The Contribution of Chest Radiography to the Clinical Management of Children Exposed to Tuberculosis.

Rationale: Although World Health Organization guidelines emphasize contact investigation for tuberculosis (TB)-exposed children, data that support chest radiography as a useful tool are lacking. Objectives: We evaluated the diagnostic and prognostic information of chest radiography in children exposed to TB and measured the efficacy of isoniazid preventive therapy (IPT) in those with relevant radiographic abnormalities. Methods: Between September 2009 and August 2012, we enrolled 4,468 TB-exposed children who were screened by tuberculin skin testing, symptom assessment, and chest radiography. Those negative for TB disease were followed for 1 year for the occurrence of new TB diagnoses. We assessed the protective efficacy of IPT in children with and without abnormal chest radiographs. Measurements and Main Results: Compared with asymptomatic children with normal chest films, asymptomatic children with abnormal radiographs were 25.1-fold more likely to have coprevalent TB (95% confidence interval [CI], 1.02-613.76) and 26.7-fold more likely to be diagnosed with incident TB disease during follow-up (95% CI, 10.44-68.30). Among the 29 symptom-negative and CXR-abnormal child contacts, 20% (3/15) of the isoniazid recipients developed incident TB, compared with 57% (8/14) of those who did not receive IPT (82% IPT efficacy). Conclusions: Our results strongly support the use of chest radiography as a routine screening tool for the evaluation of child TB contacts, which is readily available. Radiographic abnormalities not usually considered suggestive of TB may indicate incipient or subclinical disease, although TB preventive treatment is adequate in most cases.

Intestinal amyloidosis: a diagnostic challenge.

Amyloidosis is a disease caused by extracellular deposition of abnormally folded proteins. While gastrointestinal involvement is relatively frequent in its systemic form, isolated gastrointestinal disease is rare. We present the case of a 62-year-old man assessed for iron deficiency anemia and abdominal pain after starting antiplatelet therapy with acetylsalicylic acid and ticagrelor for ischemic heart disease. An esophagogastroduodenoscopy was performed as part of the study, showing thickened folds with pseudopolypoid morphology and nodular mucosa with a preserved crypt pattern in the duodenal bulb and second duodenal portion.

Intermittent endoscopic ultrasound guided fine-needle aspiration for the diagnosis of solid pancreatic lesions. A pilot study.

BACKGROUND AND PURPOSE: endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) is the method of choice for sampling pancreatic solid lesions. However, there is significant heterogeneity in terms of the technique used. Intermittent aspiration has not been evaluated in pancreatic solid lesions and could improve the diagnostic performance. METHODS: a single-blind, non-inferiority pilot study was performed. Patients with solid pancreatic lesions and an indication for EUS-FNA were prospectively included. Patients were randomly assigned to intermittent (IS) or continuous (CS) suction techniques. Diagnostic performance, cellularity, blood contamination and the number of passes required to reach a diagnosis were evaluated. MAIN RESULTS: thirty-three patients were assigned to CS (16 patients) or IS (17 patients). Diagnostic performance was 87.5 % for CS and 94.1 % for IS (OR 2.29, 95 % CI: 0.19-27.99, p = 0.51). In the IS group, samples had a higher cellularity (OR 1.83, 95 % CI: 0.48-6.91, p = 0.37) and lower blood contamination (OR 0.38, 95 % CI: 0.09-1.54, p = 0.18). The number of passes required to reach a diagnosis was 2.12 for CS and 1.94 for IS (p = 0.64). Liquid cytology was obtained in 73.3 % of IS and 61.5 % of CS (OR 1.72, 95 % CI: 0.35-8.50). CONCLUSIONS: the IS technique was not inferior to CS in terms of diagnostic accuracy in the evaluation of pancreatic solid lesions, with a tendency to obtain higher cellularity, lower blood contamination and the frequent presence of cell block.

Computational adaptive optics in phase-unstable optical coherence tomography.

We present a scheme for correction of x-y-separable aberrations in optical coherence tomography (OCT) designed to work with phase unstable systems with no hardware modifications. Our approach, termed SHARP, is based on computational adaptive optics and numerical phase correction and follows from the fact that local phase stability is sufficient for the deconvolution of optical aberrations. We demonstrate its applicability in a raster-scan polygon-laser OCT system with strong phase-jitter noise, achieving successful refocusing at depths up to 4 times the Rayleigh range. We also present in vivo endoscopic and ex vivo anterior segment OCT data, showing significant enhancement of image quality, particularly when combining SHARP results with a resolution-preserving despeckling technique like TNode.

