Phase separation and clustering of an ABC transporter in Mycobacterium tuberculosis.

Phase separation drives numerous cellular processes, ranging from the formation of membrane-less organelles to the cooperative assembly of signaling proteins. Features such as multivalency and intrinsic disorder that enable condensate formation are found not only in cytosolic and nuclear proteins, but also in membrane-associated proteins. The ABC transporter Rv1747, which is important for Mycobacterium tuberculosis (Mtb) growth in infected hosts, has a cytoplasmic regulatory module consisting of 2 phosphothreonine-binding Forkhead-associated domains joined by an intrinsically disordered linker with multiple phospho-acceptor threonines. Here we demonstrate that the regulatory modules of Rv1747 and its homolog in Mycobacterium smegmatis form liquid-like condensates as a function of concentration and phosphorylation. The serine/threonine kinases and sole phosphatase of Mtb tune phosphorylation-enhanced phase separation and differentially colocalize with the resulting condensates. The Rv1747 regulatory module also phase-separates on supported lipid bilayers and forms dynamic foci when expressed heterologously in live yeast and M. smegmatis cells. Consistent with these observations, single-molecule localization microscopy reveals that the endogenous Mtb transporter forms higher-order clusters within the Mycobacterium membrane. Collectively, these data suggest a key role for phase separation in the function of these mycobacterial ABC transporters and their regulation via intracellular signaling.

Impact of inhaled corticosteroids on the neurodevelopmental outcomes in chronically ventilated extremely low birth weight preterm infants.

BACKGROUND: Few studies have assessed the long-term impact of inhaled corticosteroids (ICS) in preterm infants. This study evaluated the neurodevelopmental outcomes of chronically ventilated extremely low birth weight (ELBW) preterm infants exposed to ICS. METHODS: The medical records of ELBW preterm infants admitted to two tertiary-level neonatal intensive care units from 2008 to 2014 were reviewed. Infants intubated for more than 28 days were included. The neurodevelopmental outcomes were compared at 24 months corrected age, between those with ICS exposure (inhaled group, IH) and those without it (non-inhaled group, NIH), by using the Bayley-Scale-of-Infant-and-Toddler Development-III (BSID-III). RESULTS: Out of the 115 infants included, 64 had an ICS exposure. The incidence of the morbidities at the time of discharge, was comparable between the two groups, except for the duration of oxygen and mechanical ventilation dependence (IH 124.8 ± 40.3 days vs. NIH: 101.0 ± 28.6 days, p < 0.001 and IH 60.0 ± 25.8 days vs. NIH: 42.3 ± 14.2 days, p < 0.001, respectively). Multiple logistic regression analysis at 24 months corrected age revealed no significant differences in the BSID-III scores and in the incidence of cerebral palsy and neurodevelopmental impairment. CONCLUSION: The late ICS exposure was not associated with neurodevelopmental impairment at 24 months corrected age in chronically ventilated ELBW infants; however, it did not reduce the duration of their dependence on oxygen and mechanical ventilation.

Prevalence of preschool children developmental disabilities in northeastern Taiwan - Screening with Taipei City Developmental Screening Checklist for Preschoolers, 2nd Version.

BACKGROUND/PURPOSE: The prevalence of developmental disabilities in Taiwan remains unclear, especially in young children under the age 3. We aimed to study the prevalence of developmental disabilities and verify a useful developmental screening tool in a community setting in Taiwan. METHODS: We conducted a prospective cross-sectional study in northeastern Taiwan from July 2008 to December 2009 in children aged 4 months to 6 years old from well-child visits. We devised a screening program using Taipei City Developmental Screening Checklist for Preschoolers, 2nd Version (Taipei-II), a validated parent-report milestone checklist tailored to the Taiwanese culture and language to assess the prevalence of developmental disabilities in Taiwan. Information about the children's medical conditions and their family were recorded. RESULTS: A total of 3214 children were recruited, of whom 365 had developmental disabilities, with an overall prevalence of 11.36%. Speech and language delay/disorders were the most common developmental problems followed by motor delays, with prevalence rates of 4.79% and 2.33%, respectively. Low economic status, prematurity and/or small for gestational age and a history of perinatal hypoxia or underlying medical disorders were the main risk factors correlated with developmental delays. However, foreign-born mother and aboriginal families were not important factors for poor developmental outcomes. CONCLUSION: The prevalence rate of developmental disabilities in northeastern Taiwan was 11.36%. Low economic status, prematurity and/or small for gestational age and a history of underlying medical disorders were the main risk factors correlated with developmental disabilities. Taipei II is an easy-to-use and effective developmental surveillance tool for Taiwanese children.

