Helicobacter pylori Infection and Light Chain Gammopathy

Objective. Helicobacter pylori provokes a host of immune alterations upon colonizing the gastric mucosa. Design. We report 22 individuals with confirmed Helicobacter pylori infection who were also managed for the concurrent elevation of immunoglobulin free light chain (kappa and lambda) levels. Result. Of the 22 patients, 15 patients (68.2%) had elevated free light chain levels: 6 patients (40%) had only kappa chain elevation, 2 patients (13.3%) had only lambda chain elevation, and 7 patients (46.7%) had both kappa and lambda chain elevation. Twenty out of the 22 patients (90.9%) were microbiologically confirmed cured with 3 patients being lost to follow-up for repeat levels. Of the 3 patients who were lost to follow-up, 1 patient had only kappa chain elevation, 1 patient had only lambda chain elevation, and 1 patient had both kappa and lambda chain elevation. For those who were cured (19 patients), 5 patients with kappa elevation had normalized values, 4 patients with lambda elevation had normalized values, and 2 patients with combined kappa and lambda elevation had normalized values. For 6 out of the 19 patients, the light chain levels remained elevated. Conclusion. We speculate that the Helicobacter pylori infection disrupts the immunoglobulin system with potential implications being discussed below

Intranasal ketamine for procedural sedation and analgesia in children: A systematic review

Background Ketamine is commonly used for procedural sedation and analgesia (PSA) in children. Evidence suggests it can be administered intranasally (IN). We sought to review the evidence for IN ketamine for PSA in children. Methods We performed a systematic review of randomized trials of IN ketamine in PSA that reported any sedation-related outcome in children 0 to 19 years. Trials were identified through electronic searches of MEDLINE (1946±2016), EMBASE (1947±2016), Google Scholar (2016), CINAHL (1981±2016), The Cochrane Library (2016), Web of Science (2016), Scopus (2016), clinical trial registries, and conference proceedings (2000±2016) without language restrictions. The methodological qualities of studies and the overall quality of evidence were evaluated using the Cochrane Collaboration\u27s Risk of Bias tool, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, respectively. Results The review included 7 studies (n = 264) of children ranging from 0 to 14 years. Heterogeneity in study design precluded meta-analysis. Most studies were associated with a low or unclear risk of bias and outcome-specific ratings for quality of evidence were low or very low. In four of seven studies, IN ketamine provided superior sedation to comparators and resulted in adequate sedation for 148/175 (85%) of participants. Vomiting was the most common adverse effect; reported by 9/91 (10%) of participants. Conclusions IN ketamine administration is well tolerated and without serious adverse effects. Although most participants were deemed adequately sedated with IN ketamine, effectiveness of sedation with respect to superiority over comparators was inconsistent, precluding a recommendation for PSA in children

Intranasal Dexmedetomidine for Procedural Distress in Children: A Systematic Review.

CONTEXT: Intranasal dexmedetomidine (IND) is an emerging agent for procedural distress in children. OBJECTIVE: To explore the effectiveness of IND for procedural distress in children. DATA SOURCES: We performed electronic searches of Medline (1946-2019), Embase (1980-2019), Google Scholar (2019), Cumulative Index to Nursing and Allied Health Literature (1981-2019), and Cochrane Central Register. STUDY SELECTION: We included randomized trials of IND for procedures in children. DATA EXTRACTION: Methodologic quality of evidence was evaluated by using the Cochrane Collaboration\u27s risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation system, respectively. The primary outcome was the proportion of participants with adequate sedation. RESULTS: Among 19 trials ( LIMITATIONS: The adequacy of sedation was subjective, which possibly led to biased outcome reporting. CONCLUSIONS: Given the methodologic limitations of included trials, IND is likely more effective at sedating children compared to oral chloral hydrate and oral midazolam. However, this must be weighed against the potential for adverse cardiovascular effects

Redistribution of nerve strain enables end-to-end repair under tension without inhibiting nerve regeneration

End-to-end repair under no or low tension leads to improved outcomes for transected nerves with short gaps, compared to repairs with a graft. However, grafts are typically used to enable a tension-free repair for moderate to large gaps, as excessive tension can cause repairs to fail and catastrophically impede recovery. In this study, we tested the hypothesis that unloading the repair interface by redistributing tension away from the site of repair is a safe and feasible strategy for end-to-end repair of larger nerve gaps. Further, we tested the hypothesis that such an approach does not adversely affect structural and functional regeneration. In this study, we used a rat sciatic nerve injury model to compare the integrity of repair and several regenerative outcomes following end-to-end repairs of nerve gaps of increasing size. In addition, we proposed the use of a novel implantable device to safely repair end-to-end repair of larger nerve gaps by redistributing tension away from the repair interface. Our data suggest that redistriubution of tension away from the site of repair enables safe end-to-end repair of larger gap sizes. In addition, structural and functional measures of regeneration were equal or enhanced in nerves repaired under tension – with or without a tension redistribution device – compared to tension-free repairs. Provided that repair integrity is maintained, end-to-end repairs under tension should be considered as a reasonable surgical strategy. All animal experiments were performed under the approval of the Institutional Animal Care and Use Committee of University of California, San Diego (Protocol S11274)

A First-Generation Multi-Functional Cytokine for Simultaneous Optical Tracking and Tumor Therapy

Creating new molecules that simultaneously enhance tumor cell killing and permit diagnostic tracking is vital to overcoming the limitations rendering current therapeutic regimens for terminal cancers ineffective. Accordingly, we investigated the efficacy of an innovative new multi-functional targeted anti-cancer molecule, SM7L, using models of the lethal brain tumor Glioblastoma multiforme (GBM). Designed using predictive computer modeling, SM7L incorporates the therapeutic activity of the promising anti-tumor cytokine MDA-7/IL-24, an enhanced secretory domain, and diagnostic domain for non-invasive tracking. In vitro assays revealed the diagnostic domain of SM7L produced robust photon emission, while the therapeutic domain showed marked anti-tumor efficacy and significant modulation of p38MAPK and ERK pathways. In vivo, the unique multi-functional nature of SM7L allowed simultaneous real-time monitoring of both SM7L delivery and anti-tumor efficacy. Utilizing engineered stem cells as novel delivery vehicles for SM7L therapy (SC-SM7L), we demonstrate that SC-SM7L significantly improved pharmacokinetics and attenuated progression of established peripheral and intracranial human GBM xenografts. Furthermore, SC-SM7L anti-tumor efficacy was augmented in vitro and in vivo by concurrent activation of caspase-mediated apoptosis induced by adjuvant SC-mediated S-TRAIL delivery. Collectively, these studies define a promising new approach to treating highly aggressive cancers, including GBM, using the optimized therapeutic molecule SM7L

BBF RFC 94: Type IIS Assembly for Bacterial Transcriptional Units: A Standardized Assembly Method for Building Bacterial Transcriptional Units Using the Type IIS Restriction Enzymes BsaI and BbsI

This RFC94 describes an assembly standard based on the Type IIS restriction enzymes BsaI and BbsI (also called BpiI). This assembly standard is based upon the Modular Cloning (MoClo) assembly strategy, which was introduced in 2011 by Weber et al. [1] and is based upon Golden Gate cloning [2]. In this RFC, we describe our proposed MoClo standard for generating a library of bacterial DNA parts for generating four-part transcriptional units (promoter : 5’UTR : CDS : 3’UTR). In this work, we define 5’UTRs as including ribosomal binding sites (RBS) and bi-cistronic design elements (BCDs) [3], and 3’UTRs as transcriptional terminators. The 2012-2014 BostonU iGEM teams completed this work and a more compact library has also been created based on this work [4]

Distinct mechanoreceptor pezo-1 isoforms modulate food intake in the nematode Caenorhabditis elegans

