Bone morphogenic protein-2 signaling in human disc degeneration and correlation to the Pfirrmann MRI grading system

BACKGROUND CONTEXTBack and neck pain secondary to disc degeneration is a major public health burden. There is a need for therapeutic treatments to restore intervertebral disc (IVD) composition and function.PURPOSETo quantify ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression in IVD specimens collected from patients undergoing surgery for disc degeneration, to correlate ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression in IVD specimens to the 5-level Pfirrmann MRI grading system, and to compare ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression between cervical and lumbar degenerative disc specimens.STUDY DESIGNAn immunohistochemical study assessing ALK3, BMP-2, pSMAD1/5/8, and MMP-13 expression levels in human control and degenerative IVD specimens.METHODSHuman IVD specimens were collected from surgical patients who underwent discectomy and interbody fusion at our institution between 1/2015 and 8/2017. Each patient underwent MRI prior to surgery. The degree of disc degeneration was measured according to the 5-level Pfirrmann MRI grading system. Patients were categorized into either the 1) control group (Pfirrmann grades I-II) or 2) degenerative group (Pfirrmann grades III-V). Histology slides of the collected IVD specimens were prepared and immunohistochemical staining was performed to assess ALK3, BMP-2, pSMAD1/5/8, and MMP-13 expression levels in the control and degenerative specimens. Expression levels were also correlated to the Pfirrmann criteria. Lastly, the degenerative specimens were stratified according to their vertebral level and expression levels between the degenerative lumbar and cervical discs were compared.RESULTSFifty-two patients were enrolled; however, 2 control and 2 degenerative patients were excluded due to incomplete data sets. Of the remaining 48 patients, there were 12 control and 36 degenerative specimens. Degenerative specimens had increased expression levels of BMP-2 (p=.0006) and pSMAD1/5/8 (p<.0001). Pfirrmann grade 3 (p=.0365) and grade 4 (p=.0008) discs had significantly higher BMP-2 expression as compared to grade 2 discs. Pfirrmann grade 4 discs had higher pSMAD1/5/8 expression as compared to grade 2 discs (p<.0001). There were no differences in ALK3 or MMP-13 expression between the control and degenerative discs (p>.05). Stratifying the degenerative specimens according to their vertebral level showed no significant differences in expression levels between the lumbar and cervical discs (p>.05).CONCLUSIONSBMP-2 and pSMAD1/5/8 signaling activity was significantly upregulated in the human degenerative specimens, while ALK3 and MMP-13 expression were not significantly changed. The expression levels of BMP-2 and pSMAD1/5/8 correlate positively with the degree of disc degeneration measured according to the Pfirrmann MRI grading system.CLINICAL SIGNIFICANCEBMP-SMAD signaling represents a promising therapeutic target to restore IVD composition and function in the setting of disc degeneration.     

Resettling into a new life: Exploring aspects of acculturation that could enhance the mental health of young refugees resettled under the humanitarian programme

Globally, the exodus of individuals who have been forced to flee their home and seek refuge in countries of safety has led to a refugee crisis. The United Kingdom (UK) has engaged with the United Nations High Commissioner for Refugees (UNHCR) in playing a significant role in the long‐term resettlement of refugees, half of whom are children and young people. One initiative of such humanitarian resettlement is the Gateway Protection Programme (GPP). To date, there is a dearth of studies investigating aspects of acculturation that affect the mental health of young refugees resettled under the UNHCR humanitarian programme. This study aimed to explore aspects of acculturation that could enhance the mental health of GPP young refugees several years after resettlement. Using narrative research, a purposive sample of 31 GPP young refugees, who had a minimum of three‐year stay in the UK, were recruited from local refugee community organizations. Data were collected through a multi‐method design combining focus group discussions (FGDs) with visual arts‐based narrative research (VABNR) and analysed thematically. Three overarching themes emerged: People and places; Its nearly all new to me; and Finding self. This study contributes important knowledge regarding the mental well‐being of young people who have engaged in a resettlement programme and offers valuable information for policymakers and mental health professionals working with GPP young refugees.     

