Physical interaction between bovine viral diarrhea virus nonstructural protein 4A and adenosine deaminase acting on RNA (ADAR)

Bovine viral diarrhea virus (BVDV) is a positive-sense RNA virus known to produce double-stranded RNA (dsRNA) during its replication in the cytoplasm. Extended dsRNA duplexes can be hyperedited by adenosine deaminase acting on RNA (ADAR), which catalyzes adenosine (A)-to-inosine (I) editing. A-to-I editing has been reported for various viruses. A number of cellular antiviral defense strategies are stimulated by dsRNA, and this may involve hyperediting of dsRNA by ADARs, followed by targeted cleavage by cytoplasmic endonucleases. Here, we identify ADAR as a binding partner of BVDV NS4A in vitro and in vivo and show that the N-terminal domain of NS4A is the ADAR-binding domain. We also show that ADAR has an inhibitory effect on BVDV replication when overexpressed in BVDV-infected bovine cells. Our findings suggest a role of NS4A in the interaction of BVDV with ADAR that favors virus replication.     

Genetic relatedness of human immunodeficiency virus-1 (HIV-1) strains in a 12-year-old daughter and her father in a household setting

Modalities of intra-familial transmission of HIV-1 are not always clear. Here we describe an uncommon case of HIV transmission in a family setting, analyzed using clinical, epidemiological and nucleic-acid-based methods, and assess risk factors for intrafamilial transmission of HIV-1 infection. All sequences from the father and the daughter were grouped in the same cluster with a 100 % bootstrap value, which means that the father and his daughter were infected with highly homologous CRF01_AE. The diversity of genetic clones between env and pol genes was insignificant (p > 0.05). Moreover, the results of analysis of drug-resistance-associated mutation positions of the two viral isolates were almost identical, indicating that both were susceptible to the first-line anti-HIV drugs prior to the initiation of antiretroviral treatment (ART), and this presented additional evidence of a high similarity between the two family members’ HIV-1 quasispecies. In this family, HIV-1 isolates from a father and his daughter had very highly genetic relatedness. By combining their clinical histories, we could draw the conclusion that the daughter was probably infected via contact with her father’s blood or other body fluids, but no obvious transmission route was found, suggesting that HIV-1 infection in similar household settings should be taken into consideration whenever the origin of HIV-1 infection cannot be identified.     

Alloy Design and Fabrication of Duplex Titanium-Based Alloys by Spark Plasma Sintering for Biomedical Implant Applications

Very often, pure Ti and (α + β) Ti-6Al-4V alloys have been used commercially for implant applications, but ensuring their chemical, mechanical, and biological biocompatibility is always a serious concern for sustaining the long-term efficacy of implants. Therefore, there has always been a great quest to explore new biomedical alloying systems that can offer substantial beneficial effects in tailoring a balance between the mechanical properties and biocompatibility of implantable medical devices. With a view to the mechanical performance, this study focused on designing a Ti-15Zr-2Ta-xSn (where x = 4, 6, 8) alloying system with high strength and low Young’s modulus prepared by a powder metallurgy method. The experimental results showed that mechanical alloying, followed by spark plasma sintering, produced a fully consolidated (α + β) Ti-Zr-Ta-Sn-based alloy with a fine grain size and a relative density greater than 99%. Nevertheless, the shape, size, and distribution of α-phase precipitations were found to be sensitive to Sn contents. The addition of Sn also increased the α/β transus temperature of the alloy. For example, as the Sn content was increased from 4 wt.% to 8 wt.%, the β grains transformed into diverse morphological characteristics, namely, a thin-grain-boundary α phase (α_GB), lamellar α colonies, and acicular α_s precipitates and very low residual porosity during subsequent cooling after the spark plasma sintering procedure, which is consistent with the relative density results. Among the prepared alloys, Ti-15Zr-2Ta-8Sn exhibited the highest hardness (s340 HV), compressive yield strength (~1056 MPa), and maximum compressive strength (~1470). The formation of intriguing precipitate–matrix interfaces (α/β) acting as dislocation barriers is proposed to be the main reason for the high strength of the Ti-15Zr-2Ta-8Sn alloy. Finally, based on mechanical and structural properties, it is envisaged that our developed alloys will be promising for indwelling implant applications.     

Asymptomatic MERS-CoV Infection in Humans Possibly Linked to Infected Dromedaries Imported from Oman to United Arab Emirates,May 2015

In May 2015 in United Arab Emirates, asymptomatic Middle East respiratory syndrome coronavirus infection was identified through active case finding in 2 men with exposure to infected dromedaries. Epidemiologic and virologic findings suggested zoonotic transmission. Genetic sequences for viruses from the men and camels were similar to those for viruses recently detected in other countries.     

Tracking working status of HIV/AIDS-trained service providers by means of a training information monitoring system in Ethiopia

Background  

The Federal Ministry of Health of Ethiopia is implementing an ambitious and rapid scale-up of health care services for the prevention, care and treatment of HIV/AIDS in public facilities. With support from the United States President's Emergency Plan for AIDS Relief, 38 830 service providers were trained, from early 2005 until December 2007, in HIV-related topics. Anecdotal evidence suggested high attrition rates of providers, but reliable quantitative data have been limited.     

