Miracle-dz/UniFAR-FTUs huggingface dataset:
Intracellular calcium and its sodium‐independent regulation in voltage‐clamped snail neurones.

1. We have used both Ca(2+)‐sensitive microelectrodes and fura‐2 to measure the intracellular free calcium ion concentration ([Ca2+]i or its negative log, pCai) of snail neurones voltage clamped to ‐50 or ‐60 mV. Using Ca(2+)‐sensitive microelectrodes, [Ca2+]i was found to be approximately 174 nM and pCai, 6.76 +/‐ 0.09 (mean +/‐ S.E.M.; n = 11); using fura‐2, [Ca2+]i was approximately 40 nM and pCai, 7.44 +/‐ 0.06 (mean +/‐ S.E.M., n = 10). 2. Depolarizations (1‐20 s) caused an increase in [Ca2+]i which was abolished by removal of extracellular Ca2+, indicating that the rise in [Ca2+]i was due to Ca2+ influx through voltage‐activated Ca2+ channels. 3. Caffeine (10‐20 mM) caused an increase in [Ca2+]i in the presence or absence of extracellular Ca2+. The effects of caffeine on [Ca2+]i could be prevented by ryanodine. 4. Thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)‐ATPase, caused a small increase in resting [Ca2+]i and slowed the rate of recovery from Ca2+ loads following 20 s depolarizations. 5. Neither replacement of extracellular sodium with N‐methyl‐D‐glucamine (NMDG), nor loading the cells with intracellular sodium, had any effect on resting [Ca2+]i or the rate of recovery of [Ca2+]i following depolarizations. 6. The mitochondrial uncoupling agent carbonyl cyanide m‐chlorophenylhydrazone (CCmP) caused a small gradual rise in resting [Ca2+]i. Removal of extracellular sodium during exposure to CCmP had no further effect on [Ca2+]i. 7. Intracellular orthovanadate caused an increase in resting [Ca2+]i and prevented the full recovery of [Ca2+]i following small Ca2+ loads, but removal of extracellular sodium did not cause a rise in [Ca2+]i. We conclude that there is no Na(+)‐Ca2+ exchanger present in the cell body of these neurones and that [Ca2+]i is maintained by an ATP‐dependent Ca2+ pump.
The Tritone Paradox: Correlate with the Listener's Vocal Range for Speech

In the tritone paradox, two tones are presented that are related by a halfoctave. Each tone consists of a set of octave-related sinusoids whose amplitudes are scaled by a bell-shaped spectral envelope; thus the usual cues to height attribution are missing. When listeners judge whether such tone pairs form ascending or descending patterns, judgments are related in an orderly fashion to the positions of the tones along the pitch class circle: Tones in one region of the circle are heard as higher and those in the opposite region as lower. However, listeners differ strikingly in the orientation of the pitch-class circle with respect to height. So far, the basis of the tritone paradox and the reasons for the individual differences in its manifestation have proved elusive. In the present study, a correlation is found between perception of the tritone paradox and the range of fundamental frequencies of the listener's speaking voice. To the authors' knowledge, this is the first demonstration of a close connection between the perception of a musical pattern on the one hand and the listener's speech characteristics on the other.
Prognostic Impact of Circulating Tumor Cells for Breast Cancer Patients Treated in the Neoadjuvant "Geparquattro" Trial

Purpose: This study aimed to evaluate the prognostic impact of circulating tumor cells (CTC) detected in patients with operable or locally advanced breast cancer before and after neoadjuvant therapy (NT) within the clinical trial GeparQuattro. Experimental Design: Data on CTCs enumerated with the CellSearch system were available for 213 and 207 patients before and after NT, respectively. Associations of CTCs with disease-free survival (DFS) and overall survival (OS) were analyzed by nonparametric Kaplan–Meier estimates and parametric Cox regression. Results: After a median follow-up of 67.1 months, the detection of ≥1 CTC/7.5 mL and ≥2 CTCs/7.5 mL before NT was associated with reduced DFS (P = 0.031 and P < 0.0001, respectively) and OS (P = 0.0057 and P < 0.0001, respectively), whereas CTCs detected after NT did not correlate with DFS or OS. In parametric univariate and multivariate Cox models, ≥1 CTC/7.5 mL, ≥2 CTCs/7.5 mL, and absolute CTC numbers before NT revealed to be independent prognostic parameters of DFS and OS. CTC-negative patients with pathologic complete response (pCR) exhibited the best prognosis, whereas those with CTCs and less tumor response were at high risk of tumor relapse. In HER2 (ERBB2)-positive and triple-negative patients, ≥2 CTCs/7.5 mL detected before NT also were significantly associated with worse DFS and OS. Conclusions: Detection of CTCs before NT is an independent prognostic factor of impaired clinical outcome, and combined with pCR, it could be helpful to stratify breast cancer patients for therapeutic interventions. Clin Cancer Res; 23(18); 5384–93. ©2017 AACR.
Ultrasound in Sports Medicine

The accuracy of sonography in evaluating various conditions of the musculoskeletal system has been demonstrated and its utility as a primary diagnostic imaging modality in the musculoskeletal system in the United States has been increasing in frequency. Sonography is universally tolerated across a broad patient population, including pediatric and pregnant patients and those in whom traditional magnetic resonance (MR) imaging is not an option, due either to absolute or relative contraindications. Sonographic examinations are relatively quick compared with an MR or computed tomographic study, and delays in scheduling are therefore minimal, an advantage for those patients who have traveled a long distance or who are in a considerable amount of discomfort at the time of their visit to the orthopedic surgeon. With portable ultrasound units, examinations can be performed on the playing field, immediately at the time of the acute injury, for rapid diagnosis. Lastly, ultrasound can be used to guide for therapeutic procedures at the same time the diagnostic exam is performed.
Liver transplantation in children: part 2 - long-term issues

This two-part review provides a comprehensive summary of clinical and research literature on paediatric liver transplantation. Part 2 focuses on the long-term physical consequences and psychological impact of transplantation and critically examines neurobehavioural, sexual development, psychosocial function and overall impact on children’s quality of life. This review highlights the implications for clinical practice in specialist and local services and suggests areas where research is required to improve the lives of children after liver transplantation.
Angiotensin II Induces Vascular Endocannabinoid Release, Which Attenuates Its Vasoconstrictor Effect via CB1 Cannabinoid Receptors*

Background: In expression systems diacylglycerol (DAG) produced during AT1 angiotensin receptor signaling can be converted to 2-arachidonoylglycerol. Results: Inhibition of CB1 receptors and DAG lipase augmented angiotensin II-induced vasoconstriction in resistance arteries. Conclusion: Angiotensin II-induced vasoconstriction is attenuated via 2-arachidonoylglycerol release and consequent CB1 receptor activation. Significance: This is the first demonstration that angiotensin II-induced endocannabinoid release can modulate vasoconstriction. In the vascular system angiotensin II (Ang II) causes vasoconstriction via the activation of type 1 angiotensin receptors. Earlier reports have shown that in cellular expression systems diacylglycerol produced during type 1 angiotensin receptor signaling can be converted to 2-arachidonoylglycerol, an important endocannabinoid. Because activation of CB1 cannabinoid receptors (CB1R) induces vasodilation and reduces blood pressure, we have tested the hypothesis that Ang II-induced 2-arachidonoylglycerol release can modulate its vasoconstrictor action in vascular tissue. Rat and mouse skeletal muscle arterioles and mouse saphenous arteries were isolated, pressurized, and subjected to microangiometry. Vascular expression of CB1R was demonstrated using Western blot and RT-PCR. In accordance with the functional relevance of these receptors WIN55212, a CB1R agonist, caused vasodilation, which was absent in CB1R knock-out mice. Inhibition of CB1Rs using O2050, a neutral antagonist, enhanced the vasoconstrictor effect of Ang II in wild type but not in CB1R knock-out mice. Inverse agonists of CB1R (SR141716 and AM251) and inhibition of diacylglycerol lipase using tetrahydrolipstatin also augmented the Ang II-induced vasoconstriction, suggesting that endocannabinoid release modulates this process via CB1R activation. This effect was independent of nitric-oxide synthase activity and endothelial function. These data demonstrate that Ang II stimulates vascular endocannabinoid formation, which attenuates its vasoconstrictor effect, suggesting that endocannabinoid release from the vascular wall and CB1R activation reduces the vasoconstrictor and hypertensive effects of Ang II.
Adhesion Molecule Expression, Clinical Features and Therapy Outcome in Childhood Acute Lymphoblastic Leukemia

In view of the relevance of adhesion molecule expression for the mechanisms of homing, trafficking and spreading of malignant cells, we have investigated the expression of surface adhesion molecules in lymphoblasts from 57 acute lymphoblastic leukemia (ALL) cases and tried to correlate the adhesive phenotype with immunological typing, prognostic factors at diagnosis and clinical follow-up. Blasts from all cases expressed adhesion molecules at high rates. β1 integrin chain (CD18) was consistently found on blasts from most ALL cases; among integrins of the β2 family, LFA-1 was detected in 58% of cases, in the virtual absence of other α chains. CD54 and CD58 were expressed in variable proportions by ALL blasts and CD44 was detected in the majority of the malignant cells, whereas the CD62L selectin was only present in 24% of cases. B-lineage ALL's displayed similar adhesion molecule phenotypes irrespective of maturational stages of the leukemic cells. We found a significantly reduced expression of β2 αL integrins in the hybrid ALL cases (CD13 and/or CD33 positive). However, these cases did not show differences in clinical presentation and behaviour in comparison with patients of other groups. We did not find a significant correlation between adhesion molecule expression and well established risk factors (age, white blood cell count, central nervous system involvement, chromosomal abnormalities), with the exception of splenomegaly, that was significantly associated with CD18 expression. In the follow-up, no evidence of significant correlation between adhesive phenotype and adverse events such as leukemic relapse and death was found. In conclusion, although expression of adhesion molecules on lymphoblasts confirms the phenotypic heterogeneity of ALL, it appears that this is not relevant for the clinical aspects of the disease and for prognosis.
Wounding-Induced Increase of Quinolizidine Alkaloid Accumulation in Lupin Leaves

Cutting-up leaflets of Lupinus polyphyllus induces a rapid increase of quinolizidine alkaloid accumulation of up to 400% within 2 to 4.5 h. In contrast to the diurnal alkaloid formation, this reaction takes place both in the light and the dark and even at 4°C. The effect is reduced in chloramphenicol-treated samples but unimpaired in cycloheximide-treated assays. Since quinolizidine alkaloids constitute probably an important means of a chemical defense system of lupins against microbes and herbivores, the wound-induction of alkaloid accumulation is discussed as a defense responsf
Heterogeneity of dimer excision in young and senescent human dermal fibroblasts

We have examined the relationship between nucleotide excision of the main UV‐induced photoproduct, the cyclobutane pyrimidine dimer and in vitro cellular senescence. An in situ semiquantitative immunocytochemical assay has demonstrated that, following a UV‐C dose of 15 J m−2, young human dermal fibroblasts maintained in a high level of serum are more efficient than senescent fibroblasts in the removal of dimers. However, in G0‐arrested cultures (serum‐starved), young fibroblasts are compromised in their ability to remove dimers and are significantly less efficient than senescent cells in this process. Supplementation of the culture medium with 0.1 mm deoxyribonucleosides enhances the removal of dimers in both young and senescent fibroblasts in proliferating or serum‐starved cells. These data indicate that overall there is a modest but significant reduction in nucleotide excision of dimer photoproducts in cells as they age in vitro. In addition, G0‐arrested young cells exhibit reduced removal of dimers, although this can be complemented by deoxyribonucleoside addition. In addition, this in situ assay has revealed heterogeneity in both susceptibility to UV‐C‐induced damage and excision. Overall, we provide evidence of reduced UV‐induced damage excision in senescent compared with young fibroblasts, and demonstrate modulation of these processes in young and senescent cells under specific growth conditions.
Glaucoma and its treatment: a review.

PURPOSE A review of glaucoma and its treatment is presented. SUMMARY Glaucoma is a common eye disease that can cause irreversible blindness if left undiagnosed and untreated. Glaucoma is a leading cause of blindness in the United States and other industrialized countries. In most cases, the symptoms of early-stage glaucoma are minimal or nonexistent. There are several different types of glaucoma, and they have been classically divided into the categories of primary or secondary open-angle or angle-closure glaucoma. Secondary forms of glaucoma are caused by various ocular or systemic diseases. Every available treatment to prevent progressive glaucomatous optic neuropathy has potential adverse effects and involves a certain amount of risk and financial expense. Conventional first-line treatment of glaucoma usually begins with the use of a topical selective or nonselective beta-blocker or a topical prostaglandin analog. Second-line drugs of choice include alpha-agonists and topical carbonic anhydrase inhibitors. Parasympathomimetic agents, most commonly pilocarpine, are considered third-line treatment options. For patients who do not respond to antiglaucoma medications, laser trabeculoplasty and incisional surgery are further methods that can be used to lower intraocular pressure. The results of clinical trials have reaffirmed the utility of antiglaucoma medications in slowing the progression of the disease. CONCLUSION Glaucoma is a common eye disease that is usually associated with an elevated intraocular pressure. Treatment options for patients with glaucoma include medications, laser therapy, and incisional surgery. The risks and benefits of each type of treatment must be carefully considered to maximize the treatment's benefits while minimizing adverse effects.
Detection of Chlamydia trachomatis and Neisseria gonorrhoeae by ligase chain reaction-based assays with clinical specimens from various sites: implications for diagnostic testing and screening

Ligase chain reaction (LCR)-based tests for the diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae infections in men and women attending a sexually transmitted disease clinic were evaluated. LCR testing of urethral swab and urine specimens from men and cervical swab and urine specimens from women was compared with culture of male urethral swabs and female cervical and urethral swabs, respectively. An expanded "gold standard" was defined as a positive culture or at least one specimen confirmed to be positive by LCR testing. The prevalence of C. trachomatis infection as detected by cell culture was 7.0% among 614 men and 5.0% among 602 women. By LCR, these values increased to 11.4 and 9.9% with urethral swabs and urine, respectively, for men and 9.6 and 9.1% with cervical swabs and urine, respectively, for women. Relative to the expanded gold standard, the sensitivity of cell culture with male urethral swabs or female cervical swabs was 57.3 and 45.5%, respectively, compared with corresponding values of 93.3 and 87.9% for LCR. The sensitivity of LCR with urine specimens was 77.3 and 78.8% for men and women, respectively. The prevalence of N. gonorrhoeae infection as detected by culture was 5.9% among 220 men and 2.9% among 383 women. The corresponding values were 8.2 and 5.5%, respectively, by LCR testing of swabs. Prevalence values by LCR testing of urine were 7.3% for men and 2.9% for women. The sensitivity of culture was 72.2% for men and 50.0% for women. The sensitivities of LCR were 100% with male urethral swabs, 95.4% with female cervical swabs, 88.9% with male urine, and 50.0% with female urine. These results indicate that the LCR-based assays represent a major improvement in C. trachomatis and N. gonorrhoeae diagnostics. The sensitivity of testing of urethral or cervical swabs by LCR was markedly greater than that by culture. The sensitivity of testing female or male urine specimens was equal to or greater than that of culturing cervical or urethral specimens. LCR testing of urine specimens may prove useful for screening for C. trachomatis.
Secondhand learning from graduates of leadership development programs

Purpose – This paper aims to explore the impact leadership development program graduates had on their workgroup, the nature of that impact and how that impact occurred. Design/methodology/approach – This research was conducted at three sites using a qualitative interview methodology with thematic data analysis. Techniques to ensure trustworthiness included purposive sampling, triangulation of researchers, member checks and code checking. Findings – Analysis of the data revealed secondhand learning as specific changes in practices, behaviors and attitudes, transferred by program graduates to their peers and supervisors. The transfer of learning was described as both intentional and informal learning during episodes of varying duration, and occurred through a variety of dyadic and group interactions in a manner generally consistent with the 4I framework of organizational learning. Research limitations/implications – The study was limited to medical educators. Recommendations for supervisors and organization.
Clinical Experience in 82 Patients with Pancreas Divisum: Preliminary Results of Manometry and Endoscopic Therapy

Although it is clear that the majority of patients with pancreas divisum have no clinical disease, there is a subset of patients who have either unexplained abdominal pain or recurrent pancreatitis. Endoscopic therapy of the minor papilla may alter the clinical course of those patients with pancreas divisum and recurrent pancreatitis. Manometric study of the minor papilla is feasible and reveals a sphincter mechanism similar to the major papilla. Clinical response to endoscopic therapy may aid in selecting patients who might benefit from surgical sphincteroplasty. Refinement of manometric study of the minor papilla offers a potential method of detecting functional obstruction of dorsal duct drainage.
Influences on Continued Use of an Information System: A Longitudinal Study

What influences encourage and discourage long-term use of an Information System (IS)? In a longitudinal study over 14 months, we examine use of a Learning Management System in an educational setting. Our findings suggest that the influences that support users' decision to adopt a technology may not be sufficient to encourage continued long-term use. New influences emerge as users employ technology to suit varying needs in work environments at varying times. Findings from the study reveal that rejection of a technology may take place long after adoption if users do not experience long-term benefits or are unable to resolve persistent issues. Localized IT and peer-support and on-going training are key factors in encouraging users to persist, resulting in long-term productivity and satisfaction.
Analysis of the action of angiotensin II on the baroreflex control of heart rate in conscious rabbits.

There is considerable evidence that angiotensin II (Ang II) attenuates the baroreflex control of heart rate (HR), but the mechanism and site of this action have not been precisely defined. In the present study the effects of systemically and centrally administered Ang II on the baroreflex control of HR were investigated in conscious, chronically prepared rabbits. Baroreflex curves (HR vs. mean arterial pressure) were generated with iv infusions of phenylephrine or nitroprusside. Background infusion of Ang II at 10 ng/kg.min increased mean arterial pressure from 77.3 +/- 3.0 to 94.3 +/- 4.1 mm Hg (P less than 0.001) without changing HR [212.1 +/- 7.2 to 218.0 +/- 9.8 beats/min (bpm)] and shifted (reset) the baroreflex curve with phenylephrine to a higher pressure level (P less than 0.001) without changing its slope (-1.40 +/- 0.40 to -1.65 +/- 0.46 bpm/mm Hg; P = 0.4). Background infusion of an equipressor dose of phenylephrine did not shift the baroreflex curve or change its slope. Ang II also shifted the baroreflex curve with nitroprusside to a higher pressure level (P less than 0.01), but again the slope was not significantly changed (-2.30 +/- 1.25 to -1.51 +/- 0.52 bpm/mm Hg; P = 0.2). Background intraventricular infusion of Ang II at 1 ng/kg.min had the same effects as iv infusion of Ang II at 10 ng/kg.min; the curve was shifted to a higher pressure level (P less than 0.001), but the slope was not changed (-0.76 +/- 0.47 to -1.143 +/- 0.48 bpm/mm Hg). Intravenous infusion of Ang II at 1 ng/kg.min had no effect on the baroreflex. The resetting of the baroreflex with phenylephrine by iv Ang II (10 ng/kg.min) was not blocked by propranolol: atropine markedly reduced the baroreflex response to phenylephrine in both the absence and presence of Ang II. These results indicate that in conscious rabbits, Ang II resets the baroreflex control of HR, but does not change its sensitivity. This effect apparently results from an action of Ang II on the brain that is mediated by withdrawal of vagal tone to the heart. The resetting of the baroreflex by Ang II can explain the ability of the peptide to increase arterial pressure without decreasing HR.
ASDIN: Percutaneous Renal Biopsy: Outpatient Observation without Hospitalization Is Safe

Percutaneous renal biopsy may be complicated by hemorrhage. Patients are frequently hospitalized for overnight observation. We evaluated prospectively the feasibility and safety of an outpatient renal biopsy protocol. During a 20‐month period, 100 consecutive patients underwent outpatient renal biopsy using a standardized protocol. The biopsy was performed by Nephrology Fellows, under direct faculty supervision. All biopsies were carried out under real‐time ultrasound guidance with a 16‐gauge spring‐loaded biopsy gun, and followed immediately by color Doppler ultrasound to exclude active bleeding. Blood pressure, heart rate, hemoglobin, and hematocrit were monitored for 8 hours postbiopsy. If there were no complications, the patients were discharged home after the observation period. A total of 91 patients required one or two needle passes, and nine needed three or four passes. A mean of 12.7 ± 9.7 glomeruli were obtained per patient. No major complications were encountered. A small (<2 × 2 cm) perinephric hematoma was observed postbiopsy in 13 patients. Four patients were hospitalized for overnight observation due to a >4% decrease in their hematocrit, but none required a transfusion or intervention. No patient experienced a delayed biopsy‐related complication. Outpatient, real‐time, ultrasound‐guided percutaneous renal biopsy is safe and effective, and minimizes the need for postbiopsy hospitalization. It can result in significant cost savings without exposing the patients to an increased risk of complications.