Publications by authors named "Patrick Kelly"

451 Publications

Synthesis and Biological Evaluation of 1-(Diarylmethyl)-1-1,2,4-triazoles and 1-(Diarylmethyl)-1-imidazoles as a Novel Class of Anti-Mitotic Agent for Activity in Breast Cancer.

Pharmaceuticals (Basel) 2021 Feb 22;14(2). Epub 2021 Feb 22.

School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Trinity Biomedical Sciences Institute, 152-160 Pearse Street, Dublin 2, DO2R590 Dublin, Ireland.

We report the synthesis and biochemical evaluation of compounds that are designed as hybrids of the microtubule targeting benzophenone phenstatin and the aromatase inhibitor letrozole. A preliminary screening in estrogen receptor (ER)-positive MCF-7 breast cancer cells identified 5-((2-1,2,3-triazol-1-yl)(3,4,5-trimethoxyphenyl)methyl)-2-methoxyphenol as a potent antiproliferative compound with an IC value of 52 nM in MCF-7 breast cancer cells (ER+/PR+) and 74 nM in triple-negative MDA-MB-231 breast cancer cells. The compounds demonstrated significant G/M phase cell cycle arrest and induction of apoptosis in the MCF-7 cell line, inhibited tubulin polymerisation, and were selective for cancer cells when evaluated in non-tumorigenic MCF-10A breast cells. The immunofluorescence staining of MCF-7 cells confirmed that the compounds targeted tubulin and induced multinucleation, which is a recognised sign of mitotic catastrophe. Computational docking studies of compounds , , and in the colchicine binding site of tubulin indicated potential binding conformations for the compounds. Compounds and were also shown to selectively inhibit aromatase. These compounds are promising candidates for development as antiproliferative, aromatase inhibitory, and microtubule-disrupting agents for breast cancer.
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http://dx.doi.org/10.3390/ph14020169DOI Listing
February 2021

Pilot study on the effects of preservatives on corneal collagen parameters measured by small angle X-ray scattering analysis.

BMC Res Notes 2021 Feb 27;14(1):78. Epub 2021 Feb 27.

Department of Clinical Sciences, Ross University of Veterinary Medicine, Basseterre, Saint Kitts and Nevis.

Objective: Small angle X-ray scattering (SAXS) analysis is a sensitive way of determining the ultrastructure of collagen in tissues. Little is known about how parameters measured by SAXS are affected by preservatives commonly used to prevent autolysis. We determined the effects of formalin, glutaraldehyde, Triton X and saline on measurements of fibril diameter, fibril diameter distribution, and D-spacing of corneal collagen using SAXS analysis.

Results: Compared to sections of sheep and cats' corneas stored frozen as controls, those preserved in 5% glutaraldehyde and 10% formalin had significantly larger mean collagen fibril diameters, increased fibril diameter distribution and decreased D-spacing. Sections of corneas preserved in Triton X had significantly increased collagen fibril diameters and decreased fibril diameter distribution. Those preserved in 0.9% saline had significantly increased mean collagen fibril diameters and decreased diameter distributions. Subjectively, the corneas preserved in 5% glutaraldehyde and 10% formalin maintained their transparency but those in Triton X and 0.9% saline became opaque. Subjective morphological assessment of transmission electron microscope images of corneas supported the SAXS data. Workers using SAXS analysis to characterize collagen should be alerted to changes that can be introduced by common preservatives in which their samples may have been stored.
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http://dx.doi.org/10.1186/s13104-021-05494-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913446PMC
February 2021

Statins as a Medical Adjunct in the Surgical Management of Chronic Subdural Hematomas.

World Neurosurg 2021 Feb 18. Epub 2021 Feb 18.

Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN 37232. Electronic address:

Introduction: By stabilizing immature leaky vessel formation in neomembranes, statin drugs have been suggested as a non-surgical treatment option for chronic subdural hematomas (cSDH). Statin therapy appears to reduce conservatively managed cSDH volume, however, the utility of these medications in supplementing surgical treatment is unknown.

Objective: To investigate the effect of concurrent statin therapy on outcomes following surgical treatment of cSDH.

Methods: A retrospective single-institution cohort study of surgically managed convexity cSDH patients between 2009-2019 was conducted. Patients receiving this diagnosis who underwent surgical decompression were included, and those without follow-up scans were excluded. Demographic, clinical and radiographic variables were collected. CSDH size was defined as maximum radial thickness in millimeters (mm) on axial computed tomography of the head. Multivariable linear regression was performed to identify factors-including statin use-which were associated with pre-op to follow-up cSDH size change.

Results: Overall, 111 patients, including 36 patients taking statins on admission were evaluated. Median time to follow-up post-operative imaging was 30 days (IQR:17-42). Patients on statins were older (median: 75 [68-78.25] vs. 69 [59-77], p=0.006) and reported more antiplatelet use (67% vs. 28%, p<0.001). Median change in follow-up size was 13 mm in both statin and non-statin groups. Adjusting for other clinical covariates, statin use was associated with greater reduction in cSDH size (CE=-6.72 mm, 95%CI -13.18- -0.26 mm, p=0.042).

Conclusions: Statin use is associated with improved cSDH size post-operatively. Statin drugs might represent a low-cost and low-risk supplement to the surgical management for cSDH patients.
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http://dx.doi.org/10.1016/j.wneu.2021.02.036DOI Listing
February 2021

The survival of reimplanted shunts following externalization: a single-institution cohort study.

J Neurosurg Pediatr 2021 Feb 12:1-9. Epub 2021 Feb 12.

1Department of Neurological Surgery, Vanderbilt University Medical Center; and.

Objective: The failure-free survival of ventriculoperitoneal shunts (VPSs) following externalization for distal catheter infection or malfunction has not been adequately explored. Conversion to a ventriculoatrial shunt (VAS) may allow earlier reinternalization in lieu of waiting for the peritoneum to be suitable for reimplantation. This option is tempered by historical concerns regarding high rates of VAS failure, and the risks of rare complications are rampant.

Methods: In this retrospective cohort study, all patients undergoing externalization of a VPS at a single institution between 2005 and 2020 were grouped according to the new distal catheter terminus location at the time of reinternalization (VPS vs VAS). The primary outcomes were failure-free shunt survival and duration of shunt externalization. Secondary outcomes included early (< 6 months) shunt failure.

