Ventilation during COVID-19 in a school for students with intellectual and developmental disabilities (IDD).

BACKGROUND: This study examined the correlation of classroom ventilation (air exchanges per hour (ACH)) and exposure to CO2 ≥1,000 ppm with the incidence of SARS-CoV-2 over a 20-month period in a specialized school for students with intellectual and developmental disabilities (IDD). These students were at a higher risk of respiratory infection from SARS-CoV-2 due to challenges in tolerating mitigation measures (e.g. masking). One in-school measure proposed to help mitigate the risk of SARS-CoV-2 infection in schools is increased ventilation. METHODS: We established a community-engaged research partnership between the University of Rochester and the Mary Cariola Center school for students with IDD. Ambient CO2 levels were measured in 100 school rooms, and air changes per hour (ACH) were calculated. The number of SARS-CoV-2 cases for each room was collected over 20 months. RESULTS: 97% of rooms had an estimated ACH ≤4.0, with 7% having CO2 levels ≥2,000 ppm for up to 3 hours per school day. A statistically significant correlation was found between the time that a room had CO2 levels ≥1,000 ppm and SARS-CoV-2 PCR tests normalized to room occupancy, accounting for 43% of the variance. No statistically significant correlation was found for room ACH and per-room SARS-CoV-2 cases. Rooms with ventilation systems using MERV-13 filters had lower SARS-CoV-2-positive PCR counts. These findings led to ongoing efforts to upgrade the ventilation systems in this community-engaged research project. CONCLUSIONS: There was a statistically significant correlation between the total time of room CO2 concentrations ≥1,000 and SARS-CoV-2 cases in an IDD school. Merv-13 filters appear to decrease the incidence of SARS-CoV-2 infection. This research partnership identified areas for improving in-school ventilation.

Adjuvant chemotherapy for adenocarcinoma arising from intraductal papillary mucinous neoplasia: multicentre ADENO-IPMN study.

BACKGROUND: The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival. METHODS: This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching. RESULTS: Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes. CONCLUSION: Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.

Consistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs.

Xenotransplantation represents a possible solution to the organ shortage crisis and is an imminent clinical reality with long-term xenograft survival in pig-to-nonhuman primate (NHP) heart and kidney large animal models, and short-term success in recent human decedent and clinical studies. However, concerns remain about safe clinical translation of these results, given the inconsistency in published survival as well as key differences between preclinical procurement and immunosuppression and clinical standards-of-care. Notably, no studies of solid organ pig-to-NHP transplantation have achieved xenograft survival longer than one month without CD40/CD154 costimulatory blockade, which is not currently an FDA-approved immunosuppression strategy. We now present consistent survival in consecutive cases of pig-to-NHP kidney xenotransplantation, including long-term survival after >3 hours of xenograft cold preservation time as well as long-term survival using FDA-approved immunosuppression. These data provide critical supporting evidence for the safety and feasibility of clinical kidney xenotransplantation. Moreover, long-term survival without CD40/CD154 costimulatory blockade may provide important insights for immunosuppression regimens to be considered for first-in-human clinical trials.

Factors influencing the bond strength of additively manufactured crown materials in dentistry: A systematic review of in vitro studies.

OBJECTIVE: The purpose of this systematic review was to investigate how different interventions can impact the bond strength of additively manufactured crown materials after cementation. DATA/SOURCES: Four online databases Ovid MEDLINE, Scopus, Web of Science and Google Scholar were searched up to January 2023. Inclusion criteria were English-language publications, full-text, and in vitro studies only. Exclusion criteria were studies that did not assess the bonding of an additively manufactured crown material to cement or did not conduct any bond strength tests. An assessment of risk of bias was done in accordance with a modified Consolidated Standards of Reporting Trials (CONSORT) checklist. Each study was analysed and compared based on the interventions and bond strength results. STUDY SELECTION: Six studies satisfied the inclusion and exclusion criteria, five of which evaluated photopolymerised resin and one that tested zirconia manufacturing via 3D printing. All studies observed a low risk of bias. The interventions applied included the type of surface pretreatments, airborne-particle abrasion pressure, cement type, taper of crown, and artificial aging. Three studies compared the bonding performance to milled materials. CONCLUSIONS: The bond strength of crown materials additively manufactured from photopolymers presented high values and are comparable to milled materials. The systematic review demonstrated there was no definite superior cement type, but airborne-particle abrasion with alumina was generally recommended. There is a clear gap in the literature regarding the bond strength of additively manufactured crowns. Therefore, further research is necessary to evaluate its clinical applicability for permanent restorations. CLINICAL SIGNIFICANCE: Factors influencing the bond strength of additively manufactured crown materials should be evaluated so dental professionals can adopt procedures that promote the strongest bond.

