Publications by authors named "James O"

515 Publications

Dysregulation in Subcellular Localization of Myelin Basic Protein mRNA Does Not Result in Altered Myelination in Amyotrophic Lateral Sclerosis.

Front Neurosci 2021 1;15:705306. Epub 2021 Sep 1.

Euan MacDonald Centre for MND Research, The University of Edinburgh, Edinburgh, United Kingdom.

Pathological hallmarks of amyotrophic lateral sclerosis (ALS), including protein misfolding, are well established in oligodendrocytes. More recently, an RNA trafficking deficit of key myelin proteins has been suggested in oligodendrocytes in ALS but the extent to which this affects myelination and the relative contribution of this to disease pathogenesis is unclear. ALS autopsy research findings showing demyelination contrasts with the routine clinical-pathological workup of ALS cases where it is rare to see white matter abnormalities other than simple Wallerian degeneration secondary to widespread neuronal loss. To begin to address this apparent variance, we undertook a comprehensive evaluation of myelination at an RNA, protein and structural level using human pathological material from sporadic ALS patients, genetic ALS patients (harboring mutation) and age- and sex-matched non-neurological controls. We performed (i) quantitative spatial profiling of the mRNA transcript encoding myelin basic protein (), (ii) quantification of MBP protein and (iii) the first quantitative structural assessment of myelination in ALS post-mortem specimens by electron microscopy. We show no differences in MBP protein levels or ultrastructural myelination, despite a significant dysregulation in the subcellular trafficking of mRNA in ALS patients compared to controls. We therefore confirm that whilst there are cell autonomous mRNA trafficking deficits affecting oligodendrocytes in ALS, this has no effect on myelin structure.
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http://dx.doi.org/10.3389/fnins.2021.705306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440970PMC
September 2021

Tissue environment, not ontogeny, defines murine intestinal intraepithelial T lymphocytes.

Elife 2021 Sep 2;10. Epub 2021 Sep 2.

Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, United Kingdom.

Tissue-resident intestinal intraepithelial T lymphocytes (T-IEL) patrol the gut and have important roles in regulating intestinal homeostasis. T-IEL include both induced T-IEL, derived from systemic antigen-experienced lymphocytes, and natural T-IEL, which are developmentally targeted to the intestine. While the processes driving T-IEL development have been elucidated, the precise roles of the different subsets and the processes driving activation and regulation of these cells remain unclear. To gain functional insights into these enigmatic cells, we used high-resolution, quantitative mass spectrometry to compare the proteomes of induced T-IEL and natural T-IEL subsets, with naive CD8 T cells from lymph nodes. This data exposes the dominant effect of the gut environment over ontogeny on T-IEL phenotypes. Analyses of protein copy numbers of >7000 proteins in T-IEL reveal skewing of the cell surface repertoire towards epithelial interactions and checkpoint receptors; strong suppression of the metabolic machinery indicating a high energy barrier to functional activation; upregulated cholesterol and lipid metabolic pathways, leading to high cholesterol levels in T-IEL; suppression of T cell antigen receptor signalling and expression of the transcription factor TOX, reminiscent of chronically activated T cells. These novel findings illustrate how T-IEL integrate multiple tissue-specific signals to maintain their homeostasis and potentially function.
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http://dx.doi.org/10.7554/eLife.70055DOI Listing
September 2021

Genome-Wide Scan for Parent-of-Origin Effects in a sub-Saharan African Cohort With Nonsyndromic Cleft Lip and/or Cleft Palate (CL/P).

Cleft Palate Craniofac J 2021 Aug 12:10556656211036316. Epub 2021 Aug 12.

Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa, IA, USA.

Objective: Nonsyndromic cleft lip and/or cleft palate (NSCL/P) have multifactorial etiology where genetic factors, gene-environment interactions, stochastic factors, gene-gene interactions, and parent-of-origin effects (POEs) play cardinal roles. POEs arise when the parental origin of alleles differentially impacts the phenotype of the offspring. The aim of this study was to identify POEs that can increase risk for NSCL/P in humans using a genome-wide dataset.

Methods: The samples (174 case-parent trios from Ghana, Ethiopia, and Nigeria) included in this study were from the African only genome wide association studies (GWAS) that was published in 2019. Genotyping of individual DNA using over 2 million multiethnic and African ancestry-specific single-nucleotide polymorphisms from the Illumina Multi-Ethnic Genotyping Array v2 15070954 A2 (genome build GRCh37/hg19) was done at the Center for Inherited Diseases Research. After quality control checks, PLINK was employed to carry out POE analysis employing the pooled subphenotypes of NSCL/P.

Results: We observed possible hints of POEs at a cluster of genes at a 1 mega base pair window at the major histocompatibility complex class 1 locus on chromosome 6, as well as at other loci encompassing candidate genes such as , , , , , , , , , lncRNAs, microRNA, antisense RNAs, , , and .

Conclusion: Findings from our study suggest that some loci may increase the risk for NSCL/P through POEs. Additional studies are required to confirm these suggestive loci in NSCL/P etiology.
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http://dx.doi.org/10.1177/10556656211036316DOI Listing
August 2021

Congenital heart defects in orofacial cleft: A prospective cohort study.

Afr J Paediatr Surg 2021 Oct-Dec;18(4):219-223

Department of Oral and Maxillofacial Surgery, College of Medicine, University of Lagos; Department of Oral and Maxillofacial Surgery, Lagos University Teaching Hospital, Lagos, Nigeria.

Background: Congenital heart defects (CHDs) are one of the most common associated anomalies in patients with an orofacial cleft (OFC). However, few studies have shown the association between cleft type and CHDs in our population. This study aimed to assess the prevalence of CHDs in a cohort of OFC patients at a tertiary health facility in Nigeria, as well as assess the risk of CHD by OFC type.

Materials And Methods: This was a prospective study design. Patients with an OFC were consecutively enrolled at a single OFC treatment facility. All subjects were assessed by a paediatric cardiologist and had echocardiography done. They were categorised based on the presence of CHDs, as well as the OFC phenotypic type (cleft lip and/or alveolus, cleft lip and palate and cleft palate only). Statistical analysis was done using STATA version 14 (College Station, Texas), and significance was set at P < 0.05.

Results: A total of 150 subjects enrolled in the study over a period of 2 years (2018-2020). The median age of subjects was 6 months (interquartile range: 2-24), and 54.7% were female. The prevalence of CHDs in the subjects reviewed was 30.7%. Based on the severity of CHDs, the majority presented with simple defects (95.6%). Overall, the most common presentation was patent foramen ovale (12.7%), followed by septal defects (8.0%). There was no significant association between cleft type and the odds of a CHD.

Conclusion: The study reports a relatively high prevalence of CHDs in patients with OFC; however, there was no association between the risk of CHD by cleft type. Although a majority of CHDs may pose a low operative risk, cardiac evaluation is recommended for all cases of OFC to aid the identification of potentially high-risk cases.
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http://dx.doi.org/10.4103/ajps.AJPS_159_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423164PMC
August 2021

Trainee perspective of the causes of stress and burnout in surgical training: a qualitative study from Wales.

BMJ Open 2021 08 2;11(8):e045150. Epub 2021 Aug 2.

School of Surgery, NHS Wales Health Education and Improvement Wales, Nantgarw, UK.

Objectives: Stress and burn-out among surgical trainees has been reported most prevalent in core surgical trainees (CST) and female trainees in particular. This study aimed to identify factors perceived by CSTs to be associated with stress and burnout in those at risk.

Design: An open-ended questionnaire was distributed to 79 CSTs and two researchers categorised responses independently, according to Michie's model of workplace stress.

Setting: A UK regional postgraduate medical region (Wales).

Participants: Sixty-three responses were received; 42 males, 21 females. The response rate was 79.7%.

Results: Inter-rater reliability was good (k=0.792 (79.2%), p<0.001). The most common theme of Michie's model related to CST stress and burnout was career development, with most statements associated with curriculum, examination and academic demands required to attain a CST certificate of completion of training, and higher surgical national training number appointment. This was closely followed by those intrinsic to the job with recurrent discussion around the difficulties balancing work perceived to be service provision (ward work and on-calls), outpatient clinic and operative experience. Conversely, the most common themes relevant to stress and burnout among female trainees were associated with relationships at work (primarily the male-dominated nature of surgery), extraorganisational factors (family-work life balance) and individual characteristics (personality and physiological differences).

Conclusion: CSTs' perceptions regarding the causes of National Health Service related stress and burnout are numerous, and these findings provide a basis for the development of targeted stressor counter-measures to improve training and well-being.
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http://dx.doi.org/10.1136/bmjopen-2020-045150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330580PMC
August 2021

Enhanced stress-resilience training for surgical trainees.

BJS Open 2021 07;5(4)

Department of Surgery, Morriston Hospital, Swansea Bay University Health Board, Swansea, UK.

Introduction: Core surgical training programmes are associated with a high risk of burnout. This study aimed to assess the influence of a novel enhanced stress-resilience training (ESRT) course delivered at the start of core surgical training in a single UK statutory education body.

Method: All newly appointed core surgical trainees (CSTs) were invited to participate in a 5-week ESRT course teaching mindfulness-based exercises to develop tools to deal with stress at work and burnout. The primary aim was to assess the feasibility of this course; secondary outcomes were to assess degree of burnout measured using Maslach Burnout Inventory (MBI) scoring.

Results: Of 43 boot camp attendees, 38 trainees completed questionnaires, with 24 choosing to participate in ESRT (63.2 per cent; male 13, female 11, median age 28 years). Qualitative data reflected challenges delivering ESRT because of arduous and inflexible clinical on-call rotas, time pressures related to academic curriculum demands and the concurrent COVID-19 pandemic (10 of 24 drop-out). Despite these challenges, 22 (91.7 per cent) considered the course valuable and there was unanimous support for programme development. Of the 14 trainees who completed the ESRT course, nine (64.3 per cent) continued to use the techniques in daily clinical work. Burnout was identified in 23 trainees (60.5 per cent) with no evident difference in baseline MBI scores between participants (median 4 (range 0-11) versus 5 (1-11), P = 0.770). High stress states were significantly less likely, and mindfulness significantly higher in the intervention group (P < 0.010); MBI scores were comparable before and after ESRT in the intervention cohort (P = 0.630, median 4 (range 0-11) versus 4 (1-10)).

Discussion: Despite arduous emergency COVID rotas ESRT was feasible and, combined with protected time for trainees to engage, deserves further research to determine medium-term efficacy.
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http://dx.doi.org/10.1093/bjsopen/zrab054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320339PMC
July 2021

Facial Anthropometry Measurements Using Three-Dimensional Stereophotogrammetry Analysis Among Nigerians.

J Craniofac Surg 2021 Jul 23. Epub 2021 Jul 23.

Department of Oral and Maxillofacial Surgery, Lagos University Teaching Hospital, Idi-Araba, Lagos Department of Archeology and Anthropology, University of Ibadan, Ibadan Department of Oral and Maxillofacial Surgery, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA Department of Orthodontics, University of Dundee, Dundee, UK Center for Craniofacial and Dental Genetics, Department of Oral Biology and Human Genetics, University of Pittsburgh, Pittsburgh, PA.

Abstract: This study aimed to determine the normative facial anthropometry measurement among Nigerians using three-dimensional stereophotogrammetry analysis.This study was carried out in Lagos, Nigeria over a period of 3 years. The sample population was Nigerians of diverse ethnic groups, age 16 and above with no history of congenital or acquired craniofacial deformities.A total of 452 subjects participated in the study with 56.2% males and 43.8% females. Most of the participants were between the ages of 25 to 49 (54.4%), 40.7% were less than 25 years of age and only 4.4% were more than 50 years old. The mean body mass index (BMI) for males was 22.7 and 23.4 for females. Mean values of upper facial height, midfacial height, lower facial height, intercanthal distance, interpupillary distance, upper facial width, and lower facial width are 69.13 ± 5.91, 49.89 ± 3.56, 67.85 ± 6.12, 35.19 ± 3.20, 67.04 ± 3.67, 139.43 ± 7.11, and 124.29 ± 9.72 mm, respectively. The upper facial height, commissure width, upper lip length, and lower jaw width were significantly affected by age, while the BMI of an individual was a determinant of the interpupillary distance, facial width, and lower jaw width.This study demonstrated that there was a statistically significant difference in the facial dimensions of males when compared to females across all ages among the study population. The authors also observed that age and BMI are significant predictors of variations in some of the measurements.
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http://dx.doi.org/10.1097/SCS.0000000000008036DOI Listing
July 2021

IL-15 and PIM kinases direct the metabolic programming of intestinal intraepithelial lymphocytes.

Nat Commun 2021 07 13;12(1):4290. Epub 2021 Jul 13.

MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK.

Intestinal intraepithelial lymphocytes (IEL) are an abundant population of tissue-resident T cells that protect and maintain the intestinal barrier. IEL respond to epithelial cell-derived IL-15, which is complexed to the IL-15 receptor α chain (IL-15/Rα). IL-15 is essential both for maintaining IEL homeostasis and inducing IEL responses to epithelial stress, which has been associated with Coeliac disease. Here, we apply quantitative mass spectrometry to IL-15/Rα-stimulated IEL to investigate how IL-15 directly regulates inflammatory functions of IEL. IL-15/Rα drives IEL activation through cell cycle regulation, upregulation of metabolic machinery and expression of a select repertoire of cell surface receptors. IL-15/Rα selectively upregulates the Ser/Thr kinases PIM1 and PIM2, which are essential for IEL to proliferate, grow and upregulate granzyme B in response to inflammatory IL-15. Notably, IEL from patients with Coeliac disease have high PIM expression. Together, these data indicate PIM kinases as important effectors of IEL responses to inflammatory IL-15.
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http://dx.doi.org/10.1038/s41467-021-24473-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277781PMC
July 2021

Missense Variants Within GJB2 Gene Locus and the Risk of Hearing Defects in Nonsyndromic Cleft Lip and Palate.

J Craniofac Surg 2021 Jun 30. Epub 2021 Jun 30.

Department of Oral and Maxillofacial Surgery, Faculty of Dental Sciences, College of Medicine University of Lagos Department of Ear, Nose and throat, Lagos University Teaching Hospital Department of Oral and Maxillofacial Surgery, Lagos University Teaching Hospital, Lagos, Nigeria College of Dentistry, University of Iowa, Iowa City, IA.

Aim: The aim of the study was to investigate the role of variants in GJB2 gene in the etiology of hearing defects in nonsyndromic cleft lip/palate.

Method: Saliva samples were obtained from cases (subjects with orofacial clefts) and control (subjects without orofacial clefts) who consented to the study. Deoxyribonucleic acid (DNA) was extracted using standardized protocol at Butali Lab (Iowa, IA). Primers for the coding region of GJB2 was designed using Primer 3 (http://bioinfo.ut.ee/primer3-0.4.0/) and optimized in the Butali lab using a gradient polymerase chain reaction to determine the annealing temperature for each primer set (forward and reverse). We measured the DNA concentration using Qubit and XY genotyping done for quality control. A concentration of 5 ng/μL of DNA was used for Sanger sequencing.

Results: A total of 150 subjects were sequenced (66 cases; 84 controls). Mutations in GJB2 gene were detected in 2 individuals with cleft palate. We found p.Arg165Trp variant in 1 case and p.Leu81Val variant in the second case. Although p.Arg165Trp was predicted to be either benign or tolerated by SIFT/POLYPHEN, the single nucleotide change from C>T, that is, CGG>TGG leads to a premature stop codon preventing the protein formation. The p.Leu81Val variant was predicted to be probably damaging/ deleterious.

Conclusions: The present study implicates variants in the GJB2 gene in the etiology of hearing defects in nonsyndromic cleft lip and palate in the Nigerian population. Screening for variations in GJB2 gene is important for genetic counseling especially in high-risk families.
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http://dx.doi.org/10.1097/SCS.0000000000007921DOI Listing
June 2021

Variant analyses of candidate genes in orofacial clefts in multi-ethnic populations.

Oral Dis 2021 Jun 1. Epub 2021 Jun 1.

Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA.

Objectives: Cleft lip with/without cleft palate and cleft palate only is congenital birth defects where the upper lip and/or palate fail to fuse properly during embryonic facial development. Affecting ~1.2/1000 live births worldwide, these orofacial clefts impose significant social and financial burdens on affected individuals and their families. Orofacial clefts have a complex etiology resulting from genetic variants combined with environmental covariates. Recent genome-wide association studies and whole-exome sequencing for orofacial clefts identified significant genetic associations and variants in several genes. Of these, we investigated the role of common/rare variants in SHH, RORA, MRPL53, ACVR1, and GDF11.

Materials And Methods: We sequenced these five genes in 1255 multi-ethnic cleft lip with/without palate and cleft palate only samples in order to find variants that may provide potential explanations for the missing heritability of orofacial clefts. Rare and novel variants were further analyzed using in silico predictive tools.

Results: Ninteen total variants of interest were found, with variant types including stop-gain, missense, synonymous, intronic, and splice-site variants. Of these, 3 novel missense variants were found, one in SHH, one in RORA, and one in GDF11.

Conclusion: This study provides evidence that variants in SHH, RORA, MRPL53, ACVR1, and GDF11 may contribute to risk of orofacial clefts in various populations.
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http://dx.doi.org/10.1111/odi.13932DOI Listing
June 2021

Awareness and acceptability of HIV pre-exposure prophylaxis (PrEP) among students at two historically Black universities (HBCU): a cross-sectional survey.

BMC Public Health 2021 05 19;21(1):943. Epub 2021 May 19.

Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.

Background: Despite young African American adults (ages 18-24) being among the highest risk groups for HIV infection, little is known about their awareness of HIV pre-exposure prophylaxis (PrEP) - a once daily pill shown to be > 90% effective in preventing HIV. To explore awareness and acceptability of PrEP among college students in this demographic, we conducted a survey of attendees at two large historically Black universities (HBCU) in North Carolina.

Methods: We administered a 14-item questionnaire to students at two HBCUs in North Carolina between February and April 2018. Questions were formatted in a yes/no or multiple choice format. Questionnaire items specifically addressed PrEP awareness and acceptability. Surveys were administered to students at a campus health fair and while transiting the campus student union via iPad. Response to all questions was optional. We fit a logistic regression model to determine association of key demographic determinants with PrEP acceptability and awareness. Statistical analyses were conducted using SAS 9.4 (SAS, Cary, NC).

Results: Overall, 210 students participated in the survey, of which 60 completed all survey items as presented. The survey cohort was 75% female, 89% heterosexual and 39% freshmen. The mean age of respondents was 19.8 years (SD: 1.8). Fifty-two percent of survey respondents reported that they were aware of PrEP prior to the time of survey administration. Only 3% of respondents reported that they were on PrEP. The most common sources of information on PrEP were campus health services (24%) and non-social media advertising (15%). Of respondents who were aware of PrEP, 61% reported that they had heard about in the 6 months prior to survey administration, while only 19% say they were aware of it for more than a year. Regarding acceptability of PrEP, 58% of respondents reported that they would take a once a day pill for HIV if they were at risk. Our logistic regression analysis found no statistically significant associations between key demographic factors and PrEP awareness. However, persons who perceived themselves to be at risk for HIV acquisition were more likely to find once daily oral PrEP (relative risk 2.66 (95% CI 1.31-5.42)) as an acceptable prevention strategy than the rest of the survey cohort.

Conclusions: African American HBCU students are becoming aware of PrEP, and generally perceive the intervention as acceptable and worth consideration.
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http://dx.doi.org/10.1186/s12889-021-10996-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132367PMC
May 2021

iPSC-derived myelinoids to study myelin biology of humans.

Dev Cell 2021 05;56(9):1346-1358.e6

UK Dementia Research Institute at the University of Edinburgh, Edinburgh EH16 4SB, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK; Euan MacDonald Centre for Motor Neurone Disease Research University of Edinburgh, Edinburgh EH16 4SB, UK; Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh EH16 4SB, UK; Centre for Brain Development and Repair, inStem, Bangalore 560065, India. Electronic address:

Myelination is essential for central nervous system (CNS) formation, health, and function. Emerging evidence of oligodendrocyte heterogeneity in health and disease and divergent CNS gene expression profiles between mice and humans supports the development of experimentally tractable human myelination systems. Here, we developed human iPSC-derived myelinating organoids ("myelinoids") and quantitative tools to study myelination from oligodendrogenesis through to compact myelin formation and myelinated axon organization. Using patient-derived cells, we modeled a monogenetic disease of myelinated axons (Nfasc155 deficiency), recapitulating impaired paranodal axo-glial junction formation. We also validated the use of myelinoids for pharmacological assessment of myelination-both at the level of individual oligodendrocytes and globally across whole myelinoids-and demonstrated reduced myelination in response to suppressed synaptic vesicle release. Our study provides a platform to investigate human myelin development, disease, and adaptive myelination.
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http://dx.doi.org/10.1016/j.devcel.2021.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098746PMC
May 2021

Hepatic Arterial Infusion Pumps: What the Radiologist Needs to Know.

Radiographics 2021 May-Jun;41(3):895-908. Epub 2021 Mar 26.

From the Departments of Radiology (K.J.N., O.G.J., B.W.T.) and Surgery (M.E.L.), Duke University Medical Center, Box 3808, Durham, NC 27710.

Hepatic arterial infusion (HAI) entails the surgical implantation of a subcutaneous pump to deliver chemotherapeutic agents directly to the liver in the setting of primary or secondary liver cancer. The purpose of HAI chemotherapy is to maximize hepatic drug concentrations while minimizing systemic toxicity, facilitating more effective treatment. HAI is used in combination with systemic chemotherapy and can be considered in several clinical scenarios, including adjuvant therapy, conversion of unresectable disease to resectable disease, and unresectable disease. Radiologists are key members of the multidisciplinary team involved in the selection and management of these patients with complex liver disease. As these devices begin to be used at more sites across the country, radiologists should become familiar with the guiding principles behind pump placement, expected imaging appearances of these devices, and potential associated complications. The authors provide an overview of HAI therapy, with a focus on the key imaging findings associated with this treatment that radiologists may encounter. RSNA, 2021.
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http://dx.doi.org/10.1148/rg.2021200130DOI Listing
March 2021

Management of Orofacial Cleft in Nigeria - A Retrospective Study.

Ann Maxillofac Surg 2020 Jul-Dec;10(2):434-438. Epub 2020 Dec 23.

Department of Oral and Maxillofacial Surgery, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria.

Introduction: Orofacial clefts (OFCs) are among the most common craniofacial developmental abnormalities worldwide and a significant cause of childhood morbidity and mortality. This study aimed to identify patterns of patient presentation, treatment approaches, and changes in our overall cleft care service between 2007 and 2019.

Methods And Methodology: A retrospective review of patients managed at a tertiary health facility in Nigeria of all OFC cases operated between 2007 and 2019 was done using the postintervention data retrieved from the Smile Train database. Data of all OFC cases operated within the period were analyzed using the Statistical Package for the Social Sciences. Descriptive statistics were performed using the Statistical Package for the Social Sciences version 20.0.

Results: A total number of 740 OFC surgeries were performed in 565 patients, consisting of 269 females (48.2%) and 289 males (51.8%). The majority (63%) of the patients presented before the age of 2 years. Thirty-seven percent presented with cleft lip and alveolus, 27.1% with cleft palate only, and 36.7% with cleft lip, alveolus, and palate. Primary cleft lip repair was the most performed surgery (n = 320, 43.2%), the mean age at repair was 2.1 years. Since 2017, additional services such as speech therapy, mixed dentition orthodontics, and nutritional support were added to services provided to our cleft patients. Fifteen patients have undergone speech assessment and three have completed speech treatment. Eight patients have undergone mixed dentition stage orthodontic treatment.

Discussion: Our services have evolved from simply providing surgical care to comprehensive care with a multidisciplinary team approach and provision of a wide range of services including nutritional counseling, pediatric care, orthodontic services, and speech therapy. We believe these will improve the overall well-being of our patients while we continue to improve on services based on clinical research outcomes.
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http://dx.doi.org/10.4103/ams.ams_104_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943976PMC
December 2020

Parental Age and the Risk of Cleft Lip and Palate in a Nigerian Population - A Case-Control Study.

Ann Maxillofac Surg 2020 Jul-Dec;10(2):429-433. Epub 2020 Aug 24.

Department of Oral and Maxillofacial Surgery, Lagos University Teaching Hospital, Idi Araba, Lagos, Nigeria.

Introduction: Orofacial clefts are one of the most common congenital malformations in the facial region. Older maternal or paternal age presents higher odds of a child with an orofacial cleft. The objective of the study was to assess the association between parental age and risk of orofacial cleft.

Materials And Methods: This was a case-control study among 110 parents of children with orofacial cleft (case group) and 110 parents of children without orofacial cleft (control group). Information on maternal age, paternal age, and type of orofacial cleft in the children were obtained. The results were analyzed using descriptive statistics, Chi-square analysis, and bivariate logistic regressions to measure the association between parental age and orofacial cleft. The value of P was <0.05, with a 95% confidence interval (CI).

Results: Information on 219 children (109 cases and 110 controls) was analyzed, of which 52% were females. One respondent from the case group withdrew from the study. The odds of a child with orofacial cleft was statistically significantly lower in mothers aged 26-35 years compared to mothers aged 25 years and less (odds ratio [OR]: 0.32; 95% CI: 0.16, 0.79). Similarly, fathers aged above 35 years had statistically significantly lower odds of children with orofacial cleft than those 25 years and less (OR: 0.18; 95% CI: 0.02, 0.99).

Discussion: Our findings suggest that mothers aged 26-35 years may have lower odds of giving birth to babies with orofacial clefts, compared to younger mothers. Similarly, fathers aged above 35 years may have lower odds of giving birth to a child with orofacial cleft compared to fathers aged 25 years and less.
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http://dx.doi.org/10.4103/ams.ams_134_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944012PMC
August 2020

Does the Initial Width of Cleft Lip Play a Role in the Occurrence of Immediate Local Complications Following Primary Cleft Lip Repairs?

J Craniofac Surg 2021 Mar-Apr 01;32(2):670-674

Department of Oral and Maxillofacial Surgery, Lagos University Teaching Hospital (LUTH), Idi-Araba.

Objective: Among the several factors implicated in the occurrence of local surgical site complications following cleft lip repair is the initial width of the cleft. The aim of the study was to examine the effect of cleft width in the occurrence of immediate local surgical site complications.

Material And Methods: All consecutive subjects with diagnosis of unilateral or bilateral cleft lip with or without cleft palate who presented at the cleft clinic and satisfied the inclusion criteria were recruited in the study. The width of the cleft lip defect as adopted for the study was measured from the peak of the Cupid bow on the non-cleft side to a point where the white roll begins to thin out on the cleft side. Measurement was done using a Vernier Calliper. Surgery was performed under general anesthesia after which subjects were evaluated for the presence or absence of immediate local surgical site complications which included dehiscence, infection, and vermillion notching of the lip.

Results: A total of 70 subjects consisting of 36 (51.4%) males and 34 (48.6%) females were included in the study. Mean age (±SD) was 9.0 ± (19.4) months with age range of 3 months to 13 years. The prevalence of early surgical site complications was 24.3%. The width of cleft above a critical level (14 mm) statistically correlate significantly with the occurrence of early surgical site complications (P = 0.048).

Conclusion: This study showed that the width of cleft lip of and above critical level of 14 mm may be associated with a clinically significant risk of immediate local surgical site complications.
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http://dx.doi.org/10.1097/SCS.0000000000007179DOI Listing
June 2021

Comparing the Treatment Outcomes of Absorbable Sutures, Nonabsorbable Sutures, and Tissue Adhesives in Cleft Lip Repair: A Systematic Review.

Cleft Palate Craniofac J 2021 Mar 3:1055665621996107. Epub 2021 Mar 3.

Department of Oral and Maxillofacial Surgery, College of Medicine, University of Lagos, Lagos, Nigeria.

Objectives: To examine the literature and synthesize the available reports for the best possible option between absorbable, nonabsorbable, and tissue adhesives in cleft lip skin closure.

Design: We conducted systematic searches for randomized controlled trials and controlled clinical trials in PubMed, Cochrane, Ovid Medline, and OpenGrey databases. Identified studies were retrieved and assessed for eligibility. All statistical analyses were done with Revman, version 5.4.

Interventions: The intervention considered in this systematic review were techniques of cleft lip repair using resorbable sutures, nonabsorbable sutures, medical adhesives, or any combination of these.

Outcome Measures: The primary outcomes assessed in the trials had to include any combination of the following: wound healing cosmesis and wound healing complications. While secondary outcomes considered were quality of life, direct and indirect costs to patients and health services, and participant satisfaction.

Results: Only 6 studies met all inclusion criteria and were selected for qualitative analysis. A more favorable wound healing cosmesis was seen when nonabsorbable suture was used in cleft lip repair compared to absorbable sutures and tissue adhesives (CI, 0.65-4.35). This advantage was overshadowed by the significantly higher prevalence of postoperative complications when nonabsorbable sutures are used.

Conclusion: Although the results point to more favorable cosmesis with nonabsorbable sutures and an overall more favorable outcome with either absorbable sutures or tissue adhesives, the 6 selected studies were assessed at an unclear risk of bias; therefore, the results of this study should be interpreted with caution and regarded as low-certainty evidence.
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http://dx.doi.org/10.1177/1055665621996107DOI Listing
March 2021

How Does Octyl-2-Cyanoacrylate Tissue Adhesive Compare With Prolene Sutures in Cleft Lip Repair?

J Oral Maxillofac Surg 2021 07 28;79(7):1540-1548. Epub 2021 Jan 28.

Professor, Department of Oral and Maxillofacial Surgery, College of Medicine, University of Lagos, Idi - Araba, Lagos, Nigeria.

Purpose: Comparative evidence of the usefulness of octyl-2-cyanoacrylate tissue adhesive in cleft lip epidermal skin closure especially in Africans is still lacking. This study aimed to compare the outcome of wound healing after the use of Dermabond tissue adhesive and 5/0 Prolene sutures in cleft lip repair.

Methods: This was a prospective randomized controlled clinical study. The sampled population was patients undergoing cleft lip repair at a tertiary health facility in Lagos, Nigeria. Study patients were randomly allocated to either group A (Dermabond) or group B (suture). The predictor variable was the type of material used in skin closure; the primary outcome variable was the esthetics of the resulting scar, and secondary outcome variables were wound healing complications. Assessment of the 3-month postoperative wound scar was performed using the cosmetic visual analog scale (CVAS) and the Hollander Wound Evaluation scale (HWES). Calculated sample size was 14 participants per group. Descriptive and comparative statistics were computed, and the P value was set at <0.05.

Results: Analysis of result included 38 participants. Median age was 4 months and 52.6% were women. Two cases (5.3%) of wound healing complications were recorded (1 in each group). Blinded evaluation of the 3-month postoperative photographs yielded a mean CVAS score of 86.0 (±11.2) and HWES score of 5.0 (±0.9) for group A and a mean CVAS score of 76.5 (±14.5) and HWES score of 4.5 (±1.1) for group B. There was no statistically significant difference between these 2 groups based on the CVAS (P = .052) and HWES (P = .152).

Conclusions: The results of this study suggest Dermabond offers a comparable cosmetic outcome as 5/0 Prolene suture in epidermal closure of cleft lip. There was no statistically significant difference in wound complications and wound cosmetic scores between the 2 groups.
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http://dx.doi.org/10.1016/j.joms.2021.01.026DOI Listing
July 2021

Predictive value of Altmetric score on citation rates and bibliometric impact.

BJS Open 2021 01;5(1)

Health Education and Improvement Wales' School of Surgery, Ty Dysgu, Nantgarw, UK.

Background: Bibliometric and Altmetric analyses provide different perspectives regarding research impact. This study aimed to determine whether Altmetric score was associated with citation rate independent of established bibliometrics.

Methods: Citations related to a previous cohort of 100 most cited articles in surgery were collected and a 3-year interval citation gain calculated. Citation count, citation rate index, Altmetric score, 5-year impact factor, and Oxford Centre for Evidence-Based Medicine levels were used to estimate citation rate prospect.

Results: The median interval citation gain was 161 (i.q.r. 83-281); 74 and 62 articles had an increase in citation rate index (median increase 2.8 (i.q.r. -0.1 to 7.7)) and Altmetric score (median increase 3 (0-4)) respectively. Receiver operating characteristic (ROC) curve analysis revealed that citation rate index (area under the curve (AUC) 0.86, 95 per cent c.i. 0.79 to 0.93; P < 0.001) and Altmetric score (AUC 0.65, 0.55 to 0.76; P = 0.008) were associated with higher interval citation gain. An Altmetric score critical threshold of 2 or more was associated with a better interval citation gain when dichotomized at the interval citation gain median (odds ratio (OR) 4.94, 95 per cent c.i. 1.99 to 12.26; P = 0.001) or upper quartile (OR 4.13, 1.60 to 10.66; P = 0.003). Multivariable analysis revealed only citation rate index to be independently associated with interval citation gain when dichotomized at the median (OR 18.22, 6.70 to 49.55; P < 0.001) or upper quartile (OR 19.30, 4.23 to 88.15; P < 0.001).

Conclusion: Citation rate index and Altmetric score appear to be important predictors of interval citation gain, and better at predicting future citations than the historical and established impact factor and Oxford Centre for Evidence-Based Medicine quality descriptors.
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http://dx.doi.org/10.1093/bjsopen/zraa039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893457PMC
January 2021

Correlation Between Height and Impacted Third Molars and Genetics Role in Third Molar Impaction.

J Maxillofac Oral Surg 2021 Mar 31;20(1):149-153. Epub 2020 Jan 31.

Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, USA.

Aim: This study sought to evaluate the relationship between height of an individual and the presence of impaction of maxillary and mandibular third molars, and to determine the role of genetics in third molar impaction.

Materials And Methods: This was a case-control study, with cases consisted of 200 subjects with third molar impactions; and 200 controls without third molar impactions. Height of subjects was measured, and saliva samples were collected from all the subjects. DNA was extracted from saliva samples. To investigate the role of selected genes in the etiology of third molar impactions, Taqman Genotyping using SNPs identified for jaw growth, height and tooth agenesis was employed. Five candidate genes were investigated using 11 markers (SNPs).

Results: The mean height of cases was significantly lower than that of the control subjects (= 0.04). No difference was found in allele frequency between cases and controls for 10 of the 11 SNPs. However, for rs6504591 the value was near significance (= 0.07) with odd ratio of 2.131. Subjects with lower third molar impactions were significantly shorter than those who have fully erupted third molars.

Conclusions: Subjects with lower third molar impactions were significantly shorter than those who have fully erupted third molars. We observed that individuals with third molar impaction tend to have T allele at the locus, suggesting that the T allele at the locus may increase the risk for having an impacted third molar. The rs6504591 G/T variation on human chromosome 17 (WNT9B gene) appears to increase risk by twofolds for impaction albeit with inability to detect significance due to small sample size.
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http://dx.doi.org/10.1007/s12663-020-01336-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855106PMC
March 2021

Gongs galore: phaleristic study of the relative risk of a healing art related New Year Honour.

Postgrad Med J 2021 Feb 9. Epub 2021 Feb 9.

School of Surgery, NHS Wales Health Education and Improvement Wales, Nantgarw, UK.

Objectives: To compare proportional representation of healthcare specialty workers, in receipt of New Year Honours (NYHs) and examine system bias.

Design: Observational study of UK honours system including comparative analysis of proportional representation of the UK medical workforce.

Participants: Recipients of NYHs from 2010 to 2019.

Main Outcome Measures: Absolute risk of receiving an NYH, related to medical specialty, gender and geographical region. Relative risk (RR) of receiving an NYH for services to healthcare related to specialty.

Results: 11 207 NYHs were bestowed, with 368 (3.3%) awarded to healthcare professionals: 212 (57.6%) women, 156 (42.4%) men. The RR of a healthcare professional receiving an NYH was 0.76 (95% CI 0.68 to 0.84, p<0.001) when compared with the remaining UK workforce. Doctors received most NYHs (n=181), with public health, clinical oncology and general medicine specialties most likely to be rewarded (RR 20.35 (95% CI 9.61 to 43.08, p<0.001), 8.43 (95% CI 2.70 to 26.30, p<0.001) and 8.22 (95% CI 6.22 to 10.86, p<0.001)), respectively; anaesthetists received fewest NYHs (RR 0.52 (95% CI 0.13 to 2.10), p=0.305). Men were more likely to receive NYHs than women (OR 0.44, 95% CI 0.36 to 0.54; p<0.001). Two hundred and fifty-four NYHs (69.0%) were bestowed on residents of England (60, 16.3% London), 49 (13.3%) Scotland (p=0.003), 39 (10.6%) Wales (p<0.001) and 26 (7.1%) Northern-Ireland (p<0.001).

Conclusions: Relative risk of receiving an NYH varied over 150-fold by specialty, twofold by gender and threefold by geographical location. Public health physicians are perceived to be the pick of the parade.
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http://dx.doi.org/10.1136/postgradmedj-2020-139368DOI Listing
February 2021

Surgical curriculum concordance: requiem for the educational dream.

Postgrad Med J 2021 Jan 29. Epub 2021 Jan 29.

School of Surgery, NHS Wales Health Education and Improvement Wales, Nantgarw, Rhondda Cynon Taff, UK.

This study aimed to analyse the degree of relative variation in speciality-specific competencies required for Certification of Completion of Training (CCT) set by the UK Joint Committee for Surgical Training (JCST) 2021 curriculum. Regulatory body guidance related to operative and non-operative surgical skill competencies required for CCT were analysed and compared. Wide inter-speciality variation was demonstrated in the minimum number of logbook cases (median 815; range 54 to 2100), indexed operations (8; 5 to 24) and procedure-based assessments (35; 6 to 110). Academic competencies related to peer-reviewed publications, communications to learned societies and audits were aligned at zero, zero and three across specialities, respectively. Mandatory courses have been standardised with Advanced Trauma Life Support being the sole pre-requisite CCT for all. JCST certification guidelines have broadly standardised competency domains, yet large discrepancies persist regarding operative indicative numbers and assessments. This article serves as a definitive CCT guide regarding prevailing changes.
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http://dx.doi.org/10.1136/postgradmedj-2020-139385DOI Listing
January 2021

The Leaning Tower of Pasta: Lessons in Team Performance and Creativity From a Core Surgical Training Boot Camp Design Challenge.

J Surg Educ 2021 Sep-Oct;78(5):1702-1708. Epub 2021 Jan 15.

Health Education and Improvement Wales' School of Surgery, Nantgarw, United Kingdom.

Aims: Unity of effort is an important component of strategic leadership and management theory associated with Core Surgical Training (CST) outcome. The aim was to determine the impact of team diversity on task completion: a creative design challenge, during CST Boot camp.

Methods: Attendees (n = 44) at a single Statutory Education Body's CST Boot camp were stratified into teams related to specialty theme, and set a design challenge as described by Peter Skillman, to build the tallest free-standing tower out of spaghetti (20 pieces), tape (1 m), and string (1 m), with a marshmallow on top in 18 minutes. Primary outcome measure was tower height.

Results: Five teams (50%) completed the task with the tallest tower measuring 70 cm (median 51, range 0-70). Median satisfaction with the simulation exercise was 4 (2-5) on a scale of 0 to 5, with 5 corresponding with highest satisfaction. Successful task completion was associated with team surgical specialty (p = 0.032), ethnicity ratio (p = 0.010,), and gender ratio (p = 0.003), respectively. On multivariable analysis, only team gender ratio was independently associated with tower height (Hazard ratio 0.515, 95% confidence interval 0.350-0.759, p = 0.001).

Conclusion: Modern leadership theory emphasizes the important dynamic relationship between individual team members, the team, and task completion. General surgery themed teams with a gender mix were most successful in completing the design challenge; whether relative simulation performance predicts strategic organizational skill and career progression will be the next question.
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http://dx.doi.org/10.1016/j.jsurg.2020.12.020DOI Listing
January 2021

Evaluating Alzheimer Disease With Flortaucipir and Florbetapir PET: A Clinical Case Series.

Clin Nucl Med 2021 Jul;46(7):605-608

From the Division of Nuclear Medicine and PET Center, Department of Radiology.

Abstract: Early, accurate diagnosis of Alzheimer disease (AD) is essential but remains challenging. Neuropathological hallmarks of AD are β-amyloid neuritic plaques and tau protein neurofibrillary tangles. 18F-Florbetapir is one of several available PET tracers for imaging cortical fibrillary β-amyloid plaques. 18F-Flortaucipir PET was recently approved for evaluating the distribution and density of aggregated neurofibrillary tangles. We present cases of mild cognitive impairment or suspected AD to depict the nuances of flortaucipir distribution and scan interpretation as well as how combined information from amyloid and tau PET may help with differential diagnosis and prognosis.
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http://dx.doi.org/10.1097/RLU.0000000000003493DOI Listing
July 2021

Multimodality cardiac imaging in the 21st century: evolution, advances and future opportunities for innovation.

Br J Radiol 2021 Jan 25;94(1117):20200780. Epub 2020 Nov 25.

Division of Cardiothoracic Imaging, Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA.

