Now showing items 41-60 of 18799

    • Span of regularization for solution of inverse problems with application to magnetic resonance relaxometry of the brain.

      Bi, Chuan; Ou, M Yvonne; Bouhrara, Mustapha; Spencer, Richard G (2022-11-23)
      We present a new regularization method for the solution of the Fredholm integral equation (FIE) of the first kind, in which we incorporate solutions corresponding to a range of Tikhonov regularizers into the end result. This method identifies solutions within a much larger function space, spanned by this set of regularized solutions, than is available to conventional regularization methods. An additional key development is the use of dictionary functions derived from noise-corrupted inversion of the discretized FIE. In effect, we combine the stability of solutions with greater degrees of regularization with the resolution of those that are less regularized. The span of regularizations (SpanReg) method may be widely applicable throughout the field of inverse problems.
    • Persistence and Evolution of Vaginal Bacterial Strains over a Multiyear Time Period.

      France, Michael; Ma, Bing; Ravel, Jacques (2022-11-22)
      It is not clear whether the bacterial strains that comprise our microbiota are mostly long-term colonizers or transient residents. Studies have demonstrated decades-long persistence of bacterial strains within the gut, but persistence at other body sites has yet to be determined. The vaginal microbiota (VMB) is often dominated by Lactobacillus, although it is also commonly comprised of a more diverse set of other facultative and obligate anaerobes. Longitudinal studies have demonstrated that these communities can be stable over several menstrual cycles or can fluctuate temporally in species composition. We sought to determine whether the bacterial strains that comprise the VMB were capable of persisting over longer time periods. We performed shotgun metagenomics on paired samples from 10 participants collected 1 and 2 years apart. The resulting sequences were de novo assembled and binned into high-quality metagenome assembled genomes. Persistent strains were identified based on the sequence similarity between the genomes present at the two time points and were found in the VMB of six of the participants, three of which had multiple persistent strains. The VMB of the remaining four participants was similar in species composition at the two time points but was comprised of different strains. For the persistent strains, we were able to identify the mutations that were fixed in the populations over the observed time period, giving insight into the evolution of these bacteria. These results indicate that bacterial strains can persist in the vagina for extended periods of time, providing an opportunity for them to evolve in the host microenvironment. IMPORTANCE: The stability of strains within the vaginal microbiota is largely uncharacterized. Should these strains be capable of persisting for extended periods of time, they could evolve within their host in response to selective pressures exerted by the host or by other members of the community. Here, we present preliminary findings demonstrating that bacterial strains can persist in the vagina for at least 1 year. We further characterized in vivo evolution of the persistent strains. Several participants were also found to not have persistent strains, despite having a vaginal microbiota (VMB) with similar species composition at the two time points. Our observations motivate future studies that collect samples from more participants, at more time points, and over even longer periods of time. Understanding which strains persist, what factors drive their persistence, and what selective pressures they face will inform the development and delivery of rationally designed live biotherapeutics for the vagina.
    • Elevated Ca2+ the triad junction underlies dysregulation of Ca2+ signaling in dysferlin-null skeletal muscle.

      Lukyanenko, Valeriy; Muriel, Joaquin; Garman, Daniel; Breydo, Leonid; Bloch, Robert J (2022-11-03)
      Dysferlin-null A/J myofibers generate abnormal Ca2+ transients that are slightly reduced in amplitude compared to controls. These are further reduced in amplitude by hypoosmotic shock and often appear as Ca2+ waves (Lukyanenko et al., J. Physiol., 2017). Ca2+ waves are typically associated with Ca2+-induced Ca2+ release, or CICR, which can be myopathic. We tested the ability of a permeable Ca2+ chelator, BAPTA-AM, to inhibit CICR in injured dysferlin-null fibers and found that 10-50 nM BAPTA-AM suppressed all Ca2+ waves. The same concentrations of BAPTA-AM increased the amplitude of the Ca2+ transient in A/J fibers to wild type levels and protected transients against the loss of amplitude after hypoosmotic shock, as also seen in wild type fibers. Incubation with 10 nM BAPTA-AM led to intracellular BAPTA concentrations of ∼60 nM, as estimated with its fluorescent analog, Fluo-4AM. This should be sufficient to restore intracellular Ca2+ to levels seen in wild type muscle. Fluo-4AM was ∼10-fold less effective than BAPTA-AM, however, consistent with its lower affinity for Ca2+. EGTA, which has an affinity for Ca2+ similar to BAPTA, but with much slower kinetics of binding, was even less potent when introduced as the -AM derivative. By contrast, a dysferlin variant with GCaMP6fu in place of its C2A domain accumulated at triad junctions, like wild type dysferlin, and suppressed all abnormal Ca2+ signaling. GCaMP6fu introduced as a Venus chimera did not accumulate at junctions and failed to suppress abnormal Ca2+ signaling. Our results suggest that leak of Ca2+ into the triad junctional cleft underlies dysregulation of Ca2+ signaling in dysferlin-null myofibers, and that dysferlin's C2A domain suppresses abnormal Ca2+ signaling and protects muscle against injury by binding Ca2+ in the cleft.
    • Role of responsive neurostimulation and immunotherapy in refractory epilepsy due to autoimmune encephalitis: A case report.

