Background: Understanding the SARS-COV-2 reinfection rate and its potential influencing factors is essential for further improvement and development of prevention and control strategies and measures to reduce the reinfection rate of SARS-CoV-2. This study aimed to quantitatively summarize the evidence of current reinfection studies. Methods: We reviewed all English studies published up to Dec 4, 2022. Information extracted from each selected articles and quality assessment of these articles was used to evaluate the risk for bias in studies. The meta-analysis was performed to examine the rate and influencing factors of SARS-CoV-2 reinfection and protective effect of primary infection on reinfection in our study. Sources of heterogeneity were identified using a subgroup analysis defined by the minimum time interval of days to reinfection and variant strains. Results: The weighted pooled rate of reinfection for SARS-CoV-2 was 1.08% ([95% CI, 0.77%-1.52%], I2 = 100%, P < 0.001). Subgroup-analysis of the minimum time interval definition for reinfection showed that rates of reinfection are 0.71%, 0.75%, 1.46% and 1.62% in less than 90 days, 90 days, greater than 90 days, unknown groups, respectively and 0.64%,1.8%,3.08%,0.95% in Alpha, Delta, Omicron, unknown groups. The weighted pooled RR value of the protective effect of primary infection on reinfection was 0.09 ([95% CI, 0.06-0.13], I2 = 92%, P < 0.01). Conclusions: Overall, the reinfection rate of SARS-CoV-2 is relatively low and appears to be on the rise as duration from the first infection to the second infection and the novel coronavirus strain mutates.

A document by Haleema Qayyum Abbasi. Click on the document to view its contents.

Presentation of idiopathic thrombocytopenic purpura (ITP) is dependent on degree of thrombocytopenia with no to mild bleeding symptoms, primarily mucocutaneous bleeding. Severe bleeding of other organ systems is a rare complication. Spontaneous hemarthrosis is rare in patients without hemophilia. We report a child presenting with oral and cutaneous petechial lesions and left knee hemarthrosis without trauma. Laboratory findings showed severe thrombocytopenia consistent with ITP. Serologic tests were consistent with Lyme disease. Hemarthrosis was presumed secondary to Lyme disease monoarticular joint inflammation with bleeding exacerbated by severe thrombocytopenia. Hemarthrosis resolved and platelet counts normalized following immunoglobulin infusion, steroid course, and antibiotics.

Cure rates for acute lymphoblastic leukemia (ALL), the most common childhood cancer have steadily improved over the past five decades. This is due to intensifying systemic therapy, recognizing and treating the central nervous system as a sanctuary site, and implementing modern risk stratification to deliver varying intensities of therapy based on age, presenting white blood count (WBC), sentinel somatic genetics, and therapy response. Recently, numerous Children’s Oncology Group trials have demonstrated the lack of benefit of intensifying traditional chemotherapy, providing evidence that new approaches are needed to cure the patients for whom cure has been elusive. Distinguishing those who require intensive or novel therapeutic approaches from others who will be cured with minimal therapy is key for future trials. Incorporating new genomic biomarkers and more sensitive measures of minimal/measurable residual disease (MRD) provide opportunities to achieve these goals.

Laboratory science sometimes looks like it’s built exclusively for young people, but if you look closely, you’ll find another group of scientists waiting to join your lab: those of us who didn’t quite launch our careers on a normal trajectory. Welcoming a second-career scientist into your lab takes time and resources, but may just be well worth it. Here’s what one second-career scientist wants you to know about supporting second careers in immunology.

Physical model building is essential for realizing digital twins in the manufacturing industry and requires much toil. We aim to develop automated physical model builder (AutoPMoB) that can automatically build physical models from literature databases. AutoPMoB requires several fundamental technologies, and domain-specific datasets play a vital role in developing such technologies. Although datasets related to variables have been created, there has been no dataset in the chemical engineering domain. To create such a dataset, in this study, we developed an algorithm for extracting variable symbols from documents and a variable annotation tool, VARAT, based on the algorithm. We used the tool and created a dataset containing about 1,733 variable symbols from 45 papers on physical models of five manufacturing processes. VARAT enables us to quickly and accurately extract the variable symbols from documents and reduces the time for annotation per paper to less than half, which streamlines the annotation process.

