Coronavirus genomic nsp14-ExoN, structure, role, mechanism, and potential application as a drug target.

The recent coronavirus disease 2019 (COVID-19), causing a global pandemic with devastating effects on healthcare and social-economic systems, has no special antiviral therapies available for human coronaviruses (CoVs). The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) possesses a nonstructural protein (nsp14), with amino-terminal domain coding for proofreading exoribonuclease (ExoN) that is required for high-fidelity replication. The ability of CoVs during genome replication and transcription to proofread and exclude mismatched nucleotides has long hindered the development of anti-CoV drugs. The resistance of SARS-CoV-2 to antivirals, especially nucleoside analogs (NAs), shows the need to identify new CoV inhibition targets. Therefore, this review highlights the importance of nsp14-ExoN as a target for inhibition. Also, nucleoside analogs could be used in combination with existing anti-CoV therapeutics to target the proofreading mechanism.

Coronavirus disease 2019 (COVID-19): An overview of the immunopathology, serological diagnosis and management.

SARS-CoV-2 is a novel human coronavirus responsible for the Coronavirus disease 2019 (COVID-19) pandemic. Pneumonia and acute respiratory distress syndrome are the major complications of COVID-19. SARS-CoV-2 infection can activate innate and adaptive immune responses and result in massive inflammatory responses later in the disease. These uncontrolled inflammatory responses may lead to local and systemic tissue damage. In patients with severe COVID-19, eosinopenia and lymphopenia with a severe reduction in the frequency of CD4+ and CD8+ T cells, B cells and natural killer (NK) cells are a common feature. COVID-19 severity hinges on the development of cytokine storm characterized by elevated serum levels of pro-inflammatory cytokines. Moreover, IgG-, IgM- and IgA-specific antibodies against SARS-CoV-2 can be detected in most patients, along with the viral RNA, forming the basis for assays that aid in patient diagnosis. Elucidating the immunopathological outcomes due to COVID-19 could provide potential targets for immunotherapy and are important for choosing the best clinical management by consultants. Currently, along with standard supportive care, therapeutic approaches to COVID-19 treatment involve the use of antiviral agents that interfere with the SARS-CoV-2 lifecycle to prevent further viral replication and utilizing immunomodulators to dampen the immune system in order to prevent cytokine storm and tissue damage. While current therapeutic options vary in efficacy, there are several molecules that were either shown to be effective against other viruses such as HIV or show promise in vitro that could be added to the growing arsenal of agents used to control COVID-19 severity and spread.

Genetic diversity of human immunodeficiency virus-1 in Nigeria: 2002-2017 - systematic review and meta-analysis.

Nigeria was ranked second highest country with human immunodeficiency virus (HIV) burden worldwide. HIV-1 subtypes and circulating recombinant forms genetic variability affect the protease and reverse transcriptase genes which code for viral enzymes and are the main targets for antiretroviral drugs. Therefore, this study was aimed at reviewing and pooling such HIV-1 subtypes in Nigeria to represent the collective prevalence of each subtype. Studies of HIV-1 subtypes in Nigeria published from 2002 to 2017 were retrieved and synthesised from different sources electronically. Sixteen studies were included for random effect meta-analysis for various subtypes in each study. The pooled prevalence was charted in forest plot and effect estimates from individual studies against some measure of study size or precision were presented in funnel plots. The pooled prevalence of Subtype G, CRF02_AG, CRF06_cpx, Subtype A and Subtype C were 38.27% (95% Confidence Interval [CI]: 21.27%- 55.98%), 37.81% (95% CI: 20.37%- 55.25%), 6.6% (95% CI: 7.10%-7.10%), 14.05% (95% CI: 9.06% - 19.04%) and 2.80% (95% CI: 2.70%- 8.30%) respectively. This study suggests HIV-1 subtypes G, CRF02_AG and A are the most prevalent in Nigeria.

Pattern of prevalent Hepatitis B virus genotypes in Zaria, Nigeria.

