study revealed informative data associated with long COVID in Thailand. More attention should be given to long COVID caused by unique virus variants and other biological factors to prepare a healthcare management strategy for COVID-19 patients after recovery. [ABSTRACT FROM AUTHOR]

Chronic non-cancer pain is a highly prevalent health issue with personal and societal consequences. Patients suffering from chronic non-cancer pain are mainly cared for by primary care physicians, but research shows that the latter perceive treating chronic pain as difficult. This qualitative descriptive study aimed to explore how primary care physicians in Switzerland manage patients with chronic non-cancer pain and what factors influence patient management. Data were collected through semi-structured interviews amongst primary care physicians in the German speaking part of Switzerland. A thematic analysis of the interviews allowed to identify four main themes: Investigation of chronic pain; patient-provider relationship; patient characteristics, and medical recommendations. These themes were closely interconnected and influenced each other. Physicians not only enquired about the origin of pain but also about the patients' beliefs and expectations towards it. They stressed the role of communication in fostering a good patient-physician relationship and to help patients cope with their pain. In addition to purely medical considerations, the psychological, social and economic situation of their patients and their possible impacts on the management of chronic non-cancer pain played a crucial role when recommending a treatment. This study highlighted the complexity of chronic pain management, which entails that primary care physicians need to figure out a unique strategy for each patient. By integrating patients' values and beliefs, as well as socioeconomic aspects, primary care physicians are in a position to take the lead in chronic non-cancer pain management. However, considering the burden of this disease, more continuous medical education on chronic pain is needed for primary care physicians, especially to better take into account the social determinants of pain. [ABSTRACT FROM AUTHOR]

Background: Seroprevalence studies provide information on the true extent of infection and capture demographic and geographic differences, indicating the level of immunity against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). We sought to provide local evidence of SARS-CoV-2 exposure in school-aged children during in-class teaching in Maputo City and Province, Mozambique. Methods: Between August and November 2022, we performed a cross-sectional study in school-aged children in four schools in rural, peri-urban, and urban areas of Maputo City and Province. A point-of-care test was used to evaluate SARS-CoV-2 antigens and anti-SARS-CoV-2-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies. Descriptive statistics were used to estimate the prevalence of the antigens and antibodies. Multiple logistic regression models were used to estimate the adjusted odds ratio (AOR) for the factors associated with anti-SARS-CoV-2 antibodies. Results: A total of 736 school-aged children were analyzed. The prevalence of the SARS-CoV-2 antigen was 0.5% (4/736). The prevalence of SARS-CoV-2 antigens was 0.0% (0/245), 0.8% (2/240) and 0.8% (2/251), in the rural, peri-urban and urban areas respectively. The overall seroprevalence of the anti-SARS-CoV-2 antibodies (IgG or IgM) was 80.7% (594/736). In rural area anti-SARS-CoV-2 IgG or IgM antibodies were detected in 76.7% (188/245), while in peri-urban area they were detected in 80.0% (192/240) and in urban area they were detected in 85.3% (214/251). In the adjusted logistic regression model, school-aged children from the urban area were more likely to have anti-SARS-CoV-2 IgG or IgM antibodies than were school-aged children from the rural area (adjusted odds ratio: 1.679; 95% CI: 1.060–2.684; p-value = 0.028). Conclusions: During the in-class teaching period, active SARS-CoV-2 cases in school-aged children were observed. More than half of the school-aged children were exposed to SARS-CoV-2, and SARS-CoV-2 was significantly more common in the schools at the urban area than in the school in the rural area at Maputo City and Province. [ABSTRACT FROM AUTHOR]

