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Aims: Hospitalized patients can have inconsistent nutritional intake due to acute illness, changing diet, or unpredictable meal delivery. The aim of this study was to evaluate whether implementation of a hospital-wide policy shifting nutritional insulin administration from pre-meal to post-meal was associated with changes in glycemic control or length of stay (LOS)., Methods: This retrospective study performed at a community hospital evaluated adult inpatients receiving nutritional insulin across three time periods. pre-intervention, immediate post-intervention, and distant post-intervention. Outcomes included rates of hypoglycemia (glucose ≤ 70 mg/dL), moderate hypoglycemia (< 54 mg/dL), severe hypoglycemia (≤ 40 mg/dL), severe hyperglycemia (≥ 300 mg/dL), daily mean glucose level, and LOS., Results: The number of patient-days analyzed across the cohorts were 1948, 1751, and 3244, respectively. After multivariate adjustment, risk of developing any hypoglycemia and severe hypoglycemia significantly decreased over time (p = 0.001 and p = 0.009, respectively). Daily mean glucose increased over time (194.6 ± 62.5 vs 196.8 ± 65.5 vs 199.3 ± 61.5 mg/dL; p = 0.003), but there were no significant differences among rates of severe hyperglycemia (p = 0.10) or LOS (p = 0.74)., Conclusions: Implementing a hospital-wide shift to postprandial nutritional insulin administration significantly reduced hypoglycemia rates without increasing severe hyperglycemia. This suggests a promising strategy for improving patient safety, but further prospective randomized controlled trials are warranted to confirm these findings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.P.D. has received grant funding from DexCom, Inc for an unrelated outpatient study in patients with T1D. M.Z. discloses consulting for DexCom, Inc. and EMD Serono. All other authors have no declarations of interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

The collection, cryopreservation, thawing, and culture of peripheral blood mononuclear cells (PBMCs) can profoundly influence T cell viability and immunogenicity. Gold-standard PBMC processing protocols have been developed by the Office of HIV/AIDS Network Coordination (HANC); however, these protocols are not universally observed. Herein, we have explored the current literature assessing how technical variation during PBMC processing can influence cellular viability and T cell immunogenicity, noting inconsistent findings between many of these studies. Amid the mounting concerns over scientific replicability, there is growing acknowledgement that improved methodological rigour and transparent reporting is required to facilitate independent reproducibility. This review highlights that in human T cell studies, this entails adopting stringent standardised operating procedures (SOPs) for PBMC processing. We specifically propose the use of HANC's Cross-Network PBMC Processing SOP , when collecting and cryopreserving PBMCs, and the HANC member network International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) PBMC Thawing SOP when thawing PBMCs. These stringent and detailed protocols include comprehensive reporting procedures to document unavoidable technical variations, such as delayed processing times. Additionally, we make further standardisation and reporting recommendations to minimise and document variability during this critical experimental period. This review provides a detailed overview of the challenges inherent to a procedure often considered routine, highlighting the importance of carefully considering each aspect of SOPs for PBMC collection, cryopreservation, thawing, and culture to ensure accurate interpretation and comparison between studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Browne, Miller and Doolan.)

Specialized cancer treatments have the potential to exploit glutamine dependence to increase patient survival rates. Glutamine diagnostics capable of tracking a patient's response to treatment would enable a personalized treatment dosage to optimize the tradeoff between treatment success and dangerous side effects. Current clinical glutamine testing requires sophisticated and expensive lab-based tests, which are not broadly available on a frequent, individualized basis. To address the need for a low-cost, portable glutamine diagnostic, this work engineers a cell-free glutamine biosensor to overcome assay background and signal-to-noise limitations evident in previously reported studies. The findings from this work culminate in the development of a shelf-stable, paper-based, colorimetric glutamine test with a high signal strength and a high signal-to-background ratio for dramatically improved signal resolution. While the engineered glutamine test is important progress towards improving the management of cancer and other health conditions, this work also expands the assay development field of the promising cell-free biosensing platform, which can facilitate the low-cost detection of a broad variety of target molecules with high clinical value.

Venetoclax-azacitidine is approved for treatment of patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive chemotherapy based on the interim overall survival (OS) analysis of the VIALE-A study (NCT02993523). Here, long-term follow-up is presented to address survival benefit and long-term outcomes with venetoclax-azacitidine. Patients with newly diagnosed AML who were ineligible for intensive chemotherapy were randomized 2:1 to receive venetoclax-azacitidine or placebo-azacitidine. OS was the primary endpoint; complete remission with/without blood count recovery (CR/CRi) was a key secondary endpoint. This final analysis was conducted when 100% of the predefined 360 OS events occurred. In VIALE-A, 431 patients were enrolled to venetoclax-azacitidine (n = 286) or placebo-azacitidine (n = 145). At 43.2 months median follow-up, median OS was 14.7 months (95% confidence interval [CI], 12.1-18.7) with venetoclax-azacitidine, and 9.6 months (95% CI, 7.4-12.7) with placebo-azacitidine (hazard ratio, 0.58 [95% CI, 0.47-0.72], p < .001); the estimated 24-month OS rate was 37.5% and 16.9%, respectively. Median OS for patients with IDH1/2 mutations and those with measurable residual disease responses was reached in this final analysis. CR/CRi rate was similar to interim analysis. Any-grade hematologic and gastrointestinal adverse events were most common in venetoclax-azacitidine and placebo-azacitidine arms, including thrombocytopenia (47% and 42%) and neutropenia (43% and 29%). No new safety signals were identified. Long-term efficacy and safety confirm venetoclax-azacitidine is an improvement in standard-of-care for patients with AML who are not eligible for intensive chemotherapy because of advanced age or comorbidities., (© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

While most research on West Nile virus (WNV) and its main vector, the Culex mosquito, has been conducted in laboratory or urban settings, studies with field-caught mosquitoes in rural areas, such as west-central Illinois, are lacking. The objective of this research was to investigate key abiotic factors using macroclimate data, including temperature, precipitation, and wind speed, to determine their influence on field-caught mosquito abundance in 4 rural counties in Illinois from 2014 to 2016. Additionally, the relationship between minimum infection rate (MIR) and thermal time was examined. Using gravid traps at 15 sites, Culex mosquitoes were collected twice a week. A total of 5,255 adult female Culex mosquitoes (Cx. pipiens, Cx. quinquefasciatus, and Cx. restuans) were collected in 2014; 9,138 in 2015; and 5,702 in 2016. Regression models were developed based on outcomes of relationships between field-caught mosquitoes and abiotic factors. Precipitation and thermal time had the most significant relationship with mosquito abundance (r2 = 0.993 and r2 = 0.993, respectively), while wind speed was less (r2 = 0.714). The greatest number of Culex and the highest annual MIR were observed in 2015, which was also the driest of the 3 sampling seasons. Mosquito abundance was observed to increase with warmer degree days and MIR was found to increase with abundance in mosquitoes. These models can be used for other mosquito surveillance and monitoring studies in various climate types and environments., (Copyright © 2024 by The American Mosquito Control Association, Inc.)

Loperamide, an oral over-the-counter μ-opioid receptor agonist used to treat diarrhea, acts primarily in the gut and, when used as recommended, has little to no systemic effect. At high doses, it may cause a "high" like other opioids. Recent literature describes an increasing incidence of loperamide misuse and overdose in the setting of the US opioid epidemic. In this case, we describe a 16-year-old with anorexia nervosa who developed dizziness, syncope, and constipation at the time of weight loss. These symptoms were originally attributed to malnutrition; however, after weight restoration, her symptoms worsened. She did not respond to initial management of suspected postural orthostatic tachycardia syndrome (POTS). She then developed acute urinary retention requiring hospitalization. Her symptoms were ultimately found to be caused by chronic surreptitious high-dose loperamide use. Her symptoms rapidly improved after cessation. This case illustrates the non-specific symptoms associated with loperamide misuse and the potential overlap with other common adolescent conditions. Adolescent medicine clinicians must be aware of the signs and symptoms of loperamide misuse as well as familiar with recommendations for both the management of acute complications and the treatment of the substance misuse., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

In 1938, the first distal femur of a fossil Australopithecus was discovered at Sterkfontein, South Africa. A decade later, another distal femur was discovered at the same locality. These two fossil femora were the subject of a foundational paper authored by Kingsbury Heiple and Owen Lovejoy in 1971. In this paper, the authors discussed functionally relevant anatomies of these two fossil femora and noted their strong affinity to the modern human condition. Here, we update this work by including eight more fossil Australopithecus distal femora, an expanded comparative dataset, as well as additional linear measurements. Just as Heiple and Lovejoy reported a half-century ago, we find strong overlap between modern humans and cercopithecoids, except for inferiorly flattened condyles and a high bicondylar angle, both of which characterize modern humans and Australopithecus and are directly related to striding bipedalism. All other measured aspects of the femora are by-products of these key morphological traits. Additional fossil material from the early Pliocene will help to inform the evolution of the hominin distal femur and its condition in the Pan-Homo common ancestor that preceded bipedal locomotion., (© 2023 Wiley Periodicals LLC.)

