Protein Derivative Research Articles

The Enterococcus faecalis FabT Transcription Factor Regulates Fatty Acid Biosynthesis in Response to Exogeneous Fatty Acids.

The phospholipid acyl chains of Enterococcus faecalis can be derived either by de novo synthesis or by incorporation of exogenous fatty acids through the fatty acid kinase complex (Fak)-phosphate acyltransferase (PlsX) pathway. Exogenous fatty acids suppress fatty acid synthesis through the transcriptional repressor FabT, the loss of which eliminated regulation of de novo fatty acid biosynthesis and resulted in decreased incorporation of exogenous unsaturated fatty acids. Purified FabT bound to the promoters of several fatty acid synthesis genes that contain a specific palindromic sequence and binding was enhanced by acylated derivatives of acyl carrier protein B (acyl-AcpB). The loss of the PlsX pathway blocked FabT-dependent transcriptional repression in the presence of oleic acid. Transcriptional repression was partially retained in a E. faecalis ΔacpB strain which showed decreased fatty acid biosynthesis in the presence of exogenous unsaturated fatty acids. The FabT-dependent activity remaining in the ΔacpB strain indicates that acylated derivatives of AcpA were weak enhancers of FabT binding although AcpA is believed to primarily function in de novo fatty acid synthesis.

Triple Intralesional Antigen Immunotherapy versus Monoantigen in the Treatment of Multiple Recalcitrant Warts.

IntroductionWarts can be resistant to treatment or recur despite the use of various destructive and immunotherapeutic modalities. Combination immunotherapy might contribute to better response rates. The aim of this study was to assess the effectiveness and safety of a triple intralesional immunotherapy combination composed of purified protein derivative (PPD), Candida antigen, and measles–mumps–rubella vaccine (MMR), versus each agent alone, in the management of multiple recalcitrant warts.MethodsIn total, 160 patients with numerous resistant extragenital warts were included in the research. They were randomly assigned to one of four groups (each with 40 patients): PPD, Candida antigen, and MMR, or combination of the three antigens. Injections into the biggest wart were repeated every 2 weeks until clearance or for a total of five sessions.ResultsComplete wart clearance was reported in 31 patients (77.5%) who received triple-antigen immunotherapy, 23 patients (57.5%) who received intralesional PPD, 29 patients (72.5%) injected with Candida antigen, and 25 patients (62.5%) who received MMR. The combined therapy was found to be superior to the other therapies and had the lowest recurrence rate, but the difference was not statistically significant.ConclusionsTriple intralesional antigen immunotherapy is as safe as, and more effective than, monoantigen immunotherapy, and can be added to the armamentarium against recalcitrant human papilloma virus (HPV) infections.

Intralesional immunotherapy for multiple recalcitrant plantar warts: Candida antigen is superior to intralesional purified protein derivative.

Treatment of recalcitrant plantar warts represent a highly challenging issue for both patients and physicians. Candida antigen and purified protein derivative (PPD) have shown promising efficacy in the treatment of warts, however no previous studies have compared both antigens for recalcitrant plantar warts. To assess the efficacy and safety of intralesional Candida antigen versus intralesional PPD in the management of recalcitrant plantar warts. The study included 120 adult patients with multiple recalcitrant plantar warts. They were randomly assigned to one of three groups; Candida antigen, PPD, or normal saline. Injections into the largest wart were repeated every 2 weeks until clearance or for a maximum of five sessions. Complete wart clearance was reported in 33 patients (82.5%) of the Candida antigen group, in 22 patients (55.6%) of the PPD group, and in one patient (5%) of the control saline group. A statistically significant difference was found between the studied groups in favor of Candida antigen. Adverse effects were mild and insignificant in the three groups. Intralesional antigen immunotherapy by Candida antigen or PPD is a promising, safe, and cost-effective therapeutic option for multiple recalcitrant plantar warts, with statistically significant superiority of Candida antigen.

Clinical diagnostic algorithm in defining tuberculous unilateral pleural effusion in high tuberculosis burden areas short of diagnostic tools.

BackgroundEmpirical treatment was introduced when pathological or microbiological results of tuberculosis (TB) were not available. This report was designed to evaluate an algorithm based on empirical treatment in defining tuberculous pleural effusion (TPE) in high burden areas but short of diagnostic tools.MethodsIn this retrospective study, a total of 924 eligible patients were enrolled and 203 (22.0%) were primarily diagnosed as TPE by our diagnostic algorithm based on effusion characteristics [adenosine deaminase (ADA) and exudate] and immunoassays [purified protein derivative (PPD), M. tuberculosis antibody (TB-Ab) and interferon-gamma release assay (IGRA)]. All diagnosed cases received World Health Organization (WHO) standard anti-TB treatment and 187 of them had at least one year of follow-up. The final diagnosis and prognosis of these patients were traced and recorded.ResultsA total of 177 (94.65%) cases benefited from standard treatment, 5 (2.67%) failed due to early termination or drug resistance, and 5 (2.67%) were finally confirmed as misdiagnosis. Regarding diagnostic efficacy, 72 (30.13%) patients received four TB tests, and the combination of the four tests could increase the diagnosis of TPE. Besides, receiving operating characteristics curve (ROC) analysis revealed that our algorithm was the best method to differentiate TPE from malignant pleural effusion (MPE) with higher sensitivity and specificity than other serum markers.ConclusionsThis clinical diagnostic algorithm was an efficient and available method for the diagnosis of TPE. This diagnostic algorithm should be implemented in regions with high TB prevalence but short of diagnostic tools.

A case of multiple sclerosis diagnosed with tuberculosis during teriflunomide therapy

A case of pulmonary tuberculosis (TB) in a patient with multiple sclerosis (MS) receiving teriflunomide is described. A 56-year-old woman with MS started interferon beta-1a treatment in 2009. Due to side effects, her physician switched her to glatiramer acetate. Over the last three years, she opted not to continue the glatiramer acetate. At the end of 2017, her symptoms reappeared, and her radiological and clinical examination showed disease progression. Teriflunomide (14 mg/day) treatment was started, and in the 15th month of teriflunomide use, a rash on the skin, coughing, night sweating fits, weakness and back pain developed. She was diagnosed with pulmonary TB based on pulmonary examination. Her purified protein derivative (PPD) score was 22. Anti-TB therapy was initiated immediately. At last visit in January 2020, TB was discovered. Her blood tests were within normal limits. Her expanded disability status score (EDSS) score was 2.5. Subcutaneous glatiramer acetate was re-initiated. A rare case of pulmonary TB under teriflunomide use is described in this case. Teriflunomide therapy should be considered in cases in which latent TB may be re-activated.

Freeze-Drying Improved the Stability of Tuberculin Purified Protein Derivative (PPD) in Mammals

Freeze-Drying Improved the Stability of Tuberculin Purified Protein Derivative (PPD) in Mammals

Pembuatan Gelatin dari Tulang Ikan Nila (Oreochromis niloticus) Menggunakan Metode Asam untuk Pengental Sirup Nanas

Imports of gelatin in Indonesia have increased according to demand. Gelatin is a protein derivative from collagen fibers derived from bone extraction. Gelatin contains protein, water and minerals. Gelatin is used to thicken, concentrate, and stabilize fluids such as water, acetic acid, and alcohol. The raw material used in the study was tilapia bone due to the lack of utilization of tilapia bone waste treatment. The purpose of this study was to examine the effect of sulfuric acid concentration on gelatin yield and to apply gelatin as a thickener for pineapple syrup. The methods are degreasing, extraction, and application of pineapple syrup. Variations in the concentration of H2SO4 were 1%, 3%, 5%, and variations in immersion time were 10 hours, 24 hours, and 36 hours. The analysis carried out on tilapia bone gelatin consisted of yield, acidity (pH) and viscosity. The best yield was produced using 1% H2SO4 and 10 hours immersion, which was 13.77%. The largest pH was produced at 2.47 with the use of 5% H2SO4 and immersion for 24 hours, and the largest viscosity was produced at 7.66 cP with the use of 5% H2SO4 and immersion for 36 hours.