Individuals with depression experience more negative imagery and less vivid positive imagery, and the late positive potential (LPP) is considered as a viable biomarker for negative attentional and memory biases in depression; however, the LPP response to emotional imagery in depressed individuals remains unclear. This study aims to investigate neural response to emotional imagery in depressed individuals. ERPs were recorded from 40 depressed participants and 44 healthy controls during the encoding-imagery task. Depressed participants scored significantly lower in the valence rating of sad and neutral imagery compared to healthy participants. Importantly, the LPP amplitudes to sad imagery in depressed participants were significantly larger than healthy controls, particularly in the middle (800-1,400 ms) and late time windows(1,400-2,000 ms). Furthermore, depressed individuals exhibited significantly higher LPP amplitudes for sad imagery compared to happy imagery, whereas healthy participants showed the opposite pattern. The present study provides evidence that depressed individuals display abnormal electrophysiological reactivity to sad imagery, which offers a new perspective for understanding the mechanisms underlying depression.

Learning, and detection of regularities allows us to make predictions about our environment and process stimuli more efficiently. Using EEG, we found an electrophysiological signature linked to how the brain uses and interprets auditory information in the time domain. We used sequences of five tones with different pitches, with one of three distinct temporal regularities, using a short-long-short-long, long-short-long-short, or isochronous ISI pattern. They were designed so the second tone carried temporal-sequence information, by being presented after a short, medium, or long ISI, allowing recognition of the pattern. Participants heard two tone sequences with the same temporal regularity and had to indicate if the tone pitches were identical. In one experiment, the three types of regularities were randomly intermixed, whereas they were blocked in a control experiment. A frontal and frontocentral positivity increased for the first set of the first experiment (when temporal pattern was not previously known), compared to that same set in the control experiment (pattern known), starting around the earliest time the second tone could be presented, and peaking shortly after actual tone onset. Although these temporal patterns were task irrelevant, and most participants were unaware of them when asked, our results suggest the brain disambiguates its variable environment based on the earliest available information, and that it does so rapidly, pre-attentively, and automatically.

Identifying the biotic factors underlying invasion success is critical to understand the dynamics of biological invasions; and while some studies suggest that intraspecific diversity may play an important role, there has not been a systematic evaluation of the evidence. We performed a meta-analysis on 34 experimental studies and 106 effect sizes to test two hypotheses: (1) higher intraspecific diversity in a resident population decreases the likelihood of it being successfully invaded by other species, and (2) higher intraspecific diversity in an invading population increases its ability to invade another species or community. We found small effects in the direction of our hypotheses, but these were not significant and were influenced by taxon and study duration. The lack of significant findings are somewhat unexpected, given the well-understood mechanisms analogous to those offered for interspecific diversity. These include sampling effects and complementarity, in which diversity is expected to maximize resource use and increase density, thereby reducing niche availability and subsequent invasibility. Additionally, we found evidence of publication bias for studies of invader intraspecific diversity. We recommend that future research focus on a wider diversity of organisms, include longer term experiments, and measure genetic dissimilarity to better understand the role of intraspecific diversity.

