Pseudomonas aeruginosa is an important opportunistic pathogen causing a variety of acute infections including nosocomial pneumonias, sepsis, urinary tract infections, keratitis, wound and skin infections. P. aeruginosa continues to be a leading cause of infections in immunocompromised host including patients with cystic fibrosis and is among the most virulent of the opportunistic pathogens as listed by the Centers of Disease Control (CDC). P. aeruginosa has also developed mechanisms to colonize surfaces by coordinately expressing genes in a density dependent manner regulated by the production of small diffusible molecules called auto inducers or quorum sensing (QS) molecules. Activation of the QS cascade promotes formation of biofilms which provide an encapsulated communal structure that coats mucosal surfaces and invasive devices. These biofilms make conditions more favorable for bacterial persistence as embedded bacteria are inherently more difficult to eradicate by both antibiotic regimens as well as by innate immune systems as compared with those in the planktonic state. The objective of this report is to provide an overview; (i) propagation of P. aeruginosa biofilms; (ii) components of the biofilm matrix and their transcriptional regulation; (iii) key signaling pathways regulating C-di-GMP dependent biofilm dispersal; (iv) characterization of experimental models of biofilms.

In intensive care patients, due to increase in hydrostatic pressure and hyperpermeability state, pulmonary edema occurs. In this review, we discussed about definition and amount of extravascular lung water index (EVLWI) which relates to an increasing pulmonary capillary hydrostatic pressure or increasing capillary permeability. EVLWI-to-intrathoracic blood volume ratio is useful in determining the cause of pulmonary edema. EVLWI can be helpful in approximation of the amount of fluid overload and capillary leak in acute inflammatory injury. This is identified as a prognostic marker that is related to respiratory function and mortality in patients with acute respiratory distress syndrome and sepsis. Usage of EVLWI for determining of pulmonary edema in children would be beneficial.

Bacteria show a plenty of cellular shapes and can alter their forms. The bacterial cell shape is functionally important. Bacteria have a number of options to select their shapes in order to uptake more nutrient, motility, attachment to surface, symmetrical division of chromosomal elements, and localization of complex secretion apparatuses. Some factors including peptidoglycan and cytoskeleton-like proteins can regulate and keep the bacterial shape. In the case of Mycobacterium tuberculosis, the reported morphological variation in the pathogen are classified into two categories; those which frequently seen at exponential phase of growth that is rod, V, Y-shape, branched, or buds, and those that are seen occasionally under stress or environmental conditions which are round, oval, ultra-virus, spore-like, and cell wall defiant or L-forms. Growth conditions and age of the cells can influence on the shape and size of the pathogen in a range from coccobacilli to long rods. Under unsuitable conditions including starvation or oxygen deprivation, tubercle bacillus assumed a swollen shape without making the vacuolar or globoid bodies. The physical circumstances and nutritional feature will control the temporary lifestyle of the pathogen.

Background: Sarcoidosis is a multisystemic disorder with unknown causes. Mycobacterium tuberculosis has been implicated as one of the possible causes of sarcoidosis. Interferon-gamma release assays are in vitro diagnostic tests for detection of the latent tuberculosis infection (LTBI) which has been replaced by tuberculin skin test (TST) in some countries. The purpose of this study was to investigate the prevalence of LTBI in Iranian sarcoidosis patients. Methods: Ninety participants with the mean age of 42.22 ± 14.55 were enrolled in this study. They were divided into three equal groups consisted of patients with active TB, patients with sarcoidosis, and controls. TST and QuantiFERON^®-TB Gold (QFT) were performed according to the manufacturer's instructions and the result interpreted. Results: The positive rates of TST were 76.66%, 3.3%, and 6.66% in TB, sarcoidosis, and control groups, respectively. However, QFT was positive in 24 (96.66%) of the TB group, 6 (20%) of sarcoidosis patients, and 5 (16.66%) of the control group. The agreement between the aforementioned tests was low (Cohen's kappa coefficient (κ) = 0.24). Conclusions: The current study suggests that in an intermediate-incidence TB population such as Iran, QFT is much more accurate than TST for the diagnosis of LTBI in patients with sarcoidosis. The present finding increases the possibility of this hypothesis which states that nontuberculous mycobacteria may play a role in the etiology of sarcoidosis.