Effective anti-mycobacterial treatment for BCG disease in patients with Mendelian Susceptibility to Mycobacterial Disease (MSMD): a case series

BackgroundPost-vaccination BCG disease typically attests to underlying inborn errors of immunity (IEIs), with the highest rates of complications in patients with Mendelian susceptibility to mycobacterial disease (MSMD). However, therapeutic protocols for the management of BCG-osis (disseminated) and persistent BCG-itis (localized) are still controversial.MethodsTwenty-four Iranian patients with MSMD (BCG-osis or BCG-itis), followed from 2009 to 2020 in Tehran, were included in the study. Their medical records were retrospectively reviewed for demographics, clinical features, laboratory findings, and molecular diagnosis. The therapeutic protocol sheets were prepared to contain the types and duration of anti-mycobacterial agents.ResultsBCG disease either as BCG-itis (33.3%) or BCG-osis (66.7%) was confirmed in all patients by positive gastric washing test (54.2%), microbial smear and culture (58.3%), or purified protein derivative (PPD) test (4.2%). The duration between BCG-osis onset and MSMD diagnosis was 21.6 months.All except three patients were initiated on second-line anti-mycobacterial agents with either a fluoroquinolone (levofloxacin: 15 mg/kg/day, ciprofloxacin: 20 mg/kg/day, ofloxacin: 15 mg/kg/day), aminoglycoside (amikacin: 10–15 mg/kg/day, streptomycin: 15 mg/kg/day), and/or macrolide (clarithromycin: 15 mg/kg/day) along with oral rifampin (10 mg/kg/day), isoniazid (15 mg/kg/day), and ethambutol (20 mg/kg/day). Three patients showed a clinical response to rifampin, despite in vitro resistance. Fourteen (58.3%) patients received also adjuvant subcutaneous IFN-γ therapy, 50 µ/m2 every other day. At the end of survey, most patients (n = 22, 91.7%) were alive and two patients died following BCG-osis and respiratory failure.ConclusionsWe recommend the early instigation of second-line anti-mycobacterial agents in MSMD patients with BCG disease.

Latent tuberculosis testing through the ages: the search for a sleeping killer.

Tuberculosis has been present in the world’s population for as long as there has been written language. It is a disease known to the ancient Egyptians, Greeks, Romans, and Hebrews, but its etiology eluded the world for thousands of years. Even after the germ theory was accepted and early scientists hypothesized a pathogen as the cause, the identity of the sleeping killer in society remained a mystery. That is until Robert Koch was able to grow and visualize Mycobacterium tuberculosis. Koch introduced his Old Tuberculin solution as a diagnostic therapy of tuberculosis (TB), with the intent to reduce the number of infected persons and stop its spread. Old Tuberculin’s ability to treat TB proved minimal, but its diagnostic potential paved the way for more effective tests from von Pirquet, Calmette, Wolff-Eisner, and Mantoux. Florence Seibert set out to identify and purify the active principle in Koch’s Old Tuberculin and ended up creating purified protein derivative (PPD) tuberculin which is still used as the standard for the tuberculin skin test (TST). Interferon-γ release assays (IGRAs) are a more modern diagnostic tool for detecting latent TB infection that offer some benefits (and some disadvantages) to TST. TSTs and IGRAs can determine if an individual has been infected with M. tuberculosis but are equally unable to predict progression to active tuberculosis, the diagnosis of which relies on assessment of clinical symptoms, radiographic imaging, and sample culture.

Combined intralesional injection of tuberculin purified protein derivative plus cryotherapy versus each alone in the treatment of multiple common warts.

Different modalities are used for treatment of common warts, but none of them had been proved the best in achieving complete cure. We aim to compare the effect of cryotherapy, intralesional injection of tuberculin purified protein derivative (PPD) and cryotherapy combined with intralesional injection of tuberculin PPD in the treatment of multiple common warts. This study is a randomized clinical trial in which the patients were randomly divided into three groups; group (A) included 25 patients subjected to cryotherapy, group (B) included 25 patients subjected to intralesional injection of tuberculin PPD and group (C) included 25 patients subjected to cryotherapy plus intralesional injection of tuberculin PPD. All the three groups showed a significant clinical improvement (p < 0.001) with statistically significant difference between cryotherapy group (A) and intralesional injection of tuberculin PPD group (B) (p < 0.001) and between cryotherapy group (A) and cryotherapy plus intralesional injection of tuberculin PPD group (C) (p < 0.001). However, there was no statistically significant difference between both intralesional injection of tuberculin PPD group alone (B) and cryotherapy plus intralesional injection of tuberculin PPD group (C) (p=0.213). In Conclusion the cryotherapy combined with intralesional injection of PPD and intralesional injection of PPD alone are better than cryotherapy alone in treatment of multiple common warts. However, better response could be reached in combination of both cryotherapy and intralesional PPD with less number of sessions.

