Familial factors influence susceptibility to multiple sclerosis (MS) but it is unknown whether there are additional effects on the natural history of the disease.
We evaluated 1,083 families with > ...or =2 first-degree relatives with MS for concordance of age at onset, clinical course, and disease severity and investigated transmission patterns of these clinical features in affected parent-child pairs.
There is concordance for age at onset for all families (correlation coefficient 0.14; p < 0.001), as well as for affected siblings (correlation coefficient 0.15; p < 0.001), and affected parent-child pairs (correlation coefficient 0.12; p = 0.03) when each is evaluated separately. Concordance for year of onset is present among affected siblings (correlation coefficient 0.18; p < 0.001) but not the parent-child group (correlation coefficient 0.08; p = 0.15). The clinical course is similar between siblings (kappa 0.12; p < 0.001) but not affected parents and their children (kappa -0.04; p = 0.09). This influence on the natural history is present in all clinical subgroups of relapsing-remitting, and primary and secondary progressive MS, reflecting a familial effect on episodic and progressive phases of the disease. There is no concordance for disease severity within any of the considered family groups (correlation coefficients: all families analyzed together, 0.02, p = 0.53; affected sibling group, 0.02, p = 0.61; affected parent-child group, 0.02, p = 0.69). Furthermore, there are no apparent transmission patterns of any of the investigated clinical features in affected parent-child pairs and no evidence for anticipation or effects of genetic loading.
Familial factors do not significantly affect eventual disease severity. However, they increase the probability of a progressive clinical course, either from onset or after a phase of relapsing remitting disease. The familial effect is more likely to reflect genetic than environmental conditions. The results are relevant for counseling patients and have implications for the design of studies seeking to identify factors that influence the natural history of the disease.
Antimicrobial helper-compounds may reverse antimicrobial resistance. Sertraline, a antidepressant drug, has been suggested as a tetracycline helper-compound. Tetracycline is the preferred ...antimicrobial for treatment of enteric diseases in pigs. This study is the first to evaluate the potency of sertraline as a tetracycline adjuvant in pigs.
Forty-eight nursery pigs were divided into four treatment groups: Tetracycline, sertraline, tetracycline/sertraline or un-medicated control. Fecal and ileal samples were obtained before treatment, 48 h and nine days after five days of treatment, respectively. Colony forming units (CFU) of tetracycline resistant coliforms in each sample (ileal or fecal) and CFU of an orally inoculated tetracycline-resistant strain of Escherichia coli were determined at each sampling point. The microbiome of fecal and ileal and samples was analyzed by sequencing of the 16S V3-V4 region.
The results did not provide evidence that sertraline in combination with tetracycline has any impact on tetracycline resistant bacteria in either fecal or ileum samples, while in the tetracycline treated group of pigs, an increase in the prevalence of a tetracycline resistant indicator strain of Escherichia coli shortly after ended five-day treatment was observed. The ileal samples obtained shortly after ended treatment showed treatment-associated changes in the composition of the microbiota in the groups of pigs treated with tetracycline (+/-) sertraline. While tetracycline treatment increased the abundance in the reads of E. coli, sertraline/tetracycline treatment led to increased abundances of Streptococcus spp. and decreased abundances of Lactobacillus spp. However, all observed differences (on CFU counts and microbiota composition) between groups shortly after treatment had diminished in less than two weeks after last treatment day.
Sertraline (+/-) tetracycline treatment did not reduce the long-term level of tetracycline-resistant bacteria in the feces or small intestine contents of piglets compared to the un-medicated control group of pigs. The result of this study reflects the importance of in vivo studies for confirmation of the antimicrobial helper-compound potential of an in vitro active compound.
Weakly interacting massive particles (WIMPs) are a leading candidate for dark matter and are expected to produce nuclear recoil (NR) events within liquid xenon time-projection chambers. We present a ...measurement of the scintillation timing characteristics of liquid xenon in the LUX dark matter detector and develop a pulse shape discriminant to be used for particle identification. To accurately measure the timing characteristics, we develop a template-fitting method to reconstruct the detection times of photons. Analyzing calibration data collected during the 2013–2016 LUX WIMP search, we provide a new measurement of the singlet-to-triplet scintillation ratio for electron recoils (ER) below 46 keV, and we make, to our knowledge, a first-ever measurement of the NR singlet-to-triplet ratio at recoil energies below 74 keV. We exploit the difference of the photon time spectra for NR and ER events by using a prompt fraction discrimination parameter, which is optimized using calibration data to have the least number of ER events that occur in a 50% NR acceptance region. We then demonstrate how this discriminant can be used in conjunction with the charge-to-light discrimination to possibly improve the signal-to-noise ratio for nuclear recoils.
To evaluate the novel tumor biomarker YKL-40 in serial serum samples from patients with American Joint Committee on Cancer (AJCC) stage I and II melanoma from the time of diagnosis and during routine ...follow-up. Macrophages, neutrophils, and cancer cells secrete YKL-40, and a high serum level has been associated with poor prognosis in patients with several cancer types.
Serum samples from 234 patients with stage I (n = 162) and II (n = 72) melanoma were analyzed for YKL-40 by enzyme-linked immunosorbent assay. Serial samples were obtained before definitive primary surgery and during follow-up.
After a median follow-up period of 66 months (range, 1 to 97 months), 41 relapses (18%) and 39 deaths (17%) were observed. Serum YKL-40 treated as an updated continuous covariate were analyzed together with the covariates sex, age, primary tumor site, ulceration, thickness, Clark level and histologic subtype in a Cox proportional hazard model. Serum YKL-40 was an independent prognostic factor of relapse-free survival (hazard ratio HR, 1.6; 95% CI, 1.1 to 2.5; P = .03) and overall survival (HR, 1.8; 95% CI, 1.2 to 2.6; P = .002) together with thickness and ulceration. The serum level of YKL-40 (dichotomized as normal or elevated) at the time of diagnosis was also an independent prognostic factor for overall survival (HR, 3.6, 95% CI, 1.7 to 7.7; P = .001).
Serum YKL-40 may be an early biomarker of relapse and survival in patients with AJCC stage I and II melanoma. Serum YKL-40 may also be useful for patient stratification and follow-up in clinical trials. Our results need confirmation in an independent study.
Restless Legs Syndrome (RLS) is characterized by uncomfortable nocturnal sensations in the legs making sedentary activities and sleep difficult, and is thus linked with psychosocial distress. Due to ...the symptomatology and neurobiology of RLS (disrupting brain iron and dopamine) it is likely that RLS associates with poorer health-related quality of life (HRQL) and depressive disorder. The objective of this study was to investigate the RLS-HRQL and the RLS-depressive disorder links in a generally healthy population that is not biased by medications.
Complete data, including the Cambridge–Hopkins RLS questionnaire, the 12-item short-form standardized health survey (SF-12), the Major Depression Inventory (MDI), body mass index, smoking status, alcohol consumption, and education were available for 24,707 participants enrolled in the Danish Blood Donor Study from May 1, 2015 to February 1, 2017. Information on quality of sleep was available for all RLS cases. T-tests and multivariable logistic regression models were applied to examine the associations of RLS and MDI scores, and the physical and mental component scores (PCS and MCS) of SF-12, respectively. Analyses were conducted separately for men and women.
RLS associated with poorer MCS and poorer PCS. Moreover, Participants with RLS were more likely to classify with depressive disorder. Poor quality of sleep was associated with depressive disorder and poorer MCS among RLS cases, and with poorer PCS in female RLS cases.
Thus, we demonstrated that RLS is associated with a significantly lower HRQL and a higher prevalence of depressive disorder among otherwise healthy individuals.
•Restless leg syndrome (RLS) is associated with increased depressive symptoms.•RLS is associated with reduced health related quality of life.•Poor quality of sleep increases the risk of these detrimental links among RLS cases.
Background
Clinical differentiation between pain mechanisms of temporomandibular joint (TMJ) arthralgia and osteoarthritis (OA) is challenging. The aims were to compare somatosensory function at the ...TMJs and conditioned pain modulation (CPM) effects between TMJ arthralgia and OA patients diagnosed clinically and based on different imaging techniques and age- and gender-matched healthy controls (
n
= 41).
Methods
Patients (
n
= 58) underwent standard clinical examination and three different TMJ imaging modalities. After each examination, they were classified into arthralgia or OA based on the findings. TMJ region somatosensory testing was performed in all participants. Z-scores were calculated for patients based on healthy reference data. CPM was tested by comparing pressure pain thresholds (PPTs) at TMJ and thenar (control) before, during and after the application of painful and nonpainful cold stimuli. Data were analyzed using analyses of variance.
Results
Somatosensory abnormalities were commonly detected in both patient groups. Assessment of somatosensory function at the TMJ revealed that arthralgia patients were less sensitive to warmth, cold and tactile stimuli than OA patients (
P
< 0.048). OA patients showed pressure hyperalgesia compared with arthralgia patients (
P
= 0.025). There was a significant CPM effect at both test sites during painful cold application in all groups (
P
< 0.001). There was no significant difference in the relative CPM effect between groups except for clinically diagnosed arthralgia patients showing reduced CPM effect compared with controls (
P
= 0.047).
Conclusions
Pain profiles including somatosensory function differed between TMJ arthralgia and OA patients although CPM effects were similar in patients and controls. Thus, different TMJ pain conditions may share common pain mechanisms but the present study for the first time also indicated that differential pain mechanisms could be involved.
The PHENIX experiement has measured the electron-positron pair mass spectrum from 0 to 8 GeV/c^2 in p+p collisions at sqrt(s)=200 GeV. The contributions from light meson decays to e^+e^- pairs have ...been determined based on measurements of hadron production cross sections by PHENIX. They account for nearly all e^+e^- pairs in the mass region below 1 GeV/c^2. The e^+e^- pair yield remaining after subtracting these contributions is dominated by semileptonic decays of charmed hadrons correlated through flavor conservation. Using the spectral shape predicted by PYTHIA, we estimate the charm production cross section to be 544 +/- 39(stat) +/- 142(syst) +/- 200(model) \mu b, which is consistent with QCD calculations and measurements of single leptons by PHENIX.
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