Migraine and tension type headache (TTH) are two most common types of primary headaches. Though the International Classification of Headache Disorders-2 (ICHD-2) describes the diagnostic criteria, even then in clinical practice, patients may not respect these boundaries resulting in the difficulty in diagnosis of these pains.
Materials and Methods:
This cross-sectional study involved 50 subjects in each of the two groups – migraine and TTH – after screening for the inclusion and exclusion criteria. Diagnosis was made according to the ICHD-2 criteria. Their clinical history was taken in detail and noted in a semi-structured performa. They were examined for the presence of a number of factors like pericranial tenderness and muscle parafunction. Statistical analysis was done with the help of SPSS v 11.0. To compare the non-parametric issues, chi-square test was run and continuous variables were analyzed using independent sample t test.
In general, migraineurs had progressive illness (χ2=9.45; P=0.002) with increasing severity (χ2=21.86; P<0.001), frequency (χ2=8.5; P=0.04) and duration of each headache episode (χ2=4.45; P=0.03) as compared to TTH subjects. Along with the headache, they more commonly suffered orthostatic pre-syncope (χ2=19.94; P<0.001), palpitations (42%vs.18% among TTH patients; χ2=6.87; P=0.009), nausea and vomiting (68% vs. 6% in TTH; χ2=41.22; P<0.001, and 38% vs. none in TTH; χ2=23.45, P<0.001, respectively), phonophobia (χ2=44.98; P<0.001), photophobia (χ2=46.53; P<0.001), and osmophobia (χ2=15.94; P<0.001). Their pain tended to be aggravated by head bending (χ2=50.17; P<0.001) and exercise (χ2=11.41; P<0.001). Analgesics were more likely to relieve pain in migraineurs (χ2=21.16; P<0.001). In addition, post-headache lethargy was more frequent among the migraineurs (χ2=22.01; P<0.001). On the other hand, stressful situations used to trigger TTH (χ2=9.33; P=0.002) and muscle parafunction was more common in TTH patients (46% vs. 20%; χ2=7.64; P=0.006). All the cranial autonomic symptoms were more common in migraineurs as compared to TTH subjects (conjunctival injection: χ2=10.74, P=0.001; lacrimation: χ2=17.82, P<0.001; periorbital swelling: χ2=23.45, P<0.001; and nasal symptoms: χ2=6.38, P=0.01).
A number of symptoms that are presently not included in the ICHD-2 classification may help in differe-ntiating the migraine from the TTH.
Migraine; symptoms; tension type headache
MPromDb (Mammalian Promoter Database) is a curated database that strives to annotate gene promoters identified from ChIP-seq results with the goal of providing an integrated resource for mammalian transcriptional regulation and epigenetics. We analyzed 507 million uniquely aligned RNAP-II ChIP-seq reads from 26 different data sets that include six human cell-types and 10 distinct mouse cell/tissues. The updated MPromDb version consists of computationally predicted (novel) and known active RNAP-II promoters (42 893 human and 48 366 mouse promoters) from various data sets freely available at NCBI GEO database. We found that 36% and 40% of protein-coding genes have alternative promoters in human and mouse genomes and ∼40% of promoters are tissue/cell specific. The identified RNAP-II promoters were annotated using various known and novel gene models. Additionally, for novel promoters we looked into other evidences—GenBank mRNAs, spliced ESTs, CAGE promoter tags and mRNA-seq reads. Users can search the database based on gene id/symbol, or by specific tissue/cell type and filter results based on any combination of tissue/cell specificity, Known/Novel, CpG/NonCpG, and protein-coding/non-coding gene promoters. We have also integrated GBrowse genome browser with MPromDb for visualization of ChIP-seq profiles and to display the annotations. The current release of MPromDb can be accessed at http://bioinformatics.wistar.upenn.edu/MPromDb/.
