Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of the UGT2B7 promoter region and exon 2 polymorphisms and comedications on Acyl-MPAG production in vitro and in adult renal transplant patients

Introduction The polymorphic enzyme UGT2B7 metabolizes mycophenolic acid into acyl-mycophenolic acid-glucuronide (AcMPAG), a presumably toxic metabolite. This study aimed at investigating in vitro and in vivo the impact on AcMPAG production of: (i) the UGT2B7 gene G-842A single nucleotide polymorphism, in complete linkage disequilibrium with most other known single nucleotide polymorphisms in the promoter region of this gene and with the C802T single nucleotide polymorphism in exon 2 (UGT2B*2); and (ii) of the other immunosuppressants given to renal transplant patients in association with mycophenolate mofetil. Methods We compared the production of AcMPAG by human liver microsomes genotyped for the UGT2B7 G-842A and C802T single nucleotide polymorphisms, and plasma AcMPAG concentrations in genotyped renal transplant patients administered mycophenolate mofetil associated with sirolimus (n=40), tacrolimus (n=24) or cyclosporin (n=28) and decreasing doses of corticosteroids, over the first 3 months after transplant. The effect of corticosteroids was also investigated in vitro using rats' liver microsomes. Results The two polymorphisms studied were in complete reverse linkage disequilibrium. AcMPAG production was 1.25 and 1.56-fold higher in G-842A and −842AA human liver microsomes, respectively, compared with GG-842 human liver microsomes (P=0.01). Enzyme kinetics showed 1.4 and 3.7-fold higher Vmax in the respective pools of human liver microsomes. Km values were 0.20, 0.25 and 0.44 mmol/l for the GG-842, G-842A and −842AA genotypes, respectively. This clear increase in Vmax is in favor of the implication of the promoter region polymorphisms, whereas the slighter increase in Km might be due to the UGT2B7*2 single nucleotide polymorphism. Consistently, the UGT2B7 genotype significantly influenced AcMPAG area under the curve (AUC0–9 h)/dose in patients on sirolimus at months 1 and 3 after transplant (P=0.04 for both). No effect was observed in patients on tacrolimus and possibly also on cyclosporin, maybe owing to pharmacokinetic interaction with mycophenolate. AcMPAG production was increased in corticosteroid-induced rat liver microsomes, consistent with the observed in-vivo decrease of mycophenolic acid metabolites AUC0–9 h/dose with time after transplant. Conclusion Both UGT2B7 polymorphisms and comedications significantly influenced AcMPAG production, but cyclosporin and tacrolimus hindered the phenotypic impact of this trait.
I Can Carry On From Here: The Relocation of American Indians to Los Angeles

Elizabeth Murphy, a Luisefio Indian, and her new roommates at the Regina Hotel in downtown Los Angeles quickly became good friends. "We never went anywhere alone," she remembers. "We always held hands. "' For these four young women living away from home for the first time, Los Angeles in 1967 contrasted dramatically with their rural homes in Montana, South Dakota, and Southern California where running water and electricity were considered luxuries. For Elizabeth, the seemingly endless, crowded streets of downtown Los Angeles vastly differed from the dirt roads of her small community of four extended families at Pechanga.2 Although not geographically far from her home, Elizabeth's new environment required immediate, unfamiliar adjustments. Surviving in Los Angeles took on added dimensions at the Regina Hotel which was used not only by the Bureau of Indian affairs to house these American Indian women but also by the State of California for recently released prisoners. Despite the opportunities for city jobs, the exciting attractions of Los Angeles, and the many conveniences of urban life, Elizabeth and her roommates "all just talked about going home. "3 These brief glimpses into Elizabeth Murphy's first weeks in Los Angeles poignantly reveal the challenges confronting her and her roommates in Los Angeles. Like thousands of other American Indians, they had moved to Los Angeles to take part in federally-sponsored job and job training programs. Arriving from disparate communities with unique historical conditions and societal organizations, American Indians brought to Los Angeles their own different cultural systems and community experiences. Each individual, ultimately, faced the challenge of personally negotiating his or her cultural identity in the new and hostile city. As Elizabeth relates, once in Los Angeles she and her roommates immediately established close emotional ties. These bonds were continuously reinforced through their constant companionship and further supported through hand holding. For these previously unacquainted American Indians alone in downtown Los Angeles, hand-holding was not only reassuring but also physically signified to each other and publicly their collective sense of solidarity and friendship. Elizabeth's repeated emphasis on lasting notions of time, "never 'and "always,' indicates the importance of these bonds during this disorienting and often frightening process of urbanization. Elizabeth Murphy's experiences are similar to those
Issues in Understanding the Impact of the Needlestick Safety and Prevention Act on Hospital Sharps Injuries

