Expression of mTOR in normal and pathological conditions.

The mechanistic/mammalian target of rapamycin (mTOR), a protein discovered in 1991, integrates a complex pathway with a key role in maintaining cellular homeostasis. By comprising two functionally distinct complexes, mTOR complex 1 (mTORC1) and mTORC2, it is a central cellular hub that integrates intra- and extracellular signals of energy, nutrient, and hormone availability, modulating the molecular responses to acquire a homeostatic state through the regulation of anabolic and catabolic processes. Accordingly, dysregulation of mTOR pathway has been implicated in a variety of human diseases. While major advances have been made regarding the regulators and effectors of mTOR signaling pathway, insights into the regulation of mTOR gene expression are beginning to emerge. Here, we present the current available data regarding the mTOR expression regulation at the level of transcription, translation and mRNA stability and systematize the current knowledge about the fluctuations of mTOR expression observed in several diseases, both cancerous and non-cancerous. In addition, we discuss whether mTOR expression changes can be used as a biomarker for diagnosis, disease progression, prognosis and/or response to therapeutics. We believe that our study will contribute for the implementation of new disease biomarkers based on mTOR as it gives an exhaustive perspective about the regulation of mTOR gene expression in both normal and pathological conditions.

Search for 70 µeV Dark Photon Dark Matter with a Dielectrically Loaded Multiwavelength Microwave Cavity.

Microwave cavities have been deployed to search for bosonic dark matter candidates with masses of a few µeV. However, the sensitivity of these cavity detectors is limited by their volume, and the traditionally employed half-wavelength cavities suffer from a significant volume reduction at higher masses. Axion dark matter experiment (ADMX)-Orpheus mitigates this issue by operating a tunable, dielectrically loaded cavity at a higher-order mode, which allows the detection volume to remain large. The ADMX-Orpheus inaugural run excludes dark photon dark matter with kinetic mixing angle χ>10^{-13} between 65.5 µeV (15.8 GHz) and 69.3 µeV (16.8 GHz), marking the highest-frequency tunable microwave cavity dark matter search to date.

Search for Invisible Axion Dark Matter in the 3.3-4.2 µeV Mass Range.

We report the results from a haloscope search for axion dark matter in the 3.3-4.2 µeV mass range. This search excludes the axion-photon coupling predicted by one of the benchmark models of "invisible" axion dark matter, the Kim-Shifman-Vainshtein-Zakharov model. This sensitivity is achieved using a large-volume cavity, a superconducting magnet, an ultra low noise Josephson parametric amplifier, and sub-Kelvin temperatures. The validity of our detection procedure is ensured by injecting and detecting blind synthetic axion signals.

Probing Gluon Spin-Momentum Correlations in Transversely Polarized Protons through Midrapidity Isolated Direct Photons in p

Studying spin-momentum correlations in hadronic collisions offers a glimpse into a three-dimensional picture of proton structure. The transverse single-spin asymmetry for midrapidity isolated direct photons in p^{↑}+p collisions at sqrt[s]=200 GeV is measured with the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). Because direct photons in particular are produced from the hard scattering and do not interact via the strong force, this measurement is a clean probe of initial-state spin-momentum correlations inside the proton and is in particular sensitive to gluon interference effects within the proton. This is the first time direct photons have been used as a probe of spin-momentum correlations at RHIC. The uncertainties on the results are a 50-fold improvement with respect to those of the one prior measurement for the same observable, from the Fermilab E704 experiment. These results constrain gluon spin-momentum correlations in transversely polarized protons.

Extended Search for the Invisible Axion with the Axion Dark Matter Experiment.

This Letter reports on a cavity haloscope search for dark matter axions in the Galactic halo in the mass range 2.81-3.31 µeV. This search utilizes the combination of a low-noise Josephson parametric amplifier and a large-cavity haloscope to achieve unprecedented sensitivity across this mass range. This search excludes the full range of axion-photon coupling values predicted in benchmark models of the invisible axion that solve the strong CP problem of quantum chromodynamics.

Nuclear Dependence of the Transverse Single-Spin Asymmetry in the Production of Charged Hadrons at Forward Rapidity in Polarized p+p, p+Al, and p+Au Collisions at sqrt[s_{NN}]=200 GeV.

