Environmental Perturbation of the Circadian Clock Disrupts Pregnancy in the Mouse

The circadian clock has been linked to reproduction at many levels in mammals. Epidemiological studies of female shift workers have reported increased rates of reproductive abnormalities and adverse pregnancy outcomes, although whether the cause is circadian disruption or another factor associated with shift work is unknown. Here we test whether environmental disruption of circadian rhythms, using repeated shifts of the light:dark (LD) cycle, adversely affects reproductive success in mice.Young adult female C57BL/6J (B6) mice were paired with B6 males until copulation was verified by visual identification of vaginal plug formation. Females were then randomly assigned to one of three groups: control, phase-delay or phase-advance. Controls remained on a constant 12-hr light:12-hr dark cycle, whereas phase-delayed and phase-advanced mice were subjected to 6-hr delays or advances in the LD cycle every 5–6 days, respectively. The number of copulations resulting in term pregnancies was determined. Control females had a full-term pregnancy success rate of 90% (11/12), which fell to 50% (9/18; p<0.1) in the phase-delay group and 22% (4/18; p<0.01) in the phase-advance group.Repeated shifting of the LD cycle, which disrupts endogenous circadian timekeeping, dramatically reduces pregnancy success in mice. Advances of the LD cycle have a greater negative impact on pregnancy outcomes and, in non-pregnant female mice, require longer for circadian re-entrainment, suggesting that the magnitude or duration of circadian misalignment may be related to the severity of the adverse impact on pregnancy. These results explicitly link disruptions of circadian entrainment to adverse pregnancy outcomes in mammals, which may have important implications for the reproductive health of female shift workers, women with circadian rhythm sleep disorders and/or women with disturbed circadian rhythms for other reasons

Lumbar artery perforator (LAP) flap: a salvage tool for extended lumbo-sacral necrosis after bilateral internal iliac arteries embolization.

We report the case of a 52-year-old man presenting an extensive lumbosacral necrosis after bilateral internal iliac arteries embolization following unstable pelvic fracture. Coverage of the defect was performed using two extended lumbar artery perforator flaps in a propeller fashion. Good functional and esthetic result was achieved at one-year follow-up

User Guide for Luminescence Sampling in Archaeological and Geological Context

Luminescence dating provides a direct age estimate of the time of last exposure of quartz or feldspar minerals to light or heat and has been successfully applied to deposits, rock surfaces, and fired materials in a number of archaeological and geological settings. Sampling strategies are diverse and can be customized depending on local circumstances, although all sediment samples need to include a light-safe sample and material for dose-rate determination. The accuracy and precision of luminescence dating results are directly related to the type and quality of the material sampled and sample collection methods in the field. Selection of target material for dating should include considerations of adequacy of resetting of the luminescence signal (optical and thermal bleaching), the ability to characterize the radioactive environment surrounding the sample (dose rate), and the lack of evidence for post-depositional mixing (bioturbation in soils and sediment). Sample strategies for collection of samples from sedimentary settings and fired materials are discussed. This paper should be used as a guide for luminescence sampling and is meant to provide essential background information on how to properly collect samples and on the types of materials suitable for luminescence dating. La datación por luminiscencia proporciona una estimación directa de la edad del último momento en el que el cuarzo o los minerales de feldespato se expusieron a la luz o al calor y que se ha aplicado exitosamente a depósitos, superficies rocosas y materiales expuestos al fuego en distintos contextos arqueológicos y geológicos. Las estrategias de muestreo son diversas y pueden ser individualizadas dependiendo de las circunstancias locales, aunque todas las muestras de sedimentos deben incluir una muestra segura que no haya sido expuesta a la luz y material para calcular la tasa de la dosis. La exactitud y precisión de los resultados de la datación por luminiscencia están directamente relacionadas con el tipo y la calidad de los materiales muestreados y los métodos de recolección de muestras en el campo. La elección del material de estudio para su datación debe incluir las siguientes consideraciones en torno a la idoneidad de poder reposicionar la señal de luminiscencia (blanqueador óptico y térmico), la capacidad de caracterizar el ambiente radiactivo que rodea la muestra (la tasa de la dosis) y el que no exista evidencia de una alteración posdeposicional (bioperturbación en suelos y sedimentos). Se discuten las estrategias de muestreo para la recolección de muestras de contextos sedimentarios y de materiales expuestos al fuego. Este artículo debe utilizarse como una guía para el muestreo por luminiscencia y tiene la intención de proveer información básica de cómo recolectar muestras y sobre los tipos de materiales apropiados para la datación por luminiscencia

