Miracle-dz/UniFAR-FTUs huggingface dataset:
The effects of replacing dihydropyridine calcium‐channel blockers with angiotensin II receptor blocker on the quality of life of hypertensive patients

Hypertension is a major risk factor for cardiovascular events and the goal of treating hypertension is to prevent complications due to these events. However, some other properties, including few side‐effects and improvement of the quality of life (QOL), are desirable in a drug as well as its antihypertensive effect. Dehydropydine calcium‐channel blockers (DCCBs) are the most frequently used antihypertensive agents in Japan. The antihypertensive effect of DCCBs is satisfactory, but side‐effects, e.g. nocturia, flushing and palpitations, are a problem. The aim was to evaluate the effects of a change of treatment from DCCBs on the QOL of hypertensive patients. An open study was performed to evaluate the effects of switching treatment from DCCBs to angiotensin II receptor blocker (ARB) therapy on the QOL of hypertensive patients. The ARBs have been reported to be effective and well‐tolerated antihypertensive drugs. Candesartan cilexetil was selected because it is the most frequently used ARB in Japan. One hundred patients with mild to moderate hypertension, being treated with DCCBs, were randomly selected to receive candesartan cilexetil (8–12 mg once a day). The patients were followed for 3 months, while blood pressure (BP), side‐effects and QOL were monitored. BP was equally well controlled before and after the change of antihypertensive therapy. The candesartan cilexetil‐treated patients exhibited improvement of several aspects of QOL, including general symptoms, physical symptoms and well‐being, work and satisfaction and sleep scale. Emotional state and cognitive function also improved. Patients aged 65 years or younger achieved significant improvement of sexual function. Changing treatment from DCCBs to ARB therapy achieved equal BP control with a lower drug dose. Moreover, the change to cadesartan cilexetil had a positive impact on the QOL.
Molecular Basis of Red Cell Membrane Disorders

We will consider an array of genetic disorders of the red cell membrane. Some affect well-known genes. The mutations of most cases of hereditary spherocytosis (HS) are located in the following genes: ANK1, SPTB, SLC4A1, EPB42 and SPTA1, which encode ankyrin, spectrin β-chain, the anion exchanger 1 (band 3), protein 4.2 and spectrin α-chain, respectively. A dominant form of distal renal tubular acidosis also stems from distinct mutations in the SLC4A1 gene. The mutations responsible for hereditary elliptocytosis (HE) and its aggravated form, poikilocytosis (HP), lie in the SPTA1 and SPTB gene, already mentioned, and in the EPB41 gene encoding protein 4.1. Whereas in HS, the SPTA1 and SPTB gene mutations tend to abolish the synthesis of the corresponding chains, in HE/HP, they hinder spectrin tetramerization. Allele αLELY is a common polymorphic allele which plays the role of an aggravating factor when it occurs in trans of an elliptocytogenic allele of the SPTA1 gene. Southeast Asian ovalocytosis results from a 27- nucleotide deletion in the SLC4A1 gene. Besides these conditions in which the mutations were reached from known alterations in the proteins, other conditions required a positional cloning approach. Such are the genetic disorders of membrane permeability to monovalent cations. Knowledge is the most advanced as regards dehydrated hereditary stomatocytois (DHS). DHS was shown to belong to a pleiotropic syndrome: DHS + fetal edema + pseudohyperkalemia, which maps to 16q23–24. Concerning DHS and another disease of the same class, overhydrated hereditary stomatocytosis, splenectomy almost certainly appears to elicit thromboembolic accidents.
The Macrophage Is the Predominant Inflammatory Cell in Renal Allograft Intimal Arteritis

Background. Intimal arteritis defines acute vascular rejection in the Banff 97 schema. The arteritis is generally considered to be lymphocytic, although the cellular infiltrate in tubulitis is composed of both lymphocytes and macrophages. This study aimed to determine the extent of macrophage involvement in renal allograft intimal arteritis. Methods. We obtained archival biopsy material from 57 biopsies of 34 renal allografts transplanted between March 1999 and February 2002. All biopsies were diagnostic. We examined clinical and histological parameters. Biopsies were graded using the Banff 97 criteria. We identified macrophages and memory T cells using immunohistochemistry for CD68 and CD45RO, respectively. Results. In all, 24 biopsies showed borderline rejection, and 12 biopsies showed grade IA, 13 showed grade IB, and 8 showed grade II or III acute rejection. Both lymphocytes and macrophages were present in the tubulointerstitium in all grades of acute rejection. We identified intimal arteritis in 10 vessels in eight biopsies. The infiltrating cells invariably included CD68-positive cells; however, we saw intimal CD45RO-positive cells in only seven vessels. There were significantly more CD68-positive cells than CD45RO-positive cells (mean, 9.5 vs. 4.4 positive cells per vessel, P< 0.01). CD45RO cells were never the predominant component of the intimal inflammatory infiltrate. Conclusions. In the intimal arteritis of biopsies graded as Banff II or III acute rejection, the infiltrating cells were predominantly macrophages. T cells were in the minority. This finding challenges the assumption that the mononuclear cells in intimal arteritis are predominantly lymphocytic.
Development of a water calorimetry-based standard for absorbed dose to water in HDR 192Ir brachytherapy.

PURPOSE The aim of this article is to develop and evaluate a primary standard for HDR 192Ir brachytherapy based on 4 degrees C stagnant water calorimetry. METHODS The absolute absorbed dose to water was directly measured for several different Nucletron microSelectron 192Ir sources of air kerma strength ranging between 21,000 and 38,000 U and for source-to-detector separations ranging between 25 and 70 mm. The COMSOL MULTIPHYSICS software was used to accurately calculate the heat transport in a detailed model geometry. Through a coupling of the "conduction and convection" module with the "Navier-Stokes incompressible fluid" module in the software, both the conductive and convective effects were modeled. RESULTS A detailed uncertainty analysis resulted in an overall uncertainty in the absorbed dose of 1.90% (1 sigma). However, this includes a 1.5% uncertainty associated with a nonlinear predrift correction which can be substantially reduced if sufficient time is provided for the system to come to a new equilibrium in between successive calorimetric runs, an opportunity not available to the authors in their clinical setting due to time constraints on the machine. An average normalized dose rate of 361 +/- 7 microGy/(h U) at a source-to-detector separation of 55 mm was measured for the microSelectron 192Ir source based on water calorimetry. The measured absorbed dose per air kerma strength agreed to better than 0.8% (1 sigma) with independent ionization chamber and EBT-1 Gafchromic film reference dosimetry as well as with the currently accepted AAPM TG-43 protocol measurements. CONCLUSIONS This work paves the way toward a primary absorbed dose to water standard in 192Ir brachytherapy.
In Vivo Mitochondrial Import

The positive charges and structural properties of the mitochondrial leader sequence of aldehyde dehydrogenase have been extensively studied in vitro. The results of these studies showed that increasing the helicity of this leader would compensate for reduced import from positive charge substitutions of arginine with glutamine or the insertion of negative charged residues made in the native leader. In this in vivo study, utilizing the green fluorescent protein (GFP) as a passenger protein, import results showed the opposite effect with respect to helicity, but the results from mutations made within the native leader sequence were consistent between the in vitro and in vivo experiments. Leader mutations that reduced the efficiency of import resulted in a cytosolic accumulation of a truncated GFP chimera that was fluorescent but devoid of a mitochondrial leader. The native leader efficiently imported before GFP could achieve a stable, import-incompetent structure, suggesting that import was coupled with translation. As a test for a co-translational mechanism, a chimera of GFP that contained the native leader of aldehyde dehydrogenase attached at the N terminus and a C-terminal endoplasmic reticulum targeting signal attached to the C terminus of GFP was constructed. This chimera was localized exclusively to mitochondria. The import result with the dual signal chimera provides support for a co-translational mitochondrial import pathway.
Enhancing drop test efficacy for product quality improvement through interconnection shear tests

Comparison of data from high speed shear and drop test of four different tin based BGAs, DIP 34, DIP 33, DIP 18C and DIP 18B show that there is a good correlation between these two tests. The test performance ranking of the alloys from the drop test is DIP 33 > DIP 18C > DIP 18B > DIP 34 and that from the shear test is DIP 33 ~ DIP 18C > DIP 18B > DIP 34. There was a good matching of the failure mechanisms observed during these two tests. In addition, this article shows that by increasing the shear test speed, a better correlation with the drop test can be achieved. For the shear tests, there was a clear difference in the failure modes between samples having the lowest and highest shear strength values. In all the sample sets, the weakest link appears to be the component side IMC layer. This article shows that the shear test can be used as a proxy to the drop test to evaluate quality of components that are assembled in a mobile electronic product
Examining the effects of HIV self-testing compared to standard HIV testing services: a systematic review and meta-analysis

Introduction: HIV self‐testing (HIVST) is a discreet and convenient way to reach people with HIV who do not know their status, including many who may not otherwise test. To inform World Health Organization (WHO) guidance, we assessed the effect of HIVST on uptake and frequency of testing, as well as identification of HIV‐positive persons, linkage to care, social harm, and risk behaviour.
Fluoroquinolone and Quinazolinedione Activities against Wild-Type and Gyrase Mutant Strains of Mycobacterium smegmatis

ABSTRACT Quinazolinediones (diones) are fluoroquinolone-like inhibitors of bacterial gyrase and DNA topoisomerase IV. To assess activity against mycobacteria, C-8-methoxy dione derivatives were compared with cognate fluoroquinolones by using cultured Mycobacterium smegmatis. Diones exhibited higher MIC values than fluoroquinolones; however, MICs for fluoroquinolone-resistant gyrA mutants, normalized to the MIC for wild-type cells, were lower. Addition of a 3-amino group to the 2,4-dione core increased relative activity against mutants, while alteration of the 8-methoxy group to a methyl or of the 2,4-dione core to a 1,3-dione core lowered activity against mutants. A GyrA G89C bacterial variant was strikingly susceptible to most of the diones tested; in contrast, low susceptibility to fluoroquinolones was observed. Many of the bacteriostatic differences between diones and fluoroquinolones were explained by interactions at the N terminus of GyrA helix IV revealed by recently published X-ray structures of drug-topoisomerase-DNA complexes. When lethal activity was normalized to the MIC in order to minimize the effects of drug uptake, efflux, and ternary complex formation, a 3-amino-2,4-dione exhibited killing activity comparable to that of a cognate fluoroquinolone. Surprisingly, the lethal activity of the dione was inhibited less by chloramphenicol than that of the cognate fluoroquinolone. This observation adds the 2,4-dione structural motif to the list of structural features known to impart lethality to fluoroquinolone-like compounds in the absence of protein synthesis, a phenomenon that is not explained by X-ray structures of drug-enzyme-DNA complexes.
Influence of estrogen therapy on calcium, phosphorus, and other regulatory hormones in postmenopausal women: the MESA study.

BACKGROUND Estrogen therapy (ET) is associated with lower serum calcium and phosphorus concentrations and is known to increase bone mineral density (BMD). Other biomarkers of mineral metabolism may help understand the biological basis of these actions. METHODS We studied 2767 postmenopausal women in the Multi-Ethnic Study of Atherosclerosis, 862 (31%) of whom were using ET. We measured serum concentrations of calcium, phosphorus, 25-hydroxyvitamin D, 24,25-dihydoxyvitamin D, and fibroblast growth factor-23 and urinary fractional excretion of calcium (FEca) and phosphorus (FEphos). We examined the associations of ET with each biomarker. In addition, we tested whether the adjustment for biomarkers attenuated the association of ET with lumbar BMD measured by abdominal computed tomography in a subset of 810 women. RESULTS In adjusted models, women who used ET were younger in age [62 (SD 8) vs 66 (9) y, P < . 001], had lower mean serum calcium [-13 mg/dL (95% confidence interval [CI] -0.17, -0.10), P < . 001] and lower FEca [-0.15% (95% CI -0.21, -0.09), P < . 001]. Mean serum phosphorus was lower [-0.19 mg/dL (95% CI -0.23, -0.15), P < . 001] and FEphos [0.56% (95% CI 0.16, 0.96), P = . 007] was higher in women on ET. Mean 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were higher [1.52 ng/dL (95% CI 0.57, 2.47), P = . 002, and 0.26 ng/mL (95% CI 0.03, 0.48), P = . 03, respectively] in women who used ET. Mean PTH and fibroblast growth factor-23 did not differ significantly by the use of ET. ET use was strongly associated with higher lumbar BMD [12.75 mg/cm³ (95% CI 7.77-17.73), P < . 001]; however, mineral metabolism measures did not meaningfully alter this association. CONCLUSIONS In a multiethnic cohort of postmenopausal women, ET use was associated with lower serum calcium, lower FEca, lower serum phosphorus, and higher FEphos, suggesting these associations are attributable to increased calcium intake into bone and increased urinary phosphorus excretion. ET use was also associated with greater concentrations of vitamin D metabolites. ET-associated differences in these mineral metabolism measures did not meaningfully attenuate the strong association between ET use and lumbar BMD.
The value of ultrasound-guided fine-needle aspiration biopsy (FNAB) and frozen section examination (FS) in the diagnosis of thyroid cancer.

BACKGROUND AND AIMS Although only a small minority of thyroid nodules are malignant, a large proportion of operations are performed to exclude malignancy. The purpose of this study was to evaluate the role of preoperative ultrasound-guided fine-needle aspiration biopsy (FNAB) and intraoperative frozen section examination (FS) in the management of thyroid cancer. MATERIAL AND METHODS A retrospective study of 664 consecutive patients operated on for thyroid cancer from 1966 through 1994 at the Meilahti Hospital was performed. FNAB was taken with manual guidance in the sixties and seventies and with ultrasound guidance in the eighties and nineties. FS was performed in 335 cases. Malignancy was not known preoperatively in 210 cases. RESULTS Ultrasound-guided FNAB was more accurate than manually guided FNAB (75 out of 143 or 52.4% vs. 112 out of 276 or 40.6%) in detecting malignancy in spite of the fact that the tumors were smaller (23 +/- 15 mm vs. 30 +/- 22 mm, p = 0.011). A true positive FS diagnosis was given in 250 out of 335 (74.6%) of patients. However, in follicular carcinoma, the amount of true positive FS diagnoses was only 12 out of 27 (44.4%). CONCLUSIONS Ultrasound guidance has improved the sensitivity of FNAB. Follicular neoplasia is a problem for both FNAB and FS.
Rapid virological response: Is it four or eight weeks?

According to the recently released American Association for the Study of Liver Diseases (AASLD) guidelines for the treatment of hepatitis C virus (HCV) genotype 1 chronic infection, in treatment-naı̈ve subjects the association of boceprevir or telaprevir with peginterferon-alpha and ribavirin is strongly recommended as the optimal therapy. In patients treated with boceprevir, peginterferon, and ribavirin, a response-guided treatment schedule was established at week 8, through the assessment of HCV RNA level, making feasible a shortened duration of treatment (i.e., 28 weeks) in the case of undetectable viral replication. In this regard, we believe that the choice of 8 weeks for the definition of treatment duration needs some comment. The phase 2 and 3 clinical trials with boceprevir featured the use of peginterferon-ribavirin for 4 weeks (the lead-in period) before boceprevir was added. The reasons for starting with a lead-in phase would be to lower HCV-RNA before exposure to a protease inhibitor in order to reduce the risk of resistance and viral breakthrough. However, in the studies mentioned the achievement of virologic response after the lead-in therapy (4 weeks) was shown to be highly effective for the prediction of sustained virologic response (SVR; HCV-RNA undetectability leading to SVR in a percentage of patients between 89% and 100%, independently from the treatment arm). Indeed, Poordad et al. stated that in patients with undetectable HCV RNA levels after the lead-in period, boceprevir administration would not result in a higher rate of SVR than that obtained with the use of standard therapy. Therefore, the lead-in period as well as interleukin (IL)-28B genotype assessment might be used to better define the eligible patients for peginterferon introduction, thus avoiding their possible overuse with additional costs and side effects. In our opinion, it seems to be reasonable to reconsider the assessment of HCV-RNA at week 4 (end of lead-in) in the response-guided treatment guidelines of naı̈ve genotype-1-infected patients.
Induction of the dual specificity phosphatase PAC1 in rat brain following seizure activity

RECURRENT seizure activity leads to delayed neuronal death as well as to inflammatory responses involving microglia in hippocampal subfields CA1, CA3 and CA4. Since mitogen activated protein (MAP) kinases control neuronal apoptosis and trigger generation of inflammatory cytokines, their activation state could determine seizure-related brain damage. PAC1 is a dual specificity protein phosphatase inactivating MAP kinases which we have found to be undetectable in normal brain. Despite this, kainic acid-induced seizure activity lead to rapid (∼3 h) but transient appearance of PAC1 mRNA in granule cells of the dentate gyrus as well as in pyramidal CA1 neurons. This pattern changed with time and after 2–3 days PAC1 was induced in dying CA1 and CA3 neurons. At this time PAC1 mRNA was also expressed in white matter microglia as well as in microglia invading the damaged hippocampus. PAC1 may play an important role controlling MAP kinase involvement in both neuronal death and neuro-inflammation following excitotoxic damage.
Defining lupus cases for clinical studies: the Boston weighted criteria for the classification of systemic lupus erythematosus.

OBJECTIVE The 1982 American College of Rheumatology (ACR) revised criteria for the classification of systemic lupus erythematosus (SLE), updated in 1997, have become the standard for establishing eligibility of subjects for epidemiologic and clinical lupus studies. These criteria may exclude patients with limited disease, restricting the generalizability of research findings. We developed and evaluated the ability of a weighted classification system to identify a broader spectrum of patients with lupus. METHODS We constructed the Boston Weighted Criteria system for the classification of SLE, updating that developed in 1984. Using a hospital billing database, we identified 27l patients seen in our rheumatology clinic for possible SLE and reviewed medical records for all ACR criteria and the treating rheumatologist's diagnosis. We compared both the Boston Criteria and the treating rheumatologist's diagnosis to the updated 1982 ACR criteria; we also compared the Boston Criteria to the treating rheumatologist's diagnosis. RESULTS The Boston Criteria identified 190/271 patients as having SLE, the rheumatologist's diagnosis identified 179/271, and the ACR criteria identified 171/271. The Boston Criteria had a sensitivity of 93% and specificity of 69% compared to the ACR criteria, and would identify 7% more patients. CONCLUSION The Boston Criteria identify a larger number of patients compared with the current ACR criteria, while retaining face validity. This reflects the inclusion of patients with objective findings of SLE but less than 4 ACR criteria. Our Boston Criteria system could minimize selection bias and increase the generalizability of clinical SLE studies.
Application of proanthocyanidins from peanut skins as a natural yeast inhibitory agent.

UNLABELLED Proanthocyanidins were extracted from peanut skins and investigated for their antimicrobial activity against Saccharomyces cerevisiae, Zygosaccharomyces bailii, and Zygosaccharomyces bisporus in traditional growth media (Sabouraud Dextrose and Maltose broth) and a simulated apple juice beverage. Peanut skins extracts (PSE) were prepared through a multisolvent extraction procedure. The PSE extended the lag phase growth of the 3 yeasts studied at a concentration of 1 mg/mL and at 10 mg/mL yeast growth was totally inhibited for 120 h. PSE was fractionated by normal phase high performance liquid chromatography and the active components/fractions were determined. Compounds present in the fractions were identified by liquid chromatography-mass spectrometry to determine the compounds responsible for inhibition. Fractions consisting mostly of A-type proanthocyanidin dimers, trimers, and tetramers showed the highest percent inhibition toward the yeasts tested in this study. Both optical density (OD) and standard enumeration plating methods were performed in this study. The OD method led to an overestimation of the inhibitory effects of PSE, the 2 methods agreed in respect to treatment effects but not the severity of the inhibition. PRACTICAL APPLICATION There is a growing consumer demand for "fresh like" products containing reduced amounts of chemical preservatives without compromising food safety and quality. Therefore, the goal of this study was to determine if an extract of peanut skins containing flavonoid rich compounds could function as a natural antimicrobial in a model beverage system. Proteins were removed through the process of producing the peanut skin extract, thus it is unlikely to contain peanut allergens. The antimicrobial compounds mentioned in this study were successfully integrated into a model beverage system, and were found to have antimicrobial effect. However, the incorporation of these compounds would likely lead to negative sensory attributes at the concentration needed to achieve an appreciable antimicrobial effect alone.