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Dilek Gogas Yavuz,1 Omar Akhtar,2 Kaywei Low,2 Adrien Gras,2 Batu Gurser,3 Esra Safak Yilmaz,4 Amaury Basse5 1School of Medicine, Marmara University, Section of Endocrinology and Metabolism, Istanbul, Turkey; 2Healthcare Market Access, Ipsos, Singapore; 3Novo Nordisk, İstanbul, Türkiye; 4Novo Nordisk, Ankara, Türkiye; 5Novo Nordisk, Novo Nordisk Region South East Europe, Middle East & Africa, Zurich, SwitzerlandCorrespondence: Amaury Basse, Email aayb@novonordisk.comBackground: Turkey currently has the highest obesity prevalence among its European counterparts. 32% and 61% of the population live with obesity and overweight, respectively. Overweight and obesity are linked to non-communicable diseases that incur incremental health and economic costs. The significant public health concern warrants an assessment of the cost of obesity.Methods: A micro-costing approach from the public payer perspective was conducted to estimate direct healthcare costs associated with ten obesity-related comorbidities (ORCs) in Turkey. Clinical practice guidelines and a systematic literature review informed ORCs and the respective cost categories. This was subsequently validated by a steering committee comprising seven experts. Seventy public sector physicians were surveyed to estimate healthcare resource use. Unit costs were derived from Social Security Institute’s Healthcare Implementation Communique. Cost items were summed to determine the annual cost per patient per ORC, which was validated by the steering committee. Medical inflation was considered in a scenario analysis that varied resource unit costs.Results: Chronic kidney disease, heart failure and type 2 diabetes are the costliest ORCs, incurring an annual cost of 28,600 TRY, 16,639 TRY and 11,993 TRY, respectively. Individuals in Turkey with any ORC triggered direct healthcare costs ranging 1857– 28,600 TRY annually. Costs were driven by tertiary care resources arising from treatment-related adverse events, disease complications and inpatient procedures. In the scenario analysis, medical resource unit costs were inflated by 18.7% and 39.4%, triggering an average increase in cost across all ORCs of 1998 TRY and 4210 TRY, respectively.Conclusion: Our findings confirm that obesity and its complications result in significant financial burden to the public healthcare system. By quantifying the burden of obesity across a comprehensive spectrum of ORCs, our study aims to support the economic case for investing in appropriate obesity interventions.Keywords: obesity, micro-costing, cost of illness, burden of illness, healthcare resource utilization

Vivek Y Reddy,1 Yue Zhong,2 Alysha M McGovern,2 Stacey L Amorosi,2 Meghan B Gavaghan,3 Deanna S Hertz,3 Kaywei Low,3 Scott Freeman,3 David R Holmes Jr4 1Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Health Economics and Market Access, Boston Scientific, Marlborough, MA, USA; 3Ipsos Healthcare, New York, NY, USA; 4Mayo Clinic, Rochester, MN, USACorrespondence: Vivek Y Reddy, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place Box 1030, New York, NY, 10029, USA, Tel +1 212 241-7114, Fax +1 646 537-9691, Email vivek.reddy@mountsinai.orgBackground: As healthcare costs are increasingly being shifted from payers to patients, it is important to understand the economic consequences of therapeutic strategies to both payers and patients.Objective: To determine the relative costs to Medicare and Medicare beneficiaries (patients) of warfarin, non-vitamin K oral anticoagulants (NOACs), and left atrial appendage closure (LAAC) for stroke risk reduction in nonvalvular atrial fibrillation.Methods: An economic model was developed to assess costs at 5 and 10 years. For warfarin and NOACs, inputs were derived from published meta-analyses; for LAAC with the Watchman device, inputs were derived from pooled 5-year PROTECT AF and PREVAIL trial results. The model captured therapy costs vs clinical event costs, including procedural complications and follow-up clinical outcomes. Costs were based on 2023 Medicare reimbursement and copayment rates.Results: At 10 years, overall LAAC costs ($48,337) were lower than those of NOACs ($81,198) and warfarin ($52,359). Overall LAAC costs were lower than those of NOACs by year 5 and warfarin by year 9. At 5 years, patient LAAC costs were lowest at $4,764, compared to $7,146 and $6,453 for NOACs and warfarin, respectively. LAAC patient costs were lower than those of NOACs by year 3 and warfarin by year 4. Clinical events comprised 96% of overall warfarin costs vs 48% for LAAC and 40% for NOACs.Conclusion: LAAC yielded the lowest overall and patient costs. Warfarin costs were largely driven by clinical events, which may represent an unplanned financial burden for patients. These considerations should be incorporated into shared decision-making discussions about stroke prophylaxis strategies.Keywords: economic analysis, medicare, patient, warfarin, NOACs, watchman

Abstract Background Pathogens tolerate stress conditions that include low pH, oxidative stress, high salt and high temperature in order to survive inside and outside their hosts. Lipopolysaccharide (LPS), which forms the outer-leaflet of the outer membrane in Gram-negative bacteria, acts as a permeability barrier. The lipid A moiety of LPS anchors it to the outer membrane bilayer. The MsbB enzyme myristoylates the lipid A precursor and loss of this enzyme, in Salmonella, is correlated with reduced virulence and severe growth defects that can both be compensated with extragenic suppressor mutations. Results We report here that msbB (or msbB somA) Salmonella are highly sensitive to physiological CO2 (5%), resulting in a 3-log reduction in plating efficiency. Under these conditions, msbB Salmonella form long filaments, bulge and lyse. These bacteria are also sensitive to acidic pH and high osmolarity. Although CO2 acidifies LB broth media, buffering LB to pH 7.5 did not restore growth of msbB mutants in CO2, indicating that the CO2-induced growth defects are not due to the effect of CO2 on the pH of the media. A transposon insertion in the glucose metabolism gene zwf compensates for the CO2 sensitivity of msbB Salmonella. The msbB zwf mutants grow on agar, or in broth, in the presence of 5% CO2. In addition, msbB zwf strains show improved growth in low pH or high osmolarity media compared to the single msbB mutant. Conclusion These results demonstrate that msbB confers acute sensitivity to CO2, acidic pH, and high osmolarity. Disruption of zwf in msbB mutants restores growth in 5% CO2 and results in improved growth in acidic media or in media with high osmolarity. These results add to a growing list of phenotypes caused by msbB and mutations that suppress specific growth defects.

Bacteria produce a plethora of volatile organic compounds (VOCs) into the atmosphere as a means of interacting with their habitats, as well as for intra- and interkingdom communication, and to survive and thrive in nature and inside their hosts. Campylobacter, which is commonly found in poultry and ruminants, has demonstrated remarkable endurance in aquatic settings, making it one of the world's most hazardous foodborne pathogens that kill thousands of humans every year. In the present work, the VOCs released by both thermophilic (C. jejuni, C. coli, and C. lari) and non-thermophilic (C. fetus) Campylobacter of clinical significance, which were influenced by nutrient composition (media) and growth phase, were profiled using an active sampling approach, with active charcoal adsorbent and gas chromatography-mass spectrometry. Alcohols and ketones were detected only in the thermophilic Campylobacter strains, C. jejuni subsp. jejuni (1-heptadecanol; 1,8-nonadien-3-ol; 3,7,11-trimethyl-3-dodecanol; 1s,4R,7R,11R- 1,3,4,7-tetramethyltricyclo [5.3.1.0(4,11)] undec-2-en-8-one; and isophorone), C. coli (isophorone and 3,5-bis(1,1-dimethylethyl)-phenol), and C. lari (3,7,11-trimethyl-3- dodecanol and 1s,4R,7R,11R-1,3,4,7-tetramethyltricyclo [5.3.1.0(4,11)] undec-2-en-8- one) between early stationary and stationary growth phases. The non-thermophilic C. fetus produced only a range of unidentified compounds that need to be investigated further in the future. The results from the principal component analysis showed distinctive clustering of VOC markers between the four bacteria taxa and within the strains of C. jejuni, including distinguishable groupings of VOCs throughout the growth phase of each bacterium and between different culture media. This demonstrates the influence of bacterial growth and media composition on the volatilome of the studied Campylobacter spp. Overall, the VOC profiling of these foodborne pathogens, under influencing factors of growth phase and media, paves the way for future rapid identification of Campylobacter spp. in food matrices. [ABSTRACT FROM AUTHOR]

In order to identify optimal rehabilitation strategies for spinal cord injury (SCI) participants, assessment of impaired walking is required to detect, monitor and quantify movement disorders. In the proposed assessment, ten healthy and seven SCI participants were recruited to perform an over-ground walking test at slow walking speeds. SCI participants were given assistance from physiotherapists, if required, while they were walking. In agreement with other research, larger cadence and smaller step length and swing phase of SCI gait were observed as a result of muscle weakness and resultant gait instability. Muscle activation patterns of seven major leg muscles were collected. The EMG signal was processed by the RMS in frequency domain to represent the muscle activation power, and the distribution of muscle activation was compared between healthy and SCI participants. The alternations of muscle activation within the phases of the gait cycle are highlighted to facilitate our understanding of the underlying muscular activation following SCI. Key differences were observed (p-value = 0.0006) in the reduced activation of tibialis anterior (TA) in single stance phase and rectus femoris (RF) in swing phase (p-value = 0.0011). We can then conclude that the proposed assessment approach of gait provides valuable information that can be used to target and define therapeutic interventions and their evaluation; hence impacting the functional outcome of SCI individuals. (Contains 3 figures and 5 tables.)

The present meta-analysis examined the stability of vocational interests from early adolescence (age 12) to middle adulthood (age 40). Stability was represented by rank-order and profile correlations. Interest stability remained unchanged during much of adolescence and increased dramatically during the college years (age 18-21.9), where it remained for the next 2 decades. Analyses of potential moderators showed that retest time interval was negatively related to interest stability and that rank-order stability was less stable than profile stability. Although cohort standings did not moderate stability, interests of the 1940s birth cohort were less stable than those of other cohorts. Furthermore, interests reflecting hands-on physical activities and self-expressive/artistic activities were more stable than scientific, social, enterprising, and clerical interests. Vocational interests showed substantial continuity over time, as evidenced by their higher longitudinal stability when compared with rank-order stability of personality traits. The findings are discussed in the context of psychosocial development.

Mutations in pmrA were recombined into Salmonella strain ATCC 14028 msbB to determine if pmrA-regulated modifications of lipopolysaccharide could suppress msbB growth defects. A mutation that functions to constitutively activate pmrA [pmrA(Con)] suppresses msbB growth defects on EGTA-containing media. Lipid A structural analysis showed that Salmonella msbB pmrA(Con) strains, compared to Salmonella msbB strains, have increased amounts of palmitate and phosphoethanolamine but no aminoarabinose addition, suggesting that aminoarabinose is not incorporated into msbB lipid A. Surprisingly, loss-of-function mutations in the aminoarabinose biosynthetic genes restored EGTA and polymyxin sensitivity to Salmonella msbB pmrA(Con) strains. These blocks in aminoarabinose biosynthesis also prevented lipid A phosphoethanolamine incorporation and reduced the levels of palmitate addition, indicating previously unknown roles for the aminoarabinose biosynthetic enzymes. Lipid A structural analysis of the EGTA- and polymyxin-resistant triple mutant msbB pmrA(Con)pagP::Tn10, which contains phosphoethanolamine but no palmitoylated lipid A, suggests that phosphoethanolamine addition is sufficient to confer EGTA and polymyxin resistance on Sahnonella msbB strains. Additionally, palmitoylated lipid A was observed only in wild-type Salmonella grown in the presence of salt in rich media. Thus, we correlate EGTA resistance and polymyxin resistance with phosphoethanolamine-decorated lipid A and demonstrate that the aminoarabinose biosynthetic proteins play an essential role in lipid A phosphoethanolamine addition and affect lipid A palmitate addition in Salmonella msbB strains.