      Chen, Stephanie H; O'Dea, Pamela K; Sianati, Bahareh; Benavides, David R (2022-11-02)
      Autoimmune encephalitis (AE) frequently presents with seizures in the acute setting. Seizures are often refractory to anti-seizure medications (ASM) but have been shown to be responsive to immunomodulatory therapies. A subset of patients with AE continues to have refractory epilepsy, recently named "autoimmune-associated epilepsy (AAE)," for years after the acute AE presentation. Optimal treatment for AAE has not been determined. Furthermore, the efficacy of neuromodulation and immunotherapy has not been well established in AAE. Here, we report a patient with probable autoantibody negative AE who initially presented with new onset refractory status epilepticus (NORSE). After his acute presentation, he continued to have frequent seizures that were refractory to four ASMs at therapeutic doses. A responsive neurostimulation (RNS®, NeuroPace) system was implanted for diagnostic and therapeutic purposes, with minimal change in seizure frequency. Due to continued frequent seizures despite ASMs and neurostimulation, he underwent a trial of immunotherapy consisting of high-dose intravenous (IV) corticosteroids and intravenous immunoglobulin (IVIG). Despite the addition of immunotherapy to his treatment regimen, the patient experienced no significant clinical or electrographic change in seizure frequency. This case does not support the use of immunotherapy for treatment of AAE and illustrates the need for consensus guidelines in the management of patients with AAE. Further, the use of electrocorticography (ECoG) data provided an objective surrogate measure of seizure frequency; this may support the role for early neuromodulation in the management of AAE.
    • Social communication pathways to COVID-19 vaccine side-effect expectations and experience.

      Clemens, Kelly S; Faasse, Kate; Tan, Winston; Colagiuri, Ben; Colloca, Luana; Webster, Rebecca; Vase, Lene; Jason, Emily; Geers, Andrew L (2022-11-10)
      Objective: Negative beliefs about medication and vaccine side-effects can spread rapidly through social communication. This has been recently documented with the potential side-effects from the COVID-19 vaccines. We tested if pre-vaccination social communications about side-effects from personal acquaintances, news reports, and social media predict post-vaccination side-effect experiences. Further, as previous research suggests that side-effects can be exacerbated by negative expectations, we assessed if personal expectations mediate the relationships between social communication and side-effect experience. Method: In a prospective longitudinal survey (N = 551), COVID-19 vaccine side-effect information from three sources-social media posts, news reports, and first-hand accounts from personal acquaintances-as well as side-effect expectations, were self-reported pre-vaccination. Vaccination side-effect experience was assessed post-vaccination. Results: In multivariate regression analyses, the number of pre-vaccination social media post views (β = 0.17) and impressions of severity conveyed from personal acquaintances (β = 0.42) significantly predicted an increase in pre-vaccination side-effect expectations, and the same variables (βs = 0.11, 0.14, respectively) predicted post-vaccination side-effect experiences. Moreover, pre-vaccination side-effect expectations mediated the relationship between both sources of social communication and experienced side-effects from a COVID-19 vaccination. Conclusions: This study identifies links between personal acquaintance and social media communications and vaccine side-effect experiences and provides evidence that pre-vaccination expectations account for these relationships. The results suggest that modifying side-effect expectations through these channels may change the side-effects following a COVID-19 vaccination as well as other publicly discussed vaccinations and medications.
    • Increased levels of anti-PfCSP antibodies in post-pubertal females versus males immunized with PfSPZ Vaccine does not translate into increased protective efficacy.

      KC, Natasha; Church, L W Preston; Riyahi, Pouria; Chakravarty, Sumana; Seder, Robert A; Epstein, Judith E; Lyke, Kirsten E; Mordmüller, Benjamin; Kremsner, Peter G; Sissoko, Mahamadou S; et al. (2022-10-25)
      Background: While prior research has shown differences in the risk of malaria infection and sickness between males and females, little is known about sex differences in vaccine-induced immunity to malaria. Identifying such differences could elucidate important aspects of malaria biology and facilitate development of improved approaches to malaria vaccination. Methods: Using a standardized enzyme-linked immunosorbent assay, IgG antibodies to the major surface protein on Plasmodium falciparum (Pf) sporozoites (SPZ), the Pf circumsporozoite protein (PfCSP), were measured before and two weeks after administration of a PfSPZ-based malaria vaccine (PfSPZ Vaccine) to 5-month to 61-year-olds in 11 clinical trials in Germany, the US and five countries in Africa, to determine if there were differences in vaccine elicited antibody response between males and females and if these differences were associated with differential protection against naturally transmitted Pf malaria (Africa) or controlled human malaria infection (Germany, the US and Africa). Results: Females ≥ 11 years of age made significantly higher levels of antibodies to PfCSP than did males in most trials, while there was no indication of such differences in infants or children. Although adult females had higher levels of antibodies, there was no evidence of improved protection compared to males. In 2 of the 7 trials with sufficient data, protected males had significantly higher levels of antibodies than unprotected males, and in 3 other trials protected females had higher levels of antibodies than did unprotected females. Conclusion: Immunization with PfSPZ Vaccine induced higher levels of antibodies in post-pubertal females but showed equivalent protection in males and females. We conclude that the increased antibody levels in post-pubertal females did not contribute substantially to improved protection. We hypothesize that while antibodies to PfCSP (and PfSPZ) may potentially contribute directly to protection, they primarily correlate with other, potentially protective immune mechanisms, such as antibody dependent and antibody independent cellular responses in the liver.
    • The quarantine paradox: The economic cost of the increase in violence against women and girls in Sub-Saharan Africa.

      Atalay, Rediet; Ayele, Girma; Clarke, Saba; Michael, Miriam (2022-10-25)
      The worst global crisis since the Second World War, the COVID-19 pandemic, as of July 2022, has killed around 6.3 million people globally (1) and interrupted lives in countless ways. In response to the pandemic, public health officials implemented quarantine as a protective measure, while also leaving women and children to fell victim to increased violence: therein lies the paradox of the quarantine. Although “home quarantine” has proven an effective measure to fight pandemics since the fourteenth century, it has also created a pandemic of violence that dramatically increased the number of women abused by their intimate partners and the frequency of violent encounters. According to UN-Women (2), “as the pandemic raged on, the threat of a ‘shadow pandemic’ of violence against women emerged.” In addition to incurring heavy tolls for the victims, i.e., trauma and decreased quality of life, violence against women (VAW) also generates dire social and economic costs. The WHO argues that women suffer isolation, inability to work, lack of participation in regular activities, and failure to take care of themselves and their families due to intimate partners and sexual violence (3). The global cost of VAW is estimated to be 1.5 trillion dollars, which increased during the pandemic (4). The sub-Saharan African (SSA) region has the highest VAW prevalence worldwide, significantly worsening during the pandemic. This is alarming because VAW’s social and economic burden further exacerbates the already high poverty rates in the region. In addition, women in these areas lack access to essential services, a plight that worsened during the lockdown. We will discuss the prevalence of VAW in the SSA region during COVID-1
    • Bayesian multisource data integration for explainable brain-behavior analysis.

      Chen, Rong (2022-10-28)
      Different data sources can provide complementary information. Moving from a simple approach based on using one data source at a time to a systems approach that integrates multiple data sources provides an opportunity to understand complex brain disorders or cognitive processes. We propose a data fusion method, called Bayesian Multisource Data Integration, to model the interactions among data sources and behavioral variables. The proposed method generates representations from data sources and uses Bayesian network modeling to associate representations with behavioral variables. The generated Bayesian network is transparent and easy to understand. Bayesian inference is used to understand how the perturbation of representation is related to behavioral changes. The proposed method was assessed on the simulated data and data from the Adolescent Brain Cognitive Development study. For the Adolescent Brain Cognitive Development study, we found diffusion tensor imaging and resting-state functional magnetic resonance imaging were synergistic in understanding the fluid intelligence composite and the total score composite in healthy youth (9-11 years of age).
    • Editorial: "Source-tracking," molecular epidemiology and antigenic diversity of SARS-CoV-2 infections causing coronavirus disease 2019, COVID-19.

      Narh, Charles A; Manickum, Cordelia; Vajravelu, Bathri; Zella, Davide; Mosi, Lydia (2022-10-25)
      In December 2019, Chinese Health Authorities reported the first cases of COVID-19, caused by SARS-CoV-2, to the WHO Country Office in China (Zhu et al.), noting a spectrum of symptoms from mild to severe pneumonia. Following global spread of the virus, the World Health Organization (WHO), on 30 January 2020, declared COVID-19 a Public Health Emergency of International Concern (Jee, 2020). As of 22 August 2022, there have been more than 590 million cases and over 6.4 million deaths due to the SARS-CoV-2 pandemic, with several thousands of cases being confirmed daily across the WHO regions (WHO, 2022). This Research Topic sought to publish both research and review articles on the epidemiology, population genetics, antigenic diversity, transmission dynamics and evolution of SARS-CoV-2. We, the editorial team, encouraged submissions from different disciplines of SARS-CoV-2 research, and recommended 36 articles for publication following at least two peer-reviews. We hope these articles, briefly summarised with their major findings, appeal to the wider readership of the scientific community, to inform further research, clinical practice and public health control of the COVID-19 pandemic.
    • Characterization of the interactome profiling of DnaK in cancer cells reveals interference with key cellular pathways.

      Curreli, Sabrina; Benedetti, Francesca; Yuan, Weirong; Munawwar, Arshi; Cocchi, Fiorenza; Gallo, Robert C; Sherman, Nicholas E; Zella, Davide (2022-10-28)
      Chaperone proteins are redundant in nature and, to achieve their function, they bind a large repertoire of client proteins. DnaK is a bacterial chaperone protein that recognizes misfolded and aggregated proteins and drives their folding and intracellular trafficking. Some Mycoplasmas are associated with cancers, and we demonstrated that infection with a strain of Mycoplasma fermentans isolated in our lab promoted lymphoma in a mouse model. Its DnaK is expressed intracellularly in infected cells, it interacts with key proteins to hamper essential pathways related to DNA repair and p53 functions and uninfected cells can take-up extracellular DnaK. We profile here for the first time the eukaryotic proteins interacting with DnaK transiently expressed in five cancer cell lines. A total of 520 eukaryotic proteins were isolated by immunoprecipitation and identified by Liquid Chromatography Mass Spectrometry (LC-MS) analysis. Among the cellular DnaK-binding partners, 49 were shared between the five analyzed cell lines, corroborating the specificity of the interaction of DnaK with these proteins. Enrichment analysis revealed multiple RNA biological processes, DNA repair, chromatin remodeling, DNA conformational changes, protein-DNA complex subunit organization, telomere organization and cell cycle as the most significant ontology terms. This is the first study to show that a bacterial chaperone protein interacts with key eukaryotic components thus suggesting DnaK could become a perturbing hub for the functions of important cellular pathways. Given the close interactions between bacteria and host cells in the local microenvironment, these results provide a foundation for future mechanistic studies on how bacteria interfere with essential cellular processes.
    • Integrating Adolescent Mental Health into HIV Prevention and Treatment Programs: Can Implementation Science Pave the Path Forward?

      Boshe, Judith; Brtek, Veronica; Beima-Sofie, Kristin; Braitstein, Paula; Brooks, Merrian; Denison, Julie; Donenberg, Geri; Kemigisha, Elizabeth; Memiah, Peter; Njuguna, Irene; et al. (2022-11-02)
      Adolescent mental health (AMH) is a critical driver of HIV outcomes, but is often overlooked in HIV research and programming. The implementation science Exploration, Preparation, Implementation, Sustainment (EPIS) framework informed development of a questionnaire that was sent to a global alliance of adolescent HIV researchers, providers, and implementors working in sub-Saharan Africa with the aim to (1) describe current AMH outcomes incorporated into HIV research within the alliance; (2) identify determinants (barriers/gaps) of integrating AMH into HIV research and care; and (3) describe current AMH screening and referral systems in adolescent HIV programs in sub-Saharan Africa. Respondents reported on fourteen named studies that included AMH outcomes in HIV research. Barriers to AMH integration in HIV research and care programs were explored with suggested implementation science strategies to achieve the goal of integrated and sustained mental health services within adolescent HIV programs. © 2022, The Author(s).
    • International Validation of a Methicillin-Resistant Staphylococcus aureus Risk Assessment Tool for Skin and Soft Tissue Infections

      Zasowski, E. J.; Trinh, T. D.; Claeys, K. C.; Dryden, M.; Shlyapnikov, S.; Bassetti, M.; Carnelutti, A.; Khachatryan, N.; Kurup, A.; Pulido Cejudo, Abraham; et al. (2022-11-01)
      Introduction: To promote judicious prescribing of methicillin-resistant Staphylococcus aureus (MRSA)-active therapy for skin and soft tissue infections (SSTI), we previously developed an MRSA risk assessment tool. The objective of this study was to validate this risk assessment tool internationally. Methods: A multicenter, prospective cohort study of adults with purulent SSTI was performed at seven international sites from July 2016 to March 2018. Patient MRSA risk scores were computed as follows: MRSA infection/colonization history (2 points); previous hospitalization, previous antibiotics, chronic kidney disease, intravenous drug use, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), diabetes with obesity (1 point each). Predictive performance of MRSA surveillance percentage, MRSA risk score, and estimated MRSA probability (surveillance percentage adjusted by risk score) were quantified using the area under the receiver operating characteristic curves (aROC) and compared. Performance characteristics of different risk score thresholds across varying baseline MRSA prevalence were examined. Results: Two hundred three patients were included. Common SSTI were wounds (28.6%), abscess (25.1%), and cellulitis with abscess (20.7%). Patients with higher risk scores were more likely to have MRSA (P < 0.001). The MRSA risk score aROC (95%CI) [0.748 (0.678–0.819)] was significantly greater than MRSA surveillance percentage [0.646 (0.569–0.722)] (P = 0.016). Estimated MRSA probability aROC [0.781 (0.716–0.845)] was significantly greater than surveillance percentage (P < 0.001) but not the risk score (P = 0.192). The estimated negative predictive value (NPV) of an MRSA score ≥ 1 (i.e., a score of 0) was greater than 90% when MRSA prevalence was 30% or less. Conclusion: The MRSA risk score and estimated MRSA probability were significantly more predictive of MRSA compared with surveillance percentage. An MRSA risk score of zero had high predictive value and could help avoid unnecessary empiric MRSA coverage in low-acuity patients. Further study, including impact of such risk assessment tools on prescribing patterns and outcomes are required before implementation. © 2022, The Author(s).
    • Complete identity and expression of StfZ, the cis-antisense RNA to the mRNA of the cell division gene ftsZ, in Escherichia coli