Assessment of the trueness of additively manufactured mol3% zirconia crowns at different printing orientations with an industrial and desktop 3D printer compared to subtractive manufacturing.

OBJECTIVES: This study endeavours to investigate the effect of printing orientation on the trueness of additively manufactured molar zirconia crowns. The areal surface roughness and the characteristics of the marginal regions of the crowns were also considered. METHODS: Twelve molar crowns were manufactured at 0°, 45°, and, 90° printing orientations in a Lithoz and AON zirconia printer, respectively. Twelve milled crowns were used as a comparison. Samples were scanned and analysed in metrology software to determine the trueness of the groups. Regions of interest were defined as the margins, intaglio surface and contact points. Areal surface roughness and print layer thickness were further analysed using a confocal laser scanning microscope. RESULTS: The results indicate that there are clear differences between the investigated desktop (AON) and industrial (Lithoz) 3D printer. The 45° Lithoz group is the only sample group showing no significantly different results in trueness for all regions analysed compared to the milled group. Areal surface roughness analysis indicates that the print layers in the marginal regions are within clinically tolerable limits and surface characteristics. CONCLUSIONS: The printing orientation for zirconia crowns is critical to trueness, and differences are evident between different AM apparatuses. Considerations for design and orientation between different apparatuses should therefore be considered when utilising direct additive manufacturing processes. The areal surface roughness of the marginal regions is within acceptable clinical limits for all manufacturing processes and print orientations considered. CLINICAL SIGNIFICANCE: The materials and apparatuses for additive manufacturing of zirconia crowns are now clinically acceptable from the perspective of the trueness of a final crown for critical functional surfaces and areal surface roughness of the marginal regions.

Evidence for molecular subtyping in pancreatic ductal adenocarcinoma: a systematic review.

BACKGROUND: Pancreatic Ductal Adenocarcinoma (PDAC) patients exhibit varied responses to multimodal therapy. RNA gene sequencing has unravelled distinct tumour biology subtypes, forming the focus of this review exploring its impact on survival outcomes. METHODS: A systematic search across PubMed, Medline, Embase, and CINAHL databases targeted studies assessing long-term overall and disease-free survival in PDAC patients with molecular subtyping. RESULTS: Fifteen studies including 2731 patients were identified. Molecular subtyping was performed by RNA sequencing and Immunohistochemistry in 14 studies and by Mass Spectrometry in 1 study. Two main tumour subtypes were identified (classical and basal-like or squamous) with basal like associated with poorer outcomes. Further subtypes were identified in individual studies. Superior survival was seen with classical subtype in all other analyses that compared the classical and basal subtypes. High risk stromal subtypes were identified on further analysis of the stroma and were associated with a worse survival independent of the tumour subtype. CONCLUSION: Molecular subtyping of PDAC specimens can identify patients with high-risk tumour biology and poor survival outcomes. Routine subtyping is limited by the cost of RNA sequencing and the volume of raw data generated which has made its translation into routine clinical practice difficult.

Prolonged post-washing in ethanol decreases bond strength of additively manufactured crown materials.

