In vitro rescue of genital strains of Chlamydia trachomatis from interferon-γ and tryptophan depletion with indole-positive, but not indole-negative Prevotella spp.

© 2016 The Author(s). Background: The natural course of sexually transmitted infections caused by Chlamydia trachomatis varies between individuals. In addition to parasite and host effects, the vaginal microbiota might play a key role in the outcome of C. trachomatis infections. Interferon-gamma (IFN-γ), known for its anti-chlamydial properties, activates the expression of indoleamine 2,3-dioxygenase (IDO1) in epithelial cells, an enzyme that catabolizes the amino acid L- tryptophan into N-formylkynurenine, depleting the host cell's pool of tryptophan. Although C. trachomatis is a tryptophan auxotroph, urogenital strains (but not ocular strains) have been shown in vitro to have the ability to produce tryptophan from indole using the tryptophan synthase (trpBA) gene. It has been suggested that indole producing bacteria from the vaginal microbiota could influence the outcome of Chlamydia infection. Results: We used two in vitro models (treatment with IFN-γ or direct limitation of tryptophan), to study the effects of direct rescue by the addition of exogenous indole, or by the addition of culture supernatant from indole-positive versus indole-negative Prevotella strains, on the growth and infectivity of C. trachomatis. We found that only supernatants from the indole-positive strains, P. intermedia and P. nigrescens, were able to rescue tryptophan-starved C. trachomatis. In addition, we analyzed vaginal secretion samples to determine physiological indole concentrations. In spite of the complexity of vaginal secretions, we demonstrated that for some vaginal specimens with higher indole levels, there was a link to higher recovery of the Chlamydia under tryptophan-starved conditions, lending preliminary support to the critical role of the IFN-γ-tryptophan-indole axis in vivo. Conclusions: Our data provide evidence for the ability of both exogenous indole as well as supernatant from indole producing bacteria such as Prevotella, to rescue genital C. trachomatis from tryptophan starvation. This adds weight to the hypothesis that the vaginal microbiota (particularly from women with lower levels of lactobacilli and higher levels of indole producing anaerobes) may be intrinsically linked to the outcome of chlamydial infections in some women

Highly heterogeneous probiotic Lactobacillus species in healthy iranians with low functional activities

Background Lactic acid bacteria (LAB) have been considered as potentially probiotic organisms due to their potential human health properties. This study aimed to evaluate both in vitro and in vivo, the potential probiotic properties of Lactobacillus species isolated from fecal samples of healthy humans in Iran. Methods and Results A total of 470 LAB were initially isolated from 53 healthy individual and characterized to species level. Of these, 88 (86) were Lactobacillus species. Biochemical and genetic fingerprinting with Phene-Plate system (PhP-LB) and RAPD-PCR showed that the isolates were highly diverse consisted of 67(76.1) and 75 (85.2) single types (STs) and a diversity indices of 0.994 and 0.997, respectively. These strains were tested for production of adhesion to Caco-2 cells, antibacterial activity, production of B12, anti-proliferative effect and interleukin-8 induction on gut epithelial cell lines and antibiotic resistance against 9 commonly used antibiotics. Strains showing the characteristics consistent with probiotic strains, were further tested for their anti-inflammatory effect in mouse colitis model. Only one L. brevis; one L. rhamnosus and two L. plantarum were shown to have significant probiotic properties. These strains showed shortening the length of colon compared to dextran sulfate sodium and disease activity index (DAI) was also significantly reduced in mouse. Conclusion Low number of LAB with potential probiotic activity as well as high diversity of lactobacilli species was evident in Iranian population. It also suggest that specific strains of L. plantarum, L. brevis and L. rhamnosus with anti-inflammatory effect in mouse model of colitis could be used as a potential probiotic candidate in inflammatory bowel disease to decrease the disease activity index. © 2015 Rohani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Studies on Calf Diarrhoea in Mozambique: Prevalence of Bacterial Pathogens

