Both sympatric and allopatric scenarios of animal speciation typically envision slow and gradual genetic transformations of populations,

even when vicariant events in the physical environment are sudden. But unisexual vertebrate taxa break this evolutionary rule because each biotype emerges quickly (in one or a few generations) from the two (or sometimes more) sexual species that had hybridized to produce Lenvatinib molecular weight it (Dawley & Bogart, 1989; Vrijenhoek, 1994). Thus, in a temporal sense, the emergence of many parthenogenetic animal species parallels the rapid emergence of many allopolyploid plant species that also have arisen following interspecific hybridization events. Conventional wisdom holds that genetic recombination (typically via sexual reproduction in multicellular organisms) is necessary for continued adaptability to changing environments and for the long-term evolutionary persistence of any species. To assess the evolutionary ages of vertebrate clones, researchers have generated and provisionally

dated phylogenetic Epigenetics inhibitor trees (typically from mtDNA sequences and molecular-clock calibrations) for many unisexual taxa and their sexual relatives. Results proved generally consistent with the standard thesis that asexual lineages have short evolutionary durations, but there do seem to be some exceptions. For example, Quattro, Avise & Vrijenhoek (1992b) used a large geographic range and high post-formational cytonuclear genetic diversity to estimate that a monophyletic biotype of the unisexual fish Poeciliopsis monacha-occidentalis is about 60 000 years old. Although Maynard Smith (1992) rightly noted in a commentary that 60 000 years ‘is but an evening gone’ in evolutionary time, it does seem clear that at least some vertebrate clones are far more persistent than formerly realized. In any event, this and other longevity estimates for various unisexual vertebrate lineages all pale in comparison from with the ancient origins suspected for some invertebrate parthenogenetic lineages that seem to have survived without sex for tens of

millions of years (Mark Welch, Mark Welch & Meselson, 2004; Domes et al., 2007; Heethoff et al., 2007). Female parthenogens truly are sexually chaste, but females in gynogenetic and hybridogenetic vertebrate taxa might be deemed only ‘semichaste’. As under parthenogenesis, a gynogenetic female reproduces clonally except that sperm from males of a related sexual species are required to initiate cellular divisions in her unreduced ova. A sperm cell does not actually fertilize an egg but merely stimulates it to begin dividing. Thus, a gynogenetic female in effect ‘sexual parasitizes’ a foreign male who receives no genetic payoff for his sexual services. Hybridogenesis is another peculiar mode of reproduction with elements of both clonality and sexuality.

2% of the genome. Moreover, 98.5% of the occupancy sites of transcription factors previously mapped by ChIP-seq lie within accessible chromatin defined by DNase I hotspots, reaffirming their likely cell-specific regulatory role. Histone modifications associated with regulatory elements (e.g., methylation,

acetylation) were also assayed by ChIP-seq, and were found to be common in the genome (56.1%). Finally, one of the principal purposes of ENCODE was to determine what proportion of this noncoding genome is transcribed, and in which cell/tissue types. Vincristine concentration Djebali et al.15 demonstrate with ultra-deep RNA sequencing that about 75% of the genome is transcribed to RNA at some point in certain cell types. Therefore, the majority of RNA in a cell is never translated to protein, but may play important regulatory functions. Moreover, the expression of RNA transcripts from genes is not uniform—most genes express more than one isoform of a transcript, with an average of 10-12 expressed isoforms per gene per cell

line. This remarkable finding CH5424802 order has forced a re-think of our nomenclature of genomic organization, and in particular the gene as the fundamental building block of the genome. On the basis of the ENCODE data, it can be argued that the transcript is the basic unit of genomic organization, describing genes which are transcribed in different cellular environments under specific conditions. The ENCODE project has demonstrated that the vast majority of the human genome, although not coding for proteins, does contain important regions that bind proteins and RNA molecules which cooperate to regulate the function and expression of protein-coding genes. Additionally,

it seems that transcription is a lot more widespread than previously thought, MYO10 with large numbers of noncoding RNA molecules with potential regulatory roles. The immediate implications of these findings are that genome-wide approaches to determining disease risk and finding targets for therapy require reevaluation in this light. ENCODE demonstrates that noncoding regions must be considered when interpreting GWAS findings, and provides a strong basis for reinterpreting previous GWAS results. Furthermore, as mentioned above, the results of ENCODE suggest that exome-sequencing studies focusing on protein-coding sequences risk missing crucial parts of the genome and the ability to identify true causal variants. Although the prospect of characterization and validation of this new tier of genomic control is daunting, it does provide opportunity both in terms of technologies and therapeutics. Just as ENCODE disseminated technologies such as ChIP-seq and RNA-seq over the last decade, so technologies of gene editing such as zinc-finger and TAL effector-like nucleases are now scalable, and thus functional elements can be validated on a large scale.