Multi-Dimensionality Immunophenotyping Analyses of MAIT Cells Expressing Th1/Th17 Cytokines and Cytotoxic Markers in Latent Tuberculosis Diabetes Comorbidity.

Mucosal-associated invariant T (MAIT) cells are innate like, and play a major role in restricting disease caused by Mycobacterium tuberculosis (Mtb) disease before the activation of antigen-specific T cells. Additionally, the potential link and synergistic function between diabetes mellitus (DM) and tuberculosis (TB) has been recognized for a long time. However, the role of MAIT cells in latent TB (LTB) DM or pre-DM (PDM) and non-DM (NDM) comorbidities is not known. Hence, we examined the frequencies (represented as geometric means, GM) of unstimulated (UNS), mycobacterial (purified protein derivative (PPD) and whole-cell lysate (WCL)), and positive control (phorbol myristate acetate (P)/ionomycin (I)) antigen stimulated MAIT cells expressing Th1 (IFNγ, TNFα, and IL-2), Th17 (IL-17A, IL-17F, and IL-22), and cytotoxic (perforin (PFN), granzyme (GZE B), and granulysin (GNLSN)) markers in LTB comorbidities by uniform manifold approximation (UMAP) and flow cytometry. We also performed a correlation analysis of Th1/Th17 cytokines and cytotoxic markers with HbA1c, TST, and BMI, and diverse hematological and biochemical parameters. The UMAP analysis demonstrated that the percentage of MAIT cells was higher; T helper (Th)1 cytokine and cytotoxic (PFN) markers expressions were different in LTB-DM and PDM individuals in comparison to the LTB-NDM group on UMAP. Similarly, no significant difference was observed in the geometric means (GM) of MAIT cells expressing Th1, Th17, and cytotoxic markers between the study population under UNS conditions. In mycobacterial antigen stimulation, the GM of Th1 (IFNγ (PPD and WCL), TNFα (PPD and WCL), and IL-2 (PPD)), and Th17 (IL-17A, IL-17F, and IL-22 (PPD and/or WCL)) cytokines were significantly elevated and cytotoxic markers (PFN, GZE B, and GNLSN (PPD and WCL)) were significantly reduced in the LTB-DM and/or PDM group compared to the LTB-NDM group. Some of the Th1/Th17 cytokines and cytotoxic markers were significantly correlated with the parameters analyzed. Overall, we found that different Th1 cytokines and cytotoxic marker population clusters and increased Th1 and Th17 (IL-17A, IL-22) cytokines and diminished cytotoxic markers expressing MAIT cells are associated with LTB-PDM and DM comorbidities.

Интенсивность процессов окислительной модификации белков женского и коровьего молока

Breast milk is a source of all the essential nutritional components necessary for the full growth and development of the child, therefore, it is necessary to study its composition and physical and chemical properties in order to adapt human milk substitutes. Adapted infant milk formulas are produced mainly from cow's milk, bringing formula nutrient composition closer to the composition of women's milk, adapting it in accordance with the requirements of the infant body. However, technological processes for the production of dairy products contribute to the activation of oxidative reactions, the violation of protein conformation. The purpose of the study was to compare the intensity of formation of carbonyl derivatives of human and cow's milk proteins during spontaneous and metal-catalyzed oxidation. Material and methods. The object of the study were samples of mature milk of healthy nursing mothers (n=12), and samples of drinking ultra-pasteurized milk for baby nutrition (n=8) which were used as a comparison material. The intensity of oxidative modification of milk proteins was determined spectrophotometrically by the interaction of carbonyl derivatives of amino acid residues with 2.4-dinitrophenylhydrazine to form 2.4-dinitrophenylhydrazone derivatives in a native sample of biological material and under induction of protein oxidation in vitro by the Fenton reaction by adding FeSO4 and hydrogen peroxide solutions. The content of nonprotein sulfhydryl groups was determined after protein precipitation spectrophotometrically with 5.5'-dithio-bis-2-nitrobenzoic acid. Results. The intensity of spontaneous (basic) oxidation doesn't have significant differences between the indicators of breast and cow's milk. Significant differences were established in the content of carbonyl derivatives of amino acid residues of human and cow's milk proteins during metal-catalyzed oxidation. Incubation with iron ions caused 1.5-2.5 fold more formation of both aldehyde and ketone derivatives of cow's milk proteins, recorded in the visible and ultraviolet spectrum. In cow's milk during spontaneous oxidation and induction of oxidation by a metal, the percentage of aldehyde-dinitrophenylhydrazones was lower than in breast milk and, conversely, the proportion of ketone-dinitrophenylhydrazones, late markers of oxidative degradation of proteins, was significantly higher. The content of non-protein sulfhydryl groups in cow's milk was 2 times less than in fresh human milk. A significant excessive content of aldehyde-dinitrophenylhydrazones (2 times) and ketone-dinitrophenylhydrazones (2.6 times) undet metal-catalyzed protein oxidation of cow's milk in comparison with breast milk indicates a lower level of antioxidant reserves of cow's milk. This is confirmed by the reduced level of non-protein sulfhydryl groups. The results obtained indicate the need to improve the antioxidant status of dairy products for infant nutrition.