The prevalence of diarrhoea in calves was investigated in 8 dairy farms in Mozambique at 4 occasions during 2 consecutive years. A total of 1241 calves up to 6 months of age were reared in the farms, and 63 (5%) of them had signs of diarrhoea. Two farms had an overall higher prevalence (13% and 21%) of diarrhoea. Faecal samples were collected from all diarrhoeal calves (n = 63) and from 330 healthy calves and analysed for Salmonella species, Campylobacter jejuni and enterotoxigenic Escherichia coli (ETEC). Salmonella spp. was isolated in only 2% of all calves. Campylobacter was isolated in 11% of all calves, irrespective of health condition, and was more frequent (25%) in one of the 2 diarrhoeal farms (p = 0.001). 80% of the isolates were identified as C. jejuni. No ETEC strains were detected among the 55 tested strains from diarrhoeal calves, but 22/55 (40%) strains from diarrhoeal calves and 14/88 (16%) strains from healthy calves carried the K99 adhesin (p = 0.001). 6,757 E. coli isolates were typed with a biochemical fingerprinting method (the PhenePlate™) giving the same E. coli diversity in healthy and diarrhoeal calves. Thus it was concluded: i) the overall prevalence of diarrhoea was low, but 2 farms had a higher prevalence that could be due to an outbreak situation, ii) Salmonella did not seem to be associated with diarrhoea, iii) Campylobacter jejuni was common at one of the 2 diarrhoeal farms and iv) ETEC strains were not found, but K99 antigen was more prevalent in E. coli strains from diarrhoeal calves than from healthy, as well as more prevalent in one diarrhoeal farm

Resistance-gene cassettes associated with Salmonella enterica genotypes

Background: The epidemiology of salmonellosis is complex because of the diversity and different serotypes of Salmonella enterica (S. enterica) that occur in different reservoirs and geographic incidences. Objectives: To determine the genotype distribution and resistancegene content of 2 classes of integron among S. enterica isolates. Methods: Thirty-six S. enterica species were isolated and tested for their serological distribution and the resistance-gene contents of 2 classes of integron, as well as for their genetic diversity, using the pulsed-field gel electrophoresis (PFGE) genotyping method. Results: Serogroups E (36.1) and D (30.5) were dominant among the isolates. All of the isolates in serogroup D belonged to the serovar enteritidis. The aadA1 gene was found within all resistance-gene cassettes. We observed 4 common and 26 single pulsotypes among the isolates, which indicated a high degree of genetic diversity among the isolates. Using the PulseNet International standard protocol, it was found that these isolates were different from those reported previously in Iran. Conclusions: The presence of a few common and new pulsotypes among the isolates suggests the emergence and spread of new clones of S. enterica in Iran

Brain computed tomography scan findings in children with neurological impairment during the early postoperative period of open-heart surgery for congenital heart disease

Objectives: We evaluated the brain computed tomography (CT) scan findings of children with abnormal neurologic recovery during the postoperative period for corrective/palliative congenital heart surgery. Methods: This study was conducted at a referral educational pediatric hospital from May 2015 to May 2016. We included patients with congenital heart disease (CHD) who underwent corrective/palliative cardiac surgery presenting with abnormal neurologic recovery in the early postoperative period. We recorded the demographic data, past medical history, surgery details, type of neurological disorders leading to a brain CT scan, and postoperative coagulopathy. Results: From among 734 cardiac surgeries from May 2015 to May 2016, 40 (5.44) patients with abnormal neurologic recovery were assessed by brain CT scans. Among them, 55 were male and 45 were female with a mean age of 14.6 months. The most frequent heart anomaly was the transposition of great arteries (27.5), which is known as the most common cause of cardiac surgery in the first month of life. Seizure (67.5) was the most common neurologic manifestation and had the highest predictive value for the presence of an abnormal finding in the brain CT scan (91.3). Intracranial hemorrhage, specifically subarachnoid hemorrhage, was the most frequent underlying pathology in brain CT scans of patients presenting with seizure. The most common findings in brain CT scans included subarachnoid hemorrhage (82.6), intraparenchymal hemorrhage (26.08), and ischemic infarction (17.39). Data showed that a bypass time of over 180 min could significantly increase the probability of abnormal brain CT scan findings (P value = 0.03), particularly intra-parenchymal hemorrhage (P value = 0.016). The presence of coagulopathy concomitant with seizure would significantly increase the possibility of abnormal brain CT scan findings due to an acute neurologic event (P value = 0.049). Conclusions: This study showed seizure as the most common neurologic manifestation in the early postoperative period of cardiac surgery and the intracranial hemorrhage as the most common underlying pathology in patients with neurologic symptoms. Seizure in patients with coagulopathy should be considered as a great concern for physicians to evaluate acute neurologic events more precisely. © 2020, Author(s)