Letter to Editor:Title:Potentially inappropriate prescribing in middle-aged adults: A significant problem with a lack of action and evidence to address it.Authors: Dr Michael Naughton1, Frank Moriarty2, Professor Patrick Redmond3Author Affiliation:1 The Clinical Effectiveness Group, Wolfson Institute of Population Health, Queen Mary University of London2 School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine & Health Sciences3 Department of General Practice, RCSI University of Medicine & Health SciencesWord Count: 652Key words: Potentially inappropriate prescribing, middle-aged adults, intervention, medicines optimisationDear Dr Serge Cremers,Potentially inappropriate prescribing (PIP), prescribing where the potential harms outweigh the potential benefits, or where a medication that a patient would benefit from is not prescribed, is an important healthcare challenge. PIP has been well characterised among older adults and is linked to adverse drug reactions (ADRs), hospitalisations, and increased healthcare costs [1]. While studies have been conducted to address PIP in older adults, middle-aged adults remain overlooked despite also being vulnerable to PIP due to age-related chronic conditions [2].Our recently published systematic review showed that PIP is common in middle-aged adults, with an estimated 38% being exposed to PIP annually [3]. PIP in middle-aged adults is known to occur in higher risk and disadvantaged groups those with multimorbidity, polypharmacy, and those from deprived areas [4]. It has been shown to be associated with ADRs [5], and may be associated with increased healthcare utilisation [6]. A further study by our team, examined the cost of PIP in 1.2 million middle-aged adults in South London, finding that the total cost of PIP in this age group across six years was £2.8 million. The cost of adequate alternative prescribing would be £2.2 million, a cost-saving of approximately £553,874 compared with PIP [7].Following on from these studies, we conducted a further systematic search (unpublished) to examine interventions to reduce this prescribing. Searches were conducted in MEDLINE, EMBASE, CINAHL, Cochrane library, ProQuest, Web of Science, OpenGrey, Clinicaltrials.gov, and the WHO Clinical Trials Registry Platform. All English language studies that included adults aged 45-64 years, applied explicit PIP criteria, and implemented an intervention to reduce PIP and were published by June 2022, were eligible. In total, 12,384 studies underwent title and abstract screening with 248 articles identified for full text screening, however ultimately none met our inclusion criteria.Our search has revealed a literature gap, with no studies having been conducted with interventions aiming to reduce PIP in middle-aged adults. Conversely, there are numerous interventional studies to reduce PIP in older adults [8, 9]. PIP in older adults has a similar prevalence[10], but in absolute terms the largest burden of PIP exists in middle-aged adults due to the larger population size. Intervening earlier in middle age may allow patients’ medicines to be optimised and avoid adverse outcomes as they age.Furthermore, the benefits of targeting high risk prescribing independent of age, rather than concentrating only on older adults, have been demonstrated by multiple studies. Concentrating on high-risk prescribing across all age groups, these studies have shown interventions can reduce high risk prescribing, and associated adverse outcomes such as GI-bleeds, heart failure, and hospital admissions [11]. The PINCER intervention has also shown that interventions to reduce high risk prescribing can be highly cost effective [12]. The current, extremely welcome, deprescribing initiatives (https://deprescribing.org/) are applicable beyond older adults and could also be used to benefit the middle-aged in particular. Therefore, as well as extending interventions to middle-aged people specifically, it is also worth considering a whole population approach to high risk prescribing or PIP, given the demonstrated successes and cost effectiveness of these approaches previously.As practising clinical academics, we are concerned about the lack of policy and research activity to develop interventions to reduce PIP in middle-aged adults. This is an issue effecting a significant proportion of the middle-aged population and it is vital to understand how to reduce this prescribing to avoid preventable harms and unnecessary cost to the health service. I urge the British Journal of Clinical Pharmacology to prioritise the issue of appropriate prescribing outside of the narrow focus on older adults by encouraging submissions and facilitating discourse among researchers, practitioners, and policymakers. This would contribute to our understanding of PIP in other age groups, including middle-aged adults, and help to develop interventions to address the issue in wider patient groups. I hope this letter serves as a catalyst for discussion and research on this pressing issue.Yours sincerely,References:1. O’Connor MN, Gallagher P, O’Mahony D. Inappropriate Prescribing Criteria, Detection and Prevention. Drugs Aging 2012; 29: 437-52.2. Gallagher PF, O’Connor MN, O’Mahony D. Prevention of Potentially Inappropriate Prescribing for Elderly Patients: A Randomized Controlled Trial Using STOPP/START Criteria. Clin Pharmacol Ther 2011; 89: 845-54.3. Naughton M, Moriarty F, Bailey J, Bowen L, Redmond P, Molokhia M. A systematic review of the prevalence, determinants, and impact of potentially inappropriate prescribing in middle-aged adults. Drugs & Therapy Perspectives 2022; 38: 21-32.4. Khatter A, Moriarty F, Ashworth M, Durbaba S, Redmond P. Prevalence and Predictors of Potentially Inappropriate Prescribing in Middle-Aged Adults: Repeated Cross-Sectional Study. British Journal of General Practice 2021: BJGP.2020.1048.5. Smeaton T, McElwaine P, Cullen J, Santos-Martinez MJ, Deasy E, Widdowson M, Grimes TC. A prospective observational pilot study of adverse drug reactions contributing to hospitalization in a cohort of middle-aged adults aged 45-64 years. Drugs and Therapy Perspectives 2020; 36: 123-30.6. Moriarty F, Cahir C, Bennett K, Hughes CM, Kenny RA, Fahey T. Potentially inappropriate prescribing and its association with health outcomes in middle-aged people: a prospective cohort study in Ireland. Bmj Open 2017; 7: 11.7. Jayesinghe R, Moriarty F, Khatter A, Durbaba S, Ashworth M, Redmond P. Cost outcomes of potentially inappropriate prescribing in middle-aged adults: A Delphi consensus and cross-sectional study. British Journal of Clinical Pharmacology 2022; 88: 3404-20.8. Spinewine A, Schmader KE, Barber N, Hughes C, Lapane KL, Swine C, Hanlon JT. Prescribing in elderly people 1 - Appropriate prescribing in elderly people: how well can it be measured and optimised? Lancet 2007; 370: 173-84.9. Clyne B, Fitzgerald C, Quinlan A, Hardy C, Galvin R, Fahey T, Smith SM. Interventions to Address Potentially Inappropriate Prescribing in Community-Dwelling Older Adults: A Systematic Review of Randomized Controlled Trials. J Am Geriatr Soc 2016; 64: 1210-22.10. Liew TM, Lee CS, Goh SKL, Chang ZY. The prevalence and impact of potentially inappropriate prescribing among older persons in primary care settings: multilevel meta-analysis. Age Ageing 2020; 49: 570-79.11. Dreischulte T, Donnan P, Grant A, Hapca A, McCowan C, Guthrie B. Safer Prescribing — A Trial of Education, Informatics, and Financial Incentives. New England Journal of Medicine 2016; 374: 1053-64.12. Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M, Elliott RA, Howard R, Kendrick D, Morris CJ, Prescott RJ, Swanwick G, Franklin M, Putman K, Boyd M, Sheikh A. A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis. Lancet 2012; 379: 1310-19.