Singlet oxygen from cation driven superoxide disproportionation and consequences for aprotic metal-O2 batteries

Aprotic alkali metal-oxygen batteries require reversible formation of metal superoxide or peroxide on cycling. Severe parasitic reactions cause poor rechargeability, efficiency, and cycle life and have been shown to be caused by singlet oxygen (1O2) that forms at all stages of cycling. However, its formation mechanism remains unclear. We show that disproportionation of superoxide, the product or intermediate on discharge and charge, to peroxide and oxygen is responsible for 1O2 formation. While the overall reaction is driven by the stability of peroxide and thus favored by stronger Lewis acidic cations such as Li+, the 1O2 fraction is enhanced by weak Lewis acids such as organic cations. Concurrently, the metal peroxide yield drops with increasing 1O2. The results explain a major parasitic pathway during cell cycling and the growing severity in K-, Na-, and Li-O2 cells based on the growing propensity for disproportionation. High capacities and rates with peroxides are now realized to require solution processes, which form peroxide or release O2via disproportionation. The results therefore establish the central dilemma that disproportionation is required for high capacity but also responsible for irreversible reactions. Highly reversible cell operation requires hence finding reaction routes that avoid disproportionation

Beneficial contribution to glucose homeostasis by an agro-food waste product rich in abscisic acid. A results from a randomized controlled trial

The control of glucose homeostasis represents the primary goal for the prevention and management of diabetes and prediabetes. In recent decades, the hypoglycemic hormone abscisic acid (ABA) has attracted considerable interest in the scientific literature. In this regard, the high ABA concentration in immature fruits led us to consider these food matrices as candidates for diabetes control. Therefore, the beneficial efficacy of a nutraceutical formulation based on thinned nectarines (TNs) rich in ABA was tested through a three-month, three-arm, parallel-group, randomized controlled trial (RCT) conducted on sixty-one patients with type 2 diabetes (T2D). After 3 months, both the treatments with low doses of TN (500 mg 3 times/day) and high doses of TN (750 mg 3 times/day) showed a significant reduction in glycemic parameters compared to baseline. Treatment with low doses of TN showed a greater insulin-sparing effect (fasting plasma insulin, FPI: −29.2%, p &lt; 0.05 vs. baseline) compared to the high-dose group (FPI: −16.5%, p &lt; 0.05 vs. baseline). Moreover, a significant correlation between glycemia and ABA plasmatic levels was observed for both intervention groups at baseline and after 3 months. Overall, our data reasonably support TN as a promising and innovative nutraceutical product able to contribute to the management of glucose homeostasis

Modeling acute health risks associated with accidental releases of toxic gases

CHEM{_}MACCS has been developed from the radiological accident consequence code, MACCS, to perform probabilistic calculations of potential off-site consequences of the accidental atmospheric release of hazardous chemicals. The principal phenomena considered in CHEM{_}MACCS are atmospheric transport, mitigative actions based on dose projection, dose accumulation by a number of pathways, and early and latent health effects. CHEM{_}MACCS provides the following capabilities: (1) statistical weather sampling data (8,760 hourly data points per year), (2) population dose and health effect risk calculations based on site-specific population data, (3) health effects calculations including the consideration of potential site specific mitigative actions (evacuation and shielding), and (4) modeling of multiple release segments. Three different sample problems are contained in this report to show how to use CHEM{_}MACCS. Three test problems are run to compare CHEM{_}MACCS and D2PC. The doses versus the downwind centerline distances from the source for the given doses are in very close agreement

Free Versus Pedicled Anterolateral Thigh Flap for Abdominal Wall Reconstruction.

