Gait analysis in a <i>Mecp2</i> knockout mouse model of Rett syndrome reveals early-onset and progressive motor deficits

Rett syndrome (RTT) is a genetic disorder characterized by a range of features including cognitive impairment, gait abnormalities and a reduction in purposeful hand skills. Mice harbouring knockout mutations in the &lt;i&gt;Mecp2&lt;/i&gt; gene display many RTT-like characteristics and are central to efforts to find novel therapies for the disorder. As hand stereotypies and gait abnormalities constitute major diagnostic criteria in RTT, it is clear that motor and gait-related phenotypes will be of importance in assessing preclinical therapeutic outcomes. We therefore aimed to assess gait properties over the prodromal phase in a functional knockout mouse model of RTT. In male &lt;i&gt;Mecp2&lt;/i&gt; knockout mice, we observed alterations in stride, coordination and balance parameters at 4 weeks of age, before the onset of other overt phenotypic changes as revealed by observational scoring. These data suggest that gait measures may be used as a robust and early marker of &lt;i&gt;Mecp2&lt;/i&gt;-dysfunction in future preclinical therapeutic studies

Confinement and magnetic field effect on chiral ferroelectric nematic in Grandjean-Cano wedge cells

We explore the structure and magnetic field response of edge dislocations in Grandjean-Cano wedge cells filled with chiral mixtures of the ferroelectric nematic mesogen DIO. Upon cooling, the ordering changes from paraelectric in the cholesteric phase N* to antiferroelectric in the smectic SmZ_A* and to ferroelectric in the cholesteric N_F*. Dislocations of the Burgers vector b equal the helicoidal pitch P are stable in all three phases, while dislocations with b=P/2 exist only in the N* and SmZ_A*. The b=P/2 dislocations split into pairs of {\tau}(-1/2) {\lambda}(+1/2) disclinations, while the thick dislocations b=P are pairs of nonsingular {\lambda}(-1/2) {\lambda}(+1/2) disclinations. The polar order makes the {\tau}(-1/2) disclinations unstable in the N_F* phase, as they should be connected to singular walls in the polarization field. We propose a model of transformation of the composite {\tau}(-1/2) line-wall defect into a nonsingular {\lambda}(-1/2) disclination, which is paired up with a {\lambda}(+1/2) line to form a b=P dislocation. The SmZ_A* behavior in the in-plane magnetic field is different from that of the N_F* and N*: the dislocations show no zigzag instability, and the pitch remains unchanged in the magnetic fields up to 1 T. The behavior is associated with the finite compressibility of smectic layers.Comment: 28 pages, 10 figures, 1 tabl

Nodeless multiband superconductivity in stoichiometric single-crystalline CaKFe4As4

Measurements of the London penetration depth Δλ(T) and tunneling conductance in single crystals of the recently discovered stoichiometric iron-based superconductor CaKFe4As4 (CaK1144) show nodeless, two-effective-gap superconductivity with a larger gap of about 6-10 meV and a smaller gap of about 1-4 meV. Having a critical temperature Tc,onset≈35.8 K, this material behaves similar to slightly overdoped (Ba1-xKx)Fe2As2 (e.g., x=0.54,Tc≈34 K), a known multigap s± superconductor. We conclude that the superconducting behavior of stoichiometric CaK1144 demonstrates that two-gap s± superconductivity is an essential property of high-temperature superconductivity in iron-based superconductors, independent of the degree of substitutional disorderWe thank A. Gurevich, D. D. Johnson, A. Kaminski, V. G. Kogan, and Lin-Lin Wang for useful discussions. This work was supported by the US Department of Energy (DOE), Office of Science, Basic Energy Sciences, Materials Science and Engineering Division. Ames Laboratory is operated for the US DOE by Iowa State University under Contract DE-AC02-07CH11358. The work in Madrid was supported by the Spanish Ministry of Economy and Competitiveness (FIS2014-54498-R and MDM-2014-0377), by the Comunidad de Madrid through program Nanofrontmag-CM (S2013/MIT-2850) by Axa Research Fund, FP7-PEOPLE-2013-CIG 618321, and the European Research Council (Grant Agreement No. 679080). Madrid's group also acknowledges SEGAINVEX-UAM. W.R.M. was funded by the Gordon and Betty Moore Foundation's EPiQS Initiative through Grant GBMF441

