Whole-genome sequencing reveals de-novo mutations associated with nonsyndromic cleft lip/palate.

The majority (85%) of nonsyndromic cleft lip with or without cleft palate (nsCL/P) cases occur sporadically, suggesting a role for de novo mutations (DNMs) in the etiology of nsCL/P. To identify high impact protein-altering DNMs that contribute to the risk of nsCL/P, we conducted whole-genome sequencing (WGS) analyses in 130 African case-parent trios (affected probands and unaffected parents). We identified 162 high confidence protein-altering DNMs some of which are based on available evidence, contribute to the risk of nsCL/P. These include novel protein-truncating DNMs in the ACTL6A, ARHGAP10, MINK1, TMEM5 and TTN genes; as well as missense variants in ACAN, DHRS3, DLX6, EPHB2, FKBP10, KMT2D, RECQL4, SEMA3C, SEMA4D, SHH, TP63, and TULP4. Many of these protein-altering DNMs were predicted to be pathogenic. Analysis using mouse transcriptomics data showed that some of these genes are expressed during the development of primary and secondary palate. Gene-set enrichment analysis of the protein-altering DNMs identified palatal development and neural crest migration among the few processes that were significantly enriched. These processes are directly involved in the etiopathogenesis of clefting. The analysis of the coding sequence in the WGS data provides more evidence of the opportunity for novel findings in the African genome.

Expectations, Experiences and Perceptions of Oral and Maxillofacial Surgery Residents to Training in Nigeria.

PURPOSE: How surgical residents fare during their training could enhance job satisfaction and fulfilment post-training. But there is paucity of literature on the experiences of oral and maxillofacial surgery (OMS) trainees during residency training. The aim of this study was to report the expectations, experiences and perceptions of OMS residents towards training in Nigeria. METHODS: Cross-sectional study of OMS residents in accredited Nigerian training institutions was conducted between September and December, 2017. Study tool was adapted from that used for general surgery residents in the United States. Results were analysed using Microsoft Excel for Windows 10. RESULTS: Sixty-eight of seventy-three questionnaires were returned (response rate was 93%). More respondents were males (86.8%) than females (13.2%). 44.1% of all respondents were aged 35-39 years. Senior residents (n=31, 45.6%) were more than those in the junior cadre. The most important reason for choosing OMS residency training was for knowledge (72.1%) followed by the prospect of better pay (8.8%). Most residents believed their opinions were important (66.7%) and looked forward to their daily work (72.1%) but were dissatisfied with the didactic teaching aspect by consultants (57.3%) and felt the hours and stress of working were straining their family life, respectively (91.0% and 76.7%). CONCLUSION: Most OMS residents were happy and expected to gain knowledge from the training. However, some were dissatisfied with the training duration and level of didactic teaching by consultants and the impact of residency training on family life. There is need to improve didactic teaching and ensure adequate work/family balance for better OMS residency training in Nigeria.

Genomic analyses in African populations identify novel risk loci for cleft palate.

Orofacial clefts are common developmental disorders that pose significant clinical, economical and psychological problems. We conducted genome-wide association analyses for cleft palate only (CPO) and cleft lip with or without palate (CL/P) with ~17 million markers in sub-Saharan Africans. After replication and combined analyses, we identified novel loci for CPO at or near genome-wide significance on chromosomes 2 (near CTNNA2) and 19 (near SULT2A1). In situ hybridization of Sult2a1 in mice showed expression of SULT2A1 in mesenchymal cells in palate, palatal rugae and palatal epithelium in the fused palate. The previously reported 8q24 was the most significant locus for CL/P in our study, and we replicated several previously reported loci including PAX7 and VAX1.

What surgical approach has the lowest risk of the lower lid complications in the treatment of orbital floor and periorbital fractures? A frequentist network meta-analysis.

