Comparison of Commercial and Self-Initiated Weight Loss Programs in People With Prediabetes: A Randomized Control Trial

To determine if a widely available weight-management program (Weight Watchers) could achieve sufficient weight loss in persons with prediabetes compared with a Diabetes Prevention Program-based individual counseling program supported by National Diabetes Education Program materials. METHODS: We conducted an individual, randomized intervention trial in Indianapolis, Indiana, in 2013 to 2014, in 225 persons with prediabetes. We compared the Weight Watchers weight-management program (n = 112) with Your Game Plan to Prevent Type 2 Diabetes, a program developed by the National Diabetes Education Program. Outcomes were weight and metabolic markers measured at baseline, 6 months, and 12 months. RESULTS: Intervention participants lost significantly more weight than controls at 6 months (5.5% vs 0.8%) and 12 months (5.5% vs 0.2%; both P < .001). The intervention group also had significantly greater improvements in hemoglobin A1c and high-density lipoprotein cholesterol level than did controls. CONCLUSIONS: A large weight-management program is effective for achieving lifestyle changes associated with diabetes prevention. Such programs could significantly increase the availability of diabetes prevention programs worldwide making an immediate and significant public health impact

An Intervention Fidelity Framework for Technology-Based Behavioral Interventions

Despite the proliferation of health technologies, descriptions of the unique considerations and practical guidance for evaluating intervention fidelity of technology-based behavioral interventions are lacking

Status update on GPS integrity failure modes and effects analysis

GPS integrity anomalies have long been of great concern to the civil and military GPS communities for safety-of- life operations. The FAA, USCG, and their international counterparts have focused on how to accomplish integrity monitoring for safety-of-life services through the use of receiver autonomous integrity monitoring (RAIM), widearea and local-area augmentation systems such as WAAS and LAAS, maritime differential GPS (DGPS) and nationwide differential GPS (NDGPS). The military is preparing to certify PPS RAIM receivers and is in the process of developing the Joint Precision Approach and Landing System (JPALS). Integrity failure modes need to be understood in order to develop a proper monitoring capability. The main objectives of the GPS Integrity Failure Modes and Effects Analysis (IFMEA) project are to identify GPS integrity monitoring requirements, examine GPS failure data in order to identify integrity failure modes, examine the causes and effects of the failures, as well as their probability of occurrence, determine the impact of integrity anomalies on users, and recommend preventive actions. The IFMEA project is focused on integrity anomalies that are due to hardware and software failures in the satellite vehicles (SVs) and Operational Control System (OCS). This paper provides a status update on the GPS IFMEA effort which is jointly funded by the Interagency GPS Executive Board (IGEB), the GPS Joint Program Office (JPO), and the Federal Aviation Administration (FAA). The IFMEA project began in 2002 under IGEB stewardship funding. Through the IFMEA project, Aberration Characterization Sheets (ACS) have been developed and updated for all GPS satellites through the Block IIR generation and work is now beginning on Block IIR-M, IIF, and the Architecture Evolution Plan (AEP) for the OCS. There is a need by those in the user community who are developing safety of life systems to be able to easily research GPS integrity anomaly data. In support of this effort, the IFMEA team is developing a database of all GPS service anomalies that can be accessed by type of anomaly, satellite number, satellite block affected, magnitude of error, date of occurrence, and duration of event. An effects analysis for WAAS and LAAS is being conducted to determine the impact on these augmentation systems from integrity anomalies. Finally, the IFMEA project is evaluating signal quality monitoring (SQM) algorithms to ensure proper detection of integrity anomalies and identify any design constraints or modifications to the GPS SV and OCS to either prevent failures that degrade integrity or provide protection from any adverse operational impact. This work is referenced in other ION papers [1] and [2]. The benefits of this work are to gain a better understanding of integrity anomalies, their probability of occurrence, and how to monitor for them. This information is essential to the design of differential GPS networks to support safety of life operations and will assist in meeting international commitments to describe GPS performance. The work performed under this study also will provide a technical basis to update the SPS and PPS Performance Standards and help develop recommendations for improvements to future GPS satellites and the operational control system

