Effect of Progressive Muscle Relaxation on the Adverse Cardiovascular Profile in Women with Polycystic Ovarian Syndrome

Background: The altered stress reactivity in polycystic ovarian syndrome (PCOS) may constitute a link between depression, overweight, and cardiovascular risk factors. Aims: To study the effects of progressive muscle relaxation (PMR) on the stress levels of PCOS patients and their influence on the cardiovascular risk factors. Subjects and Methods: This prospective pilot project was conducted on 100 PCOS patients in a tertiary care hospital of West Bengal, after receiving approval from the Institutional Ethical Committee and informed consent of the subjects. The stress levels were assessed and conventional autonomic function tests and the lipid profi les were analyzed. The subjects were divided into two groups using an online randomizer. One group received medication, while the other group received medication and practiced progressive muscle relaxation (PMR) for three months. All parameters were re‑evaluated at the end of three months. Results: The perceived stress scale was significantly less in subjects practicing relaxation exercises, as compared to subjects only on medication. The waist/hip ratio, pulse rate, and systolic blood pressure were significantly lower, while there was no difference in the body mass index (BMI) and diastolic blood pressure. Results of the autonomic function tests showed a significant parasympathetic tilt in subjects practicing PMR. In patients with PCOS, who were on PMR, cholesterol, triglycerides, and low‑density cholesterol (LDL) were significantly lower and high‑density cholesterol HDL was significantly higher. Conclusions: PCOS patients are a high‑risk group for developing the metabolic syndrome and relaxation therapies may be recommended as an adjuvant therapy, to tilt the autonomic balance to parasympathetic dominance, to improve the cardiovascular profile.Keywords: Autonomic functions, cardiovascular system, polycystic ovarian syndrome, stres

A Prospective Study of Doppler Velocimetry in Pregnancy-induced Hypertension in a Rural Population of a Developing Country

Background: Pregnancy-induced hypertension (PIH) remains a great challenge to obstetricians. Doppler velocimetry can detect fetal compromise much before other antepartum tests.Aim: The aim of this study is to detect the changes of uterine artery, umbilical artery and middle cerebral artery in PIH by Doppler velocimetry.Subjects and Methods: This prospective study was conducted on hundred subjects with PIH. Doppler studies were carried, and parameters recorded in uterine, umbilical and middle cerebral artery (MCA) were Systolic/Diastolic ratio, Resistance Index, Cerebro Placental Index (CPI). Fetal outcomes were monitored. Statistical analysis was performed using Epi InfoTM software (Version 3.5.1, CDC, Atlanta). Test for significance was done with student’s t-test and Chi-square where applicable. A P- value of<0.05 was considered as significant.Results: Among the 100 subjects, 76 (76%) of fetuses had abnormal and 24% normal umbilical artery Doppler velocimetry; 62% had abnormal and 38% normal MCA Doppler velocimetry; 64% fetuses had abnormal and 36% normal CPI. In 95% of subjects having abnormal umbilical Doppler studies, caesarean section had to be done for acute fetal distress. Incidence of caesarean section was 61% in abnormal MCA group and 63% in abnormal CPI group. Among 14 patients who had abnormal uterine artery Doppler, four developed pre-eclampsia, 2 IUGR. In patients with notches in uterine artery Doppler, 38% developed pre-eclampsia, 38% had IUGR, 13% babies were still born and 25% of newborns required NICU admission. In umbilical artery Doppler, when S/D ratio was abnormal, 60% developed pre-eclampsia, 40% had IUGR and 40% of newborns had to be admitted in NICU.Conclusion: Doppler study for fetal surveillance in pregnancy-induced hypertension is a very useful device and abnormal umbilical artery and uterine artery velocimetry seems to have worse pregnancy outcomes in the present study. Notch as a single parameter is the best indicator with highest sensitivity and positive predicative values. However, combination of parameters is the best indicator.  Keywords: Doppler study, fetomaternal outcome, pregnancy-induced hypertensio

Alternative initiation and splicing in dicer gene expression in human breast cells

INTRODUCTION: Dicer is a ribonuclease that mediates RNA interference both at the transcriptional and the post-transcriptional levels. Human dicer gene expression is regulated in different tissues. Dicer is responsible for the synthesis of microRNAs and short temporal (st)RNAs that regulate the expression of many genes. Thus, understanding the control of the expression of the dicer gene is essential for the appreciation of double-stranded (ds)RNA-mediated pathways of gene expression. Human dicer mRNA has many upstream open reading frames (uORFs) at the 5'-leader sequences (the nucleotide sequence between the 5'-end and the start codon of the major ORF), and we studied whether these elements at the 5'-leader sequences regulate the expression of the dicer gene. METHOD: We determined the 5'-leader sequences of the dicer mRNAs in human breast cells by 5'-RACE and S1-nuclease protection analysis. We have analyzed the functions of the 5'-leader variants by reporter gene expression in vitro and in vivo. RESULTS: We found that the dicer transcripts in human breast cells vary in the sequence of their 5'-leader sequences, and that alternative promoter selection along with alternative splicing of the 5'-terminal exons apparently generate these variations. The breast cell has at least two predominant forms of dicer mRNAs, one of which has an additional 110 nucleotides at the 5'-end. Sequence comparison revealed that the first 80 nucleotides of these mRNA isoforms are encoded by a new exon located approximately 16 kb upstream of the reported start site. There are 30 extra nucleotides added to the previously reported exon 1. The human breast cells studied predominantly express two 5'-leader variants of dicer mRNAs, one with the exons 2 and 3 (long form) and the other without them (short form). By reporter gene expression analysis we found that the exon 2 and 3 sequences at the 5'-leader sequences are greatly inhibitory for the translation of the mRNA into protein. CONCLUSION: Dicer gene expression in human breast cells is regulated by alternative promoter selection to alter the length and composition of the 5'-leader sequence of its mRNA. Furthermore, alternative splicing of its exon 2 and 3 sequences of their pre-mRNA creates a more translationally competent mRNA in these cells