Introduction: Guava leaf contains low calorie, vitamins, minerals antioxidants, polyphenolic, and flavonoid compounds which may play important role in prevention of cancers, aging, cell differentiation, apoptosis and may also have immune enhancing properties while ibuprofen is a nonsteroidal anti inflammatory drug commonly used to relief pain. It reduces hormones that cause inflammation and pain in the body.This project work was therefore designed to evaluate the plasma level of pro (tumor necrosis factor alpha (TNFα)) and anti inflammatory (interleukin 4 [IL 4] and 6) cytokines, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in rabbits overdosed with ibuprofen and supplemented with guava leaf extract. Methods: Fifteen rabbits grouped into three experimental groups labeled A–C (with subgroups B1, B2, C1, and C2) with A as control were investigated. An overdose of ibuprofen of 1600 mg/kgBW was administered to Group B and C rabbits to induce toxicity, while 400 ml/kgBW guava leaf extract was used to reduce and treat ibuprofen toxicity. Plasma tumor necrosis factor alpha (TNFα), IL-4 and 6, AST, and ALT were analyzed biochemically by spectrophotometry and enzyme-linked immunosorbent assay. Results: The result obtained showed a significant increase in the plasma value of TNF-α, IL-4, IL-6, ALT, and AST in rabbits induced with 1600 mg/kgBW of ibuprofen per oral fed with normal meal for 7 days (Group B1 and C1) compared with normal rabbits fed with normal meal and water only for 7 days (Group A) (P < 0.05). There was a significant decrease in the plasma value of TNF-α, IL-4, IL-6, and AST in rabbits given 400 ml/KgBW of guava leaf extract daily for 7 days after 7 days of postibuprofen administration (Group B2 and C2) compared to when the rabbits were given 1600 mg/kgBW of ibuprofen per oral with normal meal and water observed for 7 days (B1 and C1) (P < 0.05). Conclusion: Guava aqueous extract has been demonstrated to reduce the biochemical alterations in the plasma values of (TNF-α, IL-4, IL-6, AST, and ALT) following ibuprofen overdose as a result of the phytochemical contents of the guava leaf.

Background: Finding and choice the best treatment for the plateau tibia complex fracture has always been discussed. The present study aimed to compare the therapeutic outcomes of the external hybrid fixation method with a double-plate classic method in the treatment of plateau tibia complex fracture. Methods: Forty patients with plateau tibia complex fracture were treated with either a double plate or an external hybrid fixation. A knee score and clinical-functional table were used to evaluate patients after surgery. Level of evidence for this article is level one. Results: Knee score in the double and hybrid group was good to excellent in 60% and 75% of patients, respectively (P = 0.675). In patients, the union was formed correctly and skin necrosis was not observed in any of the cases. There were no significant differences between the two groups in the complications. In the double group, the risk of deep infection of the surgical site was 2.33 times in the patients. The pin-tract infection was observed in only 8 patients (40%) of the hybrid group. Depression was observed in 5 patients in the double group (25%) and 9 patients in the hybrid group (45%) (P > 0.05). Conclusion: In the treatment of plateau tibia complex fracture, both double plate and external hybrid fixation methods have almost the same therapeutic results and complications. However, the rate of pin-tract infection in the external hybrid surgical technique of fixation and the degree of deep infection is more common in double-plate surgery.

Background: Vitamin B12 maintains normal folate metabolism during pregnancy. Maternal folate status has been associated with various adverse pregnancy outcomes. The aim of this study is to predict the risk of abortion in early pregnancy by studying the relation between folate, Vitamin B12 levels, and rate of abortion. This prospective, observational study was carried out on 100 pregnant women with singleton pregnancy of 6–12 weeks of gestation. Methods: The patients were divided into three groups, namely, Group 1 (control group) comprising of 30 normal pregnant women with no history of abortion; Group 2 (control group) comprising of 35 pregnant females with history of previous abortion; and Group 3 (study group) comprising of 35 pregnant women were coming with chief complaint of bleeding per vaginum. About 5 ml blood was taken and serum was separated using centrifugation. Serum folate and Vitamin B12 levels were estimated by chemiluminescence. Data so obtained were computed as mean + standard deviation and SPSS/ANOVA was applied. Results: Serum folate and Serum B12 levels were comparable in all the three groups and the difference was statistically significant. 26.66%, 37.13%, and 31.42% patients had folate deficiency in Groups 1, 2, and 3, respectively. Out of which, 3.33%, 5.71%, and 5.71% patients aborted from folate deficient Groups 1, 2, and 3, respectively. Thus, folate deficiency was not found to be associated with abortion (P = 0.944). Patients with Vitamin B12 deficiency were 73.33%, 82.85%, and 37.13% in Groups 1, 2, and 3, respectively; out of which 3.33% patients from Group 1, 8.57% from Group 2, and 2.85% patients from Group 3 were aborted. Correlation between maternal serum B12 deficiency and abortion was found to be insignificant (P = 0.551). Conclusion: A positive correlation was seen between serum folate and B12 levels. All females planning for conception should be given folate and Vitamin B12 supplementation.