We report on the nuclear dependence of transverse single-spin asymmetries (TSSAs) in the production of positively charged hadrons in polarized p^{↑}+p, p^{↑}+Al, and p^{↑}+Au collisions at sqrt[s_{NN}]=200 GeV. The measurements have been performed at forward rapidity (1.4<η<2.4) over the range of transverse momentum (1.8

Piezoelectrically Tuned Multimode Cavity Search for Axion Dark Matter.

The µeV axion is a well-motivated extension to the standard model. The Axion Dark Matter eXperiment (ADMX) collaboration seeks to discover this particle by looking for the resonant conversion of dark-matter axions to microwave photons in a strong magnetic field. In this Letter, we report results from a pathfinder experiment, the ADMX "Sidecar," which is designed to pave the way for future, higher mass, searches. This testbed experiment lives inside of and operates in tandem with the main ADMX experiment. The Sidecar experiment excludes masses in three widely spaced frequency ranges (4202-4249, 5086-5799, and 7173-7203 MHz). In addition, Sidecar demonstrates the successful use of a piezoelectric actuator for cavity tuning. Finally, this publication is the first to report data measured using both the TM_{010} and TM_{020} modes.

Pseudorapidity Dependence of Particle Production and Elliptic Flow in Asymmetric Nuclear Collisions of p+Al, p+Au, d+Au, and

Asymmetric nuclear collisions of p+Al, p+Au, d+Au, and ^{3}He+Au at sqrt[s_{NN}]=200 GeV provide an excellent laboratory for understanding particle production, as well as exploring interactions among these particles after their initial creation in the collision. We present measurements of charged hadron production dN_{ch}/dη in all such collision systems over a broad pseudorapidity range and as a function of collision multiplicity. A simple wounded quark model is remarkably successful at describing the full data set. We also measure the elliptic flow v_{2} over a similarly broad pseudorapidity range. These measurements provide key constraints on models of particle emission and their translation into flow.

Measurements of Multiparticle Correlations in d+Au Collisions at 200, 62.4, 39, and 19.6 GeV and p+Au Collisions at 200 GeV and Implications for Collective Behavior.

Recently, multiparticle-correlation measurements of relativistic p/d/^{3}He+Au, p+Pb, and even p+p collisions show surprising collective signatures. Here, we present beam-energy-scan measurements of two-, four-, and six-particle angular correlations in d+Au collisions at sqrt[s_{NN}]=200, 62.4, 39, and 19.6 GeV. We also present measurements of two- and four-particle angular correlations in p+Au collisions at sqrt[s_{NN}]=200 GeV. We find the four-particle cumulant to be real valued for d+Au collisions at all four energies. We also find that the four-particle cumulant in p+Au has the opposite sign as that in d+Au. Further, we find that the six-particle cumulant agrees with the four-particle cumulant in d+Au collisions at 200 GeV, indicating that nonflow effects are subdominant. These observations provide strong evidence that the correlations originate from the initial geometric configuration, which is then translated into the momentum distribution for all particles, commonly referred to as collectivity.

Nuclear Dependence of the Transverse-Single-Spin Asymmetry for Forward Neutron Production in Polarized p+A Collisions at sqrt[s_{NN}]=200 GeV.

During 2015, the Relativistic Heavy Ion Collider (RHIC) provided collisions of transversely polarized protons with Au and Al nuclei for the first time, enabling the exploration of transverse-single-spin asymmetries with heavy nuclei. Large single-spin asymmetries in very forward neutron production have been previously observed in transversely polarized p+p collisions at RHIC, and the existing theoretical framework that was successful in describing the single-spin asymmetry in p+p collisions predicts only a moderate atomic-mass-number (A) dependence. In contrast, the asymmetries observed at RHIC in p+A collisions showed a surprisingly strong A dependence in inclusive forward neutron production. The observed asymmetry in p+Al collisions is much smaller, while the asymmetry in p+Au collisions is a factor of 3 larger in absolute value and of opposite sign. The interplay of different neutron production mechanisms is discussed as a possible explanation of the observed A dependence.

