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•Femoral fracture induces an early increase in gut leakiness.•B. adolescentis prevents fracture-induced increase in intestinal permeability.•Probiotic supplementation blunted systemic ...inflammation after fracture.•Consumption of B. adolescentis accelerated fracture callus cartilage remodeling.•B. adolescentis supplementation protected vertebrae from trauma-induced bone loss.
The gut microbiota is an important contributor to both health and disease. While previous studies have reported on the beneficial influences of the gut microbiota and probiotic supplementation on bone health, their role in recovery from skeletal injury and resultant systemic sequelae remains unexplored. This study aimed to determine the extent to which probiotics could modulate bone repair by dampening fracture-induced systemic inflammation. Our findings demonstrate that femur fracture induced an increase in gut permeability lasting up to 7 days after trauma before returning to basal levels. Strikingly, dietary supplementation with Bifidobacterium adolescentis augmented the tightening of the intestinal barrier, dampened the systemic inflammatory response to fracture, accelerated fracture callus cartilage remodeling, and elicited enhanced protection of the intact skeleton following fracture. Together, these data outline a mechanism whereby dietary supplementation with beneficial bacteria can be therapeutically targeted to prevent the systemic pathologies induced by femur fracture.
Cancer stem cell (CSC), the primary source of cancer-initiating population, is involved in cancer recurrence and drug-resistant phenotypes. This study demonstrates that the loss of DAB2IP, a novel ...Ras-GTPase activating protein frequently found in many cancer types, is associated with CSC properties. Mechanistically, DAB2IP is able to suppress stem cell factor receptor (c-kit or CD117) gene expression by interacting with a newly identified silencer in the c-kit gene. Moreover, DAB2IP is able to inhibit c-kit-PI3K-Akt-mTOR signaling pathway that increases c-myc protein to activate ZEB1 gene expression leading to the elevated CSC phenotypes. An inverse correlation between CD117 or ZEB1 and DAB2IP is also found in clinical specimens. Similarly, Elevated expression of ZEB1 and CD117 are found in the prostate basal cell population of DAB2IP knockout mice. Our study reveals that DAB2IP has a critical role in modulating CSC properties via CD117-mediated ZEB1 signaling pathway.
Antecedentes: La anafilaxia perioperatoria puede amenazar la vida del paciente. La incidencia global se estima 1 entre 10.000-20.000 procedimientos. Los agentes más frecuentes son bloqueadores ...neuromusculares, látex y antibióticos. Hay muy pocos reportes de alergia a anestésicos inhalados como el sevoflurano, el cual se considera relativamente seguro en pacientes con alergia a fármacos.
Reporte de caso: Paciente de 12 años, ingresó en oncología, diagnóstico de leucemia linfoblástica aguda. Antecedente de dos reacciones de hipersensibilidad perioperatorias. En primer evento se administró lidocaína y rupivacaína, presentó urticaria, manejado con antihistamínico. Segunda ocasión recibió sólo sevofluorano y presentó anafilaxia, tratado con adrenalina intramuscular. Posteriormente durante terapia intratecal, recibió sevoflurano, presentó rash e hipotensión arterial, manejo nuevamente con adrenalina, con remisión total de síntomas. Retrospectivamente criterios de Brighton nivel I de certeza, clasificada grave por Brown. Se sospechó hipersensibilidad a sevoflurano, descartando otros anestésicos como lidocaína y rupivacaina con pruebas cutáneas intradérmicas negativas. Se solicitaron componentes moleculares para látex con resultados negativos para Hev b 1, Hev b 3, Hev b 6. Por lo anterior y asociado a las características del fármaco se realiza prueba de activación de basófilos para sevoflurano con un porcentaje de activación del 50% (positivo). Se confirma anafilaxia perioperatoria por sevoflurano.
Conclusión: Deben considerarse todos los fármacos involucrados en las reacciones de hipersensibilidad perioperatoria, para establecer alternativas adecuadas y seguras de tratamiento de este pequeño grupo de pacientes.
A graphene field-effect transistor (gFET) was non-covalently functionalised with 1-pyrenebutyric acid N-hydroxysuccinimide ester and conjugated with anti-CD63 antibodies for the label-free detection ...of exosomes. Using a microfluidic channel, part of a graphene film was exposed to solution. The change in electrical properties of the exposed graphene created an additional minimum alongside the original Dirac point in the drain-source current (I
) - back-gate voltage (V
) curve. When phosphate buffered saline (PBS) was present in the channel, the additional minimum was present at a V
lower than the original Dirac point and shifted with time when exosomes were introduced into the channel. This shift of the minimum from the PBS reference point reached saturation after 30 minutes and was observed for multiple exosome concentrations. Upon conjugation with an isotype control, sensor response to the highest concentration of exosomes was negligible in comparison to that with anti-CD63 antibody, indicating that the functionalised gFET can specifically detect exosomes at least down to 0.1 μg/mL and is sensitive to concentration. Such a gFET biosensor has not been used before for exosome sensing and could be an effective tool for the liquid-biopsy detection of exosomes as biomarkers for early-stage identification of diseases such as cancer.
