bluuebunny/crossref_metadata_2025_split huggingface dataset:
FROM MICROBIOME TO METABOLOME
Authors: Vanhaecke L. 
Published: July 2016

At least 1,000 bacterial species and 1020 individual bacterial cells have been found to inhabit the human intestine. These symbiotic and commensal organisms are in intimate communication with the host, providing the host specific capacities ranging from dietary energy recovery to protection against infectious diseases. In parallel, there is increasing awareness that many health disorders involve a significant perturbation of metabolism, which is intrinsically linked to the gut functional ecology. Unlike the human genome, the microbiome is relatively plastic. It can be rapidly altered through factors such as diet, drugs and pro‐ and prebiotics.In the latter half of the 1990 s, mainly molecular‐biological approaches using 16S rRNA gene sequencing were used to analyze the intestinal microbiota. More recently, metagenomic techniques allowed to delineate the range of structural and functional configurations in normal microbial communities of healthy populations. In the last years, metabolomics (=analysis of the whole of metabolites) has surfaced as an important tool to determine how human metabolic processes interact with those of gut microbiota and diet. By measuring the true metabolic end points at the end of the biomolecular gene‐protein‐metabolite cascade, the metabolic fingerprint provides the most accurate assessment of the biological state. In fact, metabolic fingerprinting offers new opportunities to explore individual needs in terms of foods, medication, etc. to formulate tangible biological hypotheses that can be tested at individual and population scale. Moreover, it enables the discovery of metabolic features, which characterize pathological and physiological states and may serve as diagnostic, prognostic or predictive disease biomarkers.
PROBIOTICS DELIVERY
Authors: Marzorati M. 
Published: July 2016

Probiotics can be defined as live microorganisms which when administered in adequate amounts confer a health benefit to the host. Two crucial aspects determining the success of a probiotic treatment are the resistance of the bacteria to stomach acids and bile salts in the upper gastrointestinal tract (GIT) and their capacity to compete with the indigenous microbiota in the colon by eventually adhering to the mucus layer covering the gut wall. If these requirements are fulfilled, successful colonization of the intestinal tract can be expected, which might then result in beneficial effects on human health. The capacity to colonize the gastrointestinal tract is largely depending on the intrinsic characteristics of the probiotic strains (e.g. acid and bile tolerance), yet also on the specific formulation in which they are delivered to the gut. Formulations which protect the bacteria from the harsh conditions in the stomach and small intestine allow the probiotics to reach the colon under optimal conditions, which will of course allow more efficient competition with the resident microbial community.The Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) has been used to assess how microencapsulation, gastric resistant capsules and food matrices (i.e. fermented milk or chocolate) can enhance the survival of the probiotic strains during the transition in the upper GIT under either fasted or fed conditions.
HUMAN MILK OLIGOSACCHARIDES
Authors: Soetaert W. 
Published: July 2016

Human milk oligosaccharides are very complex molecules and hence are difficult to synthesize. These specialty carbohydrates are consequently very expensive and not available in sufficient quantities. Enzymatic synthesis is efficient for relatively simple carbohydrates but cannot be used for more complex carbohydrates. For the synthesis of highly complex carbohydrates, organic synthesis is not an efficient production method because of the high chirality and excessive presence of hydroxylic groups in the carbohydrate building blocks. Also extraction of these compounds from natural sources is hampered by the substrate availability and extraction cost.To solve this problem, an efficient biotechnological production method for specialty carbohydrates has been developed. The method is based on the use of microbial cells in which a natural pathway has been expressed for the synthesis of the target specialty carbohydrate. Base strains that are engineered to generate the carbohydrate building blocks are equipped with a functional enzymatic pathway to produce the target specialty carbohydrate.Using this platform technology, any naturally occurring specialty carbohydrate can be produced. Depending on the target, a biochemical pathway will be designed and expressed in one of the base strains. Through pathway engineering and optimisation, the production strains are optimised. The target carbohydrate is then produced by fermentation and is efficiently excreted in the culture medium. After fermentation, the target carbohydrate is recovered from the fermentation broth in high yield and purity using a down‐stream processing method.This production method is generic and has been proven at pilot scale. The process is scaleable so that the availability of such carbohydrates is no longer the bottleneck. The Ghent University spin‐off company Inbiose is perfecting this technology and is currently able to produce over 100 t/a of these specialty carbohydrates.The presentation will explain the features of the platform technology and will highlight concrete examples to produce a human milk oligosaccharide.
MECHANISMS OF ANTIDIARRHEAL EFFECT BY PROBIOTICS
Authors: Guarino A. , Ruberto E. , Buccigrossi V. 
Published: July 2016

Gastroenteritis is a major cause of morbidity and mortality worldwide. Several microbial pathogens cause secretory diarrhea such as Vibrio cholerae and enterotoxigenic Escherichia coli as well as enteric viruses such as Rotavirus (RV) and Norovirus and parasites including Cryptosporidium. Other agents induce inflammatory diarrhea such as Clostridium difficile, Shigella and selected strains of pathogenic E. coli.Gastroenteritis is the result of multiple mechanisms that may mainly be summarized in enterotoxic (secretory diarrhea) or cytotoxic (osmotic diarrhea) as a consequence of ion secretion and epithelial damage, respectively. Other indirect mechanisms of infectious diarrhea include inflammation or altered regulatory processes involving hormones and neurotransmitters.The first‐line treatment of acute gastroenteritis in children is the administration of oral rehydration solution (ORS) but this neither shortens the duration of diarrhea nor reduces the frequency of stool outputs. Therefore, active therapies are now recommended in adjunct to ORS for children with gastroenteritis.The use of the specific probiotic strains, namely Lactobacillus rhamnosus GG (LGG) and Saccharomyces boulardii, is included ESPGHAN/ESPID guidelines for the management of children with AGE as an adjunct to rehydration therapy.Antidiarrheal drugs act at the luminal side of intestinal epithelium and modulate apical pathways, induce ion absorption or limit secretion, influence microbiome, modulate permeability, bind secretory moieties such as enterotoxins or bile acids. Probiotics are not drugs, but are rapidly effective in acute diarrhea reducing its duration and their effects have been linked to intestinal permeability and the modulation of intestinal microbiota and‐ indirectly‐ of inflammation. Those mechanisms are not consistent with the rapid effects of probiotics observed in children with acute diarrhea within hours since their initial administration. Evidence exists in favor of direct effects induced by probiotics on the enterocyte. Saccharomyces boulardii secreted moieties prevented RV‐induced oxidative stress and chloride secretion in human enterocytes. LGG exerted an ion proabsorptive effect through a direct antioxidant mechanisms and also promoted cell growth and differentiation acting on MAPKs. Those data indicate that the rapid and effective clinical effects by probiotics on acute diarrhea are probably the results of the direct microbe‐enterocyte rather than to the microbe‐microbiota or microbe‐immune interaction. This data provide an entirely new scenario for understanding the antidiarrheal mechanisms of probiotics in diarrhea.
MICROBIOTA AND HELICOBACTER PYLORI
Authors: Bontems P. 
Published: July 2016

Long, the stomach was considered sterile because of its hostile environment for bacteria (acid pH, proteolytic enzymes, etc), its main functions being said to initiate the digestion and to inactivate pathogenic microorganisms present in the alimentation. Indeed, an hypochlorhydria or achlorhydria due to gastric anti‐secretory drugs or following gastric atrophy was known to increases the sensitivity to intestinal infections. The discovery of the pathogenic role of Helicobacter pylori (H. pylori) in 1982, however, ended this dogma.It is now clear, however, from various studies performed over the past 10 years, that H. pylori is not the only bacterium able to colonize the human stomach. Different other bacteria have been isolated from the gastric lumen as well as from the outer and the inner part of the mucus layer in close contact with the mucosa. The composition of the gastric microbiota is not perfectly known at present since it remains difficult to distinguish in gastric samples the living bacteria from the dead ones but also to distinguish those that colonize the stomach of those that have been swallowed with food or saliva.The most common component and numerically the largest gastric microbiota component is clearly H. pylori. For about 50 years, the prevalence of H. pylori, however, has decreased in developed countries and the possible consequences of this disappearance on human health are still not well known. Some studies suggest a role of its disappearance in increasing allergic disorders and oesophageal cancer.The density and the diversity of the gastric microbiota is low in comparison with the intestinal microbiota. It has been estimated that about 200 different species can coexist in the stomach. The composition of the gastric microbiota may be influenced by food and mode of delivery at birth but also by the reduction of acid secretion (following the anti‐secretory drugs or following gastric atrophy) and the abundance of H. pylori. The gastric microbiota changes also affect the gut microbiota. There are no clinical implication for the analysis of the gastric microbiota for the moment but this is a fascinating research topic.
PROBIOTICS FOR THE PREVENTION OF PEDIATRIC UPPER RESPIRATORY TRACT INFECTIONS
Authors: Ozen M. 
Published: July 2016

Acute upper respiratory infections (URTIs) are the most common reason for physician referral in childhood period and contribute substantially to pediatric morbidity and mortality worldwide. Prevention of these infections is a very important public health challenge. Even a minimal reduction, 5–10%, in the incidence of URTIs would have important clinical and economical impact on human race.An URTI prevention method should be simple, easily‐available, low cost and without adverse reactions. The previous systematic reviews including adult and childhood populations reported that probiotics seem promising, but with modest evidence. The currently available studies suggest that probiotics in otherwise healthy children have a moderate effect in prevention of URTIs and diminish the severity of the infection symptoms. At least one beneficial effect of prophylactic probiotic use either on the incidence of URTIs or severity of a single episode was observed in the majority of randomized controlled studies (RCTs).Furthermore, the long‐term administration of probiotics appeared to have a good safety profile in childhood and none of the studies did report any serious adverse events related to probiotic strain. A better understanding of the effects of different probiotic strains and a deeper insight into their mechanisms of action are needed. Further RCTs better study and report biological and microbiological effects of probiotic strains in order to validate the potential to modify the frequency and severity of URTIs in infants and children.
PROBIOTICS IN URINARY TRACT INFECTION
Authors: Kara Ates 
Published: July 2016

Urogenital infections, defined as that affect the bladder, kidneys, vagina, urethra, periurethra, and cervix, constitute a worldwide problem that affects both children and adults especially women. The main clinical outcome is morbidity and discomfort, in addition in developing world it is the leading cause of chronic renal disease and also enormous costs to the health care system for treatment.Majority (≈70%) of urinary tract infection (UTI) nonhospitalized community is caused by Escherichia coli, followed by other enterobacteriaciae and Staphylococcus saprophyticus.The origin of the uropathogens in uncomplicated UTI is the fecal flora. The key factor in the development of UTI is the ability of the pathogens to attach to epithelial cells, by this way they gained a niche that multiply, spread, and avoid host defenses. There are also, host susceptibility factors, including genetic determinants, age‐related changes, and mucosal differences that increased the risk of infection.It has been shown that more than 50 species colonize the healthy vagina in adult women. Studies have shown that urogenital cells are covered by dense bacterial biofilms whose composition changes constantly but in which lactobacilli predominate. Uropathogenic organisms emerge from the intestine and come into contact with these biofilms on vaginal and urethral cells. It is presumed that uropathogens can either bypass the microflora or successfully enter the biofilms, survive, and continue their ascension into the bladder.Studies have shown that antibiotic exposure can cause disruption of the urogenital microflora and increase risk of infection.The dominant presence of lactobacilli in the urogenital microflora and the obliteration of lactobacilli in patients who develop UTI. Lactobacilli are gram‐positive rods, primarily facultative or strict anaerobes that generally have a fastidious growth requirement. They prefer an acidic environment and help create one by producing lactic and other acids.The use of probiotics per se and lactobacilli specifically has received greater attention as an alternative, and natural remedy to restore and maintain health. Two strains, Lactobacillus GG and Lactobacillus rhamnosus appear to be effective at colonizing and protecting the intestine and urogenital tract, against microbial infection.There is now growing evidence that certain species and strains present in the healthy urogenital tract protect the host against infection by pathogenic microorganisms. Many properties required to confer this protection have been identified, but evidence of their expression in vivo is scant and the relative significance of each is unknown. The concept of treating and preventing urogenital infection by instillating probiotic organisms has great appeal to patients and caregivers.
Recognizing Privilege and Bias: An Interactive Exercise to Expand Health Care Providers’ Personal Awareness
Authors: Holm Amanda L. , Rowe Gorosh Marla , Brady Megan , White-Perkins Denise 
Published: July 2016