BACKGROUND: Hepatitis B virus (HBV) is hyperendemic in Nigeria. Available literature reveal genotype E as being predominant in West Africa. This study aimed at identifying the current pattern and prevalent genotypes of HBV in Zaria, Nigeria. MATERIALS AND METHODS: Four millilitre of blood was collected in ethylenediaminetetraacetic acid-container from each of 165 HBV surface antigen-positive participants recruited purposively from the gastroenterology clinic from May to August, 2017. Plasma was separated and frozen at -20°C till analysis. Multiplex-nested polymerase chain reaction using type-specific primers was used to identify the various HBV genotypes. RESULTS: Median (and interquartile range) age of the participants was 31.0 (25.5-39.0) years, with males constituting 107 (64.8%). Majority (83.6%) of the samples analysed were HBV-DNA-positive with 82.6% of the HBV-DNA-positive samples being mixed genotype infections. Irrespective of mode of occurrence, five HBV genotypes were identified with HBV/E (97.1%) being the most predominant, followed by HBV/B (82.6%), HBV/A (24.6%), then HBV/C (17.4%), while HBV/D (0.7%) was the least prevalent. CONCLUSION: In most (99.1%) of the mixed-infection were a combination of genotype E, the predominant genotype, with other genotypes predominantly genotype B. HBV genotypes E, B, A, C and D are the prevalent genotypes in Zaria, Nigeria, as they occur in single genotype and in mixed-genotypes pattern.

Clinical Evidence of Retrograde Axonal Growth in Chronic Brachial Plexus Injury.

Nerve axons grow from proximal to distal after axonometric injury; however, they have been seen to regenerate via alternate routes, with some also demonstrating retrograde growth in neuromas. We present the case of a 33-year-old male with a 16-year-old traumatic brachial plexus injury presenting with neuropathic pain and isolated spontaneous recovery. Following a successful pre-operative anaesthetic block, a neurectomy of the median and ulnar nerves was planned for pain relief. Intraoperatively, median nerve stimulation resulted in muscle contractions in the pectoralis major (PM) and extensor carpi radialis brevis (ECRB). This was confirmed by electrical and mechanical stimuli. Histological analysis confirmed the presence of viable axons in the median nerve despite no distal nerve function. Post-surgery motor activity was preserved. A plausible explanation for the intraoperative observations, suggesting neural connectivity between the median nerve and PM and ECRB, would be retrograde growth into various nerve pathways. Alternative explanations such as axonal bifurcation, light anaesthesia, or anatomical variations were considered but the evidence favoured retrograde axonal regrowth. These findings challenge conventional understanding and offer potential new approaches to nerve reconstruction.

The role of implants and implant prostheses on the accuracy and artifacts of cone-beam computed tomography: an in-vitro study.

To assess the accuracy of CBCT in implant-supported prostheses and to evaluate metal artifacts with and without implants or implant prostheses. Accuracy and artifacts were assessed in the dried mandible at three points on the buccal and lingual cortical plates on the mandible's body near the crest and the base. On the buccal cortical plate, these points were labelled as A, B and C near the crest and D, E and F near the base of the body of the mandible. Similarly, points a to f were marked on the lingual cortical plate corresponding to points A to F. The study had two control groups, C0 for physical linear measurement (PLM) and C1 for radiographic linear measurement (RLM) and artifact assessment. There were seven test groups, TG 1 to 7, progressing from a single implant to implant full-arch prosthesis. For accuracy assessment, PLM was compared to RLM. CBCT artifacts were investigated in images integrated at 0.25 mm, 10 mm, and 20 mm at regions of interest on concentric circles at different intersecting angles by comparing grayscale values at C1 and TG1 to 7. The data were collected and statistically analyzed. A significant difference was observed between C0 and C1, and RLM in test groups at the superior axial plane. Similarly, PLM and test RLM in the sagittal plane at A-B, B-C, and D-E were statistically significant. A significant difference between PLM and RLM was also observed in the vertical plane at A-D, B-E, and C-F. Quantification of CBCT artifacts in the presence of implants or prostheses revealed that full-arch prostheses had the highest mean grayscale value, whereas single implants with a prosthesis had the lowest. The mean grayscale change was greatest around the implant and implant prosthesis. The mean grayscale value was maximum at 20 mm voxel integration scales (VIS) and lowest at 0.25 mm. CBCT is a clinically reliable device. Metal in implants or implant-supported prostheses prevents true assessment of the peri-implant area; therefore, lower VIS is suggested in the presence of implants or implant prostheses.

In Vivo Anti-Hepatocellular Carcinoma Effects of the Chloroform Root Extract of Clausena excavata Burm.