T‐705‐modified ssRNA in complex with Lassa virus nucleoprotein exhibits nucleotide splaying and increased water influx into the RNA‐binding pocket

Lassa virus infection is clinically characterized by multiorgan failure in humans. Without an FDA‐approved vaccine, ribavirin is the frontline drug for the treatment but with attendant toxicities. 6‐Fluoro‐3‐hydroxy‐2‐pyrazinecarboxamide (T‐705) is an emerging alternative drug with proven anti‐Lassa virus activity in experimental model. One of the mechanisms of action is its incorporation into nascent single‐strand RNA (ssRNA) which forms complex with Lassa nucleoprotein (LASV‐NP). Here, using molecular dynamics simulation, the structural and electrostatics changes associated with LASV‐NP‐ssRNA complex have been studied when none, one, or four of its bases has been substituted with T‐705. The results demonstrated that glycosidic torsion angle χ (O4′‐C1′‐N1‐C2) rotated from high‐anti‐ (?110° and ?60°) to the syn‐ conformation (+30) with increased T‐705 substitution. Similarly, increased T‐705 substitution resulted in increased splaying (55°–70°), loss of ssRNA‐LASV‐NP H‐bond interaction, increased water influx into the ssRNA‐binding pocket, and decreased electrostatic potentials of ssRNA pocket. Furthermore, strong positively correlated motion observed between α6 residues (aa: 128–145) and its contact ssRNA bases (5–7) is weakened in Apo biosystem and transitioned into anticorrelated motions in ssRNA‐bound LASV‐NP biosystem. Finally, LASV genome may become more accessible to cellular ribonuclease access with T‐705 incorporation due to loss of NP interaction.     

Barium chloride dose‐dependently induced heart and lung injury in Wistar rats

Barium (Ba) is one of the environmental pollutant metals that incite deleterious effects on human health. The present study investigated the effects of exposure to different doses of barium chloride (BaCl₂) on heart and lung of Wistar rats. Rats were exposed to BaCl₂ at 150, 300, and 600 mg/L for seven consecutive days. Results indicated that exposure to Ba caused heart and lung damage evidenced by significant increase in plasma lactate dehydrogenase and creatine kinase activities, total cholesterol, triglyceride, and low‐density lipoprotein‐cholesterol levels, while high‐density lipoprotein‐cholesterol level decreased when compared with control. Moreover, BaCl₂ significantly decreased superoxide dismutase, catalase, and acetylcholinesterase activities as well as glutathione level in heart and lung of the treated rats. Furthermore, the dose‐dependent increase in cardiac and lung lipid peroxidation, advanced oxidative protein product and nitric oxide levels were accompanied by marked increase in metallothionein in the BaCl₂‐treated rats. Administration of BaCl₂ altered hematological parameters and significantly increased concentrations of interleukin‐6 in the treated rats. Histology analysis showed significant alteration in the heart and lung tissues of Ba‐treated rats. In conclusion, BaCl₂‐induced heart and lung damages via disruption of antioxidant defense systems, and activation of inflammatory mediators and alteration in hematological parameters in rats.     

Covid-19 pandemic: chronicle of responses and experiences of the infection prevention and control committee at a tertiary hospital in southwest Nigeria

Since the advent of 2019-Corona virus Disease (COVID-19) in Nigeria in February 2020, the number of confirmed cases has risen astronomically to over 61,307 cases within 8 months with more than 812 healthcare workers infected and some recorded deaths within their ranks.Infection prevention and control is a key component in ensuring safety of healthcare workers in the hospital as healthcare-associated infection is one of the most common complications of healthcare management. Unbridled transmission of infection can lead to shortage of healthcare personnel, reduced system efficiency, increased morbidity and mortality among patients and in some instances, total collapse of healthcare delivery services. The Infection Prevention and Control Committee is a recognised group by the Centre for Disease Control and Prevention with their core programmes including drawing up activities, procedures and policies designed to achieve above-stated objectives before, during and after any disease outbreak, especially emerging and re-emerging ones such as the 2019 Coronavirus Disease. In this report, we highlight the roles played by the Infection Prevention and Control Committee of the University of Medical Sciences Teaching Hospital to prevent the spread of COVID-19 within and outside the hospital community and the lessons learned to date.     