The Impact of Routine Vaccinations on Alzheimer\u27s Disease Risk in Persons 65 Years and Older: A Claims-Based Cohort Study using Propensity Score Matching

Background: Accumulating evidence suggests that adult vaccinations can reduce the risk of developing Alzheimer’s disease (AD) and Alzheimer’s disease related dementias. Objective: To compare the risk for developing AD between adults with and without prior vaccination against tetanus and diphtheria, with or without pertussis (Tdap/Td); herpes zoster (HZ); or pneumococcus. Methods: A retrospective cohort study was performed using Optum’s de-identified Clinformatics® Data Mart Database. Included patients were free of dementia during a 2-year look-back period and were≥65 years old by the start of the 8-year follow-up period. We compared two similar cohorts identified using propensity score matching (PSM), one vaccinated and another unvaccinated, with Tdap/Td, HZ, or pneumococcal vaccines. We calculated the relative risk (RR) and absolute risk reduction (ARR) for developing AD. Results: For the Tdap/Td vaccine, 7.2% (n = 8,370) of vaccinated patients and 10.2% (n = 11,857) of unvaccinated patients developed AD during follow-up; the RR was 0.70 (95% CI, 0.68–0.72) and ARR was 0.03 (95% CI, 0.02–0.03). For the HZ vaccine, 8.1% (n = 16,106) of vaccinated patients and 10.7% (n = 21,417) of unvaccinated patients developed AD during follow-up; the RR was 0.75 (95% CI, 0.73–0.76) and ARR was 0.02 (95% CI, 0.02–0.02). For the pneumococcal vaccine, 7.92% (n = 20,583) of vaccinated patients and 10.9% (n = 28,558) of unvaccinated patients developed AD during follow-up; the RR was 0.73 (95% CI, 0.71–0.74) and ARR was 0.02 (95% CI, 0.02–0.03). Conclusion: Several vaccinations, including Tdap/Td, HZ, and pneumococcal, are associated with a reduced risk for developing AD

Atud Gabbro-Diorite Complex: Glimpse of the Cryogenian Mixing, Assimilation, Storage, and Homogenization Zone beneath the Eastern Desert of Egypt

We analysed gabbroic and dioritic rocks from the Atud igneous complex in the Eastern Desert of Egypt to understand better the formation of juvenile continental crust of the Arabian–Nubian Shield. Our results show that the rocks are the same age (U–Pb zircon ages of 694.5 ± 2.1 Ma for two diorites and 695.3 ± 3.4 Ma for one gabbronorite). These are partial melts of the mantle and related fractionates (εNd₆₉₀ = +4.2 to +7.3, ⁸⁷Sr/⁸⁶Sr_i = 0.70246–0.70268, zircon δ¹⁸O ∼ +5‰). Trace element patterns indicate that Atud magmas formed above a subduction zone as part of a large and long-lived (c. 60 myr) convergent margin. Atud complex igneous rocks belong to a larger metagabbro–epidiorite–diorite complex that formed as a deep crustal mush into which new pulses of mafic magma were periodically emplaced, incorporated and evolved. The petrological evolution can be explained by fractional crystallization of mafic magma plus variable plagioclase accumulation in a mid- to lower crustal MASH zone. The Atud igneous complex shows that mantle partial melting and fractional crystallization and plagioclase accumulation were important for Cryogenian crust formation in this part of the Arabian–Nubian Shield

Risk of Alzheimer\u27s Disease Following Influenza Vaccination: A Claims-Based Cohort Study Using Propensity Score Matching