Objective: Zuranolone is a positive allosteric modulator of both synaptic and extrasynaptic γ-aminobutyric acid (GABA) type A receptors and a neuroactive steroid approved in the United States as an oral, once-daily, 14-day treatment course for adults with postpartum depression and under investigation for adults with major depressive disorder (MDD). Interim results from the open-label, longitudinal, phase 3 SHORELINE Study (NCT03864614) that evaluated the long-term safety and efficacy of zuranolone in adults with MDD are reported., Methods: This interim report includes patients who were enrolled and had the opportunity to be on study for up to 1 year between February 2019 and September 2021. Adults aged 18-75 years with MDD diagnosed per DSM-5 criteria and a 17-item Hamilton Rating Scale for Depression (HAMD-17) total score ≥ 20 received an initial 30-mg or 50-mg 14-day zuranolone course. HAMD-17 responders (≥ 50% reduction from baseline) at Day (D)15 of the initial treatment period were allowed to continue in the study beyond D28 and were followed up for ≤ 1 year, during which repeat treatment courses were permitted. The primary endpoint was safety and tolerability of the initial and repeat treatment courses through 1 year. Secondary endpoints included change from baseline (CFB) in HAMD-17 total score and need for repeat treatment course(s)., Results: As of September 2021, among patients in the 30-mg (n = 725) and 50-mg (n = 199) Cohorts who received a zuranolone dose, 493 (68.0%) and 137 (68.8%), respectively, reported a treatment-emergent adverse event (TEAE); most patients who experienced TEAEs reported mild/moderate events (30-mg Cohort, 90.9% [448/493]; 50-mg Cohort, 85.4% [117/137]). Mean (standard deviation) CFB HAMD-17 total score at D15 of the initial treatment period was -15.2 (7.1) and -16.0 (6.0) for the 30-mg and 50-mg Cohorts, respectively; similar improvements were observed after repeat treatment courses. The proportion of patients who received only 1 treatment course during their time on study was 42.9% (210/489) in the 30-mg Cohort and 54.8% (80/146) in the 50-mg Cohort; 57.1% (279/489) and 45.2% (66/146) patients, respectively, received 2-5 total treatment courses. The majority of patients who initially responded to zuranolone received ≤ 2 total treatment courses (30-mg Cohort, 68.5% [335/489]; 50-mg Cohort, 79.5% [116/146])., Conclusions: Of patients who experienced TEAEs, most reported mild or moderately severe events, and responders to zuranolone experienced improvements in depressive symptoms with initial and repeat treatment courses., Trial Registration: ClinicalTrials.gov identifier: NCT03864614., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

Background: Obstetric brachial plexus injuries (OBPI) can have mental health implications on parents coping with this injury to their newborn. The purpose of this study was to assess the mental health of mothers with newborns with an OBPI and identify resources that can help screen and treat mental health needs., Material and Methods: Three groups of mothers were prospectively given a self-reported survey: 1) Newborns with OBPI; 2) Newborns in the nursery without OBPI; 3) Newborns in the neonatal intensive care unit (NICU). The survey consisted of demographic questions, the PHQ-9 and PCL-S screening tools, and parents' exposure to community violence, family support and use of drugs or alcohol., Results: Fifty-seven mothers were prospectively enrolled, and 30% (17/57) of mothers screened in for post-traumatic stress disorder (PTSD). OBPI mothers had significantly higher rates of PTSD symptoms when compared to mothers of children in the full-term nursery (difference = 36.4%; p < 0.01). No statistically significant difference was found between groups regarding depression symptoms., Conclusions: OBPI can be very difficult to cope with for parents and family members. Forty-two percent of mothers with newborns with OBPI or children in the NICU screened in for PTSD symptoms. OBPI clinics should be staffed similarly to the NICU with clinical social workers to appropriately screen and treat parents with PTSD and depression symptoms., (© 2023 Catherine Miller et al., published by Sciendo.)

Transcription elongation requires elaborate coordination between the transcriptional machinery and chromatin regulatory factors to successfully produce RNA while preserving the epigenetic landscape. Recent structural and genomic studies have highlighted that suppressor of Ty 6 (Spt6), a conserved histone chaperone and transcription elongation factor, sits at the crux of the transcription elongation process. Other recent studies have revealed that Spt6 also promotes DNA replication and genome integrity. Here, we review recent studies of Spt6 that have provided new insights into the mechanisms by which Spt6 controls transcription and have revealed the breadth of Spt6 functions in eukaryotic cells., Competing Interests: Declaration of interests The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The poor quality of life associated with the loss of teeth can be improved by the placing of dental implants. However, successful implantation relies on integration with soft tissues or peri-implant inflammatory disease that can lead to the loss of the implant. Pharmacological agents, such as antibiotics and antiseptics, can be used as adjunct therapies to facilitate osseointegration; however, they can have a detrimental effect on cells, and resistance is an issue. Alternative treatments are needed. Hence, this study aimed to examine the safety profile of bergenin (at 2.5 μM and 5 μM), a traditional medicine, towards human gingival fibroblasts cultured on acid-etched zirconia implant surfaces. Cellular responses were analysed using SEM, resazurin assay, and scratch wound healing assay. Qualitative assessment was conducted for morphology (day 1) and attachment (early and delayed), and quantitative evaluation for proliferation (day 1, 3, 5 and 7), and migration (0 h, 6 h and 24 h). The concentrations of bergenin at 2.5 μM and 5 μM did not demonstrate a statistically significant effect with regard to any of the cellular responses ( p > 0.05) tested. In conclusion, bergenin is non-cytotoxic and is potentially safe to be used as a local pharmacological agent for the management of peri-implant inflammatory diseases.

Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.

The novel Coronavirus (COVID-19) is a highly contagious viral illness that has caused the most significant global health crisis in recent human history. Individuals experiencing homelessness represent one of the more vulnerable populations for COVID-19 infection and morbidity. Amongst individuals experiencing homelessness in Phoenix, a student-led interprofessional organization called Street Medicine Phoenix (SMP) sought to both reduce the risk of COVID-19 transmission and morbidity/mortality related to infection. Through collaborations with the Maricopa County Department of Public Health and various community organizations, SMP developed a format for street-based vaccination clinics. SMP deployed these clinics on numerous occasions to the streets directly surrounding the community homeless shelter, allowing SMP to vaccinate individuals directly in their encampments. Through SMP's efforts starting in February 2021, 400 individuals experiencing homelessness have received at least one COVID-19 vaccine. Challenges encountered included low health literacy, lack of established rapport and trust, low vaccine confidence, difficulty verifying patients' vaccination status, difficulty obtaining sufficient information from patients to create a record in the Arizona State Immunization Information System (ASIIS), monitoring patients post-vaccination, transporting vaccine supplies from encampment to encampment, and lack of patient awareness of the mobile vaccine clinic services. Despite challenges, SMP's outreach efforts have demonstrated the feasibility and importance of mobile public health services to reach homeless encampments, particularly mobile vaccination clinics in response to disease outbreaks, and the necessity of strategic partnerships with community agencies to effectively meet the needs of underserved populations.