Abstract Aims This bibliometric study aim to analyse the top 100 most cited articles since inception (1964-2021) and in the recent years (2015-2021) to explore the trends of most cited papers using data from the Scopus database. Methods We bibliometrically analysed the most cited articles (n=100) extracted from the Scopus online database from inception (1964-2021) and again in the recent years (2015-2021) using VOSviewer v1.6.15 and Publish or Perish v8 software. Information such as ATC/drug class, model type, software used, studied population, authors’ institutions, journals, collaborations between countries, and funding sources was extracted and compared. Results Majority of the studies (65%) described in the 100 most cited articles were population PK modelling studies, with the proportion of the population PKPD modelling studies increasing over time (from 30 to 43%). A large percentage of the impactful articles (43%) were published by top five journals, analysed adult data (84%) and used NONMEM® (80%), which has not changed much over time. Most of the impactful articles studied chemotherapeutic and immunomodulating (33%), anti-infective (29%), and central nervous system (22%) ATC class of drugs, with articles analysing immunosuppressant drug class increasing the most over time (from 10% to 18%). Conclusion We used a bibliometric approach and investigated research trends in top 100 most cited articles involving PK(/PD) modelling. Apart from the changes mentioned above most other metrics that we compared remained relatively unchanged over time

Forest restoration can mitigate biodiversity loss and climate change. Frugivorous facilitate restoration by bringing seeds to restoration areas. However, the species contribution. We studied seed rain in the Atlantic Forest, Brazil, examining bird diet and movement preferences. Using spatially-explicit individual-based models with frugivory interactions, bird movements and seed retention times data, we simulated seed rain in 10 landscapes along a fragmentation gradient (9 - 69% forest cover). Birds’ contribution to seed rain varied with traits and fragmentation. Small birds dispersed more seeds, but with lower carbon storage potential, while large birds dispersed larger seeds with greater carbon storage potential. Landscapes with > 38% forest cover and < 112 meters between fragments maintained effective seed dispersal, avoiding the need for active regeneration. By recognizing animals’ role in forest restoration, we aim to influence restoration and climate change mitigation policies, to go beyond carbon sequestration goals to counter current species extinction rates.

Portugal has a vast and intricate public health system that is being impacted by rising costs. The concepts of New Public Management, together with foreign experience, drove the creation of public-private partnership (PPP) models around the turn of the century to enhance the focus on performance and cost-effectiveness in healthcare. The first wave of PPPs, which began in 2001, featured an innovative and integrated concept that linked hospital infrastructure building and administration with clinical service delivery. The growth of PPP projects to avoid financial limitations reveals a lack of strategic thinking and the government’s short-term perspective on contracts lasting up to 30 years. Various procedural delays, miscalculated costs, and external advice on contract monitoring have exposed the public sector’s incapacity to handle complex projects and contracts properly. Following a widely criticized first wave that resulted in some clinical service delivery going back to the public sector, Portugal is now seeking to establish a second wave of hospital PPPs that do not include this problematic component. In response, this work suggests Portugal’s first strategic management method for managing healthcare PPPs. This paper initially examines the Portuguese legal framework before doing an organic SWOT analysis that combines the expertise of national PPP specialists. Filling existing knowledge gaps in public institutions, increasing tight collaboration and accountability with the private sector, and examining methods to contract management, renegotiation, and value-for-money evaluations are all recommended in the strategic formulation.