Liver cancer is the most common cancer among males in Africa. The disease has a poor prognosis and its treatment is associated with toxicity and resistance. For this reason, numerous herbal combinations are being subjected to anticancer screening to circumvent the shortcomings of the conventional anticancer drugs. In the current study, the in vivo anti-cancer effects of the chloroform root extract of the herb, Clausena excavata Burm were investigated. Liver cancer was induced in mice by a single intraperitoneal injection of diethylnitrosamine (DEN) followed by oral administration of the promoter of carcinogenesis, 2-aminoacetyl fluorine that was mixed with the mice feed. The cytotoxicity of the root extract of C. excavata on liver cancer cells was investigated using liver enzyme, histology, DNA fragmentation and caspases assays. Real time qPCR was conducted to evaluate the effect of the extract on apoptotic genes. The findings revealed that the extract of C. excavata significantly decreased the progression of hepatocarcinogenesis and the toxicity-induced production of the liver enzymes, alanine and aspartate aminotransferases. The histological analyses of the liver tissues revealed evidence of apoptotic cell death. The extract also provoked significant (p < .05) expressions of caspase 9 protein and gene as well as other apoptotic genes (P53, P27, Apaf-1, cytochrome C, bax and bid). Therefore, we postulate that the chloroform root extract of C. excavata induces apoptosis of liver cancer in mice.

Prosthetic rehabilitation of a hemisected maxillary molar: a rare entity.

Gingival recession beyond grade III and grade IV level involving furcation defects can lead to tooth loss if not intervened at appropriate time. The treatment options include scaling and root planing, Furcation-plasty, Tunnel preparation, Root separation and resection. The chief complaint of the patient was pain in the upper left first molar because of grade III furcation involvement. Since it was a four rooted molar, the treatment of choice was hemisection of the tooth and extraction of the distal half following endodontic treatment. As the second molar was mesially tilted the prosthodontic rehabilitation was done with a hybrid prosthesis involving a full coverage conventional porcelain fused to metal retainer on the hemisected molar and a resin bonded partial coverage retainer on the tilted second molar. The resultant prosthesis is termed as "Hybrid prosthesis".

Public knowledge of the symptoms of myocardial infarction: a street survey in Birmingham, England.

BACKGROUND: Myocardial infarction (MI) is a leading cause of death in the UK. A good clinical outcome depends on rapid treatment following the onset of symptoms. A person's knowledge of typical symptoms determines how quickly they present to the medical services. OBJECTIVES: To investigate knowledge of MI symptoms among the general population and the relationship between age, gender and socio-economic status with knowledge. METHODS: Street survey of 302 participants in Birmingham, UK, using an interviewer-assisted questionnaire. RESULTS: Of seven symptoms accepted in the medical literature as typical of an MI, central chest pain was the most frequently identified (75% of the sample), followed by arm pain or numbness (40%), shortness of breath (35%), fainting or dizziness (21%) and sweating (21%). Feeling or being sick and neck or jaw pain were mentioned by 8.1% and 5.9%, respectively, while an atypical or inapplicable symptom, collapse (9.9%) was mentioned more often than these. Over half the sample knew only two or fewer MI symptoms. The mean number of typical symptoms identified was 2.2 (SD = 1.28). Respondents from professional occupations and those with previous experience of MI, whether direct or indirect, showed better awareness. CONCLUSIONS: The study demonstrated a paucity of knowledge of MI symptoms among the general public. Such findings provide a baseline to guide public health campaigns targeting awareness of MI.

Juvenile aggressive ossifying fibroma.

Ossifying fibroma, also the cement ossifying fibroma radiographically, represents a well-demarcated mixed radiolucency/radio-opacity with smooth and often sclerotic borders. These lesions are usually solitary and most commonly seen in the mandible; cases in the maxilla have also reported. Histologically, they contain a relatively avascular cellular fibrous stroma with reticular bone trabeculae and cementum-like spherules. We present a case report of an 11-year-old boy with a 2-month history of an asymptomatic swelling seen on the left side of the angle of the mandible. An initial diagnosis of ossifying fibroma was made by an incisional biopsy, and considering the age as a factor surgical resection of the tumor was done under general anesthesia following closure by a two-layer suturing under proper antibiotic and analgesic coverage. The patient has been on regular follow-ups with no adverse effects and satisfactory healing.

A review of teleradiology in Africa - Towards mobile teleradiology in Nigeria.

