Miracle-dz/UniFAR-FTUs huggingface dataset:
Submicroscopic deletions at 7q region are associated with recurrent chromosome abnormalities in acute leukemia.

BACKGROUND AND OBJECTIVES Loss of heterozygosity (LOH) on the long arm of chromosome 7 (7q) has been frequently reported in several types of human cancer including hematologic malignancies. Moreover, monosomy of chromosome 7 and 7q deletions have been associated in acute myeloid leukemia (AML) with aggressive disease and poor prognosis. DESIGN AND METHODS Using a panel of 11 polymorphic microsatellite markers at bands 7q21-q36, we investigated fifty patients (acute myeloid leukemia [AML], n=33 and acute lymphoid leukemia [ALL], n=17) for LOH, a hallmark of possible involvement of tumor suppressor genes. In parallel, the same acute leukemia (AL) cases were studied by conventional cytogenetics. RESULTS A total of 48 spots of allelic loss were observed in 16 (32%) out of 50 patients (AML, n=11 and ALL, n=5). Among LOH+ve cases 3 showed chromosome 7 monosomies, whereas no cytogenetically detectable abnormalities were observed in chromosome 7 in the remaining 13. INTERPRETATION AND CONCLUSIONS Comparison with karyotypic results indicated that presence of LOH at 7q21-q36 was significantly associated with other chromosomal aberrations. In fact, an altered karyotype was detectable in 87% of LOH+ve and in 52% of LOH(-ve) AL cases (p=0.024). In addition, LOH at 7q was prevalently associated with unfavorable cytogenetic lesions (p=0.013). Our study represents the first report of a significant association between LOH and recurrent chromosomal abnormalities in AL patients suggesting that the 7q21-q36, region may be an unstable area prone to chromosome breakage in patients with an abnormal karyotype.
Localization and quantification of 5‐hydroxytryptophan and serotonin in the central nervous systems of Tritonia and Aplysia

Serotonin (5‐hydroxytryptamine, 5‐HT) plays a central role in several behaviors in marine molluscs and other species. In an effort to better understand the regulation of 5‐HT synthesis, we used high performance liquid chromatography (HPLC) with electrochemical detection and immunohistochemistry to measure and map the distribution of the immediate precursor of 5‐HT, 5‐hydroxytryptophan (5‐HTP), in two model opisthobranch molluscs, the nudibranch Tritonia diomedea and the anaspid Aplysia californica. HPLC measurements showed that 5‐HTP is present at approximately the same level as the 5‐HT metabolite, 5‐hydroxyindolacetic acid (5‐HIAA) but is more than 100 times lower in concentration than either 5‐HT or dopamine in the same tissue. Specific 5‐HTP immunoreactivity was colocalized with serotonin in both species. The overall intensity of 5‐HTP immunoreactivity in individual ganglia agreed with HPLC measurements for those ganglia. The intensity of 5‐HTP immunolabeling varied between cell types and was correlated with the intensity of 5‐HT immunolabeling. In particular, differences in staining intensity were consistently seen among the three dorsal swim interneurons of the Tritonia swim central pattern generator circuit. Some nonserotonergic neurons also displayed low levels of 5‐HTP immunolabeling that were above background levels. Together, these results support the notion that production of 5‐HTP is a rate‐limiting step in serotonin synthesis and suggest that there may be additional regulation that allows 5‐HTP to accumulate to varying levels. J. Comp. Neurol. 437:91–105, 2001. © 2001 Wiley‐Liss, Inc.
Neonatal vs delayed-onset fourth branchial pouch anomalies: therapeutic implications.