PURPOSE: Evidence on the best surgical approach with the lowest lower lid complications (LLCs) in the treatment of orbital floor (OF) and periorbital fractures (POFs) is limited because of the absence of head-to-head studies. We performed this network meta-analysis (NMA) to compare various surgical approaches in treatment of OFs and POFs, with respect to LLCs. MATERIALS AND METHODS: This NMA based on PRIMSA guidelines studied the incidence of the LLCs among various surgical approaches in the treatment of the OFs and POFs. We searched several databases from 1970 to March 2018. All clinical studies comparing different surgical approaches in treatment of OFs and POFs were included. Outcome variables were ectropion, entropion, scleral show and other complications. Predictor variables were transconjunctival approach (TCA), subciliary approach (SCA), subtarsal approach (STA) and infraorbital approach (IOA). Frequentist NMA was performed using STATA software. RESULTS: A total of 47 studies with 5267 cases of the OFs and POFs received ORIF using 4 surgical approaches with 6 comparisons were included. TCA significantly reduces the prevalence of ectropion than SCA (OR = 3.54, CI1.28-9.84), but no significant difference was found between TCA and, STA or TCA and IOA. SCA and STA significantly reduce the prevalence of entropion than TCA (OR = 5.02, CI, 1.79-14.06, OR = 0.11, CI, 0.02-0.57) respectively. We found no significant difference between the 6 comparisons with respect to other complications. CONCLUSION: This NMA shows that the application of various surgical approaches leads to different incidences of LLCs. While TCA appears to have the lowest overall LLCs rate, STA has lowest rate among the transcutaneous approaches. The choice of an appropriate surgical approach for a given fracture should take these among other factors into consideration. Owing to the limitations of this study, we suggest that the results be interpreted with caution.

Identification of paternal uniparental disomy on chromosome 22 and a de novo deletion on chromosome 18 in individuals with orofacial clefts.

BACKGROUND: Orofacial clefts are the most common malformations of the head and neck region. Genetic and environmental factors have been implicated in the etiology of these traits. METHODS: We recently conducted genotyping of individuals from the African population using the multiethnic genotyping array (MEGA) to identify common genetic variation associated with nonsyndromic orofacial clefts. The data cleaning of this dataset allowed for screening of annotated sex versus genetic sex, confirmation of identify by descent and identification of large chromosomal anomalies. RESULTS: We identified the first reported orofacial cleft case associated with paternal uniparental disomy (patUPD) on chromosome 22. We also identified a de novo deletion on chromosome 18. In addition to chromosomal anomalies, we identified cases with molecular karyotypes suggesting Klinefelter syndrome, Turner syndrome and Triple X syndrome. CONCLUSION: Observations from our study support the need for genetic testing when clinically indicated in order to exclude chromosomal anomalies associated with clefting. The identification of these chromosomal anomalies and sex aneuploidies is important in genetic counseling for families that are at risk. Clinicians should share any identified genetic findings and place them in context for the families during routine clinical visits and evaluations.

Affordable Laparoscopic Camera System (ALCS) Designed for Low- and Middle-Income Countries: A Feasibility Study.

BACKGROUND: Minimally invasive surgical techniques (MISTs) could have tremendous benefits in resource-poor environment. There is growing interest in MISTs in most low- and middle-income countries (LMIC), but its adoption has remained limited; this is largely due to high cost of the initial setup, lack of technological backup and limited access to training among others. An affordable laparoscopic setup will go a long way in improving access to MISTs. METHODS: A common zero degrees 10 mm scope is attached on the camera of a low-price smartphone. Two elastic bands are used to fix the scope right in front of the smartphone's main camera; alternatively, a low-cost camera coupler can be used. The device is covered with sterile transparent drapes and a light source connected with a fiber-optic cable for endoscopic use. The image can be seen in real time on a common TV screen through an HDMI connection to the smartphone, with a sterile drape. RESULTS: We were able to perform the five tasks of the Fundamentals of Laparoscopic Surgery curriculum, using our vision system with proficiency. In a pig model, we performed a tubal ligation to simulate an appendectomy and we were able to suture. No major differences were measured between the two connection systems. CONCLUSIONS: A low-cost laparoscopic camera system can benefit surgeons and trainees in LMICs. The system is already attractive for use during training, but further studies are needed to evaluate its potential clinical role in LMICs.

Geriatric dentistry education and context in a selection of countries in 5 continents.