Median age was 42.7 years (18-75), 64% of the patients were male LBH589 in vivo and 85% were genotype 1b. Median follow-up time was 5.4 years. The median number of previous KT was 1 (1-3) with no significant differences between treated and untreated patients. Antiviral therapy consisted in interferon monotherapy in 15 patients (25%), pegylated interferon monotherapy in 31 (51.7%), pegylated interferon and ribavirin in 14 (23.3%). Forty-three percent of the treated patients achieved SVR, 13% were non-responders, 13% relapsed and 31% discontinued therapy due to adverse

events (intolerance in 12%, hematological disorders in 8%, severe infections in 3%, and other in 8%). Anemia (hemoglobin ≤ 10 g/dL) was the most common adverse event and was observed in 27 patients (45%). Twenty-six out of the 100 patients at risk (24 patients underwent previous trans-plantectomy)

presented GIS during the follow-up. Five (12%) episodes occurred in patients receiving antiviral therapy and 21 (36%) in untreated patients (p=0.009). Median time since the beginning of HD and the appearance of GIS was significantly different Luminespib between treated and untreated patients (4.2 vs. 0.6 years, respectively; p<0.001). Sixteen (62%) GIS episodes occurred within the first year on HD. Among the 10 GIS episodes that appeared after the first year, 5 appeared during antiviral therapy but the remaining 5 episodes occurred in untreated patients.

CONCLUSIONS: Antiviral therapies based on interferon are able to cure almost half of the KT on HD, despite the high drop-out rate due to adverse events. However, IBT did not seem to increase the risk of GIS after the first year on HD. Disclosures: Xavier Forns – Consulting: Jansen, MSD, Abbvie; Grant/Research Support: Roche, MSD, Gilead The following people have nothing to disclose: Javier-Enrique Hernandez Blanco, Josep M. Barrera, Sabela Lens, Zoe Mariño, Francesc Maduell, Josep-Maria Campistol, Maria-Carlota Londono Purpose: We report the SVR12 final analysis of a Phase 3 study of telaprevir with peginterferon (P)/ribavirin (R) in HCV-geno-type 1, treatment-naïve and -experienced patients with HCV/ HIV co-infection (INSIGHT). Amine dehydrogenase Methods: Patients receiving stable, suppressive HIV antiretroviral therapy (ARV), containing atazanavir/ritonavir, efavirenz, darunavir/ritonavir, raltegravir, etravirine or rilpivirine, received telaprevir 750mg q8h (1125mg q8h if on efavirenz) plus P (180μg once-weekly) and R (800mg/day) for 12 weeks, followed by an additional 12 weeks (non-cirrhotic HCV treatment-naïve and relapse patients with extended rapid viral response [eRVR]) or 36 weeks (all others) of PR alone. Analysis was performed when all patients had completed the follow-up visit 12 weeks after last planned dose.

Galectin-9 is not the sole suppressive molecule expressed on HCC-associated KCs. We have previously demonstrated that KCs express high

levels of B7-H1 (PD-L1) in HCC, interact with PD-1+ T cells, Selleckchem Decitabine and mediate T-cell exhaustion.17 The pathological relevance of the B7-H1/PD-1 signaling pathway has been observed in many other types of human cancer, and the B7-H1/PD-1 signaling pathway is the justified target for treating human cancer.17 Interestingly, PD-1+ and Tim-3+ T cells are two distinct T-cell populations in HCC. Our studies support the notion that KCs play a negative role in anti-HCC immunity through two distinct molecular pathways, namely, Tim-3/galectin-9 and B7-H1/PD-1. As the expression of B7-H118, 19 and Tim-3 (this work) is negatively associated with HCC patient outcome, it is tempting to speculate BGB324 that simultaneous blockade of the B7-H1/PD-1 and Tim-3/galectin-9 signaling pathways may synergistically recover T-cell immunity and improve HBV-associated HCC patient outcome. In addition to its clinical relevance, our work raises an important issue that IFN-γ may play dual roles in tumor immunity.41

The immune stimulatory role of IFN-γ has been well appreciated. IFN-γ is elevated in patients with HCC. It is thought that uncontrolled immune activation, including large amounts of IFN-γ, may result in liver damage.42, 43 We have observed that tumor-infiltrating T-cell-derived IFN-γ potently stimulates galectin-3 expression on KCs in HCC. Interestingly, IFN-γ also induces B7-H1 expression on APCs.44, 45 Thus, galectin-3 and B7-H1 induced by T-cell-derived

IFN-γ may be able to fine-tune and temper local immune response, and to avoid over T-cell activation-mediated liver damage. However, this mechanism may be beneficial for tumors to evade tumor immunity. In further support of this possibility, in addition to galectin-3 and B7-H1, IFN-γ can induce the expression of noncognate MHC class I,46 indoleamine-2,3-dioxygenase (IDO),47 and arginase,48 which limit T-cell activation, proliferation, and effector function.49 Furthermore, a recent study has shown that UVB irradiation induces an IFN-γ-associated gene signature in murine melanocytes and results in increased tumorigenesis.50 These immune regulatory roles of IFN-γ are consistent with several studies in patients with cancer. Most clinical trials of IFN-γ treatment Tenofovir order did not demonstrate clinical efficacy in patients with melanoma.51-54 Multiple clinical trials have demonstrated that IFN-γ-treated patients fare worse than untreated patients.55, 56 Thus, although IFN-γ is a potent immune effector cytokine, it induces B7-H1, IDO, arginase, nonclassical MHC expression, and galectin-3, which may participate in a feedback mechanism to efficiently down-regulate antitumor immunity. In order to achieve clinical efficacy, novel regimens of tumor immune vaccination and therapy may have to maximize beneficial effects and minimize detrimental effects of IFN-γ.

However, how SOCS3 activates p53 remains unknown. SOCS1 has been reported to form a ternary complex with p53 and ataxia telangiectasia mutated kinase through the KIR domain of SOCS1, followed by activating p53, increasing p53 protein expression, and, subsequently, promoting oncogene-induced senescence.18 SOCS3 also contains a KIR, which suggests that the KIR in SOCS3 might be responsible for SOCS3 binding to and activating p53 and resulting in HSC senescence. Although many studies have suggested that senescent

cells eventually succumb to p53-mediated cell death,25 our findings C59 wnt order imply that IL-22 promotes HSC senescence and does not induce, but rather prevents, HSC apoptosis. We suspect that this may be because IL-22 activates STAT3, which not only promotes cell senescence through the induction of p53, but also acts as a key transcriptional factor for

cell survival through the induction of the antiapoptotic genes, Bcl-2 and B-cell lymphoma extra large. Interestingly, other groups have also reported the simultaneous observation of resistance to apoptosis and senescence in human fibroblasts.26 The induction of activated HSC senescence plays an important role in limiting fibrogenic response, which is likely mediated by enhancing the in vivo clearance of senescent HSCs, presumably by NK cells, the down-regulation of collagen and TIMP Kinase Inhibitor Library clinical trial expression, and the up-regulation of MMP expression.9, 10 Interestingly, in vitro treatment of HSCs with IL-22 not only induces HSC senescence, but also down-regulates α-SMA expression in these cells (Fig. 5). Because senescent HSCs are not associated with the down-regulation of α-SMA,10 the decreased α-SMA expression in response to IL-22 may not be directly the result of senescence, and a distinct mechanism

may be involved, which will require further studies to elucidate. In addition to the IL-22/STAT3 induction of HSC senescence, the well-documented hepatoprotective and mitogenic effects of IL-22/STAT3 in hepatocytes4, 5 may also contribute to the observed amelioration of liver Florfenicol fibrosis by IL-22. Indeed, the administration of Ad-IL-22 markedly inhibited liver fibrosis in STAT3Hep−/− mice, but the degree of inhibition was lower, when compared to that in WT mice, indicating that IL-22 inhibits liver fibrogenesis through hepatocyte STAT3-dependent and -independent mechanisms. Moreover, the administration of Ad-IL-22 increased liver regeneration (Supporting Fig. 4E), which is shown to ameliorate liver fibrosis and may contribute to the antifibrotic effect of IL-22.17 Although the hepatoprotective effects of IL-22 have been well documented,4, 5 IL-22TG mice displayed a similar extent of liver injury after chronic CCl4 treatment, when compared to WT mice (Supporting Fig. 3D). Thus, in our model of CCl4-induced liver injury, the IL-22-mediated inhibition of liver fibrosis is not completely mediated by its hepatoprotective effects.