Two PIEZO mechanosensitive cation channels, PIEZO1 and PIEZO2, have been identified in mammals, where they are involved in numerous sensory processes. While structurally similar, PIEZO channels are expressed in distinct tissues and exhibit unique properties. How different PIEZOs transduce force, how their transduction mechanism varies, and how their unique properties match the functional needs of the tissues they are expressed in remain all-important unanswered questions. The nematode Caenorhabditis elegans has a single PIEZO ortholog (pezo-1) predicted to have 12 isoforms. These isoforms share many transmembrane domains but differ in those that distinguish PIEZO1 and PIEZO2 in mammals. We used transcriptional and translational reporters to show that putative promoter sequences immediately upstream of the start codon of long pezo-1 isoforms predominantly drive green fluorescent protein (GFP) expression in mesodermally derived tissues (such as muscle and glands). In contrast, sequences upstream of shorter pezo-1 isoforms resulted in GFP expression primarily in neurons. Putative promoters upstream of different isoforms drove GFP expression in different cells of the same organs of the digestive system. The observed unique pattern of complementary expression suggests that different isoforms could possess distinct functions within these organs. We used mutant analysis to show that pharyngeal muscles and glands require long pezo-1 isoforms to respond appropriately to the presence of food. The number of pezo-1 isoforms in C. elegans, their putative differential pattern of expression, and roles in experimentally tractable processes make this an attractive system to investigate the molecular basis for functional differences between members of the PIEZO family of mechanoreceptors.Fil: Hughes, Kiley. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Shah, Ashka. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Bai, Xiaofei. National Institutes of Health; Estados UnidosFil: Adams, Jessica. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Bauer, Rosemary. University of Chicago; Estados UnidosFil: Jackson, Janelle. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Harris, Emily. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Ficca, Alyson. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Freebairn, Ploy. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Mohammed, Shawn. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Fernandez, Eliana Mailen. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Bainbridge, Chance. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Brocco, Marcela Adriana. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Stein, Wolfgang. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Vidal Gadea, Andrés G.. University Of Illinois. Deparment Of Biological Science; Estados Unido

Planetary Candidates Observed by Kepler IV: Planet Sample From Q1-Q8 (22 Months)

We provide updates to the Kepler planet candidate sample based upon nearly two years of high-precision photometry (i.e., Q1-Q8). From an initial list of nearly 13,400 Threshold Crossing Events (TCEs), 480 new host stars are identified from their flux time series as consistent with hosting transiting planets. Potential transit signals are subjected to further analysis using the pixel-level data, which allows background eclipsing binaries to be identified through small image position shifts during transit. We also re-evaluate Kepler Objects of Interest (KOI) 1-1609, which were identified early in the mission, using substantially more data to test for background false positives and to find additional multiple systems. Combining the new and previous KOI samples, we provide updated parameters for 2,738 Kepler planet candidates distributed across 2,017 host stars. From the combined Kepler planet candidates, 472 are new from the Q1-Q8 data examined in this study. The new Kepler planet candidates represent ~40% of the sample with Rp~1 Rearth and represent ~40% of the low equilibrium temperature (Teq<300 K) sample. We review the known biases in the current sample of Kepler planet candidates relevant to evaluating planet population statistics with the current Kepler planet candidate sample.Comment: 12 pages, 8 figures, Accepted ApJ Supplemen

Planetary Candidates Observed by Kepler VI: Planet Sample from Q1-Q16 (47 Months)

\We present the sixth catalog of Kepler candidate planets based on nearly 4 years of high precision photometry. This catalog builds on the legacy of previous catalogs released by the Kepler project and includes 1493 new Kepler Objects of Interest (KOIs) of which 554 are planet candidates, and 131 of these candidates have best fit radii <1.5 R_earth. This brings the total number of KOIs and planet candidates to 7305 and 4173 respectively. We suspect that many of these new candidates at the low signal-to-noise limit may be false alarms created by instrumental noise, and discuss our efforts to identify such objects. We re-evaluate all previously published KOIs with orbital periods of >50 days to provide a consistently vetted sample that can be used to improve planet occurrence rate calculations. We discuss the performance of our planet detection algorithms, and the consistency of our vetting products. The full catalog is publicly available at the NASA Exoplanet Archive.Comment: 18 pages, to be published in the Astrophysical Journal Supplement Serie