Tension-type headache in the Emergency Department Diagnosis and misdiagnosis: The TEDDi study.

Headache is a common reason to visit the emergency department (ED). Tension-type headache (TTH) is the commonest headache. The diagnosis of TTH implies a mild condition, with no need for special tests. We evaluated the use of the International Classification of Headache Disorders (ICHD) criteria for TTH in the ED. We performed a cross-sectional study including all ED patients with a definite TTH diagnosis in their discharge report for 2.5 years. We evaluated whether the ICHD criteria for TTH were referenced and met. We analysed discrepancies concerning anamnesis or prior history and reclassified patients. A total of 211 out of 2132 patients fulfilled the criteria (9.9%). Only five patients fulfilled TTH criteria. Criteria A-D were referenced in 60-84% of patients and met in 16-74% of these patients. Anamnesis was discrepant in 87.5% as was prior history in 20.8%. After re-reclassification, 21 patients fulfilled the criteria for TTH (five) or probable TTH (16). In 106 patients, another headache was diagnosed, with migraine in 40 (18.9%), secondary headache in 64 (30.3%), and a life-threatening disorder in 13 (6.1%). In our sample, TTH was overdiagnosed. Only a minority of patients fulfilled the ICHD criteria. Inconsistencies in prior medical history or anamnesis were frequent.

Trends in Academic Dentistry and Oral Health Research Funding by Gender.

INTRODUCTION: Dental and oral health researchers compose a small share of the research workforce, and within this group female researchers form a much smaller share than male researchers. Additionally, a majority of full-time faculty appointments at dental schools are held by men, with women making up only 39% of full-time appointments. These factors suggest that there could be disparities between men and women in obtaining research funding. OBJECTIVE: The focus of our study was to determine whether there are gender differences in award funding obtained from the National Institute of Dental and Craniofacial Research or the National Institutes of Health (NIH). METHODS: NIH administrative data were analyzed by focusing on Research Project Grants (RPGs), the primary and most commonly used mechanism to support investigator-initiated research projects. Analyses involved 1 or 2 of the following variables: number of unique applicants or awardees, fiscal years 2007 to 2016, average age of unique applicants, awardee's degrees, awardee's age at first R01, and award rates. RESULTS: About two-thirds of RPG applicants and awardees were men. Although there were significantly more male applicants and awardees, there was no significant difference in award rate by gender, and there was no significant award rate variation through time or by degrees. The average ages of RPG applicants were similar for genders for all degrees, except that male dentists and PhD-dentists applying to the National Institute of Dental and Craniofacial Research were older and male MDs and PhD-dentists from dental schools applying to the NIH were older. CONCLUSIONS: This study demonstrated that men in the dental/oral health workforce submit more applications and receive more NIH awards than do women; however, there was no difference in award rates between women and men and no difference in ages by gender at which the first R01 awards are received. KNOWLEDGE TRANSFER STATEMENT: Analyses of the implications of this study by the academic dentistry and oral health community could lead to establishing opportunities to expand the representation of women in dental and oral health research. Increasing the number of applications submitted by women may help achieve an equitable balance of grantees in the workforce.

Autochthonous Chagas disease in the southern United States: A case report of suspected residential and military exposures.

Chagas disease is a parasitic infection that can result in a progressive dilated cardiomyopathy. Here, we present the epidemiologic details of a suspected locally acquired transmission case originating from the southern United States. This is the first published report of Chagas disease in a young, healthy United States veteran with repeat triatomine exposures in Arizona. Military personnel and Arizona residents should be aware of their Chagas disease transmission risks.

Sylvatic Transmission of Trypanosoma cruzi Among Domestic and Wildlife Reservoirs in Texas, USA: A Review of the Historical Literature.

