•Hair-cell and auditory-nerve loss were quantified in 20 “normal” humans 0–86 yrs.•Age-related loss of nerve fibers exceeded the rate of hair cell loss by almost 3:1.•In 10/16 ears over 50 yrs, >50% ...of auditory-nerve connections had degenerated.•This neural degeneration degrades hearing ability without affecting the audiogram.
The noise-induced and age-related loss of synaptic connections between auditory-nerve fibers and cochlear hair cells is well-established from histopathology in several mammalian species; however, its prevalence in humans, as inferred from electrophysiological measures, remains controversial. Here we look for cochlear neuropathy in a temporal-bone study of “normal-aging” humans, using autopsy material from 20 subjects aged 0–89 yrs, with no history of otologic disease. Cochleas were immunostained to allow accurate quantification of surviving hair cells in the organ Corti and peripheral axons of auditory-nerve fibers. Mean loss of outer hair cells was 30–40% throughout the audiometric frequency range (0.25–8.0 kHz) in subjects over 60 yrs, with even greater losses at both apical (low-frequency) and basal (high-frequency) ends. In contrast, mean inner hair cell loss across audiometric frequencies was rarely >15%, at any age. Neural loss greatly exceeded inner hair cell loss, with 7/11 subjects over 60 yrs showing >60% loss of peripheral axons re the youngest subjects, and with the age-related slope of axonal loss outstripping the age-related loss of inner hair cells by almost 3:1. The results suggest that a large number of auditory neurons in the aging ear are disconnected from their hair cell targets. This primary neural degeneration would not affect the audiogram, but likely contributes to age-related hearing impairment, especially in noisy environments. Thus, therapies designed to regrow peripheral axons could provide clinically meaningful improvement in the aged ear.
Summary
Background
Whether 10‐day or 14‐day sequential therapy is superior to 14‐day triple therapy in the first‐line treatment of Helicobacter pylori remains controversial.
Aim
To compare the ...efficacy of 10‐day or 14‐day sequential therapy vs. 14‐day triple therapy.
Methods
Randomised controlled trials (RCTs) comparing 10‐day or 14‐day sequential therapy and 14‐day triple therapy as first‐line treatment in adults were searched from the PubMed and Cochrane databases from 2000 to October 2015. s from international annual conferences were also searched. The primary and secondary outcomes were the eradication rate according to the intention‐to‐treat analysis and adverse effects, respectively.
Results
Of the 109 articles identified, 13 RCTs including 2749 patients in the sequential therapy group and 2424 patients in the 14‐day triple therapy group were eligible. Overall, sequential therapy for 10 or 14 days was not significantly superior to 14‐day triple therapy Risk ratio (RR) 1.04, 95% confidence interval (CI) 0.99–1.08, P = 0.145. However, there was significant heterogeneity (I2 = 57.6%, P = 0.005). In the subgroup analysis of four trials, we found that 14‐day sequential therapy was significantly more effective than 14‐day triple therapy (RR: 1.09, 95% CI: 1.04–1.16, P = 0.002), and there was no significant heterogeneity (I2 = 0%, P = 0.624) in this comparison. Sequential therapy given for 10 days was not superior to 14‐day triple therapy (RR: 1.03, 95% CI: 0.98–1.09, P = 0.207). There was no significant difference in the risk of adverse effects.
Conclusion
Sequential therapy given for 14 days, but not 10 days, was more effective than 14‐day triple therapy as first‐line treatment.
South Korea is experiencing the largest outbreak of Middle East respiratory syndrome coronavirus infections outside the Arabian Peninsula, with 166 laboratory-confirmed cases, including 24 deaths up ...to 19 June 2015. We estimated that the mean incubation period was 6.7 days and the mean serial interval 12.6 days. We found it unlikely that infectiousness precedes symptom onset. Based on currently available data, we predict an overall case fatality risk of 21% (95% credible interval: 14–31).
Arbuscular mycorrhizal fungi (AMF) is an effective way to remove heavy metals’ inhibition on plants, however, few relevant research attempts have been made to determine the contribution of AMF to the ...physiological and biochemical changes related to the enhanced copper tolerance of Phragmites australis under metal‐stressed conditions.
In this study, the effects of AMF inoculation on P. australis under different concentrations of copper stress were investigated according to the changes in the parameters related to growth and development, and photosynthetic charateristics. Then, differentially expressed proteins (DEPs) were evaluated by the Isobaric Tag for Relative and Absolute Quantification (iTRAQ) system, which could accurately quantify the DEPs by measuring peak intensities of reporter ions in tandem mass spectrometry (MS/MS) spectra.
It was found that AMF inoculation may relieve the photosynthesis inhibition caused by copper stress on P. australis and thus promote growth. Proteomic analysis results showed that under copper stress, the inoculation of R. irregularis resulted in a total of 459 differently‐expressed proteins (200 up‐regulated and 259 down‐regulated) in root buds. In addition, the photosynthetic changes caused by AMF inoculation mainly involve the up‐regulated expression of transmembrane protein–pigment complexes CP43 (photosystem II) and FNR (ferredoxin‐NADP+ oxidoreductase related to photosynthetic electron transport).
These results indicate that AMF could effectively improve the growth and physiological activity of P. australis under copper stress, and thus provides a new direction and instructive evidence for determining the mechanisms by which AMF inoculation enhances the copper tolerance of plants.
Arbuscular mycorrhizal fungi could effectively improve the growth and physiological activity of P. australis under copper stress, and thus provides a new direction and instructive evidence for determining the mechanisms by which AMF inoculation enhances the copper tolerance of plants.
Primary cosmic-ray elemental spectra have been measured with the balloon-borne Cosmic Ray Energetics And Mass (CREAM) experiment since 2004. The third CREAM payload (CREAM-III) flew for 29 days ...during the 2007-2008 Antarctic season. Energies of incident particles above 1 TeV are measured with a calorimeter. Individual elements are clearly separated with a charge resolution of ∼0.12 e (in charge units) and ∼0.14 e for protons and helium nuclei, respectively, using two layers of silicon charge detectors. The measured proton and helium energy spectra at the top of the atmosphere are harder than other existing measurements at a few tens of GeV. The relative abundance of protons to helium nuclei is 9.53 0.03 for the range of 1 TeV/n to 63 TeV/n. This ratio is considerably smaller than other measurements at a few tens of GeV/n. The spectra become softer above ∼20 TeV. However, our statistical uncertainties are large at these energies and more data are needed.
Summary
Background
Aspirin increases the risk of gastrointestinal bleeding.
Aim
To investigate the risk of lower gastrointestinal bleeding (LGIB) in aspirin users.
Methods
Low‐dose (75‐325 mg daily) ...aspirin users and controls matched by age, gender and enrollment time in a 1:5 ratio were selected from 1 million randomly sampled subjects in the National Health Insurance Research Database of Taiwan. Cox proportional hazard regression models were developed to evaluate the predictors of LGIB with adjustments for age, gender, comorbidities including coronary artery disease, ischaemic stroke, diabetes, hypertension, chronic kidney disease, liver cirrhosis, chronic obstructive pulmonary disease, dyslipidemia, uncomplicated peptic ulcer disease, history of peptic ulcer bleeding, and concomitant use of clopidogrel, ticlopidine, warfarin, nonsteroidal anti‐inflammatory drugs (NSAIDs), cyclooxygenase‐2 inhibitors, steroids, proton pump inhibitors (PPIs), histamine‐2 receptor antagonists (H2RAs), nitrates, alendronate, selective serotonin reuptake inhibitors (SSRIs) and calcium channel blockers.
Results
A total of 53 805 aspirin users and 269 025 controls were included. Aspirin group had a higher incidence of LGIB within 1 year than control group (0.20% vs 0.06%, P<.0001). Aspirin (hazard ratio HR: 2.75, 95% confidence interval CI: 2.06‐3.65), NSAIDs (HR: 8.61, 95% CI: 3.28‐22.58), steroids (HR: 10.50, 95% CI: 1.98‐55.57), SSRIs (HR: 11.71, 95% CI: 1.40‐97.94), PPIs (HR: 8.47, 95% CI: 2.26‐31.71), and H2RAs (HR: 10.83, 95% CI: 2.98‐39.33) were significantly associated with LGIB.
Conclusions
The risk of LGIB was higher in low‐dose aspirin users than in aspirin nonusers in this nationwide cohort. Low‐dose aspirin, NSAIDs, steroids, SSRIs, PPIs and H2RAs were independent risk factors for LGIB.
Linked ContentThis article is linked to Taha and Chen et al papers. To view these articles visit https://doi.org/10.1111/apt.14114 and https://doi.org/10.1111/apt.14138.