Screening of Preselected Libraries Targeting Mycobacterium abscessus for Drug Discovery.

Mycobacterium abscessus is intrinsically resistant to many antimycobacterial antibiotics, which presents serious problems in therapy. Here, we describe the development of a novel phenotype-based microscopic and computerized imaging drug screening approach. A pilot screen of 568 compounds from two libraries identified 17 hits. Eleven of these compounds are described for the first time as active against M. abscessus The impact of growth media on the activity of these compounds was tested, revealing that cation-adjusted Mueller-Hinton broth (MHII) supports better growth of actively replicating M. abscessus and improves the activity of associated compounds.

Probiotic supplementation modifies the gut microbiota profile of very low birth weight preterm infants during hospitalization.

BACKGROUND: Probiotic supplementation is increasingly being given to very low birth weight (VLBW) preterm infants. This preliminary observational study aimed to investigate the effects of multiple-strain probiotics on the gut microbiota of VLBW preterm infants. METHODS: We collected meconium and stool samples on days 14, 30, and 60 after birth from 49 VLBW infants with a gestational age of <32 weeks. The infants were divided into the probiotics (n = 24) and control (n = 25) groups. The microbial composition and diversity in the gut of the two groups were analyzed using 16 S rRNA gene sequencing. RESULTS: The relative abundance of Bifidobacterium and Lactobacillus was significantly higher in the probiotics group than in the control group on days 14, 30, and 60 (Bifidobacterium: p = 0.002, p < 0.0001, and p < 0.0001, respectively; Lactobacillus: p = 0.012, p < 0.0001, and p < 0.0001, respectively). The control group exhibited a significantly higher proportion of participants with a low abundance (<1%) of Bifidobacterium or Lactobacillus on days 14, 30, and 60 than those in the probiotic group. Moreover, the probiotics group exhibited a significantly lower abundance of Klebsiella on days 14 and 30 (2.4% vs. 11.6%, p = 0.037; and 7.9% vs. 16.6%, p = 0.032, respectively) and of Escherichia-Shigella on day 60 than the control group (6.1% vs. 12.3%, p = 0.013). Beta diversity analysis revealed that the microbiota profile was clearly divided into two groups on days 30 and 60 (p = 0.001). CONCLUSION: Probiotic supplementation significantly increased the relative abundance of Bifidobacterium and Lactobacillus and inhibited the growth of potential pathogens. Furthermore, probiotic supplementation led to a distinct gut microbiota profile. Further research is needed to identify probiotic strains that exert significant influence on the gut microbiome and their long-term health implications in preterm infants.

Genome-Wide Sequencing Modalities for Children with Unexplained Global Developmental Delay and Intellectual Disabilities-A Narrative Review.

Unexplained global developmental delay (GDD) and intellectual disabilities (ID) together affect nearly 2% of the pediatric population. Establishing an etiologic diagnosis is crucial for disease management, prognostic evaluation, and provision of physical and psychological support for both the patient and the family. Advancements in genome sequencing have allowed rapid accumulation of gene-disorder associations and have accelerated the search for an etiologic diagnosis for unexplained GDD/ID. We reviewed recent studies that utilized genome-wide analysis technologies, and we discussed their diagnostic yield, strengths, and limitations. Overall, exome sequencing (ES) and genome sequencing (GS) outperformed chromosomal microarrays and targeted panel sequencing. GS provides coverage for both ES and chromosomal microarray regions, providing the maximal diagnostic potential, and the cost of ES and reanalysis of ES-negative results is currently still lower than that of GS alone. Therefore, singleton or trio ES is the more cost-effective option for the initial investigation of individuals with GDD/ID in clinical practice compared to a staged approach or GS alone. Based on these updated evidence, we proposed an evaluation algorithm with ES as the first-tier evaluation for unexplained GDD/ID.