PrEP Knowledge and Attitudes Among Adults Attending Public Health Clinics in Southern Arizona.

HIV pre-exposure prophylaxis (PrEP) is underutilized among Hispanics, women, and low-income individuals. To better understand PrEP barriers in this population, questionnaires were administered to 500 patients attending public health clinics in southern Arizona which provide family planning and sexually transmitted infections care. Sixty-three percent believed that they had no risk of HIV infection. When asked "Before today, did you know that there was a pill that can prevent HIV infection?" 80% of persons answered no. Among women, 88% answered no to this question. As expected, individuals with a higher perceived HIV risk (OR 1.76) or one HIV risk factor (OR 5.85) had a higher probability of knowledge. Among survey participants 87% would take a daily pill, 91% would visit a health-care provider every 3 months, and 92% would have laboratory testing every 3 months. Fifty-four percent would not be afraid or embarrassed if friends or family knew they were taking PrEP. Seventy-two percent would take PrEP despite temporary nausea. Sixty-two percent would pay ≥ $40 every 3 months for PrEP. Lack of knowledge, rather than patient attitudes, is the more important barrier to wider utilization of PrEP among individuals, especially women, attending public health clinics in Southern Arizona. Future efforts need to focus on education and access to PrEP in underserved populations including women and Hispanics.

Severe Enteropathy and Hypogammaglobulinemia Complicating Refractory Mycobacterium tuberculosis Complex Disseminated Disease in a Child with IL-12Rß1 Deficiency.

PURPOSE: Mendelian susceptibility to mycobacterial disease is a rare clinical condition characterized by a predisposition to infectious diseases caused by poorly virulent mycobacteria. Other infections such as salmonellosis and candidiasis are also reported. The purpose of this article is to describe a young boy affected with various infectious diseases caused by Mycobacterium tuberculosis complex, Salmonella sp, Klebsiella pneumonie, Citrobacter sp., and Candida sp, complicated with severe enteropathy and transient hypogammaglobulinemia. METHODS: We reviewed medical records and performed flow cytometry staining for lymphocyte populations, lymphocyte proliferation in response to PHA, and intracellular IFN-γ production in T cell PHA blasts in the patient and a healthy control. Sanger sequencing was used to confirm the genetic variants in the patient and relatives. RESULTS: Genetic analysis revealed a bi-allelic mutation in IL12RB1 (C291Y) resulting in complete IL-12Rß1 deficiency. Functional analysis demonstrated the lack of intracellular production of IFN-γ in CD3+ T lymphocytes from the patient in response to rhIL-12p70. CONCLUSIONS: To our knowledge, this is the third patient with MSMD due to IL-12Rß1 deficiency complicated with enteropathy and hypogammaglobulinemia and the first case of this disease to be described in Colombia.

Vortex-enhanced coherent-illumination phase diversity for phase retrieval in coherent imaging systems.

We propose a phase-retrieval method based on the numerical optimization of a new objective function using coherent phase-diversity images as inputs for the characterization of aberrations in coherent imaging systems. By employing a spatial light modulator to generate multiple-order spiral phase masks as diversities, we obtain an increase in the accuracy of the retrieved phase compared with similar state-of-the-art phase-retrieval techniques that use the same number of input images. We present simulations that show a consistent advantage of our technique, and experimental validation where our implementation is used to characterize a highly aberrated 4F optical system.

Rates of vascular access use in transcatheter aortic valve replacement: A look into the next generation.

OBJECTIVE/BACKGROUND: As smaller TAVR delivery systems emerge we sought to identify differences in vascular access use. METHODS: We analyzed all patients who had undergone TAVR in a single-center from March 2012 to May 2014. We identified all patients who had undergone nonfemoral TAVR and reviewed their femoral dimensions using CT imaging taking into vascular pathology and minimal lumen diameter (MLD). We then identified those patients in whom a smaller delivery system could have been used if such technology was available at that time. RESULTS: In total 208 consecutive TAVRs were performed, 129 cases using femoral arterial access and 75 cases using non-femoral access; 28 transapical, 27 transcaval, 12 transaortic, and 8 via an antegrade transseptal venous approach. Of the 75 nonfemoral access cases, 63 were completed using commercially available first-generation valves (Sapien Valve) and 12 using second-generation valves under research protocols (Sapien XT Valve). Of the 63 cases performed via a non-femoral route using a first generation valve, 31 cases could have been approached via a transfemoral (TF) route using second-generation delivery systems; and 48 cases could have been approached via a TF route using third generation delivery systems (S3 Valve). Of the 12 cases performed via a nonfemoral route using a second-generation valve, 4 cases could have been approached via a TF route using a third-generation delivery system. In total, only 11% of patients undergoing TAVR could not accommodate smaller second and third generation devices. CONCLUSIONS: As second and third generation devices become commercially available, we anticipate that 89% of cases will be preformed using a TF approach.

A Blueprint to Address Research Gaps in the Development of Biomarkers for Pediatric Tuberculosis.

Childhood tuberculosis contributes significantly to the global tuberculosis disease burden but remains challenging to diagnose due to inadequate methods of pathogen detection in paucibacillary pediatric samples and lack of a child-specific host biomarker to identify disease. Accurately diagnosing tuberculosis in children is required to improve case detection, surveillance, healthcare delivery, and effective advocacy. In May 2014, the National Institutes of Health convened a workshop including researchers in the field to delineate priorities to address this research gap. This blueprint describes the consensus from the workshop, identifies critical research steps to advance this field, and aims to catalyze efforts toward harmonization and collaboration in this area.

Incidence of multidrug-resistant tuberculosis disease in children: systematic review and global estimates.

BACKGROUND: Multidrug-resistant tuberculosis threatens to reverse recent reductions in global tuberculosis incidence. Although children younger than 15 years constitute more than 25% of the worldwide population, the global incidence of multidrug-resistant tuberculosis disease in children has never been quantified. We aimed to estimate the regional and global annual incidence of multidrug-resistant tuberculosis in children. METHODS: We developed two models: one to estimate the setting-specific risk of multidrug-resistant tuberculosis among child cases of tuberculosis, and a second to estimate the setting-specific incidence of tuberculosis disease in children. The model for risk of multidrug-resistant tuberculosis among children with tuberculosis needed a systematic literature review. We multiplied the setting-specific estimates of multidrug-resistant tuberculosis risk and tuberculosis incidence to estimate regional and global incidence of multidrug-resistant tuberculosis disease in children in 2010. FINDINGS: We identified 3403 papers, of which 97 studies met inclusion criteria for the systematic review of risk of multidrug-resistant tuberculosis. 31 studies reported the risk of multidrug-resistant tuberculosis in both children and treatment-naive adults with tuberculosis and were used for evaluation of the linear association between multidrug-resistant disease risk in these two patient groups. We identified that the setting-specific risk of multidrug-resistant tuberculosis was nearly identical in children and treatment-naive adults with tuberculosis, consistent with the assertion that multidrug-resistant disease in both groups reflects the local risk of transmitted multidrug-resistant tuberculosis. After application of these calculated risks, we estimated that around 999,792 (95% CI 937,877-1,055,414) children developed tuberculosis disease in 2010, of whom 31,948 (25,594-38,663) had multidrug-resistant disease. INTERPRETATION: Our estimates underscore that many cases of tuberculosis and multidrug-resistant tuberculosis disease are not being detected in children. Future estimates can be refined as more and better tuberculosis data and new diagnostic instruments become available. FUNDING: US National Institutes of Health, the Helmut Wolfgang Schumann Fellowship in Preventive Medicine at Harvard Medical School, the Norman E Zinberg Fellowship at Harvard Medical School, and the Doris and Howard Hiatt Residency in Global Health Equity and Internal Medicine at the Brigham and Women's Hospital.

A Photoactivatable Platinum(IV) Anticancer Complex Conjugated to the RNA Ligand Guanidinoneomycin.

A photoactivatable platinum(IV) complex, trans,trans,trans-[Pt(N3 )2 (OH)(succ)(py)2 ] (succ=succinylate, py=pyridine), has been conjugated to guanidinoneomycin to study the effect of this guanidinum-rich compound on the photoactivation, intracellular accumulation and phototoxicity of the pro-drug. Surprisingly, trifluoroacetic acid treatment causes the replacement of an azido ligand and the axial hydroxide ligand by trifluoroacetate, as shown by NMR spectroscopy, MS and X-ray crystallography. Photoactivation of the platinum-guanidinoneomycin conjugate in the presence of 5'-guanosine monophosphate (5'-GMP) led to the formation of trans-[Pt(N3 )(py)2 (5'-GMP)](+) , as does the parent platinum(IV) complex. Binding of the platinum(II) photoproduct {PtN3 (py)2 }(+) to guanine nucleobases in a short single-stranded oligonucleotide was also observed. Finally, cellular uptake studies showed that guanidinoneomycin conjugation improved the intracellular accumulation of the platinum(IV) pro-drug in two cancer cell lines, particularly in SK-MEL-28 cells. Notably, the higher phototoxicity of the conjugate in SK-MEL-28 cells than in DU-145 cells suggests a degree of selectivity towards the malignant melanoma cell line.

