Mimicking sarcolemmal damage in vitro: a contractile 3D model of skeletal muscle for drug testing in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is the most prevalent neuromuscular disease diagnosed in childhood. It is a progressive and wasting disease, characterized by a degeneration of skeletal and cardiac muscles caused by the lack of dystrophin protein. The absence of this crucial structural protein leads to sarcolemmal fragility, resulting in muscle fiber damage during contraction. Despite ongoing efforts, there is no cure available for DMD patients. One of the primary challenges is the limited efficacy of current preclinical tools, which fail in modeling the biological complexity of the disease. Human-based three-dimensional (3D) cell culture methods appear as a novel approach to accelerate preclinical research by enhancing the reproduction of pathophysiological processes in skeletal muscle. In this work, we developed a patient-derived functional 3D skeletal muscle model of DMD that reproduces the sarcolemmal damage found in the native DMD muscle. These bioengineered skeletal muscle tissues exhibit contractile functionality, as they responded to electrical pulse stimulation. Sustained contractile regimes induced the loss of myotube integrity, mirroring the pathological myotube breakdown inherent in DMD due to sarcolemmal instability. Moreover, damaged DMD tissues showed disease functional phenotypes, such as tetanic fatigue. We also evaluated the therapeutic effect of utrophin upregulator drug candidates on the functionality of the skeletal muscle tissues, thus providing deeper insight into the real impact of these treatments. Overall, our findings underscore the potential of bioengineered 3D skeletal muscle technology to advance DMD research and facilitate the development of novel therapies for DMD and related neuromuscular disorders

Optical Properties of Superconducting Nanowire Single-Photon Detectors

We measured the optical absorptance of superconducting nanowire single photon detectors. We found that 200-nm-pitch, 50%-fill-factor devices had an average absorptance of 21% for normally-incident front-illumination of 1.55-um-wavelength light polarized parallel to the nanowires, and only 10% for perpendicularly-polarized light. We also measured devices with lower fill-factors and narrower wires that were five times more sensitive to parallel-polarized photons than perpendicular-polarized photons. We developed a numerical model that predicts the absorptance of our structures. We also used our measurements, coupled with measurements of device detection efficiencies, to determine the probability of photon detection after an absorption event. We found that, remarkably, absorbed parallel-polarized photons were more likely to result in detection events than perpendicular-polarized photons, and we present a hypothesis that qualitatively explains this result. Finally, we also determined the enhancement of device detection efficiency and absorptance due to the inclusion of an integrated optical cavity over a range of wavelengths (700-1700 nm) on a number of devices, and found good agreement with our numerical model.Comment: will appear in optics express with minor revision

Terminology of Geological Time: Establishment of a Community Standard

It has been recommended that geological time be described in a single set of terms and according to metric or SI (“Système International d’Unités”) standards, to ensure “worldwide unification of measurement”. While any effort to improve communication in scientific research and writing is to be encouraged, we are also concerned that fundamental differences between date and duration, in the way that our profession expresses geological time, would be lost in such an oversimplified terminology. In addition, no precise value for ‘year’ in the SI base unit of second has been accepted by the international bodies.Under any circumstances, however, it remains the fact that geological dates – as points in time – are not relevant to the SI. Known dates may define durations, just as known durations may define dates, or dates may simply be punctual references that support historical narratives, but dates are not quantities. Furthermore, dates, as datum points, belong to a specific type of guiding information that is in constant use not only by the disciplines that explore the unwritten past, but in the physical sciences and engineering as well. Accordingly, we recommend a new standardization of the distinction between geohistorical date, in years before present expressed in ‘annus’, symbol ‘a’,with the multiples ‘ka’, ‘Ma’, and ‘Ga’ for thousands, millions and billions of years ago, according to a convention that has been very widely adopted during the last 30 years, and geohistorical duration, expressed in ‘year’, symbol ‘yr’, with multiples ‘kyr’, ‘Myr’ and ‘Gyr’, respectively, as the most appropriate among the various formats in the current literature. Agreement on these two sets of terms throughout the wide community that deals with paleochronology would remove a false impression of improvisation and uncertainty as to appropriate terminology, and would lead to more effective communication in areas where a simplified but needlessly SI-conisistent terminology would be less, not more useful

Moments of Inertia of Nuclei in the Rare Earth Region: A Relativistic versus Non-Relativistic Investigation

A parameter free investigation of the moments of inertia of ground state rotational bands in well deformed rare-earth nuclei is carried out using Cranked Relativistic Hartree-Bogoliubov (CRHB) and non-relativistic Cranked Hartree-Fock-Bogoliubov (CHFB) theories. In CRHB theory, the relativistic fields are determined by the non-linear Lagrangian with the NL1 force and the pairing interaction by the central part of finite range Gogny D1S force. In CHFB theory, the properties in particle-hole and particle-particle channels are defined solely by Gogny D1S forces. Using an approximate particle number projection before variation by means of the Lipkin Nogami method improves the agreement with the experimental data, especially in CRHB theory. The effect of the particle number projection on the moments of inertia and pairing energies is larger in relativistic than in non-relativistic theory.Comment: 18 pages + 2 PostScript figure

Protocol for the detection and nutritional management of high-output stomas

Introduction: An issue of recent research interest is excessive stoma output and its relation to electrolyte abnormalities. Some studies have identified this as a precursor of dehydration and renal dysfunction. A prospective study was performed of the complications associated with high-output stomas, to identify their causes, consequences and management.Materials and methods: This study was carried out by a multidisciplinary team of surgeons, gastroenterologists, nutritionists and hospital pharmacists. High-output stoma (HOS) was defined as output ≥1500 ml for two consecutive days. The subjects included in the study population, 43 patients with a new permanent or temporary stoma, were classified according to the time of HOS onset as early HOS (<3 weeks after initial surgery) or late HOS (≥3 weeks after surgery). Circumstances permitting, a specific protocol for response to HOS was applied. Each patient was followed up until the fourth month after surgery.Results: Early HOS was observed in 7 (16 %) of the sample population of 43 hospital patients, and late HOS, in 6 of the 37 (16 %) non-early HOS population. By type of stoma, nearly all HOS cases affected ileostomy, rather than colostomy, patients. The patients with early HOS remained in hospital for 18 days post surgery, significantly longer than those with no HOS (12 days). The protocol was applied to the majority of EHOS patients and achieved 100 % effectiveness. 50 % of readmissions were due to altered electrolyte balance. Hypomagnesaemia was observed in 33 % of the late HOS patients.Conclusion: The protocol developed at our hospital for the detection and management of HOS effectively addresses possible long-term complications arising from poor nutritional status and chronic electrolyte alteration

Smart on-chip Fourier-transform spectrometers harnessing machine learning algorithms

Miniaturized silicon photonics spectrometers have great potential for mass market applications like medicine and hazard detection. However, the performance of state-of-the-art silicon spectrometers is limited by fabrication imperfections and temperature variations. In this work, we present a fundamentally new strategy that combines machine learning algorithms and on-chip spatial heterodyne Fourier-transform spectroscopy to identify specific absorption features operated under a wide range of temperatures in the presence of fabrication imperfections. We experimentally show differentiation of four different input spectra with unknown temperature variations as large as 10 °C. This is about 100x increase in operational range, compared to state-of-the-art retrieval techniques

Paciente con síndrome de intestino corto y progresión atípica de adenocarcinoma de endometrio

The most common location of distant metastasis of endometrial adenocarcinoma is the lung, although sometimes it could appear soft tissue involvement. Short bowel syndrome can potentially cause serious electrolite changes that require a global management. Patient admitted for severe electrolyte changes secondary to a short bowel syndrome after an intestinal resection. Octreotide LAR was successfully used to control intestinal losses. During the outpatient follow up was detected two soft tissue masses in gluteal region compatible with tumour progression of an endometrial adenocarcinoma diagnosed 10 years before. The usefulness of octreotide to control chronic diarrhoea in short bowel syndrome and other diseases should be taken into account as an option for the management of these diseases. The presence of soft tissue masses in a patient with a history of endometrial adenocarcinoma should alert on the possibility of tumour progression at that level.La afectación metastásica del adenocarcinoma de endometrio más frecuente es la pulmonar, ocasionalmente puede progresar a nivel de partes blandas. El síndrome de intestino corto puede provocar alteraciones iónicas potencialmente graves. Paciente que ingresa por alteraciones iónicas graves secundarias a un síndrome de intestino corto tras una resección por bridas. Para lograr un óptimo control de las pérdidas intestinales se utilizó con éxito octreótido LAR. Durante su seguimiento ambulatorio se detectaron dos masas de partes blandas en región glútea compatibles con progresión tumoral del adenocarcinoma de endometrio que había sido diagnosticado más de 10 años antes. La utilidad del octreótido para el control de la diarrea crónica en casos de síndrome de intestino corto y otras patologías, debe ser tenida en cuenta como una opción más a valorar de forma individualizada en cada enfermo. La presencia de masas de partes blandas en un paciente con antecedentes de adenocarcinoma de endometrio debe alertar sobre la posibilidad de una progresión tumoral a dicho nivel

