DNA polymerase β deficiency is linked to aggressive breast cancer: A comprehensive analysis of gene copy number,mRNA and protein expression in multiple cohorts

Short arm of chromosome 8 is a hot spot for chromosomal breaks, losses and amplifications in breast cancer. Although such genetic changes may have phenotypic consequences, the identity of candidate gene(s) remains to be clearly defined. Pol β gene is localized to chromosome 8p12‐p11 and encodes a key DNA base excision repair protein. Pol β may be a tumour suppressor and involved in breast cancer pathogenesis. We conducted the first and the largest study to comprehensively evaluate pol β in breast cancer. We investigated pol β gene copy number changes in two cohorts (n = 128 & n = 1952), pol β mRNA expression in two cohorts (n = 249 & n = 1952) and pol β protein expression in two cohorts (n = 1406 & n = 252). Artificial neural network analysis for pol β interacting genes was performed in 249 tumours. For mechanistic insights, pol β gene copy number changes, mRNA and protein levels were investigated together in 128 tumours and validated in 1952 tumours. Low pol β mRNA expression as well as low pol β protein expression was associated high grade, lymph node positivity, pleomorphism, triple negative, basal‐like phenotypes and poor survival (ps < 0.001). In oestrogen receptor (ER) positive sub‐group that received tamoxifen, low pol β protein remains associated with aggressive phenotype and poor survival (ps < 0.001). Artificial neural network analysis revealed ER as a top pol β interacting gene. Mechanistically, there was strong positive correlation between pol β gene copy number changes and pol β mRNA expression (p < 0.0000001) and between pol β mRNA and pol β protein expression (p < 0.0000001). This is the first study to provide evidence that pol β deficiency is linked to aggressive breast cancer and may have prognostic and predictive significance in patients.     

Clinicopathologic, ophthalmic, visual profiles and management of mucoceles in blacks

The study aimed at finding out the clinicopathologic, ophthalmic and visual profiles, management and outcome of mucoceles of the paranasal sinuses in Nigerians. The study was a retrospective review of 20 cases of mucoceles who presented to the ENT clinic and referred to the eye clinic of the University College Hospital Ibadan, Nigeria. These included nine males and 11 females with a male:female ratio of approximately 1:1. Mucoceles commonly involved more than one sinus on the same side. The sinuses commonly involved were the frontoethmoidal sinuses, frontal sinus and maxillary sinuses. The preoperative visual acuity in 16 (80%) patients was 6/4-6/9, three (15%) had between 6/9-6/18, and one (5%) patient was CF ("count fingers") in the affected eyes. The majority (90%) of our patients presented with multiple ophthalmic features; however, proptosis was the most popular and ophthalmic presentation and occurred in 15 (75%) patients. Proptosis was nonaxial in all cases with inferior, lateral or inferolateral displacement. Degree of proptosis ranged from 1-20 mm. Other presentations were squint (leading to diplopia) observed in one (5%) patient and epiphora in another [one (5%)] patient. Poor vision appeared to be the main problem in one (5%) patient, while in another [one (5%)] patient, the affected eye was completely immobilized. One (5%) patient presented with orbital cellulitis. Common radiological findings included classical expansive appearance with loss of the normal scalloping appearance with dehiscence of the wall of the affected sinus as was observed in nine (45%) of our patients. All 20 patients had excision of mucoceles (frontoethmoidectomies). At surgery, 11 (55%) patients had a combination of dehiscence of medial and/or posterior walls, and/or floor of the orbit. Materials evacuated were mucopurulent in 15 (75%) cases, moldy in three (15%) and cheesy in two (10%). Nine (45%) patients had intact walls. Three (15%) patients developed orbital cellulitis as postoperative complication. Postoperatively, proptosis regressed spontaneously within one week of surgery in 17 (85%) patients. By six weeks, all the patients had a complete regression of proptosis and visual acuity returned to preoperative visual acuity level except the patient with preoperative visual acuity of CF. This patient later deteriorated and became NPL (no perception of light) in the affected eye. This was a peculiar case in that operative findings in this patient were suggestive of another coexisting pathology, which was later confirmed to be a non-Hodgkin's lymphoma of the orbit. After two months, only three (15%) reported back for follow-up. The study concluded that proptosis is a common feature of mucoceles of the paranasal sinuses and that visual affectation was rather uncommon. Also whilst mucopurulent materials formed the content of most mucoceles, surgical intervention caused proptosis to regress dramatically. However, due to the high default rate in our study, no categorical statement can be made about recurrence rate of these swellings.     

Association between serum CA125 levels in preeclampsia and its severity among women in Lagos,South-West Nigeria