We present a case of an iatrogenic left ulnar nerve injury caused during the basilic vein cut down in a 25-year-old woman presenting with a ruptured ectopic pregnancy and requiring an emergency laparotomy. Two months after her discharge from the hospital, the patient presented to the hand surgery clinic with a weak grip strength and paraesthesias in the left hand, diagnosed to be resulting from a deficient ulnar nerve function. Surgical exploration of the nerve showed a complete section of the nerve. End to end repair and anterior transposition of the nerve was done. At 10 months follow up, the patient showed recovery in the flexor digitorum profundus and flexor carpi ulnaris, thus partially improving the grip strength. The patient was still under follow-up at the time this report was prepared.
Trimethylated lysine 27 of histone H3 (H3K27me3) is an epigenetic mark for gene silencing and can be demethylated by the JmjC domain of UTX. Excessive H3K27me3 levels can cause tumorigenesis, but little is known about the mechanisms leading to those cancers. Mutants of the Drosophila H3K27me3 demethylase dUTX display some characteristics of Trithorax group mutants and have increased H3K27me3 levels in vivo. Surprisingly, dUTX mutations also affect H3K4me1 levels in a JmjC-independent manner. We show that a disruption of the JmjC domain of dUTX results in a growth advantage for mutant cells over adjacent wild-type tissue due to increased proliferation. The growth advantage of dUTX mutant tissue is caused, at least in part, by increased Notch activity, demonstrating that dUTX is a Notch antagonist. Furthermore, the inactivation of Retinoblastoma (Rbf in Drosophila) contributes to the growth advantage of dUTX mutant tissue. The excessive activation of Notch in dUTX mutant cells leads to tumor-like growth in an Rbf-dependent manner. In summary, these data suggest that dUTX is a suppressor of Notch- and Rbf-dependent tumors in Drosophila melanogaster and may provide a model for UTX-dependent tumorigenesis in humans.
Alternative promoters that are differentially used in various cellular contexts and tissue types add to the transcriptional complexity in mammalian genome. Identification of alternative promoters and the annotation of their activity in different tissues is one of the major challenges in understanding the transcriptional regulation of the mammalian genes and their isoforms. To determine the use of alternative promoters in different tissues, we performed ChIP-seq experiments using antibody against RNA Pol-II, in five adult mouse tissues (brain, liver, lung, spleen and kidney). Our analysis identified 38 639 Pol-II promoters, including 12 270 novel promoters, for both protein coding and non-coding mouse genes. Of these, 6384 promoters are tissue specific which are CpG poor and we find that only 34% of the novel promoters are located in CpG-rich regions, suggesting that novel promoters are mostly tissue specific. By identifying the Pol-II bound promoter(s) of each annotated gene in a given tissue, we found that 37% of the protein coding genes use alternative promoters in the five mouse tissues. The promoter annotations and ChIP-seq data presented here will aid ongoing efforts of characterizing gene regulatory regions in mammalian genomes.
To determine the predictors of distress in older patients with cancer.
Patients and Methods
Patients age ≥ 65 years with a solid tumor or lymphoma completed a questionnaire that addressed these geriatric assessment domains: functional status, comorbidity, psychological state, nutritional status, and social support. Patients self-rated their level of distress on a scale of zero to 10 using a validated screening tool called the Distress Thermometer. The relationship between distress and geriatric assessment scores was examined.
The geriatric assessment questionnaire was completed by 245 patients (mean age, 76 years; standard deviation [SD], 7 years; range, 65 to 95 years) with cancer (36% stage IV; 71% female). Of these, 87% also completed the Distress Thermometer, with 41% (n = 87) reporting a distress score of ≥ 4 on a scale of zero to 10 (mean score, 3; SD, 3; range, zero to 10). Bivariate analyses demonstrated an association between higher distress (≥ 4) and poorer physical function, increased comorbid medical conditions, poor eyesight, inability to complete the questionnaire alone, and requiring more time to complete the questionnaire. In a multivariate regression model based on the significant bivariate findings, poorer physical function (increased need for assistance with instrumental activities of daily living [P = .015] and lower physical function score on the Medical Outcomes Survey [P = .018]) correlated significantly with a higher distress score.
Significant distress was identified in 41% of older patients with cancer. Poorer physical function was the best predictor of distress. Further studies are needed to determine whether interventions that improve or assist with physical functioning can help to decrease distress in older adults with cancer.
Chromatin in the nucleus of all eukaryotes is organized into a system of loops and domains. These loops remain fastened at their bases to the fundamental framework of the nucleus, the matrix or the scaffold. The DNA sequences which anchor the bases of the chromatin loops to the matrix are known as Scaffold/Matrix Attachment Regions or S/MARs. Though S/MARs have been studied in yeast and higher eukaryotes and they have been found to be associated with gene organization and regulation of gene expression, they have not been reported in protists like Giardia. Several tools have been discovered and formulated to predict S/MARs from a genome of a higher eukaryote which take into account a number of features. However, the lack of a definitive consensus sequence in S/MARs and the randomness of the protozoan genome in general, make it a challenge to predict and identify such sequences from protists.
Here, we have analysed the Giardia genome for the probable S/MARs predicted by the available computational tools; and then shown these sequences to be physically associated with the nuclear matrix. Our study also reflects that while no single computational tool is competent to predict such complex elements from protist genomes, a combination of tools followed by experimental verification is the only way to confirm the presence of these elements from these organisms.
This is the first report of S/MAR elements from the protozoan parasite Giardia lamblia. This initial work is expected to lay a framework for future studies relating to genome organization as well as gene regulatory elements in this parasite.
Four-corner fusion of the wrist is an option for management of non-union scaphoid with painful arthritis of the wrist. Various surgical techniques have been devised for four-corner fusion, with inconsistent results. We present our experience of four-corner fusion achieved using a standard H-plate, designed originally for anterior cervical plating.
Materials and Methods:
The study is a retrospective analysis of six cases of painful wrist arthritis resulting from nonunion of scaphoid treated by four-corner fusion, between 1996 and 2004. The average duration of follow-up was 5.8 years. Each patient was evaluated clinically according to the rating scales described by Bach.
The mean grip-strength calculated as a percentage of the uninvolved side was 47% pre-operatively, and 74% post- operatively at the final follow-up. The difference between the preoperative and postoperative ‘pain ratings’ and ‘activity ratings’ was found to be statistically significant (P<0.001). Mean time to fusion was 16.1 weeks. Dorsal impingement was the most common associated problem.
H-plate, used for four-corner fusion, provides rigid fixation, ensures fusion, and is a good alternative to the available options.
Four corner fusion; Cervical H-plate; nonunion scaphoid
The objective of this study was to assess the outcome of operations on acetabular fractures from a developing country in the presence of locally available facilities. Sixty-three acetabular fractures were assessed at an average follow up of 52.94 months after operation. Twenty-six patients operated upon in the first three years and 37 operated thereafter were separately studied to discover the effect of the learning curve. Regarding the fractures, 47 of 63 (74.6%) had excellent/good results (Harris Hip Score>80). The complications included broken drill bit in eight patients (12.69%), deep infection and heterotopic ossification in five patients (7.93%), avascular necrosis and sciatic nerve palsy in two patients (3.17%) and implant failure in one patient (1.58%). The results collected during the learning curve were inferior in the complex fractures (p value<0.001). Complications were common in patients opting for local implants and in those operated after over 2 weeks delay.
Use of alternative gene promoters that drive widespread cell-type, tissue-type or developmental gene regulation in mammalian genomes is a common phenomenon. Chromatin immunoprecipitation methods coupled with DNA microarray (ChIP-chip) or massive parallel sequencing (ChIP-seq) are enabling genome-wide identification of active promoters in different cellular conditions using antibodies against Pol-II. However, these methods produce enrichment not only near the gene promoters but also inside the genes and other genomic regions due to the non-specificity of the antibodies used in ChIP. Further, the use of these methods is limited by their high cost and strong dependence on cellular type and context.