BACKGROUND: Prior studies have found a reduced risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions. However, the effect of influenza vaccination on Alzheimer\u27s disease (AD) risk in a general cohort of older US adults has not been characterized. OBJECTIVE: To compare the risk of incident AD between patients with and without prior influenza vaccination in a large US claims database. METHODS: Deidentified claims data spanning September 1, 2009 through August 31, 2019 were used. Eligible patients were free of dementia during the 6-year look-back period and≥65 years old by the start of follow-up. Propensity-score matching (PSM) was used to create flu-vaccinated and flu-unvaccinated cohorts with similar baseline demographics, medication usage, and comorbidities. Relative risk (RR) and absolute risk reduction (ARR) were estimated to assess the effect of influenza vaccination on AD risk during the 4-year follow-up. RESULTS: From the unmatched sample of eligible patients (n = 2,356,479), PSM produced a sample of 935,887 flu-vaccinated-unvaccinated matched pairs. The matched sample was 73.7 (SD, 8.7) years of age and 56.9% female, with median follow-up of 46 (IQR, 29-48) months; 5.1% (n = 47,889) of the flu-vaccinated patients and 8.5% (n = 79,630) of the flu-unvaccinated patients developed AD during follow-up. The RR was 0.60 (95% CI, 0.59-0.61) and ARR was 0.034 (95% CI, 0.033-0.035), corresponding to a number needed to treat of 29.4. CONCLUSION: This study demonstrates that influenza vaccination is associated with reduced AD risk in a nationwide sample of US adults aged 65 and older

Duty Hour Reform and the Outcomes of Patients Treated by New Surgeons

Despite concerns that duty hour reform might adversely affect the performance of new surgeons, this national study found no impact on patient outcomes, including 30-day mortality rates, failure-to-rescue, length of stay, and use of intensive care units. These findings should allay fears that reduced work hours during residency would produce surgeons less prepared for practice than their more experienced colleagues

Inflammatory myofibroblastic tumor of epididymis: a case report and review of literature

Background Epididymal inflammatory myofibroblastic tumor, also known by various other synonyms is a rare benign disease. Only eight cases have been reported to date. The most common presentation is a scrotal mass of variable duration. For a scrotal mass it is difficult to distinguish a benign or malignant etiology, in addition to the origin whether from testis or epididymis. As a result the definitive diagnosis can only be established by surgical exploration. Case presentation We report the ninth case of epididymal IMT who based on clinical and radiological findings underwent radical orchidectomy, with the histology suggestive of inflammatory myofibroblastic tumor. At 4 years follow up the patient is free of disease recurrence. Conclusion IMT though rare should be considered in the differential diagnosis of epididymal mass. Clinically it is often difficult to distinguish the origin of mass and even though the disease has benign nature and course it is crucial to counsel patients for orchidectomy as definitive diagnosis is established on surgical exploration

Evaluation of the performance of high phosphorous with germanium codoped multimode optical fiber for use as a radiation sensor at low dose rates

We propose a GeO(2)-P(2)O(5)-codoped step index multimode (SIMM) fiber having a core diameter of around 50 mu m with numerical aperture of around 0.21-0.22. The proposed SIMM fiber shows excellent linear radiation response behavior with sensitivity of around 0.69-0.97 dB/m/100 rad at a 505 nm wavelength within the dose rate range of 10-100 rad/h, as well as very low recovery at room temperature using a (60)Co gamma radiation source. This enables its practical application in fiber optic personal dosimeters for measurement of low dose gamma radiation. (C) 2011 Optical Society of Americ

Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer Via Downregulation of Nuclear p65 and HIF-1 alpha

Piceatannol (PIC) is known to have anticancer activity, which has been attributed to its ability to block the proliferation of cancer cells via suppression of the NF-kB signaling pathway. However, its effect on hypoxia-inducible factor (HIF) is not well known in cancer. In this study, PIC was loaded into bovine serum albumin (BSA) by desolvation method as PIC-BSA nanoparticles (NPs). These PIC-BSA nanoparticles were assessed for in vitro cytotoxicity, migration, invasion, and colony formation studies and levels of p65 and HIF-1α. Our results indicate that PIC-BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1α in colon cancer cells as compared to free PIC. We also observed a significant reduction in inflammation induced by chemical colitis in mice by PIC-BSA NPs. Furthermore, a significant reduction in tumor size and number of colon tumors was also observed in the murine model of colitis-associated colorectal cancer, when treated with PIC-BSA NPs as compared to free PIC. The overall results indicate that PIC, when formulated as PIC-BSA NPs, enhances its therpautice potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possiable human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients