Miracle-dz/UniFAR-FTUs huggingface dataset:
FDA statement on relationship between bisphosphonate use and atypical subtrochanteric and femoral shaft fractures: a considered opinion.

563 The location and description of the lowimpact fractures reported was consistent, and all patients had been undergoing longterm bisphosphonate therapy. To these authors, the fracture location and appearance was unique, unlike those seen in other conditions or causes. Specifically, insufficiency fractures of the lateral cortex of the femur with or without associated frank, complete fractures in patients with osteoporosis who do not take bisphosphonates are exceedingly rare, if indeed they occur at all. Schilcher and Aspenberg [6] calculated that when this pattern of femoral fracture was identified, the chance that the patient was undergoing longterm bisphosphonate therapy was 46 to 1. The association of this very specific pattern of femoral fracture and long-term bisphosphonate therapy seemed clear. These reports did not maintain that all fractures of the femur were related to long-term bisphosphonate use, only that this specific pattern of femoral fracture appeared to be so related. Furthermore, they did not claim that bisphosphonates have increased the number of femoral fractures. Many patients undergo bisphosphonate therapy. On the other hand, the related femoral fractures are quite rare. The signal-to-noise ratio is therefore quite low. Such fractures are difficult to identify in databases without specific information on the nature and specific imaging features of such fractures.
Lamina propria dendritic cells in the physiology and pathology of the gastrointestinal tract

Purpose of review The mucosal immune system constantly surveys the intestinal microbiota. The outcome of this interaction is determined by the functional properties of dendritic cells, which play a key role in immune response by facilitating antigen sampling and pathogen recognition, as well as innate host defenses. Recent findings Recent advances have provided insight into the diverse mechanisms involved in the acquisition of intestinal antigens and led to a new appreciation of organ-specific functional subspecification of dendritic cell subsets. Dendritic cells are not a rare cell type in the intestine but populate the entire lamina propria of the gastrointestinal tract as an extensive network. Distinct dendritic cell subsets may be associated with specific immune functions in the lamina propria and Peyer's patches. Newly discovered routes of antigen acquisition, such as the formation of transepithelial dendrites, allow dendritic cells direct access to the intestinal lumen to obtain information about commensal and pathogenic microorganisms. Dendritic cells emerge as key regulators of the intestinal immune system with their ability to direct intestine-specific migration and control of T cells. Summary Dendritic cells play a major role in the complex interactions between the gut microbiota and the innate and adaptive immune system, leading to tolerance and immunity. Recent contributions have yielded important information that may aid in the development of novel therapeutic approaches to the treatment of inflammatory bowl disease and intestinal infections and to new immunization strategies.
Intestinal and hepatic metabolism of glutamine and citrulline in humans

Glutamine plays an important role in nitrogen homeostasis and intestinal substrate supply. It has been suggested that glutamine is a precursor for arginine through an intestinal–renal pathway involving inter‐organ transport of citrulline. The importance of intestinal glutamine metabolism for endogenous arginine synthesis in humans, however, has remained unaddressed. The aim of this study was to investigate the intestinal conversion of glutamine to citrulline and the effect of the liver on splanchnic citrulline metabolism in humans. Eight patients undergoing upper gastrointestinal surgery received a primed continuous intravenous infusion of [2‐15N]glutamine and [ureido‐13C–2H2]citrulline. Arterial, portal venous and hepatic venous blood were sampled and portal and hepatic blood flows were measured. Organ specific amino acid uptake (disposal), production and net balance, as well as whole body rates of plasma appearance were calculated according to established methods. The intestines consumed glutamine at a rate that was dependent on glutamine supply. Approximately 13% of glutamine taken up by the intestines was converted to citrulline. Quantitatively glutamine was the only important precursor for intestinal citrulline release. Both glutamine and citrulline were consumed and produced by the liver, but net hepatic flux of both amino acids was not significantly different from zero. Plasma glutamine was the precursor of 80% of plasma citrulline and plasma citrulline in turn was the precursor of 10% of plasma arginine. In conclusion, glutamine is an important precursor for the synthesis of arginine after intestinal conversion to citrulline in humans.
Assessing natural resource management through integrated environmental and social-economic accounting