A molecular simulation study of hepatitis B virus core protein and the nuclear protein allosteric modulators of phthalazinone derivatives.

Hepatitis B virus, causing hepatitis, cirrhosis, liver failure, and liver cancer, poses a serious threat to human health, and the currently approved drugs still cannot eliminate the virus completely. HBV core protein allosteric modulators (CpAMs) with a phthalazinone structure which targets the HBV core (HBc) protein have been seen as a new kind of drug because of their excellent antiviral effects. This study explores the structure-activity relationship and binding mechanism of phthalazinone molecules through three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking, molecular dynamics, and binding free energy calculation and decomposition studies. In addition, CoMFA and CoMSIA models revealed that the steric field, the hydrophobic field, and the hydrogen bond acceptor field may play important roles in the binding process. The molecular docking and dynamics disclosed the most likely binding pose of phthalazinone derivatives with the HBc protein. The binding free energy calculation and decomposition analysis indicated that the van der Waals force was the driving force and that ValE124, ThrD109, ThrE128, LeuD140, IleD105, PheD110, ThrD33, and TrpD102 were the key residues. This study provides an important theoretical basis for the design and optimization of phthalazinone compounds.

Intralesional Purified Protein Derivative of Tuberculin Versus Intralesional Mycobacterium W Vaccine in Treatment of Recalcitrant Extragenital Warts: A Randomized, Single-Blinded, Comparative Study.

Introduction:Of late, immunotherapy has emerged as a promising therapeutic modality for the treatment of recalcitrant and difficult to treat warts. Purified protein derivative of tuberculin (PDD) and mycobacterium w (Mw) vaccine hold promising prospects for the treatment of verruca, especially in a country like ours where a majority of the population is already sensitized to mycobacterium tuberculosis both due to disease endemicity and Bacillus Calmette-Guérin (BCG) vaccination.Aims and Objectives:We aimed at evaluating the treatment outcome of intralesional PPD tuberculin and Mw vaccine in the treatment of recalcitrant extragenital warts in immunocompetent subjects.Materials and Methods:The patients included immunocompetent subjects between the ages of 16 and 65 years with two or more extragenital warts. The patients were randomized into two groups, namely A (PPD Tuberculin) and B (Mw vaccine). In both groups, 0.1 mL of active intralesional immunogen was injected at the base of the largest wart. The doses were repeated at 4 weeks' intervals for a maximum of 5 injections. Additionally, the improvement in quality of life was measured using the Hindi-validated version of the Dermatology Quality of Life Index (DLQI) questionnaire.Results:Ninety-seven patients completed the study, with 46 in group A and 51 in group B. In group A, 24 (52.17%) patients had complete clearance in all warts, and in group B, 32 (62.75%) (P = 0.38). The most common adverse event in patients of group A was transient injection site erythema and swelling, whereas that in group B was mild transient fever. None of the patients showed any signs of recurrence in the ensuing follow-up period. There was a statistically significant improvement in the mean DLQI scores after treatment in both groups (P < 0.0001).Conclusion:Both PPD Tuberculin and Mw vaccine are effective in the treatment of recalcitrant warts with minimal recurrence rate. The safety profile of PPD is superior to Mw vaccine. We suggest both to be used as first-line therapy in the treatment of difficult to treat warts.