1 Abstract The numerical solution of partial differential equations is often performed on a numerical grid, where the grid points are used for estimating the partial derivatives. The grid can be fully static as in Eulerian type of solution method, or the grid points can move during the solution, which is the case in Lagrangian type of method. In the current article, a numerical solution method is presented , where the grid points are located on iso-contours of the two-dimensional field. The method calculates the local movement of the iso-contours according to an evolution equation described by the PDE, and the solution proceeds by moving the grid points towards the calculated direction. Additional stability is obtained by setting the grid points to move along the iso-contour line. To exemplify the application of the method, numerical examples are calculated for the two-dimensional diffusion equation. 2 Introduction In the previous study [1], the movement of a phase interface was simulated with level-set type method using a physical science based model which takes into account the transformation strains and carbon partitioning and diffusion. In that study the connection to the Allen-Cahn equation [1] was made, which connected it's solution to the level-set approach. As a extension of this idea, the connection between a general partial differential equation (PDE) with first order time derivative and the level set formulation is investigated in the current study. The current approach is closely connected with the level-set method [2], which is often applied for simulations involving phase boundary movement. Level set methods usually perform the solution of a partial differential equation (PDE) in a grid that is not based on the points contained on the isocontours. The level-set method can be used in any types of grids, even in completely Eu-lerian framework [3, 4], where the computational grid does not need to move.

In the study of sentencing disparities, class related hypotheses have received considerably less attention than explanations based on offenders' ethnicity. This is unfortunate since the two mechanisms are likely interrelated, at the very least as a result of their overlap in the population, with ethnic minorities being generally more deprived than the White majority. In this registered report we propose exploring the mediating and moderating effects between offenders' area deprivation and their ethnic background using a novel administrative dataset capturing all offences processed through the England and Wales Crown Court. Specifically, we seek to test whether the reported ethnic disparities in sentencing are explained away by area deprivation, and whether White offenders from deprived areas are more disadvantaged than the average ethnic minority offender. Results from this empirical analysis will shed new light on the underlying causes of sentencing disparities, but crucially-if deprivation is shown to play a major role in the generation of ethnic disparities-they will also help inform the adequate policy responses to redress this problem.