Chagas disease (Trypanosoma cruzi infection) is one of the most important neglected tropical diseases affecting the Americas. The transmission dynamic of this parasite is a complicated process that involves three genera of Triatominae subfamily and over 100 known mammalian reservoirs composed of domestic, peridomestic and wildlife species. Understanding the complex relationship between vector species and mammalian hosts is important for preventing transmission to humans. We performed a historical literature review to assess the disease burden in the Texas wildlife and domestic animal population. Reports of sylvatic transmission in Texas date back to the 1940s. We found that up to 23 species can serve as reservoirs for T. cruzi in the state with wood rats, raccoons, and wild and domestic canine species most frequently reported as positive for the parasite. We finish with a discussion of the current research gaps, implications for high-risk populations and future directions for research.

Trypanosoma cruzi screening in Texas blood donors, 2008-2012.

Chagas disease is an important emerging disease in Texas that results in cardiomyopathy in about 30% of those infected with the parasite Trypanosoma cruzi. Between the years 2008 and 2012, about 1/6500 blood donors were T. cruzi antibody-confirmed positive. We found older persons and minority populations, particularly Hispanic, at highest risk for screening positive for T. cruzi antibodies during routine blood donation. Zip code analysis determined that T. cruzi is associated with poverty. Chagas disease has a significant disease burden and is a cause of substantial economic losses in Texas.

Effectiveness and predictors of failure of noninvasive mechanical ventilation in acute respiratory failure.

OBJECTIVE: To assess the effectiveness and identify predictors of failure of noninvasive ventilation. DESIGN: A retrospective, longitudinal descriptive study was made. SETTING: Adult patients with acute respiratory failure. PATIENTS: A total of 410 consecutive patients with noninvasive ventilation treated in an Intensive Care Unit of a tertiary university hospital from 2006 to 2011. PROCEDURES: Noninvasive ventilation. MAIN VARIABLES OF INTEREST: Demographic variables and clinical and laboratory test parameters at the start and two hours after the start of noninvasive ventilation. Evolution during admission to the Unit and until hospital discharge. RESULTS: The failure rate was 50%, with an overall mortality rate of 33%. A total of 156 patients had hypoxemic respiratory failure, 87 postextubation respiratory failure, 78 exacerbation of chronic obstructive pulmonary disease, 61 hypercapnic respiratory failure without chronic obstructive pulmonary disease, and 28 had acute pulmonary edema. The failure rates were 74%, 54%, 27%, 31% and 21%, respectively. The etiology of respiratory failure, serum bilirubin at the start, APACHEII score, radiological findings, the need for sedation to tolerate noninvasive ventilation, changes in level of consciousness, PaO2/FIO2 ratio, respiratory rate and heart rate from the start and two hours after the start of noninvasive ventilation were independently associated to failure. CONCLUSIONS: The effectiveness of noninvasive ventilation varies according to the etiology of respiratory failure. Its use in hypoxemic respiratory failure and postextubation respiratory failure should be assessed individually. Predictors of failure could be useful to prevent delayed intubation.

Clinical predictors of disease severity during the 2009-2010 A(HIN1) influenza virus pandemic in a paediatric population.

A novel influenza virus emerged in the United States in spring 2009, rapidly becoming a global pandemic. Children were disproportionally affected by the novel influenza A(H1N1) pandemic virus [A(H1N1)pdm]. This retrospective electronic medical record review study aimed to identify clinical predictors of disease severity of influenza A(HIN1)pdm infection in paediatric patients. Disease severity was defined on an increasing three-level scale from non-hospitalized, hospitalized, and admitted to the intensive care unit (ICU). From April 2009 to June 2010, 696 children presented to Texas Children's Hospital's emergency department, 38% were hospitalized, and 17% were admitted to the ICU. Presenting symptoms associated with severe influenza were dyspnoea [odds ratio (OR) 5·82], tachycardia (OR 2·61) and fatigue (OR 1·96). Pre-existing health conditions associated with disease severity included seizure disorder (OR 4·71), obesity (OR 3·28), lung disease (OR 2·84), premature birth (OR 2·53), haematological disease (OR 2·22), and developmental delay (OR 2·20). According to model fitness tests, presenting symptoms were more likely to predict severe influenza than underlying medical conditions. However, both are important risk factors. Recognition of clinical characteristics associated with severe disease can be used for triaging case management of children during future influenza outbreaks.