Results: Among 36 patients, 43 shunt externalization procedures were performed. Shunts were reinternalized as VPSs in 25 cases and VASs in 18 cases. The median failure-free survival was 1002 (interquartile range [IQR] 161-3449) days for VPSs and 1163 (IQR 360-2927) days for VASs. There was no significant difference in shunt survival according to the new distal catheter terminus (log-rank, p = 0.73). Conversion to a VAS was not associated with shorter duration of shunt externalization (Wilcoxon rank-sum, p = 0.64); the median duration was 7 (IQR 5-11) days for VPSs and 8 (IQR 6-15) days for VASs. No rare complications occurred in the VAS group.

Conclusions: Shunt failure-free survival rates following externalization are similar to published survival rates for nonexternalized shunts. There was no significant difference in survival between reinternalized VPSs and VASs. Although the VAS was not associated with a shortened duration of externalization, this finding is confounded by strong institutional preference for the VPS over the VAS. Early conversion to the VAS may be a viable treatment option in light of reassuring modern VAS survival data.
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http://dx.doi.org/10.3171/2020.8.PEDS20533DOI Listing
February 2021

Community Belonging and Attitudes Towards HIV Pre-Exposure Prophylaxis (PrEP) Among Transgender Women.

AIDS Behav 2021 Feb 11. Epub 2021 Feb 11.

Center of Excellence for Transgender Health, University of California, San Francisco, San Francisco, CA, USA.

For transgender (trans) women, community belonging may play an important role in shaping perceptions of HIV Pre-exposure Prophylaxis (PrEP). A cluster analysis was performed using data obtained from a survey administered to 128 trans women residing in Philadelphia, PA and the San Francisco Bay area, CA. Six items assessing feelings of community belongingness among trans women produced three distinct clusters. Associations were examined between cluster membership and perceptual items including beliefs about PrEP, experiences with healthcare, patient self-advocacy, and perceived trusted sources for PrEP information. Clusters were demographically comparable apart from age. There were significant differences noted between trust in various communication channels and perceptions of PrEP; the least community-connected cluster had less trust and more negative perceptions of PrEP. Analyses suggest that psychographic differences exist based on perceived community belongingness in this population, and this in turn may be consequential in determining how information about PrEP is communicated and diffused to trans women for whom PrEP may be indicated.
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http://dx.doi.org/10.1007/s10461-021-03183-2DOI Listing
February 2021

Looking backwards and forwards: tracking and persistence of weight status between early childhood and adolescence.

Int J Obes (Lond) 2021 Feb 8. Epub 2021 Feb 8.

Faculty of Medicine and Health, School of Public Health, University of Sydney, Sydney, NSW, Australia.

Background/objective: Many studies have shown that child BMI or weight status tracks over time, but the demographic predictors of high tracking have not been investigated. Our objective was to identify demographic predictors of persistence (duration) of healthy weight and overweight/obesity throughout childhood, and to examine whether tracking was age dependent.

Methods: We conducted secondary data analysis of 4606 children from the Birth cohort and 4983 children from the Kindergarten cohort of the Longitudinal Study of Australian Children with follow-up to age 12/13 and 16/17 years, respectively. Retrospective and prospective tracking were examined descriptively. Time-to-event analysis determined demographic predictors of persistence of healthy weight and overweight/obesity beyond age 4-5 years, after controlling for child BMI z-score. Weight status was determined using WHO methods.

Results: Tracking of healthy weight was consistently higher than that of overweight/obesity, and incident overweight was equally likely throughout childhood and adolescence. Tracking of overweight was lower for children under 7 years than in middle childhood and adolescence (2-year probability 65%, compared with 80%; 2-year resolution of overweight 35 and 20%). Children of lower socioeconomic position, those from culturally and linguistically diverse backgrounds, and girls were more likely to move into overweight (hazard ratios [95%CI] for incident overweight: 1.39 [1.26-1.52], 1.16 [1.02-1.31] and 1.12 [1.02-1.23], respectively) and less likely to resolve their overweight (hazard ratios for resolution of overweight/obesity: 0.77 [0.69-0.85], 0.8 [0.69-0.92] and 0.79 [0.71-0.81], respectively) during childhood. However, persistence of weight status was not significantly affected by rurality or Indigenous status (P > 0.05).

Conclusions: Lowest tracking and highest natural resolution of overweight in children under 7 years suggests this may be an opportune time for interventions to reduce overweight. Primary and secondary prevention programmes during the school years should be designed with special consideration for lower socioeconomic communities, for culturally and linguistically diverse populations and for girls.
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http://dx.doi.org/10.1038/s41366-021-00751-3DOI Listing
February 2021

Advocacy to Government and Stakeholders.

World Neurosurg 2021 Feb 3. Epub 2021 Feb 3.

Department of Neurosurgery, University of South Alabama, Mobile, Alabama, USA; Department of Political Science, University of South Alabama, Mobile, Alabama, USA. Electronic address:

Participation in the health care and government advocacy arena may represent new and challenging perspectives for the traditional neurosurgeon. However, those with a strong understanding of the laws, rules, regulations, and fiscal allocation process can directly influence the practice of neurosurgery in the United States. We seek to shine light on the black box of how health care laws are passed, the influence and techniques of lobbying, and the role and rules surrounding political action committees. This practical review of health care advocacy is supplemented by a blueprint for engagement in the political arena for the practicing neurosurgeon.
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http://dx.doi.org/10.1016/j.wneu.2021.01.129DOI Listing
February 2021

Adaptive Plasticity as a Fitness Benefit of Mate Choice.

Trends Ecol Evol 2021 Feb 2. Epub 2021 Feb 2.

Department of Biology, Coker Hall, CB#3280, University of North Carolina, Chapel Hill, NC 27599-3280, USA. Electronic address:

Phenotypic plasticity and sexual selection can each promote adaptation in variable environments, but their combined influence on adaptive evolution is not well understood. We propose that sexual selection can facilitate adaptation in variable environments when individuals prefer mates that produce adaptively plastic offspring. We develop this hypothesis and review existing studies showing that diverse groups display both sexual selection and plasticity in nonsexual traits. Thus, plasticity could be a widespread but unappreciated benefit of mate choice. We describe methods and opportunities to test this hypothesis and describe how sexual selection might foster the evolution of phenotypic plasticity. Understanding this interplay between sexual selection and phenotypic plasticity might help predict which species will adapt to a rapidly changing world.
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http://dx.doi.org/10.1016/j.tree.2021.01.001DOI Listing
February 2021

Interviews with health professionals about the National Child Protection Alert System.

