Suppression of Bone Necrosis around Tooth Extraction Socket in a MRONJ-like Mouse Model by E-rhBMP-2 Containing Artificial Bone Graft Administration

Medication-related osteonecrosis of the jaw (MRONJ) is related to impaired bone healing conditions in the maxillomandibular bone region as a complication of bisphosphonate intake. Although there are several hypotheses for the onset of MRONJ symptoms, one of the possible causes is the inhibition of bone turnover and blood supply leading to bone necrosis. The optimal treatment strategy for MRONJ has not been established either. BMP-2, a member of the TGF-β superfamily, is well known for regulating bone remodeling and homeostasis prenatally and postnatally. Therefore, the objectives of this study were to evaluate whether cyclophosphamide/zoledronate (CY/ZA) induces necrosis of the bone surrounding the tooth extraction socket, and to examine the therapeutic potential of BMP-2 in combination with the hard osteoinductive biomaterial, β-tricalcium phosphate (β-TCP), in the prevention and treatment of alveolar bone loss around the tooth extraction socket in MRONJ-like mice models. First, CY/ZA was intraperitoneally administered for three weeks, and alveolar bone necrosis was evaluated before and after tooth extraction. Next, the effect of BMP-2/β-TCP was investigated in both MRONJ-like prevention and treatment models. In the prevention model, CY/ZA was continuously administered for four weeks after BMP-2/β-TCP transplantation. In the treatment model, CY/ZA administration was suspended after transplantation of BMP-2/β-TCP. The results showed that CY/ZA induced a significant decrease in the number of empty lacunae, a sign of bone necrosis, in the alveolar bone around the tooth extraction socket after tooth extraction. Histological analysis showed a significant decrease in the necrotic alveolar bone around tooth extraction sockets in the BMP-2/β-TCP transplantation group compared to the non-transplanted control group in both MRONJ-like prevention and treatment models. However, bone mineral density, determined by micro-CT analysis, was significantly higher in the BMP-2/β-TCP transplanted group than in the control group in the prevention model only. These results clarified that alveolar bone necrosis around tooth extraction sockets can be induced after surgical intervention under CY/ZA administration. In addition, transplantation of BMP-2/β-TCP reduced the necrotic alveolar bone around the tooth extraction socket. Therefore, a combination of BMP-2/β-TCP could be an alternative approach for both prevention and treatment of MRONJ-like symptoms.

Psychological Treatment Models for Survivors of Critical Illness

There is consensus that being critically ill contributes to the development of both new and worsening cognitive and psychological difficulties that impact functioning across multiple domains, including educational, social, and employment settings. Psychologists have become more aware of the scope and magnitude of these problems in recent years and are increasingly engaged in the provision of clinical services to this underserved medical cohort, both as individual providers and as key members of interdisciplinary teams. This chapter reviews key issues related to the needs of ICU survivors with postintensive care syndrome, discusses current outpatient treatment models, and offers a series of suggestions to help optimize the cognitive, mental, and functional health and quality of life of individuals after critical illness.

Telehealth for Medication for Opioid Use Disorder Treatment

Medication for Opioid Use Disorder (mOUD), a type of Medications for Addiction Treatment (MAT), has proven to be the most efficacious and cost-effective treatment for individuals suffering from opioid use disorder (OUD). Early initiation of mOUD has been shown to increase retention in addiction treatment. Models of care integrating telehealth with mOUD offer the potential to implement mOUD in point-of-care settings, achieving effective tertiary prevention. Integrating telehealth and mOUD also addresses barriers to addiction treatment continuity, like transportation concerns and stigma. Funding for use of telehealth for addiction treatment is achieved primarily through government grants and insurance reimbursements. There are many legal constructs regarding the dissemination of mOUD, and while not usually permitted, guidelines during the COVID-19 pandemic have allowed for practitioners to be able to prescribe mOUD via telehealth without the requirement of an initial in-person examination.

