Miracle-dz/UniFAR-FTUs huggingface dataset:
Tolerability and Efficacy of Naratriptan Tablets in the Acute Treatment of Migraine Attacks for 1 Year

Objective and design: This open‐label study was conducted to evaluate the tolerability and efficacy of the 5HT1 agonist naratriptan with repeated use in the acute treatment of migraine attacks for 1 year. Four hundred and seventeen (417) migraine patients treated 15 301 migraine attacks over the course of the study. Results: The results show that 84% of attacks treated with a single 2.5 mg dose of naratriptan were not associated with the occurrence of an adverse event. The percentage of attacks associated with an adverse event did not increase with number of doses used to treat a given attack (1 vs. 2) or duration of use (0–6 months vs. > 6–12 months). The only adverse events experienced in > 2% of attacks throughout the 1‐year study were nausea (3% of attacks), hyposalivation (2% of attacks), and drowsiness/sleepiness (2% of attacks). Headache relief 4 h post‐dose was reported in a median 70% of moderate or severe attacks and a median 86% of mild attacks treated with naratriptan tablets 2.5 mg. The percentages of patients reporting headache relief did not diminish as a function of increased duration of treatment (0–6 months vs. > 6–12 months) or frequency of use (for > 36 vs. < 36 attacks). The mean number of tablets taken per attack was 1.2. A second naratriptan 2.5 mg tablet was taken for headache recurrence in a mean 16% (median 8%) of attacks. Conclusion: The results of this study demonstrate that naratriptan tablets 2.5 mg taken for acute migraine attacks over a 1‐year period are well‐tolerated and effective.
FBXO15 regulates P‐glycoprotein/ABCB1 expression through the ubiquitin–proteasome pathway in cancer cells

Expression of P‐glycoprotein (P‐gp)/ABCB1 on cancer cell surfaces is a critical determinant of anticancer drug resistance. Regulators of P‐gp expression and function are key molecules controlling drug resistance. Here we report the mechanism underlying the ubiquitin–proteasome pathway‐mediated degradation of P‐gp. The proteasome inhibitor MG132 increased the P‐gp level, enhanced its ubiquitination, and delayed the disappearance of the ubiquitinated P‐gp. To search for regulators of P‐gp ubiquitination, MALDI–time of flight mass spectrometry analyses were carried out, and 22 candidates were identified as P‐gp binding partners. Among them, FBXO15/Fbx15 is known as an F‐box protein in the ubiquitin E3 ligase complex, Skp1‐Cullin1‐FBXO15 (SCFFbx15); therefore, we further studied the involvement of FBXO15 on P‐gp degradation. Coprecipitation assays revealed that FBXO15 bound to P‐gp. We screened ubiquitin‐conjugating enzyme E2s that bind to FBXO15 and P‐gp; Ube2r1/Cdc34/Ubc3 was found to be a binding partner. Exogenous FBXO15 expression enhanced P‐gp ubiquitination, but FBXO15 knockdown suppressed it. FBXO15 knockdown increased P‐gp expression without affecting its mRNA level. Ube2r1 knockdown decreased P‐gp ubiquitination, and simultaneous knockdown of Ube2r1 with FBXO15 further suppressed the ubiquitination. Ube2r1 knockdown increased P‐gp expression, suggesting that Ube2r1 is a partner of FBXO15 in P‐gp ubiquitination. FBXO15 knockdown enhanced vincristine resistance and lowered intracellular levels of rhodamine 123. These data suggest that FBXO15 and Ube2r1 regulate P‐gp expression through the ubiquitin–proteasome pathway.
Phase I/II study of bortezomib‐melphalan‐prednisolone for previously untreated Japanese patients with multiple myeloma