Evolutionary dynamics of cancer in response to targeted combination therapy

In solid tumors, targeted treatments can lead to dramatic regressions, but responses are often short-lived because resistant cancer cells arise. The major strategy proposed for overcoming resistance is combination therapy. We present a mathematical model describing the evolutionary dynamics of lesions in response to treatment. We first studied 20 melanoma patients receiving vemurafenib. We then applied our model to an independent set of pancreatic, colorectal, and melanoma cancer patients with metastatic disease. We find that dual therapy results in long-term disease control for most patients, if there are no single mutations that cause cross-resistance to both drugs; in patients with large disease burden, triple therapy is needed. We also find that simultaneous therapy with two drugs is much more effective than sequential therapy. Our results provide realistic expectations for the efficacy of new drug combinations and inform the design of trials for new cancer therapeutics. DOI: http://dx.doi.org/10.7554/eLife.00747.00

Post-COVID-19 chest imaging evaluation: which patients should be prioritized for follow-up pulmonary assessment?

Objectives: The current study evaluated the long‑term lung abnormalities based on initial and follow‑up chest computed tomography (CT) images of COVID‑19 patients and investigates the possible factors associated with them. Methods: One hundred and twenty‑four hospitalized COVID‑19 patients who received a follow‑up chest CT scan in three hospitals in Tehran between February 20, 2021 and September, 2021, were included. Based on the presence of persistent lesions in the follow‑up images, patients were divided into residual and nonresidual groups, and logistic regression analysis was performed to investigate the association between different disease characteristics and long‑term lung abnormalities. Results: The most frequent abnormality in the initial imaging was ground‑glass opacities which was observed in 95.3% of patients, and residual lesions were observed in 39.8% of patients at the follow‑up date. Patients in the residual group were generally older, more frequently suffered from hypertension and dyspnea, and had lower oxygen saturation and lymphocyte count, and lymphopenia was more prevalent among them. Moreover, patients in the residual group had higher initial lung involvement score, and the presence of lymphadenopathy and consolidation was more frequent among them. After adjustment for age, gender, and intervals between the two imagings, logistic regression results showed that hospitalization period, dyspnea, decreased oxygen saturation, decreased lymphocyte count, lymphopenia, consolidation, lymphadenopathy, and high initial lung involvement were strongly associated with the presence of long‑term abnormalities. Conclusion: The current study revealed multiple discrepancies between residual and nonresidual groups, which can be used to better identify the patients at risk of long‑term COVID‑19 lung complications

Determination of characteristics of erythromycin resistant Streptococcus pneumoniae with preferred PCV usage in Iran

Amongst 100 Streptococcus pneumoniae isolated from clinical cases and nasopharynx of healthy individuals, 60 erythromycin resistant strains were isolated and characterized using MLST, PFGE, transposon analysis and Quellung reaction. Most of the S. pneumoniae erythromycin resistant (80) were found to be attributable to the ermB-edncoded ribosome methylase activity which differs from the dominant mechanism of macrolide resistance seen in North America. The most predominant transposons were; Tn 1545/6003(27), Tn6002 (22), Tn2009 (20), Tn2010 (17). Number of the clinical isolates carrying Tn2010 was more significant than the normal flora. The serotypes found were; 14 (33), 3 (22), 23F (15), 19F (15), 19A (7), 6A (3), 9V (3) and 6B (2). The most prevalent serotypes among the clinical (n = 28) and normal flora (n = 32) isolates were serotypes 14 (46) and 3 (31), respectively. The most prevalent vaccine serotypes amongst the clinical isolates and the healthy individuals were pneumococcal conjugate vaccines (PCV) 13 and PCV10, respectively. PFGE revealed 34 pulsotypes with 9 common and 25 single types. Significant number of the normal isolates belonged to CT5 and CT6. On the other hand, significant number of clinical isolates belonged to CT8 as compared to the normal flora isolates. MLST showed 2 dominant sequence types. ST3130 (23) and ST180 (22) were the most predominant sequence types in the clinical and normal isolates, respectively. There was no significant difference in other sequence types between clinical and normal flora isolates. Three polyclonal complexes including Sweden15A -25, Spain23F-1 and Spain9V-3 constituted 58 of the isolates. Our results suggest that the genetic diversity and transposon distribution were high among S. pneumoniae, particularly in the isolates containing erm(B) and double antibiotic resistant genes (erm/mef). The results presented here could influence the change in the current vaccination practices in Iran which currently calls for vaccination with PCV7 or PCV10. � 2016 Talebi et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited