Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever.

Infection with Lassa virus (LASV) can cause Lassa fever, a haemorrhagic illness with an estimated fatality rate of 29.7%, but causes no or mild symptoms in many individuals. Here, to investigate whether human genetic variation underlies the heterogeneity of LASV infection, we carried out genome-wide association studies (GWAS) as well as seroprevalence surveys, human leukocyte antigen typing and high-throughput variant functional characterization assays. We analysed Lassa fever susceptibility and fatal outcomes in 533 cases of Lassa fever and 1,986 population controls recruited over a 7 year period in Nigeria and Sierra Leone. We detected genome-wide significant variant associations with Lassa fever fatal outcomes near GRM7 and LIF in the Nigerian cohort. We also show that a haplotype bearing signatures of positive selection and overlapping LARGE1, a required LASV entry factor, is associated with decreased risk of Lassa fever in the Nigerian cohort but not in the Sierra Leone cohort. Overall, we identified variants and genes that may impact the risk of severe Lassa fever, demonstrating how GWAS can provide insight into viral pathogenesis.

Morinda lucida Aqueous Stem Bark Extract Ameliorates Hepato-Renal Dysfunctions in Experimental Diabetes Model.

Diabetes Mellitus (DM) is a leading pan-systemic endocrine disorder with attendant high morbidity and mortality owing to its deleterious effects on vital body organs caused by untreated chronic hyperglycemia, attendant oxidative stress and glycation processes. The present study is designed to investigate possible protective role and mechanism(s) of action 125-500 mg/kg/day of Morinda lucida aqueous stem bark extract (MLASE) on renal and hepatic functions in alloxan-induced hyperglycemic rats for 8 days. Forty-two alloxan-induced hyperglycemiic male Wistar rats were randomly allotted to Groups II-VI and orally treated with 10 ml/kg/day distilled water, 5 mg/kg/day glibenclamide, 125 mg/kg MLASE, 250 mg/kg MLASE, and 500 mg/kg/day MLASE, respectively. Group I normal rats served as untreated control and were orally treated with 10 ml/kg of distilled water, all under same sham-handling. Blood samples were taken for measurement of fasting blood glucose, renal and hepatic function profile. Liver and kidney tissue samples were taken for determination of the activities of oxidative stress markers such as malondialdehyde (MDA), reduced glutathione (GSH), and glutathione peroxidase (GPx), catalase (CAT) and superoxidase dismutase (SOD). Results showed that intraperitoneal injection with 120 mg/kg of alloxan in cold 0.9% normal saline reliably and significantly induced a steadily sustained hyperglycemia which were ameliorated by short-term oral treatment with 125-500 mg/kg/day of MLASE, dose dependently, similar to that ameliorated by the standard antihyperglycemic drug, glibenclamide. Similarly, MLASE significantly mitigated against derangements in the measured renal and hepatic function parameters as well as oxidative stress induced by alloxan-induced hyperglycemia. In conclusion, results of this study showed the protective role of 125-500 mg/kg/day of MLASE in chronic hyperglycemia-associated renal and hepatic dysfunctions which was mediated via antioxidant and free radical scavenging activities of MLASE.

Acute Lassa Virus Encephalitis with Lassa Virus in the Cerebrospinal Fluid but Absent in the Blood: A Case Report with a Positive Outcome.

It is rare both to have the central nervous system (CNS) as the main focus in the acute phase of Lassa fever infection without associated bleeding, and to find Lassa virus (LAV) in the cerebrospinal fluid (CSF) but not in the serum. We report the case of a 38-year-old Nigerian woman with mainly CNS manifestation of Lassa fever. She was admitted twice within 11 days because of persistent fever. A clinical diagnosis of acute LAV encephalitis was made because of a high index of suspicion and CNS involvement confirmed by positive reverse transcriptase polymerase chain reaction (RT-PCR) for LAV in the CSF, while her blood was repeatedly negative for LAV by RT-PCR test. She recovered fully following supportive care coupled with treatment with an 18-day course of ribavirin, and suffered no long-term neurological complication or relapse. Post-treatment CSF examination by RT-PCR did not detect LAV.

A clinico-pathologic review of 56 cases of ossifying fibroma of the jaws with emphasis on the histomorphologic variations.

OBJECTIVE: This study aims at contributing to the definitive diagnosis of ossifying fibroma (OF) based on histomorphological features. The study also aims to determine some demographic features of OF, common sites of occurrence and to determine whether behavior correlates well with the histomorphological variations seen in the lesion. MATERIALS AND METHODS: A total of 80 patients who were diagnosed either as cementifying fibroma CF, OF and cemento-ossifying fibroma (COF) of the jaws from the files of the Oral Pathology Department of the University of the Witwatersrand Dental School were retrieved and the histology slides of each case were reviewed with the most recent diagnostic criteria for OF and the authors additional criteria. A total of 56 cases that met the set criteria were analyzed. RESULTS: The patients were clustered within the third and fourth decades of life ( n = 39, 69.6%). Majority of the patients were black (83.93%), whereas the rest were whites (12.50%) and Asians (3.57%). There were 17 males (30.4%) and 39 females (69.6%), giving a male to female ratio of 1:2.3. Most of the lesions (70.3%) occurred in the mandible, involving the premolar molar region (56.7%). Scanty fibrous tissues in highly cellular lesions were found in 36 (64.3%) of the cases. There were globular, dystrophic or granular calcifications mixed with irregularly shaped trabeculae of lamellar or cellular woven bone or osteoid were found, in 36 (64.3%) cases. CONCLUSION: Demographic data, clinicoradiologic features, combined with histopathology will continue to be relevant in the definitive diagnosis of OF and in predicting its behavior. Highly aggressive lesions with shorter duration in people below 15 years were called juvenile OF and treated as such, while OF applies to other conventional ones.