Objective. Measuring the effect of the Needlestick Safety and Prevention Act (NSPA) is challenging. No agreement exists on a common denominator for calculating injury rates. Does it make a difference? How are the law and safety-engineered devices related? What is the effect on injuries and costs? This study examines those issues in assessing the impact of the legislation on hospital worker percutaneous injuries. Methods. Using a historic prospective design, we analyzed injury data from 85 hospitals. Injury rates were calculated per 100 full-time equivalents, 100 staffed beds, and 100 admissions each year from 1995 to 2005. We compared changes for each denominator. We measured the proportion of the injury rate attributed to safety-engineered devices. Finally, we estimated a national change in injuries and associated costs. Results. For all denominators, a precipitous drop in injury rates of greater than one-third (P<.001) occurred in 2001, immediately following the legislation. The decrease was sustained through 2005. Concomitant with the decrease in rates, the proportion of injuries from safety-engineered devices nearly tripled (P <.001) across all denominators. We estimated annual reductions of more than 100,000 sharps injuries at a cost savings of $69-$415 million. Conclusions. While the data cannot demonstrate cause and effect, the evidence suggests a reduction in hospital worker injury rates related to the NSPA, regardless of denominator. It also suggests an association between the increase in safety-engineered devices and the reduction in overall injury rates. The decreases observed translate into significant reductions in injuries and associated costs.
Challenges Addressing Unmet Need for Contraception: Voices of Family Planning Service Providers in Rural Tanzania

Provider perspectives have been overlooked in efforts to address the challenges of unmet need for family planning (FP). This qualitative study was undertaken in Tanzania, using 22 key informant interviews and 4 focus group discussions. The research documents perceptions of healthcare managers and providers in a rural district on the barriers to meeting latent demand for contraception. Social-ecological theory is used to interpret the findings, illustrating how service capability is determined by the social, structural and organizational environment. Providers' efforts to address unmet need for FP services are constrained by unstable reproductive preferences, low educational attainment, and misconceptions about contraceptive side effects. Societal and organizational factors--such as gender dynamics, economic conditions, religious and cultural norms, and supply chain bottlenecks, respectively--also contribute to an adverse environment for meeting needs for care. Challenges that healthcare providers face interact and produce an effect which hinders efforts to address unmet need. Interventions to address this are not sufficient unless the supply of services is combined with systems strengthening and social engagement strategies in a way that reflects the multi-layered, social institutional problems.
Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of torasemide in rabbits

The pharmacokinetics and pharmacodynamics of torasemide were evaluated after intravenous administration of the same total dose of torasemide at a dose of 1mg/kg to rabbits with different infusion times, 1 min (treatment I), 30 min (treatment II) and 2 h (treatment III). The loss of water and electrolytes in urine induced by torasemide was immediately replaced with infusion of an equal volume of lactated Ringer's solution. All the pharmacokinetic parameters of torasemide, such as total area under the plasma concentration–time curve from time zero to time infinity (AUC), total body clearance (CL), apparent volume of distribution at steady state (Vss), terminal half‐life and mean residence time (MRT), were independent of infusion times. However, the 8h urine output (235, 534 and 808 ml) and 8h urinary excretion of sodium (24.2, 80.1 and 89.2 mmol) and chloride (27.1, 89.2 and 94.0 mmol) were significantly greater in treatments II and III than those in treatment I, although the total 8 h urinary excretion of unchanged torasemide (1210, 1210 and 1310 µg) were not significantly different among the three treatments. This could be due to the higher diuretic efficiencies in treatments II and III. Copyright © 2004 John Wiley & Sons, Ltd.
The Recognition Memory Deficit Caused by Mediodorsal Thalamic Lesion in Non‐human Primates: A Comparison with Rhinal Cortex Lesion

