Development of diagnostic assays for differentiation of atypical Aeromonas salmonicida vapA type V and type VI in ballan wrasse (Labrus bergylta, Ascanius).

Aeromonas salmonicida (As) is a highly heterogeneous bacterial species, and strains' host specificity has been reported. Ballan wrasse (Labrus bergylta Ascanius, 1767) is susceptible to atypical As (aAs) vapA type V and type VI in Scotland and Norway. Identification of the bacterium is achieved by culture and molecular techniques; however, the available methods used to distinguish the As types are costly and time-consuming. This paper describes the development of a PCR and a restriction enzyme assay for the detection of aAs vapA type V and type VI in ballan wrasse, respectively. Type V-specific primers were designed on conserved regions of the vapA gene, and the restriction enzyme assay was performed on the PCR products of the hypervariable region of vapA gene for the detection of type VI isolates. Amplification product was produced for type V (254 bp) and restriction bands (368 and 254 bp) for type VI isolates only. In addition, the assays detected type V and type VI isolates in spiked water samples and type V in diagnostic tissue samples. The assays are fast, specific and cost-effective and can be used as specific diagnostic tools for cleaner fish, to detect infectious divergence strains, and to manage and mitigate aAs disease outbreaks through vaccine development.

Associations between vaginal bacteria implicated in HIV acquisition risk and proinflammatory cytokines and chemokines.

OBJECTIVES: Recent studies have identified vaginal bacterial taxa associated with increased HIV risk. A possible mechanism to explain these results is that individual taxa differentially promote cervicovaginal inflammation. This study aimed to explore relationships between concentrations of bacteria previously linked to HIV acquisition and vaginal concentrations of proinflammatory cytokines and chemokines. METHODS: In this cross-sectional analysis, concentrations of 17 bacterial taxa and four proinflammatory cytokines (interleukin (IL)-1ß, IL-6, IL-10 and tumour necrosis factor alpha (TNFα)) and two proinflammatory chemokines (IL-8 and interferon gamma-induced protein 10) were measured in vaginal swabs collected from 80 HIV-uninfected women. Cytokine and chemokine concentrations were compared between women with bacterial concentrations above or below the lower limit of detection as determined by quantitative PCR for each taxon. Principal component analysis was used to create a summary score for closely correlated bacteria, and linear regression analysis was used to evaluate associations between this score and increasing concentrations of TNFα and IL-1ß. RESULTS: Detection of Dialister micraerophilus (p=0.01), Eggerthella sp type 1 (p=0.05) or Mycoplasma hominis (p=0.03) was associated with higher TNFα concentrations, and detection of D. micraerophilus (p<0.01), Eggerthella sp type 1 (p=0.04), M. hominis (p=0.02) or Parvimonas sp type 2 (p=0.05) was associated with significantly higher IL-1ß concentrations. Seven bacterial taxa (D. micraerophilus, Eggerthella sp type 1, Gemella asaccharolytica, Sneathia sp, Megasphaera sp, M. hominis and Parvimonas sp type 2) were found to be highly correlated by principal component analysis (eigenvalue 5.24, explaining 74.92% of variability). Linear regression analysis demonstrated associations between this principal component and concentrations of TNFα (ß=0.55, 95% CI 0.01 to 1.08; p=0.048) and IL-1ß (ß=0.96, 95% CI 0.19 to 1.74; p=0.016). CONCLUSIONS: This study provides evidence that several highly correlated vaginal bacterial taxa may influence vaginal cytokine and chemokine concentrations. These results suggest a mechanism where the presence of specific bacterial taxa could influence HIV susceptibility by increasing vaginal inflammation.

Behavioral preference for viewing drug v. pleasant images predicts current and future opioid misuse among chronic pain patients.