      Anand, Deepak; Jakkala, Kishor; Nair, Rashmi Ravindran; Sharan, Deepti; Pradhan, Atul; Mukkayyan, Nagaraja; Ajitkumar, Parthasarathi (2022-10-19)
      Bacteria regulate FtsZ protein levels through transcriptional and translational mechanisms for proper cell division. A cis-antisense RNA, StfZ, produced from the ftsA-ftsZ intergenic region, was proposed to regulate FtsZ level in Escherichia coli. However, its structural identity remained unknown. In this study, we determined the complete sequence of StfZ and identified the isoforms and its promoters. We find that under native physiological conditions, StfZ is expressed at a 1:6 ratio of StfZ:ftsZ mRNA at all growth phases from three promoters as three isoforms of 366, 474, and 552 nt RNAs. Overexpression of StfZ reduces FtsZ protein level, increases cell length, and blocks cell division without affecting the ftsZ mRNA stability. We did not find differential expression of StfZ under the stress conditions of heat shock, cold shock, or oxidative stress, or at any growth phase. These data indicated that the cis-encoded StfZ antisense RNA to ftsZ mRNA may be involved in the fine tuning of ftsZ mRNA levels available for translation as per the growth-phase-specific requirement at all phases of growth and cell division. Copyright © 2022 Anand, Jakkala, Nair, Sharan, Pradhan, Mukkayyan and Ajitkumar.
    • Creating 3d printed assistive technology through design shortcuts: Leveraging digital fabrication services to incorporate 3d printing into the physical therapy classroom

      Higgins, Erin; Easley, William Berkley; Gordes, Karen L.; Hurst, Amy; Hamidi, Foad (2022-10-22)
      Digital fabrication methods have been shown to be an effective method for producing customized assistive technology (AT). However, the skills required to utilize these tools currently require a high level of technical skill. Previous research showed that integration of these skills within physical therapy training is appropriate but that the level of technical difficulty required can be an issue. We worked to address these issues by introducing a group of PT students to maker concepts and having them develop custom AT for real end users with the help of makers. We present three considerations when integrating making into PT curriculum: 1) including all stakeholders, 2) developing interdisciplinary competencies for PTs and makers, and 3) leveraging academic training programs to connect makers and PT students. In this paper, we contribute to knowledge on how to facilitate the 3D printing of customized ATs for PT students by connecting them with a community organization that provides digital fabrication services and technical expertise. By connecting multiple stakeholders (i.e., PT students, digital fabricators, and AT users), we offer an approach to overcome time and capacity constraints of PT students to utilize advanced fabrication technologies to create customized ATs through connecting them to professional makers. © 2022 ACM.
    • Adjuvant stereotactic radiosurgery with or without postoperative fractionated radiation therapy in adults with skull base chordomas: a systematic review.

      Bin-Alamer, Othman; Mallela, Arka N; Palmisciano, Paolo; Gersey, Zachary C; Elarjani, Turki; Labib, Mohamed A; Zenonos, Georgios A; Dehdashti, Amir R; Sheehan, Jason P; Couldwell, William T; et al. (2022-11)
      OBJECTIVE: The objective of this retrospective study was to compare the survival of patients with biopsy-proven skull base chordoma who had undergone stereotactic radiosurgery (SRS) with versus without prior fractionated radiation therapy (RT). METHODS: Relevant articles from database inception to September 2021 were retrieved from the PubMed, Scopus, Web of Science, and Cochrane databases for a systematic review of treatment protocols. Studies were included if they 1) involved adult patients (age ≥ 18 years) with histologically and radiologically confirmed chordomas located within the clival skull base region and treated with SRS; 2) reported data on clinical features, SRS protocols, and outcomes; and 3) were written in the English language. Studies were excluded if they 1) were literature reviews, case reports, technical notes, abstracts, or autopsy reports; 2) did not clearly differentiate the data of patients with chordomas from the data of patients with different tumors or the data of patients with chordomas in locations other than the skull base; or 3) lacked histological confirmation or treatment and outcome data. Extracted data included the following: study author and publication year, patient age and sex, symptoms, cranial nerve involvement, invaded structures, lesion size, treatment modality, surgical details, histopathological type, RT modality, SRS parameters, complications, postradiosurgery outcomes, complications, and survival outcomes. RESULTS: After the selection process, 15 articles describing 130 patients met the study eligibility criteria, including 94 patients who had undergone postresection SRS (NoRT group) and 36 who had undergone postresection fractionated RT and subsequent SRS (RT group). The NoRT and RT groups were comparable in age (51.3 vs 47.4 years, respectively), sex (57.1% vs 58.3% male), tumor volume (9.5 vs 11.2 cm3), SRS treatment parameters (maximum dose: 35.4 vs 42.2 Gy, marginal dose: 19.6 vs 20.6 Gy, treatment isodose line: 60.2% vs 65.2%), and SRS adverse effects (10.9% vs 17.6%). For the entire cohort, the 3-, 5-, and 10-year progression-free survival (PFS) rates were 23%, 9%, and 3%, respectively, and the overall survival (OS) rates were 94%, 82%, and 76%, respectively. In the NoRT group, SRS was adjuvant treatment after resection in 38 patients (40.4%), salvage treatment for recurrent tumor treated with resection alone in 10 (10.6%), and not specified in 46 (48.9%). In the RT group, SRS was boost treatment in 9 patients (25.0%), salvage treatment after recurrence in 22 (61.1%), and not specified in 5 (13.9%). There was no difference between the two groups in terms of median PFS (24.0 months [Q1 34.0, Q3 15.0] vs 23.8 months [34.0, 18.0], respectively; p = 0.8) or median OS (293.0 months [not reached, 137.4] vs not reached [not reached, 48.0], respectively; p = 0.36). The adverse radiation effect rates were comparable between the groups (10.9% vs 17.6%, respectively; p = 0.4). CONCLUSIONS: The role of SRS in the management of skull base chordomas is still evolving. This systematic literature review of biopsy-proven chordoma revealed that tumor control and survival rates for SRS alone after chordoma surgery were not inferior to those encountered after SRS plus fractionated RT.
    • Effects of Electroconvulsive Therapy on Glycemic Control in Type 1 Diabetes.