Abstract: Hospital autopsies frequently reveal errors in diagnosis that could have affected the patient's clinical outcome. The aims of this study were (1) to investigate the ability of autopsy at our institution to elucidate unrecognized antemortem diagnoses and (2) to pilot a method for tabulating diagnostic discrepancies on a prospective basis. The study sample consisted of 296 cases from our hybrid hospital/forensic autopsy service during the period 2016 to 2018. Discrepancies in autopsy and clinical diagnosis were reported by pathologists at the time of autopsy report generation using a standard form. The rates of major discrepancies between autopsy and clinical diagnoses were 37.5% for in-hospital cases and 25% for patients who died outside our hospital (P < 0.05). The most common discrepant category was infection. The overall rates of discrepant causes of death were 14% (in hospital) and 8% (out of hospital) (ns). Overall percentages of cases with major diagnostic discrepancies were higher in our study than have been previously reported. It is possible that the nature of our patient population plays a role in this result. This study describes an important prospective reporting tool that will allow us to track rates of medical errors and improve diagnosis and treatment of the critically ill., Competing Interests: The authors report no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Ontogeny provides critical information about the evolutionary history of early hominin adult morphology. We describe fossils from the southern African sites of Kromdraai and Drimolen that provide insights into early craniofacial development in the Pleistocene robust australopith Paranthropus robustus . We show that while most distinctive robust craniofacial features appear relatively late in ontogeny, a few do not. We also find unexpected evidence of independence in the growth of the premaxillary and maxillary regions. Differential growth results in a proportionately larger and more postero-inferiorly rotated cerebral fossa in P. robustus infants than in the developmentally older Australopithecus africanus juvenile from Taung. The accumulated evidence from these fossils suggests that the iconic SK 54 juvenile calvaria is more likely early Homo than Paranthropus. It is also consistent with the hypothesis that P. robustus is more closely related to Homo than to A. africanus .

Bone tissue engineering (BTE) is a topic of interest for the last decade, and advances in materials, processing techniques, and the understanding of bone healing pathways have opened new avenues of research. The dual responsibility of BTE scaffolds in providing load-bearing capability and interaction with the local extracellular matrix to promote bone healing is a challenge in synthetic scaffolds. This article describes the usage and processing of multi-materials and hierarchical structures to mimic the structure of natural bone tissues to function as bioactive and load-bearing synthetic scaffolds. The first part of this literature review describes the physiology of bone healing responses and the interactions at different stages of bone repair. The following section reviews the available literature on biomaterials used for BTE scaffolds followed by some multi-material approaches. The next section discusses the impact of the scaffold's structural features on bone healing and the necessity of a hierarchical distribution in the scaffold structure. Finally, the last section of this review highlights the emerging trends in BTE scaffold developments that can inspire new tissue engineering strategies and truly develop the next generation of synthetic scaffolds., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Histone chaperones are an important class of proteins that regulate chromatin accessibility for DNA-templated processes. Spt6 is a conserved histone chaperone and key regulator of transcription and chromatin structure. However, its functions outside of these roles have been little explored. In this work, we demonstrate a requirement for S. cerevisiae Spt6 in DNA replication and, more broadly, as a regulator of genome stability. Depletion or mutation of Spt6 impairs DNA replication in vivo. Additionally, spt6 mutants are sensitive to DNA replication stress-inducing agents. Interestingly, this sensitivity is independent of the association of Spt6 with RNA polymerase II (RNAPII), suggesting that spt6 mutants have a transcription-independent impairment of DNA replication. Specifically, genomic studies reveal that spt6 mutants have decreased loading of the MCM replicative helicase at replication origins, suggesting that Spt6 promotes origin licensing. Our results identify Spt6 as a regulator of genome stability, at least in part through a role in DNA replication., Competing Interests: Declaration of interests The authors have no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: This study assesses the impact of the Interprofessional Global Health Course (IPGHC) on students' fundamental global health knowledge and personal viewpoints on global health domains. It explores the evolution of students' understanding of global health specifically in relation to the COVID-19 pandemic., Methods: Ninety-nine students were selected from 123 McGill student applicants based on their motivation and commitment to take part in IPGHC's ten-week 2020 curriculum. These IPGHC students were eligible to participate in the study. The study's design is sequential explanatory mixed methods. The cross-sectional survey (quantitative phase) appraises students' global health learning outcomes using pre- and post-course surveys, with the use of 5-point Likert-scale questions. The descriptive qualitative survey (qualitative phase) further explores the impact of IPGHC on student's understanding of global health and the reflections of students on the COVID-19 pandemic after IPGHC. The post-course survey included a course evaluation for quality improvement purposes., Results: Of the 99 students, 81 students across multiple undergraduate and graduate disciplines participated in the study by completing the course surveys. Mean knowledge scores of the following 11 global health topics were increased between pre- and post-course survey: Canadian Indigenous health (P < 0.001), global burden of disease (P < 0.001), global surgery (P < 0.001), infectious diseases and neglected tropical diseases (P < 0.001), refugee and immigrant health (P < 0.001), research and development of drugs (P < 0.001), role of politics and policies in global health (P = 0.02), role of technology in global health (P < 0.001), sexual violence (P < 0.001), systemic racism in healthcare (P = 0.03), and trauma in the global health context (P < 0.001). A positive change in student viewpoints was observed in response to questions regarding their perception of the importance of global health education in their own professional health care programs (P < 0.001), and their understanding of the roles and responsibilities of other healthcare professionals (P < 0.001). In the post-course survey open-ended questions, students exemplified their knowledge gained during the course to create a more informed definition of global health. Several recurring themes were identified in the student reflections on the COVID-19 pandemic, notably policy and politics, followed by access to healthcare and resources., Conclusion: This study emphasizes the need for interprofessional global health education at the university level and demonstrates how rapidly global health learners can apply their knowledge to evolving contexts like the COVID-19 pandemic., (© 2023. The Author(s).)

Background: As the opioid epidemic accelerates in the United States, numerous sociodemographic factors have been implicated its development and are, furthermore, a driving factor of the disparities in postoperative pain management. Recent studies have suggested potential associations between the influence of race and ethnicity on pain perception but also the presence of unconscious biases in the treatment of pain in minority patients., Objective: To characterize the perioperative opioid requirements across racial groups after spine surgery., Methods: A retrospective, observational study of 1944 opioid-naive adult patients undergoing a neurosurgical spine procedure, from June 2012 to December 2019, was performed at a large, quaternary care institute. Postoperative inpatient and outpatient opioid usage was measured by oral morphine equivalents, across various racial groups., Results: Case characteristics were similar between racial groups. In the postoperative period, White patients had shorter lengths of stay compared with Black and Asian patients ( P < .05). Asian patients used lower postoperative inpatient opioid doses in comparison with White patients ( P < .001). White patients were discharged with significantly higher doses of opioids compared with Black patients ( P < .01); however, they were less likely to be readmitted within 30 days of discharge ( P < .01)., Conclusion: In a large cohort of opioid-naive postoperative neurosurgical patients, this study demonstrates higher inpatient and outpatient postoperative opioid usage among White patients. Increasing physician awareness to the effect of race on inpatient and outpatient pain management would allow for a modified opioid prescribing practice that ensures limited yet effective opioid dosages void of implicit biases., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

A comprehensive surveillance of Aedes mosquitoes in west-central Illinois has not been conducted in recent years, resulting in incomplete distribution records for several Illinois counties. As of 2014, out of 102 Illinois counties, active populations of Ae. japonicus had been confirmed in 15 counties, and Ae. albopictus confirmed in 34 counties. The Miller laboratory at Western Illinois University (WIU) began the WIU Vector Biology Initiative (WIU-VBI) in 2014 to address the lack of mosquito surveillance in west-central Illinois. Through this effort, the presence of Ae. japonicus was confirmed for the 1st time in Fulton, Hancock, and Schuyler counties, IL, from 2014 to 2018. Actively breeding populations were confirmed in Cass, Fulton, McDonough, and Schuyler counties, IL. Additionally, Ae. albopictus was observed for the 1st time in Cass, Fulton, Hancock, McDonough, and Schuyler counties, IL, in 2016 and 2017, with active breeding populations in Cass and McDonough counties, IL., (Copyright © 2023 by The American Mosquito Control Association, Inc.)

