Clinical Case Report: Ultrastructural Evidence of Skeletal Muscle Mitochondrial Dysfunction in Patients With Subclinical Hypothyroidism

Abstract. Objective: The lack of overt signs and symptoms and controversies surrounding the thyroid stimulating hormone (TSH) reference range variability make the management of subclinical hypothyroidism (sHT) a challenge. Because muscle cramps and weakness have been noted in sHT, histological skeletal muscle examination may be of diagnostic significance as the presence of abnormalities would substantiate a significant consequence of the mild thyroid failure presumed to be present in the individual with sHT. The objective of this study was to investigate the ultrastructural and histological changes of skeletal muscle associated with sHT. Design: Skeletal muscle biopsies from the vastus lateralis were obtained from four subjects with sHT. Samples were fixed, sectioned, and stained for quantitative and qualitative electron and light microscopic analysis. Main Outcome: Analyses revealed characterizable morphological and ultrastructural alterations and quantitative mitochondrial variations between subjects, indicative of skeletal muscle mitochondrial dysfunction in sHT patients. For the 4 subjects, mean mitochondrial perimeter (MP) was 1.09 ± 0.312 ì, mean mitochondrial area (MA) was 0.10 ± 0.05 ì², and mean mitochondrial volume density was 1.92 ± 0.95. Conclusions: The observed and quantified mitochondrial alterations and the noted morphological and ultrastructural alterations identify previously undocumented pathological skeletal muscle alterations associated with sHT. The observed morphological and ultrastructural alterations lend support to a trend of progression of sHT into overt hypothyroidism as a result of mitochondrial dysfunction and associated metabolic shift. The identification of these skeletal muscle alterations as sequelae of sHT may lend convincing objective evidence of a pathophysiologically significant abnormality in patients with sHT. If so, this should diminish the substantial resistance to treatment of these patients at an early stage of disease and attenuate the progression to overt hypothyroidism

Fast-, Light-Cured Scintillating Plastic for 3D-Printing Applications

Additive manufacturing techniques enable a wide range of possibilities for novel radiation detectors spanning simple to highly complex geometries, multi-material composites, and metamaterials that are either impossible or cost prohibitive to produce using conventional methods. The present work identifies a set of promising formulations of photocurable scintillator resins capable of neutron-gamma pulse shape discrimination (PSD) to support the additive manufacturing of fast neutron detectors. The development of these resins utilizes a step-by-step, trial-and-error approach to identify different monomer and cross-linker combinations that meet the requirements for 3D printing followed by a 2-level factorial parameter study to optimize the radiation detection performance, including light yield, PSD, optical clarity, and hardness. The formulations resulted in hard, clear, PSD-capable plastic scintillators that were cured solid within 10 s using 405 nm light. The best-performing scintillator produced a light yield 83% of EJ-276 and a PSD figure of merit equaling 1.28 at 450–550 keVee

Post-Menopausal Effects of Resistance Training on Muscle Damage and Mitochondria

Manfredi, TG, Monteiro, MA, Lamont, LS, Singh, MF, Foldvari, M, White, S, Cosmas, AC, and Urso, ML. Postmenopausal effects of resistance training on muscle damage and mitochondria. J Strength Cond Res 27(2): 556–561, 2013—The purpose of this study was to measure the effects of a 12-month progressive resistance training intervention on muscle morphology and strength gains in postmenopausal women. Skeletal muscle biopsies were obtained from the vastus lateralis of 5 independent community-dwelling women (mean age: 75.6 ± 4.28 years; mean height: 163 ± 5.34 cm; mean weight: 72 ± 17.5 kg) before 6 months and 12 months after progressive resistance training. Muscle strength (1 repetition maximum) was measured at the same time points. After 6 months of training, morphological analysis revealed evidence of increased proteolysis and tissue repair, and rudimentary fiber development. The percent of Z-bands with mild Z-band disruption increased from 43.9% at baseline to 66.7% after 6 months of training (p \u3c 0.01). Mitochondrial volume also increased (percent of mitochondria = 0.86% at baseline, 1.19% at 6 months, and 1.04% at 12 months, p \u3c 0.05), and there was a shift to larger sized mitochondria. The training did not result in statistically significant increases in muscle leg strength (p \u3c 0.18). It appears that mild Z-band disruption acts as a precursor for increased protein synthesis and stimulates an increase in mitochondrial mass. Therefore, although a progressive resistance training program in this population did not increase muscle strength, it did demonstrate clinical applications that lend support to the importance of resistance training in older adults