OBJECTIVES To determine the presentation of third or fourth branchial pouch anomalies in various age groups of children and evaluate endoscopic cauterization as a treatment technique. DESIGN Retrospective study of patients treated from 2000 to 2009. SETTING Tertiary care children's hospital. PATIENTS Pediatric patients aged 0 to 18 years (mean age, 5.5 years), including 5 neonates. INTERVENTIONS Endoscopic and/or open surgical management of third and fourth branchial pouch anomalies; clinical and endoscopic follow-up. MAIN OUTCOME MEASURES Absence of clinical recurrence; closure of the sinus tract. RESULTS Two forms of presentation were identified: a neonatal form, characterized by a voluminous and compressive cervical mass (5 of 20 [25%]) and a childhood form, presenting as a cervical abscess (15 of 20 [75%]). The vast majority of our patients regardless of presentation were treated endoscopically (n = 19), with a success rate of 68% (13 of 19) after 1 procedure, 79% (15 of 19) after 2 procedures, and 89% (17 of 19) after 3 procedures. Neonatal and adult presentations require slightly different therapeutic approaches. CONCLUSIONS Third and fourth branchial pouch anomalies can present in 2 distinct forms: a neonatal form and a childhood form. The endoscopic technique should be the favored approach for both forms: whenever possible, in view of its simplicity, rapidity, and the lack of serious postoperative complications. Recurrences can be treated by repeated cauterization using the same technique, with good long-term outcomes. An age-based management algorithm has been developed.
An Immunohistochemical Study of the Expression of the Hypoxia Markers Glut-1 and Ca-IX in Canine Sarcomas

Tumor hypoxia has been associated with increased malignancy, likelihood of metastasis, and increased resistance to radiotherapy and chemotherapy in human medicine. Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that is induced by tumor hypoxia and regulates the pathways involved in cellular response and adaptation to the hostile tumor microenvironment. HIF-1 induces transcription of different proteins, including Ca-IX and Glut-1, which are considered endogenous markers of chronic hypoxia in solid tumors in humans. In this study, sections from 40 canine sarcomas (20 histiocytic sarcomas and 20 low-grade soft-tissue sarcomas) were immunostained for these markers. Expression of Glut-1 was scored based on percentage of positive staining cells (0 = <1%; 1 = 1%–50%; 2 = >50%) and intensity of cellular staining (1 = weak; 2 = strong); Ca-IX was scored based on percentage of positive cells (0 = <1%; 1 = 1%–30%; 2 = >30%). Intratumoral microvessel density was measured using CD31 to assess intratumoral neoangiogenesis. Histiocytic sarcomas showed statistically significant higher Glut-1 immunoreactivity and angiogenesis than did low-grade soft-tissue sarcomas. Intratumoral microvessel density in histiocytic sarcomas was positively associated with Glut-1 immunoreactivity score. These findings suggest a potential role of hypoxia in the biology of these tumors and may provide a base for investigation of the potential prognostic use of these markers in naturally occurring canine tumors.
Sitagliptin added to previously taken antidiabetic agents on insulin resistance and lipid profile: a 2‐year study evaluation

The aim of this study was to evaluate whether the positive effects of sitagliptin on glycemic control and insulin resistance were maintained also after 2 years of therapy and whether sitagliptin could be effective also in improving lipid profile. In this randomized, double‐blind, placebo‐controlled trial, 205 patients with type 2 diabetes in therapy with different antidiabetic drugs were randomized to add sitagliptin 100 mg once a day or placebo to their current therapy. We evaluated at the baseline and after 6, 12, 18, and 24 months the following parameters: body mass index, glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA‐IR), total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), triglycerides (Tg). Sitagliptin, added to previously taken antidiabetic agents, proved to be effective in improving glycemic profile, reducing HbA1c by −17.5%, FPG by −12.7%, PPG by −20.5%. Regarding insulin resistance, sitagliptin decreased FPI by −8.3% and HOMA‐IR by −20.0%, confirming that what have been already reported in short‐term studies can be applied also after 2 years of treatment. Sitagliptin also reduced body weight by −4.3%. Our study also showed the positive effect of sitagliptin on lipid profile; in particular, sitagliptin decreased TC by −13.3%, LDL‐C by −20.4%, and Tg by −32.3%, and also increased HDL‐C by + 13.6%. Sitagliptin proved to be effective on glycemic profile and insulin resistance even after 2 years of therapy and to be effective in improving body weight and lipid profile.
Functional analysis of the Fusarium graminearum phosphatome.

Phosphatases are known to play important roles in the regulation of various cellular processes in eukaryotes. However, systematic characterization of the phosphatome has not been reported in phytopathogenic fungi. The wheat scab fungus Fusarium graminearum contains 82 putative phosphatases. The biological functions of each phosphatase were investigated in this study. Although 11 phosphatase genes appeared to be essential, deletion mutants of the other 71 phosphatase genes were obtained and characterized for changes in 15 phenotypes, including vegetative growth, nutrient response and virulence. Overall, the deletion of 63 phosphatase genes resulted in changes in at least one of the phenotypes assayed. Interestingly, the deletion of four genes (Fg06297, Fg03333, Fg03826 and Fg07932) did not dramatically affect hyphal growth, but led to strongly reduced virulence. Western blot analyses showed that three phosphatases (Fg10516, Fg03333 and Fg12867) functioned as negative regulators of the mitogen-activated protein kinase signaling pathways. In addition, we found, for the first time, that FgCdc14 is dispensable for growth, but plays an important role in ribosome biogenesis. Overall, in this first functional characterization of the fungal phosphatome, phosphatases important for various aspects of hyphal growth, development, plant infection and secondary metabolism were identified in the phytopathogenic fungus F. graminearum.
Antipsychotic‐Induced Hyperprolactinemia

Use of antipsychotic agents has been associated with hyperprolactinemia, or elevated prolactin levels; this hormonal abnormality can interfere with the functioning of repro ductive, endocrine, and metabolic systems. As antipsychotic agents are increasingly used for both United States Food and D rug Administratio n‐a ppro ved and nonapprove d indicatio ns, many individuals are at risk for developing antipsychotic‐induced hyperprolactinemia. First‐generation antipsychotics pose the greatest risk of causing this adverse effect; however, second‐generation antipsychotics, particularly risperidone and paliperidone, also often increase prolactin secretion. Hyperprolactinemia has short‐ and long‐term consequences that can seriously affect quality of life: menstrual disturbances, galactorrhea, sexual dysfunction, gynecomastia, infertility, decreased bone mineral density, and breast cancer. Although many of these are definitively connected to elevated prolactin levels, some, such as breast cancer, require further study. Both clinicians and patients should be aware of hyperprolactinemia‐associated effects. To prevent or alleviate the condition, tailoring an antipsychotic drug regimen to each individual patient is essential. In addition, the risk of hyperprolactinemia can be minimized by using the lowest effective dose of the antipsychotic agent. If the effects of prolactin are evident, the drug can be changed to another agent that is less likely to affect prolactin levels; alternatively, a dopamine agonist may be added, although this may compromise antipsychotic efficacy. Additional research is needed to clarify the appropriate level of monitoring, the long‐term effects, and the optimal treatment of antipsychotic‐induced hyperprolactinemia.
Clinical and Laboratory Investigations Impaired sweating function in adult atopic dermatitis: results of the quantitative sudomotor axon reflex test

Background Impaired sweating is thought to be a cause of barrier dysfunction in atopic dermatitis (AD). Objectives To examine the sweating function in AD in a quantitative manner. Methods We investigated the sweating response of lesional and non-lesional skin of adult patients with AD by a quantitative sudomotor axon reflex test in which the axon reflex is stimulated by acetylcholine iontophoresis. Sweat volume on the volar aspect of the forearm was measured in 18 adult patients with AD and in 40 non-atopic controls; five patients with Sjögren’s syndrome were also studied as disease comparators. We also evaluated the sweating function in four AD patients after topical corticosteroid therapy. Latency time, direct (DIR) sweat volume and axon reflexmediated indirect (AXR) sweat volume were the variables studied. Results The latency time in AD patients was significantly prolonged and AXR sweat volume significantly reduced compared with those in non-atopic control subjects. The latency time and AXR sweat volume of lesional AD skin were significantly more prolonged and reduced, respectively, than those of non-lesional skin. In contrast, the DIR sweat volume of lesional or non-lesional AD skin induced by direct stimulation with acetylcholine was only slightly reduced when compared with that in non-atopic controls. Latency time and sweat volumes of lesional and non-lesional AD skin improved after topical corticosteroid therapy. Conclusions These results suggest that the impaired sweat response in AD is attributable to an abnormal sudomotor axon reflex, which is reversed by topical corticosteroid administration.
Poor Prognosis in Children with Acute Nonlymphoblastic Leukemia in Turkey

Two hundred fourteen children with acute nonlymphoblastic leukemia (ANLL) were diagnosed between July 1975 to January 1987 in our center. Only 106 (50%) of the children could be treated. An initial hematologic remission was attained in 61 (58%) with a median duration of hematologic remission of 7.5 months and median survival of 12 months. Five patients who completed 36 months of therapy are still in initial remission, <84 months. Exophthalmos at presentation, which is clearly related to shorter duration of remission, was observed in 11% of these children. In two cases, it was the first sign of leukemia, 6 and 7 months prior to obvious bone marrow involvement. Twenty percent of the 61 patients who achieved remission discontinued their chemotherapy during the course of treatment while they were in remission, which indicates a different problem in the treatment of these patients in Turkey. Despite administration of similar treatment protocols, the prognosis of our patients was worse than the results observed in developed countries. We conclude that poor socioeconomic and nutritional conditions should also be considered among the high-risk factors for children with ANLL, as experienced in our patients with acute lymphoblastic leukemia (ALL).
Educational campaign for proper medication disposal.

OBJECTIVE To assess the effect of an educational intervention on pharmacists' attitudes and knowledge about medication disposal. METHODS In September 2005, a survey was mailed to 488 registered pharmacists serving as experiential education preceptors to Massachusetts College of Pharmacy and Health Sciences students in 27 states throughout the country. Mailing of this presurvey occurred 2 months before an educational intervention. An identical postsurvey was mailed to the 223 respondents to the presurvey 3 months after the intervention. The main outcome measure was change in pharmacist attitudes and knowledge about medication disposal after educational intervention. RESULTS 158 pharmacists (32% response rate) completed the pre- and postsurveys. Before the intervention, 47% of pharmacists perceived inappropriate medication disposal to be an environmental problem compared with 57% after the intervention (P = 0.03). Similarly, when asked about medication disposal, 10% correctly indicated that patients could arrange for hazardous waste pick up compared with 20% postintervention (P < 0.01). Conversely, 19% incorrectly indicated that patients should wash medications down the sink compared with 5.6% postintervention (P < 0.01). CONCLUSION A brief educational intervention is effective at changing pharmacists' attitudes and knowledge of inappropriate and environmentally unsafe medication disposal practices. Pharmacists receiving the educational intervention were more likely to report that they would recommend appropriate methods of medication disposal. Further educational efforts are necessary for improving pharmacists' knowledge regarding safe medication disposal practices.
Upregulation of osteoclast α2β1 integrin compensates for lack of αvβ3 vitronectin receptor in Iraqi‐Jewish‐type Glanzmann thrombasthenia

Summary. Osteoclasts utilize αvβ3 integrin adhesion to bone matrix during bone resorption. We have generated osteoclasts from the peripheral blood of Iraqi‐Jewish patients with Glanzmann thrombasthenia (GT) who are completely deficient in β3 integrin and exhibit a haemorrhagic diathesis resulting from the absence of platelet αIIbβ3. We show that, in contrast to osteoclasts generated from normal subjects or patients with αIIb integrin deficiency, GT osteoclasts lack αvβ3. These osteoclasts exhibited a two‐ to fourfold increase in α2 and β1 integrin expression, whereas other αv integrins, including αvβ5, were not significantly affected. An accompanying decrease in bone resorption was observed, with 44% and 59% declines in pit number and depth, respectively, and resorption lacunae showed abnormal morphology on scanning electron microscopy. However, osteoclasts from GT developed in similar numbers to controls and exhibited an otherwise ‘normal’ phenotype. We conclude that the observed rise in α2β1 expression compensates for the chronic genetic deficiency of αvβ3 in osteoclasts from patients with GT and is sufficient to enable bone resorption to proceed, albeit to a submaximal extent. This explains why Iraqi‐Jewish patients with GT do not have osteopetrosis.
Oxidized Alkyl Phospholipids Are Specific, High Affinity Peroxisome Proliferator-activated Receptor γ Ligands and Agonists*

Synthetic high affinity peroxisome proliferator-activated receptor (PPAR) agonists are known, but biologic ligands are of low affinity. Oxidized low density lipoprotein (oxLDL) is inflammatory and signals through PPARs. We showed, by phospholipase A1 digestion, that PPARγ agonists in oxLDL arise from the small pool of alkyl phosphatidylcholines in LDL. We identified an abundant oxidatively fragmented alkyl phospholipid in oxLDL, hexadecyl azelaoyl phosphatidylcholine (azPC), as a high affinity ligand and agonist for PPARγ. [3H]azPC bound recombinant PPARγ with an affinity (K d (app) ≈40 nm) that was equivalent to rosiglitazone (BRL49653), and competition with rosiglitazone showed that binding occurred in the ligand-binding pocket. azPC induced PPRE reporter gene expression, as did rosiglitazone, with a half-maximal effect at 100 nm. Overexpression of PPARα or PPARγ revealed that azPC was a specific PPARγ agonist. The scavenger receptor CD36 is encoded by a PPRE-responsive gene, and azPC enhanced expression of CD36 in primary human monocytes. We found that anti-CD36 inhibited azPC uptake, and it inhibited PPRE reporter induction. Results with a small molecule phospholipid flippase mimetic suggest azPC acts intracellularly and that cellular azPC accumulation was efficient. Thus, certain alkyl phospholipid oxidation products in oxLDL are specific, high affinity extracellular ligands and agonists for PPARγ that induce PPAR-responsive genes.
Single-session high intensity focussed ablation (HIFU) versus open cervical hemithyroidectomy for benign thyroid nodule: analysis on early efficacy, safety and voice quality

Abstract Background: High intensity focussed ultrasound (HIFU) is a promising non-surgical treatment for symptomatic benign thyroid nodule. We aimed to compare early efficacy, safety and voice quality between HIFU ablation and open thyroidectomy. Methods: Consecutive patients who underwent single-session HIFU ablation or a hemithyroidectomy for symptomatic benign thyroid nodule were included. The 6-month extent of nodule shrinkage, symptom improvement score, thyroid function, hospital stay and cost were compared between the two procedures. Safety was defined by absence of major complications like recurrent laryngeal nerve injury and skin burn. Voice quality was assessed by a computerised multi-dimensional voice programme and a Voice Handicap Index (VHI) questionnaire 1-month after treatment. Results: Altogether, 43 patients had HIFU and 103 patients had a hemithyroidectomy. In the HIFU group, the extent of nodule shrinkage at 6-month was 51.71 ± 16.04%. No patients in the HIFU group suffered skin burn or hypothyroidism. The HIFU group had a significantly shorter length of hospital stay (0.3 vs. 1.0 day, p < 0.001), lower incidence of subclinical hypothyroidism (1/43 vs. 21/103, p = 0.008), higher symptom improvement score (p = 0.009) and was less costly (USD 1923.1 vs. USD 5384.6). Relative to HIFU, pitch quality also worsen after surgery (p < 0.05). Conclusions: Relative to surgery, single HIFU ablation appeared efficacious and safe. Apart from shorter hospital stay, less subclinical hypothyroidism, being scar-less, lower cost and more symptom improvement, HIFU patients were less affected by a pitch problem in the first month. This study provides a strong argument for HIFU ablation as a treatment for symptomatic benign thyroid nodule.
[Evaluation of patient compliance among hypertensive patients treated by specialists].

OBJECTIVES To evaluate compliance with antihypertensive therapy by a self-report in patients referred to hypertension specialists. METHODS We studied 484 treated hypertensive subjects referred to several hypertension clinics and who were treated since at least one year. Patients were asked to fill in the Compliance Evaluation Test (CET), a questionnaire with 6 questions previously validated to assess factors that could affect medication compliance. We defined patients as "good compliant" when "No" was answered to the 6 items, as "minor noncompliant" when 1 or 2 "Yes" were answered, and as "noncompliant" when 3 or more "Yes" were answered. A good agreement was demonstrated between CET score and compliance evaluated by the number of pills missed during the previous month according to patient interview. RESULTS We observed 8% of "noncompliant", 53% of "minor noncompliant" and 39% of "good compliant". [table: see text] Logistic regression analysis including age, sex, education level, blood pressure level and the number of antihypertensive tablets confirm the statistical differences observed. CONCLUSIONS In clinical practice, a method of assessing medication compliance is to ask the patient for a self-report interview. We demonstrated that the compliance evaluation test is able to detect factors usually associated with poor compliance (young age, elevated blood pressure, number of tablets per day). The use of the compliance evaluation test may help physicians to face the problem of nonadherence among their hypertensive patients.