Problem
Despite increasing awareness of the social determinants of health, health care disparities among sociocultural groups persist. Health care providers’ unconscious bias resulting from unrecognized social privilege is one contributor to these disparities.

Approach
In 2009, Henry Ford Health System initiated the Healthcare Equity Campaign both to raise employees’ awareness of inequalities related to the social determinants of health and to increase their motivation to reduce them. After conducting awareness-raising activities to increase employees’ understanding of the social determinants of health, a curriculum team developed the interactive Privilege and Responsibility Curricular Exercise (PRCE) and incorporated it into a series of trainings. The team designed the exercise to enhance participants’ awareness of privilege in their lives and work, to improve their understanding of the impact of privilege on their own and others’ lived experiences as a step beyond cultural competence toward cultural humility, and to encourage them to leverage their advantages to reduce health care inequities.

Outcomes
About 300 participants of diverse professional and personal backgrounds from across the health system completed the training between the spring of 2009 and the spring of 2012, and many provided qualitative feedback about the exercise. Evaluations showed the exercise’s potential as a powerful learning experience that might enhance a variety of equity- or diversity-related trainings, and also showed that participants considered the PRCE a highlight of the training.

Next Steps
The PRCE is worthy of additional study and could prove valuable to other organizations.
Entrusting Observable Practice Activities and Milestones Over the 36 Months of an Internal Medicine Residency
Authors: Warm Eric J. , Held Justin D. , Hellmann Michael , Kelleher Matthew , Kinnear Benjamin , Lee Caroline , O’Toole Jennifer K. , Mathis Bradley , Mueller Caroline , Sall Dana , Tolentino Jonathan , Schauer Daniel P. 
Published: July 2016

Purpose
Competency-based medical education and milestone reporting have led to increased interest in work-based assessments using entrustment over time as an assessment framework. Little is known about data collected from these assessments during residency. This study describes the results of entrustment of discrete work-based skills over 36 months in the University of Cincinnati internal medicine (IM) residency program.

Method
Attending physician and peer/allied health assessors provided entrustment ratings of resident performance on work-based observable practice activities (OPAs) mapped to Accreditation Council for Graduate Medicine Education/American Board of Internal Medicine reporting milestones for IM. These data were translated into milestones data and tracked longitudinally. The authors analyzed data from this new entrustment system’s first 36 months (July 2012–June 2015).

Results
During the 36-month period, assessors made 364,728 milestone assessments (mapped from OPAs) of 189 residents. Residents received an annualized average of 83 assessment encounters, producing means of 3,987 milestone assessments and 4,325 words of narrative assessment. Mean entrustment ratings (range 1–5) from all assessors for all milestones rose from 2.46 for first-month residents to 3.92 for 36th-month residents (r
2 = 0.9252, P < .001). Attending physicians’ entrustment ratings were lower than peer/allied health assessors’ ratings. Medical knowledge and patient care milestones were rated lower than professionalism and interpersonal and communication skills milestones.