Effects of erythropoietin in neonates with hypoxic-ischemic encephalopathy receiving therapeutic hypothermia.

BACKGROUND: Minimizing multiple organ dysfunction-related mortality and morbidity is a critical issue for patients with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH). Although erythropoietin (EPO) has demonstrated protective effects on various hypoxic-ischemic organs in animal studies and clinical trials in adults, its effects on neonates with HIE require further investigation. METHODS: This study retrospectively analyzed the medical records of neonates with HIE who received TH with or without EPO (TH+EPO vs TH groups) administration in a tertiary referral hospital from January 2016 to January 2021. Data regarding patient characteristics, medical treatment, and clinical (neurological, cardiac, respiratory, gastrointestinal, hepatic, and renal) function assessments were collected. To control for confounding factors and selection bias between the two groups, a 1:1 propensity matching method was applied. RESULTS: A total of 45 neonates with HIE received TH during the study period, with 24 patients (53%) in the TH+EPO group. After matching, each group enrolled 13 cases. No significant difference in mortality or hospital stay between the two groups was noted. During the first 3 days, the patients in the TH+EPO group showed significantly higher blood pressure (BP) than those in the TH group ( p < 0.05 on day 1). The TH+EPO group showed trends of higher blood hemoglobin ( p > 0.05) and creatinine ( p > 0.05) levels and lower estimated glomerular filtration rate ( p > 0.05) and urine output ( p > 0.05) during the first 2 weeks than TH group. CONCLUSION: The use of EPO in addition to TH is safe for neonates with HIE. The neonates with moderate or severe HIE who received EPO may have a lesser risk of hypotension than those who received TH alone. Further clinical studies on renal and cardiac functions and long-term neurological effects of EPO are required.

Fatal Fulminant Cerebral Edema in Six Children With SARS-CoV-2 Omicron BA.2 Infection in Taiwan.

Acute fulminant cerebral edema in children following SARS-CoV-2 infection has been rarely reported. Such patients frequently demonstrate rapid progression and are usually fatal. In this retrospective study, we describe the detailed clinical, laboratory, and neuroimaging features of six fatal cases in Taiwan. All patients had shock initially, five showed rapid progression to multiorgan failure and disseminated intravascular coagulation, and three developed acute respiratory distress syndromes. The inflammatory biomarkers in the first 3 days, including interleukin 6, ferritin, lactate dehydrogenase, and D-dimer, showed significant elevation in all cases. The hyperinflammatory response may play a role in the pathophysiology.

Association of mode of delivery with short-term and neurodevelopmental outcomes in periviable singleton infants: A nationwide database study.

OBJECTIVE: To evaluate the association of mode of delivery (MOD) with short-term and neurodevelopmental outcomes at 2 years of corrected age (CA) in periviable singleton infants. METHODS: This retrospective cohort study of the Taiwan Premature Infant Follow-up Network database between 2010 and 2016 compared non-anomalous singleton deliveries (cesarean delivery [CD] vs vaginal delivery [VD]) between 22 0/7 and 25 6/7 gestational weeks. Major morbidities, mortality, and neurodevelopmental outcomes were evaluated at 2-year CA. RESULTS: The CD and VD groups included 354 and 472 infants, respectively. The intraventricular hemorrhage (IVH) rate was lower in the CD group (54% vs 66%, P = 0.001), but severe IVH differed non-significantly between groups (20% vs 26%, P = 0.057). In the small-for-gestational age subgroup, CD was associated with lower IVH (56% vs 84%, adjusted odds ratio [aOR] 0.17, 95% confidence interval [CI] 0.04-0.69) and better survival without neurodevelopmental impairment (29% vs 8%, aOR, 6.64, 95% CI 1.02-43.29) after controlling for potential confounders. CONCLUSION: The optimal MOD for periviable singleton birth and its impact are unclear. CD in periviable singleton births is associated with a decreased IVH risk, without improvement in severe IVH, mortality, or neurodevelopment at 2-year CA. The small-for-gestational age subgroup may benefit from CD for better survival without neurodevelopmental impairment.