The primary objective is to compare the annual bleeding rate of individualized tailored prophylaxis treatment with the historical annual bleeding rate from the on-demand study GENA-01 (58.1 haemorrhages per year). Secondary objectives are to compare the spontaneous

annual bleeding rate of individualized tailored prophylaxis with the historical annual bleeding rate from the on-demand study GENA-01 (38.5 haemorrhages per year); to compare the annual bleeding rate in patients on twice weekly or less prophylaxis with the historical annual bleed rate from the GENA-01 selleckchem study and to assess the pharmacokinetics of Human-cl rhFVIII. Individualized prophylaxis will be given for 6 months and the observation period will be 8 months on average for each patient. Further individualized

prospective measures have been integrated into the study protocol such as thrombin generation assay (TGA) evaluation to analyze the correlation among FVIII plasma levels, thrombin generation PLX3397 supplier potential and the frequency of breakthrough bleeding events. The trial will recruit 50 evaluable adult PTPs and will run until 2015. Twenty-seven centres in 10 countries (including the UK, Spain, Germany and Poland) have been recruited. In the initial pharmacokinetic evaluation phase, Human-cl rhFVIII will be given for 72 h at 60 ± 5 IU kg−1. In Phase I of the prophylactic treatment, Human-cl rhFVIII will be administered at 30–40 IU kg−1 every other day or three times a week for 1–3 months until the individual pharmacokinetic variables are analyzed. Once available, patients will switch to Phase II, the individually tailored

prophylaxis treatment that will be given for 6 months. Trough and peak FVIII:C and TGA will be measured at 2, 4 and 6 months. Both NuProtect and NuPreviq have the potential to show the favourable features of the first recombinant and unmodified FVIII from a human cell line. The available data show that this human rFVIII product is not associated with the development of inhibitors or serious adverse reactions in 135 PTPs treated PRKD3 so far. Its efficacy is clearly stated and prophylaxis is associated with very high efficacy rates in various haemophilia populations. Immunogenicity and pharmacokinetics have to be further investigated, and it will be extremely interesting to see if there is a link between the production of a recombinant human FVIII in a human cell line and immunogenicity. In this context, PTMs, which are differently introduced on the recombinant protein by human cell lines and murine cell lines, might play a major role. NGS will be useful in the future to better guide the use of factor concentrates and better identify the genes and proteins implicated in protection or predisposition with regard to inhibitor formation.

Trees were visualized with MEGA5. The annotated C. reinhardtii plastid genome (GenBank# FJ423446) was used to identify homologous positions and reading frame in Esoptrodinium psbA through multiple sequence alignment as above. Esoptrodinium

was observed to ingest eight of 14 different living microorganisms tested as potential prey, and feeding responses were similar for all Esoptrodinium isolates (Table 1). Overall, Esoptrodinium ingested microalgae that were roughly selleck chemicals llc similar or slightly smaller in size to itself, representing diverse taxa (diatom, chlorophyte, chrysophyte, cyptophyte, dinoflagellate, and euglenoid microalgae). Microorganisms that were significantly smaller in size, nonmotile, and/or noneukaryotic (i.e., two yeast species and the cyanobacterium Gloeocapsa sp.) were not ingested. Likewise, tested protists that were markedly larger Smoothened Agonist than Esoptrodinium were not ingested (i.e., the dinoflagellate Gymnodinium fuscum and two ciliate species). Although living yeasts and ciliates were not ingested, Esoptrodinium cells were observed to feed upon freeze-injured yeast cells, and attach to and/or partially ingest freeze-injured ciliates (Table 1). Of all examined potential prey, only the cryptophyte microalga C. ovata elicited a feeding/growth response by Esoptrodinium so robust as to visibly eliminate all prey cells from the culture

medium within 2–3 d. In other treatments in which prey were ingested, feeding by Esoptrodinium appeared less robust and prey cells were not visibly eliminated by the dinoflagellates over ≥7 d of observation. Unlike all other treatments (including prey-free controls), Esoptrodinium cells incubated with the chrysophyte Ochromonas danica apparently died during the experimental period; no dinoflagellate cells were observed in this treatment

after 5 d. The observed mechanism of phagotrophy was the same for all Esoptrodinium isolates regardless of prey type, and was most easily observed in dense, growing cultures with C. ovata as prey. Motile Esoptrodinium cells phagocytized whole prey cells (phagotrophy sensu stricto) through a food uptake structure Ribonucleotide reductase (peduncle, Schnepf and Elbrächter (1992)) located on the ventral episome (Fig. 1). When viewed by LM, the most prominent characteristic of the incipient peduncle was a thickened, rod or band-shaped structure that formed its outer edge (Fig. 1A), herein referred to as the ABP. The ABP was continuous with the ventral-apical margin of the cell episome and opened like a hatch door to expose the peduncle aperture through which prey cells were ingested. Peduncle length did not increase significantly during feeding, but rather the diameter of the distal end of the peduncle increased as the ABP swung out from the cell (Fig. 1, A and B).

Trees were visualized with MEGA5. The annotated C. reinhardtii plastid genome (GenBank# FJ423446) was used to identify homologous positions and reading frame in Esoptrodinium psbA through multiple sequence alignment as above. Esoptrodinium

was observed to ingest eight of 14 different living microorganisms tested as potential prey, and feeding responses were similar for all Esoptrodinium isolates (Table 1). Overall, Esoptrodinium ingested microalgae that were roughly I-BET-762 purchase similar or slightly smaller in size to itself, representing diverse taxa (diatom, chlorophyte, chrysophyte, cyptophyte, dinoflagellate, and euglenoid microalgae). Microorganisms that were significantly smaller in size, nonmotile, and/or noneukaryotic (i.e., two yeast species and the cyanobacterium Gloeocapsa sp.) were not ingested. Likewise, tested protists that were markedly larger see more than Esoptrodinium were not ingested (i.e., the dinoflagellate Gymnodinium fuscum and two ciliate species). Although living yeasts and ciliates were not ingested, Esoptrodinium cells were observed to feed upon freeze-injured yeast cells, and attach to and/or partially ingest freeze-injured ciliates (Table 1). Of all examined potential prey, only the cryptophyte microalga C. ovata elicited a feeding/growth response by Esoptrodinium so robust as to visibly eliminate all prey cells from the culture

medium within 2–3 d. In other treatments in which prey were ingested, feeding by Esoptrodinium appeared less robust and prey cells were not visibly eliminated by the dinoflagellates over ≥7 d of observation. Unlike all other treatments (including prey-free controls), Esoptrodinium cells incubated with the chrysophyte Ochromonas danica apparently died during the experimental period; no dinoflagellate cells were observed in this treatment

after 5 d. The observed mechanism of phagotrophy was the same for all Esoptrodinium isolates regardless of prey type, and was most easily observed in dense, growing cultures with C. ovata as prey. Motile Esoptrodinium cells phagocytized whole prey cells (phagotrophy sensu stricto) through a food uptake structure CYTH4 (peduncle, Schnepf and Elbrächter (1992)) located on the ventral episome (Fig. 1). When viewed by LM, the most prominent characteristic of the incipient peduncle was a thickened, rod or band-shaped structure that formed its outer edge (Fig. 1A), herein referred to as the ABP. The ABP was continuous with the ventral-apical margin of the cell episome and opened like a hatch door to expose the peduncle aperture through which prey cells were ingested. Peduncle length did not increase significantly during feeding, but rather the diameter of the distal end of the peduncle increased as the ABP swung out from the cell (Fig. 1, A and B).

41 reported that PPAR-γ activation

induces the expression of p16INK4α and G1 arrest in human bladder cancer cells. Moreover, Lu et al.42 revealed that a PPAR-γ agonist accelerates TRAIL-induced apoptosis and cell cycle arrest in cancer cells. Additionally, STAT inhibitor a recent study reported that PPAR-γ promotes cellular senescence by inducing p16INK4α expression in human diploid fibroblasts.43 These previous studies indicate that PPAR-γ might play a pivotal role in cellular senescence. Returning to our study, the SMP30 KO mice revealed elevated PPAR-γ levels relative to the WT mice, although the SMP30 KO mice are well known to have a shorter life span. Related to this aging factor, our findings show that the inhibition of p-Smad2/3 nuclear translocation by overexpressed PPAR-γ suggests the possibility that the chronic inflammatory cells were severely suppressed to induce LY2109761 age-related chronic inflammation. Recently, Krizhanovsky et al.44 reported that senescent activated HSCs down-regulate extracellular matrix production, which suggests that the senescence of activated HSCs limits liver fibrosis. Additionally, several studies demonstrated that PPAR-γ is a negative regulator of various inflammatory responses.45, 46 Therefore, based on the previous studies, it is believed that the decreases in cellular responses, including inflammatory reactions, might be caused by cellular senescence of the SMP30

