Objective: In patients with isolated soleal vein thrombosis (SVT), the relation between acute thrombi and positive anti-nuclear antibody (ANA) was investigated.
Subjects and Methods: The subjects were 116 lower extremities in 86 patients with SVT. They were diagnosed and examined by ultrasonography and blood serum analysis (D-dimer, ANA), and had been followed up every three months.
Results: They had acute SVT in 35 limbs (30%) and chronic SVT in 86 limbs (70%), and they had positive ANA in 63%. They had recurrent SVT in 26%, and all were positive for ANA.
Conclusion: ANA-positivity might be a risk factor for acute thrombi in patients with SVT. (*English Translation of J Jpn Coll Angiol 2010; 50: 417-422.)
isolated soleal vein thrombosis; recurrent deep vein thrombosis; risk factor; antinuclear antibody
Small interfering RNA (siRNA)-based therapeutics have been used in humans and offer distinct advantages over traditional therapies. However, previous investigations have shown that there are several technical obstacles that need to be overcome before routine clinical applications are used. Currently, we are launching a novel class of RNAi therapeutic agents (PnkRNA™, nkRNA) that show high resistance to degradation and are less immunogenic, less cytotoxic, and capable of efficient intracellular delivery. Here, we develop a novel platform to promote naked RNAi approaches administered through inhalation without sophisticated delivery technology in mice. Furthermore, a naked and unmodified novel RNAi agent, such as ribophorin II (RPN2-PnkRNA), which has been selected as a therapeutic target for lung cancer, resulted in efficient inhibition of tumor growth without any significant toxicity. Thus, this new technology using aerosol delivery could represent a safe, potentially RNAi-based strategy for clinical applications in lung cancer treatment without delivery vehicles.
While liganded nuclear receptors are established to regulate Pol II-dependent transcription units, their role in regulating Pol III-transcribed DNA repeats remains largely unknown. Here, we report that ~2–3% of the ~100,000–200,000 human DR2 Alu repeats in proximity to activated Pol II transcription units are activated by retinoic acid receptor in human embryonic stem cells to generate Pol III-dependent RNAs. These transcripts are processed, initially in a DICER-dependent fashion, into small RNAs (~28–65nt.), referred to as riRNAs, that cause degradation of a subset of critical stem cell mRNAs, including Nanog, modulating exit from the proliferative stem cell state. This regulation requires AGO3-dependent accumulation of processed DR2 Alu transcripts and subsequent recruitment of AGO3-associated decapping complexes to the target mRNA. In this way, the RAR and Pol III-dependent DR2 Alu transcriptional events in stem cells functionally complement the Pol II-dependent neuronal transcriptional program.
Radioisotopes and fluorescent compounds are frequently used for RNA labeling but are unsuitable for clinical studies of RNA drugs because of the risk from radiation exposure or the nonequivalence arising from covalently attached fluorophores. Here, we report a practical phosphoramidite solid-phase synthesis of 18O-labeled RNA that avoids these disadvantages, and we demonstrate its application to quantification and imaging. The synthesis involves the introduction of a nonbridging 18O atom into the phosphate group during the oxidation step of the synthetic cycle by using 18O water as the oxygen donor. The 18O label in the RNA was stable at pH 3–8.5, while the physicochemical and biological properties of labeled and unlabeled short interfering RNA were indistinguishable by circular dichroism, melting temperature and RNA-interference activity. The 18O/16O ratio as measured by isotope ratio mass spectrometry increased linearly with the concentration of 18O-labeled RNA, and this technique was used to determine the blood concentration of 18O-labeled RNA after administration to mice. 18O-labeled RNA transfected into human A549 cells was visualized by isotope microscopy. The RNA was observed in foci in the cytoplasm around the nucleus, presumably corresponding to endosomes. These methodologies may be useful for kinetic and cellular-localization studies of RNA in basic and pharmaceutical studies.
The purpose of this study was to examine task-related changes in prefrontal cortex (PFC) activity during a dual-task in both healthy young and older adults and compare patterns of activation between the age groups. We also sought to determine whether brain activation during a dual-task relates to executive/attentional function and how measured factors associated with both of these functions vary between older and younger adults.
Thirty-five healthy volunteers (20 young and 15 elderly) participated in this study. Near-infrared spectroscopy (NIRS) was employed to measure PFC activation during a single-task (performing calculations or stepping) and dual-task (performing both single-tasks at once). Cognitive function was assessed in the older patients with the Trail-making test part B (TMT-B). Major outcomes were task performance, brain activation during task (oxygenated haemoglobin: Oxy-Hb) measured by NIRS, and TMT-B score. Mixed ANOVAs were used to compare task factors and age groups in task performance. Mixed ANOVAs also compared task factors, age group and time factors in task-induced changes in measured Oxy-Hb. Among the older participants, correlations between the TMT-B score and Oxy-Hb values measured in each single-task and in the dual-task were examined using a Pearson correlation coefficient.
Oxy-Hb values were significantly increased in both the calculation task and the dual-task within patients in both age groups. However, the Oxy-Hb values associated with there were higher in the older group during the post-task period for the dual-task. Also, there were significant negative correlations between both task-performance accuracy and Oxy-Hb values during the dual-task and participant TMT-B scores.
Older adults demonstrated age-specific PFC activation in response to dual-task challenge. There was also a significant negative correlation between PFC activation during dual-task and executive/attentional function. These findings suggest that the high cognitive load induced by dual-task activity generates increased PFC activity in older adults. However, this relationship appeared to be strongest in participants with better baseline attention and executive functions.
Dual-task; Near-infrared spectroscopy; Executive function; Attentional function
The association between hyper-inflammatory states and numerous diseases is widely recognized, but our understanding of the molecular strategies that have evolved to prevent uncontrolled activation of inflammatory responses remains incomplete. Here, we report a critical, non-transcriptional role of GPS2 as a guardian against hyperstimulation of the TNFα-induced gene program. GPS2 cytoplasmic actions are required to specifically modulate RIP1 ubiquitylation and JNK activation by inhibiting TRAF2/Ubc13 enzymatic activity. In vivo relevance of GPS2 anti-inflammatory role is confirmed by inhibition of TNFα target genes in macrophages and by improved insulin signaling in the adipose tissue of aP2-GPS2 transgenic mice. As the non-transcriptional role is complemented by GPS2 functioning as positive and negative cofactor for nuclear receptors, in vivo overexpression also results in elevated circulating level of Resistin and development of hepatic steatosis. Together, these studies define GPS2 as a molecular guardian required for precise control of inflammatory responses involved in immunity and homeostasis.
RNA interference (RNAi) is being widely used in functional gene research and is an important tool for drug discovery. However, canonical double-stranded short interfering RNAs are unstable and induce undesirable adverse effects, and thus there is no currently RNAi-based therapy in the clinic. We have developed a novel class of RNAi agents, and evaluated their effectiveness in vitro and in mouse models of acute lung injury (ALI) and pulmonary fibrosis. The novel class of RNAi agents (nkRNA®, PnkRNA™) were synthesized on solid phase as single-stranded RNAs that, following synthesis, self-anneal into a unique helical structure containing a central stem and two loops. They are resistant to degradation and suppress their target genes. nkRNA and PnkRNA directed against TGF-β1mRNA ameliorate outcomes and induce no off-target effects in three animal models of lung disease. The results of this study support the pathological relevance of TGF-β1 in lung diseases, and suggest the potential usefulness of these novel RNAi agents for therapeutic application.
Although eukaryotic nuclei contain distinct architectural structures associated with noncoding RNAs (ncRNAs), their potential relationship to regulated transcriptional programs remains poorly understood. Here, we report that methylation/demethylation of Polycomb 2 protein (Pc2) controls relocation of growth control genes between Polycomb bodies (PcGs) and interchromatin granules (ICGs) in response to growth signals. This movement is the consequence of binding of methylated and unmethylated Pc2 to the ncRNAs, TUG1 and MALAT1/NEAT2, located in PcGs and ICGs, respectively. These ncRNAs mediate assembly of multiple co-repressors/co-activators, and can alter the histone marks read by Pc2 in vitro. Additionally, binding of NEAT2 to unmethylated Pc2 promotes E2F1 SUMOylation, leading to activation of the growth control gene program. These observations delineate a molecular pathway linking the actions of subnuclear structure-specific ncRNAs and non-histone protein methylation to relocation of transcription units in the three-dimensional space of the nucleus, thus achieving coordinated gene expression programs.
Noncoding RNA; Nuclear Architecture; Subnuclear Structures; Suv39h1; Pc2; Methylation; KDM4C; Polycomb Body; Interchromatin Granules; E2F1; SUMOylation; Ubiquitination
Mammalian genomes are populated with thousands of transcriptional enhancers that orchestrate cell type-specific gene expression programs1-4, but how those enhancers are exploited to institute alternative, signal-dependent transcriptional responses remains poorly understood. Here we present evidence that cell lineage-specific factors, such as FoxA1, can simultaneously facilitate and restrict key regulated transcription factors, exemplified by the androgen receptor (AR), to act on structurally- and functionally-distinct classes of enhancers. Consequently, FoxA1 down-regulation, an unfavorable prognostic sign in certain advanced prostate tumors, triggers dramatic reprogramming of the hormonal response by causing a massive switch in AR binding to a distinct cohort of pre-established enhancers. These enhancers are functional, as evidenced by the production of enhancer-templated non-coding RNA (eRNA5) based on global nuclear-on (GRO-seq) analysis6, with a unique class apparently requiring no nucleosome remodeling to induce specific enhancer-promoter looping and gene activation. GRO-seq data also suggest that liganded AR induces both transcription initiation and elongation. Together, these findings reveal a large repository of active enhancers that can be dynamically tuned to elicit alternative gene expression programs, which may underlie many sequential gene expression events in development, cell differentiation and disease progression.
While reversible histone modifications are linked to an ever-expanding range of biological functions1–5, the demethylases for histone H4 lysine 20 and their potential regulatory roles remain unknown. Here, we report that the PHD and Jumonji C (JmjC) domain-containing protein, PHF8, while utilizing multiple substrates, including H3K9me1/2 and H3K27me2, also functions as an H4K20me1 demethylase. PHF8 is recruited to promoters by its PHD domain based on interaction with H3K4me2/3 and controls G1/S transition in conjunction with E2F1, HCF-1 and Set1A, at least in part, by removing the repressive H4K20me1 mark from a subset of E2F1-regulated gene promoters. Phosphorylation-dependent PHF8 dismissal from chromatin in prophase is apparently required for the accumulation of H4K20me1 during early mitosis, which might represent a component of the Condensin II loading process. Accordingly, the HEAT repeat clusters in two non-SMC Condensin II subunits, N-CAPD3 and N-CAPG2, are capable of recognizing H4K20me1, and ChIP-seq. analysis demonstrate a significant overlap of Condensin II and H4K20me1 sites in mitotic HeLa cells. Thus, the identification and characterization of the first H4K20me1 demethylase, PHF8, has revealed an intimate link between this enzyme and two distinct events in cell cycle progression.
Though medicines that target mRNA are under active investigation, there has been little or no effort to develop mRNA itself as a medicine. Here, we report the synthesis of a 130-nt mRNA sequence encoding a 33-amino-acid peptide that includes the sequence of glucagon-like peptide-1, a peptide that stimulates glucose-dependent insulin secretion from the pancreas. The synthesis method used, which had previously been developed in our laboratory, was based on the use of 2-cyanoethoxymethyl as the 2′-hydroxy protecting group. We also developed novel, highly reactive phosphotriester pyrophosphorylating reagents to pyrophosphorylate the 5′-end of the 130-mer RNA in preparation for capping. We completed the synthesis of the artificial mRNA by the enzymatic addition of a 5′-cap and a 3′-poly(A) tail to the pyrophosphorylated 130-mer and showed that the resulting mRNA supported protein synthesis in a cell-free system and in whole cells. As far as we know, this is the first time that mRNA has been prepared from a chemically synthesized RNA sequence. As well as providing a research tool for the intracellular expression of peptides, the technology described here may be used for the production of mRNA for medical applications.
Chromosomal translocations are a hallmark of leukemia/lymphoma and also appear in solid tumors, but the underlying mechanism remains elusive. By establishing a cellular model that mimics the relative frequency of authentic translocation events without proliferation selection, we report mechanisms of nuclear receptor-dependent tumor translocations. Intronic binding of liganded-AR first juxtaposes translocation loci by triggering intra- and interchromosomal interactions. AR then promotes site-specific DNA double-stranded breaks (DSBs) at translocation loci by recruiting two types of enzymatic machinery induced by genotoxic stress and liganded-AR, including Activation-Induced Cytidine Deaminase (AID) and the LINE-1 repeat-encoded ORF2 endonuclease. These enzymatic machineries synergistically generate site-selective DSBs at juxtaposed translocation loci that are ligated by Non-Homologous Ending Joining (NHEJ) pathway for specific translocations. Our data suggest that the confluence of two parallel pathways initiated by liganded-nuclear receptor and genotoxic stress underlie non-random tumor translocations, which may function in many types of tumors and pathological processes.
Tumor Translocations; Prostate Cancer; Androgen Receptor; AID; PIWIL1; Nuclear Architecture; LINE-1 Repeats; ORF2; DNA Damage/Repair; LNCaP Cells
The Mini-Mental State Examination (MMSE) is one of the most commonly used instruments in the evaluation of global cognitive status. Few studies have investigated the relationship among its components in terms of factorial structure in Japanese individuals suffering from dementia. The aims of this study were: 1) to analyze the factorial structure of MMSE in Japanese dementia patients, 2) to clarify the MMSE static structure in identifying different cognitive profiles and understanding how these profiles are related to levels of dysfunction in subsets of dementia patients.
30,895 consecutive outpatients with dementia were evaluated. The 11 subtests composing the MMSE and the global MMSE score were analyzed. Factor analysis based on principal component analysis with Promax rotation was applied to the data representing the frequency of failures in each subtest as identified by the MMSE.
Factor analysis identified three factors that explained approximately 44.57% of the total variance. The first factor, immediate memory, essentially constituted a simple index of the reading and writing subtests. The second factor, orientation and delayed recall, expressed the ability to handle new information. The third factor, working memory, was most closely related to the severity of dementia at the time of test administration.
Japanese dementia patients appear to develop difficulty handling new information in the early stages of their disease. This finding, and our finding that there is a factor associated with disease severity, suggest that understanding the specific factors related to subtest items, which underlie the total MMSE score may be useful to clinicians in planning interventions for Japanese patients in the early stages of dementia.
This study was to measure changes in frontal brain activation in young children during picture book reading with their mothers.
The cross-sectional sample consisted of 15 young Japanese children (8 girls and 7 boys, mean age 23.1±3.4). Two experimental tasks were presented as follows: Task 1 (picture book reading with their mothers); Task 2 (viewing of book-on-video). Duration of task stimulus was 180 sec and the 60 sec interval was filled. Brain activation was measured using an optical topography system.
Significant increases in oxy-Hb were observed in both right and left frontal areas in response to Task 1 compared to Task 2. There were significant correlations between child’s brain activity and mothers’ and children’s verbal – nonverbal behaviors.
There was greater frontal lobe activation in children when they were engaged in a picture book reading task with their mothers, as opposed to passive viewing of a videotape in which the story was read to them. Social and verbal engagement of the mother in reading picture books with her young child may mediate frontal brain activity in the child.
picture book reading; verbal – nonverbal behaviors; frontal brain activation; near-infrared spectroscopy (NIRS)
To establish an index to predict ART outcomes and to identify infertile patients who need LH supplementation during ovarian stimulation.
Serum LH concentrations were measured during the mid- and late-follicular phase in 86 normogonadotropic infertile patients who underwent ART treatment using GnRH-agonist long protocol with recombinant-FSH. The relationships between serum LH concentrations at both time points and ART outcomes were retrospectively analyzed, and the relationships between the ratio of late-follicular to mid-follicular LH concentrations and ART outcomes were also evaluated.
There were no significant correlations between the mid- or late-follicular LH concentrations and ART outcomes. The ratio of late-follicular to mid-follicular LH concentrations <1.0 was considered the relatively LH decreased group (RD group) and ratio ≥ 1.0 was considered the relatively LH increased group (RI group). The number of usable embryos in RD group was similar to that in RI group, but the pregnancy and implantation rates in the RD group (9.7% and 5.8%) were significantly lower than those in the RI group (31.1% and 17.2%; p < 0.05).
Relatively decreased LH concentrations during ovarian stimulation using GnRH-agonist long protocol with rec-FSH had a negative effect on ART outcomes. Therefore, the ratio of mid- to late-follicular phase LH concentrations is suggested to be an efficient index to identify patients who might benefit from LH supplementation.
ART outcome; GnRH-agonist; LH concentration; Long protocol; Recombinant-FSH; Pregnancy rate
Deciphering the epigenetic “code” remains a central issue in transcriptional regulation. Here, we report the identification of a MPN+/JAMM domain-containing histone H2A deubiquitinase (2A-DUB, or KIAA1915/MYSM1) specific for monoubiquitinated H2A (uH2A), that has permitted delineation of a strategy for specific regulatory pathways of gene activation. 2A-DUB regulates transcription by coordinating histone acetylation and deubiquitination, and destabilizing the association of linker histone H1 with nucleosomes. 2A-DUB interacts with p/CAF in a co-regulatory protein complex, with its deubiquitinase activity modulated by the status of acetylation of nucleosomal histones. Consistent with this mechanistic role, 2A-DUB participates in transcriptional regulation events in androgen receptor-dependent gene activation, and the levels of uH2A are dramatically decreased in prostate tumors, serving as a cancer-related mark. We suggest that H2A ubiquitination represents a widely-used mechanism for many regulatory transcriptional programs, and predict that various H2A ubiquitin ligases/deubiquitinases will be identified for specific cohorts of regulated transcription units.
To evaluate the cystectomy-induced damage on the follicular growth and ovulation of an affected ovary during natural cycles.
Twenty-eight infertile patients with unilateral ovarian endometriomas who underwent laparoscopic cystectomy were retrospectively evaluated. The ovulation rate of an affected ovary during natural cycles was compared before and after cystectomy in each patient, and it was also determined if ovulation from the affected ovaries resulted in pregnancy.
After surgery, the ovulation rate was significantly lower than that before cystectomy (16.9 ± 4.5% vs. 34.4 ± 6.6%, P = 0.013). After surgery, 14 pregnancies were achieved without IVF treatment, and only 2 of them (14.3%) were achieved from an operated-side ovary. However, the pregnancy rate per ovulatory cycle of the operated-side ovary was not different from that of the intact ovary (8.8% vs. 5.8%, P = 0.750).
Laparoscopic cystectomy is an invasive treatment in that it reduces the frequency of ovulation; however the pregnancy rate per ovulation did not deteriorate.
Endometrioma; Enucleation; Natural cycle; Ovarian reserve; Ovulation rate
For this study, the impact of basal FSH levels on ART outcomes was assessed.
From June 2003 to May 2006, 191 ART cycles were performed in our hospital. All cases were treated with GnRH-a long protocol. The patients were classified according to their basal FSH level as follows: group A: FSH < 10 IU/l, group B: 10 ≦ FSH < 15 IU/l, and group C: 15 IU/l ≦ FSH. ART outcomes were compared among the three groups.
The number of retrieved oocytes in group A was significantly higher than in group B, but fertilized oocytes and the pregnancy rates were comparable. The pregnancy rate in group C was not significantly lower than those found in either group A or B, but the trend was lower.
Oocytes retrieved from the patients who showed basal FSH levels below 15 IU/l were found to possess significant pregnancy potential.
ART; Basal FSH; Pregnancy rate
A key strategy to achieve regulated gene expression in higher eukaryotes is to prevent illegitimate signal-independent activation by imposing robust control on the dismissal of corepressors. Here, we report that many signaling pathways, including Notch, NFkB, and nuclear receptor ligands, are subjected to a dual repression “check point” based on distinct corepressor complexes. Gene activation requires the release of both CtBP1/2- and NCoR/SMRT-dependent repression, through the coordinate action of two highly related exchange factors, the transducer β-like proteins TBL1 and TBLR1, that license ubiquitylation and degradation of CtBP1/2 and NCoR/SMRT, respectively. Intriguingly, their function and differential specificity resides in only five specific Ser/Thr phosphorylation site differences, regulated by direct phosphorylation at the level of the promoter, as exemplified by the role of PKCδ in TBLR1-dependent dismissal of NCoR. Thus, our data reveal a strategy of dual- factors repression checkpoints, in which dedicated exchange factors serve as sensors for signal- specific dismissal of distinct corepressors, with specificity imposed by upstream signaling pathways.
TBL1; TBLR1; nuclear receptors; N-CoR; CtBP; ubiquitylation; repression; transcription
Solving the biological roles of covalent histone modifications, including monoubiqutination of histone H2A, and the molecular mechanisms by which these modifications regulate specific transcriptional programs, remains a central question for all eukaryotes. Here, we report that the N-CoR/HDAC1/3 complex specifically recruits a previously-unidentified specific histone H2A ubiquitin ligase, 2A-HUB/hRUL138, to a subset of regulated gene promoters. 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. We suggest that distinct H2A ubiquitinases, each recruited based on interactions with different corepressor complexes, contribute to effective distinct transcriptional repression programs.
Puerose: To demonstrate our hypothesis that a correlation exists between oocyte maturity and a decrease in intraovarian blood flow resistance in assisted reproductive technology (ART) treatment cycles, oocyte maturity and total antioxidant status (TAOS) in follicular fluid was examined.
Methods: A total of 59 cycles involving 51 infertile patients undergoing ART treatment in our hospital were recruited in this study. The ART cycles were divided into two groups: deeply decreased (DD) group and not-deeply decreased (NDD) group, according to the pulsatility index (PI) values for perifollicular arterial blood flow before and after hCG administration. The PI values that showed a decrease in their PI after hCG administration of 10% or more were defined “deeply decreased” and showed a decrease of less than 10% were considered “not-deeply decreased.” The recovery rates of mature and immature oocytes and TAOS in follicular fluid were compared between the two groups.
Results: Mature and immature oocyte recovery rates in the DD group (62.5% and 17.2%) were significantly higher and lower, respectively, than those in the NDD group (41.7% and 38.3%, p < 0.05). The TAOS (1.55 ± 0.44 mmol/L) of the DD group was significantly lower than that in the NDD group (1.68 ± 0.47 mmol/L, p < 0.05).
Conclusions: The decrease in intraovarian arterial blood flow resistance measured after hCG administration may be a good indicator of retrieving mature oocyte.
ART; Intraovarian blood flow resistance; Oocyte maturity; Total antioxidant status (TAOS)
Nuclear receptors undergo ligand-dependent conformational changes that are required for corepressor-coactivator exchange, but whether there is an actual requirement for specific epigenetic landmarks to impose ligand dependency for gene activation remains unknown. Here we report an unexpected and general strategy that is based on the requirement for specific cohorts of inhibitory histone methyltransferases (HMTs) to impose gene-specific gatekeeper functions that prevent unliganded nuclear receptors and other classes of regulated transcription factors from binding to their target gene promoters and causing constitutive gene activation in the absence of stimulating signals. This strategy, based at least in part on an HMT dependent inhibitory histone code, imposes a requirement for specific histone demethylases, including LSD1, to permit ligand- and signal dependent activation of regulated gene expression. These events link an inhibitory methylation component of the histone code to a broadly used strategy that circumvents pathological constitutive gene induction by physiologically regulated transcription factors.
A long RNA oligomer, a 110mer with the sequence of a precursor-microRNA candidate, has been chemically synthesized in a single synthesizer run by means of standard automated phosphoramidite chemistry. The synthetic method involved the use of 2-cyanoethoxymethyl (CEM), a 2′-hydroxyl protecting group recently developed in our laboratory. We improved the methodology, introducing better coupling and capping conditions. The overall isolated yield of highly pure 110mer was 5.5%. Such a yield on a 1-μmol scale corresponds to 1 mg of product and emphasizes the practicality of the CEM method for synthesizing oligomers of more than 100 nt in sufficient quantity for biological research. We confirmed the identity of the 110mer by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, as well as HPLC, electrophoretic methods, and RNase-digestion experiments. The 110mer also showed sense-selective specific gene-silencing activity. As far as we know, this is the longest chemically synthesized RNA oligomer reported to date. Furthermore, the identity of the 110mer was confirmed by both physicochemical and biological methods.
Purpose: Intraovarian arterial blood flows before and after follicular rupture in ovulation induced cycles were examined by transvaginal color flow Doppler imaging. The changes observed in the intraovarian arterial resistance before and after ovulation in relation to the regularity of menstruation and several other parameters were analyzed.
Methods: In a prospective study, 22 patients undergoing infertility treatment in our center were recruited. Patients were divided into two subgroups, according to their menstrual regularity (regular menstrual group and oligomenorrheal group) and 42 cycles were studied. All patients received the same FSH low-dose stimulation treatment. The relationship between the post and preovulatory arterial pulsatility indexes (PI) was analyzed. Cycles that showed a decrease in their PI after ovulation of 10% or more were considered “profoundly decreased cycles.” Cycles from the same patients without ovulatory stimulation (natural cycles) were used as control.
Results: In the regular menstrual group the rate of profoundly decreased cycles during FSH stimulation was 63.2%, which was similar to the rate observed in natural cycles. In the oligomenorrheal group the rate of profoundly decreased cycles during natural cycles was 14.3%, but in FSH ovulation induction cycles this rate was significantly increased (47.6%, p < 0.05). In addition, the pregnancy rate per cycle in the oligomenorrheal group was significantly higher than that in the regular menstrual group (p = 0.03).
Conclusions: Oligomenorrheal patients presented a higher rate in the decrease of their PI values after FSH stimulation, which is essential to achieve pregnancy. This elevated rate of reduction implies that oligomenorrheal patients have increased incidence of disturbance in their ovulatory process when compared to normal cycling patients. Thus, ovulation induction with FSH, in oligomenorrheal patients resulted in a higher pregnancy rate in this group.
Low-dose FSH step-up protocol; oligomenorrhea; ovulation induction; pregnancy.
Background: Infants with neonatal cerebral insults are susceptible to excessive crying as a result of difficulties with self-regulation.
Aims: To compare the effectiveness of swaddling versus massage therapy in the management of excessive crying of infants with cerebral insults.
Methods: Randomised three-week parallel comparison of the efficacy of two intervention methods. Infants with symptoms of troublesome crying and their parents were randomly assigned to a swaddling intervention group (n = 13) or a massage intervention group (n = 12).
Results: The amount of total daily crying decreased significantly in the swaddling group, but did not decrease significantly in the massage group. Infant behavioural profiles and maternal anxiety levels improved significantly in the swaddling group post-intervention. Parents in the swaddling group were more satisfied with the effectiveness of the intervention in reducing crying than parents in the massage group.
Conclusion: Results indicate that swaddling may be more effective than massage intervention in reducing crying in infants with cerebral injuries.