Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment of Osteoporosis

Liječenje Osteoporoze Osteoporoza je jedna od najčešćih metaboličkih bolesti i zahvaća 8 % do 10 % stanovništva. Budući da je prijelom najteža posljedica osteoporoze, vrlo je važno otkriti bolesnike koji imaju rizik nastanka prijeloma, dati im farmakološku terapiju i savjetovati im promjenu načina života. Nekoliko je lijekova pokazalo sposobnost smanjenja broja prijeloma kralježnice i/ili perifernog skeleta u bolesnika s osteoporozom. Antiresorptivni su lijekovi temelj terapije, ali su i anabolički lijekovi odnedavno proširili mogućnosti liječenja. Antiresorptivni lijekovi, estrogeni, selektivni modulatori estrogenskih receptora, bisfosfonati i kalcitonin, djeluju tako da smanjuju koštanu pregradnju. Paratireoidni hormon potiče novo stvaranje kosti popravljajući arhitekturu i gustoću kosti. Stroncijev ranelat smanjuje rizik osteoporotičnih prijeloma djelujući na oboje - smanjenje razgradnje i povećanje izgradnje kosti. Druga potencijalna liječenja osteoporoze također su opisana u ovome članku. Treatment of Osteoporosis Osteoporosis is among the most frequent metabolic diseases affecting 8 % to 10 % of the population. Since the most disturbing outcome of osteoporosis is a fracture, it is important to identify patients at risk and intervene with pharmacologic therapies and lifestyle changes. Several drugs have shown their ability to reduce vertebral and/or peripheral fractures in patients with osteoporosis. Antiresorptive agents are a basis of therapy, but anabolic drugs have recently widened therapeutic options. Antiresorptive medications, estrogens, selective estrogen receptor modulators, bisphosphonates and calcitonins, work by reducing the rates of bone remodeling. Parathyroid hormone stimulates new bone formation, repairing architectural defects and improving bone density. Strontium ranelate reduces the risk for osteoporotic fractures by both inhibiting bone resorption and increasing bone formation. Other potential therapies for osteoporosis are also reviewed in this article.
The effect of the trolox equivalent antioxidant capacity (TEAC) in plasma on the formation of 4-aminobiphenylhaemoglobin adducts in smokers

Smokers are exposed to a number of carcinogenic compounds including aromatic amines such as 4-aminobiphenyl. Antioxidants are thought to be involved in the defence against the damaging effect of such carcinogens. Recently it has been shown that plasma antioxidant status in smokers is diminished compared with non-smokers. In this study we investigated in 40 smokers whether the trolox equivalent antioxidant capacity (TEAC) in plasma could be quantitatively related to exposure to cigarette smoke. The biomarkers 4-aminobiphenylhaemoglobin (4-ABP-Hb) adduct and cotinine were determined as indices of cigarette smoke exposure. A correlation between 4-ABP-Hb adduct levels and plasma cotinine levels was found for the whole population studied, who smoked 4-70 cigarettes per day (n = 40, r2 = 0.12, p = 0.03). A significant inverse relationship was found between TEAC and 4-ABP-Hb levels (n = 40, r2 = 0.17, p = 0.008). Multiple regression analysis showed a strong relationship between 4-ABP-Hb levels and plasma TEAC and cotinine levels (n = 40, r2 =0.29, p = 0.002). These findings provide strong evidence that the 4- ABP-Hb adduct represents a valuable biomarker of (internal) exposure to tobacco smoke, and also that the formation of this marker is dependent on the plasma antioxidant status. The multiple regression analysis results show that the measure of effect (4-ABP-Hb adduct formation) is largely determined by dose (cotinine) and protection (TEAC).
Are rehabilitation programmes enabling clients to return to work? Return to work perspectives of individuals with mild to moderate brain injury in South Africa.