Local natural resource management in its diverse manifestations holds core to its principles that the marginal and vulnerable households are empowered to manage valuable natural resources to improve social and economic equality and conserve biodiversity. Yet studies aiming to identify the impacts often show inconsistent results. Through constructing an integrated Environmental and Social Accounting Matrix (ESAM), we aim to assess how natural resources are used in different sectors and by different livelihoods, thus delivering different direct and indirect benefits to the community. The study was conducted in Namibia’s Sikunga Conservancy, which manages wildlife and fish resources in the Zambezi region. Our village-level ESAM shows an economic structure that strongly disadvantages remote households and identifies a small sector of the economy that benefits significantly from the use of natural resources. The ESAM approach is able to isolate undesirable socioeconomic developments such as unequal benefit sharing, which hinders community development.
The Bile Acid Receptor TGR5 Does Not Interact with β-Arrestins or Traffic to Endosomes but Transmits Sustained Signals from Plasma Membrane Rafts*

Background: The TGR5 bile acid receptor controls energy balance, inflammation, and digestion, but TGR5 signaling is poorly understood. Results: TGR5 does not interact with β-arrestins, internalize, or desensitize, but signals from plasma membrane rafts. Conclusion: TGR5 transmits sustained signals close to the cell surface. Significance: Understanding TGR5 signaling will facilitate design of TGR5 agonists for metabolic, inflammatory, and digestive disorders. TGR5 is a G protein-coupled receptor that mediates bile acid (BA) effects on energy balance, inflammation, digestion, and sensation. The mechanisms and spatiotemporal control of TGR5 signaling are poorly understood. We investigated TGR5 signaling and trafficking in transfected HEK293 cells and colonocytes (NCM460) that endogenously express TGR5. BAs (deoxycholic acid (DCA), taurolithocholic acid) and the selective agonists oleanolic acid and 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N, 5-dimethylisoxazole-4-carboxamide stimulated cAMP formation but did not induce TGR5 endocytosis or recruitment of β-arrestins, as assessed by confocal microscopy. DCA, taurolithocholic acid, and oleanolic acid did not stimulate TGR5 association with β-arrestin 1/2 or G protein-coupled receptor kinase (GRK) 2/5/6, as determined by bioluminescence resonance energy transfer. 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N, 5-dimethylisoxazole-4-carboxamide stimulated a low level of TGR5 interaction with β-arrestin 2 and GRK2. DCA induced cAMP formation at the plasma membrane and cytosol, as determined using exchange factor directly regulated by cAMP (Epac2)-based reporters, but cAMP signals did not desensitize. AG1478, an inhibitor of epidermal growth factor receptor tyrosine kinase, the metalloprotease inhibitor batimastat, and methyl-β-cyclodextrin and filipin, which block lipid raft formation, prevented DCA stimulation of ERK1/2. Bioluminescence resonance energy transfer analysis revealed TGR5 and EGFR interactions that were blocked by disruption of lipid rafts. DCA stimulated TGR5 redistribution to plasma membrane microdomains, as localized by immunogold electron microscopy. Thus, TGR5 does not interact with β-arrestins, desensitize, or traffic to endosomes. TGR5 signals from plasma membrane rafts that facilitate EGFR interaction and transactivation. An understanding of the spatiotemporal control of TGR5 signaling provides insights into the actions of BAs and therapeutic TGR5 agonists/antagonists.
Suboptimal medication adherence in Parkinson's disease