We trained and tested different state-of-art ensemble and meta classification methods for identification of Pol-II enriched promoter and Pol-II enriched non-promoter sequences, each of length 500 bp. The classification models were trained and tested on a bench-mark dataset, using a set of 39 different feature variables that are based on chromatin modification signatures and various DNA sequence features. The best performing model was applied on seven published ChIP-seq Pol-II datasets to provide genome wide annotation of mouse gene promoters.
We present a novel algorithm based on supervised learning methods to discriminate promoter associated Pol-II enrichment from enrichment elsewhere in the genome in ChIP-chip/seq profiles. We accumulated a dataset of 11,773 promoter and 46,167 non-promoter sequences, each of length 500 bp, generated from RNA Pol-II ChIP-seq data of five tissues (Brain, Kidney, Liver, Lung and Spleen). We evaluated the classification models in building the best predictor and found that Bagging and Random Forest based approaches give the best accuracy. We implemented the algorithm on seven different published ChIP-seq datasets to provide a comprehensive set of promoter annotations for both protein-coding and non-coding genes in the mouse genome. The resulting annotations contain 13,413 (4,747) protein-coding (non-coding) genes with single promoters and 9,929 (1,858) protein-coding (non-coding) genes with two or more alternative promoters, and a significant number of unassigned novel promoters.
Our new algorithm can successfully predict the promoters from the genome wide profile of Pol-II bound regions. In addition, our algorithm performs significantly better than existing promoter prediction methods and can be applied for genome-wide predictions of Pol-II promoters.
We describe a case of arthroscopic retrieval of a bullet from the hip joint of an 18-year-old boy, who sustained the injury four months back, accidentally, while bird hunting with a country made shotgun. The surgery was performed with the standard ordinary instrumentation of knee arthroscopy. The patient became pain-free the same evening and started partial weight bearing on the next day of surgery. At 13 months follow-up, the patient had returned to normal activity without any functional limitations.
Arthroscopy; bullet injury; hip
A primary headache, particularly migraine, is associated with oxidative stress during the attack. However, data regarding the interictal state in migraineurs and in those with tension-type headache (TTH) is limited.
(1) To assess the oxidative stress in migraineurs and TTH subjects in between the episodes and (2) to see if there is a difference in the degree of oxidative stress in the different subtypes of migraine and TTH.
Materials and Methods:
Fifty migraineurs, 50 patients with TTH, and 50 control subjects were included in this study after screening for the exclusion criteria. Diagnosis of headache was made according to the International Classification of Headache Disorders (ICHD)-2 criteria. A venous blood sample was collected from the antecubital vein at least 3 days after the last attack of headache. The sample was centrifuged immediately and the plasma was stored at –70°C. The ferric reducing activity of plasma (FRAP) and the malondialdehyde (MDA) levels were assessed using colorimetric methods. Statistical analysis was done with the help of SPSS for Windows, v 11.0. One way ANOVA with post hoc Tukey test, independent sample t test, univariate regression, and multivariate regression analysis were done as indicated.
Migraineurs had higher values of MDA and FRAP than the subjects in the other two groups (P<0.001). No difference was observed between the TTH group and the control group. FRAP levels were significantly higher in subjects who had mixed migraine (migraine with aura and without aura) as compared to those with only migraine without aura (mean difference 196.1; 95% CI = 27.3 to 364.9; P = 0.01). Similarly, oxidative stress was significantly higher in patients with episodic TTH as compared to those with chronic TTH (FRAP t = 3.16; P = 0.003 and MDA t = 2.75; P = 0.008).
This study suggests that oxidative stress continues even between headache episodes in migraineurs but not in those with TTH. This could probably be consequent to the different pathophysiological mechanisms of TTH and migraine.