Novel neutralization mechanism of a human antibody with pan-coronavirus reactivity

The recurrent outbreak of coronaviruses and variants underscores the need for broadly reactive antivirals and vaccines. Here, a novel broad-spectrum human antibody named 76E1 was isolated from a COVID-19 convalescent patient and showed broad neutralization activity against multiple α- and β-coronaviruses, including the SARS-CoV-2 variants and also exhibited the binding breath to peptides containing the epitope from γ- and δ- coronaviruses. 76E1 cross-protects mice from SARS-CoV-2 and HCoV-OC43 infection in both prophylactic and treatment models. The epitope including the fusion peptide and S2’ cleavage site recognized by 76E1 was significantly conserved among α-, β-, γ- and δ- coronaviruses. We uncovered a novel mechanism of antibody neutralization that the epitope of 76E1 was proportionally less exposed in the prefusion trimeric structure of spike protein but could be unmasked by binding to the receptor ACE2. Once the epitope exposed, 76E1 inhibited S2’ cleavage, thus blocked the membrane fusion process. Our data demonstrate a key epitope targeted by broadly-neutralizing antibodies and will guide next-generation epitope-based pan-coronavirus vaccine design.

Evaluating the utility of rule OP-35 to define preventability of ED visits for oncology patients at an academic cancer center.

272 Background: Rule OP-35, which characterizes treatment-related complications of patients receiving outpatient chemotherapy that result in a potentially avoidable emergency department (ED) visit or hospitalization, was developed to encourage practices to build treatment models that reduce such events. However, defining visits as potentially avoidable based on symptoms may not capture the complexity of caring for oncology patients. We aim to evaluate the effectiveness of OP-35 in identifying preventable ED visits by real world standards at an academic institution. Methods: A retrospective analysis was performed reviewing ED visits at the Sidney Kimmel Cancer Center (SKCC) at Thomas Jefferson University for oncology patients from 10/1/2020 to 1/31/2021. Each patient received care at SKCC had received intravenous or oral chemotherapy in the preceding 30 days, and each encounter was classified as potentially avoidable by OP-35 criteria. Two investigators independently conducted chart reviews to determine whether these visits were potentially avoidable, recording whether the patient attempted to contact their care team prior to the ED encounter and assessing if the concern could have been managed in a timely manner in an outpatient setting. The two records were then compared, and the principal investigator served as an arbiter for determining if a visit was potentially avoidable in instances where the investigators disagreed. Results: We reviewed 144 total encounters and excluded events from patients with either acute leukemia or breast cancer on hormone therapy only, leaving 107 encounters for analysis. After evaluating the clinical circumstances, we determined that 29% of these ED encounters were potentially avoidable. Applying New York University Emergency Department Algorithm (NYU-EDA) criteria, 69% of encounters were considered potentially avoidable. Patients called for advice before seeking ED care in 53% of unavoidable encounters compared to 26% of potentially avoidable encounters. An additional 14% of visits deemed unavoidable were from patients sent directly from clinic. For potentially avoidable encounters, 60% of patients were discharged directly from the ED. In comparison, 8% of unavoidable encounters led to discharge from the ED. Pain was the most common reason for encounters and 53% of these visits were considered potentially avoidable. Conclusions: We found that approximately 30% of ED encounters deemed avoidable by OP-35 criteria were considered potentially avoidable following clinician review. In the majority of cases patients were referred to the ED following initial outpatient attempts at management. NYU-EDA criteria for preventability did not correlate with OP-35 nor clinician consensus regarding potentially avoidable encounters. More work remains in refining tools to identify potentially avoidable ED visits for oncology patients.

Shame, culture, and gender: rethinking the treatment model for couple therapy after an affair

Both the trauma-based and object relations treatment models for couple therapy after an affair can be counterproductive and insufficient because they do not adequately address the powerful motivators of behaviour embedded within cultural and gender norms. In this context, it is essential for therapists to be aware of the impact of culture on our sense of self and couple relationships. We need to make visible deeply internalised gender and cultural norms earlier in the therapeutic process. These hidden values often manifest themselves through the core emotion of shame. Understanding how shame operates intrapsychically, relationally, therapeutically, and socially is a critical task for practitioners. Couple therapy practice must go beyond the "trauma" of an affair to include the larger social cultural political reality.

Modelling temperature dynamics in sewer systems – comparing mechanistic and conceptual modelling approaches

The vast majority of the energy consumed for urban water services is used to heat tap water. Heat recovery from wastewater is consequently an area of rapidly growing concern, both in research and by commercial interest, promoting the path towards a circular economy. To facilitate a system-wide evaluation of heat recovery from wastewater, this paper compares two one-dimensional models (mechanistic and conceptual) that can describe wastewater temperature dynamics in sewer pipe systems. The models are applied to successfully predict downstream wastewater temperature for sewer stretches in two Swedish cities (Linköping & Malmö). The root mean squared errors for the mechanistic model (Linköping Dataset1 – 0.33 °C; Linköping Dataset2 – 0.28 °C; Malmö – 0.40 °C) and the conceptual model (Linköping Dataset1 – 0.32 °C; Linköping Dataset2 – 0.20 °C; Malmö – 0.44 °C) indicate that both models have similar predictive capabilities, encouraging the use of conceptual models to reduce data requirements and model calibration efforts. Both models are freely distributed and can be easily integrated with wastewater generation and treatment models to facilitate system-wide wastewater temperature dynamics analysis.

The Clinical Significance Of Circulating Mir-21, Mir-142, Mir-143, And Mir-146a In Patients With Prostate Cancer

Prostate cancer (PCa) is the most common type of solid tissue cancer among men in western countries. To enlighten the underlying molecular mechanisms in the pathophysiology of PCa and to help the development of new diagnostics and treatment models, we planned to determine the levels of circulating miR-21, miR-142, miR-143, miR-146a, and RNU 44 levels as controls for the early diagnosis of PCa. The circulating miRNA levels in peripheral blood samples from 43 localized PCa patients, 12 metastatic PCa (MET) patients, and as a control group, 42 benign prostate hyperplasia (BPH) patients with a total of 97 volunteers were determined the by PCR method. No differences in the ΔCT values were found among the groups. In PCa and PCaMet groups the expression of miR21 and miR142 were higher compared to the BHP group. No other differences were observed among the other groups. miR21 expression in the PCa group was 6.29 folds upregulated whereas in the PCaMet group 10.84 folds upregulated. When the total expression of miR142 is evaluated, it showed a positive correlation with mir21 and mir 146 (both p<0.001). Also, the expression of miR146 shows a positive correlation with both miR21 and miR143 (both p<0.001). Expression of miRNAs was found to be an independent diagnostic factor in patients with Gleason score, PSA, and free PSA levels. In conclusion, our study showed that co-expression of miR-21, miR-142, miR-143, and miR-146a and the upregulation of miR-21 resulted in increased prostate carcinoma cell growth. In the PCaMet group, miR21 is the most upregulated of all miRNAs. These miRNA markers that are expressed in different levels may provide a novel diagnostic tool to help diagnose PCa with aggressive behavior.

Implementing Attachment-Based Family Therapy for Depressed and Suicidal Adolescents and Young Adults in LGBTQ+ Services

Background: Suicide is a serious public health problem for LGBTQ+ adolescents and young adults. Attachment-based family therapy (ABFT) is one of the few suicide treatment models that has been tested with this population. The challenge remains in how to implement ABFT into the ecology of LGBTQ+ service settings. Aims: In this study, we tested the feasibility, acceptability, and preliminary effectiveness of ABFT in LGBTQ+ community settings. Method: Ten participants were enrolled in 16 weeks of ABFT across three LGBTQ+ organizations. Feasibility (treatment completion) and acceptability (Working Alliance Inventory [WAI]; opinions about treatment [OAT]) were measured for youth and caregivers. Depression and suicide outcomes were assessed for nine participants. Results: ABFT was demonstrated to be both feasible and acceptable. All participants completed treatment, and there were no dropouts. Adolescents/young adults and their caregivers reported high WAI and adequate OAT scores throughout treatment. There was a significant decrease in suicidal ideation (β = −12.16, t(10) = −3.14, p < .01). Decreases in depression, however, were not significant (β = −1.83, t(9.11) = −0.88, p = .40). Limitations: The small sample limits our ability to estimate treatment effectiveness. A larger effectiveness trial is warranted. Conclusion: ABFT is a promising treatment for LGBTQ+ service settings.