This phase I/II study was conducted to evaluate the safety and efficacy of bortezomib‐melphalan‐prednisolone in Japanese patients with previously untreated multiple myeloma who are ineligible for hematopoietic stem cell transplantation. One hundred and one patients were enrolled, and 99 patients received up to nine 6‐week cycles of bortezomib (0.7/1.0/1.3 mg/m2) on days 1, 4, 8, 11, 22, 25, 29, and 32 in cycles 1–4 and on days 1, 8, 22, and 29 in cycles 5–9, with melphalan (9 mg/m2) and prednisolone (60 mg/m2) on days 1–4 of each cycle. The recommended dose was determined in the phase I portion, and the overall response rate and safety of bortezomib‐melphalan‐prednisolone at the recommended dose were assessed in the phase II portion. The recommended dose of bortezomib was determined to be 1.3 mg/m2. Grade 3 or higher non‐hematological adverse events included diarrhea (12%) and peripheral neuropathy (10%); grade 4 hematological adverse events included lymphopenia (41%), neutropenia (30%), and thrombocytopenia (22%). Eleven patients had lung injury associated with bortezomib; two had grade 3 disease, and the other nine had grade 1 or 2 disease. Of the 86 patients treated with 1.3‐mg/m2 bortezomib in phases I and II, the median number of treatment cycles was 4.5, and the overall response rate was 70% (95% confidence interval: 59–79%). Bortezomib‐melphalan‐prednisolone with 1.3‐mg/m2 bortezomib was considered to be tolerable and effective in Japanese patients with previously untreated multiple myeloma. However, further investigation is needed to refine the administration schedule.
Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients

Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients Ben Goldacre. Harper Collins 4th Estate. 2012. £13.99 (pb). 364 pp. ISBN: 9780007350742 Bad Pharma isn’t funny - unlike the much praised predecessor, Bad Science . Goldacre’s style is as sharp and entertaining as ever, but his
RUBELLA IgG ANTIBODY IN WOMEN OF CHILD-BEARING AGE IN OYO STATE.

230 females of childbearing age from four different towns in Oyo State were screened for rubella specific IgG antibody using a sandwich ELISA test kit. Rubella IgG was detected in 215 (93.5%) of the females. 96% of the non-pregnant, 87.5% of the primigravida and 76% of the multigravida screened positive to the antibody. Ogbomoso, Ibadan, Oyo and Iseyin respectively had 96.1%, 94.2%, 90.5% and 88.2% of their samples positive for the rubella IgG antibody in them. It is imperative for the government to ensure that rubella vaccine is made available and routine so as to avert the risk of congenital rubella syndrome. African Journal of Clinical and Experimental Microbiology Vol. 9 (2) 2008 pp. 78-81
Weather Forecasting and Parallel Processing: a View from ECMWF

Operational numerical weather prediction requires that all available main-frame computing power be harnessed to the one task, in order to maintain operational schedules. ECMWF therefore became involved in parallel processing as soon as it became available on supercomputers. The main operational programs were restructured to use multitasking on a limited number of processors, currently 8. The availability of supercomputers with massively parallel architecture which is expected in the near future raises quite a number of major problems. These areas have been discussed in the biennial workshops held at ECMWF since 1984. Besides the user environment, the inter-dependency of hardware architecture and algorithms needs most attention. To study these questions, ECMWF became involved in the GENESIS project sponsored by the European Community. Initial results of this co-operation in the form of benchmark results will be presented. The challenges posed by new developments in weather prediction strategies will be highlighted and an assessment of the impact parallel computing will have on their being met will be made.
Tying the knot between cytokine and toll‐like receptor signaling in gastrointestinal tract cancers

Inflammation‐associated malignancies of the gastrointestinal tract (GI), including those of the stomach and colon, collectively rank as the highest cause of cancer‐related deaths worldwide. It has been well documented that the deregulated activation of the archetypal pro‐inflammatory and oncogenic transcription factors nuclear factor‐kappa B (NF‐κB) and signal transducer and activator of transcription (STAT)3 is a common feature of GI cancers that invariably correlates with poor prognosis. Signal transducer and activator of transcription 3 and NF‐κB are key downstream signal transducers of the interleukin (IL)‐6 cytokine and toll‐like receptor (TLR) families, respectively, and until recently, the potential involvement of these two families in the pathogenesis of cancer has been investigated in isolation. However, there is now emerging evidence of the complex interplay between the IL‐6 cytokine and TLR families in GI tract cancers, with a surprising twist in the identification of a non‐immune role for specific TLR family members. In this review, we discuss the molecular mechanisms associated with cross‐talk between the IL‐6 cytokine family/STAT3 signaling network and the TLR family/NF‐κB signaling network, and we address the potential benefit of their therapeutic targeting in gastric and colorectal cancers.
Columnar metaplasia in a surgical mouse model of gastro‐esophageal reflux disease is not derived from bone marrow‐derived cell

The incidence of esophageal adenocarcinoma has increased in the last 25 years. Columnar metaplasia in Barrett's mucosa is assumed to be a precancerous lesion for esophageal adenocarcinoma. However, the induction process of Barrett's mucosa is still unknown. To analyze the induction of esophageal columnar metaplasia, we established a mouse gastro‐esophageal reflux disease (GERD) model with associated development of columnar metaplasia in the esophagus. C57BL/6 mice received side‐to‐side anastomosis of the esophagogastric junction with the jejunum, and mice were killed 10, 20, and 40 weeks after operation. To analyze the contribution of bone marrow‐derived cells to columnar metaplasia in this surgical GERD model, some mice were transplanted with GFP‐marked bone marrow after the operation. Seventy‐three percent of the mice (16/22) showed thickened mucosa in esophagus and 41% of mice (9/22) developed columnar metaplasia 40 weeks after the operation with a mortality rate of 4%. Bone marrow‐derived cells were not detected in columnar metaplastic epithelia. However, scattered epithelial cells in the thickened squamous epithelia in regions of esophagitis did show bone marrow derivation. The results demonstrate that reflux induced by esophago‐jejunostomy in mice leads to the development of columnar metaplasia in the esophagus. However, bone marrow‐derived cells do not contribute directly to columnar metaplasia in this mouse model.
Diurnal Variations of Blood Constituents in Young Thoroughbred Horses.

To delineate points to be attended to in utilizing blood constituents as parameters for diagnostic examination of race horses, serial changes of blood constituents were followed on a day of resting and a day of physical exercise in five 2-year-old Thoroughbred horses (2 males and 3 females) currently under a course of training equivalent to that for young prospective race horses. Of 31 blood constituent parameters assessed which are commonly measured in the clinical setting, 27 parameters revealed significant within-day variations(P<0.05). Variations by 20% or more which are presumed to be of practical value from their nature were observed for 14 parameters: total leukocyte counts, neutrophil counts, lymphocyte counts, eosinophil counts, and serum levels of lactate dehydrogenase, glutamic dehydrogenase, total bilirubin, uric acid, glucose, triglyceride, potassium, inorganic phosphorus, triiodothyronine and thyroxine. Whilst the principal source of variations was physical exercise, there were several parameters which were inferred to be affected by such factors as feeding and daytime/night. Thus the present data indicated importance of due consideration of feeding conditions including quality and amount of physical exercise and of blood sampling time, for more accurate interpretation of data of hematologic and blood chemical tests.
ACE D/I polymorphism, migraine, and cardiovascular disease in women

Background: Interrelationships among the ACE deletion/insertion (D/I) polymorphism (rs1799752), migraine, and cardiovascular disease (CVD) are biologically plausible but remain controversial. Methods: Association study among 25,000 white US women, participating in the Women’s Health Study, with information on the ACE D/I polymorphism. Migraine and migraine aura status were self-reported. Incident CVD events were confirmed after medical record review. We used logistic regression to investigate the genotype-migraine association and proportional hazards models to evaluate the interrelationship among genotype, migraine, and incident CVD. Results: At baseline, 4,577 (18.3%) women reported history of migraine; 39.5% of the 3,226 women with active migraine indicated aura. During 11.9 years of follow-up, 625 CVD events occurred. We did not find an association of the ACE D/I polymorphism with migraine or migraine aura status. There was a lack of association between the ACE D/I polymorphism and incident major CVD, ischemic stroke, and myocardial infarction. Migraine with aura doubled the risk for CVD, but only for carriers of the DD (multivariable-adjusted relative risk [RR] = 2.10; 95% CI = 1.22–3.59; p = 0.007) and DI genotype (multivariable-adjusted RR = 2.31; 95% CI = 1.52–3.51; p < 0.0001). The risk was not significant among carriers of the II genotype, a pattern we observed for myocardial infarction and ischemic stroke. Conclusions: Data from this large cohort of women do not suggest an association of the ACE deletion/insertion (D/I) polymorphism with migraine, migraine aura status, or cardiovascular disease (CVD). The increased risk for CVD among migraineurs with aura was only apparent for carriers of the DD/DI genotype. Due to limited number of outcome events, however, future studies are warranted to further investigate this association.
Evalution of an Epidural Intracranial Pressure Monitoring System in Cats

Summary The accuracy of an inexpensive, easily implantable, epidural intracranial pressure (ICP) monitoring system was assessed in six normal cats by comparing measurements from this system to those obtained with a fiberoptic intraparenchymal monitoring system. The epidural monitoring system consisted of a three-way stopcock and saline-filled extension tubing, connected to a standard blood pressure transducer. Each cat was placed under halothane anesthesia and mechanically ventilated. Both an epidural and a fiberoptic intraparenchymal monitoring device were placed in the left cranium of each cat; correct placement was verified by computed tomography. Mean ICP values were simultaneously recorded from both monitoring devices. After obtaining baseline ICP measurements, the ICP was manipulated via ventilation, jugular compression, and pharmacologic agents. Arterial blood pressure levels, arterial blood gas values, end-tidal carbon dioxide levels, and end-tidal halothane levels were recorded throughout the study. Cerebral perfusion pressure was calculated for each level of ICP. Repeated measures analysis of variance method was used to compare mean ICP values between the two monitoring systems. No significant differences in ICP values obtained from the two systems were found (p>0.05) at any level of ICP. The results of this study show that the epidural monitoring system is a reliable alternative to the fiberoptic intraparenchymal ICP monitoring system in normal cats. The accuracy of the epidural monitoring system in pathologic states needs to be investigated.
On Reasoning About Rings

Distributed protocols are often composed of similar processes connected in a unidirectional ring network. Processes communicate by passing a token in a fixed direction; the process that holds the token is allowed to perform certain actions. Usually, correctness properties are expected to hold irrespective of the size of the ring. We show that the question of checking many useful correctness properties for rings of all sizes can be reduced to checking them on ring of sizes up to a small cutoff size. We apply our results to the verification of a mutual exclusion protocol and Milner's scheduler protocol.
On simulating a class of parallel architectures

The purpose of this paper is twofold. On one hand, we introduce the concept of P system with dynamic communication graphs in its full generality, independent of applications. On the other hand, we illustrate one application of it to the simulation of a class of parallel architectures. In this last direction we extend previous work concerned with the simulation of particular architectures.
Anterior nucleus of the thalamus

The anterior nucleus of thalamus (ANT) is a key component of the hippocampal system for episodic memory. The ANT consist of 3 subnuclei with distinct connectivity with the subicular cortex, retrosplenial cortex, and mammillary bodies. Via its connections with the anterior cingulate and orbitomedial prefrontal cortex, the ANT may also contribute to reciprocal hippocampal-prefrontal interactions involved in emotional and executive functions. As in other thalamic nuclei, neurons of the ANT have 2 different state-dependent patterns of discharge, tonic and burst-firing; some ANT neurons also contribute to propagation of the theta rhythm, which is important for mechanisms of synaptic plasticity of the hippocampal circuit. Clinical and experimental evidence indicate that damage of the ANT or its inputs from the mammillary bodies are primarily responsible for the episodic memory deficit observed in Wernicke-Korsakoff syndrome and thalamic stroke. Experimental models also indicate that the ANT may have a role in the propagation of seizure activity both in absence and in focal seizures. Because of its central connectivity and possible role in propagation of seizure activity, the ANT has become an attractive target for deep brain stimulation (DBS) for treatment of medically refractory epilepsy. The ANT is one of the nuclei preferentially affected in prion disorders, such as fatal familial insomnia, but the relationship between ANT involvement and the clinical manifestations of these disorders remains unclear. The connectivity patterns and electrophysiology of the ANT have been the subject of several reviews.1–4
Contraceptive practice in a tertiary hospital in south-south Nigeria

Background: The high maternal and infant mortality in sub-Saharan Africa has been associated with unplanned pregnancy, high parity and short birth intervals. Use of effective contraceptive methods significantly reduce maternal and infant mortality and improved quality of life. This study determines the contraceptive practice among clients in a tertiary hospital. Method: The record cards of all clients that accepted contraceptive methods in the family planning clinic at the University of Uyo Teaching Hospital, Uyo over a 7-year period were reviewed. Results: There were 1094 new contraceptive acceptors during the study period. The modal age group of the clients was 25 – 34 years (59.3%); majority of the clients were multiparous (59.8%), christians (99.6%) and 71.0% had at least secondary school education. The most commonly accepted contraceptive methods were the intrauterine contraceptive device (45.0%) and oral contraceptive pills (28.1%), while clinic personnel (63.1%), and friends and relatives (20.1%) were the most common sources of information on contraception. Conclusion: Intrauterine contraceptive device and oral contraceptive pills were the most frequently accepted methods of contraception. We advocate increase in the contraceptive options including implants. The print and electronic media should be more involved in the awareness programs on contraception.
Reduced expression of hsa-miR-27a-3p in CSF of patients with Alzheimer disease

Objective: We evaluated microRNAs (miRNAs) as potential biomarkers for Alzheimer disease (AD) by analyzing the expression level of miRNAs in CSF of patients with AD dementia and nonaffected control subjects. Methods: Using quantitative PCR, we profiled the expression level of 728 miRNAs in CSF of nonaffected control subjects and patients with clinically ascertained AD dementia, and we further compared the expression level of candidate miRNAs in 37 control subjects and 35 patients with AD dementia. Results: The level of hsa-miR-27a-3p in CSF is reduced in patients with dementia due to AD in 2 different cohorts of subjects (cohort 1: p = 0.008; cohort 2: p = 0.015; 2-tailed unpaired Welch t test). Moreover, low levels of hsa-miR-27a-3p were accompanied by high CSF tau levels and low CSF β-amyloid levels. Conclusions: Our pilot study highlights hsa-miR-27a-3p as a candidate biomarker for AD and provides the groundwork for further confirmation studies in larger cohorts and in other hospitals.
Antibody Against N‐terminal Domain of Phospholipid Scramblase 1 Induces Apoptosis in Colorectal Cancer Cells Through the Intrinsic Apoptotic Pathway

Phospholipid scramblase 1 involve in biological processes including phospholipid movement, proliferation, and apoptosis. Treatment with an antiphospholipid scramblase 1 antibody (NP1) has been demonstrated to inhibit cell proliferation in colorectal cancer. This study aimed to explore the role of NP1 treatment in the apoptosis of colorectal cancer cells. Results showed that NP1 treatment significantly increases the apoptosis of colorectal cancer cells via the activation of caspase 8, caspase 9, and caspase 3. Moreover, pretreatment with a caspase 8 inhibitor did not fully prevent the apoptotic effects of NP1. Taken together, these data indicate NP1 induces cell apoptosis primary through the intrinsic apoptotic pathway. NP1 may serve as a potential therapeutic agent.
Educational Considerations for Implanted Children: A Self-Contained Oral Program

In 1980, the first child in the United States was implanted with the 3M/House singlechannel device at the House Ear Institute in Los Angeles (Thielemier, Tonokowa, Peterson, 8c Eisenberg, 1985). Since that time, cochlear implants have proved to be beneficial to hearing-impaired children, and two other devices have become available to this population—the Nucleus 22-Channel Cochlear Implant System, which was approved by the FDA for general use in children, and the Clarion, which is currently approved for investigational use in children (see Koch, this issue). In the last 15 years, research studies have addressed numerous issues involved with pediatric cochlear implantat ion, including rehabilitation strategies, medical safety, candidacy, device improvements, and how to educate implanted children most effectively (e.g., Osberger, Miyamoto, Phillips, Kemink, Stroer, Firszt, & Novak, 1991; Osberger & Stroer, 1992: National Institutes of Health, 1995). This chapter describes how an auditory/oral educational strategy can help implanted children use auditory information to enhance listening skills and spoken language.
Cultural barriers to diabetes care in South Asians: arranged marriage – arranged complications?

ABSTRACT Social and cultural differences that are present in South Asian diabetic patients mayaffect their diabetes care. We present a case concerning a young South Asian girl withtype 2 diabetes mellitus who, despite persistent attempts at education andencouragement by health care professionals, was unwilling to accept treatment of herdiabetes. It was felt by both herself and her family that acceptance of the diagnosis ofdiabetes would adversely affect her marriage prospects. As a result she developedsevere microvascular complications before she finally agreed to treatment.Understanding potential cultural barriers to diabetes care may be vital in managingSouth Asian diabetic patients and it is important to establish education programmesspecifically aimed at removing the perceived stigma of diabetes in this population.Copyright © 2004 John Wiley & Sons, Ltd. Practical Diabetes Int 2004; 21(4): 154–156 KEY WORDS Asian; type 2 diabetes; cultural barriers Nirupam Goenka, MRCP(UK), SpecialistRegistrar in Diabetes and Endocrinology,Department of Diabetes and Endocrinology,Whiston Hospital, Prescot, Merseyside