Cardiovascular imaging has significantly evolved since the turn of the century. Progress in the last two decades has been marked by advances in every modality used to image the heart, including echocardiography, cardiac magnetic resonance, cardiac CT and nuclear cardiology. There has also been a dramatic increase in hybrid and fusion modalities that leverage the unique capabilities of two imaging techniques simultaneously, as well as the incorporation of artificial intelligence and machine learning into the clinical workflow. These advances in non-invasive cardiac imaging have guided patient management and improved clinical outcomes. The technological developments of the past 20 years have also given rise to new imaging subspecialities and increased the demand for dedicated cardiac imagers who are cross-trained in multiple modalities. This state-of-the-art review summarizes the evolution of multimodality cardiac imaging in the 21st century and highlights opportunities for future innovation.
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http://dx.doi.org/10.1259/bjr.20200780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774683PMC
January 2021

Risk of congenital cardiovascular anomalies in patients with non-syndromic orofacial cleft: A preliminary case-control study.

Niger J Clin Pract 2020 Nov;23(11):1561-1565

Department of Oral and Maxillofacial Surgery, University of Lagos; Department of Oral and Maxillofacial Surgery, Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria.

Background: Orofacial clefts (OCs) are one of the most common craniofacial anomalies and are reported to be associated with congenital cardiovascular anomalies (CCAs). However, there is paucity of data in African populations on the risk of CCAs in OC patients compared to the general population.

Aims: This study aims to determine the odds of congenital cardiovascular anomalies in patients with OC compared to the general population.

Subjects And Methods: A case-control study design was used. Case subjects were non-syndromic OC subjects, while controls were non-syndromic subjects without OC. All subjects were thoroughly assessed by a pediatric cardiologist for CCAs; and grouped by OC phenotypic type (cleft lip and/or alveolus, cleft lip and palate, cleft palate only and Tessier cleft). Statistical analysis was done using STATA version 14 (College Station, Texas), and significance was placed at P value ≤0.05.

Results: A total of 120 subjects (60 cases and 60 controls) were enrolled in the study. In total, 23.3% of the subjects had CCAs. Among the case group, 40% had CCAs compared to 6.7% in the control group. Patent foramen ovale (18.3%) and atrial septal defects (10.0%) were the most common type of CCAs in cases, respectively. Further, cases had significantly higher odds of CCAs compared to controls (OR: 9.3; CI: 2.8, 39.4).

Conclusions: Our finding reveals that the odds of CCAs are significantly higher in patients with OC than the general population. Future studies could assess the effect of CCAs on surgical outcome.
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http://dx.doi.org/10.4103/njcp.njcp_176_20DOI Listing
November 2020

A Comparative Neuro-Histological Assessment of Gluteal Skin Thickness and Cutaneous Nociceptor Distribution in Horses and Humans.

Animals (Basel) 2020 Nov 11;10(11). Epub 2020 Nov 11.

Sydney School of Veterinary Science, University of Sydney, Sydney, NSW 2006, Australia.

The current project aims to build on knowledge of the nociceptive capability of equine skin to detect superficial acute pain, particularly in comparison to human skin. Post-mortem samples of gluteal skin were taken from men ( = 5) and women ( = 5), thoroughbreds and thoroughbred types (mares, = 11; geldings, = 9). Only sections that contained epidermis and dermis through to the hypodermis were analysed. Epidermal depth, dermal depth and epidermal nerve counts were conducted by a veterinary pathologist. The results revealed no significant difference between the epidermal nerve counts of humans and horses ( = 0.051, = 0.960). There were no significant differences between epidermal thickness of humans (26.8 µm) and horses (31.6 µm) for reference (left side) samples ( = 0.117, = 0.908). The human dermis was significantly thinner than the horse dermis ( = -2.946, = 0.007). Epidermal samples were thicker on the right than on the left, but only significantly so for horses ( = 2.291, = 0.023), not for humans ( = 0.694, = 0.489). The thicker collagenous dermis of horse skin may afford some resilience versus external mechanical trauma, though as this is below the pain-detecting nerve endings, it is not considered protective from external cutaneous pain. The superficial pain-sensitive epidermal layer of horse skin is as richly innervated and is of equivalent thickness as human skin, demonstrating that humans and horses have the equivalent basic anatomic structures to detect cutaneous pain. This finding challenges assumptions about the physical capacity of horses to feel pain particularly in comparison to humans, and presents physical evidence to inform the discussion and debate regarding the ethics of whipping horses.
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http://dx.doi.org/10.3390/ani10112094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696388PMC
November 2020

Strategic organisational skills predict surgical training success.

Postgrad Med J 2020 Nov 12. Epub 2020 Nov 12.

School of Surgery, NHS Wales Health Education and Improvement Wales, Nantgarw, UK.

Introduction: Surgical career progression is determined by examination success and Annual Review of Competence Progression (ARCP) outcome, yet data on organisational skills are sparse. This study aimed to determine whether organisational skills related to Core Surgical Training (CST) outcome. Primary outcome measures include operative experience, publications, examination success (Membership of the Royal College of Surgeons or the Diploma in Otolaryngology-Head and Neck Surgery (MRCS/DO-HNS)) and ARCP outcome.

Methods: The study was conducted prospectively at three consecutive CST induction boot camps (2017-2019) providing clinical and simulation training for 125 trainees. Arrival time at course registration was the selected surrogate for organisational skills. Trainees were advised to arrive promptly at 8:45 for registration and that the course would start at 9:00. Trainee arrival times were grouped as follows: (before 8:45), (8:45-8:59am) or (after 9:00). Arrival times were compared with primary outcome measures.

Setting: Health Education and Improvement Wales' School of Surgery, UK.

Results: Median arrival time was 8:53 (range 7:55-10:03), with 29 trainees (23.2%) arriving early, 63 (50.4%) on-time and 33 (26.4%) late. Arrival time was associated with operative experience (early vs late; 206 vs 164 cases, p=0.012), publication (63.2% vs 18.5%, p=0.005), MRCS/DO-HNS success (44.8% vs 15.2%, p=0.029), ARCP outcome (86.2% vs 60.6% Outcome 1, p=0.053), but not National Training Number success (60.0% vs 53.3%, p=0.772).

Conclusions: Better-prepared trainees achieved 25% more operative experience, were four-fold more likely to publish and pass MRCS, which aligned with consistent desirable ARCP outcome. Timely arrival at training events represents a skills-composite of travel planning and is a useful marker of strategic organisational skills.
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http://dx.doi.org/10.1136/postgradmedj-2020-138763DOI Listing
November 2020
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