Presentation of viral antigens restricted by H-2Kb,Db or Kd in proteasome subunit LMP2-and LMP7-deficient cells

In the class II region of the major histocompatibility complex (MHC), four genes implicated in MHC class I-mediated antigen processing have been described. Two genes (TAP 1 and TAP 2) code for multimembrane-spanning ATP-binding transporter proteins and two genes (LMP 2 and LMP 7) code for subunits of the proteasome. While TAP 1 and TAP 2 have been shown to transport antigenic peptides from the cytosol into the endoplasmic reticulum, where the peptides associate with MHC class I molecules, the role of LMP 2/7 in antigen presentation is less clear. Using antigen processing mutant T2 cells that lack TAP 1/2 and LMP 2/7 genes, it was recently shown that expression of TAP 1/2 alone was sufficient for processing and presentation of the influenza matrix protein M1 as well as the minor histocompatibility antigen HA-2 by HLA-A2. To understand if presentation of a broader range of viral antigens occurs in the absence of LMP 2/7, we transfected T2 cells with TAP 1, TAP 2 and either of the H-2K^b, D^b or K^d genes and tested their ability to present vesicular stomatitis vires and influenza virus antigens to virus-specific cytotoxic T lymphocytes. We found that T2 cells, expressing TAP 1/2 gene products, presented all tested viral antigens restricted through either the H-2K^b, D^b or K^d class I molecules. We conclude that the proteasome subunits LMP 2/7 as well as other gene products in the MHC class II region, except from TAP 1/2, are not generally necessary for presentation of a broader panel of viral antigens to cytotoxic T cells. However, the present results do not exclude that LMP 2/7 in a more subtle way may, or in rare cases completely, affect processing of antigen for presentation by MHC class I molecules.     

“Pulmonary tongue” a right ventricle phase abnormality in muga studies in patients with pulmonary hypertention

Pulmonary hypertension (PH) produces strain followed by hypertrophy and later dilatation of the right ventricle (RV) and pulmonary artery. The signs and symptoms are nonspecific. There is a need for a noninvasive sensitive way to diagnose PH. The purpose of this study is to evaluate phase abnormalities in radionuclide MUGA studies of patients with referred diagnosis of PH. In a retrospective analysis of 44 patients who had a radionuclide multigated study (MUGA) and contrast ventriculography (CV), 19 had high mean pulmonary pressure (over 20 mmHg) and a high pulmonary vascular resistance index (over 2.0). In 15 patients, a delayed phase segment in the RV corresponding to the pulmonary infundibulum and pulmonary conus was noted The Pulmonary Tongue sign (PT), 12 had PH (True positive) and 3 did not (false positive) on CV. No PT was seen in the remaining 29 patients, only 7 of them had PH (False negative). The sensitivity, specificity and accuracy of the PT sign in detecting PH was 80%, 72% and 77% respectively. The number of patients was too small to calculate the correlation of the grade of PT with the severity of PH. We conclude that The Pulmonary Tongue sign on a MUGA study is clinically useful in detecting PH.This project is supported by research project MLNO13 and funded by research Council, Kuwait University     

Barriers of Adherence among Palestinian Healthcare Professionals towards the Protocol of Health Education and Counselling on Healthy Behaviours for Non-Communicable Diseases

BackgroundDespite the huge numbers of the universally produced and employed protocols, the adherence with them is still low to moderate in the healthcare settings. This study was employed to assess the attitudes of Palestinian healthcare professionals in Gaza Strip to health education and counseling on healthy behaviours protocol (WHO-PEN Protocol 2), for patients with non-communicable diseases in the Ministry of Health primary healthcare centers.MethodsThis cross-sectional study was conducted with a census sample of all governmental family physicians and nurses (n=175). The study questionnaire was developed based on Cabana theoretical framework. The Arabic version questionnaire was developed based on the cross-cultural adaptation framework. The psychometric properties of the Arabic version questionnaire was finally evaluated.ResultsThe psychometric properties of the Arabic version questionnaire showed good construct validity and internal consistency reliability. The overall adherence level to WHO-PEN Protocol 2 was 70.0, SD=6.9. The main perceived barriers were lack of incentive, patients'' factors, and lack of time. In general, most of healthcare professional respondents had a positive attitude toward the protocol, but this attitude was not predictor to protocol adherence.ConclusionThe good validity and reliability of the questionnaire can provide support for the accuracy of the study results. Varied implementation strategies targeting the major barriers derived from the study are extremely required for addressing the lack of incentives, patients'' factors and time constraints.     

