Does "Fight or Flight" Need Updating?

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Evidence Based Complementary Intervention for Insomnia

Increasing scientific evidence point to a non-pharmacological complementary treatment for insomnia: white noise. Its presentation has been shown to induce sleep in human neonates and adults, probably by reducing the signal-to-noise ratio of ambient sound. White noise may be a simple, safe, cost-effective alternative to hypnotic medication in many psychiatric disorders, especially acute stress disorder and PTSD

The human fear-circuitry and fear-induced fainting in healthy individuals The paleolithic-threat hypothesis

The Paleolithic-Threat hypothesis reviewed here posits that habitual efferent fainting can be traced back to fear-induced allelic polymorphisms that were selected into some genomes of anatomically, mitochondrially, and neurally modern humans (Homo sapiens sapiens) in the Mid-Paleolithic because of the survival advantage they conferred during periods of inescapable threat. We posit that during Mid-Paleolithic warfare an encounter with “a stranger holding a sharp object” was consistently associated with threat to life. A heritable hard- wired or firm-wired (prepotentiated) predisposition to abruptly increase vagal tone and collapse flaccidly rather than freeze or attempt to flee or fight in response to an approaching sharp object, a minor injury, or the sight of blood, polymorphism for the hemodynamically “paradoxical” flaccid- immobility in response to these stimuli may have increased some non-combatants’ chances of survival. This is consistent with the unusual age and sex pattern of fear-induced fainting. The Paleolithic-Threat hypothesis also predicts a link to various hypo-androgenic states (e.g. low dehydroxyepiandrosterone-sulfate. We offer five predictions testable via epidemiological, clinical, and ethological/primatological methods. The Paleolithic-Threat hypothesis has implications for research in the aftermath of man-made disasters, such as terrorism against civilians, a traumatic event in which this hypothesis predicts epidemics of fear-induced faintin

Evidence based complementary intervention for insomnia.

Increasing scientific evidence point to a non-pharmacological complementary treatment for insomnia: white noise. Its presentation has been shown to induce sleep in human neonates and adults, probably by reducing the signal-to-noise ratio of ambient sound. White noise may be a simple, safe, cost-effective alternative to hypnotic medication in many psychiatric disorders, especially acute stress disorder and PTSD

Reevaluating the Management of Chronic Temporomandibular Pain Are We Treating PTSD with Debridement and Lavage?

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Naphthalocyanine-Based Biodegradable Polymeric Nanoparticles for Image-Guided Combinatorial Phototherapy

Image-guided phototherapy is extensively considered as a promising therapy for cancer treatment. To enhance translational potential of this modality, we developed a single agent-based biocompatible nanoplatform that provides both real time near-infrared (NIR) fluorescence imaging and combinatorial phototherapy with dual photothermal and photodynamic therapeutic mechanisms. The developed theranostic nanoplatform consists of two building blocks: (1) silicon naphthalocyanine (SiNc) as NIR fluorescence imaging and phototherapeutic agent and (2) a copolymer, poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) as the biodegradable SiNc carrier. Our simple, highly reproducible and robust approach results in preparation of spherical, monodisperse SiNc-loaded PEG-PCL polymeric nanoparticles (SiNc-PNP) with a hydrodynamic size of 37.66 ± 0.26 nm (polydispersity index = 0.06) and surface charge of -2.76 ± 1.83 mV. The SiNc-loaded nanoparticles exhibit a strong NIR light absorption with an extinction coefficient of 2.8 x 10⁵ M⁻¹cm⁻¹ and efficiently convert the absorbed energy into fluorescence emission (Φ[subscript F] = 11.8%), heat (ΔT ~ 25 °C) and reactive oxygen species. Moreover, the SiNc-PNP are characterized by superior photostability under extensive photoirradiation and structure integrity during storage at room temperature over a period of 30 days. Following intravenous injection, the SiNc-PNP accumulated selectively in tumors and provided high lesion-to-normal tissue contrast for sensitive fluorescence detection. Finally, Adriamycin-resistant tumors treated with a single intravenous dose of SiNc-PNP (1.5 mg/kg) combined with 10 min of a 785 nm light irradiation (1.3 W/cm²) were completely eradicated from the mice without cancer recurrence or side effects. The reported characteristics make the developed SiNc-PNP a promising platform for future clinical application.This is the author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the American Chemical Society and can be found at: https://doi.org/10.1021/acs.chemmater.5b0312

Extensive somatic L1 retrotransposition in colorectal tumors

L1 retrotransposons comprise 17% of the human genome and are its only autonomous mobile elements. Although L1-induced insertional mutagenesis causes Mendelian disease, their mutagenic load in cancer has been elusive. Using L1-targeted resequencing of 16 colorectal tumor and matched normal DNAs, we found that certain cancers were excessively mutagenized by human-specific L1s, while no verifiable insertions were present in normal tissues. We confirmed de novo L1 insertions in malignancy by both validating and sequencing 69/107 tumor-specific insertions and retrieving both 5′ and 3′ junctions for 35. In contrast to germline polymorphic L1s, all insertions were severely 5′ truncated. Validated insertion numbers varied from up to 17 in some tumors to none in three others, and correlated with the age of the patients. Numerous genes with a role in tumorigenesis were targeted, including ODZ3, ROBO2, PTPRM, PCM1, and CDH11. Thus, somatic retrotransposition may play an etiologic role in colorectal cancer

American College of Rheumatology Provisional Criteria for Clinically Relevant Improvement in Children and Adolescents With Childhood-Onset Systemic Lupus Erythematosus

10.1002/acr.23834ARTHRITIS CARE & RESEARCH715579-59