PURPOSE/AIM: To summarize and discuss how geriatric dentistry has been addressed in dental schools of different countries regarding to (1) teaching students at the predoctoral level; (2) advanced training, and (3) research. METHOD AND MATERIALS: A convenience sample of faculty members from a selection of high, upper-middle and lower-middle income countries were recruited to complete the survey. The survey had 5 open-ended main topics, and asked about (1) the size of their elderly population, (2) general information about dental education; (3) the number of dental schools teaching geriatric dentistry, and their teaching methods; (4) advanced training in geriatric dentistry; (5) scholarship/research in geriatric dentistry. RESULTS AND CONCLUSION: (1) There is great variation in the size of elderly population; (2) duration of training and content of dental education curriculum varies; (3) geriatric dentistry has not been established as a standalone course in dental schools in the majority of the countries, (4) most countries, with the exception of Japan, lack adequate number of dentists trained in geriatric dentistry as well as training programs, and (5) geriatric dentistry-related research has increased in recent years in scope and content, although the majority of these papers are not in English.

Novel GREM1 Variations in Sub-Saharan African Patients With Cleft Lip and/or Cleft Palate.

OBJECTIVE: Cleft lip and/or cleft palate (CL/P) are congenital anomalies of the face and have multifactorial etiology, with both environmental and genetic risk factors playing crucial roles. Though at least 40 loci have attained genomewide significant association with nonsyndromic CL/P, these loci largely reside in noncoding regions of the human genome, and subsequent resequencing studies of neighboring candidate genes have revealed only a limited number of etiologic coding variants. The present study was conducted to identify etiologic coding variants in GREM1, a locus that has been shown to be largely associated with cleft of both lip and soft palate. PATIENTS AND METHOD: We resequenced DNA from 397 sub-Saharan Africans with CL/P and 192 controls using Sanger sequencing. Following analyses of the sequence data, we observed 2 novel coding variants in GREM1. These variants were not found in the 192 African controls and have never been previously reported in any public genetic variant database that includes more than 5000 combined African and African American controls or from the CL/P literature. RESULTS: The novel variants include p.Pro164Ser in an individual with soft palate cleft only and p.Gly61Asp in an individual with bilateral cleft lip and palate. The proband with the p.Gly61Asp GREM1 variant is a van der Woude (VWS) case who also has an etiologic variant in IRF6 gene. CONCLUSION: Our study demonstrated that there is low number of etiologic coding variants in GREM1, confirming earlier suggestions that variants in regulatory elements may largely account for the association between this locus and CL/P.

Pattern of traumatised anterior teeth among adult Nigerians and complications from late presentation.

BACKGROUND: The objectives of this study were to determine the prevalence and pattern of traumatic dental injury (TDI) among adults presenting in a tertiary health care facility in Nigeria, the time interval between injury and presentation in the hospital, the reasons for seeking treatment, and the complications arising due to late presentation. METHODS: Information obtained from history taking and clinical examination included Patient's demographics, the when, where, and how of the injury, previous history of trauma, time elapsed between injury and presentation at the hospital, reason for seeking treatment, tooth/teeth involved, sensibility, tenderness to percussion, mobility, presence of discolouration, swelling, sinus tract, and mobility. Radiographic findings such as periapical radiolucency, pulp canal obliteration, and root resorption were also documented. TDI was classified using the Andreasen's classification. RESULTS: Out of the 2645 adult patients that attended the outpatient clinic, 184 Presented with TDI giving a prevalence of 6.96 %. Their age range and mean age were 17-69 years and 30.6 ± 11.2 years respectively. Falls accounted for most (26.4 %) of the trauma to anterior teeth followed by motor cycle accidents (18.4 %) and domestic accidents (12.9 %), while opening bottle cork accounted for 1.2 %. The most common type of injury was enamel-dentine fracture accounting for 28.8 %, followed by complicated crown fracture 18.6 %, and avulsion 11.7 %. The maxillary central incisors were the most commonly affected followed by the maxillary lateral incisors and canines. More than half (51.5 %) of the patients presented in the hospital more than 1 year after injury. Majority of patients in the age groups ≤20 and 51-60 sought treatment because of pain, while more of those in the age groups 21-30 and 31-40 sought treatment because of aesthetic considerations. Seventy three (45.3 %) of the patients presented with complications involving 138 teeth. Majority of the complications were in teeth with enamel-dentine fracture (93.4 %), followed by concussion injury (55.6 %). CONCLUSIONS: The prevalence of TDI in this study falls within previously reported figures. However, the high number of teeth developing complications may have resulted from late presentation for care.