Background: Preeclampsia is a syndrome of unknown etiology characterized by hypertension, proteinuria, and/or organ dysfunction. CA125 is an antigenic determinant recognized by the murine monoclonal antibody OC125 quantified by radioimmunoassay. Its role in obstetrics is yet to be fully understood as most clinical trials advocating its uses are widely experimental in nature and unacknowledged. Aim: This study was done to assess the relationship between serum concentration of CA125 in normal pregnancies and those complicated with preeclampsia. Methods: A case–control study involving 70 women diagnosed with preeclampsia and 70 healthy controls matched for age, parity, and gestational age at enrollment. Venous samples were collected from each participant after informed consent was obtained. The preeclampsia group was further subdivided into mild and severe preeclampsia and all participants were followed up till delivery with records of delivery, maternal, and neonatal outcomes obtained thereafter. Serum CA125 levels were determined by standard enzyme-linked immunosorbent assay (ELISA) method. Hypothesis testing was done using chi-square test for categorical variables, and the independent-samples t-test and ANOVA for numerical variables. All significances were reported at P < 0.05. Results: The mean serum level of CA125 in women with preeclampsia was significantly greater than those with normal pregnancy (54.17 IU/mL vs. 12.49 IU/mL, P < 0.05). CA125 level also correlated positively with systolic blood pressure (r = 0.406, P < 0.05), diastolic blood pressure (r = 0.433, P < 0.05), serum uric acid levels (r = 0.407, P = 0.001), platelet levels (r = 0.341, P = 0.001), and urinary protein levels (r = 0.325, P = 0.002). The CA125 levels between the three categories of participants in the study were: normotensive control (12.49 ± 6.62 mIU/L), mild preeclampsia (29.43 ± 3.7 mIU/L), and severe preeclampsia (64.25 ± 9.21 mIU/L), respectively (P = 0.023). Conclusion: We can infer from this study that increased maternal serum CA 125 levels are associated with the preeclampsia and its severity. However, further validation of these findings with more robust multicenter prospective and longitudinal characterization of maternal serum CA125 profiles in pregnancy should be carried out in subsequent investigations to determine its suitability as a predictive biomarker for preeclampsia in women of African descent.     

Low flow vascular malformations of the head and neck: a study on brightness mode,color coded duplex and spectral Doppler sonography

The clinical presentation of low flow vascular malformations of the head and neck (LFVM) can range from a birthmark to severe disfigurement, functional impairment or relevant hemorrhage. The values of Brightness mode (B-mode) ultrasound and Doppler sonography in the investigation, identifying and differentiating of these lesions has been sparingly documented in the literature. This study evaluates the sonografic features of different morphological subtypes of LFVM. This is a 2-year retrospective study of 51 patients who presented with LFVM based on routine ultrasound exam in the context of their clinical consultation. Diagnosis was based on the clinical and histological findings. B-mode, color coded duplex and spectral Doppler measurements were performed for venous, lymphatic, capillary, and mixed venous-lymphatic lesions of the head and neck. The echogenicity of the majority of venous malformations was heterogenic, of most lymphatic malformations hypoechoic, and of all capillary malformations isoechoic. Blood flow was detected in only 11 cases (36.7%) of venous malformations with a monophasic pattern. There was a statistical significant difference in the mean minimum and maximum Doppler shifts between venous and lymphatic malformation for cases when the blood flow was evident. No statistical significant difference in Doppler parameters existed between capillary and lymphatic, neither between venous and capillary nor mixed malformations. Phleboliths were present in eight cases (26.7%) of venous malformations and were not detectable in any other subtype of LFVM. The detection of flow in ultrasound was only possible in a small portion of LFVM. When considering differentiating among LFVM, features such as the echogenecity, spectral Doppler wave forms, and the evidence of phleboliths contribute to establish the correct diagnosis.     

Spousal Communication, Changes in Partner Attitude, and Contraceptive Use Among the Yorubas of Southwest Nigeria

Objective:

This paper highlights the relevance of spousal communication on males'' attitude towards their partners'' contraceptive use.

Design:

This was a cross-sectional study.

Materials and Methods:

Data for the study were obtained from a survey carried out in three states, Oyo, Osun, and Ondo, mainly inhabited by the Yorubas.

Results:

The results show that men have a significant role to play in the adoption of contraception. About 37% of the respondents reported joint decision making on when to have another child, 40.8% on whether to stop having children, and 44% on what to do to stop childbearing. Communication between a husband and wife on reproductive matters was also recognized as a factor that may influence male participation in family planning.

Conclusion:

This study has shown that the male partner may be highly motivated to obtain contraceptives. The results therefore suggest that male involvement in family planning should be encouraged through inter-spousal communication.     

Pattern of eye diseases and visual impairment among students in southwestern Nigeria

Purpose The aim of the study was to determine the prevalence and causes of eye diseases and visual impairment in students in the Ilesa East local government area of Osun state, Nigeria. Methods A cross-sectional survey that utilised a multistage random sampling method to select 1,144 primary and secondary school students. Results A total of 1,144 students (504 males and 640 females) were involved in the study. Their ages ranged from 4 to 24 years. The majority (97.8%) of them were below 18 years of age. A total of 177 (15.5%) of the school children were found to have eye diseases. The major ocular disorders were in the following order: conjunctiva 91 (51.4%), refractive error 66 (37.3%), lid 7 (4.0%), corneal, including staphyloma and keratoconus 5 (2.8%) and then others. These included conjunctival diseases 91 (8%) constituted mainly by allergic/vernal conjunctivitis 85 (7.4%), refractive error 66 (5.8%), lid disorders 6 (0.6%), squint 3 (0.3%), corneal scarring 3 (0.3%) and cataract 2 (0.2%). A total of 15 students were visually impaired, with a prevalence of 1.26%. Only two students were blind, with a prevalence of 0.17%. Causes of visual impairment were refractive error 10 (0.87%), bilateral immature cataract 1 (0.08%), corneal opacities 2 (0.2%), amblyopia leading to squint 1 (0.08%) and cataract 1 (0.08%). The causes of blindness in students were bilateral corneal scars presumed to be due to vitamin A deficiency in one (0.08%) student and complicated bilateral keratoconus with complicated vernal ulcers in another (0.08%). Conclusions Eye diseases are common amongst Nigerian students. Eye examination for all new intakes and regular screening in both public and private primary and secondary schools is advocated. Wearing of corrective glasses should be emphasised for children with refractive error. Causes of blindness and visual impairment in children attending regular schools in Nigeria were avoidable.