Conditions for Set Agreement with an Application to Synchronous Systems

The $k$-set agreement problem is a generalization of the consensus problem: considering a system made up of $n$ processes where each process proposes a value, each non-faulty process has to decide a value such that a decided value is a proposed value, and no more than $k$ different values are decided. While this problem cannot be solved in an asynchronous system prone to $t$ process crashes when $t \geq k$, it can always be solved in a synchronous system; $\lfloor \frac{t}{k} \rfloor +1$ is then a lower bound on the number of rounds (consecutive communication steps) for the non-faulty processes to decide. The {\it condition-based} approach has been introduced in the consensus context. Its aim was to both circumvent the consensus impossibility in asynchronous systems, and allow for more efficient consensus algorithms in synchronous systems. This paper addresses the condition-based approach in the context of the $k$-set agreement problem. It has two main contributions. The first is the definition of a framework that allows defining conditions suited to the $\ell$-set agreement problem. More precisely, a condition is defined as a set of input vectors such that each of its input vectors can be seen as ``encoding'' $\ell$ values, namely, the values that can be decided from that vector. A condition is characterized by the parameters $t$, $\ell$, and a parameter denoted $d$ such that the greater $d+\ell$, the least constraining the condition (i.e., it includes more and more input vectors when $d+\ell$ increases, and there is a condition that includes all the input vectors when $d+\ell>t$). The conditions characterized by the triple of parameters $t$, $d$ and $\ell$ define the class of conditions denoted ${\cal S}_t^{d,\ell}$, $0\leq d\leq t$, $1\leq \ell \leq n-1$. The properties of the sets ${\cal S}_t^{d,\ell}$are investigated, and it is shown that they have a lattice structure. The second contribution is a generic synchronous $k$-set agreement algorithm based on a condition $C\in {\cal S}_t^{d,\ell}$, i.e., a condition suitedto the $\ell$-set agreement problem, for $\ell \leq k$. This algorithm requires at most $\left\lfloor \frac{d-1+\ell}{k} \right\rfloor +1$ rounds when the input vector belongs to $C$, and $\left\lfloor \frac{t}{k} \right\rfloor +1$ rounds otherwise. (Interestingly, this algorithm includes as particular cases the classical synchronous $k$-set agreement algorithm that requires $\left\lfloor \frac{t}{k} \right\rfloor+1$ rounds (case $d=t$ and $\ell=1$), and the synchronous consensus condition-based algorithm that terminates in $d+1$ rounds when the input vector belongs to the condition, and in $t+1$ rounds otherwise (case $k=\ell=1$).

Microcin H47 System: An Escherichia coli Small Genomic Island with Novel Features

Genomic islands are DNA regions containing variable genetic information related to secondary metabolism. Frequently, they have the ability to excise from and integrate into replicons through site-specific recombination. Thus, they are usually flanked by short direct repeats that act as attachment sites, and contain genes for an integrase and an excisionase which carry out the genetic exchange. These mobility events would be at the basis of the horizontal transfer of genomic islands among bacteria

The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex

The impact of glucose-insulin-potassium infusion in acute myocardial infarction on infarct size and left ventricular ejection fraction [ISRCTN56720616]

BACKGROUND: Favorable clinical outcomes have been observed with glucose-insulin-potassium infusion (GIK) in acute myocardial infarction (MI). The mechanisms of this beneficial effect have not been delineated clearly. GIK has metabolic, anti-inflammatory and profibrinolytic effects and it may preserve the ischemic myocardium. We sought to assess the effect of GIK infusion on infarct size and left ventricular function, as part of a randomized controlled trial. METHODS: Patients (n = 940) treated for acute MI by primary percutaneous coronary intervention (PCI) were randomized to GIK infusion or no infusion. Endpoints were the creatinine kinase MB-fraction (CK-MB) and left ventricular ejection fraction (LVEF). CK-MB levels were determined 0, 2, 4, 6, 24, 48, 72 and 96 hours after admission and the LVEF was measured before discharge. RESULTS: There were no differences between the two groups in the time course or magnitude of CK-MB release: the peak CK-MB level was 249 ± 228 U/L in the GIK group and 240 ± 200 U/L in the control group (NS). The mean LVEF was 43.7 ± 11.0 % in the GIK group and 42.4 ± 11.7% in the control group (P = 0.12). A LVEF ≤ 30% was observed in 18% in the controls and in 12% of the GIK group (P = 0.01). CONCLUSION: Treatment with GIK has no effect on myocardial function as determined by LVEF and by the pattern or magnitude of enzyme release. However, left ventricular function was preserved in GIK treated patients