OBJECTIVES: This study aimed to investigate the effect of post-washing duration and crown thickness on the bond strength between additively manufactured crown materials and dental cement in vitro. METHODS: Rectangular-shaped specimens of two thicknesses (1.5 and 2.0 mm) were additively manufactured from permanent VarseoSmile Crown (VC) and long-term temporary NextDent (ND) materials. The specimens were post-washed (n = 160) in ethanol for 5 min, 10 min, 1 h, and 8 h then cemented with dual-cure resin cement. Twenty PMMA (TC) were milled as a control. A chevron-notch test was performed to measure the maximum load until failure (N). Interfacial bond strength (J/m2) was calculated and statistically analysed. The mode of failure was analysed by scanning electron microscopy (SEM). RESULTS: There was a significant difference in the bond strength between all groups (p < 0.01). VC at 1.5mm thickness post-washed for 10 min showed the highest mean bond strength (1.77 ±0.96 J/m2) while VC at 2.0mm thickness post-washed for 8 h showed the lowest (0.22 ±0.10 J/m2). Exposure to ethanol for 8 h resulted in lower bond strength. Within the type of material, there were no differences in bond strength between the thicknesses when post-washed for the same duration. CONCLUSIONS: Prolonged post-washing of AM crown materials can significantly decrease the bond strength to resin cement. There were no differences between the permanent and long-term temporary AM materials. When post-washed for 5 min, AM materials observed comparable or higher bond strength values compared to PMMA. CLINICAL SIGNIFICANCE: The output of this research serves as a guide for dental practitioners, emphasising the importance of adhering to correct post-washing procedures for optimal bond strength of additively manufactured crown materials.

Draft whole-genome sequences of three Borrelia burgdorferi isolates from Western Canada.

Whole-genome sequences are presented for three Borrelia burgdorferi, a causative agent of Lyme disease in North America, isolated from Ixodes pacificus ticks collected in British Columbia, Canada. Shotgun DNA libraries were prepared with Illumina DNA Prep and sequenced using the MiniSeq platform. Genome assemblies enabled multilocus sequence typing and ospC typing.

Transforming the Future of Surgeon-Scientists.

OBJECTIVE: To create a blueprint for surgical department leaders, academic institutions, and funding agencies to optimally support surgeon-scientists. BACKGROUND: Scientific contributions by surgeons have been transformative across many medical disciplines. Surgeon-scientists provide a distinct approach and mindset toward key scientific questions. However, lack of institutional support, pressure for increased clinical productivity, and growing administrative burden are major challenges for the surgeon-scientist, as is the time-consuming nature of surgical training and practice. METHODS: An American Surgical Association Research Sustainability Task Force was created to outline a blueprint for sustainable science in surgery. Leaders from top NIH-sponsored departments of surgery engaged in video and in-person meetings between January and April 2023. A strength, weakness, opportunities, threats analysis was performed, and workgroups focused on the roles of surgeons, the department and institutions, and funding agencies. RESULTS: Taskforce recommendations: (1) SURGEONS: Growth mindset : identifying research focus, long-term planning, patience/tenacity, team science, collaborations with disparate experts; Skill set : align skills and research, fill critical skill gaps, develop team leadership skills; DEPARTMENT OF SURGERY (DOS): (2) MENTORSHIP: Chair : mentor-mentee matching/regular meetings/accountability, review of junior faculty progress, mentorship training requirement, recognition of mentorship (eg, relative value unit equivalent, awards; Mentor: dedicated time, relevant scientific expertise, extramural funding, experience and/or trained as mentor, trusted advisor; Mentee : enthusiastic/eager, proactive, open to feedback, clear about goals; (3) FINANCIAL SUSTAINABILITY: diversification of research portfolio, identification of matching funding sources, departmental resource awards (eg, T-/P-grants), leveraging of institutional resources, negotiation of formalized/formulaic funds flow investment from academic medical center toward science, philanthropy; (4) STRUCTURAL/STRATEGIC SUPPORT: Structural: grants administrative support, biostats/bioinformatics support, clinical trial and research support, regulatory support, shared departmental laboratory space/equipment; Strategic: hiring diverse surgeon-scientist/scientists faculty across DOS, strategic faculty retention/ recruitment, philanthropy, career development support, progress tracking, grant writing support, DOS-wide research meetings, regular DOS strategic research planning; (5) COMMUNITY AND CULTURE: Community: right mix of faculty, connection surgeon with broad scientific community; Culture: building research infrastructure, financial support for research, projecting importance of research (awards, grand rounds, shoutouts); (6) THE ROLE OF INSTITUTIONS: Foundation: research space co-location, flexible start-up packages, courses/mock study section, awards, diverse institutional mentorship teams; Nurture: institutional infrastructure, funding (eg, endowed chairs), promotion friendly toward surgeon-scientists, surgeon-scientists in institutional leadership positions; Expectations: RVU target relief, salary gap funding, competitive starting salaries, longitudinal salary strategy; (7) THE ROLE OF FUNDING AGENCIES: change surgeon research training paradigm, offer alternate awards to K-awards, increasing salary cap to reflect market reality, time extension for surgeon early-stage investigator status, surgeon representation on study section, focused award strategies for professional societies/foundations. CONCLUSIONS: Authentic recommitment from surgeon leaders with intentional and ambitious actions from institutions, corporations, funders, and society is essential in order to reap the essential benefits of surgeon-scientists toward advancements of science.

