Inefficient Metabolism of the Human Milk Oligosaccharides Lacto-N-tetraose and Lacto-N-neotetraose Shifts Bifidobacterium longum subsp. infantis Physiology

Human milk contains a high concentration of indigestible oligosaccharides, which likely mediated the coevolution of the nursing infant with its gut microbiome. Specifically, Bifidobacterium longum subsp. infantis (B. infantis) often colonizes the infant gut and utilizes these human milk oligosaccharides (HMOs) to enrich their abundance. In this study, the physiology and mechanisms underlying B. infantis utilization of two HMO isomers lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT) was investigated in addition to their carbohydrate constituents. Both LNT and LNnT utilization induced a significant shift in the ratio of secreted acetate to lactate (1.7-2.0) in contrast to the catabolism of their component carbohydrates (~1.5). Inefficient metabolism of LNnT prompts B. infantis to shunt carbon toward formic acid and ethanol secretion. The global transcriptome presents genomic features differentially expressed to catabolize these two HMO species that vary by a single glycosidic linkage. Furthermore, a measure of strain-level variation exists between B. infantis isolates. Regardless of strain, inefficient HMO metabolism induces the metabolic shift toward formic acid and ethanol production. Furthermore, bifidobacterial metabolites reduced LPS-induced inflammation in a cell culture model. Thus, differential metabolism of milk glycans potentially drives the emergent physiology of host-microbial interactions to impact infant health

Determinants of Travel Participation and Experiences of Wheelchair Users Traveling to the Bodrum Region: A Qualitative Study

Although the number of people with disabilities and types of disability increases day by day, a sufficient point has not been reached regarding accessible tourism. The participation rate of people with disabilities (PWDS) in tourism activities is low, and there is a big gap in the travel and accommodation sector in this regard. Studies of previous scholars have concluded that the accessible tourism market is a significant and profitable area, but determinants of participation to travel and process of travel, such as wheelchair user expectations, are consistently ignored by the tourism industry. The main purpose of this study is to determine the determinants of travel by examining the motivations, expectations, processes and experiences of PWDS using wheelchairs to participate in tourism. Research was performed in Turkey’s Bodrum district; 25 wheelchair users were included in the study. The keywords that emerged in the theoretical framework in light of the answers given to 39 open-ended questions online were coded in the Nvivo program. The results showed that wheelchair users intended to go on vacation but were less motivated to participate due to the lack of travel conditions. Wheelchair travelers argued that a companion was required for an enjoyable holiday that could meet their needs. In addition, the results revealed that the types of wheelchairs used by disabled passengers differ. The disabled stated that the wheelchairs they use in daily life are not suitable for use on the beach, sand or water. Despite the economic, social and technological change opportunities, basic tourism service expectations of PWDS are not met. This research project is a comprehensive study that makes determinations in terms of examining the social status of disabled people in terms of social sciences, examining the place and importance of disabled tourists in the market and eliminating the deficiencies of facilities serving in tourism.publishedVersio

Bifidobacterium infantis Metabolizes 2\u27Fucosyllactose-Derived and Free Fucose Through a Common Catabolic Pathway Resulting in 1,2-Propanediol Secretion

Human milk oligosaccharides (HMOs) enrich beneficial bifidobacteria in the infant gut microbiome which produce molecules that impact development and physiology. 2\u27fucosyllactose (2\u27FL) is a highly abundant fucosylated HMO which is utilized by Bifidobacterium longum subsp. infantis, despite limited scientific understanding of the underlying mechanism. Moreover, there is not a current consensus on whether free fucose could be metabolized when not incorporated in a larger oligosaccharide structure. Based on metabolic and genomic analyses, we hypothesize that B. infantis catabolizes both free fucose and fucosyl oligosaccharide residues to produce 1,2-propanediol (1,2-PD). Accordingly, systems-level approaches including transcriptomics and proteomics support this metabolic path. Co-fermentation of fucose and limiting lactose or glucose was found to promote significantly higher biomass and 1,2-PD concentrations than individual substrates, suggesting a synergistic effect. In addition, and during growth on 2\u27FL, B. infantis achieves significantly higher biomass corresponding to increased 1,2-PD. These findings support a singular fucose catabolic pathway in B. infantis that is active on both free and HMO-derived fucose and intimately linked with central metabolism. The impact of fucose and 2\u27FL metabolism on B. infantis physiology provides insight into the role of fucosylated HMOs in influencing host- and microbe-microbe interactions within the infant gut microbiome

Effect of angiotensin converting enzyme inhibitors on periprocedural myocardial infarction in patients with metabolic syndrome

Background: Metabolic syndrome (MetS) has been reported as a risk factor for cardiovascular events. The aim of the present study is to investigate the association between chronic angiotensin-converting enzyme inhibitors (ACE-I) therapy and the rate of periprocedural myocardial infarction (PMI) after elective coronary stenting among patients with MetS. Methods: The inclusion criteria were MetS and plan for elective percutaneous coronary intervention. To assess the effect of ACE-I treatment on the incidence of PMI, measurements of cardiac biomarkers (CK-MB mass and troponin I) were performed at baseline and 24 h after the procedure. Results: A total of 459 patients fulfilling the inclusion criteria were recruited to chronic ACE-I treatment and ACE-I naive groups in a 2/1 ratio. Baseline troponin I and CK-MB levels were similar in both treatment groups, whereas they were significantly lower in ACE-I group 24 h after the procedure. Univariate analysis identified body mass index (BMI), LDL cholesterol, nitrate and ACE-I use as significant factors for the development of PMI. Multivariate regression model revealed that body mass index increased and use of nitrate and ACE-I decreased the probability of PMI independent from confounding factors (OR 1.14, 95% CI 1.05–1.23, p = 0.002 for BMI; OR 0.26, 95% CI 0.14–0.48, p = 0.01 for nitrate use, OR 0.51, 95% CI 0.27–0.93, p = 0.03 for ACE-I use). Conclusions: This prospective observational cohort trial demonstrated that chronic ACE-I therapy was an independent predictor for reduced PMI among patients with MetS who underwent elective coronary intervention

Determinants of Travel Participation and Experiences of Wheelchair Users Traveling to the Bodrum Region: A Qualitative Study

Although the number of people with disabilities and types of disability increases day by day, a sufficient point has not been reached regarding accessible tourism. The participation rate of people with disabilities (PWDS) in tourism activities is low, and there is a big gap in the travel and accommodation sector in this regard. Studies of previous scholars have concluded that the accessible tourism market is a significant and profitable area, but determinants of participation to travel and process of travel, such as wheelchair user expectations, are consistently ignored by the tourism industry. The main purpose of this study is to determine the determinants of travel by examining the motivations, expectations, processes and experiences of PWDS using wheelchairs to participate in tourism. Research was performed in Turkey’s Bodrum district; 25 wheelchair users were included in the study. The keywords that emerged in the theoretical framework in light of the answers given to 39 open-ended questions online were coded in the Nvivo program. The results showed that wheelchair users intended to go on vacation but were less motivated to participate due to the lack of travel conditions. Wheelchair travelers argued that a companion was required for an enjoyable holiday that could meet their needs. In addition, the results revealed that the types of wheelchairs used by disabled passengers differ. The disabled stated that the wheelchairs they use in daily life are not suitable for use on the beach, sand or water. Despite the economic, social and technological change opportunities, basic tourism service expectations of PWDS are not met. This research project is a comprehensive study that makes determinations in terms of examining the social status of disabled people in terms of social sciences, examining the place and importance of disabled tourists in the market and eliminating the deficiencies of facilities serving in tourism

Novel Posterior Shoulder Stretching With Rapid Eccentric Contraction and Static Stretching in Patients With Subacromial Pain Syndrome: A Randomized Trial

Background: In subacromial pain syndrome (SPS), it is unknown whether posterior shoulder stretching exercises (PSSE) with rapid eccentric contraction, a muscle energy technique, improve clinical and ultrasonographic outcomes more than no stretching or static PSSE. Hypothesis: PSSE with rapid eccentric contraction is superior to no stretching and static PSSE in improving clinical and ultrasonographic outcomes in SPS. Study Design: Randomized controlled trial. Methods: Seventy patients with SPS and glenohumeral internal rotation deficit were randomized into the modified cross-body stretching with rapid eccentric contraction group (EMCBS; n = 24), static MCBS group (SMCBS; n = 23), or control group (CG; n = 23). In addition to 4-week physical therapy, EMCBS received PSSE with rapid eccentric contraction, SMCBS static PSSE, and CG no PSSE. The primary outcome was internal rotation range of motion (ROM). Secondary outcomes were posterior shoulder tightness, external rotation ROM (ERROM), pain, modified Constant-Murley score, short form of the disabilities of the arm, shoulder, and hand questionnaire (QuickDASH), rotator cuff strength, acromiohumeral distance (AHD), supraspinatus tendon thickness, and supraspinatus tendon occupation ratio (STOR). Results: Shoulder mobility, pain, function and disability, strength, AHD, and STOR improved in all groups (P < 0.05). Conclusion: In patients with SPS, PSSE with rapid eccentric contraction and static PSSE were superior to no stretching in improving clinical and ultrasonographic outcomes. Stretching with rapid eccentric contraction was not superior to static stretching, but improved ERROM compared with no stretching

Routing and Navigation Solutions for Emergency Vehicles in Urban Emergency Management

Urban population and expansion continue to rise, as have emergencies, and emergency response times are becoming longer in the city. Response times are critical in urban emergency management. Traditional navigation systems do not consider the preferential road usage rights and requirements crucial for emergency teams such as ambulances, fire departments, and police. In traditional navigation systems, features such as safety lanes and road width are not incorporated as routing criteria. Past emergency navigation studies do not contain many variables and this causes delays in emergency response processes. As a result, applications that process real-time traffic information and provide guidance according to different vehicle types are needed for emergency management.. This study aims to develop an application capable of routing for different vehicles according to criteria such as working hours, holidays, weather conditions, and seasonal effects. The application is developed with a novel approach in this context using machine learning methods and produces alternate routes with GPS navigation based on the real-time traffic situation. Moreover, the software also provides routing solutions for trucks, freight distribution, and automobiles and recommends unique routes for emergency vehicles based on factors including safety lanes, road width, corner turning angles, and right of way. The expected outcomes upon implementing this application include easy and fast access to the emergency locations, reduced response times, and improvement in urban emergency management services

Product transfer from lab-scale to pilot-scale of quetiapine fumarate orodispersible films using quality by design approach

In this study, transfer from lab-scale non-continuous production to pilot-scale continuous production of orodispersible films was provided using solvent casting method under the framework of quality by design. Non-continuous production was carried out with petri dishes and continuous production was carried out with a coating machine. Films containing hydroxypropyl methylcellulose E5 as film forming polymer, polyethylene glycol 400 and propylene glycol as plasticizers, quetiapine fumarate as drug were formulated. Viscosity of the polymer dispersions, weight, thickness and disintegration time of the films were compared for the transfer of production. pH, moisture content, mechanical properties, folding endurance, uniformity of dosage units, dissolution, stability studies were also performed in pilot-scale orodispersible films. Finally, cytotoxicity studies were performed to determine cell viability. The study showed the possibility of producing F2-p-65/70 (pilot-scale film formulation containing 10 mg propylene glycol, dried at 65 degrees C and 70 degrees C) and F4-p-65/70 (pilot-scale film formulation containing 15 mg propylene glycol, dried at 65 degrees C and 70 degrees C), as the most suitable for further studies. Thus, a promising improvement has been achieved for schizophrenic patients by the production of quetiapine fumarate loaded orodispersible films and the process of scale-up in films has been demonstrated

Suboptimal use of non-vitamin K antagonist oral anticoagulants: Results from the RAMSES study

This study aimed to investigate the potential misuse of novel oral anticoagulants (NOACs) and the physicians' adherence to current European guideline recommendations in real-world using a large dataset from Real-life Multicenter Survey Evaluating Stroke Prevention Strategies in Turkey (RAMSES Study).RAMSES study is a prospective, multicenter, nationwide registry (ClinicalTrials.gov identifier NCT02344901). In this subgroup analysis of RAMSES study, patients who were on NOACs were classified as appropriately treated (AT), undertreated (UT), and overtreated (OT) according to the European Society of Cardiology (ESC) guidelines. The independent predictors of UT and OT were determined by multivariate logistic regression.Of the 2086 eligible patients, 1247 (59.8%) received adequate treatment. However, off-label use was detected in 839 (40.2%) patients; 634 (30.4%) patients received UT and 205 (9.8%) received OT. Independent predictors of UT included >65 years of age, creatinine clearance 50mL/min, urban living, existing dabigatran treatment, and HAS-BLED score of <3, whereas that of OT were creatinine clearance <50mL/min, ongoing rivaroxaban treatment, and HAS-BLED score of 3.The suboptimal use of NOACs is common because of physicians' poor compliance to the guideline recommendations in patients with nonvalvular atrial fibrillation (NVAF). Older patients who were on dabigatran treatment with good renal functions and low risk of bleeding were at risk of UT, whereas patients who were on rivaroxaban treatment with renal impairment and high risk of bleeding were at risk of OT. Therefore, a greater emphasis should be given to prescribe the recommended dose for the specified patients