Conclusions
Entrustment of milestones appears to rise progressively over time, with differences by assessor type, competency, milestone, and resident. Further research is needed to elucidate the validity of these data in promotion, remediation, and reporting decisions.
Preoperative Falls and Their Association with Functional Dependence and Quality of Life
Authors: Kronzer Vanessa L. , Tang Rose D. , Schelble Allison P. , Ben Abdallah Arbi , Wildes Troy S. , McKinnon Sherry L. , Sadiq Furqaan , Lin Nan , Helsten Daniel L. , Sharma Anshuman , Stark Susan L. , Avidan Michael S. 
Published: July 2016

Abstract

Background
No study has rigorously explored the characteristics of surgical patients with recent preoperative falls. Our objective was to describe the essential features of preoperative falls and determine whether they are associated with preoperative functional dependence and poor quality of life.

Methods
This was an observational study involving 15,060 surveys from adult patients undergoing elective surgery. The surveys were collected between January 2014 and August 2015, with a response rate of 92%.

Results
In the 6 months before surgery, 26% (99% CI, 25 to 27%) of patients fell at least once, and 12% (99% CI, 11 to 13%) fell at least twice. The proportion of patients who fell was highest among patients presenting for neurosurgery (41%; 99% CI, 36 to 45%). At least one fall-related injury occurred in 58% (99% CI, 56 to 60%) of those who fell. Falls were common in all age groups, but surprisingly, they did not increase monotonically with age. Middle-aged patients (45 to 64 yr) had the highest proportion of fallers (28%), recurrent fallers (13%), and severe fall-related injuries (27%) compared to younger (18 to 44 yr) and older (65+ yr) patients (P < 0.001 for each). A fall within 6 months was independently associated with preoperative functional dependence (odds ratio, 1.94; 99% CI, 1.68 to 2.24) and poor physical quality of life (odds ratio, 2.18; 99% CI, 1.88 to 2.52).

Conclusions
Preoperative falls might be common and are possibly often injurious in the presurgical population, across all ages. A history of falls could enhance the assessment of preoperative functional dependence and quality of life.
Perioperative Visual Loss in Spine Fusion Surgery
Authors: Rubin Daniel S. , Parakati Isaac , Lee Lorri A. , Moss Heather E. , Joslin Charlotte E. , Roth Steven 
Published: July 2016

Abstract

Background
Perioperative ischemic optic neuropathy (ION) causes visual loss in spinal fusion. Previous case–control studies are limited by study size and lack of a random sample. The purpose of this study was to study trends in ION incidence in spinal fusion and risk factors in a large nationwide administrative hospital database.

Methods
In the Nationwide Inpatient Sample for 1998 to 2012, procedure codes for posterior thoracic, lumbar, or sacral spine fusion and diagnostic codes for ION were identified. ION was studied over five 3-yr periods (1998 to 2000, 2001 to 2003, 2004 to 2006, 2007 to 2009, and 2010 to 2012). National estimates were obtained using trend weights in a statistical survey procedure. Univariate and Poisson logistic regression assessed trends and risk factors.

Results
The nationally estimated volume of thoracic, lumbar, and sacral spinal fusion from 1998 to 2012 was 2,511,073. ION was estimated to develop in 257 patients (1.02/10,000). The incidence rate ratio (IRR) for ION significantly decreased between 1998 and 2012 (IRR, 0.72 per 3 yr; 95% CI, 0.58 to 0.88; P = 0.002). There was no significant change in the incidence of retinal artery occlusion. Factors significantly associated with ION were age (IRR, 1.24 per 10 yr of age; 95% CI, 1.05 to 1.45; P = 0.009), transfusion (IRR, 2.72; 95% CI, 1.38 to 5.37; P = 0.004), and obesity (IRR, 2.49; 95% CI, 1.09 to 5.66; P = 0.030). Female sex was protective (IRR, 0.30; 95% CI, 0.16 to 0.56; P = 0.0002).

Conclusions
Perioperative ION in spinal fusion significantly decreased from 1998 to 2012 by about 2.7-fold. Aging, male sex, transfusion, and obesity significantly increased the risk.