Background: Genome-wide association studies (GWASs) have identified 43-associated variants with conotruncal heart defects (CTD) at P ≤ 5E-7, P ≤ 5E-6, and P ≤ 5E-5 till January 2018. Despite the GWASs still provide a growing number of associated genetic variants, the identification of their pathogenic mechanisms remains a major challenge in human genetics requiring data mining efforts and predictive models for accurate interpretation of noncoding variants especially. Hence, I applied a post-GWAS analysis approach to identify the possible mechanism of action of noncoding variants associated with CTD according to the latest update of the GWAS catalog. Method: I aimed in this study to conduct a post-GWAS analysis of the most associated noncoding variants with CTD to elucidate its probable pathogenic mechanisms. Through three GWAS traits belong to CTDs, it was used in a variety of integrated and computational algorithms to collect the available information about the selected noncoding variants and its associated partners. Results: It was found differential histone modification, motif binding, and gene expression among the CTD-associated single nucleotide polymorphisms. Through intensive analysis, it was also found that both the linked rs2517582 and rs17189763 haplotype might lead to alteration in the Pic3ca-AKT signal pathway due to a change of CTCF-binding affinity and upregulation of VARS2 gene. Conclusion: It was concluded that the indirect effect of the upregulation VARS2 gene might associates with CTD. Consequently, phosphoinositide 3-kinases/AKT (pic3ca/AKT) pathway has a pivotal role in the signal system of heart morphogenesis.

Background: Raw cucumber (Cucumis sativus) fruit juice contains phytochemicals and phytonutrients of antioxidative bioactivities while overdose of amoxicillin could bring about drug-induced toxicity and oxidative stress. Malondialdehyde (MDA) is an oxidative index while catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) are scavenging antioxidants. This work was therefore designed to determine the scavenging antioxidative bioactivities of cucumber (C. sativus) fruit juice in rabbits overdosed with amoxicillin. Methods: Fifteen rabbits of the same sex divided into three groups of 5 rabbits each were used for the study. Group A – 5 control rabbits; Group B – 5 rabbits given 30 mg/kgBW subcutaneous injection of amoxicillin every 24 h for 7 days which was followed by 30 ml raw cucumber fruit juice supplementation for 14 days; and Group C – 5 rabbits given 30 mg/kgBW subcutaneous injection of amoxicillin every 24 h and raw cucumber fruit juice supplementation for 14 days simultaneously. Plasma MDA, CAT, SOD, and GPx were determined in the rabbits biochemically by spectrophotometry, fluorometry, and ELISA. Results: The results obtained showed a significant increase in plasma value of MDA and a significant decrease in plasma CAT, SOD, and GPx when the rabbits were given 30 mg/kgBW subcutaneous injection of amoxicillin (P < 0.05). These significant biochemical changes were however reversed in the rabbits when they were supplemented with 30 ml raw cucumber fruit juice (P < 0.05). Simultaneous administration of 30 mg/kgBW subcutaneous injection of amoxicillin and 30 ml raw cucumber fruit juice showed no significant biochemical changes (P > 0.05). Conclusion: This work showed abnormal plasma values of MDA, CAT, SOD, and GPx following amoxicillin overdose which was reversed owing to possible scavenging antioxidative potentials of raw cucumber fruit juice. The raw cucumber juice could therefore be a natural antidote in drug-induced toxicity.

Background: Urinary tract infection includes infection of the kidneys and bladder. Escherichia coli is the most known cause of urinary tract infection. Severity of the infection depends on the host sensitivity and the presence of virulence factors in the bacterium. In this study, antibiotic-resistance patterns and phylogenetic grouping of urine E. coli isolates from girls referred to Shahid Motahari Hospital, Marvdasht, Iran, were investigated. Methods: In this sectional-descriptive study, urine samples of 45 girls under the age of five suspected to urinary tract infection were collected in a period of 3 months. Eleven isolates of E. coli were identified using common morphological and biochemical tests. Antibiotic resistance patterns of isolates were identified. Phylogenetic groups were determined using polymerase chain reaction methods. Results: In this study, the most antibiotic resistance of the isolates was against cephalexin and the least antibiotic resistance was against imipenem (IPM). Besides, all isolates belonged to the phylogenic Group D. Conclusion: Results shows that IPM may be high effective to treat of the patients referred to Shahid Motahari Hospital in Marvdasht. Overall, results of antibiotics susceptibility tests in different area may be different. Therefore, different antibiotics are required to administrate for patients in different regions around the world or even in a country.

