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Nilmary Grafals-Ruiz,1,2 Christian I Rios-Vicil,2,3 Eunice L Lozada-Delgado,2,4 Blanca I Quiñones-Díaz,2,5 Ricardo A Noriega-Rivera,2,5 Gabriel Martínez-Zayas,2,6 Yasmarie Santana-Rivera,2 Ginette S Santiago-Sánchez,2,5 Fatma Valiyeva,2 Pablo E Vivas-Mejía2,5 1Department of Physiology, University of Puerto Rico, San Juan, Puerto Rico; 2Comprehensive Cancer Center, University of Puerto Rico, San Juan, Puerto Rico; 3Department of Neurosurgery, University of Puerto Rico, San Juan, Puerto Rico; 4Department of Biology, University of Puerto Rico, San Juan, Puerto Rico; 5Department of Biochemistry, University of Puerto Rico, San Juan, Puerto Rico; 6Department of Chemistry, University of Puerto Rico, San Juan, Puerto RicoCorrespondence: Pablo E Vivas-MejíaComprehensive Cancer Center, University of Puerto Rico, Medical Sciences Campus, San Juan 00935, Puerto RicoTel +1787 772 8300, ext 1114Fax +1787 758 2557Email pablo.vivas@upr.eduIntroduction: Glioblastoma (GBM) is the most common and lethal of the central nervous system (CNS) malignancies. The initiation, progression, and infiltration ability of GBMs are attributed in part to the dysregulation of microRNAs (miRNAs). Thus, targeting dysregulated miRNAs with RNA oligonucleotides (RNA interference, RNAi) has been proposed for GBM treatment. Despite promising results in the laboratory, RNA oligonucleotides have clinical limitations that include poor RNA stability and off-target effects. RNAi therapies against GBM confront an additional obstacle, as they need to cross the blood-brain barrier (BBB).Methods: Here, we developed gold-liposome nanoparticles conjugated with the brain targeting peptides apolipoprotein E (ApoE) and rabies virus glycoprotein (RVG). First, we functionalized gold nanoparticles with oligonucleotide miRNA inhibitors (OMIs), creating spherical nucleic acids (SNAs). Next, we encapsulated SNAs into ApoE, or RVG-conjugated liposomes, to obtain SNA-Liposome-ApoE and SNA-Liposome-RVG, respectively. We characterized each nanoparticle in terms of their size, charge, encapsulation efficiency, and delivery efficiency into U87 GBM cells in vitro. Then, they were administered intravenously (iv) in GBM syngeneic mice to evaluate their delivery efficiency to brain tumor tissue.Results: SNA-Liposomes of about 30– 50 nm in diameter internalized U87 GBM cells and inhibited the expression of miRNA-92b, an aberrantly overexpressed miRNA in GBM cell lines and GBM tumors. Conjugating SNA-Liposomes with ApoE or RVG peptides increased their systemic delivery to the brain tumors of GBM syngeneic mice. SNA-Liposome-ApoE demonstrated to accumulate at higher extension in brain tumor tissues, when compared with non-treated controls, SNA-Liposomes, or SNA-Liposome-RVG.Discussion: SNA-Liposome-ApoE has the potential to advance the translation of miRNA-based therapies for GBM as well as other CNS disorders.Keywords: glioblastoma, GBM, central nervous system, CNS, microRNAs, RNA interference, spherical nucleic acids, liposomes

The multielemental characterization of sea sediments from an important Cuban coast was performed using instrumental neutron activation analysis. The obtained results show an impoverishment of rare earth elements in the studied zone, in comparison with the data taken from other Cuban coaster zones. [ABSTRACT FROM AUTHOR]

This paper reports the concentrations of 30 elements (major, minor and trace elements) in four Cuban samples. The samples were irradiated in a thermal neutron flux of 1012-1013 n.cm².s-1. The gamma-ray spectra were measured by high purity germanium detectors and were analyzed using ACTAN program developed in Center of Applies Studies for Nuclear Development. [ABSTRACT FROM AUTHOR]

Here we report the case of a cow with two ovaries that each exhibited hyperplasia but that otherwise had normal gross morphology. Both ovaries had a large number of tertiary follicles on the ovarian surface. Oocytes from one ovary were studied in more detail. The transcriptome was largely similar to other oocytes. Oocytes could undergo cleavage at a rate consistent with other oocytes and result in blastocyst-stage embryo formation after in vitro maturation and fertilization. Review of the literature from cattle and other species did not reveal reports of a similar type of spontaneous ovarian abnormality. Whole genome sequencing revealed many single nucleotide polymorphisms with predicted large effects on protein structure that could potentially be causative for the phenotype. The variant considered most likely to cause the observed alteration in ovarian function was a mutation in the glycoprotein-modifying enzyme MAN1A2., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Thoracentesis and thoracoscopy are used to diagnose malignant pleural effusions (MPE). Data on how sensitivity varies with tumour type is limited., Methods: Systematic review using PubMed was performed through August 2020 to determine the sensitivity of thoracentesis and thoracoscopy for MPE secondary to malignancy, by cancer type, and complication rates. Tests to identify sources of heterogeneity were performed. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 and National Institutes of Health quality assessment tools. Publication bias was tested using funnel plots., Results: Meta-analyses for sensitivity of thoracentesis for MPE secondary to malignancy, mesothelioma and lung and breast cancer included 29, eight, 12 and nine studies, respectively. Pooled sensitivities were 0.643 (95% CI 0.592-0.692), 0.451 (95% CI 0.249-0.661), 0.738 (95% CI 0.659-0.836) and 0.820 (95% CI 0.700-0.917), respectively. For sensitivity of thoracoscopy for MPE secondary to malignancy and mesothelioma, 41 and 15 studies were included, respectively. Pooled sensitivities were 0.929 (95% CI 0.905-0.95) and 0.915 (95% CI 0.871-0.952), respectively. Pooled complication rates of thoracentesis and thoracoscopy were 0.041 (95% CI 0.025-0.051) and 0.040 (95% CI 0.029-0.052), respectively. Heterogeneity was significant for all meta-analyses. Funnel plots were asymmetric., Interpretation: Sensitivity of thoracentesis varied significantly per cancer type. Pooled complication rates were low. Awareness of how sensitivity of thoracentesis changes across cancers can improve decision-making when MPE is suspected., Competing Interests: Conflicts of interest: G. Martinez-Zayas, S. Molina and D.E. Ost have no conflicts of interest to disclose and take full responsibility for this paper., (Copyright ©The authors 2022.)

The thiopurine prodrugs 6-mercaptopurine and azathioprine are among the world's essential medications for acute lymphoblastic leukemia, immunosuppression and several autoimmune conditions. Thiopurine prodrugs are efficient UVA absorbers and singlet oxygen generators and the long-term treatment with these prodrugs correlates with a high incidence of sunlight-induced skin cancer in patients. In this contribution, we show that the electronic relaxation mechanisms and photochemical properties of azathioprine are remarkably different from those of 6-mercaptopurine upon absorption of UVA radiation. UVA excitation of 6-mercaptopurine results in nearly 100% triplet yield and up to 30% singlet oxygen generation, whereas excitation of azathioprine with UVA leads to triplet yields of 15-3% depending on pH of the aqueous solution and <1% singlet oxygen generation. While photoexcitation of 6-mercaptopurine and other thiopurine prodrugs can facilitate oxidatively generated cell damage, azathioprine's poor photosensitization ability reveals the use of interchromophoric charge-transfer interactions for the molecular design of photostable prodrugs exhibiting a remarkable reduction in photocytotoxic side effects before drug metabolization., (© 2021 American Society for Photobiology.)

Background: The optimal diagnostic and staging strategy for patients with suspected lung cancer is not known., Research Question: What diagnostic and staging strategies are most cost-effective for lung cancer?, Study Design and Methods: A decision model was developed by using a hypothetical patient with a high probability of lung cancer. Sixteen unique permutations of bronchoscopy with fluoroscopy, radial endobronchial ultrasound, electromagnetic navigation, convex endobronchial ultrasound with or without rapid-onsite evaluation (ROSE), CT-guided biopsy (CTBx), and surgery were evaluated. Outcomes included cost, complications, mortality, time to complete the evaluation, rate of undetected N2-3 disease at surgery, incremental cost-complication ratio, and willingness-to-pay thresholds. Sensitivity analyses were performed on primary outcomes., Results: For a peripheral lung lesion and radiographic N0 disease, the best bronchoscopy strategy costs $1,694 more than the best CTBx strategy but resulted in fewer complications (risk difference, 14%). The additional cost of bronchoscopy to avoid one complication from a CTBx strategy was $12,037. The cost and cumulative complications of bronchoscopy strategies increased compared with CTBx strategies for small lesions. The cost and cumulative complications of bronchoscopy strategies decreased compared with CTBx strategies when a bronchus sign was present, but bronchoscopy remained more costly overall. For a central lesion and/or radiographic N1-3 disease, convex endobronchial ultrasound with ROSE followed by lung biopsy with incremental cost-effectiveness ratio, if required, was more cost-effective than any CTBx strategy across all outcomes. Strategies with ROSE were always more cost-effective than those without, irrespective of scenario. Trade-offs also exist between different bronchoscopy strategies, and optimal choices depend on the value placed on individual outcomes and willingness-to-pay., Interpretation: The most cost-effective strategies depend on nodal stage, lesion location, type of peripheral bronchoscopic biopsy, and the use of ROSE. For most clinical scenarios, many strategies can be eliminated, and trade-offs between the remaining competitive strategies can be quantified., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

For complex clinical cases where a parasitic infection is suspected, it can be difficult for clinicians to recommend an appropriate laboratory test. These tests are usually pathogen-specific and require a certain degree of suspicion for the precise etiology. A recently described assay, the universal parasite diagnostic (UPDx) can potentially provide a diagnosis of any parasite present in a specimen. Using primers that amplify DNA from all eukaryotes, UPDx differentiates several parasitic infections in blood by amplicon-based next-generation sequencing (NGS) of the 18S rDNA locus. As the state's public health reference laboratory, the Parasitology Laboratory at the Wadsworth Center (Albany, NY) receives specimens from patients who have potentially encountered a wide variety of parasites. As such, the ability to differentiate several blood parasites using a single assay is of interest. We assessed UPDx for its ability to confirm parasitic infections for 20 specimens that were previously identified by real-time PCR (RT-PCR). This included specimens positive for Babesia microti, Trypanosoma cruzi, Leishmania tropica, various Plasmodium species, and specimens comprising mixed Plasmodium sp. infections. Results obtained using UPDx were largely concordant with the RT-PCR assays. A T. cruzi positive specimen was negative by UPDx and for two mixed Plasmodium sp. infections only one species was detected. The results obtained for other specimens were concordant. We conclude that UPDx shows promise for the detection of blood parasites in diagnostic laboratories. As NGS becomes cheaper, assays like UPDx will become increasingly amenable to use in clinical settings.

Background: Two models, the Help with the Assessment of Adenopathy in Lung cancer (HAL) and Help with Oncologic Mediastinal Evaluation for Radiation (HOMER), were recently developed to estimate the probability of nodal disease in patients with non-small cell lung cancer (NSCLC) as determined by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). The objective of this study was to prospectively externally validate both models at multiple centers., Research Question: Are the HAL and HOMER models valid across multiple centers?, Study Design and Methods: This multicenter prospective observational cohort study enrolled consecutive patients with PET-CT clinical-radiographic stages T1-3, N0-3, M0 NSCLC undergoing EBUS-TBNA staging. HOMER was used to predict the probability of N0 vs N1 vs N2 or N3 (N2|3) disease, and HAL was used to predict the probability of N2|3 (vs N0 or N1) disease. Model discrimination was assessed using the area under the receiver operating characteristics curve (ROC-AUC), and calibration was assessed using the Brier score, calibration plots, and the Hosmer-Lemeshow test., Results: Thirteen centers enrolled 1,799 patients. HAL and HOMER demonstrated good discrimination: HAL ROC-AUC = 0.873 (95%CI, 0.856-0.891) and HOMER ROC-AUC = 0.837 (95%CI, 0.814-0.859) for predicting N1 disease or higher (N1|2|3) and 0.876 (95%CI, 0.855-0.897) for predicting N2|3 disease. Brier scores were 0.117 and 0.349, respectively. Calibration plots demonstrated good calibration for both models. For HAL, the difference between forecast and observed probability of N2|3 disease was +0.012; for HOMER, the difference for N1|2|3 was -0.018 and for N2|3 was +0.002. The Hosmer-Lemeshow test was significant for both models (P = .034 and .002), indicating a small but statistically significant calibration error., Interpretation: HAL and HOMER demonstrated good discrimination and calibration in multiple centers. Although calibration error was present, the magnitude of the error is small, such that the models are informative., (Copyright © 2021. Published by Elsevier Inc.)

Background: Evidence-based guidelines recommend management strategies for malignant pleural effusions (MPEs) based on life expectancy. Existent risk-prediction rules do not provide precise individualized survival estimates., Research Question: Can a newly developed continuous risk-prediction survival model for patients with MPE and known metastatic disease provide precise survival estimates?, Study Design and Methods: Single-center retrospective cohort study of patients with proven malignancy, pleural effusion, and known metastatic disease undergoing thoracentesis from 2014 through 2017. The outcome was time from thoracentesis to death. Risk factors were identified using Cox proportional hazards models. Effect-measure modification (EMM) was tested using the Mantel-Cox test and was addressed by using disease-specific models (DSMs) or interaction terms. Three DSMs and a combined model using interactions were generated. Discrimination was evaluated using Harrell's C-statistic. Calibration was assessed by observed-minus-predicted probability graphs at specific time points. Models were validated using patients treated from 2010 through 2013. Using LENT (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group performance score, neutrophil-to-lymphocyte ratio and tumor type) variables, we generated both discrete (LENT-D) and continuous (LENT-C) models, assessing discrete vs continuous predictors' performances., Results: The development and validation cohort included 562 and 727 patients, respectively. The Mantel-Cox test demonstrated interactions between cancer type and neutrophil to lymphocyte ratio (P < .0001), pleural fluid lactate dehydrogenase (P = .029), and bilateral effusion (P = .002). DSMs for lung, breast, and hematologic malignancies showed C-statistics of 0.72, 0.72, and 0.62, respectively; the combined model's C-statistics was 0.67. LENT-D (C-statistic, 0.60) and LENT-C (C-statistic, 0.65) models underperformed., Interpretation: EMM is present between cancer type and other predictors; thus, DSMs outperformed the models that failed to account for this. Discrete risk-prediction models lacked enough precision to be useful for individual-level predictions., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Systematic endobronchial ultrasound (EBUS)-guided lung cancer staging starts with hilar N3 nodes, proceeding sequentially to mediastinal N3, N2, and N1 nodes, with sampling of all enlarged nodes (size, ≥ 5 mm) by EBUS. However, procedure time is limited by patient comfort when moderate sedation is used. It is unclear if EBUS staging should start with hilar N3 nodes or whether starting with mediastinal N3 nodes suffices. Knowing the probability of hilar N3 nodes with PET-CT scan negative findings harboring occult metastasis can inform this decision., Research Question: What proportion of patients with hilar N3 nodes showing negative PET-CT scan findings have malignancy by EBUS?, Study Design and Methods: This retrospective observational, single-center cohort study included consecutive patients with clinical-radiographic T1-3, N0-3, M0 non-small cell lung cancer undergoing systematic EBUS staging with biopsy of hilar N3 nodes with negative PET-CT scan findings. The primary outcome was the proportion of patients with malignant hilar N3 nodes showing negative PET-CT scan findings. Based on expert opinion, a threshold probability of malignancy of less than 5% was considered sufficient to skip hilar N3 nodes. We used the binomial exact test to compare the observed proportion vs threshold probability of 5%., Results: Of 1,737 consecutive patients undergoing EBUS staging, 1,567 showed negative PET-CT scan findings of the hilar N3 nodes. These nodes were enlarged by EBUS and were sampled in 739 patients. Malignancy was found in the hilar N3 nodes of 5 of 739 patients (0.68%; 95% CI, 0.22%-1.57%). The proportion was significantly less than the threshold probability (P < .001). Patients with positive PET scan results of the mediastinal N3 nodes were at higher risk of having occult hilar N3 nodal metastasis (P = .003), found in 3 of 46 patients (6.5%; 95% CI, 1.4%-17.9%) with positive PET scan results of the mediastinal N3 nodes., Interpretation: When using moderate sedation, because time is limited, it is reasonable to start with the mediastinal N3 nodes if the hilar and mediastinal N3 nodes show negative PET scan results. Patients with positive PET scan findings of the mediastinal N3 nodes probably should undergo hilar N3 node sampling., (Copyright © 2020. Published by Elsevier Inc.)

Background: We conducted a Neisseria meningitidis (Nm) carriage study among men who have sex with men (MSM) to explore possible sexual transmission., Methods: We paired information on patient characteristics with oropharyngeal, rectal, and urethral Nm culture results to assess associations with Nm carriage among 706 MSM at New York City sexual health clinics. The Nm isolates were characterized by whole genome sequencing., Results: Twenty-three percent (163 of 706) of MSM were Nm carriers. Oropharyngeal carriage was 22.6% (159 of 703), rectal 0.9% (6 of 695), and urethral 0.4% (3 of 696). Oropharyngeal carriage was associated with the following recent (past 30 days) exposures: 3 or more men kissed (adjusted relative risk [aRR], 1.38; 95% confidence interval [CI], 1.03-1.86), performing oral sex (aRR, 1.81; 95% CI, 1.04-3.18), and antibiotic use (aRR, 0.33; 95% CI, 0.19-0.57). Sixteen clonal complexes were identified; 27% belonged to invasive lineages., Conclusions: Our findings suggest that oral sex and the number of recent kissing partners contribute to Nm carriage in MSM.

Rationale: When stereotactic ablative radiotherapy is an option for patients with non-small cell lung cancer (NSCLC), distinguishing between N0, N1, and N2 or N3 (N2|3) disease is important. Objectives: To develop a prediction model for estimating the probability of N0, N1, and N2|3 disease. Methods: Consecutive patients with clinical-radiographic stage T1 to T3, N0 to N3, and M0 NSCLC who underwent endobronchial ultrasound-guided staging from a single center were included. Multivariate ordinal logistic regression analysis was used to predict the presence of N0, N1, or N2|3 disease. Temporal validation used consecutive patients from 3 years later at the same center. External validation used three other hospitals. Measurements and Main Results: In the model development cohort ( n  = 633), younger age, central location, adenocarcinoma, and higher positron emission tomography-computed tomography nodal stage were associated with a higher probability of having advanced nodal disease. Areas under the receiver operating characteristic curve (AUCs) were 0.84 and 0.86 for predicting N1 or higher (vs. N0) disease and N2|3 (vs. N0 or N1) disease, respectively. Model fit was acceptable (Hosmer-Lemeshow, P  = 0.960; Brier score, 0.36). In the temporal validation cohort ( n  = 473), AUCs were 0.86 and 0.88. Model fit was acceptable (Hosmer-Lemeshow, P  = 0.172; Brier score, 0.30). In the external validation cohort ( n  = 722), AUCs were 0.86 and 0.88 but required calibration (Hosmer-Lemeshow, P  < 0.001; Brier score, 0.38). Calibration using the general calibration method resulted in acceptable model fit (Hosmer-Lemeshow, P  = 0.094; Brier score, 0.34). Conclusions: This prediction model can estimate the probability of N0, N1, and N2|3 disease in patients with NSCLC. The model has the potential to facilitate decision-making in patients with NSCLC when stereotactic ablative radiotherapy is an option.

We characterized a case of neonatal conjunctivitis in New York, USA, caused by Neisseria meningitidis by using whole-genome sequencing. The case was a rare occurrence, and the isolate obtained belonged to an emerging clade (N. meningitidis US nongroupable urethritis) associated with an increase in cases of urethritis since 2015.

Viral pneumonias cause profound worldwide morbidity, necessitating novel strategies to prevent and treat these potentially lethal infections. Stimulation of intrinsic lung defenses via inhalation of synergistically acting Toll-like receptor (TLR) agonists protects mice broadly against pneumonia, including otherwise-lethal viral infections, providing a potential opportunity to mitigate infectious threats. As intact lung epithelial TLR signaling is required for the inducible resistance and as these cells are the principal targets of many respiratory viruses, the capacity of lung epithelial cells to be therapeutically manipulated to function as autonomous antiviral effectors was investigated. Our work revealed that mouse and human lung epithelial cells could be stimulated to generate robust antiviral responses that both reduce viral burden and enhance survival of isolated cells and intact animals. The antiviral protection required concurrent induction of epithelial reactive oxygen species (ROS) from both mitochondrial and dual oxidase sources, although neither type I interferon enrichment nor type I interferon signaling was required for the inducible protection. Taken together, these findings establish the sufficiency of lung epithelial cells to generate therapeutically inducible antiviral responses, reveal novel antiviral roles for ROS, provide mechanistic insights into inducible resistance, and may provide an opportunity to protect patients from viral pneumonia during periods of peak vulnerability. IMPORTANCE Viruses are the most commonly identified causes of pneumonia and inflict unacceptable morbidity, despite currently available therapies. While lung epithelial cells are principal targets of respiratory viruses, they have also been recently shown to contribute importantly to therapeutically inducible antimicrobial responses. This work finds that lung cells can be stimulated to protect themselves against viral challenges, even in the absence of leukocytes, both reducing viral burden and improving survival. Further, it was found that the protection occurs via unexpected induction of reactive oxygen species (ROS) from spatially segregated sources without reliance on type I interferon signaling. Coordinated multisource ROS generation has not previously been described against viruses, nor has ROS generation been reported for epithelial cells against any pathogen. Thus, these findings extend the potential clinical applications for the strategy of inducible resistance to protect vulnerable people against viral infections and also provide new insights into the capacity of lung cells to protect against infections via novel ROS-dependent mechanisms., (Copyright © 2018 Kirkpatrick et al.)

Background: The effectiveness of recommended measures, such as "cover your mouth when coughing", in disrupting the chain of transmission of infectious respiratory diseases (IRD) has been questioned. The objective of the current study was to determine the effectiveness of simple primary respiratory hygiene/cough etiquette maneuvers in blocking droplets expelled as aerosol during coughing., Method: In this study, 31 healthy non-smokers performed cough etiquette maneuvers in an effort to cover their voluntarily elicited best effort coughs in an open bench format. A laser diffraction system was used to obtain accurate, non-invasive, quantitative, real time measurements of the size and number of droplets emitted during the assessed cough etiquette maneuvers., Results: Recommended cough etiquette maneuvers did not block the release and dispersion of a variety of different diameter droplets to the surrounding environment. Droplets smaller than one-micron size dominate the total number of droplets leaked when practicing assessed maneuvers., Conclusions: All the assessed cough etiquette maneuvers, performed as recommended, do not block droplets expelled as aerosol when coughing. This aerosol can penetrate profound levels of the respiratory system. Practicing these assessed primary respiratory hygiene/cough etiquette maneuvers would still permit direct, indirect, and/or airborne transmission and spread of IRD, such as influenza and Tuberculosis. All the assessed cough etiquette maneuvers, as recommended, do not fully interrupt the chain of transmission of IRD. This knowledge urges us all to critically review recommended CE and to search for new evidence-based procedures that effectively disrupt the transmission of respiratory pathogens. Interrupting the chain of transmission of IRD will optimize the protection of first responders, paramedics, nurses, and doctors working in triage sites, emergency rooms, intensive care units, and the general public against cough-droplet-spread diseases.

Objective: nab-Paclitaxel has been shown to disrupt pancreatic cancer stroma and was effective in combination with gemcitabine in a phase I/II trial. This study was designed to determine the efficacy of nab-paclitaxel monotherapy in previously treated pancreatic cancer patients., Methods: In this phase II trial, patients with advanced pancreatic cancer who progressed on gemcitabine-based therapy, received nab-paclitaxel 100 mg/m over 30 minutes on days 1, 8, and 15 of a 28-day cycle. The primary endpoint was 6-month overall survival (OS). Secondary endpoints were response rate (by Response Evaluation Criteria In Solid Tumors), progression-free survival, safety, and toxicity profile., Results: Among 19 patients treated, the median age was 61 years, 9 (47%) were male patients and 18 (95%) had stage-IV disease. The primary endpoint of the study was reached with a 6-month OS of 58% [95% confidence interval (95% CI), 33%-76%] and an estimated median OS of 7.3 months (95% CI, 2.8-15.8 mo). The median progression-free survival was 1.7 months (95% CI, 1.5-3.5 mo). One patient had a confirmed partial response and 6 (32%) had stable disease as their best response. Nonhematological toxicities were generally mild with grades 1-2 nausea, anorexia, hypocalcemia, and vomiting occurring in 63%, 47%, 37%, and 26% of patients, respectively. Grades 3-4 neutropenia, neutropenic fever, and anemia occurred in 32%, 11%, and 11% of patients, respectively. Only 2 of 15 available tumors stained positive for secreted protein acid rich in cysteine, and neither of these patients benefited from the therapy., Conclusions: nab-Paclitaxel was well tolerated, and it demonstrated preliminary evidence of activity in a subset of patients who progressed on gemcitabine-based therapy.

Background: The Influenza A H1N1 virus can be transmitted via direct, indirect, and airborne route to non-infected subjects when an infected patient coughs, which expels a number of different sized droplets to the surrounding environment as an aerosol. The objective of the current study was to characterize the human cough aerosol pattern with the aim of developing a standard human cough bioaerosol model for Influenza Pandemic control., Method: 45 healthy non-smokers participated in the open bench study by giving their best effort cough. A laser diffraction system was used to obtain accurate, time-dependent, quantitative measurements of the size and number of droplets expelled by the cough aerosol., Results: Voluntary coughs generated droplets ranging from 0.1 - 900 microns in size. Droplets of less than one-micron size represent 97% of the total number of measured droplets contained in the cough aerosol. Age, sex, weight, height and corporal mass have no statistically significant effect on the aerosol composition in terms of size and number of droplets., Conclusions: We have developed a standard human cough aerosol model. We have quantitatively characterized the pattern, size, and number of droplets present in the most important mode of person-to-person transmission of IRD: the cough bioaerosol. Small size droplets (< 1 μm) predominated the total number of droplets expelled when coughing. The cough aerosol is the single source of direct, indirect and/or airborne transmission of respiratory infections like the Influenza A H1N1 virus., Study Design: Open bench, Observational, Cough, Aerosol study., (© 2012 Zayas et al; licensee BioMed Central Ltd.)