Patients take less medication than prescribed in many disease areas but evidence for suboptimal therapy adherence in Parkinson's disease (PD) is limited. A single‐center observational study of antiparkinsonian medication was undertaken using electronic monitoring (MEMS; Aardex, Zug, Switzerland) over 3 months. Of 68 patients approached, 6 declined and 8 dropped out, leaving 54 patients (taking 117 preparations) with available data. Poorer compliance was associated significantly with younger age, with taking more antiparkinsonian tablets per day, with higher depression scores, and with poorer quality of life. Of the 54 evaluable patients, 11 (20%) had average total compliance of under 80% (underusers) and 43 (80%) had average total compliance of over 80% (satisfactory adherence). Underusers had median total compliance of 65% (interquartile range, 37–74) versus 98% (interquartile range, 93–102) in the satisfactory adherence group. Timing compliance (number of doses taken in the correct time interval) was poor in both underusers (median, 11%; interquartile range, 2–20) and those with satisfactory adherence (median, 25%; interquartile range, 11–73). In conclusion, poorer compliance is associated with younger age, depression, and more tablets per day, and one‐fifth of PD patients underuse medication. Consideration of drug therapy adherence has implications in the management of PD. © 2005 Movement Disorder Society
The mediating effect of work–family conflict in the relationship between job stress and intent to stay: The case of tourism and hospitality workers in Macau

ABSTRACT This study explores the mediating effect of work–family conflict in the relationship between job stress and intent to stay. The study revealed that once the intervention took place, employees' job stress has ceased to exert direct influence on their turnover intention. This signifies that work–family conflict is the underlying cause which discourages stressful employees to remain with their employer. The study was conducted in Macau to a group of tourism workers by means of street intercept survey.
Prevalence of IgG Antibodies to Toxoplasma gondii in Veterinary and Undergraduate Students at Virginia Tech, Blacksburg, Virginia

Toxoplasma gondii is a globally distributed parasitic protozoan that infects humans and other warm‐blooded vertebrates. Felids are the only definitive host for T. gondii, and they excrete oocysts in their faeces. The national prevalence in humans is declining in the United States. This zoonotic organism is of particular interest due to its importance in pregnant women, in individuals with altered immune systems, and in reactivated ocular infections. Exposure to the parasite in humans is usually associated with consumption of raw or undercooked meat or by accidental ingestion of oocysts. It was hypothesized that veterinary students would have a greater chance at exposure to the parasite than an average population of undergraduate students due to increased contact with cats who are infected. A commercially available ELISA was used to examine serum samples from 336 students (252 veterinary students and 84 undergraduate students) at Virginia Polytechnic Institute and State University and the Virginia‐Maryland Regional College of Veterinary Medicine for serum IgG antibodies to T. gondii antigen. The prevalence of T. gondii in these subjects was 5.6% in veterinary school students (n = 252) and 2.4% in undergraduates (n = 84). There was no significant difference (P > 0.05) in the prevalence of T. gondii antibodies in veterinary versus undergraduate students. The overall prevalence of 4.8% in all students in this study reflects the continuing decline of antibodies to T. gondii in humans in the United States.
Students with Physical Disabilities – Reflections of Their Experiences with Work Preparation Programs, Services and Accommodations in a Higher Education Institution

Part of the Accessibility Commons, Adult and Continuing Education Administration Commons, Adult and Continuing Education and Teaching Commons, Community College Education Administration Commons, Counselor Education Commons, Education Policy Commons, Higher Education Commons, Higher Education Administration Commons, Higher Education and Teaching Commons, Inequality and Stratification Commons, Junior High, Intermediate, Middle School Education and Teaching Commons, Other Educational Administration and Supervision Commons, Other Social and Behavioral Sciences Commons, Other Teacher Education and Professional Development Commons, Social Policy Commons, Special Education Administration Commons, and the Student Counseling and Personnel Services Commons
Comparison of genetic maps for two Leptospira interrogans serovars provides evidence for two chromosomes and intraspecies heterogeneity

Genetic maps were constructed for Leptospira interrogans serovars icterohaemorrhagiae and pomona. Previously we independently constructed physical maps of the genomes for these two serovars. The genomes of both serovars consist of a large replicon (4.4 to 4.6 Mb) and a small replicon (350 kb). Genes were localized on the physical maps by using Southern blot analysis with specific probes. Among the probes used were genes encoding a variety of essential enzymes and genes usually found near bacterial chromosomal replication origins. Most of the essential genes are on the larger replicon of each serovar. However, the smaller replicons of both serovars contain the asd gene. The asd gene encodes aspartate beta-semialdehyde dehydrogenase, an enzyme essential in amino acid and cell wall biosyntheses. The finding that both L. interrogans replicons contain essential genes suggests that both replicons are chromosomes. Comparison of the genetic maps of the larger replicons of the two serovars showed evidence of large rearrangements. These data show that there is considerable intraspecies heterogeneity in L. interrogans.
Vascular Barrier Regulation by PAF, Ceramide, Caveolae, and NO - an Intricate Signaling Network with Discrepant Effects in the Pulmonary and Systemic Vasculature

Increased endothelial permeability and vascular barrier failure are hallmarks of inflammatory responses in both the pulmonary and the systemic circulation. Platelet-activating factor (PAF) has been implicated as an important lipid mediator in the formation of pulmonary and extrapulmonary edema. Ostensibly, the PAF-induced signaling pathways in endothelial cells utilize similar structures and molecules including acid sphingomyelinase, ceramide, caveolae, endothelial nitric oxide synthase, and nitric oxide, in pulmonary and systemic microvessels. Yet, the constituents of these signaling pathways act and respond in distinctly different and frequently opposing ways in the lung versus organs of the systemic circulation. By confronting seemingly discrepant findings from the literature, we reconstruct the differential signaling pathways by which PAF regulates edema formation in the systemic and the pulmonary vascular bed, and trace this dichotomy from the level of myosin light chain kinase via the regulation of endothelial nitric oxide synthase and sphingomyelinase signaling to the level of caveolar trafficking. Here, we propose that PAF regulates vascular barrier function in individual organs by opposing signaling pathways that culminate in increased respectively decreased nitric oxide synthesis in the systemic and the pulmonary endothelium. The present review may provide a physiological explanation for the overall disappointing results of previous pharmacological strategies in conditions of generalized barrier failure such as sepsis, and instead advertises the development of organ-specific interventions by targeting the individual composition or trafficking of endothelial caveolae.
Does Socioeconomic Status Relate to Central Serotonergic Responsivity in Healthy Adults?

Objective: We tested whether low SES was associated with reduced central serotonergic responsivity in a community sample of adult men and women and the extent to which standardized measures of aggression and impulsivity mediate the association. Methods: A total of 270 adults who were enrolled in a clinical trial on the neurobehavioral effects of lipid lowering were given a neuropharmacologic challenge (plasma prolactin response to orally administered fenfluramine) to measure serotonergic responsivity. Measures of family income and educational attainment were standardized and summed to derive an overall index of SES. Scores from the Brown-Goodwin Life History of Aggression interview, the Barratt Impulsiveness Scale, and the Angry Hostility subscale from the NEO Personality Inventory were also standardized and summed to form an aggression/impulsivity score. Results: Low SES was correlated with low prolactin responses to the fenfluramine challenge in the full sample (r = .15) as well as in whites, men, and women evaluated separately. Although the standardized SES score was correlated inversely with aggression/impulsivity measure (r = −.19, p < .01), the association between SES and prolactin responses remained significant when statistical adjustments were made for age, gender, body mass index, and aggression/impulsivity scores. Conclusions: Blunted serotonergic responsivity is associated with low social class as measured by annual family income and educational attainment.
Simulating the longitudinal doctor−patient relationship: experiences of simulated patients in successive consultations