Pre-operative haematological investigations in paediatric orofacial cleft repair: any relevance to management outcome?

AIM AND OBJECTIVES: To determine the value of routine pre-operative haematologic investigations in children undergoing orofacial cleft repair. BACKGROUND: Although routine pre-operative laboratory screening tests are carried out traditionally, some studies suggest that they are not absolutely necessary in the management of elective surgical patients. MATERIALS AND METHODS: This is a prospective cohort study carried out at a tertiary health facility located in Nigeria. A review of the laboratory investigations in 116 paediatric orofacial cleft patients undergoing surgery during a 6-year period was undertaken. Pre-operative laboratory investigations and peri-operative transfusion records were analysed for the frequency and impact of abnormal results on treatment plan and outcome using the Statistical Packages for the Social Scientists 16.0. RESULTS: All the children had pre-operative packed cell volume (PCV) check on admission for surgery. The PCV ranged from 23% to 43%, mean was 32.9 (±3.7%). Twenty-two children (18.6%) had sub-optimal PCV (<30%). Patients with the lowest PCV values (23% and 26%) were transfused pre-operatively. The lowest post-operative PCV was 23%, mean 30.8 (±3.3%). There was no occasion of post-operative blood transfusion. Eighty-six patients (72.9%) had full or partial serum electrolyte and urea analysis. Screening for sickle-cell disease was rarely done. Fourteen intra- and post-operative complications were recorded. None of these were predictable by the results of pre-operative screening tests carried out. All the children were discharged home in satisfactory condition. CONCLUSIONS: Routine laboratory testing has minimal impact on management and outcome of orofacial cleft surgeries. However, haematocrit screening may be appropriate, particularly in clinically pale patients.

Prevention of oro-facial clefts in developing world.

Oro-facial cleft (OFC) remains a prominent health issue in developed and developing countries alike. It is the commonest craniofacial birth defect in humans. Mounting evidence suggest a polygenic, multifactorial and a list of epigenetic events. Primary prevention of OFC is based on recognition of the etiologic and risk factors. While a number of preventive strategies are in place for OFC in most developed countries of the world, the majority of developing countries are distant from achieving this goal for a number of reasons. Notable among these are a huge knowledge and practice gap in the field of genetics and dearth of accurate data. In addition, improper coordination and absenteeism from antenatal care contributed greatly to this set back. With ongoing efforts aimed at determining the genetics of nonsyndromic OFC in developing countries, researches directed at identifying environmental factors should equally be in place. Pending the outcome of these, implicated environmental and attitudinal risk factors in other populations could serve as preventive template in health education and interventions. Since risk factors vary between populations, definitive and effective preventive strategies and models would vary from place to place and from time to time. Frantic effort directed at identifying specific implicated risk factors in developing countries should include developing and keeping comprehensive national perinatal database and centralization of antenatal care protocol. Additionally, active health education at every level and a focus on developing manpower in the field of genetics should be in place. These would be designed and tailored toward identified, proven, and emerging risk factors.

Knowledge and cultural beliefs about the etiology and management of orofacial clefts in Nigeria's major ethnic groups.

OBJECTIVE: To determine the knowledge and cultural beliefs about the etiology and management of orofacial clefts in Nigeria's major ethnic groups. DESIGN: Questionnaires designed to elicit respondents' knowledge and cultural beliefs about the etiology and management of orofacial clefts. SETTING: Northern and southern Nigerian communities where the major ethnic groups reside. PARTICIPANTS: Consenting, randomly selected individuals. RESULTS: There were 650 respondents (350 women and 300 men) from 34 of Nigeria's 36 states; 65.5% were aged 21 to 40 years and 52.5% were married. There were Yoruba (33.7%), Igbo/Bini/Urhobo (40.5%), and Hausa/Fulani (25.8%), with most having attained primary and secondary education. Of those responding, 75% had seen an individual with an orofacial cleft. A significant level of ignorance about the cultural beliefs was found. The Hausa/Fulani considered it mostly an act of God; whereas, the Igbo/Bini/Urhobo and Yoruba groups displayed a greater variety of cultural beliefs. The latter groups implicated witchcraft, evil spirit or devil, the mother, and occasionally the child. Of respondents, 40% knew that surgery was a possible solution, and 22% would recommend a visit to the hospital. Respondents with higher educational attainment produced significantly more scientifically related etiologic factors and accurate treatment options. CONCLUSION: Of respondents, 75% were aware of the existence of orofacial clefts, and a fair knowledge of treatment of orofacial clefts was elicited. Diverse cultural beliefs often may present an obstacle to treatment. Improved awareness about the etiology and management of orofacial clefts is required.