The course of traumatic pancreatitis in a patient with pancreas divisum: a case report

BACKGROUND: The peculiar anatomy of pancreatic ducts in pancreas divisum (PD) may interfere with the development of acute chronic pancreatitis. In the presented case, PD influenced the evolution of lesions after pancreatic trauma. CASE PRESENTATION: A 38 years old patient refferred to our hospital with recurrent episodes of mild pancreatitis during the last two years. The first episode occurred four months after blunt abdominal trauma. Endoscopic Retrograde Cholangiopancreatography, Magnetic Resonance Imaging of upper abdomen and Magnetic Resonance Cholangiopancreatography disclosed pancreas divisum, changes consistent with chronic pancreatitis in the dorsal pancreatic duct, atrophy in the body and tail of the pancreas and a pseudocyst in the pancreatic head, that was drained endoscopically. CONCLUSION: Pancreas Divisum may interfere with the evolution of posttraumatic changes in the pancreas after blunt abdominal trauma

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter

Measurement of D-s(+) and D-s(*+) production in B meson decays and from continuum e(+)e(-) annihilation at √s=10.6 GeV

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APSNew measurements of Ds+ and Ds*+ meson production rates from B decays and from qq̅ continuum events near the Υ(4S) resonance are presented. Using 20.8 fb-1 of data on the Υ(4S) resonance and 2.6 fb-1 off-resonance, we find the inclusive branching fractions B(B⃗Ds+X)=(10.93±0.19±0.58±2.73)% and B(B⃗Ds*+X)=(7.9±0.8±0.7±2.0)%, where the first error is statistical, the second is systematic, and the third is due to the Ds+→φπ+ branching fraction uncertainty. The production cross sections σ(e+e-→Ds+X)×B(Ds+→φπ+)=7.55±0.20±0.34pb and σ(e+e-→Ds*±X)×B(Ds+→φπ+)=5.8±0.7±0.5pb are measured at center-of-mass energies about 40 MeV below the Υ(4S) mass. The branching fractions ΣB(B⃗Ds(*)+D(*))=(5.07±0.14±0.30±1.27)% and ΣB(B⃗Ds*+D(*))=(4.1±0.2±0.4±1.0)% are determined from the Ds(*)+ momentum spectra. The mass difference m(Ds+)-m(D+)=98.4±0.1±0.3MeV/c2 is also measured.This work was supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the Swiss NSF, A. P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

Acute mountain sickness.

Acute mountain sickness (AMS) is a clinical syndrome occurring in otherwise healthy normal individuals who ascend rapidly to high altitude. Symptoms develop over a period ofa few hours or days. The usual symptoms include headache, anorexia, nausea, vomiting, lethargy, unsteadiness of gait, undue dyspnoea on moderate exertion and interrupted sleep. AMS is unrelated to physical fitness, sex or age except that young children over two years of age are unduly susceptible. One of the striking features ofAMS is the wide variation in individual susceptibility which is to some extent consistent. Some subjects never experience symptoms at any altitude while others have repeated attacks on ascending to quite modest altitudes. Rapid ascent to altitudes of 2500 to 3000m will produce symptoms in some subjects while after ascent over 23 days to 5000m most subjects will be affected, some to a marked degree. In general, the more rapid the ascent, the higher the altitude reached and the greater the physical exertion involved, the more severe AMS will be. Ifthe subjects stay at the altitude reached there is a tendency for acclimatization to occur and symptoms to remit over 1-7 days

Mitochondrial ATP synthase: architecture, function and pathology

Human mitochondrial (mt) ATP synthase, or complex V consists of two functional domains: F1, situated in the mitochondrial matrix, and Fo, located in the inner mitochondrial membrane. Complex V uses the energy created by the proton electrochemical gradient to phosphorylate ADP to ATP. This review covers the architecture, function and assembly of complex V. The role of complex V di-and oligomerization and its relation with mitochondrial morphology is discussed. Finally, pathology related to complex V deficiency and current therapeutic strategies are highlighted. Despite the huge progress in this research field over the past decades, questions remain to be answered regarding the structure of subunits, the function of the rotary nanomotor at a molecular level, and the human complex V assembly process. The elucidation of more nuclear genetic defects will guide physio(patho)logical studies, paving the way for future therapeutic interventions

Just Friends? : Richard Rolle and the Possibility of Christian Friendship Between Men and Women