Synovial Hemangioma: A rare cause of chronic anterior knee painAbstract: Synovial hemangioma is an uncommon cause of chronic anterior knee pain. The non-specific clinical presentation leads to delay in diagnosis. MRI is diagnostic and should be considered early in evaluation to plan treatment and prevent functional disability. We present a case of unilateral synovial hemangioma of the knee in a child with pain, swelling and restricted knee mobility. Arthroscopy can be diagnostic and therapeutic in such cases.Introduction: Anterior knee pain is the pain occurring in the anterior and central part of the knee resulting in varying degrees of functional disability1. Evaluation of such pain is challenging as the symptoms are non-specific and the differential diagnosis is quite extensive. Patellofemoral pain syndrome (PFPS), chondromalacia patellae, Osgood-Schattler disease, Plica syndrome, patellar tendonitis and knee bursitis are amongst the common etiology of anterior knee pain2. Although bony tumors are commonly seen around the knee, tumors of the synovium are rarely seen and pose a diagnostic challenge in the evaluation of knee pain.Pigmented Villo Nodular Synovitis, Giant cell tumor, lipoma arborescence, synovial chondromatosis and Synovial Hemangioma are some of the proliferative lesions of the synovial tissue presenting as synovial tumor or tumor-like lesions.Synovial Hemangioma is a rare benign vascular tumor of the synovial membrane. It frequently affects adolescents and young adults and presents as unilateral chronic knee pain and swelling. The clinical diagnosis is often not possible due to non-specific clinical presentation and a wide array of differentials often leading to delayed diagnosis.We present as case of synovial hemangioma of the knee in a child presenting as chronic knee pain and swelling over a period of 1 year. We highlight the clinical presentation, radiological findings, management and expectant follow-up of this disease.Case ReportA 12-year-old child presented to us with a history of anterior knee pain for 1 year and swelling in the anterior aspect of knee for 6 months. The pain was progressive, localized to anterior and antero-medial aspect of the knee, sharp pin like character and aggravated with knee movements especially with squatting and climbing stairs. There were no history of trauma or constitutional symptoms. The knee pain had significantly affected the daily activities of the child including absence from school.On examination, a small tender swelling was present on the antero-medial aspect of knee joint adjacent to patellar tendon. The knee movements were painful with restricted terminal 30 degrees of knee flexion. There was no flexion deformity. Quadriceps wasting was noted.The child was evaluated with complete blood count, erythrocyte sedimentation rate, C- reactive protein, radiograph and an ultrasound of the knee. The reports were unremarkable (Figure 1).MRI was requested which revealed a well-defined, lobulated T1 hypointense, T2, PDFS and STIR hyperintense lesion in the infra patellar compartment of the knee measuring 3.2 X 4.1 X 3 cm. There were multiple tiny lobulated phleboliths within the lesion. The lesion was predominantly posterior to the patellar tendon with no obvious bony erosions or invasions (Figure 2,3).Based on these clinico-radiological features, synovial hemangioma was diagnosed.The child underwent arthroscopic excision and ablation. The tissue was sent for histopathology which confirmed Synovial Hemangioma. Post-operatively, follow-up was done at 2 weeks, 1, 3, 6 months and 1 year. Pain and swelling had completely subsided at 1 month and 1300 knee range of movement was regained at 3 months (Figure 4,5). There were no signs of recurrence of symptoms/lesion. Child was able to perform pain free routine activities and returned to school at 1 month.DiscussionSynovial Hemangioma is a rare tumor arising from the synovial membrane. It is benign vascular tumor accounting for less than 1% of all Hemangioma3. Knee is the frequently affected joint followed by elbow. It is commonly seen in adolescents and young adults presenting with chronic pain and swelling4.The location of pain, presence of swelling, and restricted movements are so non-specific that it is challenging to make an early diagnosis as was seen in our case. The child had the symptoms for 1 year and was undiagnosed due to this non-specificity.The differential diagnosis is very extensive in adolescents and includes PFPS, Osgood Schattler disease, Plica Syndrome, Patellar tendinitis, Osteochondritis dessicans, quadriceps tendinopathy, stress fractures, bursitis amongst commoner causes. Tumors of the synovium are very rare and include Pigmented Villo Nodular Synovitis, Giant cell tumor, lipoma arborescence, synovial chondromatosis and Synovial Hemangioma. Most synovial tumors result in pain due to inflammation. However, hemangioma usually results in mechanical pain5.Plain radiographs may not yield anything substantial especially in the initial stage. At a later stage, soft tissue shadow, phleboliths, joint erosions and arthritis changes may be visible. The diagnosis requires imaging studies like Ultrasonography and MRI. Ultrasound may show a homogenous hypoechoic lesion with internal vascularity6. However, USG is usually non diagnostic. The lesion was not clearly defined in our case due to its location in the infra patellar compartmental behind the patellar tendon.The gold standard for the diagnosis of synovial hemangioma is an MRI7. The lesion appears as an intra‐articular lobulated mass with a hypo or isointense signal on T1‐weighted images, hyperintensity on T2‐weighted images. The MRI defines various aspects of tumor like the size, its location and its extension to soft tissue. More importantly it helps to rule out other differential diagnoses8.MRI usually provides a clarity in diagnosis and hence a treatment plan can be made based on its features. In cases where radiological investigations are either not clear or is not possible (claustrophobia/younger child requiring anesthesia etc), Arthroscopy is definitely helpful as it not only aids in diagnosis but also provides an added advantage of therapeutic excision and ablation in the same setting. The lesions appear as bunch of grapes which bleeds on incision as was seen in our case.Histopathology is the ultimate confirmation for any biopsy lesion and so is true for synovial hemangioma. The lesions are usually small and hence therapeutic excision is performed without prior biopsy. Biopsy may still be indicated in extensive lesions posing diagnostic dilemma.There are several treatment options for Synovial Hemangioma. These include Sclerotherapy, Selective embolization, Laser ablation, Arthroscopic excision/ablation and Open excision9. We performed Arthroscopic excision and ablation. It has been reported that patients are rid of symptoms after any of the surgical procedures mentioned above. The child in our case was also pain free and resumed schooling and routine activities after 1 post operative month.Long term complications of synovial hemangioma are rare. Joint erosions, chronic arthritis and hemarthrosis are possible. Recurrence is rare after surgery, possibly seen in cases with large lesions with soft tissue extensions. To keep a check on this, long follow-up is required.ConclusionThe vast differential diagnosis of knee pain does not usually alert the possibility of rare Synovial Hemangioma. However, in cases presenting with chronic knee pain and swelling, especially in children and adolescents, the diagnosis of Synovial Hemangioma should be considered and MRI should be done to confirm and/or rule out differentials. Early diagnosis and treatment are required as the lesion has the potential to cause significant morbidity.MRI, Excision of the tumor and long-term follow-up are key features highlighted in this report on management of Synovial Hemangioma.References:Sala D, Silvestre A, Gomar-Sancho F. Intraosseous hyperpressure of the patella as a cause of anterior knee pain. Medscape Orth Sports Med. 1999;3:1–8.Houghton KM. Review for the generalist: evaluation of anterior knee pain. Pediatric Rheumatology Online Journal. 2007;5:8. doi:10.1186/1546-0096-5-8.Shyam K, Andrew D, Johny J. Progressively growing paediatric knee swelling: synovial haemangioma. BMJ Case Rep . 2021;14(9):e242694.Muramatsu K, Iwanaga R, Sakai T. Synovial hemangioma of the knee joint in pediatrics: our case series and review of literature. Eur J Orthop Surg Traumatol . 2019;29(6):1291‐1296.Slouma M, Hannech E, Msolli A, Dhahri R, Kouki S, Metoui L, Gharsallah I, Louzir B. Synovial hemangioma: A rare cause of chronic knee pain. Clin Case Rep. 2022 Jul 11;10(7):10.1002/ccr3.6007. doi: 10.1002/ccr3.6007. PMID: 35846940; PMCID: PMC9272066.Resnick D, Oliphant M. Hemophilia‐like arthropathy of the knee associated with cutaneous and synovial hemangiomas: report of 3 cases and review of the literature. Radiology . 1975;114(2):323‐326.Sasho T, Nakagawa K, Matsuki K, et al.Two cases of synovial haemangioma of the knee joint: Gd‐enhanced image features on MRI and arthroscopic excision. Knee . 2011;18(6):509‐511.Greenspan A, Azouz EM, Matthews J, Décarie JC. Synovial hemangioma: imaging features in eight histologically proven cases, review of the literature, and differential diagnosis. Skeletal Radiol . 1995;24(8):583‐590.Dunet B, Tournier C, Pallaro J, Boullet F, Fabre T. Arthroscopic treatment of an intra‐articular hemangioma in the posterior compartment of the knee. Orthop Traumatol Surg Res . 2014;100(3):337‐339.