Context The use of simulated patients (SPs) in teaching communication and practical skills at medical schools is mostly limited to single‐case use: a student has 1 consultation with an SP and receives feedback afterwards. Very little literature is available that describes consecutive consultations between the same student and SP. In this study, we explored the experiences of SPs in a new, longitudinal SP programme in which SPs met the same Year 3 students (‘GP’) in 4 consecutive consultations during the year. The SPs suffered from a chronic disease in their patient roles.
Conference on ‘ Over-and undernutrition : challenges and approaches ’ Nutrition Society Silver Medal Lecture Beyond antioxidants : the cellular and molecular interactions of flavonoids and how these underpin their actions on the brain

The consumption of flavonoid-rich foods and beverages has been suggested to limit the neurodegeneration associated with a variety of neurological disorders and to prevent or reverse normal or abnormal deteriorations in cognitive performance. Flavonoids mediate these effects via a number of routes, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation and a potential to promote memory, learning and cognitive function. Originally, it was thought that such actions were mediated by the antioxidant capacity of flavonoids. However, their limited absorption and their low bioavailability in the brain suggest that this explanation is unlikely. Instead, this multiplicity of effects appears to be underpinned by three separate processes: first, through their interactions with important neuronal and glial signalling cascades in the brain, most notably the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways that regulate prosurvival transcription factors and gene expression; second, through an ability to improve peripheral and cerebral blood flow and to trigger angiogenesis and neurogenesis in the hippocampus; third, by their capacity to directly react with and scavenge neurotoxic species and pro-inflammatory agents produced in the brain as a result of both normal and abnormal brain ageing. The present review explores the potential inhibitory or stimulatory actions of flavonoids within these three systems and describes how such interactions are likely to underlie neurological effects.
Unmeasured Investment and the Puzzling Lost Decades of the Japanese Economy

For the mid to late 1990s and early 2000s, the basic neoclassical growth theory predicts a steady Japanese economy, when in fact the Japanese economy was depressed. This study applies the new theory with intangible investment and non-­neutral technology proposed by McGrattan & Prescott (2010) to the Japanese economy, and finds that the predictions derived from the new theory are much closer to the actual data. The improvement of this extension remains robust when tangible investment adjustment costs are added. This study is the first to apply the new theory to a country other than the US, and compared with existing literature on the lost decades of Japan, this study better explains the depression in labour hours by avoiding introducing a large, unjustified labour wedge or other exogenous inputs.
Young C3H mice infected with Toxoplasma gondii are a novel experimental model of communicating hydrocephalus

Abstract The effects of leptomeningeal inflammation on the development of hydrocephalus are less understood than those of obstructing the flow of cerebrospinal fluid (CSF) in animal models. We succeeded in introducing a novel experimental model of hydrocephalus and analysed changes in histopathology and CSF flow in mice infected with an avirulent Fukaya strain of Toxoplasma gondii (T. gondii). Six to 7 week-old male mice were orally inoculated with a brain homogenate containing ten T. gondii cysts. The cerebral ventricles became enlarged in all C3H/HeN and C57BL/6 mice 4 weeks after T. gondii infection, but mildly in BALB/c mice. In addition to the lateral ventricle, the third and fourth ventricles and Sylvian aqueducts were dilated in all mice. Lymphocytes and monocytes infiltrated the subarachnoid space. Indian ink particles required more time to pass from the lateral ventricle to the cervical lymph nodes, although they reached the subarachnoid space. Computed tomography ventriculography demonstrated that the CSF was not obstructed during passage through the ventricular systems, but contrast remained static in the lateral ventricle only in infected mice. These results indicated that the infected mice developed communicating type hydrocephalus without obstructive or mass lesions in the ventricles. The hydrocephalus that arises in mice infected with T. gondii is considered a consequence of leptomeningeal inflammation that blocks CSF circulation at the subarachnoid space, implying that leptomeningeal inflammation is important in other types of hydrocephalus.