Background: Several strategies and devices have been designed to protect health care providers from acquiring transmissible respiratory diseases while providing care. In modulating the physical characteristics of the respiratory secretions to minimize the aerosolization that facilitates transmission of airborne diseases, a fundamental premise is that the prototype drugs have no adverse effect on the first line of respiratory defense, clearance of mucus by ciliary action., Methods: To assess and demonstrate the primary mechanism of our mucomodulators (XLs), we have built our evidence moving from basic laboratory studies to an ex-vivo model and then to an in-vivo large animal model. We exposed anesthetized dogs without hypersecretion to different dose concentrations of aerosolized XL "B", XL "D" and XL "S". We assessed: cardio-respiratory pattern, tracheal mucus clearance, airway patency, and mucus viscoelastic changes., Results: Exposure of frog palate mucus to XLs did not affect the clearance of mucus by ciliary action. Dogs maintained normal cardio-respiratory pattern with XL administration. Tracheal mucociliary clearance in anesthetized dogs indicated a sustained 40% mean increase. Tracheal mucus showed increased filance, and there was no mucus retention in the airways., Conclusion: The ex-vivo frog palate and the in-vivo mammalian models used in this study, appear to be appropriate and complement each other to better assess the effects that our mucomodulators exert on the mucociliary clearance defence mechanism. The physiological function of the mucociliary apparatus was not negatively affected in any of the two epithelial models. Airway mucus crosslinked by mucomodulators is better cleared from an intact airway and normally functioning respiratory system, either due to enhanced interaction with cilia or airflow-dependent mechanisms. Data obtained in this study allow us to assure that we have complied with the fundamental requirement criteria established in the initial phase of developing the concept of mucomodulation: Can we modulate the physical characteristics of the respiratory secretions to reduce aerosolization without affecting normal mucociliary clearance function, or even better improving it?

Objectives. In El Salvador, before 1999, morbidity and mortality in severely burned children were high. In 1998, all children with burns of 40% or larger size died and sepsis was found. With heparin use in 1999, some similarly burned children survived, and sepsis, pain, procedures, and scars were noted to be less. This retrospective study presents the details. Methods. A study was conducted at the National Children's Hospital in El Salvador of all children with burns over 20% size treated in 1998, when no heparin was used, and in 1999, when heparin was added to burns treatment, using an ethics committee approved protocol in use in twelve other countries. Sodium aqueous heparin solution USP from an intestinal source was infused intravenously and applied topically onto burn surfaces and within blisters for the first 1-3 days post-burn. Then heparin, in diminishing doses, was continued only topically until healing. The treatments in 1998 and 1999 were otherwise the same, except that fewer procedures were needed in 1999. Results. There were no significant differences in gender, age, weight, burn aetiology, or burn size between the burned children in 1998 and those in 1999. Burn pain was relieved and pain medicine was not needed in children treated with heparin in 1999. In 1998, one child survived who had a 35% size burn, and the eight children died who had burns of 40% and over. The survival rate was one out of nine (11%). The average burn size was 51.7%. With heparin use in 1999, six of the ten children survived burns of 50.7% average size. The increase in survival with heparin from 11% to 60% and, therefore, the decrease in mortality from 89% to 40% were significant (p < 0.04). Clinical symptoms and positive blood cultures documented bacterial sepsis in the nine children in 1998. In 1999, the blood cultures for sepsis were positive in the four children who died and negative in the six who survived. The nine versus four differences in the incidence of sepsis between 1998 and 1999 was significant (p < 0.008). The survivors had notably smooth skin. Conclusions. The use of heparin in this study relieved burn pain, significantly reduced mortality and sepsis with fewer procedures, and discernibly improved cosmetic results.