Magnetic Resonance Imaging of Pulmonary Lesions in Guinea Pigs Infected with Mycobacterium tuberculosis

We utilized magnetic resonance imaging to visualize lesions in the lungs of guinea pigs infected by low-dose aerosol exposure to Mycobacterium tuberculosis. Lesions were prominent in such images, and colorized three-dimensional reconstructions of images revealed a very uniform distribution in the lungs. Lesion numbers after 1 month were approximately similar to the aerosol exposure algorithm, suggesting that each was established by a single bacterium. Numbers of lesions in unprotected and vaccinated animals were similar over the first month but increased thereafter in the control animals, indicating secondary lesion development. Whereas lesion sizes increased progressively in control guinea pigs, lesions remained small in BCG-vaccinated animals. A prominent feature of the disease pathology in unprotected animals was rapid and severe lymphadenopathy of the mediastinal lymph node cluster, which is paradoxical given the strong state of cellular immunity at this time. Further development of this technical approach could be very useful in tracking lesion size, number, and progression in the search for new tuberculosis vaccines

Genes That Influence Swarming Motility and Biofilm Formation in Variovorax paradoxus EPS

Variovorax paradoxus is an aerobic soil bacterium associated with important biodegradative processes in nature. We use V. paradoxus EPS to study multicellular behaviors on surfaces.We recovered flanking sequence from 123 clones in a Tn5 mutant library, with insertions in 29 different genes, selected based on observed surface behavior phenotypes. We identified three genes, Varpa_4665, Varpa_4680, and Varpa_5900, for further examination. These genes were cloned into pBBR1MCS2 and used to complement the insertion mutants. We also analyzed expression of Varpa_4680 and Varpa_5900 under different growth conditions by qPCR.The 29 genes we identified had diverse predicted functions, many in exopolysaccharide synthesis. Varpa_4680, the most commonly recovered insertion site, encodes a putative N-acetyl-L-fucosamine transferase similar to WbuB. Expression of this gene in trans complemented the mutant fully. Several unique insertions were identified in Varpa_5900, which is one of three predicted pilY1 homologs in the EPS genome. No insertions in the two other putative pilY1 homologs present in the genome were identified. Expression of Varpa_5900 altered the structure of the wild type swarm, as did disruption of the chromosomal gene. The swarming phenotype was complemented by expression of Varpa_5900 from a plasmid, but biofilm formation was not restored. Both Varpa_4680 and Varpa_5900 transcripts were downregulated in biofilms and upregulated during swarming when compared to log phase culture. We identified a putative two component system (Varpa_4664-4665) encoding a response regulator (shkR) and a sensor histidine kinase (shkS), respectively. Biofilm formation increased and swarming was strongly delayed in the Varpa_4665 (shkS) mutant. Complementation of shkS restored the biofilm phenotype but swarming was still delayed. Expression of shkR in trans suppressed biofilm formation in either genetic background, and partially restored swarming in the mutant.The data presented here point to complex regulation of these surface behaviors

Correction. "The 5th edition of The World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms" Leukemia. 2022 Jul;36(7):1720-1748

We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms

Dynamic Evolution of Pathogenicity Revealed by Sequencing and Comparative Genomics of 19 Pseudomonas syringae Isolates

Closely related pathogens may differ dramatically in host range, but the molecular, genetic, and evolutionary basis for these differences remains unclear. In many Gram- negative bacteria, including the phytopathogen Pseudomonas syringae, type III effectors (TTEs) are essential for pathogenicity, instrumental in structuring host range, and exhibit wide diversity between strains. To capture the dynamic nature of virulence gene repertoires across P. syringae, we screened 11 diverse strains for novel TTE families and coupled this nearly saturating screen with the sequencing and assembly of 14 phylogenetically diverse isolates from a broad collection of diseased host plants. TTE repertoires vary dramatically in size and content across all P. syringae clades; surprisingly few TTEs are conserved and present in all strains. Those that are likely provide basal requirements for pathogenicity. We demonstrate that functional divergence within one conserved locus, hopM1, leads to dramatic differences in pathogenicity, and we demonstrate that phylogenetics-informed mutagenesis can be used to identify functionally critical residues of TTEs. The dynamism of the TTE repertoire is mirrored by diversity in pathways affecting the synthesis of secreted phytotoxins, highlighting the likely role of both types of virulence factors in determination of host range. We used these 14 draft genome sequences, plus five additional genome sequences previously reported, to identify the core genome for P. syringae and we compared this core to that of two closely related non-pathogenic pseudomonad species. These data revealed the recent acquisition of a 1 Mb megaplasmid by a sub-clade of cucumber pathogens. This megaplasmid encodes a type IV secretion system and a diverse set of unknown proteins, which dramatically increases both the genomic content of these strains and the pan-genome of the species

Cathelicidin and its role in defence against bacterial infections of epithelial cells

Cathelicidins are antimicrobial peptides (AMPs) that were first discovered to have microbicidal properties but more recently to be multifunctional immunomodulators and thus important in influencing host defence against infectious disease. Whilst roles in various organs have been demonstrated, their expression patterns in health and disease in other organs are less clear and their key immunomodulatory functions remain undefined, particularly with regard to the balance of immunomodulatory properties and microbicidal activity in their ability to promote defence against infection. I therefore set out to describe LL-37 expression (human cathelicidin) in the female reproductive tract (across the menstrual cycle) and in the lung (during specific lung diseases), to define the effects on the function of airway epithelial cells during bacterial infection and to evaluate the key in vivo roles of endogenous cathelicidin (using a knockout mouse model) as well as the effect of therapeutic administration of LL-37 in a pulmonary Pseudomonas aeruginosa infection model. I demonstrated that cathelicidin protein and transcription shows a cyclical pattern of expression in female reproductive tissues which is maintained at high levels in decidua. LL- 37 protein was also detected in hTERT endometrial epithelial cells but despite the suggestion that cathelicidin may be regulated by steroid hormones there was no direct effect of progesterone on transcription. LL-37 is barely detected in healthy airways however is well known to increase during infection or inflammation. I observed that sputum from patients with bronchiectasis showed a correlation between the level of LL-37, TNF, MPO and chronic colonisation of Pseudomonas aeruginosa. Patients with lung cancer expressed much less LL- 37 than the bronchiectasis patients but there was a trend towards increased production postsurgery compared to pre-surgery. LL-37 was previously shown by our lab to selectively promote BAX and caspase-dependant death of infected epithelial cells. I went on to show that this appears to be a partially caspase- 1 dependent mechanism and that human bronchial epithelial (HBE) cells and A549 cell lines both express several of the components required to form inflammasomes, a caspase-1 dependant form of inflammatory cell death. Finally, I showed using murine models that cathelicidin enhances bacterial clearance during pulmonary infection in vivo, a response which is defective in mice lacking endogenous cathelicidin and that administration of exogenous, synthetic LL-37 at the time of infection can promote an early protective neutrophil influx in the absence of endogenous cathelicidin production

Referral to a Commercial Weight Management Program in Patients With Coronary Heart Disease: A PILOT STUDY IN THE NETHERLANDS

To quantify the impact of a commercial weight management program on weight change in obese patients with coronary heart disease. An observational, single-center pilot study in the Netherlands. Forty-five patients diagnosed with a recent acute coronary syndrome and a body mass index of >30 kg/m2 were recruited. The commercial weight management intervention (Weight Watchers) promotes a hypoenergetic and balanced diet, increased physical activity, and group support. The program included weekly 30-minute in-hospital meetings with an experienced coach. The program was offered in parallel with a cardiac rehabilitation program. Thirty-five patients completed the program. Of these patients, 32 patients (91%) decreased body weight. Mean weight change was -5.8 kg (range: +0.6 kg to -15.4 kg), and 20 patients (57%) achieved the target of 5% weight loss of their initial weight. Twenty-seven patients continued the commercial weight loss program after 14 weeks, the mean followup of these patients was 34 weeks and their mean weight change was -9.1 kg (range: 0.0-23.0 kg). Obese patients, discharged after an acute coronary syndrome, who were referred to a commercial weight management program, achieved significant weight loss. Although this is a nonrandomized pilot study with patients who were selected by motivation and by the ability to participate in the program, the proportion of weight loss is significant and promisin