Efficacy of aquatic vs land-based therapy for pain management in women with fibromyalgia: a randomised controlled trial.

OBJECTIVE: To determine the efficacy of two physiotherapeutic interventions - aquatic therapy (AT) and land-based therapy (LBT) - for reducing pain in women with fibromyalgia. DESIGN: Single-blind, randomised controlled, equivalence trial. SETTING: Fibromyalgia, Chronic Fatigue Syndrome and Multiple Chemical Sensitivity Association in A Coruña, Spain. PARTICIPANTS: Forty women with fibromyalgia were assigned at random in a 1:1 manner to two groups: AT (n = 20) and LBT (n = 20). INTERVENTIONS: Two therapeutic exercise programmes, with 60-min sessions, were undertaken three times per week for 12 weeks. Sessions were carried out in groups by a trained physiotherapist. OUTCOME: The primary outcome was pain intensity (visual analogue scale). The secondary outcomes were pressure pain threshold (algometer), quality of life (Revised Fibromyalgia Impact Questionnaire), sleep quality (Pittsburgh Sleep Quality Index), fatigue (Multidimensional Fatigue Inventory) and physical ability (6-Minute Walk Test). Patients were evaluated at baseline, 12 weeks (post-treatment) and 18 weeks (follow-up). The statistical analysis was per-protocol. P < 0.05 was considered to indicate significance. Effect size was calculated. RESULTS: The mean age was 50 [standard deviation (SD) 9] years, with median body mass index of 27 [interquartile range (IQR) 25-30] kg/m2 and median symptom duration of 11 (IQR 6-15) years. No differences were observed between the groups post-treatment, but differences in favour of AT were found in pain intensity [2.7 (IQR 1.5-4.9) vs 5.5 (IQR 3.3-7.6); p= 0.023; large effect, Cohen's d= 0.8; 95% confidence interval (CI) 0.1-1.5] and sleep quality [12.0 (IQR 7.3-15.3) vs 15.0 (IQR 13.0-17.0); p= 0.030; large effect, Cohen's d= 0.8; 95% CI 0.1-1.5] at follow-up. CONCLUSIONS: The results suggest that AT is better than LBT for reducing pain intensity and improving sleep quality after 6 weeks of follow-up. AT may be a good treatment option for women with fibromyalgia. CLINICAL TRIALS REGISTRATION NUMBER: ClinicalTrials.gov NCT02695875 CONTRIBUTION OF THE PAPER.

Dark matter axion search using a Josephson Traveling wave parametric amplifier.

We describe the first implementation of a Josephson Traveling Wave Parametric Amplifier (JTWPA) in an axion dark matter search. The operation of the JTWPA for a period of about two weeks achieved sensitivity to axion-like particle dark matter with axion-photon couplings above 10-13 Ge V-1 over a narrow range of axion masses centered around 19.84 µeV by tuning the resonant frequency of the cavity over the frequency range of 4796.7-4799.5 MHz. The JTWPA was operated in the insert of the axion dark matter experiment as part of an independent receiver chain that was attached to a 0.56-l cavity. The ability of the JTWPA to deliver high gain over a wide (3 GHz) bandwidth has engendered interest from those aiming to perform broadband axion searches, a longstanding goal in this field.

[Short bowel syndrome in children: a diagnosis and management update]. / Síndrome de intestino corto en niños: actualidades en su diagnóstico y manejo.

Short bowel syndrome (SBS) refers to the sum of the functional alterations that are the result of a critical reduction in the length of the intestine, which in the absence of adequate treatment, presents as chronic diarrhea, chronic dehydration, malnutrition, weight loss, nutriment and electrolyte deficiency, along with a failure to grow that is present with greater frequency during the neonatal period. The aim was to carry out a review of the literature encompassing the definition and the most frequent causes of SBS, together with an understanding of its physiopathology, prognostic factors, and treatment. An Internet search of PubMed articles was carried out for the existing information published over the last 20 years on SBS in children, using the keywords "short bowel syndrome". From a total of 784 potential articles, 82 articles were chosen for the literature review. The treatment of patients presenting with SBS is quite a challenge and therefore it is necessary to establish multidisciplinary management with a focus on maintaining optimal nutritional support that covers the necessities of growth and development and at the same time provides a maximum reduction of short, medium, and long-term complications. The diagnosis and treatment of a child with SBS require a team of professionals that are experts in gastroenterologic, pediatric, and nutritional management. The outcome for the child will be directly related to opportune management, as well as to the length of the intestinal resection and the presence or absence of the ileocecal valve.

Axion Dark Matter Experiment: Detailed design and operations.

Axion dark matter experiment ultra-low noise haloscope technology has enabled the successful completion of two science runs (1A and 1B) that looked for dark matter axions in the 2.66-3.1 µeV mass range with Dine-Fischler-Srednicki-Zhitnisky sensitivity [Du et al., Phys. Rev. Lett. 120, 151301 (2018) and Braine et al., Phys. Rev. Lett. 124, 101303 (2020)]. Therefore, it is the most sensitive axion search experiment to date in this mass range. We discuss the technological advances made in the last several years to achieve this sensitivity, which includes the implementation of components, such as the state-of-the-art quantum-noise-limited amplifiers and a dilution refrigerator. Furthermore, we demonstrate the use of a frequency tunable microstrip superconducting quantum interference device amplifier in run 1A, and a Josephson parametric amplifier in run 1B, along with novel analysis tools that characterize the system noise temperature.

A Linear Model to Describe Branching and Allometry in Root Architecture.

Root architecture is a complex structure that comprises multiple traits of the root phenotype. Novel platforms and models have been developed to better understand root architecture. In this methods paper, we introduce a novel allometric model, named rhizochron index (m), which describes lateral root (LR) branching and elongation patterns across the primary root (PR). To test our model, we obtained data from 16 natural accessions of Arabidopsis thaliana at three stages of early root development to measure conventional traits of root architecture (e.g., PR and LR length), and extracted the rhizochron index (m). In addition, we tested previously published datasets to assess the utility of the rhizochron index (m) to distinguish mutants and environmental effects on root architecture. Our results indicate that rhizochron index (m) is useful to distinguish the natural variations of root architecture between A. thaliana accessions, but not across early stages of root development. Correlation analyses in these accessions showed that m is a novel trait that partially captures information from other root architecture traits such as total lateral root length, and the ratio between lateral root and primary root lengths. Moreover, we found that the rhizochron index was useful to distinguish ABA effect on root architecture, as well as the mutant pho1 phenotype. We propose the rhizochron index (m) as a new feature of the root architectural system to be considered, in addition to conventional traits in future investigations.

Divergent Axial Carpal Dislocation and Its Pathomechanics.

Background Axial carpal dislocations and fracture dislocations are 1.4 to 2.08% of all the fractures and dislocations of the wrist. These injuries are caused by high-energy blast or compression mechanisms. Only 11 cases of axial-radial-ulnar (ARU) fracture dislocations have been described in the literature. Case Description We describe a case with a traumatic transtrapezoid, peritrapezium, transhamate, peripisiform ARU in a patient with acute compartment syndrome, traumatic transverse flexor retinaculum (TFR) rupture, and radial nerve palsy. Literature Review The ARU fractures are injuries where the carpus is torn into three columns. ARU injuries have a high incidence of neurovascular, soft-tissue cover, and muscular-associated injuries. Depending on the injuries mentioned earlier, a bad functional prognosis can be expected. Nearly without exception, in ARU cases, a traumatic TFR rupture takes place. Garcia-Elias mentioned that the injury pattern is given by the speed, magnitude, and energy entry point. Clinical Relevance We describe a case of an ARU injury which has not been previously described. In an analysis of the 12 ARU cases previously reported, we observed that when two or more applied forces converge, an ARU injury pattern can occur. That suggests that in ARU injuries, one side of the injury occurs before the other. Due to the extensive carpal damage, in patients with ARU, a restricted range of motion is more likely to happen than residual instability. Thus, in all these cases, an early mobilization and intensive rehabilitation is highly necessary.

How to Improve Speaking Skills in Plastic Surgery Training? Survey in Residents Participants in Pecha Kucha Contest.