Two earlier studies found that rhinal cortex ablations in the monkey (Macaca fascicularis) impaired delayed matching‐to‐sample (DMS) when the stimuli in the experiment came from a large population of possible stimuli, but not when the stimulus population was small, while uncinate fascicle section had no effect on DMS whatever the stimulus population size. The mediodorsal thalamus receives a large projection from the rhinal cortex, and has been implicated in recognition memory performance. We trained monkeys preoperatively in delayed matching‐to‐sample with large and small stimulus populations, exactly as in the earlier studies, then examined the effect of bilaterally ablating the medial portion of the mediodorsal thalamic nucleus. Mediodorsal lesion impaired postoperative delayed matching‐to‐sample performance with a large stimulus set, but had no effect on performance of DMS with a small stimulus population. In comparison with the earlier data from rhinal cortex lesions with the same methods, wherever a deficit was seen in the rhinal‐lesioned animals the mediodorsal thalamic nucleus‐lesioned animals showed a smaller deficit. We conclude that other efferents from the rhinal cortex, possibly those to the adjacent inferior temporal cortex, enable better performance in the mediodorsal thalamic nucleus‐lesioned animals than in the animals with rhinal cortex ablation.
High-risk human papilloma virus in archival tissues of oral pathosis and normal oral mucosa

Objectives: Oral cancer ranks third among all cancers in the Indian population. Human papilloma virus (HPV) plays a significant role in oral carcinogenesis. Population-based subtype variations are present in the HPV prevalence. This study gives an emphasis on the parameters to be considered in formalin fixed paraffin embedded tissues for polymerase chain reaction (PCR)-based research work. Materials and Methods: Cross-sectional study on archival paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC), epithelial dysplasia, and normal oral mucosa surrounding impacted tooth was amplified by PCR for the E6 gene of HPV type 16 and E1 gene of HPV type 18. Results: HPV 18 was positive in three OSCC cases. There was no statistically significant association of the positivity of HPV with the age, gender or habit. The HPV positive patients had a tobacco habit and were of a younger age group. Conclusion: The presence of HPV in carcinomatous tissue highlights the possible role of HPV in carcinogenesis and archival paraffin embedded tissue specimen can be used for this analysis. Recent studies on genomic analyses have highlighted that the HPV positive tumors are a separate subgroup based on genomic sequencing. The results of a larger retrospective study will help further in our understanding of the role of HPV in carcinogenesis, this study could form the baseline for such follow-up studies.
Types and duration of symptoms prior to diagnosis of invasive or borderline ovarian tumor.

OBJECTIVE The objective was to describe and compare types and duration of symptoms among women with invasive versus borderline ovarian tumors. METHODS Cases were women, ages 20-69 years, diagnosed with invasive (616) and borderline (151) epithelial ovarian tumors from 1994 to 1998. Symptoms were obtained using a standardized in-person interview. Differences in types and duration of symptoms, time to diagnosis after consulting a physician, and primary reason for diagnosis by invasive/borderline status and histologic type were determined using bivariate and regression analyses controlling for age. RESULTS Borderline and invasive cases reported similar types of symptoms. However, borderline cases were twice as likely to report not having had symptoms as invasive cases (16 vs 8%, P = 0.005). Prediagnostic symptom duration was longer among borderline versus invasive cases (median: 6 vs 4 months, P < 0.001). The median time from first consultation with a physician to diagnosis (1 month) did not differ by invasive/borderline status. Borderline cases were twice as likely to be diagnosed through routine examination as invasive cases (28 vs 16%, P = 0.001). Invasive cases were more likely to be diagnosed because of symptoms (62 vs 48%, P = 0.002). CONCLUSIONS Because most (90%) women with ovarian tumors have symptoms and median symptom duration is 4 months, greater awareness of symptoms by women and physicians is needed for the earlier detection of ovarian tumors. The lesser likelihood of being detected by routine examination and the shorter symptom duration for invasive versus borderline cases underscores the need for effective screening and preventive strategies.
Ultrasonographic findings of painful shoulders and correlation between physical examination and ultrasonographic rotator cuff tear

The objectives of this study were to identify ultrasonographic (US) abnormalities and to compare physical examination with US findings, especially of rotator cuff abnormalities in patients with shoulder pain. A total of 120 patients with shoulder pain were prospectively studied. The physical examination of shoulders was performed as follows: (1) the area of tenderness; (2) the range of passive and active motion for abduction, forward flexion, external rotation, and internal rotation; (3) Neer and Hawkins's tests for shoulder impingement; and (4) maneuvers for determining the location of the tendon lesions. Transverse and longitudinal planes from the long head of the biceps, supraspinatus, infraspinatus, and subscapularis tendons, the subacromial-subdeltoid bursa, and the glenohumeral and acromioclavicular joints were included for US examination. The range of motion most affected by shoulder pain was abduction, followed by external rotation and forward flexion. The most frequent US finding was effusion in the long head of the biceps tendon. Among the rotator cuff tendons, supraspinatus was the most frequently involved. Physical examination had low sensitivity and specificity for the detection of tendon tear. US examination leads to an anatomical diagnosis of shoulder pain in many patients. Whether the US examination of the painful shoulder improves its treatment should be investigated.
Altered striatal amino acid neurotransmitter release monitored using microdialysis in R6/1 Huntington transgenic mice

Huntington's disease is an autosomal dominant disease which presents with striatal and cortical degeneration causing involuntary movements, dementia and emotional changes. We employed 16‐week‐old transgenic Huntington mice (R6/1 line developed by Bates and coworkers) that express exon 1 of the mutant human Huntington gene with 115 CAG triplet repeats. At this age, R6/1 mice do not exhibit an overt neurological phenotype nor any striatal neuronal loss. Using microdialysis, we monitored basal and intrastriatal N‐methyl d‐aspartate (NMDA, 100 µm, 15 min)‐ and KCl (100 mm, 15 min)‐induced increases in local aspartate, glutamate and GABA release in halothane‐anaesthetized transgenic mice and wild‐type controls. Basal striatal dialysate glutamate levels were reduced by 42% in R6/1 mice whilst aspartate and GABA levels did not differ from those observed in control mice. Intrastriatal NMDA was associated with significantly greater aspartate (at 15 min) and GABA (at 30 min) levels in the R6/1 mice compared to controls, whilst glutamate release rapidly increased to the same extent in both groups. Intrastriatal KCl was associated with enhanced increases (30 min) in local aspartate and glutamate release in the R6/1 mice above those observed in controls whilst the rapid increase (15 min) in GABA release was similar in both groups. The results provide compelling evidence for specific alterations in both basal, as well as NMDA‐ and KCl‐induced, release of striatal amino acid neurotransmitters in this transgenic model of Huntington's disease, even in the absence of manifest neurodegeneration.
Analysis of Human Epidural Pressures

Background and Objectives. During performance of epidural injection, entry into the epidural space has traditionally been determined by identification of negative pressure to the advancing needle by indirect means such as hanging drop; loss of resistance to air, saline, or water; or use of a MacIntosh balloon. Confusion in the literature regarding entry pressures versus postentry (baseline) pressures and zero reference pressure was noted. Methods. Baseline epidural pressure changes were examined using a closed system zeroed to the dorsal spine during and after injection of local anesthetics in 39 patients referred to the Pain Treatment Center, located at SUNY Health Science Center, Syracuse, New York, for epidural injections. The course of epidural pressure changes after injection and the temporal relation of epidural pressure waves to the arterial and venous wave forms were examined. Results. In contrast to previous investigations, subatmospheric pressure was found in the epidural space in only one patient. Baseline pressure for all patients was 7.7 ± 3.9 mmHg. There were significant differences in baseline pressure in patients who had undergone back surgery compared with patients who had not undergone such surgery: 11.8 ± 3.4 as opposed to 7.0 ± 3.5 mmHg, respectively ( p < 0.005). Three minutes after a 2-ml injection of local anesthetic into the epidural space, the pressure returned to baseline. This contrasted to the effects of a 6-ml injection, which resulted in the pressure remaining above baseline after 3 minutes. The epidural pressure wave forms more closely paralleled the radial artery wave form than the central venous pressure. Conclusion. Lumbar epidural pressure is greater than atmospheric pressure when referenced to zero at the dorsal spine level.
Tissue-Resident NK Cells Mediate Ischemic Kidney Injury and Are Not Depleted by Anti–Asialo-GM1 Antibody

NK cells are innate lymphoid cells important for immune surveillance, identifying and responding to stress, infection, and/or transformation. Whereas conventional NK (cNK) cells circulate systemically, many NK cells reside in tissues where they appear to be poised to locally regulate tissue function. In the present study, we tested the contribution of tissue-resident NK (trNK) cells to tissue homeostasis by studying ischemic injury in the mouse kidney. Parabiosis experiments demonstrate that the kidney contains a significant fraction of trNK cells under homeostatic conditions. Kidney trNK cells developed independent of NFIL3 and T-bet, and they expressed a distinct cell surface phenotype as compared with cNK cells. Among these, trNK cells had reduced asialo-GM1 (AsGM1) expression relative to cNK cells, a phenotype observed in trNK cells across multiple organs and mouse strains. Strikingly, anti–AsGM1 Ab treatment, commonly used as an NK cell–depleting regimen, resulted in a robust and selective depletion of cNKs, leaving trNKs largely intact. Using this differential depletion, we tested the relative contribution of cNK and trNK cells in ischemic kidney injury. Whereas anti–NK1.1 Ab effectively depleted both trNK and cNK cells and protected against ischemic/reperfusion injury, anti–AsGM1 Ab preferentially depleted cNK cells and failed to protect against injury. These data demonstrate unanticipated specificity of anti–AsGM1 Ab depletion on NK cell subsets and reveal a new approach to study the contributions of cNK and trNK cells in vivo. In total, these data demonstrate that trNK cells play a key role in modulating local responses to ischemic tissue injury in the kidney and potentially other organs.
Influence of endophyte-infected tall fescue on serum prolactin and progesterone in gravid mares.

Thirty mares in late gestation were used in a 3-yr study to assess effects of the tall fescue endophyte Acremonium coenophialum on serum prolactin (PRL) and progesterone. Two paddocks of each treatment, 0 or 100% infected 'Kentucky 31' tall fescue, were grazed by the mares for 21 d. Blood was collected three times per week until parturition. At 7-d intervals, mares were challenged with thyrotropin-releasing hormone (TRH) while grazing and blood was collected postinjection. Mares grazing 100% infected tall fescue (E+) had decreased serum PRL compared with mares grazing the 0% infected tall fescue (E-) in 2 of 3 yr. Within 8 d postgrazing, serum PRL for E+ mares equaled or surpassed values of the E- mares. Serum PRL was not different during the 3rd yr. In response to TRH, serum PRL rate of increase was similar between treatments but remained elevated (P less than .01) in the E+ mares at the 180-, 240-, and 300-min sample times. Serum progesterone was lowered (P less than .05) by E+ but increased to control values within 10 d postgrazing. It is concluded that serum PRL and progesterone in the gravid mare were decreased by the presence of A. coenophialum in 'Kentucky 31' tall fescue grass but normal levels were reestablished within 2 to 3 wk.
New Kidney Allocation System Associated With Increased Rates Of Transplants Among Black And Hispanic Patients.

Before the 2014 implementation of a new kidney allocation system by the United Network for Organ Sharing, white patients were more likely than black or Hispanic patients to receive a kidney transplant. To determine the effect of the new allocation system on these disparities, we examined data for 179,071 transplant waiting list events in the period June 2013-September 2016, and we calculated monthly transplantation rates (34,133 patients actually received transplants). Implementation of the new system was associated with a narrowing of the disparities in the average monthly transplantation rates by 0.29 percentage point for blacks compared to whites and by 0.24 percentage point for Hispanics compared to whites, which resulted in both disparities becoming nonsignificant after implementation of the new system.