Beta Oscillations in the Sensory Thalamus During Severe Facial Neuropathic Pain Using Novel Sensing Deep Brain Stimulation.

OBJECTIVE: Advancements in deep brain stimulation (DBS) devices provide a unique opportunity to record local field potentials longitudinally to improve the efficacy of treatment for intractable facial pain. We aimed to identify potential electrophysiological biomarkers of pain in the ventral posteromedial nucleus (VPM) of the thalamus and periaqueductal gray (PAG) using a long-term sensing DBS system. MATERIALS AND METHODS: We analyzed power spectra of ambulatory pain-related events from one patient implanted with a long-term sensing generator, representing different pain intensities (pain >7, pain >9) and pain qualities (no pain, burning, stabbing, and shocking pain). Power spectra were parametrized to separate oscillatory and aperiodic features and compared across the different pain states. RESULTS: Overall, 96 events were marked during a 16-month follow-up. Parameterization of spectra revealed a total of 62 oscillatory peaks with most in the VPM (77.4%). The pain-free condition did not show any oscillations. In contrast, ß peaks were observed in the VPM during all episodes (100%) associated with pain >9, 56% of episodes with pain >7, and 50% of burning pain events (center frequencies: 28.4 Hz, 17.8 Hz, and 20.7 Hz, respectively). Episodes of pain >9 indicated the highest relative ß band power in the VPM and decreased aperiodic exponents (denoting the slope of the power spectra) in both the VPM and PAG. CONCLUSIONS: For this patient, an increase in ß band activity in the sensory thalamus was associated with severe facial pain, opening the possibility for closed-loop DBS in facial pain.

Obesity and meningioma: a US population-based study paired with analysis of a multi-institutional cohort.

OBJECTIVE: Whether obesity is associated with meningioma and the impact of obesity by gender has been debated. The primary objective of this study was to investigate differences in BMI between male and female patients undergoing craniotomy for meningioma and compare those with patients undergoing craniotomy for other intracranial tumors. The secondary objective was to compare meningioma location and progression-free survival (PFS) between obese and nonobese patients in a multi-institutional cohort. METHODS: National data were obtained from the National Surgical Quality Improvement Program (NSQIP) database. Male and female patients were analyzed separately. Patients undergoing craniotomies for meningioma were compared with patients of the same sex undergoing craniotomies for other intracranial tumors. Institutional data from two academic centers were collected for all male and an equivalent number of female meningioma patients undergoing meningioma resection. Multivariate regression controlling for age was used to determine differences in meningioma location. Kaplan-Meier curves and log-rank tests were computed to investigate differences in PFS. RESULTS: From NSQIP, 4163 male meningioma patients were compared with 24,266 controls, and 9372 female meningioma patients were compared with 21,538 controls. Male and female patients undergoing meningioma resection were more likely to be overweight or obese compared with patients undergoing craniotomy for other tumors, with the odds ratio increasing with increasing weight class (all p < 0.0001). In the multi-institutional cohort, meningiomas were more common along the skull base in male patients (p = 0.0123), but not in female patients (p = 0.1246). There was no difference in PFS between obese and nonobese male (p = 0.4104) or female (p = 0.5504) patients. Obesity was associated with increased risk of pulmonary embolism in both male and female patients undergoing meningioma resection (p = 0.0043). CONCLUSIONS: Male and female patients undergoing meningioma resection are more likely to be obese than patients undergoing craniotomy for other intracranial tumors. Obese males are more likely to have meningiomas in the skull base compared with other locations, but this association was not found in females. There was no significant difference in PFS among obese patients. The mechanism by which obesity increases meningioma incidence remains to be determined.

Stereotactic electroencephalography in epilepsy patients for mapping of neural circuits related to emotional and psychiatric behaviors: a systematic review.

OBJECTIVE: Stereotactic electroencephalography (sEEG) is an increasingly utilized method for identifying electrophysiological processes underlying sensorimotor, cognitive, and emotional behaviors. In this review, the authors outline current research using sEEG to investigate the neural activity underlying emotional and psychiatric behaviors. Understanding the current structure of intracranial research using sEEG will inform future studies of psychiatric disease and therapeutics for effective neuromodulation. METHODS: The authors conducted a comprehensive systematic review of studies according to PRISMA guidelines to investigate behaviors related to psychiatric conditions in patients with epilepsy undergoing monitoring with sEEG. Articles indexed on PubMed between 2010 and 2022 were included if they studied emotions or affective behaviors or met the National Institute of Mental Health Research Domain Criteria positive and negative valence domains. Data extracted from articles included study sample size, paradigms and behavioral tasks employed, cortical and subcortical targets, EEG analysis methods, and identified electrophysiological activity underlying the studied behavior. The Newcastle-Ottawa Scale was used to assess bias risk. RESULTS: Thirty-two primary articles met inclusion criteria. Study populations ranged from 3 to 39 patients. The most common structures investigated were the amygdala, insula, orbitofrontal cortex (OFC), hippocampus, and anterior cingulate cortex (ACC). Paradigms, stimuli, and behavioral tasks widely varied. Time-frequency analyses were the most common, followed by connectivity analyses. Multiple oscillations encoded a variety of behaviors related to emotional and psychiatric conditions. High gamma activity was observed in the amygdala and anterior insula in response to aversive audiovisual stimuli and in the OFC in response to reward processing. ACC beta band power increases and hippocampal-amygdala beta coherence variations were predictive of worsening mood states. Insular and amygdalar theta oscillations encoded social pain and fear learning, respectively. Most studies performed passing recordings, allowing for the decoding of affective states and depression symptoms, while other studies utilized direct stimulation, such as in the OFC to improve mood symptoms. CONCLUSIONS: Stereotactic EEG in epilepsy has identified multiple corticolimbic structures with specific oscillatory and synchronization activity underlying a diverse range of behaviors related to emotions and affective conditions. Given the heterogeneity of psychiatric conditions, sEEG provides an opportunity to study these neural correlates to develop personalized effective neuromodulatory treatments. Future studies should focus on optimizing paradigms and tasks to investigate a broad range of behavioral phenotypes that overlap across psychiatric conditions.

Response to Preoperative Dexamethasone Predicts Postoperative Neurological Improvement of Focal Neurological Deficits in Patients With Brain Metastases.

BACKGROUND: Steroids are used ubiquitously in the preoperative management of patients with brain tumor. The rate of improvement in focal deficits with steroids and the prognostic value of such a response are not known. OBJECTIVE: To determine the rate at which focal neurological deficits respond to preoperative corticosteroids in patients with brain metastases and whether such an improvement could predict long-term recovery of neurological function after surgery. METHODS: Patients with brain metastases and related deficits in language, visual field, or motor domains who received corticosteroids before surgery were identified. Characteristics between steroid responders and nonresponders were compared. RESULTS: Ninety six patients demonstrated a visual field (13 patients), language (19), or motor (64) deficit and received dexamethasone in the week before surgery (average cumulative dose 43 mg; average duration 2.7 days). 38.5% of patients' deficits improved with steroids before surgery, while 82.3% of patients improved by follow-up. Motor deficits were more likely to improve both preoperatively ( P = .014) and postoperatively ( P = .010). All 37 responders remained improved at follow-up whereas 42 of 59 (71%) of nonresponders ultimately improved ( P < .001). All other clinical characteristics, including dose and duration, were similar between groups. CONCLUSION: A response to steroids before surgery is highly predictive of long-term improvement postoperatively in brain metastasis patients with focal neurological deficits. Lack of a response portends a somewhat less favorable prognosis. Duration and intensity of therapy do not seem to affect the likelihood of response.

Venous Sinus Stenting: Safety and Health Care Resource Evaluation for Optimal Recovery in an Evolving Health Care Environment.

BACKGROUND: Increasing evidence supports the effectiveness of venous sinus stenting (VSS) with favorable outcomes, safety, and expenses compared with shunting for idiopathic intracranial hypertension. Yet, no evidence is available regarding optimal postoperative recovery, which has increasing importance with the burdens on health care imposed by the coronavirus disease 2019 pandemic. We examined adverse events and costs after VSS and propose an optimal recovery pathway to maximize patient safety and reduce stress on health care resources. METHODS: A retrospective review was undertaken of elective VSS operations performed from May 2008 to August 2021 at a single institution. Primary data included hospital length of stay, intensive care unit (ICU) length of stay, adverse events, need for ICU interventions, and hospital costs. RESULTS: Fifty-three patients (98.1% female) met the inclusion criteria. Of these patients, 51 (96.2%) were discharged on postoperative day (POD) 1 and 2 patients were discharged on POD 2. Both patients discharged on POD 2 remained because of groin hematomas from femoral artery access. There were no major complications or care that required an ICU. Eight patients (15.1%) were lateralized to other ICUs or remained in a postanesthesia care unit because the neurosciences ICU was above capacity. Total estimated cost for initial recovery day in a neurosciences ICU room was $2361 versus $882 for a neurosurgery/neurology ward room. In our cohort, ward convalescence would save an estimated $79,866 for bed placement alone and increase ICU bed availability. CONCLUSIONS: Our findings reaffirm the safety of VSS. These patients should recover on a neurosurgery/neurology ward, which would save health care costs and increase ICU bed availability.

Socioeconomic Status and Mock Interview Performance among Prospective Medical School Applicants.

We aim to evaluate the association between family income and mock multiple mini interview (MMI) performance for prospective medical school applicants. Each applicant participated in a three-station mock MMI and were scored on four items, each on a sevenpoint scale. Of the 48 prospective applicants participating, 29 (60% survey response rate) completed the survey. Hispanic applicants were significantly more likely to have a family income of less than or equal to $20,000 versus more than $20,000 (p<.05). The adjusted analysis suggested mock MMI total score was significantly lower for prospective medical school applicants with family incomes of less than or equal to $20,000 versus more than $20,000 (ß coefficient 5.37, 95% CI 0.05-10.69, p = .048). The mock MMI performance of prospective applicants with lower family incomes indicates the need for further interview skill preparation or new interview scoring protocols.

Variation of Burkholderia cenocepacia virulence potential during cystic fibrosis chronic lung infection.

During long-term lung infection in cystic fibrosis (CF) patients, Burkholderia cenocepacia faces multiple selective pressures in this highly stressful and fluctuating environment. As a consequence, the initial infecting strain undergoes genetic changes that result in the diversification of genotypes and phenotypes. Whether this clonal expansion influences the pathogenic potential is unclear. The virulence potential of 39 sequential B. cenocepacia (recA lineage IIIA) isolates, corresponding to 3 different clones retrieved from 3 chronically infected CF patients was compared in this study using the non-mammalian infection hosts Galleria mellonella and Caenorhabditis elegans. The isolates used in this retrospective study were picked randomly from selective agar plates as part of a CF Center routine, from the onset of infection until patients' death after 3.5 and 7.5 y or the more recent isolation date after 12.5 y of chronic infection. The infection models proved useful to assess virulence potential diversification, but for some isolates the relative values diverged in C. elegans and G. mellonella. Results also reinforce the concept of the occurrence of clonal diversification and co-existence of multiple phenotypes within the CF lungs, also with respect to pathogenicity. No clear trend of decrease (or increase) of the virulence potential throughout long-term infection was found but there is an apparent tendency for a clone/patient-dependent decrease of virulence when the G. mellonella model was used. The sole avirulent variant in both infection hosts was found to lack the small third replicon previously associated to virulence. Although possible, the in vivo loss of this nonessential megaplasmid was found to be a rare event (1 among a total of 64 isolates examined).

miRNA profiling of human naive CD4 T cells links miR-34c-5p to cell activation and HIV replication.

Cell activation is a vital step for T-cell memory/effector differentiation as well as for productive HIV infection. To identify novel regulators of this process, we used next-generation sequencing to profile changes in microRNA expression occurring in purified human naive CD4 T cells in response to TCR stimulation and/or HIV infection. Our results demonstrate, for the first time, the transcriptional up-regulation of miR-34c-5p in response to TCR stimulation in naive CD4 T cells. The induction of this miR was further consistently found to be reduced by both HIV-1 and HIV-2 infections. Overexpression of miR-34c-5p led to changes in the expression of several genes involved in TCR signaling and cell activation, confirming its role as a novel regulator of naive CD4 T-cell activation. We additionally show that miR-34c-5p promotes HIV-1 replication, suggesting that its down-regulation during HIV infection may be part of an anti-viral host response.

Exosomes from bulk and stem cells from human prostate cancer have a differential microRNA content that contributes cooperatively over local and pre-metastatic niche.

The different prostate cancer (PCa) cell populations (bulk and cancer stem cells, CSCs) release exosomes that contain miRNAs that could modify the local or premetastatic niche. The analysis of the differential expression of miRNAs in exosomes allows evaluating the differential biological effect of both populations on the niche, and the identification of potential biomarkers and therapeutic targets. Five PCa primary cell cultures were established to originate bulk and CSCs cultures. From them, exosomes were purified by precipitation for miRNAs extraction to perform a comparative profile of miRNAs by next generation sequencing in an Illumina platform. 1839 miRNAs were identified in the exosomes. Of these 990 were known miRNAs, from which only 19 were significantly differentially expressed: 6 were overexpressed in CSCs and 13 in bulk cells exosomes. miR-100-5p and miR-21-5p were the most abundant miRNAs. Bioinformatics analysis indicated that differentially expressed miRNAs are highly related with PCa carcinogenesis, fibroblast proliferation, differentiation and migration, and angiogenesis. Besides, miRNAs from bulk cells affects osteoblast differentiation. Later, their effect was evaluated in normal prostate fibroblasts (WPMY-1) where transfection with miR-100-5p, miR-21-5p and miR-139-5p increased the expression of metalloproteinases (MMPs) -2, -9 and -13 and RANKL and fibroblast migration. The higher effect was achieved with miR21 transfection. As conclusion, miRNAs have a differential pattern between PCa bulk and CSCs exosomes that act collaboratively in PCa progression and metastasis. The most abundant miRNAs in PCa exosomes are interesting potential biomarkers and therapeutic targets.

Retraction for Ramos et al., MtvR is a global small noncoding regulatory RNA in Burkholderia cenocepacia.

Volume 195, no. 16, p. 3514­3523, 2013. A number of problems related to images published in this paper have been brought to our attention. Figure 1D contains duplicated images in lanes S and LE, and Fig. 4D and 6B contain images previously published in articles in this journal and in Microbiology and Microbial Pathogenesis, i.e., the following: C. G. Ramos, S. A. Sousa, A. M. Grilo, J. R. Feliciano, and J. H. Leitão, J. Bacteriol. 193:1515­1526, 2011. doi:10.1128/JB.01374-11. S. A. Sousa, C. G. Ramos, L. M. Moreira, and J. H. Leitão, Microbiology 156:896­908, 2010. doi:10.1099/mic.0.035139-0. C. G. Ramos, S. A. Sousa, A. M. Grilo, L. Eberl, and J. H. Leitão, Microb. Pathog. 48:168­177, 2010. doi: 10.1016/j.micpath.2010.02.006. Therefore, we retract the paper. We deeply regret this situation and apologize for any inconvenience to the editors and readers of Journal of Bacteriology, Microbial Pathogenesis, and Microbiology.

Regulation of Hfq mRNA and protein levels in Escherichia coli and Pseudomonas aeruginosa by the Burkholderia cenocepacia MtvR sRNA.

Small non-coding RNAs (sRNAs) are important players of gene expression regulation in bacterial pathogens. MtvR is a 136-nucleotide long sRNA previously identified in the human pathogen Burkholderia cenocepacia J2315 and with homologues restricted to bacteria of the Burkholderia cepacia complex. In this work we have investigated the effects of expressing MtvR in Escherichia coli and Pseudomonas aeruginosa. Results are presented showing that MtvR negatively regulates the hfq mRNA levels in both bacterial species. In the case of E. coli, this negative regulation is shown to involve binding of MtvR to the 5'-UTR region of the hfqEc mRNA. Results presented also show that expression of MtvR in E. coli and P. aeruginosa originates multiple phenotypes, including reduced resistance to selected stresses, biofilm formation ability, and increased susceptibility to various antibiotics.

MtvR is a global small noncoding regulatory RNA in Burkholderia cenocepacia.

Burkholderia cenocepacia J2315 is a highly epidemic and transmissible clinical isolate of the Burkholderia cepacia complex (Bcc), a group of bacteria causing life-threatening respiratory infections among cystic fibrosis patients. This work describes the functional analysis of the 136-nucleotide (nt)-long MtvR small noncoding RNA (sRNA) from the Bcc member B. cenocepacia J2315, with homologues restricted to the genus Burkholderia. Bioinformatic target predictions revealed a total of 309 mRNAs to be putative MtvR targets. The mRNA levels corresponding to 17 of 19 selected genes were found to be affected when MtvR was either overexpressed or silenced. Analysis of the interaction between MtvR and the hfq mRNA, one of its targets, showed that the sRNA binds exclusively to the 5' untranslated region (UTR) of the hfq mRNA. This interaction resulted in decreased protein synthesis, suggesting a negative regulatory effect of MtvR on the RNA chaperone Hfq. Bacterial strains with MtvR silenced or overexpressed exhibited pleiotropic phenotypes related to growth and survival after several stresses, swimming and swarming motilities, biofilm formation, resistance to antibiotics, and ability to colonize and kill the nematode Caenorhabditis elegans. Together, the results indicate that the MtvR sRNA is a major posttranscriptional regulator in B. cenocepacia.

Experimental identification of small non-coding regulatory RNAs in the opportunistic human pathogen Burkholderia cenocepacia J2315.

Small non-coding regulatory RNAs (sRNAs) play important roles in regulating gene expression at the post-transcriptional level and often require the RNA chaperone Hfq. The human opportunistic pathogen Burkholderia cenocepacia J2315 encodes two distinct RNA chaperones, Hfq and Hfq2. The present work describes the experimental identification and validation of 24 sRNAs from B. cenocepacia J2315, based on the co-purification of sRNAs with the bacterium Hfq protein, followed by conversion into cDNA, cloning, computational analysis of sequences and validation by Northern blot analysis. The sRNAs here reported escaped identification by previous studies based on transcriptomics or bioinformatic analyses. Results presented indicate that 3 sRNAs are exclusive to bacteria of the Burkholderia cepacia complex and have no homologues in other bacteria, while the other 21 share homology, at different extents, to sRNAs of other bacterial species.

PCA3 sensitivity and specificity for prostate cancer detection in patients with abnormal PSA and/or suspicious digital rectal examination. First Latin American experience.

INTRODUCTION: Prostate Cancer Gene 3 (PCA3) is a recently described and highly specific urinary marker for prostate cancer (CaP). Its introduction in clinical practice to supplement low specificity of prostate specific antigen (PSA) can improve CaP diagnosis and follow-up. However, before its introduction, it is necessary to validate the method of PCA3 detection in distinct geographic populations. OBJECTIVES: Our aim was to describe for the first time in Latin America, the application of the PROGENSA PCA3 assay for PCA3 detection in urine in Chilean men and its utility for CaP diagnosis in men with an indication of prostate biopsy. MATERIALS AND METHODS: Sixty-four Chilean patients (mean age, 64 years) with indication of prostate biopsy because of elevated PSA and/or suspicious digital rectal examination (DRE) were prospectively recruited. PCA3 scores were assessed from urine samples obtained after DRE, before biopsy, and compared with PSA levels and biopsy outcome. RESULTS: The median PSA value and mean PCA3 score were 5.8 ng/ml and 31.7, respectively. Using a cutoff PCA3 score of 35, the sensitivity and specificity for detecting CaP were 52% and 87%, respectively. The receiver operating characteristic (ROC) curve analysis showed an area under the curve of 0.77 for PCA3 and 0.57 for PSA, for the same group of patients. In patients with previous negative biopsy, PCA3 specificity increased by 2.2%. CONCLUSIONS: This is the first report in Latin America on the use of PCA3 in diagnosing CaP. Our results are comparable to those reported in other populations in the literature, demonstrating the reproducibility of the test. PCA3 score was highly specific and we specially recommend its use in patients with persistent elevated PSA and prior negative biopsies.

Laparoscopic partial nephrectomy: A series of one hundred cases performed by the same surgeon.

INTRODUCTION: Laparoscopic partial nephrectomy (LPN) has become the first-line surgical technique for the management of renal tumors smaller than 4 cm. Its main advantages are an excellent oncologic control together with the preservation of nephron units. Moreover, it implies a shorter length of hospital stay, less postoperative pain, and shorter recovering times for patients. CONTEXT: We included 100 patients who consecutively underwent LPN between years 2000 and 2010 in our institution. AIMS: The aim was to present our experience and to compare it with the results reported in the literature by other centers. SETTINGS AND DESIGN: This was a prospective study. SUBJECTS AND METHODS: One hundred consecutive patients (67 men and 33 women) who underwent LPN within years 2000 and 2010 were included in the study. In all cases, surgery was performed by the same surgeon (JMC). Data were collected retrospectively, including clinical and histopathologic information, as well as surgical and functional results. STATISTICAL ANALYSIS USED: Statistical analysis was performed using the chi-square test and SPSS v17 software. A P-value < 0.05 was considered significant in all the analyses. RESULTS: The indication for LPN was a renal tumor or a complex renal cyst in the 96% of the cases. A retroperitoneal or transperitoneal approach was performed in the 62% and 38% of the cases, respectively. The average size of the tumor was 3.3 cm (range 1-8). The mean surgical time was 103.5 min (range 40-204). The mean estimated blood loss was 193.7 cc. The average hospital length of stay was 50.2 h. Six (6%) patients had complications related to the surgery. The majority (n = 2) was due to intraoperative bleeding. With an average follow-up time of 42.1 months, there is no tumor recurrence reported up to now. CONCLUSIONS: Our results are similar to those reported in the international literature. LPN is a challenging surgical technique that in hands of a trained and experienced surgeon has excellent and reproducible results for the management of small renal masses and cysts.

The novel cis-encoded small RNA h2cR is a negative regulator of hfq2 in Burkholderia cenocepacia.

Small non-coding regulatory RNAs (sRNAs) post-transcriptionally affect multiple phenotypes in prokaryotes and eukaryotes, yet most of the underlying regulatory mechanisms and the nature of the target mRNAs remain unclear. Here we report the identification and functional analysis of the novel cis-encoded sRNA h2cR, from the human opportunistic pathogen Burkholderia cenocepacia J2315. The sRNA was found to negatively regulate the hfq2 mRNA, through binding to part of the 5'-UTR region of the hfq2 mRNA, resulting in accelerated hfq2 mRNA decay and reduced protein levels in exponentially growing cells. Both the h2cR transcript and the hfq2 mRNA are stabilized by the other B. cenocepacia RNA chaperone, Hfq. Infection experiments using the nematode Caenorhabditis elegans revealed that down-regulation of Hfq2 by h2cR decreases the B. cenocepacia ability to colonize and persist within the nematode, suggesting a role for h2cR on bacterial persistence in the host.

Synergistic action of azoreductase and laccase leads to maximal decolourization and detoxification of model dye-containing wastewaters.

The azoreductase PpAzoR from Pseudomonas putida shows a broader specificity for decolourization of azo dyes than CotA-laccase from Bacillus subtilis. However, the final products of PpAzoR activity exhibited in most cases a 2 to 3-fold higher toxicity than intact dyes themselves. We show that addition of CotA-laccase to PpAzoR reaction mixtures lead to a significant drop in the final toxicity. A sequential enzymatic process was validated through the use of 18 representative azo dyes and three model wastewaters that mimic real dye-containing effluents. A heterologous Escherichia coli strain was successfully constructed co-expressing the genes coding for both PpAzoR and CotA. Whole-cell assays of recombinant strain for the treatment of model dye wastewater resulted in decolourization levels above 80% and detoxification levels up to 50%. The high attributes of this strain, make it a promising candidate for the biological treatment of industrial dye containing effluents.

The second RNA chaperone, Hfq2, is also required for survival under stress and full virulence of Burkholderia cenocepacia J2315.

Burkholderia cenocepacia J2315 is a highly virulent and epidemic clinical isolate of the B. cepacia complex (Bcc), a group of bacteria that have emerged as important pathogens to cystic fibrosis patients. This bacterium, together with all Bcc strains and a few other prokaryotes, is unusual for encoding in its genome two distinct and functional Hfq-like proteins. In this work, we show results indicating that the 188-amino-acid Hfq2 protein is required for the full virulence and stress resistance of B. cenocepacia J2315, despite the presence on its genome of the functional 79-amino-acid Hfq protein encoded by the hfq gene. Similar to other Hfq proteins, Hfq2 is able to bind RNA. However, Hfq2 is unique in its ability to apparently form trimers in vitro. Maximal transcription of hfq was observed in B. cenocepacia J2315 cells in the early exponential phase of growth. In contrast, hfq2 transcription reached maximal levels in cells in the stationary phase, depending on the CepR quorum-sensing regulator. These results suggest that tight regulation of the expression of these two RNA chaperones is required to maximize the fitness and virulence of this bacterium. In addition, the ability of Hfq2 to bind DNA, not observed for Hfq, suggests that Hfq2 might play additional roles besides acting as an RNA chaperone.

Burkholderia cepacia Complex: Emerging Multihost Pathogens Equipped with a Wide Range of Virulence Factors and Determinants.

The Burkholderia cepacia complex (Bcc) comprises at least 17 closely-related species of the beta-proteobacteria subdivision, widely distributed in natural and man-made inhabitats. Bcc bacteria are endowed with an extraordinary metabolic diversity and emerged in the 1980s as life-threatening and difficult-to-treat pathogens among patients suffering from cystic fibrosis. More recently, these bacteria became recognized as a threat to hospitalized patients suffering from other diseases, in particular oncological patients. In the present paper, we review these and other traits of Bcc bacteria, as well as some of the strategies used to identify and validate the virulence factors and determinants used by these bacteria. The identification and characterization of these virulence factors is expected to lead to the design of novel therapeutic strategies to fight the infections caused by these emergent multidrug resistant human pathogens.

Pathogenicity, virulence factors, and strategies to fight against Burkholderia cepacia complex pathogens and related species.

The Burkholderia cepacia complex (Bcc) is a group of 17 closely related species of the beta-proteobacteria subdivision that emerged in the 1980s as important human pathogens, especially to patients suffering from cystic fibrosis. Since then, a remarkable progress has been achieved on the taxonomy and molecular identification of these bacteria. Although some progress have been achieved on the knowledge of the pathogenesis traits and virulence factors used by these bacteria, further work envisaging the identification of potential targets for the scientifically based design of new therapeutic strategies is urgently needed, due to the very difficult eradication of these bacteria with available therapies. An overview of these aspects of Bcc pathogenesis and opportunities for the design of future therapies is presented and discussed in this work.