Migraine; tension type headache; oxidative stress; ferric reducing activity of plasma; malondialdehyde
Calcitonin gene-related peptide (CGRP) is known to increase during acute attack of migraine and tension type headache (TTH). However, its concentration during inter-ictal period is not known. This may help us to understand the pathophysiology of these headaches. The objectives of this study are to find out the concentration of CGRP in plasma during inter-ictal period among migraineurs and TTH and to compare it with control group through cross-sectional study from headache clinic of a tertiary centre. Study sample comprised of three groups: migraineurs, TTH subjects as well as a healthy control group. Fifty subjects in each group were included after screening for the respective inclusion criteria and exclusion criteria. None of the subjects was blood relatives of other subject. Their venous blood was drawn and plasma was separated to be kept at −70°C. CGRP was analysed with commercially available ELISA kit. Data were analysed with the help of SPSS V 11.0 for Windows. Chi-square, independent sample t test and one-way ANOVA with post hoc Tukey and univariate regression were performed. Plasma CGRP concentration was not different among three diagnostic groups (F = 0.78; P = 0.49). Similarly, plasma CGRP concentration was not different among episodic TTH and chronic TTH groups (t = 0.32; P = 0.97) and comparison of episodic and chronic migraine groups also revealed similar results in this study (1.14 vs. 0.94 ng/ml; P = 0.23). The presence of aura did not affect the inter-ictal CGRP levels among migraineurs (F = 0.16; P = 0.85). In conclusion, this study suggests that migraine and TTH could be episodic disorders and subjects have comparable CGRP levels during inter-ictal period.
Migraine; Tension type headache; CGRP; Inter-ictal period
The present study was designed to assess whether subjective sleep patterns differ between: (i) depressed patients and controls, and (ii) between subjects with different severity of depression. Based on available literature, it was hypothesized that sleep patterns must be different between the above mentioned groups.
Materials and Methods:
This study included 60 subjects with major depressive disorder and 40 subjects in the control group. Subjects with sleep disturbance secondary to any other factor, e.g., medical illness, environmental factors, other psychiatric illness etc, were not included in the study. Depression severity was assessed in the subjects with depression with the help of Beck Depression Inventory II. Subjective sleep complaints were noted in the presence of a reliable informant, preferably bed partner. All the information was recorded in a semistructured performa. Statistical analysis was done with the help of SPSS v 11.0. The Chi square and Fisher exact tests were used for categorical variables; independent t-test and one way ANOVA were applied for numerical variables. Ordinal variables were analyzed using Mann Whitney U and Kruskall-Wallis tests.
Depression and control groups were similar in age (P = 0.32) and gender (P = 0.14) distribution. Subjects in the depression group had lesser total sleep time (P = 0.001), longer sleep latency (P = 0.001), frequent awakenings (P = 0.04), greater wake-after-sleep onset and offset times (both P = 0.001), lesser sleep efficiency, and tended to wake up early (Mann Whitney U = 913.5; P = 0.05). Subjects with severe depression were different from the mild and moderate groups with regards to total sleep time (P = 0.002), night-time sleep (P = 0.007), and sleep efficiency (P = 0.001) even when the three groups were comparable in age.
Depression is associated with sleep disturbances, not only qualitatively, but also quantitatively. Sleep disturbance arises only after a critical level of depression is reached, and depression of varying severity may selectively affect different sleep parameters.
Depression; sleep; severity of depression
Nitric oxide plays an important role in the pathogenesis of migraine as well as tension-type headache. Studies suggest that the expression of molecules involved in the pathogenesis of headache, i.e., nitric oxide and interleukin, is influenced by apolipoprotein E (APOE) and is gene specific. Hence, we hypothesized that APOE polymorphism may be associated with migraine as well as tension-type headache.The study sample comprised of three groups: migraineurs, tension-type headache subjects as well as a healthy control group. A total of 50 subjects in each group were included after screening for the inclusion and exclusion criteria. None of the subjects was a blood relative of any other subject included in the present study. Their venous blood was drawn and stored at −20°C. Genomic DNA extraction was performed with a commercial kit and simple sequence-specific primer PCR was performed to assess the APOE polymorphism. Data were analyzed with the help of SPSS V11.0 for Windows. χ2 test and logistic regression analysis were run. The results of the study showed that APOE ε2 gene increases the risk of migraine as compared to the control group and the tension-type headache group (OR = 4.85; 95% CI = 1.92–12.72; P < 0.001 and OR = 2.31; 95% CI = 1.08–4.94; P = 0.01, respectively). Interestingly, APOE ε4 gene was protective against migraine as well as tension-type headache. This study shows that APOE ε2 gene increases the risk of migraine, while APOE ε4 gene is protective against migraine and tension-type headache. Further research is required to confirm the findings of the present study in a larger sample and to elucidate the role of APOE polymorphism in headache.