Subclinical Changes in Left Heart Structure and Function at Preschool Age in Very Low Birth Weight Preterm Infants.

Background: Survivors of preterm birth are at risk of long-term cardiovascular consequences. The objective of this prospective observational study was to assess left heart function at preschool age in preterm children with very low birth weight (VLBW). Methods: We recruited children aged 5-6 years from preterm infants and full-term children. All subjects underwent conventional echocardiography and speckle-tracking echocardiography. The results were compared between the preterm and term groups. Results: Eighty-seven VLBW preterm children and 29 term controls were included in the study. After adjusting for body surface area, the preterm group compared to the full-term group had significantly smaller left ventricular (LV) end-diastolic and end-systolic internal dimensions (31.2 vs. 33.5 mm, p = 0.048; and 20.0 vs. 21.6 mm, respectively; p = 0.024), lower LV end-diastolic and end-systolic volumes (38.8 vs. 46.3 mL, p = 0.024; and 12.8 vs. 15.6 mL, respectively; p = 0.008). Left atrial (LA) maximal and minimal volume were also significantly smaller in the preterm group (15.4 vs. 18.9 mL, p = 0.017; and 6.2 vs 7.5 mL, respectively; p = 0.018). LV global longitudinal strain (-21.4 vs. -23.2%, p < 0.0001) and systolic strain rate (-1.30 vs. -1.37 /s, p = 0.001) were significantly lower in the preterm group than in the term control group. LA longitudinal strain was decreased (43.9 vs. 52.8%, p < 0.0001) and left atrial stiffness index (0.17 vs. 0.14, p < 0.0001) was increased in preterm infants. However, all the measurements in both groups were within normal range. Conclusions: Subclinical changes of left heart structure and function were found in VLBW infants at preschool age. Additional long-term follow-ups of the cardiovascular outcomes are needed in this vulnerable population.

Screening of diverse marine invertebrate extracts identified Lissoclinotoxin F, Discodermin B, and other anti-Mycobacterium tuberculosis active compounds.

Screening of a marine derived crude natural product extract library, followed by bioactivity guided fractionation, has led to isolation and structural elucidation of 10 natural products as hits active against Mycobacterium tuberculosis (Mtb). Among them, three (3, 4 and 5) were identified for the first time and the remaining 7 compounds (1, 2, 6, 7, 8, 9 and 10) were previously reported, but now assigned with anti-mycobacterial activity. Among identified hits, the oligo cyclic depsipeptide discodermin B (7) exhibited the highest potency with an MIC90 value of 0.5 µM. The polysufide alkaloid lissoclinotoxin F (1) displayed a good balance of anti Mtb potency (MIC90 = 2.6 µM) and selectivity (SI = 19 in HEK293 cells). Lissoclinotoxin F (1) was found to be active against intracellular Mtb as well as non-replicating forms of Mtb, with higher activity against Mtb compared to other gram-negative and gram-positive bacteria. Consequently, lissoclinotoxin F (1) could be used as a lead compound for development of new TB drugs. Details regarding screening techniques, structural elucidation and preliminary structural activity relationships (SAR) of the isolated hits are discussed.

Characteristics of Gut Microbiota in Small for Gestational Age Infants with Very Low Birth Weight.