A three-terminal memristor model is developed in order to improve the anti-interference performance of the memristor and address the issue that the resistance value of the conventional two-terminal memristor is readily impacted by voltage. In order to simulate and validate the function of the three-terminal memristor, the logic circuit and multiplication circuit are developed using this model in this work using the cadence ic617 program. According to the findings, the three-terminal memristor multiplication circuit uses less energy than the typical conventional multiplier circuit, consuming only 0.335 uW. The memristor offers the benefits of low power consumption, compact size, and great integratability as a nanoscale device.

Environmental enrichment (EE) has been shown to produce beneficial effects in addiction disorders; however, due to its configurational complexity, the underlying mechanisms are not yet fully elucidated. Recent evidence suggests that EE, acting as a metaplastic agent, may affect glutamatergic mechanisms underlying appetitive memory and, in turn, modulate reward-seeking behaviors: here, we have investigated such possibility following a brief EE exposure. Adult male Sprague-Dawley rats were exposed to EE for 22h and the expression of critical elements of the glutamate synapse was measured 2h after the end of EE in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and hippocampus (Hipp) brain areas, which are critical for reward and memory. We focused our investigation on the expression of NMDA and AMPA receptor subunits, their scaffolding proteins SAP102 and SAP97, vesicular and membrane glutamate transporters vGluT1 and GLT-1, and critical structural components such as proteins involved in morphology and function of glutamatergic synapses, PSD95 and Arc/Arg3.1. Our findings demonstrate that a brief EE exposure induces metaplastic changes in glutamatergic mPFC, NAc, and Hipp. Such changes are area-specific and involve postsynaptic NMDA/AMPA receptor subunit composition, as well as changes in the expression of their main scaffolding proteins, thus influencing the retention of such receptors at synaptic sites. Our data indicate that brief EE exposure is sufficient to dynamically modulate the glutamatergic synapses in mPFC-NAc-Hipp circuits, which may modulate rewarding and memory processes.

This article discusses the expanding application of botulinum neurotoxin in treating chronic migraines beyond aesthetic purposes. Special attention is given to the mechanisms underlying the therapeutic action of this treatment, namely, the blockade of neurotransmitter releases responsible for pain signal transmission, modulation of nociceptors, and its effects on the central nervous system. The article provides an analysis of existing literature, including preclinical and clinical data, to evaluate the efficacy and safety of using botulinum neurotoxin for the prevention and treatment of chronic migraine attacks. Additionally, the article explores novel approaches to using non-paralyzing botulinum molecules in the context of chronic migraines. These new molecules, such as Bitox or el-iBoNT, offer an alternative for patients who face limitations in using paralyzing forms of botulinum neurotoxin due to concerns about muscle function loss. The authors highlight research findings that confirm not only the effectiveness of these molecules in controlling chronic pain but also a reduced paralytic effect. The authors also discuss a potential cause for the diminished paralytic action of these molecules, specifically changes in the stereoisomeric parameters of the treatment. In summary, this article reviews current research that enhances our understanding of the application of botulinum neurotoxin in the context of chronic migraines and opens avenues for developing new, more efficient molecules for treating this condition.

