Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Spacing of Item Repetitions in Continuous Recognition Memory: Does Item Retrieval Difficulty Promote Item Retention in Older Adults?

Background/Study Context: Older adults exhibit an age-related deficit in item memory as a function of the length of the retention interval, but older adults and young adults usually show roughly equivalent benefits due to the spacing of item repetitions in continuous memory tasks. The current experiment investigates the seemingly paradoxical effects of retention interval and spacing in young and older adults using a continuous recognition memory procedure. Methods: Fifty young adults and 52 older adults gave memory confidence ratings to words that were presented once (P1), twice (P2), or three times (P3), and the effects of the lag length and retention interval were assessed at P2 and at P3, respectively. Results: Response times at P2 were disproportionately longer for older adults than for younger adults as a function of the number of items occurring between P1 and P2, suggestive of age-related loss in item memory. Ratings of confidence in memory responses revealed that older adults remembered fewer items at P2 with a high degree of certainty. Confidence ratings given at P3 suggested that young and older adults derived equivalent benefits from the spacing between P1 and P2. Conclusion: Findings of this study support theoretical accounts that suggest that recursive reminding and/or item retrieval difficulty promote item retention in older adults.
Effects of β-Blocker Titration on Glucose Homeostasis in Heart Failure

Background: Abnormal glucose metabolism and insulin resistance have been associated with heart failure (HF) incidence, severity, and mortality. Metabolic parameters such as hepatic glucose production may be altered by β-adrenoceptor antagonists in patients with HF. Objective: To evaluate the effects of metoprolol succinate or carvedilol up-titration on fasting glucose, insulin resistance, and β2-mediated glucose production in patients with chronic HF. Methods: This was a prospective, randomized, active comparator study in 15 patients with American Heart Association/American College of Cardiology Stage C systolic dysfunction HF that was stabilized with medical therapy. Participants were randomized to receive metoprolol succinate 25 mg daily or carvedilol 3.125 mg twice daily. Metoprolol was titrated to a target of 200 mg daily, and carvedilol was titrated to 25 mg twice daily over 8 weeks. Insulin resistance as assessed by the homeostatic model and terbutaline-induced glucose production (area under the curve from 0 to 180 … [AUC0–180]) were assessed at baseline and at 4 subsequent β-blocker titration visits over 8 weeks. Results: In all 15 patients, terbutaline-induced glucose AUC0–180 decreased (p = 0.001) as β-blocker doses increased. A significant reduction in glucose AUC0–180 compared with baseline was noted only in patients taking metoprolol 100 mg daily (–2424.6 mg/dL•min; 95% CI 372.6 to −4478.4) and 200 mg daily (–2437.2 mg/dL•min; 95% CI −15.1 to −4604.4) and was not observed in those taking carvedilol. After β-blocker titration, fasting glucose concentrations for the metoprolol and carvedilol groups were 86.9 mg/dL (95% CI 89.8 to 101.6) and 95.7 mg/dL (95% CI 89.8 to 101.6), respectively (p = 0.027), adjusted for baseline values. There was no significant difference between the effect of metoprolol and carvedilol on insulin resistance. Conclusions: Increasing doses of β-blockers are associated with decreased β2-mediated glucose production in HF. Metoprolol succinate, but not carvedilol, decreases hepatic glucose production at doses commonly used in HF.
The Mayo Clinic experience with the use of kinase inhibitors, ipilimumab, bevacizumab, and local therapies in the treatment of metastatic uveal melanoma