N Z Med J 2021 01 15;134(1528):35-45. Epub 2021 Jan 15.

Emeritus Professor, School of Psychology, University of Auckland.

Aim: The New Zealand National Child Protection Alert System is administered by multidisciplinary teams in every district health board. The aim of this study was to investigate the factors that influence multidisciplinary child protection teams' (MDTs') decisions about whether to place a child protection alert.

Method: Members of the Child Protection Alert System teams were invited to participate in semi-structured interviews. Interview data were coded and grouped into themes using inductive thematic analysis.

Results: Six themes were identified: the system works well; a wide range of factors are considered in multidisciplinary team decision-making; there are some difficulties with multidisciplinary team meetings; there are problems with the administration of the system across district health boards; there is concern about the potential for the Child Protection Alert System to stigmatise families or cause unjustified responses; improvements can be made to the system.

Conclusion: There is overall support for the National Child Protection Alert System and a consensus that the benefits outweigh any potential risks. There is a need for further improvements to the system, including consistent training, further standardisation and increased accessibility of the information to health professionals, including making information on the system available to primary healthcare.
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January 2021

Predicting for Lost to Follow-up in Surgical Management of Patients with Chronic Subdural Hematoma.

World Neurosurg 2021 Jan 4. Epub 2021 Jan 4.

Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Background: Lost to follow-up (LTF) represents an understudied barrier to effective management of chronic subdural hematoma (cSDH). Understanding the factors associated with LTF after surgical treatment of cSDH could uncover pathways for quality improvement efforts and modify discharge planning. We sought to identify the demographic and clinical factors associated with patient LTF.

Methods: A single-institution, retrospective cohort study of patients treated surgically for convexity cSDH from 2009 to 2019 was conducted. The primary outcome was LTF, with neurosurgical readmission as the secondary outcome. Univariate analysis was conducted using the student-t test and χ test. Multivariate logistic regression was performed to identify the factors associated with LTF and neurosurgical readmission.

Results: A total of 139 patients were included, 29% of whom were LTF. The mean first postoperative follow-up duration was 60 days. On univariate analysis, uninsured/Medicaid coverage was associated with increased LTF compared with private insurance/Medicare coverage (62.5% vs. 41.4%; P = 0.039). A higher discharge modified Rankin scale score was also associated with LTF (3.7 vs. 3.5; P < 0.001). On multivariate analysis, uninsured/Medicaid patients had a significantly greater risk of LTF compared with private insurance/Medicare patients (odds ratio, 2.44; 95% confidence interval, 1.13-5.23; P = 0.022). LTF was independently associated with an increased risk of neurosurgical readmission (odds ratio, 1.94; 95% confidence interval, 1.17-3.24; P = 0.011).

Conclusions: Uninsured and Medicaid patients had a greater likelihood of LTF compared with private insurance and Medicare patients. LTF was further associated with an increased risk of neurosurgical readmission. The results from the present study emphasize the need to address barriers to follow-up to reduce readmission after surgery for cSDH. These findings could inform improved discharge planning, such as predischarge repeat imaging studies and postdischarge contact.
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http://dx.doi.org/10.1016/j.wneu.2020.12.128DOI Listing
January 2021

Performance of an Antigen-Based Test for Asymptomatic and Symptomatic SARS-CoV-2 Testing at Two University Campuses - Wisconsin, September-October 2020.

MMWR Morb Mortal Wkly Rep 2021 Jan 1;69(5152):1642-1647. Epub 2021 Jan 1.

Antigen-based tests for SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), are inexpensive and can return results within 15 minutes (1). Antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in asymptomatic and symptomatic persons within the first 5-12 days after symptom onset (2). These tests have been used at U.S. colleges and universities and other congregate settings (e.g., nursing homes and correctional and detention facilities), where serial testing of asymptomatic persons might facilitate early case identification (3-5). However, test performance data from symptomatic and asymptomatic persons are limited. This investigation evaluated performance of the Sofia SARS Antigen Fluorescent Immunoassay (FIA) (Quidel Corporation) compared with real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 detection among asymptomatic and symptomatic persons at two universities in Wisconsin. During September 28-October 9, a total of 1,098 paired nasal swabs were tested using the Sofia SARS Antigen FIA and real-time RT-PCR. Virus culture was attempted on all antigen-positive or real-time RT-PCR-positive specimens. Among 871 (79%) paired swabs from asymptomatic participants, the antigen test sensitivity was 41.2%, specificity was 98.4%, and in this population the estimated positive predictive value (PPV) was 33.3%, and negative predictive value (NPV) was 98.8%. Antigen test performance was improved among 227 (21%) paired swabs from participants who reported one or more symptoms at specimen collection (sensitivity = 80.0%; specificity = 98.9%; PPV = 94.1%; NPV = 95.9%). Virus was isolated from 34 (46.6%) of 73 antigen-positive or real-time RT-PCR-positive nasal swab specimens, including two of 18 that were antigen-negative and real-time RT-PCR-positive (false-negatives). The advantages of antigen tests such as low cost and rapid turnaround might allow for rapid identification of infectious persons. However, these advantages need to be balanced against lower sensitivity and lower PPV, especially among asymptomatic persons. Confirmatory testing with an FDA-authorized nucleic acid amplification test (NAAT), such as RT-PCR, should be considered after negative antigen test results in symptomatic persons, and after positive antigen test results in asymptomatic persons (1).
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http://dx.doi.org/10.15585/mmwr.mm695152a3DOI Listing
January 2021

Donor Designation Among Mature Latinas and Lay Health Educators (): A Mixed-Methods Study.

Health Educ Behav 2020 Dec 21:1090198120976351. Epub 2020 Dec 21.

Esperanza Health Center, Philadelphia, PA, USA.

Background: Despite positive public attitudes toward solid organ donation in the United States, some of the lowest rates of donor designation persist among older adults and Latinx populations.

Aims: To identify barriers and facilitators to organ donation and donor designation among lay health educators () and mature Latina (50+ years).

Methods: An explanatory sequential mixed-method design was employed, with telephone surveys followed by focus group interviews, to assess and understand the nuances of organ donation and donor designation knowledge, attitudes, and practices among promotoras and mature Latinas in Chicago (IL), Philadelphia (PA), and San Antonio (TX). Descriptive statistics summarized quantitative survey data; thematic content analysis was performed on qualitative data.