Two-dimensional (2D) materials have been studied extensively as monolayers, vertical or lateral heterostructures. To achieve functionalization, monolayers are often patterned using soft lithography ...and selectively decorated with molecules. Here we demonstrate the growth of a family of 2D materials that are intrinsically patterned. We demonstrate that a monolayer of PtSe
can be grown on a Pt substrate in the form of a triangular pattern of alternating 1T and 1H phases. Moreover, we show that, in a monolayer of CuSe grown on a Cu substrate, strain relaxation leads to periodic patterns of triangular nanopores with uniform size. Adsorption of different species at preferred pattern sites is also achieved, demonstrating that these materials can serve as templates for selective self-assembly of molecules or nanoclusters, as well as for the functionalization of the same substrate with two different species.
Despite the advances in the diagnosis and treatment of breast cancer, breast cancers still cause significant mortality. For some patients, especially those with triple-negative breast cancer, current ...treatments continue to be limited and ineffective. Therefore, there remains an unmet need for a novel therapeutic approach. One potential strategy is to target the altered metabolic state that is rewired by oncogenic transformation. Specifically, this rewiring may render certain outside nutrients indispensable. To identify such a nutrient, we performed a nutrigenetic screen by removing individual amino acids to identify possible addictions across a panel of breast cancer cells. This screen revealed that cystine deprivation triggered rapid programmed necrosis, but not apoptosis, in the basal-type breast cancer cells mostly seen in TNBC tumors. In contrast, luminal-type breast cancer cells are cystine-independent and exhibit little death during cystine deprivation. The cystine addiction phenotype is associated with a higher level of cystine-deprivation signatures noted in the basal type breast cancer cells and tumors. We found that the cystine-addicted breast cancer cells and tumors have strong activation of TNFα and MEKK4-p38-Noxa pathways that render them susceptible to cystine deprivation-induced necrosis. Consistent with this model, silencing of TNFα and MEKK4 dramatically reduces cystine-deprived death. In addition, the cystine addiction phenotype can be abrogated in the cystine-addictive cells by miR-200c, which converts the mesenchymal-like cells to adopt epithelial features. Conversely, the introduction of inducers of epithelial-mesenchymal transition (EMT) in cystine-independent breast cancer cells conferred the cystine-addiction phenotype by modulating the signaling components of cystine addiction. Together, our data reveal that cystine-addiction is associated with EMT in breast cancer during tumor progression. These findings provide the genetic and mechanistic basis to explain how cystine deprivation triggers necrosis by activating pre-existing oncogenic pathways in cystine-addicted TNBC with prominent mesenchymal features.
Trials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently developed devices, and earlier ...intervention improve outcomes.
We randomly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever or to continue receiving alteplase alone. All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The coprimary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3). Secondary outcomes included the functional score on the modified Rankin scale at 90 days.
The trial was stopped early because of efficacy after 70 patients had undergone randomization (35 patients in each group). The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group (median, 100% vs. 37%; P<0.001). Endovascular therapy, initiated at a median of 210 minutes after the onset of stroke, increased early neurologic improvement at 3 days (80% vs. 37%, P=0.002) and improved the functional outcome at 90 days, with more patients achieving functional independence (score of 0 to 2 on the modified Rankin scale, 71% vs. 40%; P=0.01). There were no significant differences in rates of death or symptomatic intracerebral hemorrhage.
In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome. (Funded by the Australian National Health and Medical Research Council and others; EXTEND-IA ClinicalTrials.gov number, NCT01492725, and Australian New Zealand Clinical Trials Registry number, ACTRN12611000969965.).
We report a B-mode power spectrum measurement from the cosmic microwave background (CMB) polarization anisotropy observations made using the SPTpol instrument on the South Pole Telescope. This work ...uses 500 deg2 of SPTpol data, a five-fold increase over the last SPTpol B-mode release. As a result, the bandpower uncertainties have been reduced by more than a factor of two, and the measurement extends to lower multipoles: 52 < ℓ < 2301 . Data from both 95 and 150 GHz are used, allowing for three cross-spectra: 95 GHz × 95 GHz , 95 GHz × 150 GHz , and 150 GHz × 150 GHz . B -mode power is detected at very high significance; we find P ( B B < 0 ) = 5.8 × 10−71, corresponding to a 18.1σ detection of power. With a prior on the galactic dust from Planck, WMAP and BICEP2/Keck observations, the SPTpol B-mode data can be used to set an upper limit on the tensor-to-scalar ratio, r < 0.44 at 95% confidence (the expected 1σ constraint on r given the measurement uncertainties is 0.22). We find the measured B-mode power is consistent with the Planck best-fit Λ CDM model predictions. Scaling the predicted lensing B-mode power in this model by a factor Alens, the data prefer Alens = 1.17 ± 0.13 . These data are currently the most precise measurements of B-mode power at ℓ > 320.
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