Early life adversities alter the development of a still maturing nervous system and can have long-term consequences on its function at adult age. This include nociceptive circuits that are critical to shape an adaptive pain response to protect our organism from potentially damaging insults. As such, adult rats with a history of neonatal maternal separation (NMS) display a visceral and somatic nociceptive hypersensitivity and inefficient analgesic responses to stress. In this study, we have characterized the consequences of NMS on wide dynamic range neurons (WDR) in the spinal cord of anesthetized adult rat during the nociceptive processing of hot and cold noxious information. We found that WDR neurons of NMS rats display an excessive coding of mechanical and thermal information applied at the rat hindpaws. This nicely explains the hypernociceptive behaviors seen after noxious mechanical, cold and hot peripheral stimulation. A peripheral change in the expression of molecular transducers for these stimuli (i.e. TRPV1, TRPM8, TRPA1) does not seem to account for this general hyperexcitability. Instead, a decreased chloride-mediated inhibitory tone on WDR neurons may play a role as indicated by the abnormal elevated of the type 1 Na-K-Cl cotransporter transcripts. Altogether, we propose that long-term consequences of NMS is associated with a reduced spinal cord inhibition favoring the expression of pain hypersensitivity. We cannot exclude that this phenomenon is also present at supraspinal sites as other NMS-associated symptoms include also excessive anxiety and impaired sociability.

Backround and Aim: Autism is a clinically well-defined disorder that has no treatment yet. Other than behavior modification studies, medical treatments are still investigating. Rat is among the most frequently used experimental animals in such studies. Although various drugs cause autism in this animal species, propionic acid (PPA) was used in this study. Bismuth subsalicylate is frequently used in the treatment of gastrointestinal diseases in clinics and has anti-inflammatory and antacid effects. In our study, we examined the effects of bismuth in rats with autism using PPA. Materials and Methods: Thirty male rats were used in this study and 20 of them were given PPA intraperitoneally at 250 mg/kg/day for five days. Rats were randomly divided into three groups: Group 1 (no procedure was applied, n=10), Group 2 (intraperitoneal PPA+1 ml/kg/day % 0.9 salines given orally, n=10), and Group 3 (intraperitoneal PPA+60 mg/kg/day bismuth subsalicylate given orally, n = 10). After 15 days of treatment; behavioral tests, blood tests, and histopathology samples were taken. Results: A significant improvement was observed in autism-like behaviors in rats treated with bismuth. Tumor necrosis factor-alpha (TNF-α), Interleukin-17 (IL-17), IL-6, prostaglandin E2 (PGE2), and malondialdehyde (MDA) levels decreased, and brain-derived neurotrophic factor (BDNF) levels increased in the bismuth group. Conclusion: This study showed that bismuth can be used in addition to other treatments for autism. However, further studies on the subject are needed.

A document by Samit Lamichhane. Click on the document to view its contents.

This study presents a data-driven approach to extrapolate and predict Reynolds number effects on wind turbine airfoil polars. For this purpose a database is created using experimentally obtained aerodynamic coefficients from open literature for airfoils with thickness-to-chord ratio (t/c) values in the range of 15% to 30% in order to be more relevant to wind turbine blade design applications. All available airfoil geometries are parameterized using PARSEC methodology, and a Pareto analysis is performed to understand the sensitivity of maximum lift coefficient ( C l max ) and minimum drag coefficient ( C d min ) variations to geometrical inputs as well as to the Reynolds number using statistical tools. Based on this analysis, response surfaces are generated to predict C l max and C d min of a given airfoil operating at a given Reynolds number. These predicted values are then utilized in a power-law based estimation methodology to obtain predictions for full polars, which are then compared to experimental data for selected airfoil test cases. The results show that the response surfaces generated through the current data-driven approach as well as the full polar prediction methodology show better agreement with experimental results compared to those obtained using numerical simulations-based extrapolation schemes. For airfoil types that might be under-represented in the database (such as symmetrical airfoils), the prediction results can be erroneous, especially at very high Reynolds numbers that are not in the constructed database. In the power-law based polar prediction methodology, utilizing a reference Reynolds number that is closer to the target value provides more accurate predictions for both lift and drag polars.

Clinical characteristics and literature review of chronic active Epstein-Barr virus-associated enteritisYaJie Meng1+, RenDong Li2+, JieWen Ding1, Bo Xiang1,Qin Wang1,Min Wang1 *and KeJiang Tang1**Correspondence:KeJiang Tang :tttkkj@163.com and Min Wang+Equal contributors.1Department of Gastroenterology, The People’s Hospital of Nanchuan, No. 16South Street, Nanchuan District, Chongqing 408400, China2The People’s Hospital of Nanchuan, No. 16 South Street, Nanchuan District, Chongqing 408400, China