Large full thickness abdominal wall defects following malignancies can be a reconstructive challenge. The purpose of this study was to analyze long-term outcomes and complications following abdominal wall reconstruction using composite antero-lateral thigh (ALT) flaps. The study retrospectively investigated 16 consecutive patients who underwent abdominal wall reconstruction with autologous flap between May 2003 and March 2018. Volumetric flap analysis was used to assess flap atrophy over time, evaluating the role of denervation and reinnervation. The long-term outcome was assessed to compare the two groups (free vs. pedicled ALT flap reconstructions). All flaps successfully covered the defects. We found a significant increase in flap resorption in free flaps when compared to pedicled ones. Abdominal bulging was seen in 3 out of 16 (19%) patients after more than 12 months follow-up, in close correlation with mesh absence. Free flaps were shown to be equally effective as their pedicled counterparts, without significant increase in complication rate

Human platelet lysate as a potential clinical-translatable supplement to support the neurotrophic properties of human adipose-derived stem cells

Background: The autologous nerve graft, despite its donor site morbidity and unpredictable functional recovery, continues to be the gold standard in peripheral nerve repair. Rodent research studies have shown promising results with cell transplantation of human adipose-derived stem cells (hADSC) in a bioengineered conduit, as an alternative strategy for nerve regeneration. To achieve meaningful clinical translation, cell therapy must comply with biosafety. Cell extraction and expansion methods that use animal-derived products, including enzymatic adipose tissue dissociation and the use of fetal bovine serum (FBS) as a culture medium supplement, have the potential for transmission of zoonotic infectious and immunogenicity. Human-platelet-lysate (hPL) serum has been used in recent years in human cell expansion, showing reliability in clinical applications. Methods: We investigated whether hADSC can be routinely isolated and cultured in a completely xenogeneic-free way (using hPL culture medium supplement and avoiding collagenase digestion) without altering their physiology and stem properties. Outcomes in terms of stem marker expression (CD105, CD90, CD73) and the osteocyte/adipocyte differentiation capacity were compared with classical collagenase digestion and FBS-supplemented hADSC expansion. Results: We found no significant differences between the two examined extraction and culture protocols in terms of cluster differentiation (CD) marker expression and stem cell plasticity, while hADSC in hPL showed a significantly higher proliferation rate when compared with the usual FBS-Added medium. Considering the important key growth factors (particularly brain-derived growth factor (BDNF)) present in hPL, we investigated a possible neurogenic commitment of hADSC when cultured with hPL. Interestingly, hADSC cultured in hPL showed a statistically higher secretion of neurotrophic factors BDNF, glial cell-derived growth factor (GDNF), and nerve-derived growth factor (NFG) than FBS-cultured cells. When cocultured in the presence of primary neurons, hADSC which had been grown under hPL supplementation, showed significantly enhanced neurotrophic properties. Conclusions: The hPL-supplement medium could improve cell proliferation and neurotropism while maintaining stable cell properties, showing effectiveness in clinical translation and significant potential in peripheral nerve research

Biomarker phenotyping drives clinical management in axillary sentinel node: A retrospective study on women with primary breast cancer in 2002

The current study examined if cancer biomarker phenotyping could predict the clinical/pathological status of axillary nodes in women with primary breast cancer. Primary breast cancers from 2002 were analyzed for tumor size, estrogen receptor (ER), progesterone receptor (PgR), Ki.67MIB expression and Her2/neu amplification. Relationships between the clinical and pathological status of the axilla and the biological subtypes classification were analyzed using univariate, multivariate and regression tree analysis. A total of 65% of women with axillary nodes clinically involved had complete axillary node dissection (ALND) while 705 women with clinically negative axillary underwent sentinel lymph node biopsy (SLNB), 18.5% of the latter had at least one pathologically SLNB involved node. Multivariate analysis revealed that the Luminal A subtype was significantly associated (OR 0.62; P&lt;10-9) with clinical negative axilla while HER2pos/not Luminal was associated with clinical positivity (OR 1.71; P&lt;0.01). No significant association between biological subtypes and SLNB status was demonstrated. Regression tree analysis revealed that subgroups with significantly different probability of SLNB status were separated according to tumor size and PgR values. In conclusion, the current study demonstrated that biomarker breast cancer phenotyping is significantly associated with clinical status of axillary nodes but not with pathological involvement of nodes at SLNB. Regression tree analysis could represent a valid attempt to individualize some patients subgroups candidate to different surgical axilla approaches