Acquired Idiopathic Stiffness After Contemporary Total Knee Arthroplasty: Incidence,Risk Factors,and Results Over 25 Years

BackgroundAcquired idiopathic stiffness (AIS) remains a common failure mode of contemporary total knee arthroplasties (TKAs). The present study investigated the incidence of AIS and manipulation under anesthesia (MUA) at a single institution over time, determined outcomes of MUAs, and identified risk factors associated with AIS and MUA.MethodsWe identified 9771 patients (12,735 knees) who underwent primary TKAs with cemented, modular metal-backed, posterior-stabilized implants from 2000 to 2016 using our institutional total joint registry. Mean age was 68 years, 57% were female, and mean body mass index was 33 kg/m². Demographic, surgical, and comorbidity data were investigated via univariate Cox proportional hazard models and fit to an adjusted multivariate model to access risk for AIS and MUA. Mean follow-up was 7 years.ResultsDuring the study period, 456 knees (3.6%) developed AIS and 336 knees (2.6%) underwent MUA. Range of motion (ROM) increased a mean of 34° after the MUA; however, ROM for patients treated with MUA was inferior to patients without AIS at final follow-up (102° vs 116°, P < .0001). Significant risk factors included younger age (HR 2.3, P < .001), increased tourniquet time (HR 1.01, P < .001), general anesthesia (HR 1.3, P = .007), and diabetes (HR 1.5, P = .001).ConclusionAcquired idiopathic stiffness has continued to have an important adverse impact on the outcomes of a subset of patients undergoing primary TKAs. When utilized, MUA improved mean ROM by 34°, but patients treated with MUA still had decreased ROM compared to patients without AIS. Importantly, we identified several significant risk factors associated with AIS and subsequent MUA.Level of EvidenceLevel III, retrospective comparative study.     

Total Femur Antibiotic Spacers: Effective Salvage for Complex Periprosthetic Joint Infections

BackgroundA simultaneous periprosthetic joint infection (PJI) of an ipsilateral hip and knee arthroplasty is a challenging complication of lower extremity reconstructive surgery. We evaluated the use of total femur antibiotic-impregnated polymethylmethacrylate (PMMA) bone cement spacers in the staged treatment of such limb-threatening PJIs.MethodsThirteen patients were treated with a total femur antibiotic spacer. The mean age at the time of spacer placement was 65 years. Nine patients had polymicrobial PJIs. All spacers incorporated vancomycin (3.0 g/40 g PMMA) and gentamicin (3.6 g/40 g PMMA), while 8 also included amphotericin (150 mg/40 g PMMA). Eleven spacers were biarticular. Twelve spacers were implanted through one longitudinal incision, while 8 of 12 reimplantations occurred through 2 smaller, separate hip and knee incisions. Mean follow-up after reimplantation was 3 years.ResultsTwelve (92%) patients underwent reimplantation of a total femur prosthesis at a mean of 26 weeks. One patient died of medical complications 41 days after spacer placement. At latest follow-up, 3 patients had experienced PJI recurrence managed with irrigation and debridement. One required acetabular component revision for instability. All 12 reimplanted patients retained the total femur prosthesis with no amputations. Eleven (91%) were ambulatory, and 7 (58%) remained on suppressive antibiotics.ConclusionTotal femur antibiotic spacers are a viable, but technically demanding, limb-salvage option for complex PJIs involving the ipsilateral hip and knee. In the largest series to date, there were no amputations and 75% of reimplanted patients remained infection-free. Radical debridement, antimicrobial diversity, prolonged spacer retention, and limiting recurrent soft tissue violation are potential tenets of success.Level of EvidenceIV.     