eHealth is promoted as a means to strengthen health systems and facilitate universal health coverage. Sub-components (e.g. telehealth, telemedicine, mhealth) are seen as mitigators of healthcare provider shortages and poor rural and remote access. Teleradiology (including mobile teleradiology), widespread in developed nations, is uncommon in developing nations. Decision- and policy-makers require evidence to inform their decisions regarding implementation of mobile teleradiology in Nigeria and other sub-Saharan countries. To gather evidence, Scopus and PubMed were searched using defined search strings (September 2020). Duplicates were removed, and titles and abstracts reviewed using specified selection criteria. Full-text papers of selected resources were retrieved and reviewed against the criteria. Insight from included studies was charted for eight a priori categories of information: needs assessment, implementation, connectivity, evaluation, costing, image display, image capture and concordance. Fifty-seven articles were identified, duplicates removed and titles and abstracts of remaining articles reviewed against study criteria. Twenty-six papers remained. After review of full-texts, ten met the study criteria. These were summarised, and key insights for the eight categories were charted. Few papers have been published on teleradiology in sub-Saharan Africa. Teleradiology, including mobile teleradiology, is feasible in sub-Saharan Africa for routine X-ray support of patients and healthcare providers in rural and remote locations. Former technical issues (image quality, transmission speed, image compression) have been largely obviated through the high-speed, high-resolution digital imaging and network transmission capabilities of contemporary smartphones and mobile networks, where accessible. Comprehensive studies within the region are needed to guide the widespread introduction of mobile teleradiology.

The Spectrum of Postoperative Complications and Outcomes After Pancreaticoduodenectomy: A Retrospective Outlook From a Developing Country.

Background Pancreaticoduodenectomy is an extremely complex surgical procedure that mandates aggressive postoperative management. Unfortunately, in developing countries, the limited resources and poor postoperative care lead to multiple complications and abysmal outcomes. Therefore, our study aimed to evaluate the spectrum of postoperative complications and outcomes among patients undergoing pancreaticoduodenectomy. Methods This retrospective study involved a total of 97 patients who underwent pancreaticoduodenectomy for ampullary, periampullary, or pancreatic tumors. Patients with advanced metastasis and unresectable tumors were excluded from the study. Patients were studied for various parameters including the demographic details, postoperative outcomes, characteristics of the tumor, and postoperative complications. Results Out of 97 patients, 59 (60.8%) patients were males. The mean age of the study participants was 53.43 ± 17.89 years. Jaundice and abdominal pain were the most common presenting symptoms among the study participants. Of the 97 patients, 58 (59.8%) had malignant tumors. A total of 49 patients developed various postoperative complications including surgical site infections (10.3%), anastomosis leakage (9.27%), pancreatic fistula (9.27%), cholangitis (7.2%), and biliary leakage (4.1%). A total of 29 (29.9%) patients expired due to postoperative complications. Conclusions Surgical site infections, anastomosis leakage, pancreatic fistula, cholangitis, and biliary leakage are common but preventable postoperative complications after pancreaticoduodenectomy. These lead to morbidity and mortality, especially in the setting of a resource-deprived developing country. Aggressive postoperative management, improved surgical technique, better intraoperative hemostasis management, and a multi-disciplinary approach for the management of such patients can help in preventing postoperative complications and improving the postoperative outcomes.

The management of hydrocephalus in children with posterior fossa tumours: the role of pre-resectional endoscopic third ventriculostomy.

AIMS: The purpose of this retrospective case series was to determine the incidence of complications and outcomes associated with a primary management policy of endoscopic third ventriculostomy (ETV) prior to posterior fossa tumour resection in a single paediatric neurosurgical unit. METHODS: Between July 1999 and August 2007, 59 children with posterior fossa tumours were surgically managed. Based on presenting neurology, imaging criteria and cerebrospinal fluid (CSF) pressure during ventriculostomy, patients were categorised into no (n = 16), mild (6), moderate (22) or severe (15) hydrocephalus on admission. RESULTS: Thirty-seven (63%) patients underwent ETV within (mean) 1.5 days of admission, and of those, 32 (87.1%) exhibited significant improvement in presenting symptomology immediately after ETV. Complications arising after ETV included CSF infection/meningitis (n = 2) and bleeding (n = 1). ETV failed in 5/37 patients over the follow-up period. There was a significant association between increasing severity of hydrocephalus before ETV and increased number of complications (p = 0.03). CONCLUSIONS: The use of pre-resectional ETV at this institution is an effective and safe procedure with a high success rate at up to 7.5 years of follow-up. We believe that all paediatric neurosurgical institutions should review their practice regarding hydrocephalus associated with posterior fossa tumours in the light of the controversy surrounding perioperative CSF diversion.

Left circumflex artery injury postmitral valve surgery, single center experience.