The coastal semi-arid region of south Texas is known for its erratic climate that fluctuates between long periods of drought and extremely wet hurricane-induced storms. The standard precipitation ...index (SPI) and the standard precipitation evaporation index (SPEI) were used in this study in conjunction with precipitation and temperature projections from two general circulation models (GCMs), namely, the National Center for Atmospheric Research (NCAR) Parallel Climate Model (PCM) and the UK Meteorological Office Hadley Centre model (HCM) for two emission scenarios—A1B (~720 ppm CO₂ stabilization) and B1 (~550 ppm CO₂ stabilization) at six major urban centers of south Texas spanning five climatic zones. Both the models predict a progressively increasing aridity of the region throughout the twenty-first century. The SPI exhibits greater variability in the available moisture during the first half of the twenty-first century while the SPEI depicts a downward trend caused by increasing temperature. However, droughts during the latter half of the twenty-first century are due to both increasing temperature and decreasing precipitation. These results suggest that droughts during the first half of the twenty-first century are likely caused by meteorological demands (temperature or potential evapotranspiration (PET) controlled), while those during the latter half are likely to be more critical as they curtail moisture supply to the region over large periods of time (precipitation and PET controlled). The drought effects are more pronounced for the A1B scenario than the B1 scenario and while spatial patterns are not always consistent, the effects are generally felt more strongly in the hinterlands than in coastal areas. The projected increased warming of the region, along with potential decreases in precipitation, points toward increased reliance on groundwater resources which are noted to be a buffer against droughts. However, there is a need for human adaptation to climate change, a greater commitment to groundwater conservation and development of large-scale regional aquifer storage and recovery (ASR) facilities that are capable of long-term storage in order to sustain groundwater availability. Groundwater resource managers and planners must confront the possibility of an increased potential for prolonged (multi-year) droughts and develop innovative strategies that effectively integrate water augmentation technologies and conservation-oriented policies to ensure the sustainability of aquifer resources well into the next century.
Sulfur‐substituted nucleobases (a.k.a., thiobases) are among the world's leading prescriptions for chemotherapy and immunosuppression. Long‐term treatment with azathioprine, 6‐mercaptopurine and ...6‐thioguanine has been correlated with the photoinduced formation of carcinomas. Establishing an in‐depth understanding of the photochemical properties of these prodrugs may provide a route to overcoming these carcinogenic side effects, or, alternatively, a basis for developing effective compounds for targeted phototherapy. In this review, a broad examination is undertaken, surveying the basic photochemical properties and excited‐state dynamics of sulfur‐substituted analogs of the canonical DNA and RNA nucleobases. A molecular‐level understanding of how sulfur substitution so remarkably perturbs the photochemical properties of the nucleobases is presented by combining experimental results with quantum‐chemical calculations. Structure‐property relationships demonstrate the impact of site‐specific sulfur substitution on the photochemical properties, particularly on the population of the reactive triplet state. The value of fundamental photochemical investigations for driving the development of ultraviolet‐A chemotherapeutics is showcased. The most promising photodynamic agents identified thus far have been investigated in various carcinoma cell lines and shown to decrease cell proliferation upon exposure to ultraviolet‐A radiation. Overarching principles have been elucidated for the impact that sulfur substitution of the carbonyl oxygen has on the photochemical properties of the nucleobases.
Thiobases are established compounds in the WHO list of top 100 essential medicines for the treatment of leukemia, autoimmune conditions, and immunosuppression. Although they are highly effective medications, long‐term treatment of patients is associated with a 10‐fold increase in basal cell carcinomas and a 65‐ to 250‐fold increase in squamous cell carcinomas. These side effects are induced by the exposure to sunlight, which originates from the ability of the thiobases to absorb UVA radiation. An in‐depth understanding of their photochemistry can provide a route to overcoming these side effects or, alternatively, a basis for developing effective compounds for phototherapy.
Intensification of droughts in agricultural areas threaten global food security. The impacts of drought stresses vary widely across a region, not only due to climate variability but also due to ...heterogeneous soil and groundwater buffering capacities which protect against droughts. An innovative drought vulnerability index was developed by reconciling the negative effects of drought stresses against the robustness offered by hydrologic buffers. Indicators for climate stresses, soil and groundwater buffering capacities were defined using physical principles and integrated using a multi-criteria decision making (MCDM) framework. The framework was applied to delineate drought vulnerability of agricultural production systems and evaluate current cropping choices across the High Plains region of the US that is underlain by the Ogallala Aquifer. Current crop growth choices appeared to be compatible with the intrinsic drought vulnerabilities with cotton and sorghum grown in higher vulnerability areas and corn and soybean produced in areas with lower vulnerability. Nearly 50% of the aquifer region fell in the transition zone exhibiting medium to high vulnerabilities warranting the need for better water management to adapt to a changing climate.
The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice, teaching and research related to diagnostic imaging ...in women's healthcare. The ISUOG Clinical Standards Committee (CSC) has a remit to develop Practice Guidelines and Consensus Statements as educational recommendations that provide healthcare practitioners with a consensus-based approach for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practice at the time at which they are issued. Although ISUOG has made every effort to ensure that Guidelines are accurate when issued, neither the Society nor any of its employees or members accepts any liability for the consequences of any inaccurate or misleading data, opinions or statements issued by the CSC. They are not intended to establish a legal standard of care because interpretation of the evidence that underpins the Guidelines may be influenced by individual circumstances and available resources. Approved Guidelines can be distributed freely with the permission of ISUOG (info@isuog.org).
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