Three Dimensional Visualization and Fractal Analysis of Mosaic Patches in Rat Chimeras: Cell Assortment in Liver, Adrenal Cortex and Cornea

The production of organ parenchyma in a rapid and reproducible manner is critical to normal development. In chimeras produced by the combination of genetically distinguishable tissues, mosaic patterns of cells derived from the combined genotypes can be visualized. These patterns comprise patches of contiguously similar genotypes and are different in different organs but similar in a given organ from individual to individual. Thus, the processes that produce the patterns are regulated and conserved. We have previously established that mosaic patches in multiple tissues are fractal, consistent with an iterative, recursive growth model with simple stereotypical division rules. Fractal dimensions of various tissues are consistent with algorithmic models in which changing a single variable (e.g. daughter cell placement after division) switches the mosaic pattern from islands to stripes of cells. Here we show that the spiral pattern previously observed in mouse cornea can also be visualized in rat chimeras. While it is generally held that the pattern is induced by stem cell division dynamics, there is an unexplained discrepancy in the speed of cellular migration and the emergence of the pattern. We demonstrate in chimeric rat corneas both island and striped patterns exist depending on the age of the animal. The patches that comprise the pattern are fractal, and the fractal dimension changes with the age of the animal and indicates the constraint in patch complexity as the spiral pattern emerges. The spiral patterns are consistent with a loxodrome. Such data are likely to be relevant to growth and cell division in organ systems and will help in understanding how organ parenchyma are generated and maintained from multipotent stem cell populations located in specific topographical locations within the organ. Ultimately, understanding algorithmic growth is likely to be essential in achieving organ regeneration in vivo or in vitro from stem cell populations

Mitochondrial haplogroup N1a phylogeography, with implication to the origin of European farmers

<p>Abstract</p> <p>Background</p> <p>Tracing the genetic origin of central European farmer N1a lineages can provide a unique opportunity to assess the patterns of the farming technology spread into central Europe in the human prehistory. Here, we have chosen twelve N1a samples from modern populations which are most similar with the farmer N1a types and performed the complete mitochondrial DNA genome sequencing analysis. To assess the genetic and phylogeographic relationship, we performed a detailed survey of modern published N1a types from Eurasian and African populations.</p> <p>Results</p> <p>The geographic origin and expansion of farmer lineages related N1a subclades have been deduced from combined analysis of 19 complete sequences with 166 N1a haplotypes. The phylogeographic analysis revealed that the central European farmer lineages have originated from different sources: from eastern Europe, local central Europe, and from the Near East via southern Europe.</p> <p>Conclusions</p> <p>The results obtained emphasize that the arrival of central European farmer lineages did not occur via a single demic diffusion event from the Near East at the onset of the Neolithic spread of agriculture into Europe. Indeed these results indicate that the Neolithic transition process was more complex in central Europe and possibly the farmer N1a lineages were a result of a 'leapfrog' colonization process.</p

Leishmania-Induced Inactivation of the Macrophage Transcription Factor AP-1 Is Mediated by the Parasite Metalloprotease GP63

Leishmania parasites have evolved sophisticated mechanisms to subvert macrophage immune responses by altering the host cell signal transduction machinery, including inhibition of JAK/STAT signalling and other transcription factors such as AP-1, CREB and NF-κB. AP-1 regulates pro-inflammatory cytokines, chemokines and nitric oxide production. Herein we show that upon Leishmania infection, AP-1 activity within host cells is abolished and correlates with lower expression of 5 of the 7 AP-1 subunits. Of interest, c-Jun, the central component of AP-1, is cleaved by Leishmania. Furthermore, the cleavage of c-Jun is dependent on the expression and activity of the major Leishmania surface protease GP63. Immunoprecipitation of c-Jun from nuclear extracts showed that GP63 interacts, and cleaves c-Jun at the perinuclear area shortly after infection. Phagocytosis inhibition by cytochalasin D did not block c-Jun down-regulation, suggesting that internalization of the parasite might not be necessary to deliver GP63 molecules inside the host cell. This observation was corroborated by the maintenance of c-Jun cleavage upon incubation with L. mexicana culture supernatant, suggesting that secreted, soluble GP63 could use a phagocytosis-independent mechanism to enter the host cell. In support of this, disruption of macrophage lipid raft microdomains by Methyl β-Cyclodextrin (MβCD) partially inhibits the degradation of full length c-Jun. Together our results indicate a novel role of the surface protease GP63 in the Leishmania-mediated subversion of host AP-1 activity