Miracle-dz/UniFAR-FTUs huggingface dataset:
Streptococcus milleri Group Cutaneous Abscess Associated with Insulin Injection to Distal Lower Extremity in an Insulin-Dependent Diabetic Man

Purpose We report a case of Streptococcus milleri group (SMG)-associated cutaneous abscess in an older diabetic man. The infection developed after subcutaneous insulin injection to the distal lower extremity. This is the first known account of SMG-associated abscess secondary to insulin administration. Summary A 60-year-old Caucasian insulin-dependent diabetic male developed a severe cutaneous infection including abscess and surrounding cellulitis at the site of a self-administered insulin glargine injection on the medial portion of his right lower leg. The infection developed rapidly within 1 day following the injection. Cultures from purulent drainage were positive for SMG. The infection resolved rapidly with an antibiotic regimen including 1 dose of clindamycin followed by intravenous pipercillin/tazobactam plus vancomycin and concluded with outpatient treatment with sulfamethoxazole/trimethoprim. Organisms belonging to SMG are increasingly recognized as pyogenic pathogens responsible, most commonly, for abscess infections. SMG infections have been reported in diabetics; however, this is the first known case of SMG-associated abscess secondary to subcutaneous insulin administration. Conclusion A 60-year-old diabetic male experienced a severe SMG-associated abscess in the distal lower extremity after self-injection with insulin glargine. The infection resolved rapidly with intravenous and oral antibiotics. Clinicians should be aware of the potential for abscess infection from SMG at insulin injection sites.
Reasons for infertile couples to discontinue in vitro fertilisation (IVF) treatment

The aim of this study was to determine the reason for treatment discontinuation for couples who had received at least one in vitro fertilisation‐embryo transfer (IVF‐ET) treatment at the IVF centre of a university hospital in Turkey. The research was conducted with 113 couples who discontinued the IVF‐ET treatment. The questionnaires were prepared separately for the women and men following a literature review. The mean age for the women discontinuing treatment was 35.51±4.35 and for the women who discontinued the centre was 34.29±4.31. The mean age for the men discontinuing treatment was 38.72±4.74 and for the men discontinuing centre was 36.14±3.38. The women stated the most important reason for discontinuing IVF‐ET treatment was ‘unsuccessful treatments and fear of coping’; however, the men stated ‘depletion of financial resources’ as the most important reason, which was the least important reason for the women. It is assessed that this difference arises from the priorities of men and women in accordance with their roles within the family. Both women and men stated the important reasons for discontinuing the centre were ‘causes related to the centre’ and there was no statistically significant difference. Earning the trust of the couple is very important even if the treatment team carries out all treatment procedures to the letter. The study indicates that most of the women and men still want to have a child and would like to continue treatment as long as their psychological and financial status allows.
Role of Growth Hormone in the Alteration of Carbohydrate Metabolism Induced by Oral Contraceptive Agents1

To assess the role of growth hormone (GH) secretion in causing the deleterious effect of oral contraceptive agents (OCA) on carbohydrate metabolism, tolbutamide tolerance tests were performed on 13 normal females and 8 hypopituitary women on thyroid and glucocorticoid replacement before starting and 3 and 6 months after taking OCA. After a combined oral agent, the normal subjects showed no change in fasting glucose, free fatty acid (FFA), and insulin concentrations, but did manifest (after resting 45–60 min) marginally increased fasting GH and, as expected, glucocorticoid levels. There was a significant impairment of the glucose fall and an enhancement of both GH response and FFA recovery following tolbutamide. Although the insulin response was unchanged after OCA, the responses in the same subject on three separate tolbutamide tests were significantly correlated with each other. This suggests that the quickly releasable pool of insulin remains constant in a single individual and is unaffected by OCA. The.
UK single centre experience of rare and atypical variant of castrate-resistant prostate cancer: Poorly differentiated neuroendocrine small-cell carcinoma

Background: We report on the emergence of a rare and atypical variant of castrate-resistant prostate cancer (CRPC) that is characterised by transformation into poorly differentiated neuroendocrine small-cell carcinoma (NSCC). The existence of this variant was previously described in isolated case reports and small case-studies, but as yet there has been no UK series reported in the literature. Methods: Between January 2010 and January 2014, eight cases were presented in our local multi-disciplinary team meeting having a diagnosis of NSCC arising on a background of prostate cancer treated with androgen deprivation therapy. We performed a retrospective review of the clinical records of these patients, to identify the mode of presentation, diagnostic investigations, pathological characteristics, and subsequent treatment and survival outcomes. Results: The median patient age was 77 years (range, 68 – 84), with a median time interval of 25 months (range, 7 – 83) between the original diagnosis and subsequent transformation to NSCC. The median prostate-specific antigen (PSA) was 4 ng/ml, at presentation. Most patients presented with local progression, combined with high-volume and atypical sites of metastasis (e.g. brain, pancreas and penis). Patients developed a good initial response to platinum-based chemotherapy, but responses were short-lived and prognosis poor, with a median overall survival (OS) of 8 months. Conclusion: Prostate NSCC represents an atypical variant of CRPC with significant therapeutic and prognostic implications. Based on our observations, we have proposed a clinical algorithm for early diagnosis and appropriate management of these patients.
Patient involvement in the evaluation of health care: identifying key issues and considering the way forward

Abstract Patients have become increasingly involved in the evaluation of care, most often through attempts to measure their satisfaction. However, difficulties in conceptualizing and measuring satisfaction have led to a questioning of the validity and usefulness of this approach. This paper identifies the main difficulties in measuring satisfaction and considers the implications for individuals working in the area of coronary health care. It reports the findings of a study which explored the expectations and experiences of a group of cardiac patients and constructed a two-part questionnaire in an attempt to measure these experiences. This paper focuses on the qualitative findings which identified the complexity of patient expectations. Expectations were found to be multidimensional in nature and to vary in content and strength. The paper also reports the feasibility of using patient-identified expectations as the basis for developing a two-part questionnaire. Despite the popularity of the concept of satisfaction, cardiac patients rarely evaluated their care in terms of a satisfaction response during interviews. These findings contribute to current concerns that satisfaction as a concept may not adequately capture the way patients judge or evaluate their care. If we are to develop a better understanding of evaluation from the patients’ perspective, greater emphasis needs to be placed on the clarification or identification of concepts which may be of more relevance and utility to both patients and health care professionals before attempts at quantitative measurement are undertaken.
Correlation between Membrane Protein Expression Levels and Transcellular Transport Activity for Breast Cancer Resistance Protein

Emerging evidence indicates an important role for the breast cancer resistance protein (BCRP) in limiting brain penetration of substrate drugs. While in vitro transwell assays can provide an indication of BCRP substrate potential, the predictability of these assays in relation to in vivo brain penetration is still under debate. The present study examined the correlation of BCRP membrane protein expression level and transcellular transport activity across Madin-Darby canine kidney (MDCK) II monolayers. We expressed human BCRP or murine BCRP1 in MDCKII wild-type cells using BacMam2 virus transduction. The selective P-glycoprotein (P-gp) inhibitor LY335979 (1 μM) was included in the transport medium to measure BCRP-mediated transcellular transport for P-gp and BCRP cosubstrates. The BCRP levels in membrane extracts from MDCKII-BCRP or MDCKII-Bcrp1 cells were quantified by liquid chromatography–tandem mass spectrometry. The results are summarized as follows: 1) the membrane protein expression levels correlate with the corrected efflux ratios of substrates for human BCRP and murine BCRP1 within the efflux ratios investigated; 2) we demonstrate good concordance in rank order between the BCRP and BCRP1-mediated efflux ratios for 12 drugs; and 3) we propose an approach to contextualize in vitro BCRP transport data of discovery compounds by comparing them to the in vitro and in vivo transport data of the reference drug dantrolene and taking into account interbatch variation in BCRP expression. This approach correctly predicted compromised brain penetration for 25 discovery compounds in rodents, which were BCRP substrates but not P-gp or weak P-gp substrates. These results suggest that BCRP-expressing MDCKII cells are useful in predicting the in vivo role of BCRP in brain penetration.
Comparison of 19F NMR and 14C Measurements for the Assessment of ADME of BYL719 (Alpelisib) in Humans

The human mass balance study is the definitive study for the assessment of absorption, distribution, metabolism, and excretion (ADME) properties of a new chemical entity in humans. Traditionally this has been carried out by the administration of radiolabeled drug substances, typically 14C or occasionally 3H, as detection methods for these isotopes allow the absolute quantification of drug-related material (DRM) in blood, plasma, and excreta. Coupled with the use of analytical techniques such as liquid chromatography-mass spectrometry, a picture of the metabolic fate of a compound can be elucidated. In this study, we demonstrate the capabilities of 19F nuclear magnetic resonance (NMR) spectroscopy, applied as an alternative to radiolabeling, for the determination of mass balance and for metabolite profiling of an orally administered fluorinated drug. To demonstrate the capabilities of NMR, the study was conducted on remaining samples from a 14C human mass balance study conducted on Alpelisib (BYL719), a compound in late stage development at Novartis for the treatment of solid tumors. Quantitative 14C data were used to cross-validate the data obtained by NMR. The data show that, using 19F NMR, comparable data can be obtained for key human ADME endpoints including mass balance, total DRM determination in plasma and metabolite profiling and identification in plasma and excreta. Potential scenarios where NMR could be employed as an alternative to radiolabeling for the conduct of an early human ADME study are discussed.
Gonioscopia: proposta de classificação (APIC)

A brief historical review of gonioscopy since the pioneering works published by Trantas and Salzmann is presented. The techniques of examination are described and the advantages and disadvantages of each one are discussed. Based on the classifications in the literature, a new one is proposed: the APIC classification. In this classification each one of the elements of the anterior chamber angle are graduated: A = anterior chamber angle Amplitude; P = Pigmentation; I = iris Implantation; and C = iris Configuration.
Using an Internet-Based Breast Cancer Risk Assessment Tool to Improve Social-Cognitive Precursors of Physical Activity

Background. Internet-based cancer risk assessment tools might serve as a strategy for translating epidemiological risk prediction research into public health practice. Understanding how such tools affect key social-cognitive precursors of behavior change is crucial for leveraging their potential into effective interventions. Purpose. To test the effects of a publicly available, Internet-based, breast cancer risk assessment tool on social-cognitive precursors of physical activity. Methods. Women (N = 132) aged 40–78 with no personal cancer history indicated their perceived risk of breast cancer and were randomly assigned to receive personalized (www.yourdiseaserisk.wustl.edu) or nonpersonalized breast cancer risk information. Immediately thereafter, breast cancer risk perceptions and physical activity-related behavioral intentions, self-efficacy, and response efficacy were assessed. Results. Personalized information elicited higher intentions, self-efficacy, and response efficacy than nonpersonalized information, P values < 0.05. Self-efficacy and response efficacy mediated the effect of personalizing information on intentions. Women who received personalized information corrected their inaccurate risk perceptions to some extent, P values < 0.05, but few fully accepted the information. Conclusion. Internet-based risk assessment tools can produce beneficial effects on important social-cognitive precursors of behavior change, but lingering skepticism, possibly due to defensive processing, needs to be addressed before the effects can be maximized.
A Framework for Treatment Decision Making at Prostate Cancer Recurrence

Background. Of the 50,000 men in the US who elect for radical prostatectomy for prostate cancer, 24% to 40% will have a prostate-specific antigen (PSA) recurrence (PSA-R) within 10 years. Deciding whether to administer salvage therapy (ST) at PSA-R presents challenges, as treatment reduces the risk of progression to clinical metastasis but incurs unnecessary side effects should the man die before metastasis. We have developed a new harm–benefit framework using a clinical cohort to inform shared decision making between patients and physicians at PSA-R. Methods. Records of 1,045 Johns Hopkins University Hospital patients diagnosed between 1984 and 2013 who had PSA-R following radical prostatectomy were analyzed using marginal structural models to estimate the baseline risk of metastasis and the effect of ST (radiation therapy with or without hormone therapy) while accounting for selection into ST on the basis of PSA growth. The estimated model predicts the harm–benefit tradeoffs of ST within patient subgroups. The benefit of ST is the absolute reduction in the risk of metastasis within 10 years; the harm is the frequency of cancers that would not have metastasized in the patient’s lifetime in the absence of ST (overtreatment). Results. The adjusted hazard ratio associated with ST was 0.41 (95% CI, 0.31 to 0.55). Providing ST to all men at PSA-R reduced the risk of metastasis from 43% to 23% but led to 31% of men being overtreated (harm/benefit = 31/(43−23) = 1.6). Providing ST to men with Gleason score >7 reduced the risk of metastasis from 67% to 39%, with 13% of men being overtreated (harm/benefit = 13/(67−39) = 0.5). Conclusions. A quantitative framework that evaluates primary harms and benefits of ST after PSA-R will facilitate informed decision making. Immediate ST may be more appropriate in patient subgroups at elevated risk of metastasis.
Disposition of Methamphetamine and Major Metabolites in Mice: Role of Organic Cation Transporter 3 in Tissue-Selective Accumulation of Para-Hydroxymethamphetamine

Methamphetamine is one of the most widely abused illicit drugs. Although human intoxication and multiple tissue toxicities frequently occur in abusers, little is known about the distribution of methamphetamine or its primary metabolites, amphetamine and para-hydroxymethamphetamine (p-OHMA), to their sites of toxicity. This study determined the pharmacokinetics, tissue exposure, and partition ratios of methamphetamine and major metabolites in various mouse tissues and investigated the impact of organic cation transporter 3 (Oct3) following i.v. injection of methamphetamine to male Oct3+/+ and Oct3−/− mice. Methamphetamine, amphetamine, and p-OHMA were readily detectable in plasma with Oct3+/+ and Oct3−/− mice displaying similar plasma pharmacokinetic profiles for all three analytes. In addition to kidney and liver, salivary glands highly accumulated methamphetamine, amphetamine, and p-OHMA with total exposure 3.3- to 9.4-fold higher than plasma area under the concentration–time curve (AUC). Consistent with being an Oct3 substrate, p-OHMA AUC in salivary glands is reduced by 50% in Oct3−/− mice. p-OHMA AUC in skeletal muscle is also significantly reduced in Oct3−/− mice. Our data identified salivary glands as a novel site of high accumulation of methamphetamine and metabolites, which may underlie methamphetamine toxicity in this tissue. Furthermore, our study identified Oct3 as an important determinant of tissue uptake and exposure to p-OHMA in salivary glands and skeletal muscle. Our findings suggest that local tissue accumulation of methamphetamine and/or its metabolites may play a role in several of the reported peripheral toxicities of methamphetamine, and Oct3 can significantly impact tissue exposure to its substrates without affecting systemic elimination.
Inhibition of Anandamide Hydrolysis by Cyclohexyl Carbamic Acid 3′-Carbamoyl-3-yl Ester (URB597) Reverses Abuse-Related Behavioral and Neurochemical Effects of Nicotine in Rats

Emerging evidence suggests that the rewarding, abuse-related effects of nicotine are modulated by the endocannabinoid system of the brain. For example, pharmacological blockade or genetic deletion of cannabinoid CB1 receptors can reduce or eliminate many abuse-related behavioral and neurochemical effects of nicotine. Furthermore, doses of Δ9-tetrahydrocannabinol and nicotine that are ineffective when given alone can induce conditioned place preference when given together. These previous studies have used systemically administered CB1 receptor agonists and antagonists and gene deletion techniques, which affect cannabinoid CB1 receptors throughout the brain. A more functionally selective way to alter endocannabinoid activity is to inhibit fatty acid amide hydrolase (FAAH), thereby magnifying and prolonging the effects of the endocannabinoid anandamide only when and where it is synthesized and released on demand. Here, we combined behavioral and neurochemical approaches to evaluate whether the FAAH inhibitor URB597 (cyclohexyl carbamic acid 3′-carbamoyl-3-yl ester) could alter the abuse-related effects of nicotine in rats. We found that URB597, at a dose (0.3 mg/kg) that had no behavioral effects by itself, prevented development of nicotine-induced conditioned place preference (CPP) and acquisition of nicotine self-administration. URB597 also reduced nicotine-induced reinstatement in both CPP and self-administration models of relapse. Furthermore, in vivo microdialysis showed that URB597 reduced nicotine-induced dopamine elevations in the nucleus accumbens shell, the terminal area of the brain's mesolimbic reward system. These findings suggest that FAAH inhibition can counteract the addictive properties of nicotine and that FAAH may serve as a new target for development of medications for treatment of tobacco dependence.
Effect of the Multitargeted Receptor Tyrosine Kinase Inhibitor, ABT-869 [N-(4-(3-Amino-1H-indazol-4-yl)phenyl)-N′-(2-fluoro-5-methylphenyl)urea], on Blood Pressure in Conscious Rats and Mice: Reversal with Antihypertensive Agents and Effect on Tumor Growth Inhibition

ABT-869 [N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N′-(2-fluoro-5-methylphenyl)urea] is a novel multitargeted inhibitor of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor tyrosine kinase family members. ABT-869 demonstrates tumor growth inhibition in multiple preclinical animal models and in early clinical trials. VEGF receptor inhibition is also associated with reversible hypertension that may limit its benefit clinically. To evaluate optimal therapeutic approaches to prevent hypertension with VEGF receptor inhibition, we characterized the dose-dependent effects of seven antihypertensive agents from three mechanistic classes [angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs)] on hypertension induced by ABT-869 in conscious telemetry rats. We report that ABT-869-induced hypertension can be prevented and reversed with subtherapeutic or therapeutic doses of antihypertensive drugs with a general rank order of ACEi > ARB > CCB. In SCID mice, the ACE inhibitor, enalapril (C20H28N2O5·C4H4O4) at 30 mg/kg, prevented hypertension, with no attenuation of the antitumor efficacy of ABT-869. These studies demonstrate that the adverse cardiovascular effects of the VEGF/PDGF receptor tyrosine kinase inhibitor, ABT-869, are readily controlled by conventional antihypertensive therapy without affecting antitumor efficacy.
The New College Vision and Laser Data Set

In this paper we present a large dataset intended for use in mobile robotics research. Gathered from a robot driving several kilometers through a park and campus, it contains a five-degree-of-freedom dead-reckoned trajectory, laser range/reflectance data and 20 Hz stereoscopic and omnidirectional imagery. All data is carefully timestamped and all data logs are in human readable form with the images in standard formats. We provide a set of tools to access the data and detailed tagging and segmentations to facilitate its use.
The Epi.q-1 Hybrid Mobile Robot

In this paper we propose an innovative solution for a small size hybrid mobile robot called Epi.q-1. Overall dimensions are about 160 mm x 360 mm x 280 mm (height x length x width). The Epi.q-1 robot moves on flat, steep or uneven ground. It can climb over obstacles or steps, even if they are non-uniform in size. Its operating mode adapts to ground conditions and changes accordingly: from rolling (on wheels) to stepping (on legs); thanks to its great mobility it can follow complex routes. It is easy to control with just a few actuators. Robot locomotion drive-generating units employ an original driving mechanism, where degrees of freedom (DOFs) can be limited to some extent according to the operating conditions or thanks to a switching device. Locomotion units consist of a motor linked to a gear (double epicyclical chain) and an axial device (mini-motor and lead screw system) able to lock or unlock some DOFs of the kinematic chain. Moreover, the robot locomotion unit can change its size, from small to large and vice versa, in order to be able to reach restricted spaces and to overcome even quite tall obstacles. It was experimentally tested on flat ground and slopes. It can overcome 90 mm obstacles, that are 72% of the height of the locomotion unit, and climb stairs.