Uveal melanoma is the most common neoplasm of the adult eye. Many patients will develop metastatic disease, for which there is no standard of care. Therefore, we sought to review our experience with treating this neoplasm. We retrospectively reviewed all of the cases of metastatic uveal melanoma seen at the Mayo Clinic, Rochester, Minnesota, USA, between 1 January 2000 and 1 August 2013. Overall survival rates were compared among patients treated with local therapies (LTs), ipilumumab, bevacizumab, or kinase inhibitors. A total of 101 patients were included in the study, among whom 59% were male; the median age was 62 years (interquartile range 54–71), and 92% had an Eastern Cooperative Oncology Group performance status of 0–1. Treatment with LT was associated with increased median overall survival: 26 months (n=46; interquartile range 20–44) versus 9.1 months (n=55; 4.1–20, P<0.0001). No significant survival benefit was seen with the use of bevacizumab (25 vs. 12 months; P=0.09), ipilimumab (28 vs. 13 months; P=0.07), or kinase inhibitors (24 vs. 13 months; P=0.06). Multivariate analysis showed LT as the only therapy to significantly improve survival (risk ratio 0.23, P=0.0003). However, these patients had better markers of prognosis at the time of treatment. These data suggest that survival was improved in patients who were amenable to LTs; however, they had better prognostic markers at diagnosis of metastatic disease. Ongoing prospective clinical trials will define the roles of these novel agents in this patient population.
The molecular basis of Chinese herbs (Astragali and Angelica) on increasing serum albumin synthesis in nephrotic rats

SUMMARY: Our previous studies have shown that two Chinese herbs, Astragali and Angelica, combined with an adequate protein intake can ameliorate the reduction in serum albumin, and improve the ratio of protein synthesis to catabolic rate without significant influence on urinary protein in both nephrotic patients and rats. This study was designed to investigate mechanisms by studying the effect of Astragali and Angelica on albumin synthesis in experimental nephrotic syndrome (NS), measuring the effect on hepatic albumin mRNA expression and gene transcription. Male Sprague‐Dawley (SD) rats were divided into eight groups: (1) normal control, C; (2) nephrotic control, NC; (3) treated with Astragali and Angelica, Ast & Ang; (4) treated with Astragali alone, Ast; (5) treated with Angelica alone, Ang; (6) treated with Astragali polysaccharide I, Ast I (MW. 36 000); (7) treated with Astragali polysaccharide II, Ast II (MW. 12 500); (8) treated with Astragali glucoside, Ast G. Nephrotic syndrome in rats was induced by accelerated nephrotoxic nephritis. the herb extracts were force‐fed daily for 14 days, the animals were then sacrificed, and the serum and liver collected. the level of serum albumin, albumin mRNA and its gene transcription activity were measured using biochemistry, Northern blot analysis, run‐on assay and quantity in laser density screening. In the NC group, the level of serum albumin was significantly lower, the level of albumin mRNA in the liver was significantly higher and the activity of albumin gene transcription was increased compared with normal controls. In the Ast & Ang group, the urinary protein was not different to that in the NC group, while the level of serum albumin was significantly higher and both the level of albumin mRNA and the activity of albumin gene transcription were significantly higher. In each component therapy group, the effect of increasing the level of serum albumin, the levels of albumin mRNA and activities of albumin gene transcription were no different compared with the NC group. Our results suggest that Astragali and Angelica increase albumin synthesis in the nephrotic rat by increasing liver albumin mRNA expression, at least in part by improving the activity of gene transcription. the extract of Astragali and Angelica was better effect than any components tested.
The ultraviolet microscopic transmission characteristics of human stratum corneum

This study has evaluated the ultraviolet light transmission characteristics of human stratum corneum at the single cell level using a low light level video microscope to measure the mean percentage transmission of light at different wavelengths and the variation in transmission across the stratum corneum. Stratum corneum was isolated by an enzymic technique and examined on a low light level UV video microscope. Quantitative evaluation of the transmitted monochromatic light for the underside of the layer was measured directly using a Kontron UNIPS image processor or indirectly with a Quantimet 920 image processor after video recording. Transmission distribution histograms were obtained from samples of stratum corneum taken from human breast, scalp, abdomen and leg. Mean transmission values were also derived and compared with diffuse transmission values obtained using the same tissue mounted on an integrating sphere. The UV microscopic transmission characteristics of enzyme separated stratum corneum clearly demonstrated that this structure was not an ideal diffuser. Uniform light intensity on the surface of the stratum corneum led to areas of transmitted intensity in close proximity that differed by factors ofthree to six fold, e.g. between regions of high (>70%) and low (<20%) brightness. However, the average transmission was found to be compatible with published data obtained by diffuse transmission spectrophotometry, taking into account the enhanced transmission arising from stratum corneum immersion in phosphate buffered saline. This was confirmed by the elevated values obtained by diffuse transmission spectrophotometry in this study for samples of stratum corneum prepared for UV microscopy being higher than these found in published data. It is obvious from these findings that viable cells in the epidermis are not exposed to a uniform incident light intensity even when this is true for the surface of skin. Studies of skin response to ultraviolet light at the single cell level must take account of the possibility of preferential exposure of specific sites in any subsequent explanation of cell sensitivity. This is in addition to the already well established cell cycle dependent ultraviolet sensitivity.
Influence of skin cleansing preparation acidity on skin surface properties

Two long‐term trials were conducted each over eight weeks to compare the effect of the regular application of skin cleansing preparations of pH 5.5 and pH 8.5 and pH 5.5 and pH 7.0 respectively on the surface pH, roughness and transepidermal water loss (TEWL) of normal human forehead and forearm skin. Both trials were based on a cross‐over design: five healthy volunteers started with a pH 5.5 preparation and switched to the other after four weeks, five additional volunteers used the preparations in the opposite order. While the skin surface pH was markedly lower in those individuals using the pH 5.5 preparation at each examination, as compared to those using the pH 8.5 or pH 7.0 preparation, no such difference could be established with respect to skin roughness and TEWL. Hence the skin irritancy of a cleansing preparation does not seem to be linked to its pH within the pH ranges tested.
Episodic Memory and Age-Related Deficits in Inhibitory Effectiveness

Background/Study Context: Age-related deficits in inhibitory control are well established in some areas of cognition, but evidence remains inconclusive in episodic memory. Two studies examined the extent to which a loss in inhibitory effectiveness—as measured by the extent of retrieval-induced forgetting (RIF)—is only detectable in (1) the very old, and (2) that a failure to control for noninhibitory mechanisms can lead to the misinterpretation of intact inhibition in episodic memory in the very old. Methods: In Study 1, the authors employed a modified independent cue test—to provide as clean a measure of inhibitory functioning as possible—and examined whether there were significant differences in inhibitory effectiveness between younger-old (60–64 years), old (65–69 years), and older-old (70–74 years) adults. In Study 2, the authors directly manipulated the contribution of output interference (a noninhibitory mechanism) to RIF in a group of young adults (18–34 years), old (61–69 years), and older-old (70–85 years) adults. Results: In Study 1, both younger-old (60–64 years) and old (65–69 years) adults demonstrated RIF on the modified independent cue test but older-old (70–74 years) adults did not. In Study 2, all age groups demonstrated RIF in conditions where output interference was promoted. However, when output interference was controlled, only the young (18–34 years) and old (61–69 years) age groups demonstrated RIF; the older-old (70–85 years) age group did not. Conclusions: The findings suggest that inhibitory functioning remains intact in older adults under the age of 70 years. However, a misleading impression can be formed of inhibitory effectiveness in adults over the age of 70 when memory tests do not exclude the use of noninhibitory processes, such as output interference. These two issues may partly explain the previous inconclusive findings regarding inhibitory deficits in normal aging.
Endothelin-1 in the tumor microenvironment correlates with melanoma invasion

Endothelin-1 (ET-1) is a vasoactive peptide that also plays a role in the tanning response of the skin. Animal and cell culture studies have also implicated ET-1 in melanoma progression, but no association studies have been performed to link ET-1 expression and melanoma in humans. Here, we present the first in-vivo study of ET-1 expression in pigmented lesions in humans: an ET-1 immunohistochemical screen of melanocytic nevi, melanoma in situ lesions, invasive melanomas, metastatic melanomas, and blue nevi was performed. Twenty-six percent of melanocytic nevi and 44% of melanoma in situ lesions demonstrate ET-1 expression in the perilesional microenvironment, whereas expression in nevus or melanoma cells was rare to absent. In striking contrast, 100% of moderately to highly pigmented invasive melanomas contained numerous ET-1-positive cells in the tumor microenvironment, with 79% containing ET-1-positive melanoma cells, confirmed by co-staining with melanoma tumor marker HMB45. Hypopigmented invasive melanomas had reduced ET-1 expression, suggesting a correlation between ET-1 expression and pigmented melanomas. ET-1-positive perilesional cells were CD68-positive, indicating macrophage origin. Sixty-two percent of highly pigmented metastatic melanomas demonstrated ET-1 expression in melanoma cells, in contrast to 28.2% of hypopigmented specimens. Eighty-nine percent of benign nevi, known as blue nevi, which have a dermal localization, were associated with numerous ET-1-positive macrophages in the perilesional microenvironment, but no ET-1 expression was detected in the melanocytes. We conclude that ET-1 expression in the microenvironment increases with advancing stages of melanocyte transformation, implicating a critical role for ET-1 in melanoma progression, and the importance of the tumor microenvironment in the melanoma phenotype.
Aiming for the heart: targeted delivery of drugs to diseased cardiac tissue

Background: The development of a number of regenerative strategies in recent years for curing heart disease represents a paradigm shift away from conventional approaches which aim to manage heart disease. Effective administration of pharmaceutical agents targeted directly to the diseased tissue is the key to unlocking the potential of regenerative strategies, which could augment current conventional treatments. Objective: The authors review recent advances in targeted drug delivery to diseased cardiac tissue. Methods: Various therapeutic methodologies designed to selectively deliver pharmaceutical agents to diseased cardiac tissue are discussed in this review. Conclusion: Targeted delivery of survival and engraftment promoting factors to damaged cardiac tissue can be an important strategy, for example, in creating a suitable microenvironment encouraging the engraftment of stem cells. Further progress in this emerging field is contingent on the discovery of new biomarkers that are upregulated in damaged cardiac tissue and can be targeted for selective drug delivery. Once fully realized, breakthroughs in this field will have direct applications in the diagnosis and treatment of heart disease through more effective tissue-specific drug delivery and improved imaging modalities.
Psychological characteristics of early-stage melanoma patients: a cross-sectional study on 204 patients

The presence of psychological distress has a negative impact not only on cancer patients’ quality of life but also on the course of the disease, with slower recovery and increased morbidity. These issues are of particular importance in melanoma patients (MP), who remain at risk of disease progression for many years after diagnosis. This study aimed to investigate psychological distress, coping strategies, and their possible relationships with demographic–clinical features in patients with early-stage melanoma in follow-up. The investigation focused in particular on whether the psychological profile differed between patients at different melanoma stages. Data of 118 patients with melanoma in the Tis-Ia stages (MP_Tis-Ia) and 86 patients with melanoma in the Ib–IIa–IIb stages (MP_Ib–II) were gathered through a self-administered survey and compared using a cross-sectional design. The results evidenced a high percentage of anxiety (25%) and distress symptoms (44%), whereas depressive symptoms seemed less frequent (8%). Psychological distress was higher in women than in men, and in patients with a higher educational level. Nevertheless, no significant differences were found between MP_Tis-Ia and MP_Ib–II. With respect to coping style, the patients in this sample adopted predominantly positive and active strategies. Correlational analyses showed that maladaptive coping strategies such as behavioral disengagement, denial, self-distraction, and self-blame were most strongly related to increased levels of psychological distress. The high presence of anxiety and distress symptoms, their relationship, and the use of negative coping strategies underline the importance of psychological distress screening also in early-stage MP, including at long-term follow-up.
Expression and function of neurotrophins and their receptors in human melanocytes

Melanocytes and cells of the nervous system are of common ectodermal origin and neurotrophins (NT) have been shown to be released by human keratinocytes. We investigated the expression and function of NT [nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF), NT‐3, NT‐4/‐5] and their receptors in human melanocytes. Human melanocytes produce all NT in different amounts, whereas they only release NT‐4. NT‐4 release is downregulated, whereas NT‐3 is upregulated by ultraviolet (UVB) irradiation. Melanocytes treated with phorbol 12‐myristate 13‐acetate (PMA) express TrkA and TrkB, but not TrkC. NT fail to stimulate melanocyte proliferation, whereas they stimulate the synthesis of tyrosinase and tyrosinase‐related protein‐1 (TRP‐1). Finally, NT‐3, NT‐4 and NGF increase melanin production. Taken together, these results demonstrate an intriguing interaction between melanocytes and the nervous system. We speculate that NT could be considered the target of therapy for disorders of skin pigmentation.
The select panel for the promotion of child health: Injury -- Recommendations in retrospect

In 1980 recommendations were made to prevent child injuries. They addressed the following topics: (1) motor vehicle safety; (2) home and neighborhood safety; and (3) the development of a national data base from which policy can be formulated. There is evidence that progress has been made since the morbidity and mortality rates for accidents have decreased. Language: en
S100B in bone marrow aspirates in healthy individuals and malignant melanoma patients

The aim of this study was to evaluate S100B in bone marrow (BM) plasma from malignant melanoma patients. BM aspirates and peripheral blood (PB) plasma from 56 patients and BM aspirates from 29 healthy volunteers were collected. S100B was measured using an immune radiometric assay, which is a two-site sandwich assay based on monoclonal antibodies recognizing the &bgr;-subunit. In the control population, the median S100B level in BM plasma was 9.0 μg/l (26 women and three men), an unexpectedly high value compared with the median S100B level in PB<0.05 μg/l. S100B levels in BM seems to be sex dependent. Median S100B levels in samples taken from male melanoma patients was 26.7 μg/l in contrast to 9.3 μg/l in female patients (Mann–Whitney P<0.002). The elevated BM S100B in melanoma patients could not be explained by presence of melanoma cells in the BM, as the values also were increased to the same extent in patients with no detectable BM metastases. In attempts to identify the source of S100B in BM, cytospins from five patients with high S100B values were stained, but none of the BM cells stained positive. S100B levels in PB were dependent on the stage of melanoma disease and there was a significant shorter survival time in the group of patients with elevated S100B compared with the group with normal S100B values, (log rank test: P=0.04). In BM taken from melanoma patients, however, there were no association between S100B levels and survival. The median S100B level in BM aspirates from healthy female volunteers and BM samples from female melanoma patients were 8.1 and 9.3 μg/l both manifold higher than the cut-off value for S100B in PB (0.2 μg/l). The median S100B in the samples taken from male melanoma patients was nearly three times higher than in the female patients. Unlike S100B in PB, S100B in BM demonstrated no prognostic value. The explanation for the unexpected high S100B in BM remains elusive.
Temozolomide associated with PEG-interferon in patients with metastatic melanoma: a multicenter prospective phase I/II study

Metastatic melanoma treatment remains disappointing, and a combined approach by chemotherapy and immunotherapy might increase the response rates through a synergistic action. Accordingly, a clinical trial using oral temozolomide (TMZ) and subcutaneous PEG-interferon &agr;-2b (PEG) in patients with metastatic melanoma was designed to determine the maximal tolerated dosage of both drugs and the antitumoral response. A multicenter, prospective, phase I/II study was conducted in 31 metastatic melanoma patients, without cerebral metastasis. Dose escalation was performed according to the modified continual reassessment method scale and resulted in four cohorts of patients: TMZ 150 mg/m2 5 days/week each 4 weeks and PEG 0.5 μg/kg/week – TMZ 150 mg/m2 5 days/week and PEG 1.0 μg/kg/week – TMZ 200 mg/m2 5 days/week and PEG 0.5 μg/kg/week – TMZ 200 mg/m2 5 days/week and PEG 1.0 μg/kg/week. Patients received a maximum of six cycles. Thirty-three patients were enroled in this study: one in the first dose level, one in the second one, 18 in the third one and 11 in the fourth one. At level 4, four of 11 patients experienced dose-limiting toxicity and four nondose-limiting toxicity; toxicity was mainly hematologic (grade IV thrombocytopenia). An objective response was observed in five patients (two complete response and three partial response) receiving level 3 or 4 of treatment. The disease remained stable in three patients, and six of 31 patients were alive 24 months after enrolment. The association of oral TMZ with subcutaneous PEG in metastatic melanoma displayed an unacceptable hematological toxicity with the dosages of 200 mg/m2 5 days/week and 1 μg/week, respectively. At a lower level, this treatment was effective and deserves further investigations to define its indications in metastatic melanoma patients.