Risk factors for ectopic pregnancy in Lagos, Nigeria

BACKGROUND: Ectopic pregnancy is an important cause of maternal deaths in Nigeria and in other developing countries. In Lagos, Nigeria, it is responsible for 8.6% of maternal deaths, and has a case fatality rate of 3.7%. The purpose of this study was to determine the risk factors for ectopic pregnancy in Lagos. METHODS: A case-control study of 100 patients and 280 controls was performed in the three hospitals--Lagos University Teaching Hospital, Ayinke House Maternity Hospital, and Lagos Island Maternity Hospital--in Lagos from June 1999 to December 1999. Data were analyzed by using logistic regression. RESULTS: The incidence was 23.1/1000 (1 : 43) deliveries and was responsible for 48.5% of gynecologic emergencies. Age, marital status, socioeconomic status, and parity were not the significant risk factors for ectopic pregnancy. An early age of sexual debut increased the risk of ectopic pregnancy almost two-fold (adjusted OR = 1.93; 95% CI = 1.71-2.93), whereas a late age of sexual debut was protective (adjusted OR = 0.37; 95% CI = 0.19-0.59). History of multiple lifetime sexual partners, induced abortions, pelvic inflammatory disease, sexually transmitted disease (STD), miscarriage, and pelvic surgery independently and significantly increased the risk of ectopic pregnancy. Induced abortion and STD increased the risk 14-fold and nine-fold, respectively. Previous use of intrauterine contraceptive device increased the risk almost four-fold (adjusted OR = 3.76; 95% CI = 2.12-6.69), whereas the use of condoms was protective (adjusted OR = 0.35; 95% CI = 0.17-0.71). CONCLUSIONS: Proper sex education, prevention of unwanted pregnancy, and prevention and proper treatment of sexually transmitted infections will reduce the incidence of ectopic pregnancy.     

Removable partial denture design: a study of a selected population in Saudi Arabia

Determination of the incidence of various classes of removable partial dentures (RPDs) including their designs and their comparison with previous studies provide clinically useful information for dental training and continuing education. The purpose of this study is to determine the pattern of partial edentulism, the major connector, clasping, and design of 740 cobalt chromium RPD frameworks constructed for a selected population in Saudi Arabia. RPD framework design information and patient personal data were obtained from the work authorization form and the dental records respectively. The relationship among age, sex, nationality, and various Kennedy classes of the RPDs was determined by chi-square statistical analysis. Results indicate that Kennedy Class III removable partial dentures were the most frequently constructed. Although gender had no significant relationship, age and nationality had statistically significant relationship with the distribution of various Kennedy classes of removable partial dentures. Lingual bars and anterior posterior palatal straps were the most commonly used mandibular and maxillary major connectors. Lingual and palatal plates, however, were more frequently used than any major connectors for distal extension RPDs. Comparison with previous findings confirms the established variation in designing RPDs. The distribution of partially edentulousness revealed the influence of the general pattern of tooth loss, which could be modified by patient's demands and socio-economic status. Practitioners need to avail themselves fully of basic RPD design principles concerning the most commonly encountered classes of RPDs.     

Epidemiologic evidence linking oxidative stress and pulmonary function in healthy populations

Respiratory health in the general population declines regardless of the presence of pulmonary diseases. Oxidative stress has been implicated as one of the mechanisms involved in respiratory dysfunction. This review was to evaluate studies that relate oxidative stress factors with pulmonary function among the general population without prior respiratory illnesses. The search yielded 54 citations. Twenty-one studies qualified for incorporation in this review. Owing to the heterogeneity of the review, studies were discussed based on identified oxidative stress factors responsible for pulmonary dysfunction. Oxidative stress biomarkers, including gene polymorphisms of nuclear factor erythroid 2-related factor 2, heme oxygenase 1, glutathione S transferase, superoxide dismutase, and lipid peroxidation products were involved in lung function decline. In addition, the antioxidant status of individuals in reference to dietary antioxidant intake and exposure to environmental pollutants affected oxidative stress and pulmonary function, as indicated by forced expired volume in one second, forced vital capacity, and forced expiratory flow at 25%–75%_. This review indicated that oxidative stress is implicated in the gradual decline of lung function among the general population, and gene polymorphism along the antioxidant defense line and/or their interaction with air pollutants reduce lung function. Different polymorphic forms among individuals explain why the rate of lung function decline differs among people. Dietary antioxidants have respiratory health benefits in antioxidant gene polymorphic forms. Therefore, the genetic composition of an individual may be considered for monitoring and identifying people at risk of respiratory illnesses.