Genetic inactivation of the pancreatitis-inducible gene Nupr1 impairs PanIN formation by modulating Kras(G12D)-induced senescence.

Nuclear protein 1 (Nupr1), a small chromatin protein, has a critical role in cancer development, progression and resistance to therapy. Previously, we had demonstrated that Nupr1 cooperates with Kras(G12D) to induce pancreas intraepithelial neoplasias (PanIN) formation and pancreatic ductal adenocarcinoma development in mice. However, the molecular mechanisms by which Nupr1 influences Kras-mediated preneoplastic growth remain to be fully characterized. In the current study, we report evidence supporting a role for Nupr1 as a gene modifier of Kras(G12D)-induced senescence, which must be overcome to promote PanIN formation. We found that genetic inactivation of Nupr1 in mice impairs Kras-induced PanIN, leading to an increase in ß-galactosidase-positive cells and an upregulation of surrogate marker genes for senescence. More importantly, both of these cellular and molecular changes are recapitulated by the results of mechanistic experiments using RNAi-based inactivation of Nupr1 in human pancreatic cancer cell models. In addition, the senescent phenotype, which results from Nupr1 inactivation, is accompanied by activation of the FoxO3a-Skp2-p27(Kip1)-pRb-E2F pathway in vivo and in vitro. Thus, combined, these results show, for the first time, that Nupr1 aids oncogenic Kras to bypass senescence in a manner that cooperatively promotes PanIN formation. Besides its mechanistic importance, this new knowledge bears medical relevance as it delineates early pathobiological events that may be targeted in the future as a means to interfere with the formation of preneoplastic lesions early during pancreatic carcinogenesis.

Calcium and vitamin D use among adults in periodontal disease maintenance programmes.

OBJECTIVES: To determine the level of calcium and vitamin D oral supplementation in patients in periodontal disease maintenance programmes. DESIGN: Convenience survey. SETTING: St. Louis Metropolitan region. SUBJECTS AND METHODS: Patients (n = 228) in two university-based, periodontal disease maintenance programmes. MAIN OUTCOME MEASURES: Reported amounts of oral calcium and vitamin D supplementation were tested for differences based on gender and race. RESULTS: The last published recommended daily intakes from the United States (US) Food and Nutrition Board (FNB) for adults >50 years of age are 1,200 mg calcium and 400 IU vitamin D (or 600 IU if over 70). The mean age of the 228 patients (125 females and 103 males) was 63.6 +/- 11.0 years (standard deviation). Of the 228 patients surveyed: (1) 204 (89%) were >50 years of age and of these, only 15 (7%) met the US FNB's recommended intakes of calcium and vitamin D from supplementation; (2) 138 (66%) reported that they took no oral supplementation, with significantly more males (n = 82) than females (n = 56) not taking supplementation (p = 0.03); (3) 88 (39%) took calcium supplementation, with females (947 +/- 511 mg/day) taking significantly (p <0.001) more than males (632 +/- 907 mg/day); and (4) 66 (29%) took vitamin D supplementation, with females(420 +/- 227 IU/day) taking approximately the same amount as males (443 +/- 317 IU/day, p >0.05). The amounts of oral supplementation did not vary with race (p >0.05). CONCLUSION: The use of calcium and vitamin D supplementation has been promoted for years, yet the numbers of adults taking supplements remains low and the level of supplementation varies greatly. Knowledge of the benefits of supplementation needs to be better disseminated and research needs to be conducted to determine optimal levels of calcium and vitamin D supplementation.

Optical biosensors for probing at the cellular level: a review of recent progress and future prospects.

New approaches are required to understand the complex processes taking place in the smallest unit of life. Recent years have seen an increasing activity in the use of optical devices and techniques for the investigation of the properties of single cells and also populations of cells including cell to cell communication. This article reviews relevant optical technologies to date as well as new advances in biosensor development, and goes on to explore reported applications in detection of biotargets and cellular signalling pathways inside individual living cells.

