Rejected

Plenty information exists regarding the effects of chronic stress, although few data exist on the effects of short-lasting stressors, which would mimic daily challenges. Differences in craniofacial and spinal nociception have been observed, thus those observations obtained in spinally innervated areas cannot be directly applied to the orofacial region. Although, opioids are considered amongst the most effective analgesics, their use is sometimes hampered by the constipation they induce. Thus, our aims were to study if a short-lasting stressor, forced swim stress (FSS), modifies nociception, morphine antinociception and constipation in rats. Animals were submitted to 10-20min of FSS for three days, nociception and gastrointestinal transit were studied 24h after the last swimming session. Nociception and morphine (0.6-5mg/kg) antinociception were evaluated in the formalin and hypertonic saline tests in the orofacial area and limbs. Morphine-induced modifications in the GI transit were studied through radiographic techniques. Naloxone was administered, before each swimming session, to analyse the involvement of the endogenous opioid system on the effect of stress. Overall, stress did not alter nociception, although interestingly it reduced the effect of morphine in the orofacial tests and in the inflammatory phase of the formalin tests. Naloxone antagonized the effect of stress and normalized the effect of morphine. Stress did not modify the constipation induced by morphine. Opioid treatment may be less effective under a stressful situation, whilst adverse effects, such as constipation, are maintained. The prevention of stress may improve the level of opioid analgesia. Keywords.

Nonsexually acquired genital ulcers have been described among girls who are prepubertal after various viral illnesses due to mucosal inflammation from an immunologic response. Until recently, nonsexually acquired genital ulcers have only been associated with viral infections.

This study examined the factors affecting mortality and clinical severity score (CSS) of male and female patients with Coronavirus Disease 2019 (COVID-19) using clinical epidemiological information provided by the Korea Disease Control and Prevention Agency.

Pyrolae herba is the dried whole plant of Pyrola calliantha H. Andres or Pyrola decorata H. Andres (Pyrolaceae). Pyrolae herba has a long history of medicinal use in China. In ancient times, it was often used to treat pain in tendons and bones, swollen sore, cough, expectoration, bleeding, and other diseases. and was commonly used in ancient times to treat pain in the tendons and bones, swollen sore, cough, expectoration, bleeding and other diseases.

Postpartum depression has a high prevalence in the United States (~13 %) and often goes undertreated/untreated. We conducted a multicenter, open-label, proof-of-concept trial to assess the Nēsos wearable, non-invasive, transcutaneous auricular vagus nerve stimulation (taVNS) system for the treatment of major depressive disorder with peripartum onset (PPD).

Polypharmacological targeting of lipid mediator networks offers potential for efficient and safe anti-inflammatory therapy. Because of the diversity of its biological targets, curcumin (1a) has been viewed as a privileged structure for bioactivity or, alternatively, as a pan-assay interference (PAIN) compound. Curcumin has actually few high-affinity targets, the most remarkable ones being 5-lipoxygenase (5-LOX) and microsomal prostaglandin E synthase (mPGES)-1. These enzymes are critical for the production of pro-inflammatory leukotrienes and prostaglandin (PG)E, and previous structure-activity-relationship studies in this area have focused on the enolized 1,3-diketone motif, the alkyl-linker and the aryl-moieties, neglecting the rotational state of curcumin, which can adopt twisted conformations in solution and at target sites. To explore how the conformation of curcuminoids impacts 5-LOX and mPGES-1 inhibition, we have synthesized rotationally constrained analogues of the natural product and its pyrazole analogue by alkylation of the linker and/or of the ortho aromatic position(s). These modifications strongly impacted 5-LOX and mPGES-1 inhibition and their systematic analysis led to the identification of potent and selective 5-LOX (3b, IC = 0.038 µM, 44.7-fold selectivity over mPGES-1) and mPGES-1 inhibitors (2f, IC = 0.11 µM, 4.6-fold selectivity over 5-LOX). Molecular docking experiments suggest that the C2-methylated pyrazolocurcuminoid 3b targets an allosteric binding site at the interface between catalytic and regulatory 5-LOX domain, while the o, o'-dimethylated desmethoxycurcumin 2f likely binds between two monomers of the trimeric mPGES-1 structure. Both compounds trigger a lipid mediator class switch from pro-inflammatory leukotrienes to PG and specialized pro-resolving lipid mediators in activated human macrophages.

Diabetic neuropathy (DN) is a common complication of diabetes that is becoming an increasing concern as the prevalence of diabetes rapidly rises. There are several types of DN, but the most prevalent and studied type is distal symmetrical polyneuropathy, which is the focus of this review and is simply referred to as DN. It can lead to a wide range of sensorimotor and psychosocial symptoms and is a major risk factor for diabetic foot ulceration and Charcot neuropathic osteoarthropathy, which are associated with high rates of lower limb amputation and mortality. The prevention and management of DN are thus critical, and clinical guidelines recommend several strategies for these based on the best available evidence. This article aims to provide a narrative review of DN prevention and management strategies by discussing these guidelines and the evidence that supports them. First, the epidemiology and diverse clinical manifestations of DN are summarized. Then, prevention strategies such as glycemic control, lifestyle modifications and footcare are discussed, as well as the importance of early diagnosis. Finally, neuropathic pain management strategies and promising novel therapies under investigation such as neuromodulation devices and nutraceuticals are reviewed.

To investigate the association of diabetes mellitus (DM) with vertigo outcome in patients with vestibular migraine (VM).

Primary mediastinal large B-cell lymphoma (PMBCL) is a rare, non-Hodgkin, B-cell lymphoma thought to originate from thymic B cells, which occurs primarily in young adults such as in the active duty population. Primary mediastinal large B-cell lymphoma (PMBCL) presents as a large mediastinal mass, posing risks to the cardiopulmonary safety of patients and challenging the routine approach to diagnosis. We describe a case of a 23-year-old male sailor who presented to sick call on his ship while in port with shortness of breath, night sweats, 50-pound weight loss, and pruritic punched-out lesions on all extremities. An initial chest X-ray showed a large consolidation. After being seen in the pulmonary medicine clinic 5 weeks after his initial presentation, the patient was admitted to the intensive care unit after computed tomography of his chest revealed a mediastinal mass, causing compression of both the right bronchus and superior vena cava with a large pericardial effusion. Empiric high-dose dexamethasone was initiated before a formal diagnosis due to his significant risk for cardiopulmonary compromise. Following diagnosis and two cycles of chemotherapy, the patient was transferred to a medical oncology facility in the continental USA. This case demonstrates the need to educate all military providers to recognize the presentation of mediastinal masses in active duty service members and the importance of urgently escalating these patients to higher levels of care in order to avoid life-threatening complications.