Small for gestational age (SGA) birth is associated with high rates of mortality and morbidity in preterm infants. The aim of this preliminary observational study was to investigate the difference in gut microbiota between SGA and appropriate for gestational age (AGA) preterm infants with very low birth weight (VLBW). We included 20 VLBW preterm infants (SGA, n = 10; AGA, n = 10) in this study. Stool samples were collected on days 7, 14, and 30 after birth. We performed 16S ribosomal DNA sequencing to compare microbiota composition between both groups. The SGA group exhibited a lower abundance of Klebsiella on day 14 (SGA, 0.57%; AGA, 7.42%; p = 0.037). On day 30, the SGA group exhibited a lower abundance of Klebsiella (SGA 3.76% vs. AGA 16.05%; p = 0.07) and Enterobacter (SGA 5.09% vs. AGA 27.25%; p = 0.011) than the AGA group. Beta diversity demonstrated a separation of the bacterial community structure between both groups on day 30 (p = 0.019). The present study revealed that a distinct gut microbiota profile gradually develops in SGA preterm infants with VLBW during the early days of life. The role of changes in gut microbiota structure warrants further investigation.

An 18-year retrospective study on the epidemiology of early-onset neonatal sepsis - emergence of uncommon pathogens.

BACKGROUND: Nationwide group B Streptococcus agalactiae (GBS) antepartum screening was instituted in Taiwan in 2012. The impact of the policy on early-onset sepsis (EOS) has not been evaluated. This study aimed to examine the impact of the policy on the incidence of neonatal EOS. METHODS: This was a retrospective study conducted at MacKay Children's Hospital. Patients with culture-proven neonatal EOS were enrolled and divided by birth year in relation to the implementation of GBS prevention policy: Epoch 1, 2001-2004 pre-GBS screening; Epoch 2, 2005-2011 elective GBS screening; and Epoch 3, 2012-2018 universal GBS screening. The pathogens and antimicrobial resistance patterns were reviewed and analyzed. The incidence was modeled using Poisson regression. RESULTS: A total of 128 neonates met the enrollment criteria. The observed incidence of EOS was 1.52‰. The incidence rates of EOS, GBS, and Escherichia coli (E. coli) sepsis were similar in Epoch 1 and Epoch 3. E. coli and non-Enterococcal group D Streptococcus (GDS) infection increased significantly in term infants, whereas the EOS-related mortality rate declined in preterm infants. Approximately 72% of the isolated E. coli were ampicillin-resistant, and the antimicrobial sensitivity remained unaltered during the studied period. CONCLUSIONS: The overall EOS incidence has not changed from 2001 to 2018. However, changes in the causative pathogens were observed in both term and preterm infants. Clinicians should be aware of this evolving epidemiology to provide prompt appropriate perinatal management.

Impact of Early Empiric Antibiotic Regimens on the Gut Microbiota in Very Low Birth Weight Preterm Infants: An Observational Study.

Frequent use of antibiotics in preterm infants disturbs their gut microbial balance. In this preliminary observational study, we investigated the effect of different antibiotic regimens, administered during the first week of life, on microbial composition and diversity in very low birth weight (VLBW) preterm infants. We performed fecal sampling of breastfed VLBW infants on days 7, 14, and 30. After excluding stool samples from infants who received probiotics or who were administered antibiotics beyond the age of 7 days, we compared gut microbiota profiles between infants receiving a combination of ampicillin and gentamicin for 3 days (AG group, n = 10) and those receiving a combination of ampicillin and cefotaxime for 7 days (AC group, n = 14) using 16S ribosomal DNA community profiling. We also assessed the changes over time in each group. Compared to the AG group, Enterococcus species were significantly more abundant in the AC group (P = 0.002), especially in 7-day samples (12.3 vs. 0.6%, respectively, P = 0.032). No difference was observed at phylum and genus level over time within each group. Species richness in the AC group decreased significantly in the 14-day (P = 0.038) and 30-day (P = 0.03) samples compared to that in the 7-day sample. The same was observed for microbial evenness; in contrast, no significant difference in Shannon index and beta-diversity was detected between the two groups. Controlling for relevant confounding variables did not change the results. In conclusion, different antibiotic regimens affect the early development of gut microbiota in VLBW preterm infants. Prolonged use of ampicillin and cefotaxime might result in overabundance of Enterococcus. However, given that no significant differences were observed in 1-month samples, bacterial genera appear to continue colonizing the gastrointestinal tract despite previous exposure to antibiotics. The clinical relevance of these findings should be elucidated by further studies.