BACKGROUND: Little is known about educational games in Plastic Surgery training. Pecha kucha game has proved to be helpful tool to improve communicative skills. This study survey in resident participants in Pecha Kucha contest assessed how to improve speaking skills in plastic surgery training. METHODS: In the second edition of Pecha Kucha contest of the Mexican Society of Plastic Surgery, a survey was conducted with the residents to know the utility of this educational game. RESULTS: Twenty-six residents participated in the survey. Most of them from the Universidad Nacional Autonoma de México. Most of the residents considered it to be a good tool in order to improve communication skills and helpful for their future practice. The amount of time to present an idea was considered enough to express an idea. The most common proportion between words and images was 20-80% in the presentation. CONCLUSION: Pecha Kucha helped to improve communication skills during residents' training. We encourage other plastic surgery societies to incorporate educational games in their national and international meetings.

Functional Outcomes 18 Months After Total and Midarm Transplantation: A Case Report.

BACKGROUND: The function reported after arm transplantation is deemed beneficial relative to the marked disability that upper arm amputation causes. OBJECTIVE: We report a 51-year-old man with a Disabilities of the Arm, Shoulder and Hand (DASH) score of 75.83 who underwent bilateral arm transplantation in October 2015. PROCEDURE: The right arm was transplanted at the glenohumeral joint level, including transplantation of the humeral head, joint capsule, and rotator cuff ligaments and tendons. Additionally, neurorrhaphies were performed at the origin of the terminal branches of the brachial plexus, including the axillary and musculocutaneous nerves. Therefore, this was considered a total arm transplantation. The left arm was transplanted at the transhumeral level, with complete transplantation of the biceps and triceps brachii, and terminolateral neurorrhaphy of the donor musculocutaneous nerve to the receptor radial nerve. A maintenance triple immunosuppression scheme was administered, with tacrolimus levels kept at 10 ng/mL. RESULTS: At 18 months post-transplantation, the intrinsic musculature in the left hand showed electrical registry, DASH score was 67.5, Carroll test score was 28 in both extremities, Hand Transplant Score System was 67.5 in the right extremity and 77.5 in the left extremity, and Short Form-36 score was 96.1. The patient was healthy, with restored body integrity. He could lift medium-sized weightless objects, eat and go to the bathroom by himself, drink liquids with bimanual grasp, swim, dress almost independently, and drive. CONCLUSION: The functional evolution of the patient was similar to previously reported transplanted arms, even though the right arm transplant involved the glenohumeral joint and axillary and musculocutaneous nerve repair.

Protecting genomic integrity in somatic cells and embryonic stem cells.

Mutation frequencies at some loci in mammalian somatic cells in vivo approach 10(-4). The majority of these events occur as a consequence of loss of heterozygosity (LOH) due to mitotic recombination. Such high levels of DNA damage in somatic cells, which can accumulate with age, will cause injury and, after a latency period, may lead to somatic disease and ultimately death. This high level of DNA damage is untenable for germ cells, and by extrapolation for embryonic stem (ES) cells, that must recreate the organism. ES cells cannot tolerate such a high frequency of damage since mutations will immediately impact the altered cell, and subsequently the entire organism. Most importantly, the mutations may be passed on to future generations. ES cells, therefore, must have robust mechanisms to protect the integrity of their genomes. We have examined two such mechanisms. Firstly, we have shown that mutation frequencies and frequencies of mitotic recombination in ES cells are about 100-fold lower than in adult somatic cells or in isogenic mouse embryonic fibroblasts (MEFs). A second complementary protective mechanism eliminates those ES cells that have acquired a mutational burden, thereby maintaining a pristine population. Consistent with this hypothesis, ES cells lack a G1 checkpoint, and the two known signaling pathways that mediate the checkpoint are compromised. The checkpoint kinase, Chk2, which participates in both pathways is sequestered at centrosomes in ES cells and does not phosphorylate its substrates (i.e. p53 and Cdc25A) that must be modified to produce a G1 arrest. Ectopic expression of Chk2 does not rescue the p53-mediated pathway, but does restore the pathway mediated by Cdc25A. Wild type ES cells exposed to ionizing radiation do not accumulate in G1 but do so in S-phase and in G2. ES cells that ectopically express Chk2 undergo cell cycle arrest in G1 as well as G2, and appear to be protected from apoptosis.