New design strategies for ultra-specific CRISPR-Cas13a-based RNA detection with single-nucleotide mismatch sensitivity.

An increasingly pressing need for clinical diagnostics has required the development of novel nucleic acid-based detection technologies that are sensitive, fast, and inexpensive, and that can be deployed at point-of-care. Recently, the RNA-guided ribonuclease CRISPR-Cas13 has been successfully harnessed for such purposes. However, developing assays for detection of genetic variability, for example single-nucleotide polymorphisms, is still challenging and previously described design strategies are not always generalizable. Here, we expanded our characterization of LbuCas13a RNA-detection specificity by performing a combination of experimental RNA mismatch tolerance profiling, molecular dynamics simulations, protein, and crRNA engineering. We found certain positions in the crRNA-target-RNA duplex that are particularly sensitive to mismatches and establish the effect of RNA concentration in mismatch tolerance. Additionally, we determined that shortening the crRNA spacer or modifying the direct repeat of the crRNA leads to stricter specificities. Furthermore, we harnessed our understanding of LbuCas13a allosteric activation pathways through molecular dynamics and structure-guided engineering to develop novel Cas13a variants that display increased sensitivities to single-nucleotide mismatches. We deployed these Cas13a variants and crRNA design strategies to achieve superior discrimination of SARS-CoV-2 strains compared to wild-type LbuCas13a. Together, our work provides new design criteria and Cas13a variants to use in future easier-to-implement Cas13-based RNA detection applications.

Between-hospital care referrals for severe alcohol-related liver disease during the COVID-19 pandemic, 2020 to 2022.

Increased alcohol consumption during the coronavirus disease 2019 pandemic is projected to impact alcohol-related liver disease (ALD) morbidity and mortality. Inter-hospital escalation-of-care referral requests to our tertiary-care hepatology unit were analyzed from January 2020 through December 2022. Most requests to our center were for ALD with an increase in requests from intermediate care units, suggestive of higher acuity illness.

Induction of Skin Allograft Chimerism by Pharmacological Mobilization of Endogenous Bone Marrow-Derived Stem Cells.

Skin substitutes including allografts remain a standard therapeutic approach to promote healing of both acute and chronic large wounds. However, none have resulted in the regrowth of lost and damaged tissues and scarless wound healing. Here, we demonstrate skin allograft chimerism and repair through the mobilization of endogenous bone marrow-derived stem and immune cells in rats and swine. We show that pharmacological mobilization of bone marrow stem cells and immune cells into the circulation promotes host repopulation of skin allografts and restoration of the skin's normal architecture without scarring and minimal contracture. When skin allografts from DA rats are transplanted into GFP transgenic Lewis recipients with a combination of AMD3100 and low-dose FK506 (AF) therapy, host-derived GFP-positive cells repopulate and/or regenerate cellular components of skin grafts including epidermis and hair follicles and the grafts become donor-host chimeric skin. Using AF combination therapy, burn wounds with skin allografts were healed by newly regenerated chimeric skin with epidermal appendages and pigmentation and without contracture in swine.

Influence of different post-processing methods on the dimensional accuracy of 3D-printed photopolymers for dental crown applications - A systematic review.