Correlation of single-nucleotide polymorphism at interferon-gamma R1 (at Position - 56) in positive purified protein derivative health workers with COVID-19 infection.

The aim of the present study was to investigate the susceptibility of purified protein derivative (PPD) plus health-care workers to SARS-CoV-2 (COVID-19). For this reason, single-nucleotide polymorphism (SNP) of interferon-gamma (IFN-γ) gene at position +2109 and IFN-γ receptor 1 (R1) at position -56 was assessed in PPD plus group before and after COVID-19 infection (2017-2018; 2020-2021). The selected study cases (n = 100) that were working in tuberculosis (TB) unite (5-10 years) with PPD positivity &gt;15 mm (16-20 mm) were included in this investigation. Sampling was done twice, once before and after the COVID-19 pandemic. Group A contains 50 samples collected from the GenBank TB laboratory that belong to TB staff before the pandemic (2017-2018). The other sample (Group B; 2021) was collected from the same unite during the COVID-19 pandemic. The SNP in the IFN-γ gene (+2109; 670 bp) and IFN-γ R 1 (-56; 366 bp) was performed using a specific primer and the polymerase chain reaction products were digested using restriction enzyme Fau I and Bts I, respectively. Statistical analyses were used to obtain the frequency of alleles among all studied cases. The confidence intervals (CIs) and t-test were calculated using the SPSS and GraphPad Prism software. In overall, the most frequent genotype in Group A was AA (41/50; 82%) and Group B was 76% (38/50) in position + 2109 (odds ratio [OR] = 0.69, 95% CI, 0.26-1.83, and P = 0.46). Although in position -56, the most frequent genotype in Group A was TT (35/50; 70%) which significantly was than Group B TT (15/50; 30%) (OR = 0.184, 95% CI, 0.78-0.43, and P = 0.00). The frequency of allele A was more in both groups at position + 2109 (OR = 0.815, 95% CI, 0.23-2.86, and P = 0.75), whereas the dominate allele at position -56 was T in Group A (OR = 1.37, 95% CI, 0.62-3.02, and P = 0.42). No significant differences were observed in + 2109 in genotype among Group A and B. The main differences were seen in IFN-γ R1 at position (-56) between Group A and B. Hence, the IFN-γ R1 may play important role in COVID-19 infection. However, more study is needed to clear the IFN-γ correlation to COVID-19 infection.

Temporal trends and prediction of bovine tuberculosis: a time series analysis in the North-East of Iran.

Bovine tuberculosis (BTB) is a disease with high economic relevance. This study aimed to determine a fast alert surveillance system for bTB before the outbreak in the epidemic region of Iran. This cross-sectional study was conducted using the Auto-Regressive Integrated Moving Average (ARIMA) model for monthly bTB detections (reactors). These reactor cases result from the positive Tuberculin Purified Protein Derivative (PPD) test on cattle farms for the period between April 2007 and March 2019 in Razavi Khorasan province. Autocorrelation functions (ACF) and partial autocorrelation functions (PACF) plots were used to determine model parameters. The Akaike Information Criteria (AIC) were employed to select the best-fitted model. The root mean square error (RMSE) was applied for the evaluation of the models. Then, the best-fitted model was hired to predict the cases for 12 oncoming months. The data were analysed by STATA (ver. 14) software with a significant level at P≤0.05. ARIMA (3, 0, 3) 12 was introduced as a recommended fitted model according to white noise residual test (Q=22.87 and P=0.98), lower AIC (541.85), and more precise model RMSE (1.50). However, the forecast values were more than the observed values. The application and interpretation of ARIMA models are straightforward, and may be used as immediate tools for monitoring systems. However, we proposed an Auto-Regressive Integrated Moving Average with Exogenous Input (ARIMAX) model with some measurable exotic factors such as economic fluctuations, climate changes, and pulmonary tuberculosis to introduce a more precise and accurate model for the fast alert surveillance system.