Lomas Las Tetas de Cabra fauna

88 p. : ill. (1 col.), maps ; 26 cm.Includes bibliographical references (p. 64-70)."Fossil mammal and other vertebrate remains from the Lomas Las Tetas de Cabra in Baja California Norte, Mexico, provide an opportunity to examine the utility of continental scale geochronologies based on land mammal faunas. Early reports proposed a late Paleocene to early Eocene age for this fauna. Recent fieldwork and considerations of cumulative fossil discoveries strongly indicate that the Baja fauna represents the Wasatchian Land Mammal Age (early Eocene) and is strikingly similar to faunas of this age from the western interior of the United States. Wasatchian-age taxa represented in the Baja assemblage include Hyracotherium, Hyopsodus, Meniscotherium (also possibly from Clarkforkian assemblages), Diacodexis, and Prolimnocyon. Also present in the fauna are excellent specimens of Wyolestes and Esteslestes, a new genus of didelphid marsupial, as well as a badly distorted skull of a pantodont. An early Eocene age assignment is supported by analysis of the marine section adjacent to the Tetas de Cabra sequence. The marine organisms are consistent with a middle Ypresian (early Eocene) age assignment. Paleomagnetic analyses of both the terrestrial and marine sections also corroborate this age assignment. These new results substantiate the validity of the Wasatchian as a discrete temporal interval that can be applied at a continental scale. The Wasatchian thus fulfills the expectations for a mammal-based chronology. Similarities, rather than differences, between the Baja assemblage and other Wasatchian-age faunas is the dominant pattern. A choice among dispersal theories for the sources of Wasatchian mammals is not clearly indicated by the faunal evidence"--P. 3

Intraoperative radiotherapy electron boost followed by moderate doses of external beam radiotherapy in resected soft-tissue sarcoma of the extremities

To analyze the patterns of failure and the toxicity profile of intraoperative electron beam radiotherapy (IOERT) after resection of soft tissue sarcomas of the extremities (STS). PATIENTS AND METHODS: Forty-five patients with extremity STS were treated with IOERT and moderate-dose postoperative radiotherapy (45-50 Gy). Twenty-six patients were treated for primary disease (PD) and 19 patients for an isolated recurrence (ILR). Tumor size was >5 cm (maximum diameter) in 36 patients (80%), and high-grade histology in PD patients was present in 14 patients (54%). In nine patients, IOERT was used alone, due to previous irradiation or patient refusal. Chemotherapy (neoadjuvant and/or adjuvant) was mainly given to high-grade tumors. RESULTS: Nine patients relapsed in the extremity (20%), and 12 patients in distant sites (28%). Actuarial local control at 5 years was 88% for patients with negative/close margins and 57% for patients presenting positive margins (P=0.04). Five patients (11%) developed neuropathy associated with the treatment. Extremity preservation was achieved in 40 patients (88%). With a median follow-up of 93 months (range: 27-143 months) for the patients at risk, 25 patients remain alive (a 7-year actuarial survival rate of 75% for PD and 47% for ILR; P=0.01). CONCLUSIONS: IOERT combined with moderate doses of external beam irradiation yields high local control and extremity preservation rates in resected extremity STS. Peripheral nerves in the IOERT field are dose-limiting structures requiring a dose compromise in the IOERT component to avoid severe neurological damage