OBJECTIVES: To perform a systematic review that provides an overview of the current literature on the influence of different post-processing methods on the accuracy of additive-manufactured (3D-printed) photopolymer crown materials, and whether more research is needed. MATERIALS AND METHODS: The search used three online databases, Ovid (MEDLINE), Scopus and Web of Science which were screen for publications that involved assessing dimensional accuracy in post-processing of 3D printed dental crown materials. Publications that were literature reviews, abstracts, written in a language different from English, or publications that did not assess dimensional accuracy were excluded. RESULTS: The included articles were published between 1995 and 2023. After the removal of duplicates using Endnote, 135 studies remained for further screening, 13 were selected for full-text analysis, and 7 studies were included in the systematic review. A total of 7 articles were examined and categorised based on several factors, such as the type of material, number of specimens per group, print layer thickness, print angle of specimens, 3D printer used, properties of the specimens studied, and the method of analysing the accuracy of the specimens. CONCLUSION: It was found that post-processing washing times outside the prescribed instruction for use (IFU) may have an impact on the physical and biocompatibility characteristics of the material. Studies focusing on inert mediums during post-processing require more detailed investigation. The use of different post-curing conditions does not significantly affect the materials dimensional accuracy.

Managing your human capital in a department of surgery.

Human capital management in the department of surgery represents a heterogeneous array of operational and strategic activities that focus on enhancing the well-being and productivity of all team members. This is not an episodic or reactive effort but rather a constant one that occurs in an ongoing cycle. Awareness of all the human capital in one's department, tending to members with their own best interest in mind, and an approach that is communication-heavy and based on fairness and transparency will serve to elevate the productivity and wellness of the department of surgery members and the organization as a whole.

Discovery and characterization of cross-reactive intrahepatic antibodies in severe alcoholic hepatitis.

The pathogenesis of antibodies in severe alcoholic hepatitis (SAH) remains unknown. We analyzed immunoglobulins (Ig) in explanted livers from SAH patients (n=45) undergoing liver transplantation and tissues from corresponding healthy donors (HD, n=10) and found massive deposition of IgG and IgA isotype antibodies associated with complement fragment C3d and C4d staining in ballooned hepatocytes in SAH livers. Ig extracted from SAH livers, but not patient serum exhibited hepatocyte killing efficacy. Employing human and Escherichia coli K12 proteome arrays, we profiled the antibodies extracted from explanted SAH, livers with other diseases, and HD livers. Compared with their counterparts extracted from livers with other diseases and HD, antibodies of IgG and IgA isotypes were highly accumulated in SAH and recognized a unique set of human proteins and E. coli antigens. Further, both Ig- and E. coli-captured Ig from SAH livers recognized common autoantigens enriched in several cellular components including cytosol and cytoplasm (IgG and IgA), nucleus, mitochondrion, and focal adhesion (IgG). Except IgM from primary biliary cholangitis livers, no common autoantigen was recognized by Ig- and E. coli-captured Ig from livers with other diseases. These findings demonstrate the presence of cross-reacting anti-bacterial IgG and IgA autoantibodies in SAH livers.

Plasmid-encoded lactose metabolism and mobilized colistin resistance (mcr-9) genes in Salmonella enterica serovars isolated from dairy facilities in the 1980s.

Horizontal gene transfer by plasmids can confer metabolic capabilities that expand a host cell's niche. Yet, it is less understood whether the coalescence of specialized catabolic functions, antibiotic resistances and metal resistances on plasmids provides synergistic benefits. In this study, we report whole-genome assembly and phenotypic analysis of five Salmonella enterica strains isolated in the 1980s from milk powder in Munich, Germany. All strains exhibited the unusual phenotype of lactose-fermentation and encoded either of two variants of the lac operon. Surprisingly, all strains encoded the mobilized colistin resistance gene 9 (mcr-9), long before the first report of this gene in the literature. In two cases, the mcr-9 gene and the lac locus were linked within a large gene island that formed an IncHI2A-type plasmid in one strain but was chromosomally integrated in the other strain. In two other strains, the mcr-9 gene was found on a large IncHI1B/IncP-type plasmid, whereas the lac locus was encoded on a separate chromosomally integrated plasmidic island. The mcr-9 sequences were identical and genomic contexts could not explain the wide range of colistin resistances exhibited by the Salmonella strains. Nucleotide variants did explain phenotypic differences in motility and exopolysaccharide production. The observed linkage of mcr-9 to lactose metabolism, an array of heavy-metal detoxification systems, and other antibiotic resistance genes may reflect a coalescence of specialized phenotypes that improve the spread of colistin resistance in dairy facilities, much earlier than previously suspected.