Evaluation of Preschool Screening Program in the Kingdom of Bahrain: A Survey in Primary Healthcare Centers

Background: Preschool screening is one of the services provided by primary healthcare centers, in the Kingdom of Bahrain, for children aged 5 to 6 years. This service includes assessing growth and development parameters, which includes measuring hemoglobin levels, conducting vision examinations, and administering Purified Protein Derivative (PPD) tests. Objectives: To evaluate the prevalence of anemia, reduced visual acuity, and positive PPD tests, in children’s preschool screening. Methodology: This survey was conducted in 25 primary healthcare centers, between the period of January to March 2020, with a total sample size of 2,637 children. Electronic preschool screening visit sheets, of children who attended the health centers for screening, were reviewed and evaluated. Results: Out of the 2,637 records reviewed; anemia, reduced visual acuity, and positive PPD tests, were found in 19.9%, 4.7%, and 0.45% of children, respectively. Conclusion: The overall prevalence of reduced visual acuity and positive PPD tests was low. On the other hand, although the overall prevalence of anemia was also low, at about 20%, this can be reduced further by raising physicians’ adherence to anemia management guidelines, at earlier ages. Moreover, further studies are needed to assess the causes and risks of anemia in this age group. Keywords: Bahrain, Preschool, Screening, Primary Healthcare Centers, Prevalence

Challenges in Developing a Controlled Human Tuberculosis Challenge Model.

Controlled human infection models (CHIMs) have provided pivotal scientific advancements, contributing to the licensure of new vaccines for many pathogens. Despite being one of the world's oldest known pathogens, there are still significant gaps in our knowledge surrounding the immunobiology of Mycobacterium tuberculosis (M. tb). Furthermore, the only licensed vaccine, BCG, is a century old and demonstrates limited efficacy in adults from endemic areas. Despite good global uptake of BCG, tuberculosis (TB) remains a silent epidemic killing 1.4 million in 2019 (WHO, Global tuberculosis report 2020). A mycobacterial CHIM could expedite the development pipeline of novel TB vaccines and provide critical understanding on the immune response to TB. However, developing a CHIM for such a complex organism is a challenging process. The first hurdle to address is which challenge agent to use, as it would not be ethical to use virulent M. tb. This chapter describes the current progress and outstanding issues in the development of a TB CHIM. Previous and current human studies include both aerosol and intradermal models using either BCG or purified protein derivative (PPD) as a surrogate agent. Future work investigating the use of attenuated M. tb is underway.

The Application of an Enamel Matrix Protein Derivative (Emdogain) in Furcations: A Review of Literature

Periodontal disease results in the loss of the attachment apparatus. The search for techniques and products to encourage the regeneration of this tissue has received more attention over the past three decades. The results from basic research have shown that although there are not many studies on the use of EMD in the treatment of furcations, it is an essential option in the difficult management of furcations, and more research in periodontal regeneration is required. This paper aims to evaluate the effect of enamel matrix derivative (EMD) in the treatment of furcations.

Clinical characteristics of tuberculous infection following renal transplantation

ObjectiveThis study investigated the clinical characteristics of patients with tuberculosis (TB) following renal transplantation (RT) in order to identify markers or signs that can facilitate early diagnosis. MethodsA retrospective analysis was performed on 12 cases of Mycobacterium tuberculosis infection treated at our hospital between 2005 and 2020. ResultsThe incidence of TB after RT at our hospital was 0.9%, and the median postoperative onset time was 22 months. The average age of patients included in our analysis was 44.2 ± 9.4 years; 11 of the 12 patients were male, and most patients had (low) fever as the first or only manifestation. Five patients had respiratory symptoms; 5 had typical computed tomography (CT) presentation; and 2 had a confirmed history of TB. Two sputum smears from 12 patients were positive by acid fast staining, and M. tuberculosis was detected in peripheral blood samples by metagenomic next-generation sequencing (NGS). One patient had a positive result in the purified protein derivative (PPD) test, 7 were positive with the interferon gamma release assay (IGRA), 8/12 patients were confirmed to have TB infection by NGS and 1 was confirmed positive by lung biopsy. ConclusionBecause of the use of immunosuppressive agents, most patients with TB following RT have atypical clinical symptoms and CT findings, and may have a high probability of a false negative result with the traditional PPD test and a low probability of M. tuberculosis detection, making early diagnosis difficult. Therefore, in RT recipients with prolonged fever of unknown origin and unusual clinical manifestations, especially those who are unresponsive to antibiotic treatment, a diagnosis of TB should be considered. The interferon gamma release assay and NGS are relatively new detection methods with high sensitivity and specificity; these along with regular, repeated testing by various approaches can aid the early diagnosis of TB.