KO mice. To summarize, we can conclude that vitamin C deficiency ameliorated liver fibrosis by way of up-regulated PPAR-γ expression (Fig. 8). We confirmed 4��8C that WT HSCs did not express SMP30, and vitamin C supplement reinstated CCl4-induced liver fibrosis in the SMP30 KO mice; therefore, we speculated that vitamin C deficiency caused by a lack of SMP30 might be more closely connected with the inhibited liver fibrosis than SMP30 itself. Finally, we demonstrated that up-regulated PPAR-γ expression induced by vitamin C deficiency is the pivotal factor in the mechanisms

for attenuated liver fibrosis of the SMP30 KO mice. Although the present study describes that vitamin C deficiency ameliorates CCl4-induced liver fibrosis in the SMP30 KO mice, the WT mice did not show significant differences in the fibrosis grade and α-SMA expression level between the CCl4-treated WT group and the CCl4 + vitamin C supplement WT group. Thus, it appears that vitamin C does not promote liver fibrosis in the WT mice, although vitamin C treatment increased CCl4-induced liver fibrosis grade in the SMP30 KO mice. The above findings have not been published so far, and would be novel evidence that liver fibrosis is ameliorated in the vitamin C-deficient aging animal model. Additional Supporting Information may be found in the online version of this article. “
“Heart failure (HF) is, after cirrhosis, the second-most common cause of ascites. Serum B-type natriuretic peptide (BNP) plays an important role in the diagnosis of HF.

6, [−22.0, −1.0], P = .017 and −4.8, [−11.0, −1.0], P = .043, respectively). Self-efficacy and mindfulness improved in MBSR vs control (13.2 [1.0, 30.0], P = .035 and 13.1 Ibrutinib datasheet [3.0, 26.0], P = .035 respectively). MBSR is safe and feasible for adults with migraines. Although the small sample size of this pilot trial did not provide power to detect statistically significant changes in migraine frequency or severity, secondary outcomes demonstrated this intervention had a beneficial effect on headache duration, disability, self-efficacy, and mindfulness. Future studies with larger sample sizes are warranted to further

evaluate this intervention for adults with migraines. This study was prospectively registered (ClinicalTrials.gov identifier NCT01545466). “
“Background.— Migraine and symptoms that may suggest a vestibular disorder (referred to herein broadly as vestibular symptoms—VS) often co-exist. In part due to a lack of standardized diagnostic criteria, this relationship remains unknown to many physicians. Objective.— To determine common clinical features that may be associated with “vestibular migraine” (VM). Methods.— We retrospectively reviewed charts

of patients diagnosed with VM at a headache center. In this group we recorded certain demographic and clinical features related to their disorder, including the most common triggers of the VS and the specific characteristics of the symptoms that suggested VM. Results.— Our sample consisted of 147 patients (68% women, mean age = 45 years, 39% with aura). Migraine onset preceded the onset of VS by a mean of 8 years. A total of 62 patients (42%) JNK phosphorylation had gradual onset of VS, while in 48 (33%) symptoms began suddenly. The most commonly

reported symptoms that led to the diagnosis of VM were: unsteadiness (134; 91%), balance disturbance (120; 82%), “light-headedness” (113; 77%), and vertigo (84; 57%). VS and headache occurred concomitantly Nintedanib (BIBF 1120) in 48% of patients. A total of 67 (47%) patients had VS that were chronic from onset, 29 (21%) had episodic symptoms, and in 46 (32%) the VS had evolved from episodic to chronic (with an average duration of 7.04 years required for this evolution to occur). Conclusions.— Vestibular migraine is a heterogeneous condition with varying symptomatology. As with migraine itself, symptomatic expression varies along a spectrum that extends from episodic to chronic. As the histories of many of the patients we evaluated would not meet current International Classification of Headache Disorders criteria, we suggest that new criteria which account for the heterogeneity and natural history of the disorder may be required to adequately diagnose and treat those who suffer from VM. “
“We analyzed characteristics of hypnic headache (HH), migraine and the relationship between both headaches in 23 patients. HH is an uncommon primary headache characterized by exclusively sleep-related attacks.