      Stefan, Simona; Alzedaneen, Yazan; Whitlatch, Hilary B; Malek, Rana; Munir, Kashif (2022-10-12)
      Electroconvulsive therapy (ECT) is a treatment modality for refractory depression and other severe psychiatric diseases. Depression is a common comorbid condition of diabetes. Yet, evidence regarding the effect of ECT on glycemic control in patients with diabetes is limited and conflicting, with reports of both exacerbation and amelioration of hyperglycemia. A 52-year-old Caucasian man with a history of type 1 diabetes mellitus (T1DM) was admitted for ECT therapy in the setting of worsening depression refractory to medical treatment. Pre-admission glycemic control was poor. He had significant glycemic variability during his hospitalization with hyper- and hypoglycemia. He required near-daily adjustment of insulin doses and distinct "ECT day" and "non-ECT day" insulin regimens. By the conclusion of his ECT course, in addition to achieving favorable psychiatric recovery, he had a marked improvement in glycemic control. This suggests that the treatment of depression may have beneficial effects on improving glycemic control in patients with T1DM.
    • The prognostic and diagnostic value of intraleukocytic malaria pigment in patients with severe falciparum malaria.

      Srinamon, Ketsanee; Watson, James A; Silamut, Kamolrat; Intharabut, Benjamas; Phu, Nguyen Hoan; Diep, Pham Thi; Lyke, Kirsten E; Fanello, Caterina; von Seidlein, Lorenz; Chotivanich, Kesinee; et al. (2022-11-12)
      Severe falciparum malaria is a major cause of death in tropical countries, particularly in African children. Rapid and accurate diagnosis and prognostic assessment are critical to clinical management. In 6027 prospectively studied patients diagnosed with severe malaria we assess the prognostic value of peripheral blood film counts of malaria pigment containing polymorphonuclear leukocytes (PMNs) and monocytes. We combine these results with previously published data and show, in an individual patient data meta-analysis (n = 32,035), that the proportion of pigment containing PMNs is predictive of in-hospital mortality. In African children the proportion of pigment containing PMNs helps distinguish severe malaria from other life-threatening febrile illnesses, and it adds to the prognostic assessment from simple bedside examination, and to the conventional malaria parasite count. Microscopy assessment of pigment containing PMNs is simple and rapid, and should be performed in all patients hospitalised with suspected severe malaria.
    • Effect of the Modified Methacrylate-Based Root Canal Sealer in Single-Cone Technique.