Evaluation of angiogenesis with the expression of VEGF and CD34 in human non-small cell lung cancer.

Angiogenesis is an essential process in the progression of malignant tumors and the most potent angiogenic factor is the vascular endothelial growth factor (VEGF). On the other hand, the CD34 is an endothelial antigen that has been used to highlight the microvasculature vessel density (MVD) as a direct marker of the degree of neoangiogenesis. In the present study we report the VEGF expression and its relationship with MVD, measured by CD34, in two lineages of non-small cell lung cancer (NSCL): low differentiated adenocarcinomas and epidermoid carcinomas, in order to consider the possibility of using the correlation between both antibodies as a prognostic factor. Tumor sections were stained by immunohistochemistry for CD34 and VEGF. The results showed that the mean value of VEGF for adenocarcinoma was significantly higher than the one for epidermoid carcinoma (p < 0.001). However, the mean of MVD did not show significant differences between both types of tumors. The conventional factors taken into consideration (age over 60, sex, and presence of lymph nodes) was not significantly related to the angiogenic factors examined. In conclusion, we could affirm that CD34 is a better prognostic marker of neoangiogenesis in NSCLC, because both types of tumors have the same clinical prognosis, and so we expected the same behaviour from both markers.

DNA synthesis in tongue keratinocytes of hepatectomized and tumor-bearing mice.

Tongue keratinocytes have high S-phase and mitotic indices with evident circadian variation. Transplanted tumors modify the intensity and temporal structure of the S-phase index in cell populations in tumor-bearing animals; also, partial hepatectomy changes the concentrations of substances involved in cellular proliferation, leading to compensatory liver hyperplasia. The aim of our study was to analyze the interaction between tumor growth and the liver regeneration that follows partial hepatectomy, and the effects of both these processes on lingual keratinocytes. We used 380 adult male mice divided into six groups: tumor-free and tumor-bearing mice without surgery, with sham hepatectomy, and with partial hepatectomy. Each group was divided into six subgroups, which were killed at 4-h intervals until a circadian cycle was completed (from 26 until 50h post-surgery in the operated animals). Each animal was injected with 5-bromodeoxyuridine (50mg/kg) 1h before it was killed, and tongue samples were obtained and processed for histology. The sections were placed on silanized slides and incubated with the primary antibody Bu 20a (1/100 dilution). The reaction was developed using diaminobenzidine and staining was detected visually. SIs were measured as the number of labeled nuclei per thousand cells. The mean+/-S.E. of each group was calculated. Differences among experimental groups were analyzed by ANOVA and the Student-Newman-Keuls Multiple Comparisons Test. The results show that the presence of a tumor alters the normal circadian curve of SI in lingual keratinocytes, irrespective of whether the mice underwent surgery. This finding has to be considered in drug treatments for neoplasms and in experiments related to growth.

Chronobiology of the proliferative events related to angiogenesis in mice liver regeneration after partial hepatectomy.

In liver regeneration the formation of new capillary blood vessels is a fundamental requirement for cellular proliferation. Vascular endothelial growth factor (VEGF) is involved in the events of angiogenesis, the mRNA of which is expressed in both hepatocytes and non-parenchymal cells. In this experimental design we try to establish if during liver regeneration in mouse, the expression of VEGF is produced before or after the hepatocytes proliferation. C3H/S adult male mice were divided in three groups in order to study: VEGF expression; S-phase index (SI); and mitotic activity (MA) of hepatocytes. The results that were analyzed by ANOVA, show that VEGF expression starts to increase 26 h after PH with a peak at 28 h. Furthermore, the DNA synthesis (DNAs) reaches maximal level 42 h after pH, meanwhile the MA of the hepatocytes shows an increase 8h after the DNAs peak. In conclusion, it could be argued that the chronobiology of the events related to liver regeneration in mice started with a release of VEGF by the hepatocytes, followed by its DNAs and mitosis.

Development of compensatory hepatic hyperplasia in mice carrying the hepatocellular carcinoma ES12a.

In a previous paper we reported that the presence of the hepatocellular carcinoma SS1K in host mice resulted in an earlier appearance of the hepatocyte mitotic peak during liver regeneration after a partial hepatectomy as well as in an increase in the amplitude of that mitotic wave. In the present work we analyse the effect of another hepatocellular carcinoma, the ES12a (HCES12a). Adult male mice of the C3H/S strain standardised for circadian-periodicity analysis, were used. One group received a subcutaneous graft of the HCES12a tumor, while another group served as control. Fifteen days later, all animals were submitted to a partial (70%) hepatectomy at 10:00 h and beginning at 16:00 h lots of between 5 and 9 host and control animals each were sacrificed at 4 h intervals until 16:00 h on the third day thereafter. All mice were injected with 2 microg/g colchicine 4 hrs before killing, and samples of livers were processed for hematoxylin-eosin staining. We determined the hepatocyte mitotic index for each animal and the mean value +/- the standard error of the mean for each lot. The peak of mitotic activity in the tumor-bearing animals took place four hours earlier than in control mice but the average values of hepatocytic mitotic activity were similar in both groups

Biosensors in the livestock industry: an automated ovulation prediction system for dairy cows.

Biosensor technology can offer the livestock industry new types of monitoring and measuring devices of which the specificity, sensitivity, reproducibility, speed and ease of use exceed the current technology. Biosensors can be applied to the detection and identification of infectious diseases in livestock, contaminants and toxins in feed, therapeutic drug residues in animal husbandry and oestrus detection. Our team is applying biosensor technology to the livestock industry by developing a fully automated ovulation prediction system for dairy cows. The results from field-tests show that the progesterone biosensor can characterize the ovulation cycles of cows and detect pregnancy.

The genetic structure of Mexican Mestizos of different locations: tracking back their origins through MHC genes, blood group systems, and microsatellites.

Mexican Mestizos, who are the result of the admixture of Spanish, Indian, and Black genes, were analyzed for different systems. Three populations from geographical distinct areas were studied: the north (State of Nuevo Leon ), the center (State of Guanajuato), and the highlands (mainly Mexico City). Ten blood group systems (N = 229), STRs (N = 107), HLA-A*, B*, C* (N = 116-167), and DRB1, DQA1, and DQB1 (N = 40, 101, 160, respectively) were analyzed in the samples of the highlands. The three groups cluster together in the same branch: Mestizos from Venezuela, Mediterranean and Jews close to the cluster of Orientals, followed by Amerindians. All markers demonstrate that Indian genes are strongly represented in the highlands: Di(a), O, D(-)(+), s, A*0201, *0206, B*1539 (*1541), *3902, *3905, *3512, *3517, *4002, *4005, Cw*0801, *0304, *0401 among others. Cw*0501, *1203, *1204, and *1601 are of White ancestry. The most frequent haplotypes *0407-*03011-*0302 and *0802-*0401-*0402 are of Indian descent as well. The center and mainly the north show a more Caucasian and Semitic profile. The results demonstrate the high variability resulting from interethnic admixture, suggesting that this mechanism is the main factor responsible for the large diversity found in urban populations.

DQA1 and DQB1 promoter diversity and linkage disequilibrium with class II haplotypes in Mexican Mestizo population.