Tutkimus käsittelee Richard Rollen (k. 1349), englantilaisen erakon ja uskonnollisen kirjailijan, käsityksiä ystävyydestä yleensä ja erityisesti hengellisestä ystävyydestä miesten ja naisten välillä. Rolle kirjoitti useita latinan- ja keskienglanninkielisiä tutkielmia ja hengellisiä oppaita, joissa hän sivusi ystävyyden tematiikkaa sekä omaelämäkerrallisesta että teoreettisesta näkökulmasta. Tutkimuksen pääasiallisina lähteinä käytetään seitsemää Rollen omaa teosta sekä kanonisoinnin toivossa hänestä laadittua pyhimyselämäkertaa. Tutkimus esittelee Rollen ystävyysteoriaa ja suhteuttaa sen 1300-luvun Yorkshiren historialliseen kontekstiin, Rollen kirjallisiin esikuviin sekä hänen ajatteluunsa yleensä. Rolle näyttää tunteneen sekä Ciceron (k. 43 eaa.) että Aelred Rievaulxlaisen (k. 1167) teokset ystävyydestä, mutta sovelsi näiden näkemyksiä omintakeisesti. Rollen maailmankuvalle oli ominaista jyrkkä kaksijakoisuus maailman ja Jumalan rakkauden välillä, minkä vuoksi ero pyhän ja maallisen ystävyyden välillä oli ehdoton. Vääränlainen ystävyys oli vaarallista etenkin kontemplatiivista elämää harjoittaville erakoille ja anakoreeteille, joita Rolle opasti välttämään ihmiskontakteja. Jyrkkyydestään huolimatta Rolle erosi edeltäjistään ja 1300-luvun valtavirrasta puolustamalla sukupuolten välisen pyhän ystävyyden mahdollisuutta. Tutkimuksen keskeinen löytö on, että Rolle määritteli sukupuolten välisen ystävyyden hengelliseksi ohjaukseksi ja perusteli siten sen tarpeellisuutta; naiset tarvitsivat pyhien miesten neuvoja pelastuakseen. Tällainen opetusystävyys ei ollut tasa-arvoinen suhde, vaan miehen tuli opastaa ja oikaista naista tämän omaksi parhaaksi. Toisaalta Rolle uskoi naisten mahdollisuuksiin saavuttaa hengellisen elämän korkeimmat asteet. Lähteet paljastavat, että Rolle tosiasiassa opasti naisia esittämänsä mallin mukaan. Tutkimus osoittaa, että yksittäisille naisille laaditut kansankieliset opaskirjeet sisältävät opetusystävyyden keskeisiä piirteitä ja noudattavat sen hierarkista logiikkaa: Rolle esiintyy välittäjänä Jumalan ja lukijan välillä houkutellen, moittien ja neuvoen lukijaa, jotta tämä saavuttaisi yhä korkeamman pyhyyden asteen. Rollen ja anakoreetti Margaret Kirkebyn välinen suhde, jota on keskiajalla ja myöhemmin pidetty esimerkkinä pyhästä ystävyydestä, näyttää myös muiden lähteiden valossa olleen hierarkkinen opetussuhde. Tutkimuksessa argumentoidaan, että Rollen kirjoittamista motivoi tarve itsepuolustukseen ja toiminnan oikeuttamiseen; hänen kontaktinsa naisiin herättivät epäilyksiä. Rolle halusi olla hengellinen auktoriteetti, mutta hänellä ei ollut luostarisääntökunnan, kerjäläisveljestön tai pappisviran tuomaa virallista tukea, joten hänen paras mahdollisuutensa itsepuolustukseen oli kirjallinen toiminta. Oikeuttaakseen toimintansa naisten parissa Rolle esitti mallin Jumalan rakkauden elävöittämästä pyhästä elämästä, johon kuului velvollisuus opettaa naisia ystävinä. Lisäksi Rollen tuli osoittaa, että hänen oma elämänsä edusti hänen puolustamaansa mallia, jonka edellytyksenä oli välinpitämättömyys maallisia houkutuksia kohtaan. Kaiken tämän takana näyttää olleen toive tasavertaisen ystävän löytämisestä: Rolle ei ollut löytänyt vertaistaan ystävää, joka olisi jakanut hänen hengelliset kokemuksensa, joten hän pyrki hengellisen ohjauksen avulla nostamaan edes yhden oppilaistaan tasolleen. On huomionarvoista, että Rolle näyttää pitäneen naisia kelvollisina kandidaatteina tällaiseen suhteeseen