The anterior cingulate cortex (ACC) is involved in the affective and motivational aspect of pain perception. Behavioral studies show a decreased avoidance behavior to noxious stimuli without change in mechanical threshold after stimulation of the ACC. However, as part of the neural circuitry of behavioral reflexes, there is no evidence showing that ACC stimulation alters dorsal horn neuronal responses. We hypothesize that ACC stimulation has two phases: a short-term phase in which stimulation elicits antinociception and a long-term phase that follows stimulation to change the affective response to noxious input. To begin testing this hypothesis, the purpose of this study was to examine the response of spinal cord dorsal horn neurons during stimulation of the ACC. Fifty-eight wide dynamic range spinal cord dorsal horn neurons from adult Sprague-Dawley rats were recorded in response to graded mechanical stimuli (brush, pressure, and pinch) at their respective receptive fields, while simultaneous stepwise electrical stimulations (300 Hz, 0.1 ms, at 10, 20, and 30 V) were applied in the ACC. The responses to brush at control, 10, 20, and 30 V, and recovery were 14.2 +/- 1.4, 12.3 +/- 1.2, 10.9 +/- 1.2, 10.3 +/- 1.1, and 14.1 +/- 1.4 spikes/s, respectively. The responses to pressure at control, 10, 20, and 30 V, and recovery were 39.8 +/- 4.7, 25.6 +/- 3.0, 25.0 +/- 3.0, 21.6 +/- 2.4, and 34.2 +/- 3.7 spikes/s, respectively. The responses to pinch at control, 10, 20, and 30 V, and recovery were 40.7 +/- 3.8, 30.6 +/- 3.1, 27.8 +/- 2.8, 27.2 +/- 3.2, and 37.4 +/- 3.9 spikes/s, respectively. We conclude that electrical stimulation of the ACC induces significant inhibition of the responses of spinal cord dorsal horn neurons to noxious mechanical stimuli. The stimulation-induced inhibition begins to recover as soon as the stimulation is terminated. These results suggest differential short-term and long-term modulatory effects of the ACC stimulation on nociceptive circuits.

Objectives: This study assesses the knowledge, attitudes and beliefs of physiotherapists regarding non-specific chronic low back pain (NSCLBP) and explores their impact on treatment selection, ultimately enhancing quality outcomes. Methods: A total of 107 participants were involved in the study. The questionnaire comprised three sections: Demographic information, evaluation of participants' pain beliefs and attitudes using the pain attitudes and beliefs scale for physiotherapists scale and frequently employed treatment selection and plans for managing NSCLBP. The questionnaire was distributed via e-mail, WhatsApp and social media platforms using Google Forms. Results: Responses were gathered from 107 physiotherapists in India through the Google Form. Treatment orientation revealed 43.4% biomedical and 30.7% bio-psychosocial approaches. Discussion: The predominant orientation of physiotherapists in India leans towards biomedical aspects in their attitudes and beliefs. [ABSTRACT FROM AUTHOR]

Introduction: Nurturing professional identities instils behavioural standards of physicians, and this in turn facilitates consistent professional attitudes, practice and patient care. Identities are socioculturally constructed efforts; therefore, we must account for the social, cultural and local healthcare factors that shape physicians' roles, responsibilities and expectations. This study aimed to forward a programme to nurture professionalism among physicians in Singapore. Methods: A three-phase, evidenced-based approach was used. First, a systematic scoping review (SSR) was conducted to identify professionalism elements. Second, a questionnaire was created based on the findings of the SSR. Third, a modified Delphi approach, which involved local experts to identify socioculturally appropriate elements to nurture professionalism, was used. Results: A total of 124 articles were identified from the SSR; these articles revealed definitions, knowledge, skills and approaches to nurturing professionalism. Through the modified Delphi approach, we identified professional traits, virtues, communication, ethical, self-care, teaching and assessment methods, and support mechanisms. Conclusion: The results of this study formed the basis for a holistic and longitudinal programme focused on instilling professional traits and competencies over time through personalised and holistic support of physicians. The findings will be of interest to medical communities in the region and beyond. [ABSTRACT FROM AUTHOR]