Migraine; Tension-type headache; APOE polymorphism
Headache patients commonly report sleep disruption and sleep disorders. Available literature suggests that the sleep pattern of headache sufferers is different from the control group. Patients in these studies were recruited from headache clinics; they did not include tension type headache.
The aim of this study is to find out whether primary headaches affect sleep patterns.
Settings and Design:
Community based cross sectional study
Materials and Methods:
This study was conducted in three high schools. Children in the 12-19 age group were allowed to participate. They were given a questionnaire in the presence of at least one of the authors, who assisted them in filling it. They were asked to provide responses based on most severe recurrent headache that they had experienced rather than the more frequent ones. The questionnaire included questions regarding demographic data and the characteristics of headache according to International Classification of Headache Disorders-2 criteria. Part B of the questionnaire contained questions regarding sleep habits. The children were asked to provide data regarding sleep habits on a normal school day. Diagnosis was based upon the information contained in the questionnaire. A telephonic interview was also done, where the information provided was found inadequate.
Statistical Analysis Used:
Analysis was done with the help of SPSS v. 11.0., descriptive analysis, Chi square, and one way ANOVA with post hoc analysis. Kruskall-Wallis tests were run.
A total of 1862 subjects were included in the study. Migraineurs and tension type headache sufferers comprised 35.7% and 13.4% of the group respectively. Migraineurs had the highest prevalence of nocturnal awakenings (P < 0.001), abnormal movements (P=0.001) and breathing problems during sleep (P < 0.001). Approximately half the migraineurs felt sleepy during the day (P< 0.001) and spent around 1.17 hours in sleep during the day (P = 0.007). Similarly, values for frequency of nocturnal awakenings per week (P < 0.001), wake time after sleep onset and offset (P < 0.001 and 0.002 respectively) were the maximum in migraineurs. Only 32.8% migraineurs reported refreshing sleep (P< 0.001). Post hoc analysis revealed that migraineurs were different from the other two groups on most of the parameters.
Sleep disruption is more common in migraineurs than those in the tension type headache sufferers and the control group.
Migraine; sleep; sleep-disruption; tension type headache
This paper presents a novel feature vector based on physicochemical property of amino acids for prediction protein structural classes. The proposed method is divided into three different stages. First, a discrete time series representation to protein sequences using physicochemical scale is provided. Later on, a wavelet-based time-series technique is proposed for extracting features from mapped amino acid sequence and a fixed length feature vector for classification is constructed. The proposed feature space summarizes the variance information of ten different biological properties of amino acids. Finally, an optimized support vector machine model is constructed for prediction of each protein structural class. The proposed approach is evaluated using leave-one-out cross-validation tests on two standard datasets. Comparison of our result with existing approaches shows that overall accuracy achieved by our approach is better than exiting methods.
The identification and analysis of repetitive patterns are active areas of biological and computational research. Tandem repeats in telomeres play a role in cancer and hypervariable trinucleotide tandem repeats are linked to over a dozen major neurodegenerative genetic disorders. In this paper, we present an algorithm to identify the exact and inexact repeat patterns in DNA sequences based on orthogonal exactly periodic subspace decomposition technique. Using the new measure our algorithm resolves the problems like whether the repeat pattern is of period or its multiple (i.e., 2, 3, etc.), and several other problems that were present in previous signal-processing-based algorithms. We present an efficient algorithm of , where is the length of DNA sequence and is the window length, for identifying repeats. The algorithm operates in two stages. In the first stage, each nucleotide is analyzed separately for periodicity, and in the second stage, the periodic information of each nucleotide is combined together to identify the tandem repeats. Datasets having exact and inexact repeats were taken up for the experimental purpose. The experimental result shows the effectiveness of the approach.