Impairments, disabilities and needs assessment among non-fatal war injuries in south Lebanon, Grapes of Wrath, 1996

STUDY OBJECTIVE: To examine the impact of non-fatal war related injuries on physical disability in a group of war wounded civilians and to assess their needs. DESIGN: Cross sectional study. Home interviews were conducted using a structured interview schedule around one month after the injury, to assess impairments, disabilities, and needs. STUDY POPULATION AND SETTING: War wounded persons in towns and villages in South Lebanon during the attack "Grapes of Wrath" in 1996. RESULTS: The majority of the study population were young and in their productive age, mostly injured in the street or while hiding in open shelters. Around half of the injuries resulted in impairments, but, there were no age, gender or geographical differentials by severity of impairment. Almost one third (29%) of the students enrolled in schools at the time of the injury reported failure to continue their education and 42% of the working members lost their jobs with no potential for 34% of them to resume their former jobs. The impact of the injury on impairments, motor disabilities and physical independence was highest for injuries to the lower limbs (age and sex adjusted risk ratio (RR) 1.62, 95% confidence intervals (CI) 1.25, 2.10; 2.98, 95% CI 2.09, 4.23; and 2.13, 95% CI 1.39, 3.27, respectively). Despite the acute and early relief services provided by all those concerned at the time of the injury, when asked about unmet needs, the majority of the impaired (66%) reported the need for additional services, mostly medical in nature. The degree of disability was a salient factor for the need for rehabilitative services but not for medical services. CONCLUSIONS: The chronic and diverse needs of people with war injuries are often neglected and underestimated by the governmental institutions and relief agencies. Research funds as well as services should be allocated to tackle the long term and continuous health and social needs of those injured and their families.     

Development of patient information leaflets for fixed,removable, and functional appliances for Arabic-speaking orthodontic patients

ObjectiveTo develop Orthodontic Patient Information Leaflets (PILs) in Arabic.Material & methodThis study included five phases starting with Arabic translation of existing British Orthodontic Society leaflets; initial face validation with three orthodontists; content validation with ten orthodontists; final face validation with ten orthodontists, five postgraduate students, and ten patients; and re-translation to English prior to comparing the new documents with the original PILs to verify that all the necessary information were included. The content validity index (CVI) assessed item level (I-CVI) and scale level (S-CVI).ResultsThe three Arabic PILs were face validated with inclusion of mini-screws, rapid maxillary expansion, and interproximal reduction. Content validity was perfect with no item I-CVI < 0.80. The S-CVI/Ave for PIL Fixed Appliances = 0.98, PIL Removable Appliances = 0.98 and PIL Functional Appliances = 0.97. In the final face validation, the three leaflets received 100% agreement from all observers for consistency of leaflet format and style, clarity, readability and use of adequate phrases. Finally, the leaflets were re-translated and the information was checked by native English speakers to ensure the completeness of information. There were no discrepancies and face validity was excellent.ConclusionValid PILs for Arabic-speaking patients undergoing orthodontic treatment with fixed, removable, and functional appliances have been developed.     

Acutely Irreducible Ankle Fracture Dislocation: A Report of a Bosworth Fracture and its Management

Background

Acutely irreducible ankle fractures are uncommon. Irreducibility caused by interposition of soft tissue and entrapment of fracture fragments has been well described. An irreducible ankle fracture due to a locked fibular shaft fragment behind the tibia, a Bosworth fracture, is a rare injury.

Case Report

We describe a Bosworth fracture in a 19-year-old man subsequent to a fall.

Conclusion

The Bosworth fracture dislocation is a rare injury to the ankle, the correct diagnosis of which depends on awareness of the variant and careful evaluation of the initial clinical and radiographic features. As with our patient, a good outcome is achievable despite the severe nature of these injuries.     

Multiple sclerosis: expression of CD1a and production of IL-12p70 and IFN-gamma by blood mononuclear cells in patients on combination therapy with IFN-beta and glatiramer acetate compared to monotherapy with IFN-beta

Current therapy of multiple sclerosis (MS) with interferon-beta (IFN-beta) or glatiramer acetate (GA) has modest effects on the course of MS. Both compounds affect several immune variables, like expression of cell surface molecules and cytokine levels. Here we compared untreated MS, therapy with IFN-beta alone and combined with GA, and healthy controls (HC), regarding expression on HLA-DR+ blood mononuclear cells (MNC) of CD1a that is a cell surface molecule with capacity to present glycolipids to T cells, and of CD80 and CD86 which are costimulatory molecules that activate Th1 and Th2 responses. Cytokine production by MNC was also measured. Flow cytometry and ELISA were used. Cross-sectional comparisons revealed that untreated MS patients had higher CD1a+ HLA-DR+ MNC and lower IL-10 production compared to patients treated with IFN-beta or IFN-beta+GA or HC. Untreated MS patients also had higher spontaneous IFN-gamma and IL-12p70 production compared to MS patients treated with IFN-beta+GA or HC, but not when compared to MS patients on monotherapy with IFN-beta. Low CD1a+ HLA-DR+ MNC and low spontaneous production of IL-12p70 and IFN-gamma were more pronounced in patients treated with IFN-beta+GA than with IFN-beta alone. In order to clarify whether these changes reflect disease activity or treatment effects, we performed a follow up study. Nineteen MS patients with disease progression, despite monotherapy with IFN-beta for more than one year; were re-examined after one to three and four to six months of treatment with IFN-beta+GA. This combination therapy was associated with normalization of CD1a+ HLA-DR+ MNC, IL-12p70 and IFN-gamma. It remains to be shown whether these immunological changes imply a clinical benefit. Follow up studies of immune variables versus clinical effects during combined therapy of MS with IFN-beta+GA are ongoing.