Family-Based Treatment (FBT)-the most widely supported treatment for pediatric eating disorders-transitioned to virtual delivery in many programs due to COVID-19. Using a blended implementation approach, we systematically examined therapist adherence to key components of FBT and fidelity to FBT by videoconferencing (FBT-V), preliminary patient outcomes, and team experiences with our FBT-V implementation approach as well as familial perceptions of FBT-V effectiveness. We examined our implementation approach across four pediatric eating disorder programs in Ontario, Canada, using mixed methods. Participants included therapists (n = 8), medical practitioners (n = 4), administrators (n = 6), and families (n = 5; 21 family members in total). We developed implementation teams at each site, provided FBT-V training, and offered clinical and implementation consultation. Therapists submitted video recordings of their first four FBT-V sessions for fidelity rating, and patient outcomes. Therapists self-reported readiness, attitudes, confidence, and adherence to FBT-V. Focus groups were conducted with each team and family after the first four sessions of FBT-V. Quantitative data were analyzed using repeated measures ANOVA. Qualitative data were analyzed using directed and summative content analysis. Therapists adhered to key FBT components and maintained FBT-V fidelity. Changes in therapists' readiness, attitudes, and confidence in FBT-V over time were not significant. All patients gained weight. Focus groups revealed implementation facilitators/barriers, positives/negatives surrounding FBT-V training and consultation, suggestions for improvement, and effectiveness attributed to FBT-V. Our implementation approach appeared to be feasible and acceptable. Future research with a larger sample is required, furthering our understanding of this approach and exploring how organizational factors influence treatment fidelity., (© Society of Behavioral Medicine 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Mpox is a new public health outbreak that particularly threatens the homeless population. Street Medicine Phoenix (SMP) is a student-led interprofessional volunteer organization that provides medical care and other essential services to individuals experiencing homelessness in Phoenix, Arizona. In addition to core services such as wound care; health screenings (blood pressure and blood glucose.); vision screenings; HIV testing; naloxone education and distribution; flu, COVID-19, and Hepatitis A vaccinations; and community resource referrals, SMP began offering mpox education and vaccination at outreach events. During an outreach event shortly after the onset of the mpox outbreak, SMP identified 2 suspected mpox cases. Accordingly, SMP has partnered with the Maricopa County Public Health Department to set up mobile mpox vaccination clinics on the streets outside of Phoenix Arizona's largest homeless shelter. We share the details of these 2 cases along with our early efforts vaccinating individuals experiencing homelessness for mpox via our mobile vaccination clinic. Our experiences demonstrate the importance of community agencies providing direct outreach to underserved populations where they are at, particularly the homeless population, to address public health concerns such as emerging disease outbreaks like mpox. In addition, these cases highlight the potential significant impact that street medicine programs can have on their respective homeless communities in the context of infectious disease mitigation and emphasize the importance of partnerships with local health departments.

Objective: Though virtual outpatient psychotherapy for eating disorders is likely effective, less is known about virtual higher levels of care. The current study examined the clinical outcomes of a family-based virtual intensive outpatient program (vIOP) for youth with eating disorders which was developed in response to the COVID-19 pandemic, compared to the same institution's in-person partial hospital program (PHP)., Methods: Treatment outcomes were assessed via chart review in 102 patients between the ages of 9-23 (M = 15.2, SD = 2.5) who were predominantly cisgender female (84.3%) and primarily diagnosed with anorexia nervosa (64.7%) or atypical anorexia (23.5%). Participants were either treated in the in-person PHP before the pandemic (n = 49) or the vIOP during the pandemic (n = 53). Percent expected body weight (%EBW) was examined at baseline, end of treatment, 3-months post-treatment, and 6-months post-treatment, as well as the frequency of medical, psychiatric, and residential admissions before, during, and after vIOP or PHP participation., Results: Linear mixed models demonstrated no effect of treatment modality (in-person versus virtual) on %EBW over time. The duration of the vIOP was, on average, 12 calendar days longer, though the amount billed for the vIOP was lower. Survival analyses and Cox regression models did not suggest differences in the frequency of hospital and residential treatment admissions during treatment (vIOP: 9.4%, PHP: 10.0%) or post-treatment (vIOP: 15.0%, PHP: 10.2%)., Discussion: Findings support virtual family-based programs as suitable alternatives to in-person treatment and underscore the potential cost-effectiveness of a family-based IOP versus PHP., Public Significance: This study demonstrates that a virtual, family-based, intensive outpatient program for youth with eating disorders had similar treatment outcomes to an in-person partial hospitalization program. Specifically, the virtual and in-person programs had similar weight restoration outcomes and rates of medical, psychiatric, or residential treatment admissions during or after treatment initiation. Findings support the use of virtual treatment, even for youth requiring a high level of intervention., (© 2022 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Background and Objectives: Dimethyl fumarate (DMF), an oral disease-modifying therapy with an established benefit and well-described safety profile, is among the most commonly used therapies for relapsing forms of multiple sclerosis. As of 31 December 2021, >560,000 patients have been treated with DMF, representing >1,190,000 person-years of exposure. Of these, 6413 patients (14,292 person-years) were from clinical trials., Methods and Results: Progressive multifocal leukoencephalopathy (PML) has occurred in the setting of lymphopenia (<0.91 × 10 9 /L) in patients treated with DMF. We present detailed clinical characteristics and outcomes of the 12 confirmed PML cases occurring in MS patients on DMF as of 21 July 2021. The PML incidence in DMF-treated patients is 1.07 per 100,000 person-years of DMF exposure. Lymphopenia is the common risk for PML in DMF treatment., Discussion: DMF-related PML is rare but has occurred in the setting of lymphopenia, supporting the current recommendations for absolute lymphocyte count monitoring in all patients, regardless of age and time on therapy., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Jennifer Lyons, Richard Hughes, Kerry McCarthy, Nicholas Everage, Catherine Miller, Priya Singhal and Karen Smirnakis are employees of and shareholders in Biogen. Shivani Kapadia is a former employee of Biogen., (© The Author(s), 2022.)

WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: Epidermolysis bullosa (EB) causes blistering and scarring of the hands resulting in contractures fused web spaces and altered function. Surgery is needed to release contractures and web spaces and hand therapy is essential to maintain results, approaches for both differ. WHAT DOES THIS STUDY ADD?: These guidelines aim to provide information on the surgical and conservative therapeutic hand management of children and adults diagnosed with EB. They are based on available evidence and expert consensus to assist hand surgeons and therapists in decision making, planning and treatment. They highlight the importance of a holistic multidisciplinary team (MDT) approach, where patient priorities are paramount., (© 2022. The Author(s).)

The purpose of this study is to compare droplet distribution during a piezoelectric ultrasonic debridement procedure using either high-volume or slow-volume evacuation. Droplet distribution during a crown preparation with slow-volume evacuation is also examined. Fluorescein dye is added to the water reservoir and the procedures are performed by a single operator for 15 min on a dental manikin with artificial upper and lower teeth. Placement of filter paper squares (10 cm × 10 cm) in radiating lines away from the oral cavity of the dental manikin allows for visualization of droplet dispersion. Results show minimal difference in the spread of the droplets between the two evacuators during the debridement procedure; however, the slow-volume evacuator produces a higher concentration of droplets than the high-volume evacuator. An even higher concentration of droplets in the vicinity of the dental chair is observed during the crown preparation procedure. This study recommends the use of a high-volume evacuator where possible during professional debridement and crown preparation to reduce contamination around the dental chair from potentially pathogenic microorganisms.

COVID-19, the global pandemic, has significantly interrupted the provision of oral health care to many individuals. This study aims to evaluate patients' attitudes to and perceptions of dental visits in the COVID-19 pandemic and assess if socio-economic status influences their perception of risk associated with dental visits. Patients attending the dental clinic were invited to participate in this study by completing a questionnaire administered in August 2021. Composite indicators for access, attitude, perception and socio-economic status were created based on subsets of questions. A total of 247 completed questionnaires were obtained. Analysis was performed with the perception, attitude and access indicators against the socio-economic status indicator. This study found that there is a statistically significant difference between socio-economic groups and their attitudes and perceptions around dental health care services in the current COVID-19 pandemic. Individuals from lower socio-economic status groups were less influenced by the pandemic. Participants from higher socio-economic status groups were found to be more cautious around COVID-19 and its risks.

