de Sitter Vacua, Renormalization and Locality

We analyze the renormalization properties of quantum field theories in de Sitter space and show that only two of the maximally invariant vacuum states of free fields lead to consistent perturbation expansions. One is the Euclidean vacuum, and the other can be viewed as an analytic continuation of Euclidean functional integrals on $RP^d$. The corresponding Lorentzian manifold is the future half of global de Sitter space with boundary conditions on fields at the origin of time. We argue that the perturbation series in this case has divergences at the origin, which render the future evolution of the system indeterminate without a better understanding of high energy physics.Comment: JHEP Latex, 13 pages, v2. references adde

Effects of a water extract of Lepidium meyenii root in different models of persistent pain in rats

Abstract Lepidium meyenii (Walp.), commonly called maca, is an Andean crop belonging to the Brassicaceae family. Maca hypocotils are habitually consumed as customary food as well as traditional remedies for pathological conditions such as infertility. Moreover, the characterization of maca extracts revealed the presence of compounds that are able to modulate the nervous system. Aimed to evaluate the efficacy of L. meyenii in persistent pain, the present study analyzed the effects of a commercial root extract from maca in different animal models reproducing the most common causes of chronic painful pathologies. A qualitative characterization of this commercial extract by high performance liquid chromatography-mass spectrometry and tandem mass spectrometry analyses allowed us to confirm the presence of some macamides known as bioactive constituents of this root and the absence of the main aromatic glucosinolates. The acute oral administration of maca extract is able to reduce mechanical hypersensitivity and postural unbalance induced by the intra-articular injection of monoiodoacetate and the chronic-constriction injury of the sciatic nerve. Furthermore, L. meyenii extract reverts pain threshold alterations evoked by oxaliplatin and paclitaxel. A good safety profile in mice and rats was shown. In conclusion, the present maca extract could be considered as a therapeutic opportunity to relieve articular and neuropathic pain.</jats:p

Impact of COVID-19 pandemic on Italian Otolaryngology Units: a nationwide study

Objective: The aim of this study was to provide an accurate picture of the changes which have occurred during the COVID-19 pandemic, and the contributions given by Italian Otolaryngology Units. Methods: A 29-item questionnaire was completed and returned by 154 Otorhinolaryngology Units across Italy that investigated geographic distribution, the main changes which occurred in workload management and in clinical and surgical activities and screening procedures for COVID-19 in healthcare personnel and patients. Results: Nearly half of the Otolaryngology Units that responded to the questionnaire were merged with other units, while 22% were converted into COVID-19 units or temporarily closed. A reduction of 8.55% in the number of team members was reported, and about 50% of the units applied uniform work shifts for all staff. Elective activities were uniformly stopped or delayed, passing from 30,295 (pre-COVID data) to 5,684 (COVID data) weekly procedures, with a mean decrease of 81.24% (p &lt; 0.001). Conclusions: Most of the elective otolaryngology activities were suspended during the pandemic; the only procedures were for oncology and emergency patients. Italian Otolaryngologists have demonstrated a high availability to collaborate with non-surgical colleagues

Carbonic Anhydrase IV Selective Inhibitors Counteract the Development of Colitis-Associated Visceral Pain in Rats

Persistent pain affecting patients with inflammatory bowel diseases (IBDs) is still very difficult to treat. Carbonic anhydrase (CA) represents an intriguing pharmacological target considering the anti-hyperalgesic efficacy displayed by CA inhibitors in both inflammatory and neuropathic pain models. The aim of this work was to evaluate the effect of inhibiting CA IV, particularly when expressed in the gut, on visceral pain associated with colitis induced by 2,4-di-nitrobenzene sulfonic acid (DNBS) in rats. Visceral sensitivity was assessed by measuring animals’ abdominal responses to colorectal distension. Repeated treatment with the selective CA IV inhibitors AB-118 and NIK-67 effectively counteracted the development of visceral pain induced by DNBS. In addition to pain relief, AB-118 showed a protective effect against colon damage. By contrast, the anti-hyperalgesic activity of NIK-67 was independent of colon healing, suggesting a direct protective effect of NIK-67 on visceral sensitivity. The enzymatic activity and the expression of CA IV resulted significantly increased after DNBS injection. NIK-67 normalised CA IV activity in DNBS animals, while AB-118 was partially effective. None of these compounds influenced CA IV expression through the colon. Although further investigations are needed to study the underlying mechanisms, CA IV inhibitors are promising candidates in the search for therapies to relieve visceral pain in IBDs

Selective HCN1 block as a strategy to control oxaliplatin-induced neuropathy

Chemotherapy-Induced Peripheral Neuropathy (CIPN) is the most frequent adverse effect of pharmacological cancer treatments. The occurrence of neuropathy prevents the administration of fully-effective drug regimen, affects negatively the quality of life of patients, and may lead to therapy discontinuation. CIPN is currently treated with anticonvulsants, antidepressants, opioids and non-opioid analgesics, all of which are flawed by insufficient anti-hyperalgesic efficacy or addictive potential. Understandably, developing new drugs targeting CIPN-specific pathogenic mechanisms would dramatically improve efficacy and tolerability of anti-neuropathic therapies. Neuropathies are associated to aberrant excitability of DRG neurons due to the alteration in the expression or function of a variety of ion channels. In this regard, Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels are overexpressed in inflammatory and neuropathic pain states, and HCN blockers have been shown to reduce neuronal excitability and to ameliorate painful states in animal models. However, HCN channels are critical in cardiac action potential, and HCN blockers used so far in pre-clinical models do not discriminate between cardiac and non-cardiac HCN isoforms. In this work, we show an HCN current gain of function in DRG neurons from oxaliplatin-treated rats. Biochemically, we observed a downregulation of HCN2 expression and an upregulation of the HCN regulatory beta-subunit MirP1. Finally, we report the efficacy of the selective HCN1 inhibitor MEL57A in reducing hyperalgesia and allodynia in oxaliplatin-treated rats without cardiac effects. In conclusion, this study strengthens the evidence for a disease-specific role of HCN1 in CIPN, and proposes HCN1-selective inhibitors as new-generation pain medications with the desired efficacy and safety profile

Lectures on Supersymmetry Breaking

We review the subject of spontaneous supersymmetry breaking. First we consider supersymmetry breaking in a semiclassical theory. We illustrate it with several examples, demonstrating different phenomena, including metastable supersymmetry breaking. Then we give a brief review of the dynamics of supersymmetric gauge theories. Finally, we use this dynamics to present various mechanisms for dynamical supersymmetry breaking. These notes are based on lectures given by the authors in 2007, at various schools.Comment: 47 pages. v2: minor correction