The left circumflex (LCX) artery is located close to the mitral valve (MV), making it susceptible to injury during MV surgery. We are reporting our experience in the diagnosis and management of this complication. We retrospectively reviewed our surgical and coronary angiography databases for patients with documented LCX artery injury during MV surgery between January 2000 and December 2016. The complication was associated with MV replacement (9/1313, 0.7%) but not MV repair (0/393, 0.0%). Eight patients (88.9%) were female and the mean age was 40.4 ±â€¯14.2 years. There was roughly similar distribution of left and right dominant coronary circulations (5 and 4 patients, respectively). Eight patients (88.9%) had ischemic changes on electrocardiogram and ventricular arrhythmias were documented on six patients (66.7%). Three patients (33.3%) were treated with percutaneous coronary intervention while six patients (66.7%) required redo surgery to graft the LCX artery. The 30-day mortality was high (33.3%). A high index of suspicion is required to diagnose this injury. At the moment, no consensus is available on the optimal treatment strategy. We propose percutaneous approach as the first option to spare the patients from undergoing open-heart surgery for the second time.

Distribution of hepatitis B virus-positive individuals in Zaria, Nigeria, according to risk-associated practices.

BACKGROUND: An estimated 75% of Nigerians are at risk of hepatitis B virus (HBV) exposure. In an attempt to reduce the menace, the assessment of risk factors associated with HBV infection and general perception of infected individuals is a step in that direction. AIM OF THE STUDY: This study, therefore, identified exposure to risk factors and general perceptions associated with HBV infection in infected individuals in Zaria, Nigeria. METHODOLOGY: Four milliliters of blood were collected in ethylenediaminetetraacetic acid container from each of 165 HBV surface antigen (HBsAg)-positive participants recruited purposively from the gastroenterology clinic of ABUTH Zaria from May to August 2017. Plasma was separated and used to screen for HBsAg with Fastep® rapid strip. Epi Info® questionnaire database was used to collate data on sociodemographics, risk factors, and perception indices. GraphPad Prism 6 was used for statistical analysis. RESULTS: The median interquartile range age of the participants was 31.0 (25.5-39.0) years with 107 (64.8%) male participants. Sharing hair clippers, commercial pedicure, and body piercing among others were some of the risks that the study participants reported to be exposed to. One-quarter of health workers involved in the study had needlestick injury. Less than half of the study participants (47.7%) knew of hepatitis B before testing HBsAg seropositive. Knowledge of the HBV vaccine before testing and adherence was generally poor (38.6% and 44.6%, respectively). There was a significant linear relationship between the level of education and knowledge of hepatitis B. CONCLUSION: Considering the myriads of already established risks of HBV seen in Zaria, massive enlightenment campaigns need to be embarked on continuously through all available media, including social media.

The Limitations of Gram-stain Microscopy of Synovial Fluid in Concomitant Septic and Crystal Arthritis.

BACKGROUND: Rapid diagnosis of septic arthritis from Gram-stain microscopy is limited by an inherent false-negative rate of 25-78%. The presence of concomitant crystal arthritis in 5% of cases represents a particular diagnostic challenge. OBJECTIVES: This study aims to investigate the effects that a concomitant crystal arthropathy has on the ability of Gram-stain microscopy of synovial fluid to diagnose a septic arthritis. METHODS: This is a 22-year retrospective cohort study. Inclusion criteria were a positive synovial fluid culture result with a positive clinical diagnosis of septic arthritis. Results were correlated with the presence or absence of urate and calcium pyrophosphate crystals, and Gram-stain result. During this time our collection and analysis methods remained unchanged. All samples were collected in Lithium Heparin containers. Chi-squared test with a p value < 0.05 was considered significant. RESULTS: 602 synovial fluid samples were included. 162 cases of concomitant crystal arthritis were identified (27%). Of these, 16 (10%) had an initial negative Gram-stain. Out of the 440 samples with no crystals detected, 18 (4%) had an initial negative Gram-stain microscopy result (p < 0.05). CONCLUSION: The incidence of concurrent septic and crystal arthritis may be higher than previously thought. Synovial fluid samples in concomitant septic and crystal arthritis are significantly less likely to have a positive Gram-stain at microscopy than in cases of an isolated septic arthritis. We would advise the clinician to maintain a high index of suspicion for septic arthritis in these patients.

Bilateral multifocal choroiditis and optic neuropathy in a patient with AIDS: a diagnostic dilemma.

A rare case of bilateral multifocal choroiditis and optic neuropathy as the result of disseminated cryptococcal infection in a person with AIDS is described. A 30-year-old HIV-positive man presented with fever, headache, vomiting, and altered sensorium Ophthalmological examination revealed bilateral multifocal choroiditis and optic neuropathy. Laboratory examination and imaging suggested a presumptive diagnosis of disseminated Cryptococcus neoformans infection. Therapeutic response confirmed the diagnosis.