Preterm infants suffer from a higher incidence of acute diseases such as necrotising enterocolitis and sepsis. This risk can be mitigated through probiotic prophylaxis during admission. This reduction in risk is likely the result of acute modulation of the gut microbiome induced by probiotic species, which has been observed to occur up until discharge. We aimed to determine if this modulation, and the associated probiotic species, persisted beyond discharge. We conducted both a cross-sectional analysis (n = 18), at ~ 18 months of age, and a longitudinal analysis (n = 6), from admission to 18 months of the gut microbiome of preterm infants using both shotgun metagenomics and 16S rRNA profiling respectively. The 16S amplicon sequencing revealed that the microbial composition of the probiotic-supplemented infants changed dramatically over time, stabilising at discharge. However, species from the probiotic Infloran ® , as well as positive modulatory effects previously associated with supplementation, do not appear to persist beyond discharge and once prophylaxis has stopped.    Conclusions: Although differences exist between supplemented and non-supplemented groups, the implications of these differences remain unclear. Additionally, despite a lack of long-term colonisation, the presence of probiotics during early neonatal life may still have modulatory effects on the microbiome assembly and immune system training. What is Known: • Evidence suggests modulation of the microbiome occurs during probiotic prophylaxis, which may support key taxa that exert positive immunological benefits. • Some evidence suggests that this modulation can persist post-prophylaxis. What is New: • We present support for long-term modulation in association with probiotic prophylaxis in a cohort of infants from North Queensland Australia. • We also observed limited persistence of the probiotic species post-discharge., (© 2022. The Author(s).)

Background: During the COVID-19 pandemic, outpatient eating disorder care, including Family-Based Treatment (FBT), rapidly transitioned from in-person to virtual delivery in many programs. This paper reports on the experiences of teams and families with FBT delivered by videoconferencing (FBT-V) who were part of a larger implementation study., Methods: Four pediatric eating disorder programs in Ontario, Canada, including their therapists (n = 8), medical practitioners (n = 4), administrators (n = 6), and families (n = 5), participated in our study. We provided FBT-V training and delivered clinical consultation. Therapists recorded and submitted their first four FBT-V sessions. Focus groups were conducted with teams and families at each site after the first four FBT-V sessions. Focus group transcripts were transcribed verbatim and key concepts were identified through line-by-line reading and categorizing of the text. All transcripts were double-coded. Focus group data were analyzed using directed and summative qualitative content analysis., Results: Analysis of focus group data from teams and families revealed four overarching categories-pros of FBT-V, cons of FBT-V, FBT-V process, and suggestions for enhancing and improving FBT-V. Pros included being able to treat more patients and developing a better understanding of family dynamics by being virtually invited into the family's home (identified by teams), as well as convenience and comfort (identified by families). Both teams and families recognized technical difficulties as a potential con of FBT-V, yet teams also commented on distractions in family homes as a con, while families expressed difficulties in developing therapeutic rapport. Regarding FBT-V process, teams and families discussed the importance and challenge of patient weighing at home. In terms of suggestions for improvement, teams proposed assessing a family's suitability or motivation for FBT-V to ensure it would be appropriate, while families strongly suggested implementing hybrid models of FBT in the future which would include some in-person and some virtual sessions., Conclusion: Team and family perceptions of FBT-V were generally positive, indicating acceptability and feasibility of this treatment. Suggestions for improved FBT-V practices were made by both groups, and require future investigation, such as examining hybrid models of FBT that involve in-person and virtual elements. Trial registration ClinicalTrials.gov NCT04678843 ., (© 2022. The Author(s).)

Background: Preterm birth is associated with the development of acute and chronic disease, potentially, through the disruption of normal gut microbiome development. Probiotics may correct for microbial imbalances and mitigate disease risk. Here, we used amplicon sequencing to characterise the gut microbiome of probiotic-treated premature infants. We aimed to identify and understand variation in bacterial gut flora from admission to discharge and in association with clinical variables., Methods: Infants born <32 weeks gestation and <1500 g, and who received probiotic treatment, were recruited in North Queensland Australia. Meconium and faecal samples were collected at admission and discharge. All samples underwent 16S rRNA short amplicon sequencing, and subsequently, a combination of univariate and multivariate analyses., Results: 71 admission and 63 discharge samples were collected. Univariate analyses showed significant changes in the gut flora from admission to discharge. Mixed-effects modelling showed significantly lower alpha diversity in infants diagnosed with either sepsis or retinopathy of prematurity (ROP) and those fed formula. In addition, chorioamnionitis, preeclampsia, sepsis, necrotising enterocolitis and ROP were also all associated with the differential abundance of several taxa., Conclusions: The lower microbial diversity seen in infants with diagnosed disorders or formula-fed, as well as differing abundances of several taxa across multiple variables, highlights the role of the microbiome in the development of health and disease. This study supports the need for promoting healthy microbiome development in preterm neonates., Impact: Low diversity and differing taxonomic abundances in preterm gut microbiota demonstrated in formula-fed infants and those identified with postnatal conditions, as well as differences in taxonomy associated with preeclampsia and chorioamnionitis, reinforcing the association of the microbiome composition changes due to maternal and infant disease. The largest study exploring an association between the preterm infant microbiome and ROP. A novel association between the preterm infant gut microbiome and preeclampsia in a unique cohort of very-premature probiotic-supplemented infants., (© 2021. The Author(s).)

Purpose: To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with IDH1/2-mutant (mut) acute myeloid leukemia (AML)., Patients and Methods: Data were pooled from patients enrolled in a phase III study (NCT02993523) that compared patients treated with venetoclax + azacitidine or placebo + azacitidine and a prior phase Ib study (NCT02203773) where patients were treated with venetoclax + azacitidine. Enrolled patients were ineligible for intensive therapy due to age ≥75 years and/or comorbidities. Patients on venetoclax + azacitidine received venetoclax 400 mg orally (days 1-28) and azacitidine (75 mg/m2; days 1-7/28-day cycle)., Results: In the biomarker-evaluable population, IDH1/2mut was detected in 81 (26%) and 28 (22%) patients in the venetoclax + azacitidine and azacitidine groups. Composite complete remission [CRc, complete remission (CR)+CR with incomplete hematologic recovery (CRi)] rates (venetoclax + azacitidine/azacitidine) among patients with IDH1/2mut were 79%/11%, median duration of remission (mDoR) was 29.5/9.5 months, and median overall survival (mOS) was 24.5/6.2 months. CRc rates among patients with IDH1/2 wild-type (WT) were 63%/31%, mDoR 17.5/10.3 months, and mOS 12.3/10.1 months. In patients with IDH1mut, CRc rates (venetoclax + azacitidine/azacitidine) were 66.7%/9.1% and mOS 15.2/2.2 months. In patients with IDH2mut, CRc rates were 86.0%/11.1% and mOS not reached (NR)/13.0 months. Patients with IDH1/2 WT AML treated with venetoclax + azacitidine with poor-risk cytogenetics had inferior outcomes compared with patients with IDH1/2mut, who had superior outcomes regardless of cytogenetic risk (mOS, IDH1/2mut: intermediate-risk, 24.5 months; poor-risk, NR; IDH1/2 WT: intermediate, 19.2 and poor, 7.4 months). There were no unexpected toxicities in the venetoclax + azacitidine group., Conclusions: Patients with IDH1/2mut who received venetoclax + azacitidine had high response rates, durable remissions, and significant OS; cytogenetic risk did not mitigate the favorable outcomes seen from this regimen for IDH1/2mut. See related commentary by Perl and Vyas, p. 2719., (©2022 The Authors; Published by the American Association for Cancer Research.)

Purpose: To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with FLT3-mutant acute myeloid leukemia., Patients and Methods: Data were pooled from patients enrolled in a phase III study (NCT02993523) that compared patients treated with venetoclax + azacitidine or placebo + azacitidine and a prior phase Ib study (NCT02203773) where patients were treated with venetoclax + azacitidine. Enrolled patients were ineligible for intensive therapy due to age ≥75 years and/or comorbidities. Patients on venetoclax + azacitidine received venetoclax 400 mg orally (days 1-28) and azacitidine (75 mg/m2; days 1-7/28-day cycle). FLT3 mutation was analyzed centrally on pretreatment bone marrow aspirates., Results: In the biomarker evaluable population, FLT3 mutation was detected in 42 (15%) and 22 (19%) patients in the venetoclax + azacitidine and azacitidine groups. Composite complete remission [CRc; complete remission (CR) + CR with incomplete hematologic recovery (CRi)] rates (venetoclax + azacitidine/azacitidine) for FLT3-mutant patients were 67%/36%, median duration of remission (DoR) was 17.3/5.0 months, and median OS was 12.5/8.6 months. The CRc rates among FLT3 wild-type patients were 67%/25%, median DoR 18.4/13.4 months, and median OS 14.7/10.1 months. In patients treated with venetoclax + azacitidine, CRc in patients with FLT3-ITD and FLT3-TKD was 63% and 77% and median OS was 9.9 and 19.2 months, and in comutated FLT3-ITD + NPM1 patients, CRc was 70%, median DoR was not reached, and median OS was 9.1 months. There were no unexpected toxicities in the venetoclax + azacitidine group., Conclusions: When treated with venetoclax + azacitidine, patients with FLT3 mutations and FLT3 wild-type had similar outcomes. Future analyses in larger patient populations may further define the impact of venetoclax + azacitidine in patients harboring FLT3-ITD. See related commentary by Perl and Vyas, p. 2719., (©2022 The Authors; Published by the American Association for Cancer Research.)

Posttranscriptional tRNA modifications are essential for proper gene expression, and defects in the enzymes that perform tRNA modifications are associated with numerous human disorders. Throughout eukaryotes, 2'- O -methylation of residues 32 and 34 of the anticodon loop of tRNA is important for proper translation, and in humans, a lack of these modifications results in non-syndromic X-linked intellectual disability. In yeast, the methyltransferase Trm7 forms a complex with Trm732 to 2'- O -methylate tRNA residue 32 and with Trm734 to 2'- O -methylate tRNA residue 34. Trm732 and Trm734 are required for the methylation activity of Trm7, but the role of these auxiliary proteins is not clear. Additionally, Trm732 and Trm734 homologs are implicated in biological processes not directly related to translation, suggesting that these proteins may have additional cellular functions. To identify critical amino acids in Trm732, we generated variants and tested their ability to function in yeast cells. We identified a conserved RRSAGLP motif in the conserved DUF2428 domain of Trm732 that is required for tRNA modification activity by both yeast Trm732 and its human homolog, THADA. The identification of Trm732 variants that lack tRNA modification activity will help to determine if other biological functions ascribed to Trm732 and THADA are directly due to tRNA modification or to secondary effects due to other functions of these proteins., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: Dimethyl fumarate (DMF) demonstrated favorable benefit-risk in relapsing-remitting multiple sclerosis (RRMS) patients in phase-III DEFINE and CONFIRM trials, and ENDORSE extension., Objective: The main aim of this study is assessing DMF safety/efficacy up to 13 years in ENDORSE., Methods: Randomized patients received DMF 240 mg twice daily or placebo (PBO; Years 0-2), then DMF (Years 3-10; continuous DMF/DMF or PBO/DMF); maximum follow-up (combined studies), 13 years., Results: By January 2020, 1736 patients enrolled/dosed in ENDORSE (median follow-up 8.76 years (ENDORSE range: 0.04-10.98) in DEFINE/CONFIRM and ENDORSE); 52% treated in ENDORSE for ⩾6 years. Overall, 551 (32%) patients experienced serious adverse events (mostly multiple sclerosis (MS) relapse or fall; one progressive multifocal leukoencephalopathy); 243 (14%) discontinued treatment due to adverse events (4% gastrointestinal (GI) disorders). Rare opportunistic infections, malignancies, and serious herpes zoster occurred, irrespective of lymphocyte count. For DMF/DMF ( n = 501), overall annualized relapse rate (ARR) remained low (0.143 (95% confidence interval (CI), 0.120-0.169)), while for PBO/DMF ( n = 249), ARR decreased after initiating DMF and remained low throughout (ARR 0-2 years, 0.330 (95% CI, 0.266-0.408); overall ARR (ENDORSE, 0.151 (95% CI, 0.118-0.194)). Over 10 years, 72% DMF/DMF and 73% PBO/DMF had no 24-week confirmed disability worsening., Conclusion: Sustained DMF safety/efficacy was observed in patients followed up to 13 years, supporting DMF's positive benefit/risk profile for long-term RRMS treatment.

Objective: In the pivotal DEFINE and CONFIRM trials for dimethyl fumarate (DMF), patterns of brain volume changes were different, potentially due to low sample sizes and because MRIs were analyzed at two different reading centers. We evaluated effects of DMF on brain volume change in patients with multiple sclerosis (MS) through reanalysis of pooled images from DEFINE/CONFIRM trials in one reading center., Methods: MRIs from DEFINE/CONFIRM at weeks 0, 24, 48, and 96 from patients randomized to twice-daily DMF or placebo (PBO) were reanalyzed at the Cleveland Clinic to measure brain parenchymal fraction (BPF). To account for pseudoatrophy, brain volume estimates were re-baselined to calculate changes for weeks 48-96., Results: Across studies, 301 and 314 patients receiving DMF and PBO, respectively, had analyzable MRIs. In weeks 0-48, mean ± SE percentage change in BPF was -0.44 ± 0.04 vs. -0.34 ± 0.04% in DMF vs. PBO, respectively, whereas in weeks 48-96, mean ± SE percentage change in BPF was -0.27 ± 0.03 vs. -0.41 ± 0.04% in DMF vs. PBO, respectively. The mixed-effect model for repeated measures showed similar results: in weeks 48-96, estimated change (95% confidence interval) in BPF was -0.0021 (-0.0027, -0.0016) for DMF vs. -0.0033 (-0.0039, -0.0028) for PBO (35.9% reduction; p = 0.0025)., Conclusions: The lower rate of whole brain volume loss with DMF in this pooled BPF analysis in the second year vs. PBO is consistent with its effects on relapses, disability, and MRI lesions. Brain volume changes in the first year may be explained by pseudoatrophy effects also described in other MS clinical trials., Competing Interests: KN reports licensing fees from Biogen and research support from Biogen, Novartis, and Sanofi-Genzyme. OM, CM, NR, and EF were employed by Biogen. OM, CM, and EF hold stock/stock options in Biogen. DLA reports honoraria/revenue from Adelphi, Biogen, Genentech, Genzyme, MedDay, Novartis, Pfizer, Receptos, Roche, and Sanofi-Aventis; and research grant support from Biogen and Novartis. TAY reports honoraria/travel funding from Biogen, Bayer Schering, and Novartis, and research grant support from Biogen, GlaxoSmithKline, Novartis, and Schering. LK reports the following, which were received in the last 3 years and used exclusively for research support at University Hospital Basel: steering committee, advisory board, and consultancy fees from Actelion/Janssen, Bayer, Biogen, Celgene/Receptos, Genzyme, Japan Tobacco, Merck, Minoryx, Novartis, Roche, Sanofi-Aventis, and Santhera; and license fees for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Biogen, the European Union, Innosuisse, Novartis, Roche research foundations, Swiss MS Society, and Swiss National Research Foundation. NR is an employee/consultant for NeuroRx Research and a consultant for BMS, Roche, and Sanofi. KA-R is an employee of and holds stock/options in Envision Pharma Group., (Copyright © 2022 Nakamura, Mokliatchouk, Arnold, Yousry, Kappos, Richert, Ayling-Rouse, Miller and Fisher.)

Background: Preterm birth is associated with the development of both acute and chronic disease, and the disruption of normal gut microbiome development. Recent studies have sought to both characterize and understand the links between disease and the microbiome. Probiotic treatment may correct for these microbial imbalances and, in turn, mitigate disease. However, the criteria for probiotic supplementation in NICU's in North Queensland, Australia limits its usage to the most premature (<32 weeks gestation) and small for gestational age infants (<1,500 g). Here we use a combination of amplicon and shotgun metagenomic sequencing to compare the gut microbiome of infants who fulfill the criteria for probiotic-treatment and those who do not. The aims of this study were to determine if probiotic-supplemented preterm infants have significantly different taxonomic and functional profiles when compared to non-supplemented preterm infants at discharge., Methods: Preterm infants were recruited in North Queensland, Australia, with fecal samples collected just prior to discharge (36 ± 0.5 weeks gestation), to capture potential changes that could be probiotic induced. All samples underwent 16S rRNA gene amplicon sequencing, with a subset also used for shotgun metagenomics. Mixed effects models were used to assess the effect of probiotics on alpha diversity, beta diversity and taxonomic abundance, whilst accounting for other known covariates., Results: Mixed effects modeling demonstrated that probiotic treatment had a significant effect on overall community composition (beta diversity), characterized by greater alpha diversity and differing abundances of several taxa, including Bifidobacterium and Lactobacillus , in supplemented infants., Conclusion: Late preterm-infants who go without probiotic-supplementation may be missing out on stabilizing-effects provided through increased alpha diversity and the presence of commensal microbes, via the use of probiotic-treatment. These findings suggest that late-preterm infants may benefit from probiotic supplementation. More research is needed to both understand the consequences of the differences observed and the long-term effects of this probiotic-treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Westaway, Huerlimann, Kandasamy, Miller, Norton, Watson, Infante-Vilamil and Rudd.)

Objective: To evaluate the effect of routinely used physical decontamination methods on the surface characteristics of zirconia implants and subsequent ability of bacteria to adhere in vitro., Background: Physical decontamination methods commonly used in peri-implantitis therapy and routine implant maintenance can potentially alter zirconia implant surfaces., Methods: Acid-etched zirconia discs were instrumented with titanium curette (TC), plastic curette, air abrasive device, ultrasonic scaler (US) with stainless steel tip. Following instrumentation, surface topography, and surface elemental composition was analyzed using 3D-laser scanning microscopy and energy-dispersive X-ray spectroscopy, respectively. Subsequently, plaque biofilm was cultured on zirconia discs for 48 h and bacterial adhesion assessed using a turbidity test and scanning electron microscopy., Results: A significant difference in surface roughness was observed between the US and control group (p < 0.05). The US and TC caused gray surface discolouration on zirconia discs due to deposition of metallic residue as confirmed by X-ray spectroscopy. No significant difference in bacterial adhesion was noted among all treatment groups (p > 0.05)., Conclusion: TC and US with stainless steel tips should be used with caution due to deposition of metallic residue on the surface. Air abrasive devices and plastic curettes caused minimal surface alterations and are, therefore, safer for zirconia implant decontamination., (© 2021 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Background: Prior studies suggest comparable effectiveness of dimethyl fumarate (DMF) and fingolimod (FTY) in multiple sclerosis (MS) using relapse, Expanded Disability Status Score (EDSS), and magnetic resonance imaging (MRI) lesion metrics., Objective: Compare the real-world effectiveness of DMF versus FTY using quantitative, validated neuroperformance tests, MRI, and serum neurofilament light chain (sNfL) outcomes while controlling for between-group differences., Methods: Patients were eligible if on DMF or FTY when first enrolled in the MS Partners Advancing Technology and Health Solutions (MS PATHS) network and had ≥1-year follow-up in MS PATHS. Sensitivity analysis included a subgroup who started DMF/FTY ≤2 years from enrolment. After propensity score weighting, differences in means and in mean 1-year change of neuroperformance and MRI outcomes were compared. sNfL levels were assessed. This was a non-randomized comparison., Results: In the overall cohort, no significant differences were observed between DMF ( n  = 702) and FTY ( n  = 600) in neuroperformance or MRI outcomes including brain volume loss; mean time (SD) since treatment initiation was 1.98 (0.68) years for DMF and 2.02 (0.75) years for FTY. A sensitivity analysis controlling for DMF and FTY treatment duration yielded similar results., Conclusion: In this study, DMF and FTY demonstrated similar effects on physical and cognitive neuroperformance and MRI outcomes. Direct comparisons to other fumarates and S1P receptor modulators were not conducted., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Carrie M. Hersh reports speaker, consulting, and advisory board fees from Biogen, Bristol-Meyers Squibb, EMD-Serono, Genentech, Genzyme, Novartis, and TG Therapeutics; she also receives research paid directly to her institution from Biogen, Genentech, NIH - NINDS 1U01NS111678-01A1 sub-award, Novartis, and Patient-Centered Outcomes Research Institute. Nicholas Belviso, Shivani Kapadia, Carl de Moor, James Rhys Williams, and Catherine Miller are employees at and hold stock/stock options in Biogen. Arman Altincatal, Irene Koulinska, and Richard Rudick were employees at and held stock/stock options in Biogen at the time this research was conducted., (© The Author(s), 2022.)

Bipedal trackways discovered in 1978 at Laetoli site G, Tanzania and dated to 3.66 million years ago are widely accepted as the oldest unequivocal evidence of obligate bipedalism in the human lineage 1-3 . Another trackway discovered two years earlier at nearby site A was partially excavated and attributed to a hominin, but curious affinities with bears (ursids) marginalized its importance to the paleoanthropological community, and the location of these footprints fell into obscurity 3-5 . In 2019, we located, excavated and cleaned the site A trackway, producing a digital archive using 3D photogrammetry and laser scanning. Here we compare the footprints at this site with those of American black bears, chimpanzees and humans, and we show that they resemble those of hominins more than ursids. In fact, the narrow step width corroborates the original interpretation of a small, cross-stepping bipedal hominin. However, the inferred foot proportions, gait parameters and 3D morphologies of footprints at site A are readily distinguished from those at site G, indicating that a minimum of two hominin taxa with different feet and gaits coexisted at Laetoli., (© 2021. The Author(s).)

Ablative fractional laser treatment is considered the gold standard for skin rejuvenation. In order to understand how fractional laser works to rejuvenate skin, we performed microarray profiling on skin biopsies to identify temporal and dose-response changes in gene expression following fractional laser treatment. The backs of 14 women were treated with ablative fractional laser (Fraxel®) and 4 mm punch biopsies were collected from an untreated site and at the treated sites 1, 3, 7, 14, 21 and 28 days after the single treatment. In addition, in order to understand the effect that multiple fractional laser treatments have on skin rejuvenation, several sites were treated sequentially with either 1, 2, 3, or 4 treatments (with 28 days between treatments) followed by the collection of 4 mm punch biopsies. RNA was extracted from the biopsies, analyzed using Affymetrix U219 chips and gene expression was compared between untreated and treated sites. We observed dramatic changes in gene expression as early as 1 day after fractional laser treatment with changes remaining elevated even after 1 month. Analysis of individual genes demonstrated significant and time related changes in inflammatory, epidermal, and dermal genes, with dermal genes linked to extracellular matrix formation changing at later time points following fractional laser treatment. When comparing the age-related changes in skin gene expression to those induced by fractional laser, it was observed that fractional laser treatment reverses many of the changes in the aging gene expression. Finally, multiple fractional laser treatments, which cover different regions of a treatment area, resulted in a sustained or increased dermal remodeling response, with many genes either differentially regulated or continuously upregulated, supporting previous observations that maximal skin rejuvenation requires multiple fractional laser treatments. In conclusion, fractional laser treatment of human skin activates a number of biological processes involved in wound healing and tissue regeneration., Competing Interests: The authors have declared that no competing interests exist.