Slow release of nitric oxide from charged catheters and its effect on biofilm formation by Escherichia coli.

Catheter-associated urinary tract infection is the most prevalent cause of nosocomial infections. Bacteria associated with biofilm formation play a key role in the morbidity and pathogenesis of these infections. Nitric oxide (NO) is a naturally produced free radical with proven bactericidal effect. In this study, Foley urinary catheters were impregnated with gaseous NO. The catheters demonstrated slow release of nitric oxide over a 14-day period. The charged catheters were rendered antiseptic, and as such, were able to prevent bacterial colonization and biofilm formation on their luminal and exterior surfaces. In addition, we observed that NO-impregnated catheters were able to inhibit the growth of Escherichia coli within the surrounding media, demonstrating the ability to eradicate a bacterial concentration of up to 10(4) CFU/ml.

Comparisons and Refinements of Neonatal Oro-Tracheal Intubation Length Estimation Methods in Taiwanese Neonates.

Objective: This study aimed to evaluate the efficacy of Tochen's formula [TF, body weight (kg) plus 6 cm], nasal septum to ear tragus length (NTL) + 1 cm, and Neonatal Resuscitation Program gestational age (NRP-GA) and body weight (NRP-BW)-based intubation table in estimating the oro-tracheal intubation length, and to improve the estimation efficacy using anthropometric measurements in Taiwanese neonates. Study design: This was a prospective observational study conducted at a neonatal intensive care unit in Taipei, Taiwan. One hundred intubated neonates were enrolled. The estimated intubation depth was defined as being mid-tracheal concordant if it placed the endotracheal tip between the upper border of the first and the lower border of the second thoracic vertebra. A linear regression model was used to analyze the relationships between mid-tracheal depth and body weight (BW), NTL and gestational age (GA), and to revise the NRP intubation tables using our results. Results: Overall, 56% of the neonates were born at a GA ≤ 28 weeks and 48% had a BW ≤ 1,000 g. The overall mid-tracheal concordance rates for TF, NTL + 1 cm, NRP-GA, and NRP-BW estimations were 51.0, 57.0, 15.0, and 14.0%, and in the infants with a BW ≤ 1,000 g 56.3, 56.3, 8.3, and 8.3%, respectively. Our revisions of the NRP intubation tables based on the anthropometric measurements of our participants improved the efficacy of BW, GA, and NTL estimations to 63, 44, and 61%, respectively. Conclusion: TF and NTL + 1 cm were more reliable than NRP intubation tables in predicting the neonatal mid-tracheal length in neonates of all BW and GA. Considering morphological differences secondary to ethnicity, we recommend using these tailored recommendations during neonatal resuscitation in Asian neonates.

Protein tyrosine kinase, PtkA, is required for Mycobacterium tuberculosis growth in macrophages.

Protein phosphorylation plays a key role in Mycobacterium tuberculosis (Mtb) physiology and pathogenesis. We have previously shown that a secreted protein tyrosine phosphatase, PtpA, is essential for Mtb inhibition of host macrophage acidification and maturation, and is a substrate of the protein tyrosine kinase, PtkA, encoded in the same operon. In this study, we constructed a ∆ptkA deletion mutant in Mtb and found that the mutant exhibited impaired intracellular survival in the THP-1 macrophage infection model, correlated with the strain's inability to inhibit macrophage phagosome acidification. By contrast, the mutant displayed increased resistance to oxidative stress in vitro. Proteomic and transcriptional analyses revealed upregulation of ptpA, and increased secretion of TrxB2, in the ΔptkA mutant. Kinase and protein-protein interaction studies demonstrated that TrxB2 is a substrate of PtkA phosphorylation. Taken together these studies establish a central role for the ptkA-ptpA operon in Mtb pathogenesis.

Aminorifamycins and Sporalactams Produced in Culture by a Micromonospora sp. Isolated from a Northeastern-Pacific Marine Sediment Are Potent Antibiotics.

The new ansa macrolide antibiotics 1 to 4 have been isolated from cultures of a Micromonospora sp. obtained from a marine sediment. Rifamycins 1 and 2 are the first natural ansa macrolides to have a 3-amino substituent. Sporalactams A (3) and B (4) are comprised of a heterocylic core 5 and a 14-membered ansa bridge that are both unprecedented. Sporalactam B (4) shows selective and potent inhibition of Mycobacterium tuberculosis.

Nitric oxide charged catheters as a potential strategy for prevention of hospital acquired infections.

BACKGROUND: Catheter-Associated Hospital-Acquired Infections (HAI's) are caused by biofilm-forming bacteria. Using a novel approach, we generated anti-infective barrier on catheters by charging them with Nitric Oxide (NO), a naturally-produced gas molecule. NO is slowly released from the catheter upon contact with physiological fluids, and prevents bacterial colonization and biofilm formation onto catheter surfaces. AIMS AND METHODS: The aim of the study was to assess the anti-infective properties of NO-charged catheters exposed to low concentration (up to 103 CFU/ml) of microbial cells in-vitro. We assessed NO-charged tracheal tubes using Pseudomonas aeruginosa, dialysis and biliary catheters using Escherichia coli, and urinary catheters using E. coli, Candida albicans or Enterococcus faecalis. Safety and tolerability of NO-charged urinary catheters were evaluated in a phase 1 clinical study in 12 patients. Six patients were catheterized with NO-charged catheters (NO-group), followed by 6 patients catheterized with regular control catheters (CT-group). Comparison of safety parameters between the study groups was performed. RESULTS: NO-charged tracheal, dialysis biliary and urinary catheters prevented P. aeruginosa, E. coli and C. albicans attachment and colonization onto their surfaces and eradicated corresponding planktonic microbial cells in the surrounding media after 24-48 hours, while E. faecalis colonization onto urinary catheters was reduced by 1 log compared to controls. All patients catheterized with an NO-charged urinary catheter successfully completed the study without experiencing NO-related AE's or serious AE's (SAE's). CONCLUSION: These data highlight the potential of NO-based technology as potential platform for preventing catheter-associated HAI's.

Dual-time-point 18F-FDG PET/CT in the diagnosis of solitary pulmonary lesions in a region with endemic granulomatous diseases.

OBJECTIVE: Granulomatous diseases (GDs) can be metabolically active and indistinguishable from lung cancer on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging. Evaluation of solitary pulmonary lesions remains a diagnostic challenge in regions with endemic GD. This study sought to determine the efficacy of dual-time-point (DTP) 18F-FDG PET/computed tomography (CT) imaging in diagnosing solitary pulmonary lesions from such regions. METHODS: A total of 50 patients with solitary pulmonary nodules or masses with confirmed histopathological diagnoses underwent DTP 18F-FDG PET/CT imaging at 1 and 3 h after tracer injection. The maximum standardized uptake value (SUVmax) on early and delayed scans (SUV1h and SUV3h, respectively) and retention index (RI) were calculated for each pulmonary lesion. Receiver operating characteristic analysis was performed to evaluate the discriminating validity of the parameters. RESULTS: There were 37 malignant and 13 benign solitary pulmonary lesions. Eight of the 13 (62 %) benign lesions were GDs. The sensitivity/specificity/accuracy of SUV1h, SUV3h and RI were 84/69/80 %, 84/85/84 %, and 81/54/74 %, respectively. SUV3h had the best diagnostic performance, especially regarding specificity. The values of SUV1h and SUV3h were significantly different between malignant lesions and GD, while the RI values of malignant lesions and GD were both high (18.6 ± 19.5 and 18.7 ± 15.3 %, respectively; P = not significant). CONCLUSION: SUV3h appeared to improve the diagnostic specificity of 18F-FDG PET/CT in evaluating solitary pulmonary lesions from regions with endemic GD.