Objective of this narrative review is to elucidate the complex relationship among dietary habits, sarcopenia, and gut microbiota composition, with an eye toward enhancing patient management and outcomes. Given the burgeoning interest in the influence of diet on CMP, a detailed examination of the current literature is warranted. Nutritional intake is a critical determinant of the gut microbiota profile, which, in turn, is linked to musculature integrity and performance, potentially leading to sarcopenia. The development of sarcopenia can aggravate CMP owing to diminished muscular strength and functionality. Additionally, disruptions in the gut microbiota may directly modulate nociception, intensifying CMP manifestations. Thus, nutritional optimization emerges as a viable approach to CMP management. Emphasizing a diet conducive to a healthy gut microbiome could forestall or mitigate sarcopenia, thereby attenuating CMP intensity. Nevertheless, the domain calls for further empirical exploration to unravel the nuances of these interactions and to forge efficacious dietary strategies for individuals with CMP. Beyond mere analgesia, comprehensive patient care for CMP requires acknowledgment of the complex and multifactorial nature of pain and its foundational elements. Embracing an integrative treatment model allows healthcare practitioners to promise better patient prognoses, enriched life quality, and a decrease in the sustained healthcare costs associated with CMP. Plain Language Summary: Chronic musculoskeletal pain (CMP) is long-lasting pain in the bones, muscles, and joints, and it's a common problem affecting over 1.7 billion people worldwide. This kind of pain can really disrupt someone's daily life, making it hard to do everyday things and causing a lot of stress. This review is like a deep dive into how eating habits, muscle loss, and the tiny organisms living in our guts all connect to this pain. As we are becoming more curious about how food affects CMP, it's important to look closely at what we already know. What we eat can change the tiny bugs in our guts, which has a big impact on our muscles. If our muscles get weak and shrink (a condition called sarcopenia), it can make CMP worse because weak muscles cannot support our bodies well. Also, if the balance of bugs in our gut is off, it might even make us feel pain more intensely. So, changing what we eat might be a good way to tackle CMP. Eating foods that keep our gut bugs happy might help prevent muscle loss and reduce pain. But we still need to do more research to understand this better and to figure out the best foods to eat for this purpose. Treating CMP is not just about getting rid of the pain; it's about looking at the whole picture and all the things that contribute to the pain. By considering everything — from our diet to our muscles to our gut bugs — doctors can help improve the lives of people with CMP, making them more comfortable and possibly reducing medical costs in the long run. [ABSTRACT FROM AUTHOR]

The present study combined a supervised machine learning framework with an unsupervised method, finite mixture modeling, to identify prognostically meaningful subgroups of diverse chronic pain patients undergoing interdisciplinary treatment. Questionnaire data collected at pre-treatment and 1-year follow up from 11,995 patients from the Swedish Quality Registry for Pain Rehabilitation were used. Indicators measuring pain characteristics, psychological aspects, and social functioning and general health status were used to form subgroups, and pain interference at follow-up was used for the selection and the performance evaluation of models. A nested cross-validation procedure was used for determining the number of classes (inner cross-validation) and the prediction accuracy of the selected model among unseen cases (outer cross-validation). A four-class solution was identified as the optimal model. Identified subgroups were separable on indicators, predictive of long-term outcomes, and related to background characteristics. Results are discussed in relation to previous clustering attempts of patients with diverse chronic pain conditions. Our analytical approach, as the first to combine mixture modeling with supervised, targeted learning, provides a promising framework that can be further extended and optimized for improving accurate prognosis in pain treatment and identifying clinically meaningful subgroups among chronic pain patients. [ABSTRACT FROM AUTHOR]

Background: Liver transplant (LT) recipients are classified as a high-risk group and should receive regular surveillance for COVID-19 and are expected to have higher viral load and prolonged viral shedding. Virus-specific neutralizing antibodies (NAb), induced by infection, can prevent viral infection by deactivating viral access to host receptors. Aim: To estimate the incidence of SARS-CoV-2 infections and ascertain the levels of NAb among LT recipients. Method: This cross-sectional study included LT recipients. The survey included 14 parameters about demography, date since operation, and immunosuppressant medications and 11 parameters about COVID-19 infection. NAb was done by electrochemiluminescence immunoassay. Results: Only 39 LT recipients responded to this survey. Their median age was 57, and 74.4% of them were men. Comorbidities were present in 64% of cases, and DM was the most common comorbidity. Immunosuppressants used were Tacrolimus in 56.4% and Tacrolimus with mycophenolate mofetil in 15.4%. Fifteen cases (38.5%) had suspected infection, and 2 (5.1%) had confirmed infection. Three patients (17.6%) were hospitalized with no mortality. NAb was done in 34 cases, and it was positive in 5 cases (14.7%) with a median level (range) of 0.075 (0.04–27). Three out of 5 cases with a positive NAb test did not give a history of either suspected or confirmed COVID-19 infection. Conclusion: COVID-19 surveillance in LT recipients is important and suggests a relatively favorable clinical course despite the presumed challenges of immunosuppression. COVID-19 was associated with low hospitalization in LT recipients. NAb indicates a potential immune response even in asymptomatic LT recipients. Trial registration: Clinical Trial.gov NCT04565782. September 15 2022. [ABSTRACT FROM AUTHOR]

Background: Curcubita ficifolia Bouché (Cucurbitaceae) has high value as a food crop and medicinal plant, and also has horticultural value as rootstock for other melon species. China is home to many different cultivars, but the genetic diversity of these resources and the evolutionary relationships among them, as well as the differences between C. ficifolia and other Cucurbita species, remain unclear. Results: We investigated the chloroplast (cp) genomes of 160 C. ficifolia individuals from 31 populations in Yunnan, a major C. ficifolia production area in China. We found that the cp genome of C. ficifolia is ~151 kb and contains 128 genes, of which 86 are protein coding genes, 34 encode tRNA, and eight encode rRNAs. We also identified 64 SSRs, mainly AT repeats. The cp genome was found to contain a total of 204 SNP and 57 indels, and a total of 21 haplotypes were found in the 160 study individuals. The reverse repeat (IR) region of C. ficifolia contained a few differences compared with this region in the six other Cucurbita species. Sequence difference analysis demonstrated that most of the variable regions were concentrated in the single copy (SC) region. Moreover, the sequences of the coding regions were found to be more similar among species than those of the non-coding regions. The phylogenies reconstructed from the cp genomes of 61 representative species of Cucurbitaceae reflected the currently accepted classification, in which C. ficifolia is sister to the other Cucurbita species, however, different interspecific relationships were found between Cucurbita species. Conclusions: These results will be valuable in the classification of C. ficifolia genetic resources and will contribute to our understanding of evolutionary relationships within the genus Cucurbita. [ABSTRACT FROM AUTHOR]

The oral biguanide metformin is used to treat type 2 diabetic mellitus (T2DM). Anti-cancer effects have been proven by metformin in different hormone-sensitive tumors, including breast, pancreatic, colon, and prostate cancer. Therefore, we investigated whether metformin could defend against small intestine damage in Dunning's prostate cancer. The study divided the six groups of male Copenhagen rats into the following categories: control, diabetic (D), cancer (C), diabetic + cancer (DC), cancer + metformin (CM), and diabetic + cancer + metformin (DCM). After sacrifice, the small intestines were removed to assess biochemical markers and histopathological evaluation. Biochemical evaluations showed that glutathione (reduced) levels and other enzyme activities related antioxidant systems, paraoxonase, sodium potassium ATPase, acetylcholinesterase activities were decreased. In contrast, lipid peroxidation, total oxidant status, reactive oxygen species, interleukin-1β, interleukin-6, tumor necrosis factor-α, sucrase, maltase, trypsin, myeloperoxidase, xanthine oxidase activities, protein carbonyl contents and sialic acid levels were raised in the damaged groups. Treatment with metformin restored all of this. The histological assessment revealed moderate to severe damage in the small intestine following processes D and C. According to the study's findings, metformin treatment led to a notable decline in histopathological damage in the C and DC. A slight lowering in inflammatory cells and an improvement in the damaged gland integrity in the small intestine were noted with metformin treatment.​ Metformin use protected the small intestinal tissue damage and decreased oxidative stress., Competing Interests: Declarations Ethical approval All experimental protocols were approved by the Animal Care and Use Committee of the Istanbul University, Istanbul, Turkey (ethics committee decision number 2014/28) and carried out in compliance with the ARRIVE guidelines. All animal experiments were conducted following the national guidelines and the relevant national laws on the protection of animals. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: We previously conducted a primary survey of pregnant women with hereditary thrombophilia based on national surveillance in Japan, but did not examine their thrombosis-related characteristics. Antithrombin (AT) deficiency, protein C (PC) deficiency and protein S (PS) deficiency are the major types of hereditary thrombophilia in Japan. Methods: We examined their detailed information related to thrombosis, and evaluated peripartum outcomes in comparison with control data obtained from the Japan Society of Obstetrics and Gynecology. Results: Definite or probable AT deficiency, PC deficiency and PS deficiency were observed in 80, 50, and 317 pregnancies, respectively, from 2014 to 2018 in Japan, with prevalence rates among total deliveries of 0.011%, 0.007%, 0.044%. The number of pregnancies with AT, PC and PS deficiency might have been as many as 27, 17 and 108 every year if complete answers had been provided. In the peripartum period of current pregnancies, 27.5% of women with AT deficiency, 28.0% with PC deficiency and 13.2% with PS deficiency developed thrombosis (p < 0.001 vs. control). Pregnant women with AT and PC deficiency were more susceptible to thrombosis than those with PS deficiency (P < 0.01). Of the thromboses, 92.3% occurred during pregnancy, 62.8% at less than 15 gestational weeks. The earliest onset of thrombosis was 5 gestational weeks. Prophylactic anticoagulation significantly prevented the onset of both antepartum and postpartum thrombosis (p < 0.0001). The rate of recurrent pregnancy loss in women with low PC or PS activities was significantly higher than in controls (p < 0.0001); however, it is unknown whether recurrent pregnancy loss is related to hereditary PS deficiency. There seem to have been few serious maternal or fetal/neonatal complications due to placental insufficiency related to a hypercoagulable state other than growth restriction. Conclusions: This survey revealed the thrombosis-related characteristics of pregnant women with hereditary thrombophilia in Japan. We suggest prophylactic anticoagulation to prevent maternal or fetal/neonatal complications. [ABSTRACT FROM AUTHOR]

Background: Pain is highly burdensome, affecting over 30% of long-term care (LTC) residents. Pain significantly reduces residents' health-related quality of life (HRQoL), limits their ability to perform activities of daily living (ADLs), restricts their social activities, and can lead to hopelessness, depression, and unnecessary healthcare costs. Although pain can generally be prevented or treated, eliminating pain may not always be possible, especially when residents have multiple chronic conditions. Therefore, improving the HRQoL of LTC residents with pain is a priority goal. Understanding factors influencing HRQoL of LTC residents with pain is imperative to designing and evaluating targeted interventions that complement pain management to improve residents' HRQoL. However, these factors are poorly understood, and we lack syntheses of available research on this topic. This systematic review protocol outlines the methods to identify, synthesize, and evaluate the available evidence on these factors. Methods: This mixed methods review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We will systematically search Medline, EMBASE, PsycINFO, CINAHL, Scopus, Cochrane Database of Systematic Reviews and ProQuest Dissertation and Thesis Global from database inception. We will include primary studies and systematically conducted reviews without restrictions to language, publication date, and study design. We will also include gray literature (dissertation and reports) and search relevant reviews and reference lists of all included studies. Two reviewers will independently screen articles, conduct quality appraisal, and extract data. We will synthesize results thematically and conduct meta-analyses if statistical pooling is possible. Residents and family/friend caregivers will assist with interpreting the findings. Discussion: This proposed systematic review will address an important knowledge gap related to the available evidence on factors influencing HRQoL of LTC residents with pain. Findings will be crucial for researchers, LTC administrators, and policy makers in uncovering research needs and in planning, developing, and evaluating strategies in addition to and complementary with pain management to help improve HRQoL among LTC residents with pain. Systematic review registration: PROSPERO CRD42023405425 [ABSTRACT FROM AUTHOR]

This study aimed to evaluate community pharmacists' knowledge of opioid-containing medications and their attitude toward opioid use problems. Materials and methods: A cross-sectional study was conducted using a self-administered, structured questionnaire distributed to 105 community pharmacists from July 1– 30, 2023 in Bahir Dar City, Ethiopia. The tool included demographic information and questions designed to assess participants' knowledge and attitudes. Results: Out of the 105 pharmacists included in this study, majority were males (54.3%), nearly half held a bachelor's degree (49.5%), and slightly above one-third had over a decade experience (39%). Regarding knowledge and attitude towards opioids, 62 individuals (59%) exhibited good knowledge, and 64 (61%) demonstrated less stigma toward opioid usage. Factors affecting knowledge include: education level (AOR (95% CI): 8.43 (1.76– 40.35) and 9.93 (1.04– 85.33) for bachelors and postgraduates respectively and age 1.45 (1.20– 1.77)]. Meanwhile, experience [AOR (95% CI): 4.64(1.20– 17.90) and 4.29 (1.23– 15.05)] for 5– 9 years and ≥ 10 years respectively and education level [AOR (95% CI): 4.08 (1.40– 11.93) for bachelors and 6.40 (1.42– 28.96)] for postgraduates were linked to attitude. Conclusion: A gap in knowledge and more stigmatizing behavior was observed among community pharmacists. These findings imply the importance of tailored educational interventions to address knowledge gaps and promote positive attitudes toward opioid usage among community pharmacists. Therefore, it is imperative to deliver up-to-date information on opioids, emphasizing their high addiction potential, to ensure pharmacists are well-equipped with the latest information. [ABSTRACT FROM AUTHOR]

Background: Herpes simplex virus (HSV) encephalitis (HSE) is a serious and potentially life-threatening disease, affecting both adults and newborns. Progress in understanding the virus and host factors involved in neonatal HSE has been hampered by the limitations of current brain models that do not fully recapitulate the tissue structure and cell composition of the developing human brain in health and disease. Here, we developed a human fetal organotypic brain slice culture (hfOBSC) model and determined its value in mimicking the HSE neuropathology in vitro. Methods: Cell viability and tissues integrity were determined by lactate dehydrogenase release in supernatant and immunohistological (IHC) analyses. Brain slices were infected with green fluorescent protein (GFP-) expressing HSV-1 and HSV-2. Virus replication and spread were determined by confocal microscopy, PCR and virus culture. Expression of pro-inflammatory cytokines and chemokines were detected by PCR. Cell tropism and HSV-induced neuropathology were determined by IHC analysis. Finally, the in situ data of HSV-infected hfOBSC were compared to the neuropathology detected in human HSE brain sections. Results: Slicing and serum-free culture conditions were optimized to maintain the viability and tissue architecture of ex vivo human fetal brain slices for at least 14 days at 37 °C in a CO2 incubator. The hfOBSC supported productive HSV-1 and HSV-2 infection, involving predominantly infection of neurons and astrocytes, leading to expression of pro-inflammatory cytokines and chemokines. Both viruses induced programmed cell death—especially necroptosis—in infected brain slices at later time points after infection. The virus spread, cell tropism and role of programmed cell death in HSV-induced cell death resembled the neuropathology of HSE. Conclusions: We developed a novel human brain culture model in which the viability of the major brain-resident cells—including neurons, microglia, astrocytes and oligodendrocytes—and the tissue architecture is maintained for at least 2 weeks in vitro under serum-free culture conditions. The close resemblance of cell tropism, spread and neurovirulence of HSV-1 and HSV-2 in the hfOBSC model with the neuropathological features of human HSE cases underscores its potential to detail the pathophysiology of other neurotropic viruses and as preclinical model to test novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

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INTRODUCTION: Clinical decision support tools support prescribers and pharmacists as they select and verify appropriate opioid regimens in efforts to combat the high variability in opioid prescribing. This study seeks to examine the impact of alerts within the electronic medical record and pharmacy system on day supply of initial opioid prescribing and dispensing. METHODS: This retrospective study compared a 6-month pre- and postimplementation of clinical decision support tool alerts at an integrated health care system. Data were analyzed to assess changes in the day supply of an opioid at the point of initial prescribing and dispensing based on alerts. RESULTS: The best practice alert in the electronic medical record was associated with a 27% change (p = 0.007) in prescribing by the physician, which resulted in a reduction of average day supply from 12.09 to 6.58 days. The alert in the pharmacy system was associated with a 41.3% change (p < 0.001) in dispensing, which resulted in a reduction of average day supply from 13.46 to 6.96 days. DISCUSSION: To promote judicious opioid prescribing, the best practice alert in the electronic medical record led to a statistically significant change in prescribing. To support appropriate dispensing, the alert in the pharmacy system led to a statistically significant change in dispensing. CONCLUSION: Implementation of two clinical decision support tools that mirrored Centers for Disease Control and Prevention recommendations of prescribing less than a 7-day supply when initiating opioids resulted in a decrease in day supply of the opioid prescription for patients identified as opioid-naïve at the point of prescribing and dispensing. [ABSTRACT FROM AUTHOR]

Background: When theoretically discussing pain, the distinction between acute and chronic pain is not always taken into consideration. By contrast, informed by the pain medicine distinction between acute and chronic pain, the present theoretical paper analyses the phenomena of chronicity and chronification in the pain setting.Methods: Philosopher Fredrik Svenaeus and his paper The phenomenology of chronic pain: embodiment and alienation (Continental Philosophy Review 2015;48:107– 122) is used as a dialogue partner.Results: Three aspects, relevant for clinicians, are discussed: (1) the distinction between emotion and mood, arguing that the process of chronification entails pain evolving from the former to the latter; (2) chronification as a process in which the pain patient becomes aware of his/her temporality, both the past and the future coming to the fore (as opposed to severe acute pain in which only the present counts, ie, getting rid of the pain now); (3) the acquisition of a pain-related narrative identity, interdisciplinary pain rehabilitation programs being described as helping patients regain a narrative identity that is not dominated by pain or by a fruitless chase after pain relief.Conclusion: Chronic pain reminds us of our temporality and of the narrative character of our lives.Plain Language Summary: It is important to distinguish acute pain from chronic pain. When pain is discussed by philosophers of medicine, this distinction is not always made. In the present paper, the phenomenon of chronic pain is analysed. It is argued that chronic pain reminds us of the fact that human beings are subject to time and that our lives can be viewed as a story unfolding in time. When pain persists, both past and future come to the fore. This contrasts with severe acute pain in which only the present counts, ie, getting rid of the pain now. This has practical and clinical implications, and it is argued that one of the potential benefits of interdisciplinary pain rehabilitation programs is to help patients reclaim the story of their lives from the dominion of pain and a fruitless chase after pain relief. [ABSTRACT FROM AUTHOR]

Purpose: Widely used therapeutic approaches, such as cognitive-behavioral and mindfulness-based therapies, can improve pain and functioning in people with chronic back pain, but the magnitude and duration of their effects are limited. Our team developed a novel 12-week program, psychophysiologic symptom relief therapy (PSRT), to substantially reduce or eliminate pain and disability. This study examined whether PSRT helped more patients achieve large-magnitude (≥ 30%, ≥ 50%, ≥ 75%) reductions in back pain-related disability compared to mindfulness-based stress reduction (MBSR) and usual care (UC), and if the beneficial effects of PSRT were explained by reductions in pain-related anxiety following treatment.Patients and Methods: Data from a three-armed randomized controlled trial were used (N=35 adults with chronic back pain). Change scores (baseline to 4-, 8-, 13-, and 26-weeks post-enrollment) were computed for back pain disability (RDQ) and pain-related anxiety (PASS-20). Fisher's exact tests and mediation analyses were conducted.Results: Compared to MBSR and UC, PSRT helped significantly more patients achieve ≥ 75% reductions in back pain disability at all timepoints and in pain anxiety at all timepoints except 13-weeks. Change in pain anxiety significantly mediated the relationship between treatment group and change in back pain disability from baseline to 26-weeks.Conclusion: PSRT helped more patients achieve substantial reductions in disability than an established treatment (MBSR) and usual care. Findings indicate reduced pain anxiety may be a mechanism by which PSRT confers long-term benefits on disability. Importantly, this work aims to move the field toward more precise and effective treatment for chronic back pain. [ABSTRACT FROM AUTHOR]

Explore perceptions and preoccupations regarding use of medical cannabis against chronic musculoskeletal pain, among patients and physicians.Design: Qualitative study using interviews with patients and physicians, based on the Theory of Planned Behavior (TPB).Setting: The study was conducted in Quebec, Canada, in spring 2020.Subjects: We included 27 adult patients and 11 physicians (GPs, anesthesiologists, psychiatrists, and a rheumatologist); the mean age of patients was 48.2 years; 59.3% of patients and 36.4% of physicians were women; 59.3% of patients used no medical cannabis at the time of study; 45.5% of physicians had never authorized it.Methods: Semi-structured interviews were conducted, transcribed and for the qualitative analysis codes were developed in a hybrid, inductive and deductive approach. Guided by the TPB, facilitators and barriers, perceived benefits and harms, and perceived norms that may influence cannabis use or authorization were documented.Results: Although medical cannabis is an interesting avenue for the relief of chronic musculoskeletal pain, doctors and patients agreed that it remained a last line option, due to the lack of scientific evidence regarding its safety and efficacy. The norms surrounding medical cannabis also play an important role in the social and professional acceptance of this therapeutic option.Conclusion: Medical cannabis is seen as a last line option among interventions in the management of chronic pain, and attitudes and prior experiences play a role in the decision to use it. Study results may contribute to improved shared decision making between patients and physicians regarding this option.Plain Language Summary: Little is known about the motivations, perceptions, and preoccupations of patients with chronic pain and their physicians regarding the use of medical cannabis against chronic pain. A qualitative study was done on the attitudes and perceptions of these patients and their physicians. We performed semi-structured interviews, guided by the Theory of Planned Behavior, with chronic pain patients and with physicians treating such patients. Results indicate that both patients and physicians consider medical cannabis as a last line therapeutic option against chronic pain. Also, both groups expressed a need for stronger evidence on the effectiveness and safety of medical cannabis, as well as for more and clearer guidance on when and how to use this additional option in the treatment of chronic pain. [ABSTRACT FROM AUTHOR]