BACKGROUND: The USA is currently enduring an opioid crisis. Identifying cost-effective, easy-to-implement behavioral measures that predict treatment outcomes in opioid misusers is a crucial scientific, therapeutic, and epidemiological goal. METHODS: The current study used a mixed cross-sectional and longitudinal design to test whether a behavioral choice task, previously validated in stimulant users, was associated with increased opioid misuse severity at baseline, and whether it predicted change in opioid misuse severity at follow-up. At baseline, data from 100 prescription opioid-treated chronic pain patients were analyzed; at follow-up, data were analyzed in 34 of these participants who were non-misusers at baseline. During the choice task, participants chose under probabilistic contingencies whether to view opioid-related images in comparison with affectively pleasant, unpleasant, and neutral images. Following previous procedures, we also assessed insight into choice behavior, operationalized as whether (yes/no) participants correctly self-reported the image category they chose most often. RESULTS: At baseline, the higher choice for viewing opioid images in direct comparison with pleasant images was associated with opioid misuse and impaired insight into choice behavior; the combination of these produced especially elevated opioid-related choice behavior. In longitudinal analyses of individuals who were initially non-misusers, higher baseline opioid v. pleasant choice behavior predicted more opioid misuse behaviors at follow-up. CONCLUSIONS: These results indicate that greater relative allocation of behavior toward opioid stimuli and away from stimuli depicting natural reinforcement is associated with concurrent opioid misuse and portends vulnerability toward future misuse. The choice task may provide important medical information to guide opioid-prescribing practices.

Risk estimation of the SARS-CoV-2 acute respiratory disease outbreak outside China.

BACKGROUND: On December 31, 2019, the World Health Organization was alerted to the occurrence of cases of pneumonia in Wuhan, Hubei Province, China, that were caused by an unknown virus, which was later identified as a coronavirus and named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to estimate the reproductive number of SARS-CoV-2 in the Hubei Province and evaluate the risk of an acute respiratory coronavirus disease (COVID-19) outbreak outside China by using a mathematical model and stochastic simulations. RESULTS: We constructed a mathematical model of SARS-CoV-2 transmission dynamics, estimated the rate of transmission, and calculated the reproductive number in Hubei Province by using case-report data from January 11 to February 6, 2020. The possible number of secondary cases outside China was estimated by stochastic simulations in various scenarios of reductions in the duration to quarantine and rate of transmission. The rate of transmission was estimated as 0.8238 (95% confidence interval [CI] 0.8095-0.8382), and the basic reproductive number as 4.1192 (95% CI 4.0473-4.1912). Assuming the same rate of transmission as in Hubei Province, the possibility of no local transmission is 54.9% with a 24-h quarantine strategy, and the possibility of more than 20 local transmission cases is 7% outside of China. CONCLUSION: The reproductive number for SARS-CoV-2 transmission dynamics is significantly higher compared to that of the previous SARS epidemic in China. This implies that human-to-human transmission is a significant factor for contagion in Hubei Province. Results of the stochastic simulation emphasize the role of quarantine implementation, which is critical to prevent and control the SARS-CoV-2 outbreak outside China.

Impacts of reopening strategies for COVID-19 epidemic: a modeling study in Piedmont region.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), the causative agent of the coronavirus disease 19 (COVID-19), is a highly transmittable virus. Since the first person-to-person transmission of SARS-CoV-2 was reported in Italy on February 21st, 2020, the number of people infected with SARS-COV-2 increased rapidly, mainly in northern Italian regions, including Piedmont. A strict lockdown was imposed on March 21st until May 4th when a gradual relaxation of the restrictions started. In this context, computational models and computer simulations are one of the available research tools that epidemiologists can exploit to understand the spread of the diseases and to evaluate social measures to counteract, mitigate or delay the spread of the epidemic. METHODS: This study presents an extended version of the Susceptible-Exposed-Infected-Removed-Susceptible (SEIRS) model accounting for population age structure. The infectious population is divided into three sub-groups: (i) undetected infected individuals, (ii) quarantined infected individuals and (iii) hospitalized infected individuals. Moreover, the strength of the government restriction measures and the related population response to these are explicitly represented in the model. RESULTS: The proposed model allows us to investigate different scenarios of the COVID-19 spread in Piedmont and the implementation of different infection-control measures and testing approaches. The results show that the implemented control measures have proven effective in containing the epidemic, mitigating the potential dangerous impact of a large proportion of undetected cases. We also forecast the optimal combination of individual-level measures and community surveillance to contain the new wave of COVID-19 spread after the re-opening work and social activities. CONCLUSIONS: Our model is an effective tool useful to investigate different scenarios and to inform policy makers about the potential impact of different control strategies. This will be crucial in the upcoming months, when very critical decisions about easing control measures will need to be taken.

BMI but not central obesity predisposes to airway closure during bronchoconstriction.

BACKGROUND AND OBJECTIVE: Obesity produces restrictive effects on lung function. We previously reported that obese patients with asthma exhibit a propensity towards small airway closure during methacholine challenge which improved with weight loss. We hypothesized that increased abdominal adiposity, a key contributor to the restrictive effects of obesity on the lung, mediates this response. This study investigates the effect of body mass index (BMI) versus waist circumference (WC) on spirometric lung function, sensitivity to airway narrowing and closure, and airway closure during bronchoconstriction in patients with asthma. METHODS: Participants underwent spirometry and methacholine challenge. Sensitivity to airway closure and narrowing was assessed from the dose-response slopes of the forced vital capacity (FVC) and the ratio of forced expiratory volume in 1 s (FEV1 ) to FVC, respectively. Airway closure during bronchoconstriction (closing index) was computed as the percent reduction in FVC divided by the percent reduction in FEV1 at maximal bronchoconstriction. RESULTS: A total of 116 asthmatic patients (56 obese) underwent methacholine challenge. Spirometric lung function was inversely related to WC (P < 0.05), rather than BMI. Closing index increased significantly during bronchoconstriction in obese patients and was related to increasing BMI (P = 0.01), but not to WC. Sensitivity to airway closure and narrowing was not associated with BMI or WC. CONCLUSION: Although WC is associated with restrictive effects on baseline lung function, increased BMI, rather than WC, predisposes to airway closure during bronchoconstriction. These findings suggest that obesity predisposes to airway closure during bronchoconstriction through mechanisms other than simple mass loading.

Different susceptibility to fatty liver-haemorrhagic syndrome in young and older layers and the interaction on blood LDL-C levels between oestradiols and high energy-low protein diets.

1. The objective of the study was to investigate the susceptibility of young and older laying hens to fatty liver-haemorrhagic syndrome (FLHS) and to evaluate the reliability of different blood lipid fractions for predicting or diagnosing FLHS. 2. Forty young hens and 40 older hens were caged individually. Each group of hens was randomly allotted to four treatments for 21 days: either a control, an oestradiol group, a high energy-low protein diet (HELPD) group or a HELPD + oestradiol group. Blood levels of oestradiol, triglyceride (TG), cholesterol (CHOL), high density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C), liver total lipids, hepatic haemorrhagic scores and productive performance were assessed. 3. In older hens, ß-oestradiol increased (P < 0.05) liver total lipids, hepatic haemorrhagic scores and the incidence of FLHS but reduced (P < 0.05) productive performance; however, such changes were not observed in young hens. 4. In two groups of hens, serum TG, CHOL and HDL-C levels were increased (P < 0.001) by ß-oestradiol. Hens with FLHS had higher serum TG, CHOL and HDL-C (P < 0.001) than non-FLHS birds in the older layer group of hens. 5. An interaction (ß-oestradiol × HELPD) (P < 0.05) for LDL-C levels was observed in both groups of hens. In young hens, ß-oestradiol induced a decrease (P = 0.004) in serum LDL-C levels but the effect was attenuated by HELPD. In older hens, HELPD caused an increase (P = 0.02) in serum LDL-C although the effect depended on the presence of ß-oestradiol. 6. In conclusion, older layers were more susceptible to FLHS than young layers after oestradiol treatment. Blood TG, CHOL and HDL-C rather than LDL-C levels can be used as a prediction tool for the overall susceptibility to FLHS in older rather than young layers. There were interactions between oestradiol and HELPD on blood LDL-C levels in laying hens.