The role of dentists as a stop-gap in the initial management of patients with delusional halitosis.

OBJECTIVE: This article proposes a 'stop-gap protocol'for the initial management of delusional halitosis, which dental practitioners can apply where a multidisciplinary team of dentists and mental health experts (psychiatrist and psychologist) cannot be assembled. METHODS: A 4-year prospective study of delusional halitosis patients managed with a 3-step 'Stop-gap protocol' is presented in this paper, to demonstrate our experience in applying the 'Stop-gap protocol'. RESULTS: Twenty three (23) patients diagnosed with delusional halitosis were managed with the 'Stop-gap protocol' within the study period. There were 13 (56.5%) males and 10 (43.5%) females, giving a male to female ratio of 1.3:1.Most of the patients were in the 3rd decade of life (n=10, 43.5%), the mean duration of the bad breath complaint was 5 years, with unknown trigger factor (n=19, 82.6%) in most of the patients and a mean psychological score of 7 ± 1.8. No clinical oral malodour was observed in all of these patients. A normal oral flora was observed in 13 (56.5%) of the cases and a low level of volatile sulphur compound (VSC) was found in 12 (52.2%) of the patients, with a mean VSC level of 22.3 ± 2 ppb. Twenty (87.0%) of the patients presented for follow up /counselling and the mean duration of follow up was 13 weeks. Three (13.0%) patients responded to referral to the joint clinic with mental health experts. CONCLUSION: Although we do not claim that the 'Stop-gap protocol' is comprehensive, it is hoped that this paper will serve as a useful guide for dentists practising in health facilities without mental health specialists and also to encourage the formation of multi-disciplinary teams in centres where they are present.

Ectopic pregnancy following in vitro fertilisation and embryo transfer.

BACKGROUND: ectopic pregnancy is one of the recognised complications of in vitro fertilisation (IVF) and embryo transfer. OBJECTIVE: to review cases of ectopic pregnancy following IVF at a fertility unit, with the aim of raising awareness towards its increased incidence and pattern of presentation. METHODS: case records of patients who had ectopic pregnancy following IVF over a three-year-period (July 2005-June 2008) were retrieved from the medical records department. Data including age, parity, risk factors for ectopic pregnancy as well as management modality were extracted and analysed. RESULTS: There were 64 clinical pregnancies during the study period. Of these, five were ectopic pregnancies, given a frequency of 7.8%. The minimum number of embryos transferred was two and maximum four. All the five cases had easy embryo transfer. There was one case of heterotopic pregnancy. Two (40%) patients had previous ectopic pregnancies with one having a third ectopic pregnancy despite previous bilateral salpingectomies. Four (80%) of the five cases had laparotomy done. Three (60%) cases had ruptured ectopic pregnancies. One case was managed conservatively with methotrexate. CONCLUSION: ectopic pregnancy can present following IVF procedures. A high index of suspicion is necessary even in cases with previous bilateral salpingectomies or easy embryo transfer.

Evaluation of oral and extra-oral factors predisposing to delusional halitosis.

OBJECTIVE: This study evaluated the role of patients' associated oral and extra-oral factors, as well as previous dental treatment, as possible predisposing (triggering) factors in the development delusional halitosis. METHOD: Forty-six patients diagnosed of delusional halitosis, over a consecutive period of 2 years (2003-2004) were selected for this study. Diagnosis was based on: use of standard halitosis questionnaire (to confirm the presence of psychological component) modified to obtain data on oral and extra-oral factors, as well as previous dental treatment linked by patients as cause of oral malodour; clinical assessment without objective evidence of oral malodour; absence of reliable third party to confirm patients' claim of oral malodour; and screening with sulphur monitor (RH-17 Series Halimeter, Interscan, Chatsworth, CA) that was within normal range (80-140ppb). RESULTS: All the 46 patients studied had normal halimeter measurement and no reliable third party to confirm the patients' claim of oral malodour. Twenty-four (52.2%) patients had associated possible predisposing factors. The most common associated factors were bitter taste (25.0%), oral deposits (20.8%), carious tooth (16.7%) and previous tooth extraction (16.7%). Associated factors were divided into oral, extra-oral and dental treatment. Patients' associated oral factors were significantly correlated as predisposing factors for delusional halitosis (p<0.01) CONCLUSION: This study shows significant correlation of patients' associated oral factors as the triggering event, which could predispose those individuals who may have underlying psychosomatic tendencies to developing delusional halitosis.

Frequency of delusional halitosis in a university community

Objective: This study reviewed the prevalence of delusional halitosis and analyzed the frequency of this condition within the University Community; over a period of three years. Method: Sixty-eight (68) patients with delusional halitosis were diagnosed over a period of three years (2001 to 2003); at the Dental Hospital; University of Benin; Nigeria. Results: Within the University Community; there were 14 cases (20.1) and the largest group was within 20 to 29 years; 12 cases (17.7). Conclusion: The study suggests an increased level of awareness or an increased prevalence of this condition within the same population. A fifth of the patients were within the University Community; mostly male students who suffered social embarrassment and poor academic performance