Results: Twenty-nine promotoras and 45 mature Latina participated in both the surveys and focus groups ( = 74). Most participants (90%) had limited knowledge of organ donation but reported being "somewhat" or "strongly" in favor of donation (70%); 40.5% were registered donors. Participants lacked knowledge about the registration process and its legal standing and upheld concerns that registered donors would be vulnerable to organ traffickers or targets for murder. Themes emerging from the group interviews revealed additional barriers to designation including distrust of the medical establishment, perceptions of inequities in organ allocation, and family resistance to discussing death.

Discussion: Low donor designation rates are primarily driven by concerns about organ trafficking and the fairness of the allocation system, particularly for undocumented immigrants.

Conclusions: The results informed development of a culturally targeted educational and communication skills intervention to increase donor designation in Latinx communities.

Trial Registration: ClinicalTrials.gov NCT04007419.
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http://dx.doi.org/10.1177/1090198120976351DOI Listing
December 2020

Ambient air pollution, lung function and COPD: cross-sectional analysis from the WHO Study of AGEing and adult health wave 1.

BMJ Open Respir Res 2020 12;7(1)

School of Public health, The University of Sydney, Sydney, New South Wales, Australia.

Background: Long-term exposure to ambient air pollution leads to respiratory morbidity and mortality; however, the evidence of the effect on lung function and chronic obstructive pulmonary disease (COPD) in older adult populations is inconsistent.

Objective: To address this knowledge gap, we investigated the associations between particulate matter (PM), nitrogen dioxide (NO) exposure and lung function, as well as COPD prevalence, in older Chinese adults.

Methods: We used data from the WHO Study on global AGEing and adult health (SAGE) China Wave 1, which includes 111 693 participants from 64 townships in China. A cross-sectional analysis explored the association between satellite-based air pollution exposure estimates (PM with an aerodynamic diameter of ≤10 µm [PM], ≤2.5 µm [PM] and NO) and forced expiratory volume in one second (FEV), forced vital capacity (FVC), the FEV/FVC ratio and COPD (defined as post-bronchodilator FEV/FVC <70%). Data on lung function changes were further stratified by COPD status.

Results: Higher exposure to each pollutant was associated with lower lung function. An IQR (26.1 µg/m) increase in PM was associated with lower FEV (-71.88 mL, 95% CI -92.13 to -51.64) and FEV/FVC (-2.81 mL, 95% CI -3.37 to -2.25). For NO, an IQR increment of 26.8 µg/m was associated with decreases in FEV (-60.12 mL, 95% CI -84.00 to -36.23) and FVC (-32.33 mL, 95% CI -56.35 to -8.32). A 31.2 µg/m IQR increase in PM was linked to reduced FEV (-8.86 mL, 95% CI -5.40 to 23.11) and FEV/FVC (-1.85 mL, 95% CI -2.24 to -1.46). These associations were stronger for participants with COPD. Also, COPD prevalence was linked to higher levels of PM (POR 1.35, 95% CI 1.26 to 1.43), PM (POR 1.24, 95% CI 1.18 to 1.29) and NO (POR 1.04, 95% CI 0.98 to 1.11).

Conclusion: Ambient air pollution was associated with lower lung function, especially in individuals with COPD, and increased COPD prevalence in older Chinese adults.
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http://dx.doi.org/10.1136/bmjresp-2020-000684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747603PMC
December 2020

Induced Disassembly of a Virus-like Particle under Physiological Conditions for Venom Peptide Delivery.

Bioconjug Chem 2021 Jan 11;32(1):111-120. Epub 2020 Dec 11.

Department of Chemistry and Biochemistry, Hunter College, 695 Park Avenue, New York, New York 10065, United States.

Virus-like particles (VLPs) show considerable promise for the delivery of therapeutic compounds such as bioactive venom peptides. While loading and targeting protocols have been developed for numerous VLP prototypes, induced disassembly under physiological conditions of neutral pH, moderate temperature, and aqueous medium remain a challenge. Here, we implement and evaluate a general mechanism, based on ring-opening metathesis polymerization (ROMP), for controllable VLP disassembly. This mechanism is independent of cell-specific factors or the manipulation of environmental conditions such as pH and temperature that cannot be readily controlled The ROMP substrate norbornene is covalently conjugated to surface-exposed lysine residues of a P22 bacteriophage-derived VLP, and ROMP is induced by treatment with the water-soluble ruthenium catalyst AquaMet. Disruption of the P22 shell and release of a GFP reporter is confirmed via native agarose electrophoresis, TEM, and dynamic light scattering (DLS) analyses. Our ROMP disassembly strategy does not depend on the particular structure or morphology of the P22 nanocontainer and is adaptable to other VLP prototypes for the potential delivery of venom peptides for pharmacological applications.
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http://dx.doi.org/10.1021/acs.bioconjchem.0c00494DOI Listing
January 2021

Operating room time as a limited resource: ethical considerations for allocation.

J Med Ethics 2020 Dec 10. Epub 2020 Dec 10.

Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Scheduling surgical procedures among operating rooms (ORs) is mistakenly regarded as merely a tedious administrative task. However, the growing demand for surgical care and finite hours in a day qualify OR time as a limited resource. Accordingly, the objective of this manuscript is to reframe the process of OR scheduling as an ethical dilemma of allocating scarce medical resources. Recommendations for ethical allocation of OR time-based on both familiar and novel ethical values-are provided for healthcare institutions and individual surgeons.
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http://dx.doi.org/10.1136/medethics-2020-106519DOI Listing
December 2020

Inhibition of fatty acid synthase with FT-4101 safely reduces hepatic de novo lipogenesis and steatosis in obese subjects with non-alcoholic fatty liver disease: Results from two early-phase randomized trials.

Diabetes Obes Metab 2021 Mar 21;23(3):700-710. Epub 2020 Dec 21.

Forma Therapeutics, Watertown, Massachusetts.

Aims: To assess the therapeutic potential of fatty acid synthase (FASN) inhibition with FT-4101, a potent, selective, orally bioavailable, small-molecule by (a) evaluating the dose-response of single FT-4101 doses (3, 6 and 9 mg) on hepatic de novo lipogenesis (DNL) in healthy participants (Study 1) and (b) demonstrating the safety, tolerability and efficacy on hepatic steatosis after 12 weeks of FT-4101 dosing in patients with non-alcoholic fatty liver disease (NAFLD; Study 2).

Materials And Methods: In Study 1, three sequential cohorts of healthy men (n = 10/cohort) were randomized to receive a single dose of FT-4101 (n = 5/cohort) or placebo (n = 5/cohort) followed by crossover dosing after 7 days. Hepatic DNL was assessed during fructose stimulation from C-acetate incorporation. In Study 2, men and women with NAFLD (n = 14) randomly received 12 weeks of intermittent once-daily dosing (four cycles of 2 weeks on-treatment, followed by 1 week off-treatment) of 3 mg FT-4101 (n = 9) or placebo (n = 5). Steady-state DNL based on deuterated water labelling, hepatic steatosis using magnetic resonance imaging-proton density fat fraction and sebum lipids and circulating biomarkers were assessed.

Results: Single and repeat dosing of FT-4101 were safe and well tolerated. Single FT-4101 doses inhibited hepatic DNL dose-dependently. Twelve weeks of 3 mg FT-4101 treatment improved hepatic steatosis and inhibited hepatic DNL. Decreases in sebum sapienate content with FT-4101 at week 11 were not significant compared to placebo and rebounded at week 12. Biomarkers of liver function, glucose and lipid metabolism were unchanged.

Conclusions: Inhibition of FASN with 3 mg FT-4101 safely reduces hepatic DNL and steatosis in NAFLD patients.
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http://dx.doi.org/10.1111/dom.14272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898808PMC
March 2021

Intrafraction motion during frameless radiosurgery using Varian HyperArc and BrainLab Elements immobilization systems.

J Radiosurg SBRT 2020 ;7(2):149-156

Department of Radiation Oncology, Orlando Health UF Health Cancer Center, Orlando, FL, USA.

Commercial systems such as Varian HyperArcTM and BrainLab Elements MultiMetTM have been developed that allow radiosurgery treatment of multiple brain metastases using a single isocenter. Each software package places increased demands on frameless immobilization and requires the use of a specific immobilization system: the QFix-Encompass system for Varian and the BrainLab frameless-mask system for BrainLab. At our institution, patients receiving traditional radiosurgery (one isocenter per target lesion) were treated using both immobilization systems. Intrafraction motion was determined for each patient using multiple cone-beam CT scans and the same image-registration software during treatment. There were no statistically-significant differences in mean absolute translational shifts between the two mask systems, with a mean 3D-vector motion of approximately 0.43 mm for both systems. There were also no statistically-significant differences in the mean absolute rotational shifts between the two mask systems. Although the average residual errors were insignificant between the mask systems, special attention should be paid to individual maximum shifts with both systems. Large maximum rotational misalignments could present significant misalignment of lesions as distance increases from the isocenter. Finally, large maximum shifts highlight the need for real-time monitoring of patient movement during radiosurgery of multiple lesions using a single isocenter.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717095PMC
January 2020

Traumatic Cerebrovascular Injuries Associated with Gunshot Wounds to the Head: A Single-Institution Ten-Year Experience.

World Neurosurg 2021 Feb 21;146:e1031-e1044. Epub 2020 Nov 21.

Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Background: Cerebrovascular injury (CVI) is a potentially devastating complication of gunshot wounds to the head (GSWH), with yet unclear incidence and prognostic implications. Few studies have also attempted to define CVI risk factors and their role in patient outcomes. We aimed to describe 10 years of CVI from GSWH and characterize these injury patterns.

Methods: Single-institution data from 2009 to 2019 were queried to identify patients presenting with dural-penetrating GSWH. Patient records were reviewed for GSWH characteristics, CVI patterns, management, and follow-up.

Results: Overall, 63 of 297 patients with GSWH underwent computed tomography angiography (CTA) with 44.4% showing CVI. The middle cerebral artery (22.2%), dural venous sinuses (15.9%), and internal carotid artery (14.3%) were most frequently injured. Arterial occlusion was the most prominent injury type (22.2%) followed by sinus thrombosis (15.9%). One fifth of patients underwent delayed repeat CTA, with 20.1% showing new/previously unrecognized CVI. Bihemispheric bullet tracts were associated with CVI occurrence (P = 0.001) and mortality (P = 0.034). Dissection injuries (P = 0.013), injuries to the vertebrobasilar system (P = 0.036), or the presence of ≥2 concurrent CVIs (P = 0.024) were associated with increased risk of mortality. Of patients with CVI on initial CTA, 30% died within the first 24 hours.

Conclusions: CVI was found in 44.4% of patients who underwent CTA. Dissection and vertebrobasilar injuries are associated with the highest mortality. CTA should be considered in any potentially survivable GSWH. Longitudinal study with consistent CTA use is necessary to determine the true prevalence of CVI and optimize the use of imaging modalities.
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http://dx.doi.org/10.1016/j.wneu.2020.11.078DOI Listing
February 2021

Evaluation of cine imaging during multileaf collimator and gantry motion for real-time magnetic resonance guided radiation therapy.

J Appl Clin Med Phys 2020 Dec 23;21(12):178-187. Epub 2020 Nov 23.

Department of Radiation Oncology, Orlando Health - UF Health Cancer Center, Orlando, FL, USA.

Purpose: Real-time magnetic resonance guided radiation therapy (MRgRT) uses 2D cine imaging for target tracking. This work evaluates the percent image uniformity (PIU) and spatial integrity of cine images in the presence of multileaf collimator (MLC) and gantry motion in order to simulate sliding window and volumetric modulated arc therapy (VMAT) conditions.

Methods: Percent image uniformity and spatial integrity of cine images were measured (1) during MLC motion, (2) as a function of static gantry position, and (3) during gantry rotation. PIU was calculated according to the ACR MRI Quality Control Manual. Spatial integrity was evaluated by measuring the geometric distortion of 16 measured marker positions (10 cm or 15.225 cm from isocenter).

Results: The PIU of cine images did not vary by more than 1% from static linac conditions during MLC motion and did not vary by more than 3% during gantry rotation. Banding artifacts were present during gantry rotation. The geometric distortion in the cine images was less than 0.88 mm for all points measured throughout MLC motion. For all static gantry positions, the geometric distortion was less than 0.88 mm at 10 cm from isocenter and less than 1.4 mm at 15.225 cm from isocenter. During gantry rotation, the geometric distortion remained less than 0.92 mm at 10 cm from isocenter and less than 1.60 mm at 15.225 cm from isocenter.

Conclusion: During MLC motion, cine images maintained adequate PIU, and the geometric distortion of points within 15.225 cm from isocenter was less than the 1 mm threshold necessary for real-time target tracking and gating. During gantry rotation, PIU was negatively affected by banding artifacts, and spatial integrity was only maintained within 10 cm from isocenter. Future work should investigate the effects imaging artifacts have on real-time target tracking during MRgRT.
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http://dx.doi.org/10.1002/acm2.13085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769407PMC
December 2020

Identification of Rickettsia felis DNA in the blood of domestic cats and dogs in the USA.

Parasit Vectors 2020 Nov 18;13(1):581. Epub 2020 Nov 18.

Department of Pathobiology, Auburn University College of Veterinary Medicine, Auburn, AL, 36832, USA.

Background: The main vector and reservoir host of Rickettsia felis, an emerging human pathogen causing flea-borne spotted fever, is the cat flea Ctenocephalides felis. While cats have not been found to be infected with the organism, significant percentages of dogs from Australia and Africa are infected, indicating that they may be important mammalian reservoirs. The objective of this study was to determine the presence of R. felis DNA in the blood of domestic dogs and cats in the USA.

Methods: Three previously validated PCR assays for R. felis and DNA sequencing were performed on blood samples obtained from clinically ill domestic cats and dogs from 45 states (2008-2020) in the USA. The blood samples had been submitted for the diagnosis of various tick-borne diseases in dogs and feline infectious peritonitis virus, feline immunodeficiency virus, and Bartonella spp. in cats. Phylogenetic comparisons were performed on the gltA nucleotide sequences obtained in the study and those reported for R. felis and R. felis-like organisms.

Results: Low copy numbers of R. felis DNA (around 100 copies/ml whole blood) were found in four cats (4/752, 0.53%) and three dogs (3/777, 0.39%). The very low levels of infection in clinically ill animals is consistent with R. felis being an unlikely cause of disease in naturally infected dogs and cats. The low copy numbers we found emphasize the requirement for very sensitive PCRs in prevalence studies.

Conclusions: The low prevalence of naturally infected PCR-positive cats is further evidence that cats are unlikely to be important reservoirs of R. felis. Similarly, the low prevalence in dogs suggests they are not important reservoirs in the USA. Investigations should continue into the role other mammalian species may be playing in the epidemiology of R. felis infections.
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http://dx.doi.org/10.1186/s13071-020-04464-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672164PMC
November 2020

The cost of a single concussion in American high school football: a retrospective cohort study.

Concussion 2020 Oct 28;5(4):CNC81. Epub 2020 Oct 28.

Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Aim: The potential financial burden of American football-related concussions (FRC) is unknown. Our objective was to describe the healthcare costs associated with an FRC and determine factors associated with increased costs.

Methodology/results: A retrospective cohort study of concussed high school football players presenting between November 2017 and March 2020 was undertaken; 144 male high school football players were included. Total costs were about $115,000, for an average direct healthcare cost of $800.10/concussion. Visiting the emergency department (β = 502.29, 95% CI: 105.79-898.61; p = 0.01), the initial post-concussion symptom scale score (β = 0.39, 95% CI: 0.11-0.66; p = 0.01) and a post-concussion syndrome diagnosis (β = 670.37, 95% CI: 98.96-1241.79; p = 0.02) were each independently associated with total costs.

Conclusion: A granular understanding of cost-driving factors associated with FRC is the first step in understanding the cost-effectiveness of prevention and treatment methods.
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http://dx.doi.org/10.2217/cnc-2020-0012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653506PMC
October 2020

Effect of Proposed Episode-Based Payment Models on Advanced Radiotherapy Procedures.

JCO Oncol Pract 2020 Nov 10:OP2000495. Epub 2020 Nov 10.

Department of Radiation Oncology, Orlando Health UF Health Cancer Center, Orlando, FL.

Purpose: An episode-based payment model, the Radiation Oncology Alternative Payment Model (RO-APM), has been proposed for Medicare reimbursement of radiation services provided to oncology patients. RO-APM may have significant impact on reimbursement for specific patient populations.

Methods: This investigation compares historical fee-for-service technical reimbursement estimates at a large hospital-based system to the RO-APM for advanced radiotherapy treatment of specific cancer types. These advanced techniques, stereotactic radiosurgery (SRS), stereotactic body radiotherapy (SBRT), online-adaptive SBRT, and proton therapy, were specifically chosen because they are resource intensive and are correspondingly among the most expensive radiation oncology procedures. A total of 203 Medicare patients were analyzed.

Results: RO-APM base-rate reimbursements were similar for SRS and were 38%-47% higher for SBRT. The proposed rates were 1%-31% lower for online-adaptive SBRT, and 48%-71% lower for proton therapy.

Conclusion: These data suggest that the RO-APM may have the desired effect of encouraging shorter courses of radiotherapy, such as SBRT. However, emerging technologies that require large capital and operating investments may see an overall significant reduction in proposed reimbursement.
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http://dx.doi.org/10.1200/OP.20.00495DOI Listing
November 2020

Effects of seasonality and land use on the diversity, relative abundance, and distribution of mosquitoes on St. Kitts, West Indies.

Parasit Vectors 2020 Nov 2;13(1):543. Epub 2020 Nov 2.

Odum School of Ecology, University of Georgia, Athens, GA, 30602, USA.

Background: Mosquito surveys that collect local data on mosquito species' abundances provide baseline data to help understand potential host-pathogen-mosquito relationships, predict disease transmission, and target mosquito control efforts.

Methods: We conducted an adult mosquito survey from November 2017 to March 2019 on St. Kitts, using Biogents Sentinel 2 traps, set monthly and run for 48-h intervals. We collected mosquitoes from a total of 30 sites distributed across agricultural, mangrove, rainforest, scrub and urban land covers. We investigated spatial variation in mosquito species richness across the island using a hierarchical Bayesian multi-species occupancy model. We developed a mixed effects negative binomial regression model to predict the effects of spatial variation in land cover, and seasonal variation in precipitation on observed counts of the most abundant mosquito species observed.

Results: There was high variation among sites in mosquito community structure, and variation in site level richness that correlated with scrub forest, agricultural, and urban land covers. The four most abundant species were Aedes taeniorhynchus, Culex quinquefasciatus, Aedes aegpyti and Deinocerites magnus, and their relative abundance varied with season and land cover. Aedes aegypti was the most commonly occurring mosquito on the island, with a 90% probability of occurring at between 24 and 30 (median = 26) sites. Mangroves yielded the most mosquitoes, with Ae. taeniorhynchus, Cx. quinquefasciatus and De. magnus predominating. Psorophora pygmaea and Toxorhynchites guadeloupensis were only captured in scrub habitat. Capture rates in rainforests were low. Our count models also suggested the extent to which monthly average precipitation influenced counts varied according to species.

Conclusions: There is high seasonality in mosquito abundances, and land cover influences the diversity, distribution, and relative abundance of species on St. Kitts. Further, human-adapted mosquito species (e.g. Ae. aegypti and Cx. quinquefasciatus) that are known vectors for many human relevant pathogens (e.g. chikungunya, dengue and Zika viruses in the case of Ae. aegypti; West Nile, Spondweni, Oropouche virus, and equine encephalitic viruses in the case of Cx. quinqefasciatus) are the most wide-spread (across land covers) and the least responsive to seasonal variation in precipitation.
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http://dx.doi.org/10.1186/s13071-020-04421-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607626PMC
November 2020

No evidence for sylvatic cycles of chikungunya, dengue and Zika viruses in African green monkeys (Chlorocebus aethiops sabaeus) on St. Kitts, West Indies.

Parasit Vectors 2020 Oct 30;13(1):540. Epub 2020 Oct 30.

Department of Clinical Sciences, Ross University School of Veterinary Medicine, West Farm, Basseterre, St. Kitts and Nevis.

Background: Dengue, chikungunya and Zika viruses (DENV, CHIKV and ZIKV) are transmitted in sylvatic transmission cycles between non-human primates and forest (sylvan) mosquitoes in Africa and Asia. It remains unclear if sylvatic cycles exist or could establish themselves elsewhere and contribute to the epidemiology of these diseases. The Caribbean island of St. Kitts has a large African green monkey (AGM) (Chlorocebus aethiops sabaeus) population and is therefore ideally suited to investigate sylvatic cycles.

Methods: We tested 858 AGM sera by ELISA and PRNT for virus-specific antibodies and collected and identified 9704 potential arbovirus vector mosquitoes. Mosquitoes were homogenized in 513 pools for testing by viral isolation in cell culture and by multiplex RT-qPCR after RNA extraction to detect the presence of DENV, CHIKV and ZIKVs. DNA was extracted from 122 visibly blood-fed individual mosquitoes and a polymorphic region of the hydroxymethylbilane synthase gene (HMBS) was amplified by PCR to determine if mosquitoes had fed on AGMs or humans.

Results: All of the AGMs were negative for DENV, CHIKV or ZIKV antibodies. However, one AGM did have evidence of an undifferentiated Flavivirus infection. Similarly, DENV, CHIKV and ZIKV were not detected in any of the mosquito pools by PCR or culture. AGMs were not the source of any of the mosquito blood meals.

Conclusion: Sylvatic cycles involving AGMs and DENV, CHIKV and ZIKV do not currently exist on St. Kitts.
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http://dx.doi.org/10.1186/s13071-020-04419-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598228PMC
October 2020

Safety and Biovigilance in Organ Donation (SAFEBOD): Protocol for a Population-Based Cohort Study.

JMIR Res Protoc 2020 10 26;9(10):e18282. Epub 2020 Oct 26.

See Acknowledgments, .

Background: Tension lies between the need to increase access to organ transplantation and the equally urgent need to prevent inadvertent transmission of infectious diseases or cancer from organ donors. Biovigilance, or the evaluation of potential donors, is often time-pressured and may be based on incomplete information.

Objective: The Safety and Biovigilance in Organ Donation (SAFEBOD) study aims to improve estimates of infection and cancer transmission risk and explore how real-time data access could support decision-making.

Methods: We will link existing donor referral, actual donor, recipient, and health-outcome data sets from 2000-2015 in New South Wales. Organ donor data sets will include the Organ Donor Characterizing Risk-Profile of Donors Study, the National Organ Matching System, the Australian and New Zealand Organ Donor Register, and the Australian and New Zealand Living Donor Kidney Register. Recipient data sets will include the Australian and New Zealand Dialysis and Transplant Register, the Australian and New Zealand Cardiothoracic Register, the Australian and New Zealand Islet and Pancreas Register, and the Australian and New Zealand Liver Transplant Register. New South Wales health outcome data sets will include HIV and AIDS Notifications and Surveillance Data, the Notifiable Conditions Information Management System, Admitted Patient Data Collection, Emergency Department Data Collection, the Central Cancer Registry, and the Cause of Death Data Collection. We will link organ donors to transplant recipients and health outcomes data sets using probabilistic data-matching based on personal identifiers. Transmission and nontransmission events will be determined by comparing previous cases in donors and posttransplant cases in recipients. We will compare the perceived-risk at referral with the verified risk from linked health outcome data sets and the odds of cancer or contracting an infectious disease in organ recipients from donors based on their transmission-risk profile and estimate recipient survival by donor transmission risk group.

Results: Data were requested from each of the listed registries in September 2018, and data collection is ongoing. Linked data from all listed data sets are expected to be complete in September 2020.

Conclusions: The SAFEBOD study will overcome current limitations in organ donation by accessing comprehensive information on referred organ donors and recipients in existing data sets. The study will provide robust estimates of disease transmission and nontransmission events based on recent data. It will also describe the agreement between perceived risk estimated at the time of referral and verified risk when all health outcome data are accessible. The improved understanding of transmission and nontransmission events will inform clinical decisions and highlight where current policies can be revised to broaden the acceptance of deceased donors.

International Registered Report Identifier (irrid): DERR1-10.2196/18282.
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http://dx.doi.org/10.2196/18282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652689PMC
October 2020

Auditory Brainstem Response Pass Rates Correlate with Newborn Hour of Life and Delivery Mode.

J Pediatr 2021 Mar 21;230:100-105. Epub 2020 Oct 21.

Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Northwestern Medicine Prentice Women's Hospital, Feinberg School of Medicine, Chicago, IL.

Objective: To determine whether hour of life and mode of delivery affect auditory brainstem response (ABR) results in healthy infants with a gestational age of >35 weeks.

Study Design: This retrospective cohort study reviewed 31 984 infants tested during a standard birth hospitalization from 2014 to 2016 at Prentice Women's Hospital of Chicago. Per policy, ABRs were performed after 6 and 12 hours of life for vaginally and cesarean-delivered infants, respectively. Testing was repeated before discharge for infants who were referred once. For those infants who referred again, a third ABR was offered at no cost to families 10-14 days after discharge starting in 2016.

Results: ABR pass rates consistently and significantly increased with advancing hour of life at testing, starting at 10-11 hours of life for vaginally born infants and 30-32 hours for cesarean-born infants. This steady, incremental increase in the pass rate was maintained overall until the vaginal and cesarean groups reached plateaus at 42-44 and 48-52 hours of life, respectively. In 2016 and beyond, a third hearing screen after discharge lowered the referral rate to just 0.77%.

Conclusions: This study of the results of ABR tests in over 30 000 well newborns demonstrates that delaying hearing screening until 10-11 hours for vaginally born infants and 30-32 hours for cesarean-born infants results in a statistically significant improvement in hearing pass rates.
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http://dx.doi.org/10.1016/j.jpeds.2020.10.036DOI Listing
March 2021

Radiation Therapy for Rectal Cancer: Executive Summary of an ASTRO Clinical Practice Guideline.

Pract Radiat Oncol 2021 Jan-Feb;11(1):13-25. Epub 2020 Oct 21.

Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas. Electronic address:

Purpose: This guideline reviews the evidence and provides recommendations for the indications and appropriate technique and dose of neoadjuvant radiation therapy (RT) in the treatment of localized rectal cancer.

Methods: The American Society for Radiation Oncology convened a task force to address 4 key questions focused on the use of RT in preoperative management of operable rectal cancer. These questions included the indications for neoadjuvant RT, identification of appropriate neoadjuvant regimens, indications for consideration of a nonoperative or local excision approach after chemoradiation, and appropriate treatment volumes and techniques. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength.

Results: Neoadjuvant RT is recommended for patients with stage II-III rectal cancer, with either conventional fractionation with concurrent 5-FU or capecitabine or short-course RT. RT should be performed preoperatively rather than postoperatively. Omission of preoperative RT is conditionally recommended in selected patients with lower risk of locoregional recurrence. Addition of chemotherapy before or after chemoradiation or after short-course RT is conditionally recommended. Nonoperative management is conditionally recommended if a clinical complete response is achieved after neoadjuvant treatment in selected patients. Inclusion of the rectum and mesorectal, presacral, internal iliac, and obturator nodes in the clinical treatment volume is recommended. In addition, inclusion of external iliac nodes is conditionally recommended in patients with tumors invading an anterior organ or structure, and inclusion of inguinal and external iliac nodes is conditionally recommended in patients with tumors involving the anal canal.

Conclusions: Based on currently published data, the American Society for Radiation Oncology task force has proposed evidence-based recommendations regarding the use of RT for rectal cancer. Future studies will look to further personalize treatment recommendations to optimize treatment outcomes and quality of life.
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http://dx.doi.org/10.1016/j.prro.2020.08.004DOI Listing
October 2020

Hydroxymethylbilane synthase (HMBS) gene-based endogenous internal control for avian species.

AMB Express 2020 Oct 7;10(1):181. Epub 2020 Oct 7.

Yangzhou University College of Veterinary Medicine, Yangzhou, Jiangsu, China.

With PCR becoming one of the most important and widely-used diagnostic tools for infectious diseases of poultry, an urgent need has developed for an endogenous internal control (EIC) that monitors the quality and quantity of poultry DNA in test samples. In this study we developed a SYBR-qPCR to target the poultry homolog of the hydroxymethylbilane synthase (HMBS) gene as an EIC for avian species. The avian HMBS-based qPCR was very sensitive, detecting one HMBS gene copy in a 20 µL reaction, and is highly specific for avian species. It amplified DNA from 11 organs and tissues of chickens showing it can be used as an EIC on a large variety of samples. The application of the established EIC on clinically and experimentally infected samples demonstrated that false negativity and result variations could result from samples being collected using different operators, techniques, preservatives, and storage times. The high sensitivity and specificity of the avian HMBS-based qPCR, its ability to quantify DNAs extracted from a wide range of tissues and poultry species along with its usefulness in reducing false negativity in PCR results associated with inadequate sampling and storage degradation makes it an ideal EIC for poultry DNA and RNA PCR diagnostics. The study also highlights the importance of appropriate sampling and storage of samples in ensuring accuracy of molecular diagnostic testing.
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http://dx.doi.org/10.1186/s13568-020-01112-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539256PMC
October 2020

Correction to: Implementation of the goal-directed medication review electronic decision support system (G-MEDSS)© into home medicines review: a protocol for a clusterrandomised clinical trial in older adults.

BMC Geriatr 2020 Oct 2;20(1):378. Epub 2020 Oct 2.

NHMRC Cognitive Decline Partnership Centre, Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s12877-020-01681-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532095PMC
October 2020

Impact of the Goal-directed Medication Review Electronic Decision Support System on Drug Burden Index: A cluster-randomised clinical trial in primary care.

Br J Clin Pharmacol 2021 Mar 2;87(3):1499-1511. Epub 2020 Nov 2.

NHMRC Cognitive Decline Partnership Centre, Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, St Leonards, New South Wales, Australia.

Aims: The Goal-directed Medication Review Electronic Decision Support System (G-MEDSS) assesses and reports a patient's goals, attitudes to deprescribing and Drug Burden Index (DBI) score, a measure of cumulative exposure to anticholinergic and sedative medications. This study evaluated the effect of implementing G-MEDSS in home medicines reviews (HMRs) on DBI exposure and clinical outcomes.

Methods: A cluster-randomised clinical trial was performed across Australia. Accredited clinical pharmacists were randomised into intervention (G-MEDSS with usual care HMR) or comparison groups (usual care HMR alone). Patients were recruited by pharmacists from those routinely referred by general practitioners for HMR. The primary outcome was the proportion of patients with any reduction in DBI at 3-months follow-up. Secondary outcomes included change in DBI continuous score at 3-months, HMR recommendations to change DBI and clinical outcomes.

Results: There were 201 patient participants at baseline (n = 88 intervention, n = 113 comparison), with 159 followed-up at 3-months (n = 63 intervention, n = 96 comparison). The proportion of patients with a reduction in DBI was not significantly different at 3-months (intervention 17%, comparison 11%; adjusted odds ratio 1.44, 95% confidence interval 0.56-3.80). Regarding secondary outcomes, there was no difference in change in DBI score at 3-months. However, the HMR report made recommendations to reduce DBI for a significantly greater proportion of patients in the intervention than in the comparison group (intervention 37%, comparison 14%; adjusted odds ratio 3.20, 95% confidence interval 1.50-6.90). No changes were observed in clinical outcomes.

Conclusion: Implementation of G-MEDSS within HMR did not reduce patients' DBI at 3 months compared with usual care HMR.
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http://dx.doi.org/10.1111/bcp.14557DOI Listing
March 2021