Miracle-dz/UniFAR-FTUs huggingface dataset:
Steady-state pharmacokinetics of the enantiomers of citalopram and its metabolites in humans.

The steady-state pharmacokinetics in serum and urine of the enantiomers of citalopram and its metabolites, demethylcitalopram (DCT) and didemethylcitalopram (DDCT), were investigated after multiple doses of rac-citalopram for 21 consecutive days (40 mg per day) to healthy human subjects who were extensive metabolisers of sparteine and mephenytoin. Comparable pharmacokinetic variability was noted for (+)-(S)-, (-)-(R)- and rac-citalopram. Enantiomeric (S/R) serum concentration ratios for citalopram were always less than unity and were constant during the steady-state dosing interval. A modest, but statistically significant, stereoselectivity in the disposition of citalopram and its two main metabolites was observed. Serum levels of the (+)-(S)-enantiomers of citalopram, DCT, and DDCT throughout the steady-state dosing interval investigated were 37 +/- 6%, 42 +/- 3% and 32 +/- 3%, respectively, of their total racemic serum concentrations. The (+)-(S)-enantiomers of citalopram, DCT, and DDCT were eliminated faster than their antipodes. For (-)-(R)- and (+)-(S)-citalopram, respectively, the serum t1/2 averaged 47 +/- 11 and 35 +/- 4 h and AUCss averaged 4,193 +/- 1,118 h.nmol/l and 2,562 +/- 1,190 h.nmol/l. The observed enantiospecificities were apparently more related to clearance, rather than to distributional mechanisms.
Human papillomavirus infection and disease in men: Impact of HIV

There is growing evidence of a significant burden of human papillomavirus (HPV) infection and associated disease in men. High rates of HPV infection have been observed in men from sub-Saharan Africa where HIV prevalence is high. HIV infection increases HPV prevalence, incidence and persistence and is strongly associated with the development of anogenital warts and anal, penile and head and neck cancers in men. Despite increasing access to antiretroviral therapy, there appears to be little benefit in preventing the development of these cancers in HIV-positive men, making prevention of infection a priority. New prevention options that are being introduced in many African countries include male circumcision and HPV vaccination. However, more data are needed on the burden of HPV disease in men before boys are included in HPV vaccination programmes.
Retroviral cDNA Integration: Stimulation by HMG I Family Proteins

ABSTRACT To replicate, a retrovirus must synthesize a cDNA copy of the viral RNA genome and integrate that cDNA into a chromosome of the host. We have investigated the role of a host cell cofactor, HMG I(Y) protein, in integration of human immunodeficiency virus type 1 (HIV-1) and Moloney murine leukemia virus (MoMLV) cDNA. Previously we reported that HMG I(Y) cofractionates with HIV-1 preintegration complexes (PICs) isolated from freshly infected cells. PICs depleted of required components by treatment with high concentrations of salt could be reconstituted by addition of purified HMG I(Y) in vitro. Here we report studies using immunoprecipitation that indicate that HMG I(Y) is associated with MoMLV preintegration complexes. In mechanistic studies, we show for both HIV-1 and MoMLV that each HMG I(Y) monomer must contain multiple DNA binding domains to stimulate integration by HMG I(Y)-depleted PICs. We also find that HMG I(Y) can condense model HIV-1 or MoMLV cDNA in vitro as measured by stimulation of intermolecular ligation. This reaction, like reconstitution of integration, depends on the presence of multiple DNA binding domains in each HMG I(Y) monomer. These data suggest that binding of multivalent HMG I(Y) monomers to multiple cDNA sites compacts retroviral cDNA, thereby promoting formation of active integrase-cDNA complexes.
Assembly and function of small RNA – Argonaute protein complexes

Abstract Small RNAs such as microRNAs (miRNAs), short interfering RNAs (siRNAs) or Piwi-interacting RNAs (piRNAs) are important regulators of gene expression in various organisms. Small RNAs bind to a member of the Argonaute protein family and are incorporated into larger structures that mediate diverse gene silencing events. The loading of Argonaute proteins with small RNAs is aided by a number of auxiliary factors as well as ATP hydrolysis. This review will focus on the mechanisms of Argonaute loading in different organisms. Furthermore, we highlight the versatile functions of small RNA-Argonaute protein complexes in organisms from all three kingdoms of life.
Relevance of cosmeceuticals to the dermatologic surgeon.

BACKGROUND The dermatologic surgeon is the dermatologist with special expertise in the surgical care of the health and beauty of the skin. OBJECTIVES, METHODS, RESULTS There is no better arena for the use of topical regimens to preserve skin quality than in the time interval devoted to before and after care with respect to surgical procedures. CONCLUSION Many of these regimens can be tailor devised with topical drugs and cosmeceuticals together in proper balance in the patient's best interest for affordable health care.
Growth and nutrition in Rett syndrome

Purpose / Method : In this paper we review the existing literature on factors that contribute to growth failure in Rett syndrome (RS) with particular emphasis on the extent and nature of the feeding difficulties that arise. Data on growth and feeding related problems, collected over four years in a specialized clinic for females with Rett syndrome are presented and management protocols developed in the clinic discussed. Results / Conclusion : Feeding related problems and growth failure occur commonly in Rett syndrome yet our understanding of the mechanisms causing growth failure are poorly understood. Both nutritional and non-nutritional factors are thought to contribute and it has not been possible to develop efficacious intervention strategies. Consequently, clinical management of growth failure in Rett syndrome is not evidence based.
Nonmotor Symptoms in Parkinson's Disease

ABSTRACT The recognition and treatment of nonmotor symptoms are increasingly emphasized in the care of Parkinson's disease (PD) patients. This manuscript will review signs and symptoms localized, generally, to the cortex, basal ganglia, brainstem, spinal cord, and peripheral nervous system. Cortical manifestations include dementia, mild cognitive impairment, and psychosis. Apathy, restlessness (akathisia), and impulse control disorders will be linked as basal ganglia symptoms. Symptoms attributed to the brainstem comprise depression, anxiety, and sleep disorders. Peripheral nervous system disturbances may lead to orthostatic hypotension, constipation, pain, and sensory disturbances.
THE SELF-CONCEPT OVER TIME: Research Issues and Directions

Although theoretical attention has been devoted to the situational variability of the self-concept, empirical investigations continue to rely on one-shot methodologies. Such efforts assume that data obtained through these methods can be generalized to other situations in the person's life, even to subsequent years or stages in the life course. Self-concept is a structural product of reflexive activity, but it is also susceptible to change as the individual encounters new roles, situations, and life transitions. The data reviewed in this paper suggest that: (i) self-evaluation generally becomes more favorable through the life-span; (ii) self-evaluation is represented by a "moving baseline" from which situational fluctuations emerge; (iii) self-concept is characterized by both stability and change over the life course; and (iv) environmental stability plays an important role in self-concept stability. Several avenues of research are recommended to develop an accurate, meaningful, and testable theory of the self-concept over time.
Polymorphic AAAG Repeat Length in Estrogen-Related Receptor Gamma (ERRγ) and Risk of Breast Cancer in Iranian Women

Estrogen-related receptors (ERRs) alpha, beta, and gamma are orphan nuclear receptors that modulate the estrogen signaling pathway and play roles in the regulation of breast cancer cell growth. To determine the association between breast cancer risk and alleles of the tetranucleotide repeat (AAAG)n in the intron of ERRγ gene, a case–control study of 200 breast cancer patients and 200 controls was performed in Iranian women. Our results demonstrate that women with short AAAG repeat are at higher risk of breast cancer (OR 7). This result suggests a possible involvement of polymorphic AAAG repeat of ERRγ gene in regulating its expression.
The Preterm Prediction Study: the value of serum alkaline phosphatase, alpha-fetoprotein, plasma corticotropin-releasing hormone, and other serum markers for the prediction of spontaneous preterm birth.

OBJECTIVE High levels of a number of analytes are found in maternal blood; alkaline phosphatase,alpha-fetoprotein, and corticotropin-releasing hormone have been associated with spontaneous preterm birth. We investigated the relationship between 8 potential blood markers and subsequent spontaneous preterm birth in asymptomatic pregnant women. STUDY DESIGN We performed a nested case control study that involved 127 women who were enrolled in the preterm prediction study and who had a singleton spontaneous preterm birth at <35 weeks and 127 women who had a term birth and served as matched (age, parity, center) controls. Serum that was collected at 24 and 28 weeks was analyzed for alkaline phosphatase, alpha-fetoprotein, corticotropin-releasing hormone, and 5 other analytes. RESULTS Alkaline phosphatase, alpha-fetoprotein, and corticotropin-releasing hormone, but not other analytes, were significantly elevated in pregnancies that ended in spontaneous preterm birth. For alkaline phosphatase at 24 weeks, the odds ratio for spontaneous preterm birth at <32 weeks was 6.8 (range, 1.4-32.8) and for spontaneous preterm birth at <35 weeks 5.1 (range, 1.7-15.6). Similar results were found at 28 weeks. For alpha-fetoprotein at 24 weeks, the odds ratio for spontaneous preterm birth at <32 weeks was 8.3 (range,2.2-30.9) and for spontaneous preterm birth at <35 weeks was 3.5 (range, 1.8-6.7). The levels at 28 weeks were still predictive but less so than at 24 weeks. Corticotropin-releasing hormone, at 28 weeks but not at 24 weeks, was predictive for spontaneous preterm birth at <35 weeks, with an odds ratio 3.4 (range, 1.0-10.9). CONCLUSION Elevated alkaline phosphatase and alpha-fetoprotein are associated with subsequent spontaneous preterm birth in asymptomatic pregnant women at 24 and 28 weeks. Elevated corticotropin-releasing hormone levels at 28 weeks are associated with spontaneous preterm birth at <35 weeks.
Incidence of second primary malignancies in patients with esophageal cancer: a comprehensive review

Abstract Background: Development of a second primary malignancy (SPM) after an index esophageal cancer is fairly rare, primarily due to decreased survival in patients with esophageal cancer. However, with advances in early detection and therapy, the number of long-term survivors is increasing, as is the incidence of SPMs in this population. Scope: We review herein the published literature on the incidence of SPMs after an index esophageal cancer as well as its associated risk factors, prognosis and surveillance. We discuss predisposing factors that may contribute to the development of SPMs, epidemiology and attempts at chemoprevention. Findings: Data from population-based studies, retrospective reviews and case reports indicate an increased risk of SPMs in patients with esophageal cancer with reported incidence rates between 8.3 and 27.1%. Index esophageal squamous cell carcinomas have a higher association with other tobacco-related cancers such as those of the head and neck and lung. They have also shown an association with second primary cancers of the breast, stomach, thyroid, and kidney. Individuals with esophageal adenocarcinomas are at a higher risk of developing second cancers of the stomach, oropharynx and lung/bronchus. Other primary cancer sites involved include the kidney, colorectum and pancreas. Common risk factors including lifestyle and genetic alterations may explain the increased incidence of second primary cancers in this patient population. Conclusions: Risk of developing a second malignancy should be anticipated after curative treatment of esophageal cancer, and raises concerns for optimal surveillance and therapy of these patients. Recent literature suggests similar survival rates in esophageal cancer patients with and without SPMs. With the increasing incidence of SPMs in subjects with esophageal cancer, there may be benefit to close screening for and aggressive therapy of SPMs. However, further studies are needed to elucidate optimal management strategies.
The entropic penalty of ordered water accounts for weaker binding of the antibiotic novobiocin to a resistant mutant of DNA gyrase: a thermodynamic and crystallographic study.

Novobiocin is an antibiotic which binds to a 24 kDa fragment from the B subunit of DNA gyrase. Naturally occurring resistance arises from mutation of Arg-136 which hydrogen bonds to the coumarin ring of novobiocin. We have applied calorimetry to characterize the binding of novobiocin to wild-type and R136H mutant 24 kDa fragments. Upon mutation, the Kd increases from 32 to 1200 nM at 300 K. The enthalpy of binding is more favorable for the mutant (DeltaH degrees shifts from -12.1 to -17.5 kcal/mol), and the entropy of binding is much less favorable (TDeltaS degrees changes from -1.8 to -9.4 kcal/mol). Both of these changes are in the direction opposite to that expected if the loss of the Arg residue reduces hydrogen bonding. The change in heat capacity at constant pressure upon binding (DeltaCp) shifts from -295 to -454 cal mol-1 K-1. We also report the crystal structure, at 2.3 A resolution, of a complex between the R136H 24 kDa fragment and novobiocin. Although the change in DeltaCp often would be interpreted as reflecting increased burial of hydrophobic surface on binding, this structure reveals a small decrease. Furthermore, an ordered water molecule is sequestered into the volume vacated by removal of the guanidinium group. There are large discrepancies when the measured thermodynamic parameters are compared to those estimated from the structural data using empirical relationships. These differences seem to arise from the effects of sequestering ordered water molecules upon complexation. The water-mediated hydrogen bonds linking novobiocin to the mutant protein make a favorable enthalpic contribution, whereas the immobilization of the water leads to an entropic cost and a reduction in the heat capacity of the system. Such a negative contribution to DeltaCp, DeltaH degrees , and TDeltaS degrees appears to be a general property of water molecules that are sequestered when ligands bind to proteins.
Drug-induced Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS-TEN overlap: a multicentric retrospective study.

BACKGROUND Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare immune-mediated severe cutaneous adverse reactions with incidence rate of 0.05 to 2 persons per million populations per year. Drugs are the most commonly implicated in 95% of cases. AIMS To audit the causative drugs, clinical outcome, and cost of management in SJS, TEN, and SJS-TEN overlap. SETTING AND DESIGN Tertiary care hospitals-based multicentric retrospective study (case series). MATERIALS AND METHODS Indoor case papers of SJS, TEN, and SJS-TEN overlap admitted between January 2006 and December 2009 in four tertiary care hospitals of Gujarat were scrutinized. Data were collected for demographic information, causative drugs, investigations, treatment given, duration of hospital stay, time interval between onset of symptoms and drug intake, clinical outcome, and complications. Data were analyzed to find out proportion of individual drugs responsible, major complications, and clinical outcome in SJS, TEN, and SJS-TEN overlap. Total cost of management was calculated by using cost of drugs, investigations, and consumables used during entire hospital stay. STATISTICAL ANALYSIS One-way Analysis of Variance followed by Tukey-Kramer multiple comparison test was used for comparison of incubation period, duration of hospital stay, and cost of management. RESULTS Antimicrobials (50%), nonsteroidal anti-inflammatory drugs (22.41%), and antiseizure drugs (18.96%) were the most commonly associated groups. Nevirapine (28.12%) was the most common drug. Antiseizure drugs were more often associated with serious form of adverse reaction (TEN: 81.8%) than other drugs. Duration of hospital stay (20.6 vs 9.7 days) and cost of management (7,910/- vs 2,460/-) were significantly higher in TEN than SJS (P=0.020 and P<0.001, respectively). Time duration between drug intake and onset of symptoms (17.7 vs 27.5 days) was nonsignificantly lower in TEN as compared with SJS. Secondary infection (28.12%) was the most common complication noted. Mortality rate was 15.6% among all cases; 9% in SJS and 26.7% in TEN. CONCLUSION Antimicrobial drugs are the most commonly implicated drugs and cost of managing these adverse drug reactions is higher than other serious ADRs.
Analysis of ammonia‐oxidizing bacteria populations in acid forest soil during conditions of moisture limitation

R.C. HASTINGS, C. BUTLER, I. SINGLETON, J.R. SAUNDERS and A.J. McCARTHY.2000. Ammonia‐oxidizer numbers decreased under conditions of moisture limitation in litter, fermentation and humus layers of forest soil in the field, but the extent of regrowth after rehydration varied between layers. Nitrosospira 16S rRNA genes were amplified from all layers, regardless of moisture content or soil pH which varied between 4·1 and 5·2. Nitrosomonas spp. were detected less often, but appeared to exhibit more rapid recovery than the Nitrosospira spp. when drought conditions were relieved by rainfall.
Decreased apopto-phagocytic gene expression in the macrophages of systemic lupus erythematosus patients

The clearance of apoptotic cells has an important role in the maintenance of tissue homeostasis and in the protection of tissues from the inflammatory and immunogenic contents of dying cells. A defect in the recognition and phagocytosis of apoptotic cells contributes to the development of chronic inflammation and autoimmune disorders. We have observed that compared with healthy donors, differentiated macrophages from patients with untreated systemic lupus erythematosus (SLE) showed decreased phagocytosis of apoptotic neutrophils. A TaqMan Low Density Array was designed to determine the mRNA expression levels of 95 apopto-phagocytic genes in differentiated non-phagocytosing and phagocytosing macrophages. In the macrophages of clinically and immunoserologically active SLE patients, 39 genes were expressed at lower levels than in the control macrophages. When inactive patients were compared with those with minor immunoserological abnormalities or patients in an immunoserologically active state, a relationship was observed between the altered gene expression profile and the disease state. In the macrophages of patients with engulfing apoptotic cells, an upregulation of genes involved in inflammation, autophagy, and signaling was observed. These results indicate that novel immune-pathological pathways are involved in SLE and suggest targets for potential therapeutic modulation.
Two-port network analyzer calibration using an unknown 'thru'

A procedure performed by using a genuine two-port reciprocal network instead of a standard 'thru' in a full two-port error correction of an automatic network analyzer is presented. Although it can be applied to any type of waveguide system, the proposed technique is particularly useful with noninsertable coaxial or one-wafer devices. Experimental comparisons show that the suggested procedure provides a great degree of accuracy. <<ETX>>
Small molecule αv integrin antagonists: novel anticancer agents

The members of the integrin family are targets that potentially provide both therapeutic and diagnostic opportunities. Advances in the understanding of the signalling pathways, transcriptional regulation and the structure/function relationships of the adhesion molecules to extracellular matrix proteins have all contributed to these opportunities. The role of the integrins in pathological processes in both acute and chronic diseases, include ocular, cancer (solid tumours and metastasis), cardiovascular (stroke and heart failure) and inflammatory (rheumatoid arthritis) conditions. Various therapeutic candidates, including antibodies, cyclic peptides and peptidomimetics, have been identified. This review will focus on the key role of the v integrin (vβ3 and vβ5) in angiogenic processes in tumours, including its potential use in cancer diagnostics and therapy.
Automated decision support for response time analysis of real time task set — an approach paper

Response time analysis plays a critical role in the design of real time application and ensures that the design meets the real time constraints. Often it is arduous task to perform response time analysis manually. It involves various steps and parameters for calculating the Response time for a given task set based on which schedulability is decided. One such successful attempt has been made and is presented in this paper.
Human decidual stromal cells express HLA-G: Effects of cytokines and decidualization.

BACKGROUND Decidual stromal cells (DSC) are the main cellular component of the decidua, the maternal tissue in close contact with fetal trophoblast. Although of mesenchymal origin, DSC exert numerous immune functions that seem to be relevant for the immunological relationship between the mother and fetus. HLA-G, an antigen preferentially expressed by trophoblast, appears to participate in the immune tolerance by the mother of the semiallogeneic fetus. METHODS AND RESULTS We show by flow cytometry, fluorescence microscopy, western blotting and RT-PCR that DSC isolated and maintained in culture express HLA-G weakly but consistently. We also detected this antigen by flow cytometry in fresh DSC. Interleukin (IL)-10, a cytokine associated with normal pregnancy, increased the expression of HLA-G by DSC (P < 0.00001), whereas IL-2, a cytokine involved in spontaneous abortion, showed no effect. Decidualization by progesterone and cAMP also up-regulated the expression of HLA-G by DSC (P < 0.001). Interferon gamma, a cytokine implicated in the vascular remodelling of the decidua necessary for embryo implantation, also increased the expression of HLA-G by DSC (P < 0.05). CONCLUSIONS Our results suggest the existence of a network in which hormones together with cytokines regulate the expression of HLA-G by DSC, and that may be of relevance in the maintenance of maternal-fetal tolerance.
Hysteresis Modeling in Li-Ion Batteries

This paper investigates the applicability of the scalar Preisach model to describe the hysteresis in the state of charge versus open-circuit voltage plane of lithium-iron-phosphate batteries. The model is implemented using the Everett function, identified with experimental data related to first-order reversal hysteresis branches. To show the effectiveness of the approach and the predictive capabilities of the Preisach model in this peculiar application, numerical simulations of a major hysteresis loop and a set of minor loops are compared with the experimental data.
Longitudinal study of cerebral blood flow SPECT in Parkinson's disease with dementia, and dementia with Lewy bodies

People with Parkinson's disease (PD) have an increased risk of developing dementia (PDD), which often has clinical features similar to dementia with Lewy bodies (DLB). Whilst perfusion studies have shown parieto‐occipital hypoperfusion in DLB and PDD relative to controls, there have not been any longitudinal studies of perfusion changes in PDD and DLB.