The upstream sequences in the 5' flanking region of HLA class II genes, regulate their expression and contribute to the development of immunological diseases. We analyzed 105 healthy unrelated Mexican Mestizos for QAP and QBP polymorphism. DNA typing for DRB1, DQA1, DQB1, QAP1 and QBP1 was done using a standardized PCR-SSOP. Although all QAP alleles previously described were found in Mexicans, the distribution differed as compared to other populations. QAP-3.1, 4.1 and 4.2 were the most frequent alleles and were associated with DQA1*03, *0501 and *0402 respectively. The prevalent QBP alleles were 3.21, 3.1 and 4.1 found mainly associated with DQB1*0302, *0301 and *0501. Linkage disequilibria between the promoter and the corresponding DQA1 and DQB1 allele, are in general the same as described by others. A total of 61 different haplotypes were defined, only six of them with a frequency above 4%. The haplotypes DRB1*0407-QAP-3.1-DQA1*03-QBP-3.21-DQB1*0302 (HF = 14.37%) and DRB1*0802-QAP-4.2-DQA1*0401-QBP-4.1-DQB1*0402 (HF = 14.22%), which have an Amerindian ancestry, are the most frequent in Mexicans. Some rare combinations were detected such as DRB1*0405-QAP-1.3-DQA1*0101/4-QBP-5.11/5.12-DQB1*0501 and DRB1*0403-QAP-3.2-DQA1*03-QBP-3.21-DQB1*0302, probably due to ancient recombination events. This knowledge is relevant as a basis to evaluate functional implications and to explore the role of promoter diversity in disease expression.

Effect of partial and sham hepatectomy on the growth of a hepatocellular carcinoma.

We examined the effect of partial hepatectomy on the proliferation of hepatoma ES12a grafted into C3H/S mice compared to tumor growth in sham-hepatectomized controls. The animals were sacrificed every 4 hrs during three days from the 6th to the 78th h following each type of surgery. Unoperated tumor-bearing mice were likewise killed as controls, but only during one complete circadian period. All animals received 2 microg of colchicine per g of body weight intraperitoneally 4 hrs before decapitation. Measurement of mitotic indices in hematoxylineosin-stained tumor samples revealed a decrease in proliferation and a modification of the diurnal mitotic-activity profile in the hepatectomized and sham-operated animals from the first day after surgery. These differences persisted by the third postoperative day only in the hepatectomized animals. Thus, although surgical stress may initially affect tumor growth, the latter results must be the effect of the influence of the hepatic regeneration.

Circadian rhythm of DNA synthesis and mitotic activity in tongue keratinocytes.

Tongue keratinocytes have a high mitotic index (MI) with an evident circadian variation. Our study set out to compare and contrast two phases of the cell cycle: DNA synthesis (S-phase), with inmunocytochemical detection by bromodeoxyuridine (BrdU), and mitosis (M-phase), by the colchicine-arrest of metaphase method, exploring both the dorsal and ventral surfaces of the mouse tongue throughout a circadian period. Adult male mice standardized for light periodicity used for MI experiment were injected intraperitoneally with colchicine. Other animals were injected intraperitoneally with 5-BrdU for S-phase determination. Animals given both treatments were divided into six groups and killed at 4 h intervals until 20:00 h. Tongue samples were processed for histology and immuno-histochemistry. S and M indices were expressed as labelled nuclei or colchicine metaphases, respectively, per 1000 nuclei. Peak MI occurred at 12:00, with the minimum value at 20:00 on dorsal and ventral tongue surfaces. Peak S-phase was at 04:00, whereas the minimum value was at 16:00 for both surfaces. These results show that the proliferative activity of the tongue epithelium is of similar intensity and temporal distribution on both surfaces.

DNA synthesis and nucleolar organizer regions circadian rhythm in mouse regenerating liver hepatocytes.

DNA synthesis and Nucleolar Organizer Regions (NORs) were studied in C3HS inbred mice standardized for periodicity analysis. Immunohistochemical detection of Bromodeoxyuridine (BrdU) incorporated into DNA with a monoclonal antibody and silver staining of NORs (AgNORs) were assessed by means of a digital image analysis system in histological sections of regenerating liver. Tissue samples were obtained at different times after hepatectomy along a circadian span. The results showed a strong correlation of values between DNA synthesis (BrdU labelling index) and AgNOR numbers, with higher counts during the activity period of animals at 00:00/38 and 04:00/42 hours Time of Day/Hours Post-Hepatectomy (TD/HPH), being the differences with other time points highly significant. Our observations demonstrate the existence of a strong correlation of DNA synthesis measured by BrdU incorporation and AgNOR numbers with a defined circadian rhythm in mouse regenerating hepatocytes.