Background and Objectives: Emerging data suggest the coronavirus disease 2019 (COVID-19) pandemic has been associated with worsening symptoms of eating disorders (EDs) among both adults and adolescents. With this study, we sought to determine if medical admission patterns among adolescents admitted to our institution for restrictive EDs changed during the pandemic, relative to prepandemic counts of admissions per month., Methods: We performed a chart review of patients aged 10 to 23 years admitted to our children's hospital for restrictive EDs from March 2017 through March 2021 and completed an interrupted time series analysis of admission counts per month. Demographic variables for admitted patients were compared by using χ 2 , Fisher's exact, and 2-sample t tests., Results: ED-related medical admissions at our institution increased significantly during the COVID-19 pandemic. The total number of admissions during the first 12 months of the COVID-19 pandemic (April 1, 2020, through March 31, 2021, n = 125) was more than double the mean number of admissions per year for the same time frame (April 1 through March 31) for the previous 3 years (mean = 56). Patient demographics were similar before and during the pandemic, with the exception that patients admitted during the COVID-19 pandemic were less likely than those admitted before the pandemic to have public insurance., Conclusions: Medical admissions related to restrictive EDs among adolescents increased significantly during the COVID-19 pandemic. Pediatric providers in a variety of settings should be prepared to care for adolescents with restrictive EDs during the pandemic., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Purpose: Peri-implantitis therapy and implant maintenance are fundamental practices to enhance the longevity of zirconia implants. However, the use of physical decontamination methods, including hand instruments, polishing devices, ultrasonic scalers, and laser systems, might damage the implant surfaces. The aim of this systematic review was to evaluate the effects of physical decontamination methods on zirconia implant surfaces., Methods: A systematic search was conducted using 5 electronic databases: Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane. Hand searching of the OpenGrey database, reference lists, and 6 selected dental journals was also performed to identify relevant studies satisfying the eligibility criteria., Results: Overall, 1049 unique studies were identified, of which 11 studies were deemed suitable for final review. Air-abrasive devices with glycine powder, prophylaxis cups, and ultrasonic scalers with non-metal tips were found to cause minimal to no damage to implant-grade zirconia surfaces. However, hand instruments and ultrasonic scalers with metal tips have the potential to cause major damage to zirconia surfaces. In terms of laser systems, diode lasers appear to be the most promising, as no surface alterations were reported following their use., Conclusion: Air-abrasive devices and prophylaxis cups are safe for zirconia implant decontamination due to preservation of the implant surface integrity. In contrast, hand instruments and ultrasonic scalers with metal tips should be used with caution. Recommendations for the use of laser systems could not be fully established due to significant heterogeneity among included studies, but diode lasers may be the best-suited system. Further research-specifically, randomised controlled trials-would further confirm the effects of physical decontamination methods in a clinical setting., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2021. Korean Academy of Periodontology.)

Introduction: Persistence to multiple sclerosis (MS) disease-modifying therapy is fundamental for maximal treatment outcomes. Diroximel fumarate (DRF) is approved in the USA for relapsing MS. Following oral administration, DRF is metabolized to monomethyl fumarate, the active metabolite of dimethyl fumarate (DMF). DRF showed clinically significant improvements in gastrointestinal (GI) tolerability versus DMF in a head-to-head clinical trial; however, real-world persistence/adherence has not been assessed. We evaluated persistence/adherence in DRF-treated patients in a real-world clinical practice., Methods: This retrospective analysis of the AcariaHealth Specialty Pharmacy Program included patients initiating DRF from 4 December 2019 through 3 April 2020 and followed until data extraction (31 August 2020). Exclusion criteria included undetermined treatment status (e.g., DRF prescription transfer to a different pharmacy). Endpoints included persistence (overall proportion of patients remaining on DRF), discontinuation rate due to GI adverse events (AEs), and adherence (proportion of days covered [PDC]). GI AEs included GI-related AEs occurring at any time, or any unknown AE without details about the nature of the event if the unknown AE occurred ≤ 90 days after DRF initiation., Results: Overall, 160 patients with MS were included. Median (range) patient age was 51 (20-79) years, 80.6% (129/160) of patients were female, and 16.3% (26/160) had prior DMF treatment. Median (range) treatment duration was 7.6 (0.1-10.4) months. Estimated proportion of patients remaining persistent on DRF treatment at 8 months was 88.6% (95% confidence interval [CI] 82.5-2.7). Overall, 3.8% (6/160) of patients discontinued due to GI AEs. Mean PDC was 91.4% (95% CI 89.1-93.7). In a DMF-to-DRF switch subgroup, 92.3% (24/26) remained persistent on DRF, and 3.8% (1/26) discontinued DRF due to GI AEs., Conclusion: This real-world analysis of DRF-treated patients showed high overall persistence, low discontinuation rate due to GI AEs, and high adherence to therapy, aligning with expectations based on DRF clinical trials. Data were consistent in the DMF-to-DRF subgroup. INFOGRAPHIC.

The present systematic review evaluates the safety of placing dental implants in patients with a history of antiresorptive or antiangiogenic drug therapy. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. PubMed, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and OpenGrey databases were used to search for clinical studies (English only) to July 16, 2019. Study quality was assessed regarding randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases using a modified Newcastle-Ottawa scale and the Joanna Briggs Institute critical appraisal checklist for case series. A broad search strategy resulted in the identification of 7542 studies. There were 28 studies reporting on bisphosphonates (5 cohort, 6 case control, and 17 case series) and 1 study reporting on denosumab (case series) that met the inclusion criteria and were included in the qualitative synthesis. The quality assessment revealed an overall moderate quality of evidence among the studies. Results demonstrated that patients with a history of bisphosphonate treatment for osteoporosis are not at increased risk of implant failure in terms of osseointegration. However, all patients with a history of bisphosphonate treatment, whether taken orally for osteoporosis or intravenously for malignancy, appear to be at risk of "implant surgery-triggered" medication-related osteonecrosis of the jaw (MRONJ). In contrast, the risk of MRONJ in patients treated with denosumab for osteoporosis was found to be negligible. In conclusion, general and specialist dentists should exercise caution when planning dental implant therapy in patients with a history of bisphosphonate and denosumab drug therapy. Importantly, all patients with a history of bisphosphonates are at risk of MRONJ, necessitating this to be included in the informed consent obtained before implant placement.

The evolution of bipedalism and reduced reliance on arboreality in hominins resulted in larger lower limb joints relative to the joints of the upper limb. The pattern and timing of this transition, however, remains unresolved. Here, we find the limb joint proportions of Australopithecus afarensis , Homo erectus , and Homo naledi to resemble those of modern humans, whereas those of A. africanus , Australopithecus sediba , Paranthropus robustus , Paranthropus boisei , Homo habilis , and Homo floresiensis are more ape-like. The homology of limb joint proportions in A. afarensis and modern humans can only be explained by a series of evolutionary reversals irrespective of differing phylogenetic hypotheses. Thus, the independent evolution of modern human-like limb joint proportions in A. afarensis is a more parsimonious explanation. Overall, these results support an emerging perspective in hominin paleobiology that A. afarensis was the most terrestrially adapted australopith despite the importance of arboreality throughout much of early hominin evolution., Competing Interests: AP, CM, TP, JS, SW, JD No competing interests declared, (© 2021, Prabhat et al.)

Background: Delayed-release dimethyl fumarate (DMF) demonstrates sustained efficacy and safety for relapsing forms of MS. Absolute lymphocyte count (ALC) is reduced initially, then stabilizes on treatment., Objective: PROCLAIM, a 96-week, prospective, open-label, phase 3b study, assessed lymphocyte subsets and immunoglobulin (Ig) levels during 48 and 96 weeks (W) of DMF treatment., Methods: Patients received 240 mg DMF BID. Endpoints: lymphocyte subset count changes (primary); Ig isotypes and ALC changes (secondary); adverse events and relationship between ALC changes and ARR/EDSS (exploratory); and neurofilament assessment (ad hoc)., Results: Of 218 patients enrolled, 158 (72%) completed the study. Median ALC decreased 39% from baseline to W96 (BL-W96), stabilizing above the lower limit of normal (baseline: 1.82 × 10 9 /L; W48: 1.06 × 10 9 /L; W96: 1.05 × 10 9 /L). CD4  +  and CD8  +  T cells correlated highly with ALC from BL-W96 ( p  < 0.001). Relative to total T cells, naive CD4  +  and CD8  +  T cells increased, whereas CD4  +  and CD8  +  central and effector memory T cells decreased. Total IgA, IgG, IgM, and IgG1-4 subclass levels remained stable. Adverse event rates were similar across ALC subgroups. ARR, EDSS, and neurofilament were not correlated with ALCs., Conclusion: Lymphocyte decreases with DMF were maintained over treatment, yet immunoglobulins remained stable. No increase in infection incidence was observed in patients with or without lymphopenia., Support: Biogen.