OBJECTIVE To describe the perceptions and experiences of individuals with brain injury with regard to return to work rehabilitation programmes. PARTICIPANTS Nine males and one female who were diagnosed with a moderate to mild brain injury participated in the study. METHODS In-depth interviews were conducted and data were analyzed using a qualitative approach to explicate patterns and themes. RESULTS Two themes emerged that reflected the lived experiences of individuals with brain injury regarding intervention programmes that influenced their ability to return to work after the brain injury: 1) Enablers of return to work programmes, 2) Barriers related to return to work programmes. CONCLUSIONS Occupational therapy practitioners as well as rehabilitation personnel should identify and eliminate the barriers that impact on return to work intervention programmes, incorporate the enablers identified in this study when designing return to work programmes.
Biochemical characterization of Drosophilaγ‐glutamyl carboxylase and its role in fly development

To investigate structure‐function relationships in γ‐glutamyl carboxylases, the enzyme from Drosophila melanogaster was characterized. Four cysteine residues were shown to be important determinants for enzymatic activity. Native Drosophila substrates have not yet been identified, but propeptides of human prothrombin and factor IX are recognized by the Drosophila enzyme. The presence of the propeptide region increased apparent affinity by ∼200‐fold, and mutation of a hydrophobic residue of factor IX propeptide (F‐16A) decreased carboxylation by 90%, as in the human enzyme. Substrate recognition appears to be highly conserved between the human and Drosophilaγ‐glutamyl carboxylases. Inactivation of Drosophilaγ‐glutamyl carboxylase by non‐sense mutations or insertional mutagenesis by P‐element insertion have no apparent effects on growth and fertility under laboratory conditions.
The effects of acebutolol and metoprolol on walking distances and distal blood pressure in hypertensive patients with intermittent claudication.

The effects of acebutolol (with intrinsic sympathomimetic activity (ISA] and metoprolol (without ISA) on arm blood pressure, ankle systolic blood pressure, claudication distances (CD) and maximal walking distances (MWD) were compared in patients with essential hypertension and intermittent claudication. Fourteen patients participated in a long-term, open, randomized cross-over study. After randomization the patients received either acebutolol, 200 mg b.i. d. , or metoprolol, 100 mg b.i. d. After eight weeks the drugs were shifted and after another eight weeks they were withdrawn. Arm and ankle blood pressure, CD and MWD were determined before randomization and after 4, 8, 12 and 16 weeks, and again 4-6 weeks after withdrawal of the drugs. The arm blood pressure was reduced by 20/13 mmHg after acebutolol and by 22/21 mmHg after metoprolol. In spite of a significant decrease in arm blood pressure there were no significant changes in ankle blood pressure, CD or MWD after the two drugs. After withdrawal of the drugs and after the arm blood pressure had returned to the control value no significant changes were seen in CD, MWD or ankle blood pressure. It is concluded that beta-blockers have no deleterious effect on CD, MWD or ankle blood pressure in patients with hypertension and intermittent claudication. No effect of ISA was demonstrated.
FASTPAT: a fast and efficient algorithm for string searching in DNA sequences

A new string searching algorithm is presented aimed at searching for the occurrence of character patterns in longer character texts. The algorithm, specifically designed for nucleic acid sequence data, is essentially derived from the Boyer-Moore method (Comm. ACM, 20, 762-772, 1977). Both pattern and text data are compressed so that the natural 4-letter alphabet of nucleic acid sequences is considerably enlarged. The string search starts from the last character of the pattern and proceeds in large jumps through the text to be searched. The data compression and searching algorithm allows one to avoid searching for patterns not present in the text as well as to inspect, for each pattern, all text characters until the exact match with the text is found. These considerations are supported by empirical evidence and comparisons with other methods.
Role of the ligand in intracellular receptor function: receptor affinity determines activation in vitro of the latent dioxin receptor to a DNA-binding form

To reconstitute the molecular mechanisms underlying the cellular response to soluble receptor ligands, we have exploited a cell-free system that exhibits signal- (dioxin-)induced activation of the latent cytosolic dioxin receptor to an active DNA-binding species. The DNA-binding properties of the in vitro-activated form were qualitatively indistinguishable from those of in vivo-activated nuclear receptor extracted from dioxin-treated cells. In vitro activation of the receptor by dioxin was dose dependent and was mimicked by other dioxin receptor ligands in a manner that followed the rank order of their relative affinities for the receptor in vitro and their relative potencies to induce target gene transcription in vivo. Thus, in addition to triggering the initial release of inhibition of DNA binding and presumably allowing nuclear translocation, the ligand appears to play a crucial role in the direct control of the level of functional activity of a given ligand-receptor complex.
Regional Assessment of Left Ventricular Surface Shape from Magnetic Resonance Imaging

Left ventricular functional abnormalities are postulated to be associated with regional modification of surface curvature. This study describes the computation of the differential properties of the LV surface via an analytic approach using local surface fitting. Quantification was implemented with cine magnetic resonance imaging (MRI), which was used as the source to derive 3D wire-frame models and the related shape descriptors. Based on these shape descriptors, the shape of LV could be represented in both static and dynamic manners. These may have implications for diverse cardiac diseases.
Information Of Lung Tumorigenesis By Tea

Tea and tea constituents have been shown by different investigators to inhibit lung tumorigenesis in different animal model systems. This includes lung tumorigenesis in A/J mice induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosodiethylamine, benzo[a]pyrene, N-nitrosomethylurea, or cisplatin. Inhibition of lung tumorigenesis has also been demonstrated in C3H mice treated with N-nitrosodiethylamine. In most of these experiments, reduction in tumor number and tumor size has been observed in the tea-treated group, and in some experiments, decreased tumor incidence has also been observed. The green tea constituent, epigallocatechin-3-gallate (EGCG), and the black tea constituent, theaflavins, have also been shown to be effective. Black tea preparations have been shown to reduce the incidence and number of spontaneously generated lung adenocarcinomas and rhabdomyosarcoma in A/J mice, as well as inhibit the progression of lung adenoma to adenocarcinoma. The mechanisms for the inhibitory action have not been well elucidated. It may be related to the antiproliferative, proapoptotic, and antiangiogenic activities of tea constituents that have been demonstrated in some experiments. These activities may be a result of the inhibition of key protein kinases involved in signal transduction and cell cycle regulation. Tea catechins, such as EGCG, have been suggested to be the effective components. However, a study suggests that caffeine is the key effective constituent for the inhibitory activity of lung tumorigenesis in Fisher 344 rats by black tea. In many of the experiments, tea consumption resulted in the reduction of body fat and body weight; these factors may also contribute to the inhibition of tumorigenesis.
Effective flywheel energy storage (FES) offer strategies for frequency regulation service provision

The recent, deepening penetration of variable energy resources (VERs) subjects power systems to the highly variable, rapidly changing and uncertain generation outputs that the operators must manage effectively to provide reliable service. Such variability poses additional challenges to the management of the continual variability in system loads. Consequently, the frequency regulation service requirements are substantially increased over those for systems without these VERs. The attractive rapid response and fast ramping capability characteristics of flywheel energy storage (FES) technology can be exploited in the FES deployment for frequency regulation service provision. Such deployment requires the effective management of the limited FES capacity and storage capability. In this paper, we construct optimized frequency regulation service offer strategies for an FES unit into the day-ahead markets (DAMs) and their associated real-time markets (RTMs). An independent grid operator (IGO) procures the service competitively through such offers. The FES offer strategies are obtained from the deployment of a robust optimization approach, which explicitly considers the uncertain nature of automatic generation control (AGC) signals and the amount of FES stored energy. The optimization objective is to maximize the FES service provision into the DAMs and the RTMs. To meet this objective, the FES offers only into particular DAMs and provides additional frequency regulation service in the RTMs by taking advantage of the most recent information of FES stored energy, even in those hours in which the FES does not participate in the DAMs. A salient characteristic of the proposed offer strategies is that all offered services are guaranteed to be provided, regardless of the actual AGC signals. We illustrate the effectiveness of the proposed strategies with simulation studies that use PJM Interconnection historical AGC signal data. Representative results indicate that the proposed FES offer strategies result in guaranteed service provision without any exceptions. Such service provision represents a major improvement over that under the conventional strategy that offers the full FES capacity into each DAM but satisfies, on average, only 47.7 % of the regulation service requests. We also study the impacts of the Federal Energy Regulatory Commission (FERC) Order No. 764 that allows DAM periods shorter than one hour. Specifically, we quantify the significant benefits emanating from the flexibility for limited storage capability devices such as FES units in frequency regulation service provision via simulation studies.
Identification of Conductive Hearing Loss in Young Infants Using Tympanometry and Wideband Reflectance

Objective: The goal of the study was to evaluate the effectiveness of tympanometry and wideband reflectance (WBR) in detecting conductive hearing loss (CHL) in young infants. Methods: Type of hearing loss was determined using auditory brainstem response using air- and bone-conducted tone bursts in 84 ears from 70 infants (median age = 10 weeks). Of these 84 ears, 60 are included in the current analysis: 43 with normal hearing (NH) and 17 with CHL. Tympanometry was measured using probe tone frequencies of 226, 678, and 1000 Hz. Tympanograms were evaluated in two ways: (1) Acoustic middle ear admittance (Ya, in millimhos); and (2) two-category classification (normal/abnormal), as described by Baldwin (2006). Measures of Ya were evaluated in two ways: by admittance-magnitude tympanograms and calculated admittance magnitude from subcomponents (conductance and susceptance). WBR was measured in response to a chirp stimulus after probe calibration. WBR was analyzed into thirteen 1/3 octave bands. Tests for statistical differences for two-category classification were analyzed using Chi-squared and Ya, and WBR were analyzed using repeated-measures analyses of variances. Cohen’s d and likelihood ratios were computed for comparison with statistically significant differences. Results: Ya measured with 678- and 1000 Hz probe tones was significantly different between ears with CHL and NH. Two-category classification of tympanograms using a 1000 Hz probe tone was significantly different between ears with CHL and NH. Neither two-category classification nor Ya was significantly different between ears identified with CHL and NH using a 226 Hz probe tone. WBR was significantly higher in the frequency bands 800 to 2500 Hz and in the frequency band centered at 6300 Hz in infants with CHL. Effect sizes (Cohen’s d) were greater than 2 for several WBR frequency bands and Ya measured with 1000 Hz probe tones. The results were similar for calculations of Ya from admittance-magnitude and subcomponent tympanograms. Positive likelihood ratios for WBR ranged between 8.1 and 38, and those for Ya using 1000 Hz ranged between 12.5 and 32. Conclusions: CHL in young infants can be detected well with WBR or tympanometry using probe frequencies of 678 and 1000 Hz.
A controlled release system for simultaneous delivery of three human perivascular stem cell‐derived factors for tissue repair and regeneration

Transplanted stem/progenitor cells improve tissue healing and regeneration anatomically and functionally, mostly due to their secreted trophic factors. However, harsh conditions at the site of injury, including hypoxia, oxidative and inflammatory stress, increased fibrosis and insufficient angiogenesis, and in some cases immunological response or incompatibility, are detrimental to stem cell survival. To overcome the complexity and deficiencies of stem cell therapy, the coacervate delivery platform is deemed promising because it offers controlled and sustained release using heparin to recapitulate the binding and stabilization of extracellular proteins by heparan sulphates in native tissues. Here we show that recombinant alternatives of three key factors [vascular endothelial growth factor (VEGF), monocyte chemoattractant protein‐1 (MCP‐1) and interleukin‐6 (IL‐6)], commonly produced by perivascular stem cells under various stress conditions, can be successfully incorporated into a heparin‐based coacervate. We characterized the release profile of the triply incorporated factors from the complex coacervate. The coacervate‐released factors were able to exert their desired biological activities in vitro: VEGF stimulated human umbilical vein endothelial cell proliferation, MCP‐1 elevated macrophage migration and IL‐6 increased IgM production by IL‐6‐dependent cell line. Thus, a controlled release system can be used for simultaneous delivery of three stem cell‐derived factors and could be useful for tissue repair and regenerative medicine.
Evaluation of microcapsule permeability via inverse size exclusion chromatography.

Inverse aqueous size exclusion chromatography (SEC) was adopted to measure the permeability of microcapsules (hollow hydrogel spheres with diameter < 1 mm) using dextran molecular weight standards. Alginate/poly(L-lysine)/alginate microcapsules were chosen as a column substrate. Data from column SEC experiments were verified by kinetic studies of solute size exclusion. The permeability of tested microcapsules was modified by the reaction time with 0.05wt. % poly(L-lysine) (PLL). The exclusion limit of the microcapsules prepared at 5-min reaction time was found to be 100,000, while the microcapsules that were allowed to react with PLL for 20 min became less permeable and their exclusion limit was approximately 50,000. Based on relationships between solute size and molecular weight, the exclusion limits determined with dextrans were converted to the size and approximate molecular weight of protein presumably excluded by the capsular membrane at "ideal" conditions. The results from both column SEC and batch experiments suggest that the standard alginate/PLL/alginate capsules are permeable to immunoglobulins of IgG class. Unlike other techniques which utilize only a limited number of solutes, inverse SEC enables one to examine the capsule permeability to a homologous series of molecular weight standards. Inverse SEC also provides an opportunity to evaluate the properties of a large series of capsules directly by comparing their calibration curves. In addition, undesirable enthalpic effects in permeability studies with globular proteins as test solutes can be minimized or eliminated by using the inert molecular weight standards such as polysaccharides.
Na+ Binding of V-type Na+-ATPase inEnterococcus hirae *

Rotation catalysis theory has been successfully applied to the molecular mechanism of the ATP synthase (F0F1-ATPase) and probably of the vacuolar ATPase. We investigated the ion binding step toEnterococcus hirae Na+-translocating V-ATPase. The kinetics of Na+ binding to purified V-ATPase suggested 6 ± 1 Na+ bound/enzyme molecule, with a single high affinity (K d(Na+) = 15 ± 5 μm). The number of cation binding sites is consistent with the model that V-ATPase proteolipids form a rotor ring consisting of hexamers, each having one cation binding site. Release of the bound22Na+ from purified molecules in a chasing experiment showed two phases: a fast component (about two-thirds of the total amount of bound Na+;k exchange > 1.7 min−1) and a slow component (about one-third of the total;k exchange = 0.16 min−1), which changes to the fast component by adding ATP or ATPγS. This suggested that about two-thirds of the Na+ binding sites of the Na+-ATPase are readily accessible from the aqueous phase and that the slow component is important for the transport reaction.
Effects of the Serine/Threonine Kinase SGK1 on the Epithelial Na+ Channel (ENaC) and CFTR: Implications for Cystic Fibrosis

Cystic fibrosis (CF) is characterized by impaired Cl- secretion and increased Na+ reabsorption in several tissues including respiratory epithelium. Many CFTR mutations have been identified over the past years. However, only a poor correlation between the genotype and lung phenotype was found suggesting additional factors influencing the phenotype and course of the disease. The serine/threonine kinase SGK1 has recently been shown to stimulate the activity of the epithelial Na+ channel ENaC. A variety of stimuli such as aldosterone, cell shrinkage, insulin or TGF-β1 stimulate transcription and activate the SGK1 kinase. Here we further examined the effects of SGK1 on ENaC and CFTR which have mutual interactions and we analyzed sgk1 mRNA abundance in lung tissue from CF patients. Coexpression of CFTR and h-SGK1 in Xenopus oocytes increased ENaC currents as previously described. In addition CFTR mediated currents were also stimulated. h-SGK1 accelerated the expression of the amiloride sensitive Na+- current in Xenopus oocytes paralleled by increased ENaC-protein abundance in the oocyte membrane, an effect which was reversed by a h-SGK1K127R mutation lacking the ATP-binding site. The cation selectivity or Na+ affinity were not affected. However, coexpression of h-SGK1 with ENaC altered the sensitivity of the Na+-channel to the inhibitors amiloride and triamterene. The inhibitory effect of CFTR expression on ENaC current was not affected by coexpression of h-SGK1 in Xenopus oocytes. Lung tissue from CF patients strongly expressed the serine/threonine kinase h-sgk1 which was not the case for non-CF lung tissue. Loss of CFTR function itself in a CF lung epithelial cell line did not increase SGK1 expression. In summary, enhanced expression of h-SGK1 in epithelial cells of CF-lung tissue may be a novel pathophysiological factor contributing to increased Na+ channel activity and thus to increased Na+ transport in CF. .