      Fan, Yu; Wang, Zheng; Sun, Yan; Guo, Xiao; Wang, Haohao; Xu, Hockin H K; Wang, Suping; Zhou, Xuedong; Li, Bolei; Cheng, Lei (2022-10-23)
      This study aimed to modify EndoREZ with 2.5% dimethylaminododecyl methacrylate (DMADDM) and 1% magnetic nanoparticles (MNP) to study its sealing property, penetration and long-term antibacterial and therapeutic effect in the single-cone technique (SCT) compared with EndoREZ and iRoot SP. Thirty single-root human maxillary premolars were assigned into three groups and obturated with three different root canal sealers by SCT. Every specimen was then scanned using micro-CT to analyze void fraction, and void volumes and confocal laser scanning microscope (CLSM) was used to study the dentin penetration. The long-term antimicrobial effects were tested in vitro before and after aging 1 and 4 weeks by the single-strain Enterococcus faecalis biofilm model. In addition, the beagle canine model of apical periodontitis (AP) was utilized to judge and compare the therapeutic effect of three sealers in SCT. The void fraction and void volumes of the modified root canal sealer were not significantly different from iRoot SP (p &gt; 0.05) but were lower than EndoREZ (p &lt; 0.05). The modified root canal sealant displayed a greater penetration, long-term antibacterial property, and treatment effect than the other groups (p &lt; 0.05). This indicated that after being modified with DMADDM and MNP, it showed better performance in SCT.
    • Supramolecular Protein-Polyelectrolyte Assembly at Near Physiological Conditions-Water Proton NMR, ITC, and DLS Study.

      Marin, Alexander; Taraban, Marc B; Patel, Vanshika; Yu, Y Bruce; Andrianov, Alexander K (2022-11-01)
      The in vivo potency of polyphosphazene immunoadjuvants is inherently linked to the ability of these ionic macromolecules to assemble with antigenic proteins in aqueous solutions and form physiologically stable supramolecular complexes. Therefore, in-depth knowledge of interactions in this biologically relevant system is a prerequisite for a better understanding of mechanism of immunoadjuvant activity. Present study explores a self-assembly of polyphosphazene immunoadjuvant-PCPP and a model antigen-lysozyme in a physiologically relevant environment-saline solution and neutral pH. Three analytical techniques were employed to characterize reaction thermodynamics, water-solute structural organization, and supramolecular dimensions: isothermal titration calorimetry (ITC), water proton nuclear magnetic resonance (wNMR), and dynamic light scattering (DLS). The formation of lysozyme-PCPP complexes at near physiological conditions was detected by all methods and the avidity was modulated by a physical state and dimensions of the assemblies. Thermodynamic analysis revealed the dissociation constant in micromolar range and the dominance of enthalpy factor in interactions, which is in line with previously suggested model of protein charge anisotropy and small persistence length of the polymer favoring the formation of high affinity complexes. The paper reports advantageous use of wNMR method for studying protein-polymer interactions, especially for low protein-load complexes.
    • The Preventive Effect of A Magnetic Nanoparticle-Modified Root Canal Sealer on Persistent Apical Periodontitis.

      Guo, Xiao; Sun, Yan; Wang, Zheng; Ren, Biao; Xu, Hockin H K; Peng, Xian; Li, Mingyun; Wang, Suping; Wang, Haohao; Wu, Yao; et al. (2022-10-28)
      Persistent apical periodontitis is a critical challenge for endodontists. Developing root canal filling materials with continuous antibacterial effects and tightly sealed root canals are essential strategies to avoid the failure of root canal therapy and prevent persistent apical periodontitis. We modified the EndoREZ root canal sealer with the antibacterial material dimethylaminododecyl methacrylate (DMADDM) and magnetic nanoparticles (MNPs). The mechanical properties of the modified root canal sealer were tested. The biocompatibility of this sealer was verified in vitro and in vivo. Multispecies biofilms were constructed to assess the antibacterial effects of the modified root canal sealer. We applied magnetic fields and examined the extent of root canal sealer penetration in vitro and in vivo. The results showed that EndoREZ sealer containing 2.5% DMADDM and 1% MNP had biological safety and apical sealing ability. In addition, the modified sealer could increase the sealer penetration range and exert significant antibacterial effects on multispecies biofilms under an external magnetic field. According to the in vivo study, the apices of the root canals with the sealer containing 2.5% DMADDM and 1% MNP showed no significant resorption and exhibited only a slight increase in the periodontal ligament space, with a good inhibitory effect on persistent apical periodontitis.