Knowledge, attitude, and practice of Nigerian commercial motorcyclists in the use of crash helmet and other safety measures.

OBJECTIVE: This study was designed to evaluate the knowledge, attitude, and practice of some commercial motorcyclists in Nigeria in the use of crash helmet and other cycling safety measures. METHODS: At randomly selected commercial motorcycle parks from two South Western Nigerian locations (Lagos and Ile-Ife), we obtained verbal consent from commercial motorcyclists (randomly selected) and thereafter administered structured questionnaires to consenting motorcyclists. The questionnaire sought to know the respondents' biodata (age, gender, and educational attainment inclusive), cycling background, and experience (trainer, duration of training and cycling, and history of crashes). Furthermore, risk factors and practices like alcoholism, maintenance history of the motorcycle, maximum number of pillion passengers carried, and use of crash helmet were elicited. Respondents' knowledge of available safety measures was also investigated. Data was entered into an IBM compatible computer and analyzed using the SPSS 11.0 statistical software. Statistical significance was inferred at p value<0.05. RESULTS: There were 224 male respondents aged 15-58 years. Their peak age was 25-29 years and mean 35.1+/-8.9 years; 8.4% had no formal education; 10.3% received formal training but the majority were either trained by self (35.5%) or an acquaintance (34.6%). Training lasted

Clinicopathological analysis of histological variants of ameloblastoma in a suburban Nigerian population.

BACKGROUND: This study was carried out to establish the relative incidence and provide clinico-pathologic information on the various histological types of ameloblastoma seen at the Obafemi Awolowo University Teaching Hospital complex, Ile-Ife in order to provide a baseline data which will be of significance to the pathologist and clinician. METHODS: Clinico-pathologic data on a total of 77 histologically diagnosed cases of ameloblastoma archieved at the Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife over a 15 year period were obtained and analysed descriptively. RESULTS: Follicular ameloblastoma was the most common histological type (50 cases, 64.9%), followed by plexiform ameloblastoma (10 cases, 13.0%). 4 (5.2%) cases of desmoplastic and 3 (3.9%) cases of acanthomatous ameloblastoma were seen while the basal cell variant accounted for 2 (2.6%) cases. Only 1 case of the unicystic type was seen. Some of the 77 cases presented as a mixture of two or more histological types. Ameloblastoma occurred over an age range of 11 to 70 years with a peak age incidence in the 3rd decade. CONCLUSION: This study provides a baseline data on variants of ameloblastoma as obtained in a suburban Nigerian population. Since variants of ameloblastoma differ in biologic behaviour, the data collected in this study provides clinicopathologic information which is of significance to the pathologist and clinician.

Dental anxiety among patients undergoing various dental treatments in a Nigerian teaching hospital.

The aim of the present study is to evaluate the levels of dental anxiety among patients undergoing various dental treatments and to compare the anxiety levels with those of similar studies conducted with subjects from different socio-cultural backgrounds. Dental anxiety was evaluated by the administration of a questionnaire based on the Corah's Dental Anxiety Scale (DAS). Student t-test and analysis of variance (ANOVA) with Bonferoni correction was employed to compare the mean DAS scores. Females recorded higher total DAS scores than males (7.49 +/- 2.96 and 7.16 +/- 3.44, respectively). Patients in the 24-34 year age group showed the highest total DAS scores (8.25 +/- 3.20) followed by the <24 year age group. The total DAS scores for age groups 35-39 and >50 years differ significantly from those of age groups <24 and 24-34 years. The highest DAS score was recorded for root canal therapy (9.30 +/- 2.84) followed by extraction. The level of dental anxiety among this study population is lower than those reported elsewhere. The observed avoidance of dental treatment among Nigerians, despite the seemingly low mean DAS scores, may be related to dental anxiety. The authors are, however, of the opinion poor dental awareness may be a contributory factor.