Introduction: Malaise involves general discomfort, uneasiness, or pain which could indicate microbial infection or other diseases which could be as a result of immune response. Methods: The study population was 200 malaise anicteric hepatitis B surface antigen (HBsAg)-seronegative patients (females – 100; males – 100) aged 5–76, and 111 apparently healthy anicteric nonmalaise age-matched subjects who were HBsAg-seronegative (females – 56 and males – 55) were recruited as test and control subjects, respectively. Immunochemical assay of anti-HBe, anti-HCV, HBsAg, and HBeAg was carried out in all the participants by enzyme-linked immunosorbent assay, while anti-HIV was determined in the participants by immunochromatographic and Western blot assay. Results: The results obtained in HBsAg-seronegative anicteric malaise patients revealed the frequency of occurrence of 3% (6) HBeAg; 9.5% (19) HBeAb; 3.5% (7) anti-HIV; 6.5% (13) anti-HCV; 1% (2) anti-HIV + HBeAg; 0.5% (1) anti-HIV + HBeAb; 0.5% (1) anti-HIV + anti-HCV; and 0.5% (1) anti-HIV + anti-HCV + HBeAg, with 9.5% (19) HBeAb found to be most frequent followed by 6.5% (13) anti-HCV; 3.5% (7) anti-HIV and 3% (6) HBeAg were more in female than male. About 25% (50/200) malaise HBsAg-seronegative patients expressed at least one of the HIV, HCV, and HBV serologic markers compared with 9.9% (11/111) in the control subjects. There was a low frequency of coexpression of viral biomarkers (0.5%–1%). Conclusion: Malaise in HBsAg-seronegative patients could be associated with the expression of serologic biomarkers of HCV, HIV, and HBV.

Introduction: Vascular endothelial cell senescence has been involved in endothelial dysfunction and inflammation and promotes atherosclerosis; moreover, vascular endothelial cells with senescent phenotype have been found in the human atherosclerotic plaques. The mechanism of senescence of endothelial cell through telomere length (TL) shortening has been explained but, with reference to micronutrient status, was not fully clarified. To our knowledge, there is no study on the level of telomere/telomerase with the combination of micronutrient levels in coronary artery disease (CAD). Methods: Twenty patients of angiographically diagnosed CAD and twenty age-matched controls (≤40 years) without CAD were studied for their circulatory endothelial progenitor cells (EPCs) by flow cytometry. EPC-TL was studied by real-time quantitative polymerase chain reaction. Copper (Cu), zinc (Zn), and selenium levels in serum were analyzed by atomic absorption spectrophotometry. The association across the serum trace elements and TL was made and correlated with disease condition. Results: EPC count in CAD patients was observed to be lower than that compared with controls (0.18% vs. 0.049%) (P < 0.0001). Cellular TL in CAD statistically decreased compared to that of normal controls (4.21 vs. 5.32) kb/genome (P = 0.008). Serum Zn and Cu levels were significantly low in CAD compared with the controls (P < 0.001). TL and Cu and Zn levels were found positively correlated in the CAD patients and controls (P < 0.001). Conclusion: Reduced levels of telomerase may be due to lower concentration of Cu and Zn, which leads to decreased antioxidant capacity. Establishing a standardized method of evaluating TL and trace elements involved in cholesterol metabolism is essential before its routine use in preventive cardiology.

Introduction: Drug resistant tuberculosis (TB) among the new and retreatment cases was seen to be 5%. Multidrug resistant TB to at least isoniazid and Rifampicin is an alarming threat to the community and the scenario is even worse for retreatment cases showing rising trend over the years. A systematic analysis of the nature of the resistance conferred may contribute in understanding the common as well as rare genetic alterations that ultimately led to the genotypic resistance. The study thus involves a probe into the most common and rare patterns of genetic mutation that have led to the rifampicin resistance among the retreatment cases. The common and rare codons along with their change in amino acid sequences involved in conferring the resistance were looked for. Methods: The detection of the patterns genetic mutation is done by the Genotype MTBDR plus V2 kits (Hains Life Sciences) based on DNA strip technology (line probe assay). Results: The analysis has shown that only around 14.93% cases reflected exclusive mutations at around 531-533 region of the RpoB gene. Presence of both the wild and mutant gene segments simultaneously (WildType [WT] and MUT3) accounted to a striking percentage of 60.3% showing a heterogenous generation of susceptible and resistant strains at the same time. This pattern analysis showing maximum of heterogenous strains may be suggestive of capturing a generation under the process of conversion from WT to mutant type. About 95% reproducibility in liquid culture system further established the fact that most of the strains might be a cause for the rising attrition toward the first line of drugs. Conclusion: This pattern analysis showing maximum of heterogenous strains may be suggestive of capturing a generation under the process of conversion. The retrospective analysis showed how heterogenous population prevailed in the retreatment groups.

Background: Tuberculosis (TB) still remains the major public health threat in India. Early diagnosis, so as to initiate early treatment is a priority as any delay, may complicate the prognosis further leading to the failure of an effective control. India accounts for 6% incidence of pediatric TB cases in a population that has 40% as estimated latent TB cases. Implementation of cartridge-based nucleic acid amplification tests (CBNAATs) in diagnosis of pediatric TB has augmented the detection rates. The study involves a retrospective multidimensional analysis of the increased pediatric TB case detection by CBNAAT at the Intermediate Reference laboratory, State TB Demonstration and Training Centre in West Bengal, India. A total of 14,088 samples from pediatric patients coming from all the districts were tested from May 2014 to April 2018. This included pulmonary (sputum, bronchoalveolar lavage, gastric lavage, and gastric aspirate) and extrapulmonary (cerebrospinal fluid [CSF], pus, ascitic fluid, pericardial fluid, lymph node aspirate) samples. Although detection levels showed variation in the nature of the samples, the study explored percentage contribution of the types of samples and the proportion positive rates among them. Percentage-wise propensity with regard to age, clinical presentations, type of samples, and smear result were observed. The predominant geographical location in terms of incidences and periodic prevalence were studied. The resistant cases were retested with line probe assay by MTBDRplus and V2 Hains for concordance analysis. This was done based on the parameters in the erstwhile evaluations. Methods: Pulmonary and extrapulmonary pediatric samples were tested on CBNAAT by Xpert Mycobacterium tuberculosis rifampicin (RIF) (Cepheid) based on the manufacturer's instruction. All necessary aseptic measures were taken. The data were captured in the Xpert software automatically during the tests and exported to the Microsoft Excel sheets for further analysis. A defined study design against each and every objective was set up. Results: It was found that a point prevalence of 6%–7% of pediatric TB exists among the tested specimens every quarter. The periodic prevalence was found to be 5%, the incidence rates ranged from 4.5% to 5%. RIF resistance detection showing a seasonal variation ranged from 13% to 15% among the CBNAAT-positive cases. Gastric lavage showed a major detection in children below 6 months of age of whom collecting sputum samples were difficult. This prompted suboptimal detection levels due to the dearth of sample collection modalities at the peripheries. CSF accounted for 2.37% of positivity. Conclusions: The study concluded that more skilled collection centers for biological specimens are required to address the undetected pulmonary TB cases among the pediatric age group, especially below the 6 months of age. About 5% prevalence and around 4.9% incidence is an alarming situation in the TB control scenario of West Bengal. Focus on the universal drug-susceptibility testing is a prerequisite.

Background: Anthracosis is a chronic pulmonary disease with black pigmentation of the bronchial mucosa, caused by carbon accumulation in the lungs, and in some cases, associated with pulmonary tuberculosis (TB). The purpose of this study is to evaluate the serum and bronchoalveolar lavage (BAL) fluid levels of the CD4/CD8 ratio and interleukin 8 (IL-8), as the potential diagnosis and prognosis biomarkers for anthracosis. Methods: Of 60 patients, referred to the Masih Daneshvari Hospital, 30 anthracosis patients, confirmed by bronchoscopy, were included as the case group. BAL sample and blood samples were collected from all individuals and sent to the immunology laboratory. Patients with no anthracosis on bronchoscopy, and suspected to have TB, were included in the control group. In addition, BAL samples were used for BK-polymerase chain reaction. Results: In this case–control study, 30 anthracosis patients and 30 controls were investigated. There were no significant differences in IL-8 of patients with anthracosis, compared to others. There were significant differences of the CD4/CD8 ratio in BAL fluid, between anthracosis cases and the control group (1.01 ± 0.77 vs. 2.41 ± 3.50; P = 0.04), and significant differences were seen in serum levels of two groups (P = 0.02). The rate of the confirmed pulmonary TB which was 88.9% in patients with anthracosis was significantly higher than the control group. Conclusion: These outcomes suggest that changes in the CD4/C8 levels in serum and BAL fluid may have a leading role in the diagnosis or prognosis of anthracosis. In addition, due to the strong association of anthracosis and pulmonary TB, TB should be considered in patients with anthracosis, which in turn can eventuate to the early distinguish and cure of the patients.