Feasibility of the salivary transcriptome as a novel biomarker in determining disease susceptibility.

BACKGROUND AND OBJECTIVE: The salivary transcriptome may present as a readily available and non-invasive source of potential biomarkers. The development of chronic periodontitis is determined by individual patient susceptibility; hence, the aim of this study was to determine the potential of the salivary transcriptome as a biomarker of disease susceptibility using chronic periodontitis as an example. MATERIAL AND METHODS: Using an Oragene® RNA kit, the total RNA was purified from the saliva of 10 patients with chronic periodontitis and 10 patients without chronic periodontitis. The quantity and quality of the total RNA was determined, and a measure of gene expression via cDNA was undertaken using the Affymetrix microarray system. The microarray profiling result was further validated by real-time quantitative polymerase chain reaction. RESULTS: Spectrophotometric analysis showed the total RNA purified from each participant ranged from 0.92 µg/500 µL to 62.85 µg/500 µL. There was great variability in the quantity of total RNA obtained from the 2 groups in the study with a mean of 10.21 ± 12.71 µg/500 µL for the periodontitis group and 15.97 ± 23.47 µg/500 µL for the control group. Further the RNA purity (based on the A260 /A280 ratio) for the majority of participants (9 periodontitis and 6 controls) were within the acceptable limits for downstream analysis (2.0 ± 0.1). The study samples, showed 2 distinct bands at 23S (3800 bp) and 16S (1500 bp) characteristic of bacterial rRNA. Preliminary microarray analysis was performed for 4 samples (P2, P6, H5 and H9). The percentage of genes present in each of the 4 samples was not consistent with about 1.8%-18.7% of genes being detected. Quantitative real-time polymerase chain reaction confirmed that the total RNA purified from each sample was mainly bacterial RNA (Uni 16S) with minimal human mRNA. CONCLUSION: This study showed that minimal amounts of human RNA were able to be isolated from the saliva of patients with periodontitis as well as controls. Further work is required to enhance the extraction process of human mRNA from saliva if the salivary transcriptome is to be used in determining individual patient susceptibility.

Consumers Can Now Buy a Blood Test to Evaluate Their Alzheimer Disease Risk, but Should They?

This Medical News feature discusses a Quest Diagnostics blood biomarkers test that is supposed to help consumers assess their Alzheimer disease risk.

Muscle cramp susceptibility increases following a volitionally induced muscle cramp.

INTRODUCTION: Muscle cramping may increase peripheral nervous system excitability. It is unknown if, and how long, cramp susceptibility is affected by previous cramping. We tested whether volitionally induced muscle cramps (VIMCs) lowered cramp threshold frequency (TFc ) and how long TFc was affected post-VIMC. METHODS: Fifteen cramp-prone participants volitionally induced a flexor hallucis brevis (FHB) cramp on 4 separate days. FHB TFc was measured before VIMC (i.e., baseline) and 5, 30, and 60 min post-VIMC. VIMC electromyography (EMG) amplitude, VIMC duration, and perceived VIMC intensity were measured to ensure consistency of VIMC between days. RESULTS: VIMC EMG amplitude, duration, and perceived intensity were similar between days (P > 0.05). VIMC lowered TFc ; baseline TFc (18 ± 6 Hz) was higher than 5-min (14 ± 6 Hz), 30-min (14 ± 5 Hz), and 60-min TFc (14 ± 5 Hz; P < 0.05). DISCUSSION: Acute VIMCs increase cramp susceptibility. Clinicians should apply treatments for at least 60 min postcramp to decrease the probability of cramp recurrence. Muscle Nerve 56: E95-E99, 2017.

Electrocardiographic changes during exercise in acute hypoxia and susceptibility to severe high-altitude illnesses.

BACKGROUND: The goals of this study were to compare ECG at moderate exercise in normoxia and hypoxia at the same heart rate, to provide evidence of independent predictors of hypoxia-induced ECG changes, and to evaluate ECG risk factors of severe high-altitude illness. METHODS AND RESULTS: A total of 456 subjects performed a 20-minute hypoxia exercise test with continuous recording of ECG and physiological measurements before a sojourn above 4000 m. Hypoxia did not induce any conduction disorder, arrhythmias, or change in QRS axis. The amplitude of the P wave in V1 was lower in hypoxia than in normoxia. The amplitudes of the R, S, and T waves and the Sokolow index decreased in hypoxia. Under hypoxia, the amplitude of the ST segment decreased in II and V6 and increased in V1, the ST slope rose in V5 and V6, and the J point was lower in II, V5, and V6. Multivariate regression of hypoxic/normoxic ratios of electrophysiological parameters and clinical characteristics showed a correlation between the decrease in Sokolow index and T-wave amplitude in V5 with desaturation at exercise. Trained status and low body mass index were associated with a smaller decrease in T-wave amplitude in V5 and V6. Comparison of ECG between subjects suffering or not suffering from severe high-altitude illness failed to show any difference. CONCLUSIONS: During a hypoxia exercise test, a dose-dependent hypoxia-induced decrease in the amplitude of the P/QRS/T waves was observed. No standard ECG characteristic predicted the risk of developing severe high-altitude illness. Further studies are required to clarify the cause of these electric changes and their potential predictive role in cardiac events.

Peer Victimization and Harsh Parenting Predict Cognitive Diatheses for Depression in Children and Adolescents.

The current study examined peer victimization and harsh parenting as longitudinal predictors of broadband and narrowband cognitions associated with the etiology of depression in children and adolescents. The sample consisted of 214 elementary and middle school students. At the start of the study, their average age was 12.2 years (SD = 1.0). The sex ratio was 112 girls to 102 boys. The sample was ethnically diverse (58.9% Caucasian, 34.1% African American, 10.7% Hispanic, 3.3% Asian, and 5.2% other). Children and their parents completed measures of peer victimization and harsh parenting. At two waves 1 year apart, children also completed questionnaire measures of negative and positive broadband cognitive style (e.g., personal failure, global self-worth) and narrowband self-perceptions (e.g., perceived social threat, social acceptance). Every Wave 2 cognitive variable was predicted by peer victimization or harsh parenting or both, even after controlling for a Wave 1 measure of the same cognitive variable. Peer victimization more consistently predicted narrowband social/interpersonal cognitions, whereas harsh parenting more consistently predicted broadband positive and negative cognitions. Furthermore, controlling for positive and negative self-cognitions eliminated a statistically significant effect of harsh parenting and peer victimization on depressive symptoms. Support emerged for the social learning of negative self-cognitions. Support also emerged for negative self-cognitions as a mediator of depressive symptoms. Implications for theory and practice are discussed.

Evaluation of different models to segregate Pelibuey and Katahdin ewes into resistant or susceptible to gastrointestinal nematodes.

This study evaluated four models based on the number of eggs per gram of faeces (EPG) to segregate Pelibuey or Katahdin ewes during the lactation period into resistant or susceptible to gastrointestinal nematodes (GIN) in tropical Mexico. Nine hundred and thirty EPG counts of Pelibuey ewes and 710 of Katahdin ewes were obtained during 10 weeks of lactation. Ewes were segregated into resistant, intermediate and susceptible, using their individual EPG every week. Then, data of every ewe was used to provide a reference classification, which included all the EPG values of each animal. Then, four models were evaluated against such reference. Model 1 was based on the 10-week mean EPG count ± 2 SE. Models 2, 3 and 4 were based on the mean EPG count of 10, 5 and 2 weeks of lactation. The cutoff points for the segregation of ewe in those three models were the quartiles ≤Q1 (low elimination) and ≥Q3 (high elimination). In all the models evaluated, the ewes classified as resistant had lower EPG than intermediates and susceptible (P < 0.001) while ewes classified as susceptible had higher EPG than intermediate and resistant (P < 0.001). According to J Youden test, models presented concordance with the reference group (>70 %). Model 3 tended to show higher sensitivity and specificity with the reference data, but no difference was found with other models. The present study showed that the phenotypic marker EPG might serve to identify and segregate populations of adult ewes during the lactation period. All models used served to segregate Pelibuey and Katahdin ewes into resistant, intermediate and susceptible. The model 3 (mean of 5 weeks) could be used because it required less sampling effort without losing sensitivity or specificity in the segregation of animals. However, model 2 (mean of 2 weeks) was less labour-intensive.

Family history, not lack of medication use, is associated with the development of postpartum depression in a high-risk sample.

We sought to determine clinical predictors of postpartum depression (PPD), including the role of medication, in a sample of women followed prospectively during and after pregnancy. Women with a history of mood disorder were recruited and evaluated during each trimester and 1 week, 1 month, and 3 months postpartum. DSM-IV criteria for a major depressive episode were assessed by a psychiatric interview at each time point. Sixty-three women with major depression and 30 women with bipolar disorder entered the study and 75.4 % met DSM-IV criteria for a MDE during pregnancy, postpartum, or both. We modeled depression in a given time period (second trimester, third trimester, or 1 month postpartum) as a function of medication use during the preceding period (first, second, or third trimester). The odds of being depressed for those who did not use medication in the previous period was approximately 2.8 times that of those who used medication (OR 2.79, 95 % CI 1.38-5.66, p = 0.0048). Of 38 subjects who were psychiatrically well during the third trimester, 39.5 % (N = 15) met the criteria for a MDE by 4 weeks postpartum. In women who developed PPD, there was a high rate of a family history of PPD (53.3 %) compared to women who did not develop PPD (11.8 %, p = 0.02). While the use of psychiatric medications during pregnancy reduced the odds of being depressed overall, the use of psychiatric medications during pregnancy may not protect against PPD in women at high risk, particularly those with a family history of PPD.

Is previous history a reliable predictor for acute mountain sickness susceptibility? A meta-analysis of diagnostic accuracy.

PURPOSE: The goal of this meta-analysis was to determine the clinical utility of acute mountain sickness (AMS) history to predict future incidents of AMS. METHOD: 17 studies (n=7921 participants) were included following a systematic review of the literature. A bivariate random-effects model was used to calculate the summary sensitivity and specificity of the diagnostic test, and moderator variables were tested to explain the heterogeneity across studies. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) method was used to assess concerns for bias and applicability for the included studies. RESULTS: The history of AMS had a low diagnostic accuracy for the prediction of future AMS incidents: the summary sensitivity was 0.50 (95% CI (0.40 to 0.59)) and the summary specificity was 0.72 (95% CI (0.66 to 0.78)). There was significant heterogeneity in the sensitivity and specificity across studies, which we modelled using moderator analysis. Studies that restricted the use of acetazolamide and dexamethasone had not only a higher sensitivity (0.66) relative to those that did not (0.44; p=0.03) but also an increased false-positive rate (0.39 vs 0.23, p=0.03). The QUADAS-2 analysis showed that AMS histories were insufficiently detailed, and few studies controlled for prophylactic medication use or recent altitude exposure, leading to high risks of bias and concerns for applicability. CONCLUSIONS: The use of AMS history to guide prophylactic strategies for high-altitude ascent is not supported by the literature; however, the low sensitivity and specificity of this diagnostic test could reflect the quality of the available studies. Ensuring that the characteristics of the history and future ascents are similar may improve the clinical utility of AMS history.

Susceptibility of the conventional criteria for mild cognitive impairment to false-positive diagnostic errors.

BACKGROUND: We assessed whether mild cognitive impairment (MCI) subtypes could be empirically derived within the Alzheimer's Disease Neuroimaging Initiative (ADNI) MCI cohort and examined associated biomarkers and clinical outcomes. METHODS: Cluster analysis was performed on neuropsychological data from 825 MCI ADNI participants. RESULTS: Four subtypes emerged: (1) dysnomic (n = 153), (2) dysexecutive (n = 102), (3) amnestic (n = 288), and (4) cluster-derived normal (n = 282) who performed within normal limits on cognitive testing. The cluster-derived normal group had significantly fewer APOE ε4 carriers and fewer who progressed to dementia compared with the other subtypes; they also evidenced cerebrospinal fluid Alzheimer's disease biomarker profiles that did not differ from the normative reference group. CONCLUSIONS: Identification of empirically derived MCI subtypes demonstrates heterogeneity in MCI cognitive profiles that is not captured by conventional criteria. The large cluster-derived normal group suggests that conventional diagnostic criteria are susceptible to false-positive errors, with the result that prior MCI studies may be diluting important biomarker relationships.

Association of genetic loci for migraine susceptibility in the she people of China.

BACKGROUND: The purpose of this study was to investigate the association of the genotype and allele frequencies of the polymorphisms rs4379368, rs10504861, rs10915437, rs12134493 and rs13208321 in She people of China with migraine headache susceptibility. The five alleles were previously identified as being associated with migraine in a Western population, but it was not known if this association would hold in a She population. rs4379368 is in the succinic HMG coenzyme A transferase (C7orf10) gene; rs10504861 is near the matrix metallopeptidase 16 (MMP16) gene; rs10915437 is near the adherens junctions associated protein 1 (AJAP1) gene; rs12134493 is upstream of the tetraspanin 2 (TSPAN2) gene; and rs13208321 is within the four and a half LIM domains protein 5 (FHL5) gene. METHODS: This was a case-controlled study conducted in She people of Fujian province in China. Polymerase chain reaction-restriction fragment length polymorphism and direct sequencing were performed. Univariate and multivariate analyses were used to assess the association of the different genotypes of each SNP with migraine. RESULTS: The rs4379368 T allele was not in Hardy-Weinberg equilibrium and was more common than the C allele in subjects with migraine (58.7 %; P = 0.049), possibly suggesting a selection bias for T allele in this population. In support of this, the CT and TT genotypes were more frequent in the migraine compared with the control groups (54.0 % and 31.7 % vs. 48.0 % and 28.7 %, respectively; P = 0.019). These genotypes were also more common in females with migraines than females without migraines (53.8 % and 30.9 % vs. 46.7 % and 27.6 %; P = 0.026). Univariate and multivariate analyses found the CC genotype of rs4379368 and AA or AG genotype of rs13208321 were associated with a reduced risk of migraine (P values ≤0.039). CONCLUSIONS: Our findings suggest that rs4379368 and rs13208321 are potential genetic markers for migraine in this She population. The findings of this study and others indicate important differences between ethnic populations in regard to genetic markers of migraine susceptibility.

A genomics approach to identify susceptibilities of breast cancer cells to "fever-range" hyperthermia.

BACKGROUND: Preclinical and clinical studies have shown for decades that tumor cells demonstrate significantly enhanced sensitivity to "fever range" hyperthermia (increasing the intratumoral temperature to 42-45°C) than normal cells, although it is unknown why cancer cells exhibit this distinctive susceptibility. METHODS: To address this issue, mammary epithelial cells and three malignant breast cancer lines were subjected to hyperthermic shock and microarray, bioinformatics, and network analysis of the global transcription changes was subsequently performed. RESULTS: Bioinformatics analysis differentiated the gene expression patterns that distinguish the heat shock response of normal cells from malignant breast cancer cells, revealing that the gene expression profiles of mammary epithelial cells are completely distinct from malignant breast cancer lines following this treatment. Using gene network analysis, we identified altered expression of transcripts involved in mitotic regulators, histones, and non-protein coding RNAs as the significant processes that differed between the hyperthermic response of mammary epithelial cells and breast cancer cells. We confirmed our data via qPCR and flow cytometric analysis to demonstrate that hyperthermia specifically disrupts the expression of key mitotic regulators and G2/M phase progression in the breast cancer cells. CONCLUSION: These data have identified molecular mechanisms by which breast cancer lines may exhibit enhanced susceptibility to hyperthermic shock.