Developing and testing of an Egyptian version of Children's Health Locus of Control scale

The purpose of this study is to develop and test the reliability and validity of an Egyptian version of the Children's Health Locus of Control scale. A cross sectional study design was applied using a stratified random sample of 930 students from the final two grades of primary and all grades of the preparatory schools. A further convenience sample of 120 students was selected to examine test-retest reliability of the scale. A preliminary instrument was developed and consisted of 40 statements having one of two response forms; a Yes/No format and a 4-point Likert scale format From data analysis the later format showed higher validity and reliability than the former one. Construct validity of the scale is evidenced by the factor analysis which revealed five factors (Internal, Chance, Powerful Others, Fate and Self blame) consistent with the previous theoretical model of HLC. As indicated by eta coefficient the scale and the subscales showed strong discriminating power between subjects. The known group comparison indicated a good criterion validity of the scale and the subscales. The scale showed a considerable reliability as alpha coefficient was 0.73 with test-retest reliability of 0.65. Comparison of different groups of students indicated that the scale could be used with confidence for all age groups, though it was more reliable for the preparatory phase, for private and governmental schools for males and females and for different social strata. Further testing of the developed scale is indicated among Egyptian children in different cultures.     

An indoor bio-contaminants air quality

Both the quantity and quality of microorganisms (mold, actinomycetes and bacteria) were investigated in the air of five clean rooms indoors, outdoor air sampling was a routine work of the present study. Total viable bacterial counts were recorded in a mean value of 103 cfu/m3, whereas mold counts ranged between 102-103 cfu/m3. The highest mold counts were recorded at some places investigated such as research laboratories and a library. Moreover, the types, percentages and frequencies of occurance of viable mold were studied. Penicillium, Cladosporium and Aspergillus were the predominant mold genera. These organisms are aeroallergens. Actinomycetes were detected in low numbers compared with other organisms (range between 0-102 cfu/m3). Yellow, grey and white colour series were dominant streptomycetes. The mold and streptomycetes spore sizes were measured microscopically. The sizes of major mold spores ranged between 2.5-10 mum, whereas that of streptomycetes spores ranged between 1.2-2.5 mum. The particles < 5 mum in sizes are likely to reach the alveoli which may elicit potential risk for exposed residents. However, a low number of air microorganisms does not mean a clean and healthy environment.     

DNA minor-groove binders: results and design of new antitumor agents.

DNA minor-groove binding drugs have been extensively studied in the last years in order to influence the regulation of gene expression in neoplastic disorders by means of specific interactions with DNA bases. Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs), CC-1065 and distamycins are three classes of minor-groove alkylating agents which showed interesting cytotoxicity profiles, but they cannot be used in humans for various toxicity problems. For this reason many groups applied heterocyclic substitutions extensively, in order to either modify the reactivity profile or introduce extra interactions within the minor groove, thus changing the binding site or modulating the binding sequence.     

Evaluation of crude and purified Toxocara canis antigens in serodiagnosis of human toxocariasis

Three serological tests: Immunodiffusion (ID), Counterimmunoelectrophoresis (CIEP) and Enzyme-linked immunosorbent assay (ELISA) were used to study the role of crude adult worm antigen (CAWA) of Toxocara canis and each of its purified fractions in the serodiagnosis of human toxocariasis. Sensitivities of the three tests were lower in the ocular than in the visceral group, using different antigens. Purified fraction 1 showed more sensitive and specific reactions in the three tests, compared to CAWA or purified fraction 2 (P-F2) antigen. The other purified fractions (P-F3, P-F4 and P-F5) gave no positive reactions in any of the three tests. Using P-F1 antigen, ELISA was the most sensitive technique for diagnosis of both visceral and ocular toxocariasis followed by CIEP and then ID and the difference was statistically significant. However, CIEP was the most specific test followed by ELISA and lastly ID test. The ELISA test using Excretory-Secretory (E-S) larval antigen of Toxocara canis was less sensitive than the ELISA test using P-F1, although it was 100% specific. Thus, ELISA test using P-F1 is the test of choice for diagnosis of human toxocariasis, but when the specificity of a reaction is in doubt, CIEP test using the same antigen can be of value.