Cerium oxide as a promoter for the electro-oxidation reaction of ethanol: in situ XAFS characterization of the Pt nanoparticles supported on CeO2 nanoparticles and nanorods.

In this study we probe the electrocatalytic activity of Pt nanoparticles supported on ceria nanoparticles (NPs) and nanorods (NRs) in the ethanol oxidation reaction (EOR) in alkaline media. The goal of this study was to relate morphology, support structure and composition to the EOR catalytic activity by using in situ X-ray absorption fine structure (XAFS) studies. Cyclic voltammetry experiments showed that both ceria supported catalysts (NP vs. NR) had similar peak current densities at fast scan rates, however at slow scan rates, the ceria NR catalyst showed superior catalytic activity. In situ XAFS studies in KOH showed that both ceria supported catalysts had more electron density in their d-band (with the ceria NR having more electron density overall) than ceria - free Pt/Vulcan standard. However, in an ethanol solution the ceria NR catalyst had the least electron density. We propose that this change is due to the increased charge transfer efficiency between the ceria nanorod support and platinum. In the KOH solution, the increased electron density makes the platinum less electrophilic and hinders Pt-OH bond formation. In the EtOH solution, platinum's increased nucleophilicity facilitates the bond formation between Pt and the electron deficient carbon in ethanol which in turn withdraws the electron density from platinum and increases the white line intensity as observed in the XAS measurements.

Rituximab as successful adjunct treatment in a patient with disseminated nontuberculous mycobacterial infection due to acquired anti-interferon-γ autoantibody.

An acquired immune deficiency due to interferon gamma (IFN-γ) autoantibodies was diagnosed in a 78-year-old Japanese man with treatment-refractory disseminated nontuberculous mycobacterial infection. In addition to standard antimycobacterial therapy, he was successfully treated with rituximab to eliminate B cells and thereby the autoantibody. Subsequently, he obtained a sustained remission from infection.

Telephone screening for mild cognitive impairment in hispanics using the Alzheimer's questionnaire.

UNLABELLED: BACKGROUND/STUDY CONTEXT: There is a need for a simple and reliable screening test to detect individuals with mild cognitive impairment (MCI). The authors analyzed the relationship between performance of the Alzheimer's Questionnaire (AQ), an informant-rated measure of dementia-related behaviors, relative to the Telephone Interview for Cognitive Status-modified (TICS-m), Memory Impairment Scale-telephone version (MIS-t), and the Telephone Executive Assessment (TEXAS) as predictors of MCI. METHODS: Comparative cross-sectional design, with data collected from participants in the Texas Alzheimer's Research and Care Consortium's (TARCC) San Antonio site. One-hundred percent of our sample was Hispanic. The San Antonio subset of TARCC sample is highly enriched with Mexican Americans (MAs). Fifty-five percent of the interviews were conducted in Spanish. Of the 184 persons enrolled, 124 were normal controls (NCs), and 60 participants had MCI. MCI status and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) were determined through clinical consensus and performed blind to telephone assessments. Controlling for age, gender, education, and language of interview, the association between telephone measures and CDR-SOB was evaluated by multivariate regression. RESULTS: AQ scores were not affected by education, gender, and language of interview, but subject's age did show a positive correlation with informant AQ ratings. The AQ predicted CDR-SOB independently of the cognitive measures, adding variance above and beyond demographics. The TICS-m and the TEXAS appear to have additive value in improving the detection of cognitively impaired patients. The MIS-t failed to contribute significantly to CDR-SOB, independent of the other measures. CONCLUSION: The AQ may have utility as a culture-fair telephone screening for MCI. The AQ was able to modestly distinguish MCI from NCs. The TEXAS adds variance to a model of dementia severity independent of the AQ, suggesting that the latter may weakly assess that cognitive domain (executive control function). On the other hand, the AQ attenuates the MIS-t effect. This suggests a prominent AQ bias in favor of detecting memory impairment. Additional studies are required to determine if the AQ can distinguish between amnestic and dysexecutive MCI subtypes, or between MCI and Alzheimer's disease in Hispanics.

Effects of cadmium, copper and zinc on growth of four isolated algae from a highly polluted Argentina river.

Toxicity of cadmium, copper and zinc was tested on four green algal species (Ankistrodesmus fusiformis, Chlorella ellipsoidea, Monoraphidium contortum and Scenedesmus acuminatus) isolated from a highly polluted river (Matanza-Riachuelo River, Buenos Aires, Argentina). The relative abundance of these species in river waters showed that C. ellipsoidea was the most abundant species (mean 4,540 ind mL(-1)), whereas the less abundant species was S. acuminatus (mean 220 ind mL(-1)). The most sensitive species was A. fusiformis, which EC50 were Cd = 141 µg L(-1), Cu = 72 µg L(-1), and Zn = 199 µg L(-1), whereas C. ellipsoidea was the most resistant species to copper (EC50 = 489 µg L(-1)) and cadmium (EC50 = 429 µg L(-1)), and M. contortum and S. acuminatus were the most resistant species to zinc (EC50 = 381 and 394 µg L(-1), respectively).

Feasibility and utility of a combined nasogastric-tube-and-string-test device for bacteriologic confirmation of pulmonary tuberculosis in young children.

For microbiological confirmation of pediatric pulmonary tuberculosis (PTB), gastric aspirates (GA) are often operationally unfeasible without hospitalization, and the encapsulated orogastric string test is not easily swallowed in young children. The Combined-NasoGastric-Tube-and-String-Test (CNGTST) enables dual collection of GA and string specimens. In a prospective cohort study in Kenya, we examined its feasibility in children under five with presumptive PTB and compared the bacteriological yield of string to GA. Paired GA and string samples were successfully collected in 95.6 % (281/294) of children. Mycobacterium tuberculosis was isolated from 7.0 % (38/541) of GA and 4.3 % (23/541) of string samples, diagnosing 8.2 % (23/281) of children using GA and 5.3 % (15/281) using string. The CNGTST was feasible in nearly all children. Yield from string was two-thirds that of GA despite a half-hour median dwelling time. In settings where the feasibility of hospitalisation for GA is uncertain, the string component can be used to confirm PTB.

Three new genera in Chytridiales from aquatic habitats in Argentina.

Sampling for chytrids in a variety of habitats has resulted in pure cultures that when analyzed have yielded hypotheses of relationships based on molecular and zoospore ultrastructural markers. To extend our understanding of diversity of Chytridiales in eastern Argentina and USA, we isolated and examined the morphology, ultrastructure and 28S and ITS1-5.8S-ITS2 rDNA sequences of numerous chytrids from aquatic habitats from these two regions. Three family-level lineages (Chytridiaceae, Chytriomycetaceae, family incertae sedis) are represented in our molecular phylogeny, and three new genera (Avachytrium, Odontochytrium in Chytriomycetaceae, Delfinachytrium in family incertae sedis) are described. These findings of new genera and species emphasize the potential for discovery of additional diversity.

Design and characterization of color printed polyurethane films as biomedical phantom layers.

We propose a new, user-friendly and accessible approach for fabricating thin phantoms with controllable absorption properties in magnitude, spectral shape, and spatial distribution. We utilize a standard office laser color printer to print on polyurethane thin films (40 - 60 µm), commonly available as medical film dressings and ultrasound probe covers. We demonstrate that the optical attenuation and absorption of the printed films correlate linearly with the printer input settings (opacity), which facilitates a systematic phantom design. The optical and acoustic properties of these polyurethane films are similar to biological tissue. We argue that these thin phantoms are applicable to a wide range of biomedical applications. Here, we introduce two potential applications: (1) homogeneous epidermal melanin phantoms and (2) spatially resolved absorbers for photoacoustic imaging. We characterize the thin phantoms in terms of optical properties, thickness, microscopic structure, and reproducibility of the printing process.

Tracking the dynamics of thrombus formation in a blood vessel-on-chip with visible-light optical coherence tomography.

Thrombus formation is a physiological response to damage in a blood vessel that relies on a complex interplay of platelets, coagulation factors, immune cells, and the vessel wall. The dynamics of thrombus formation are essential for a deeper understanding of many disease processes, like bleeding, wound healing, and thrombosis. However, monitoring thrombus formation is challenging due to the limited imaging options available to analyze flowing blood. In this work, we use a visible-light optical coherence tomography (vis-OCT) system to monitor the dynamic process of the formation of thrombi in a microfluidic blood vessel-on-chip (VoC) device. Inside the VoC, thrombi form in a channel lined with a monolayer of endothelial cells and perfused by human whole blood. We show that the correlation of the vis-OCT signal can be utilized as a marker for thrombus formation. By thresholding the correlation during thrombus formation, we track and quantify the growth of the thrombi over time. We validate our results with fluorescence microscopic imaging of fibrin and platelet markers at the end of the blood perfusion assay. In conclusion, we demonstrate that the correlation of the vis-OCT signal can be used to visualize both the spatial and temporal behavior of the thrombus formation in flowing human whole blood.