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Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb). Mtb can overcome macrophage intracellular killing and lead to persistent infections. The proteases of Mtb are critical virulence factors that participate in immune responses. We determined that Rv3090 is a cell wall-associated protease and a potential pathogenic factor. To characterize the role of Rv3090 in Mtb, recombinant Msg_Rv3090 and Msg_pAIN strains were constructed to infect macrophages and mice. Lactate dehydrogenase assays and flow cytometry results showed that Rv3090 induces late macrophage apoptosis. In vivo infection experiments indicated that Rv3090 could induce hepatocyte and lung cell apoptosis and cause pathological damage to the spleen, liver and lungs. Msg_Rv3090 specifically stimulated the secretion of inflammatory cytokines including TNF-α, IL-6 and IL-1β. Overexpression of Rv3090 significantly promoted the survival of Msg in livers and lungs. Thus, Rv3090 protease triggered late cell apoptosis and contributed to the pathogenicity and dissemination of Mtb.

Trigeminal neuropathic pain (TNP) is an intense pain condition characterized by hyperalgesia and allodynia; however, its neural mechanisms are not completely understood. Its management is complex, and studies that investigate its biochemical mechanisms are important for improving clinical approaches. This study aimed to evaluate the involvement of GABAergic, glutamatergic, and opioidergic systems and brain-derived neurotrophic factor (BDNF) levels in the TNP process in rats. TNP is induced by chronic constriction injury of the infraorbital nerve (CCI-ION). Nociceptive responses were evaluated using the facial von Frey test before and after the administration of GABAergic and opioidergic agonists and glutamatergic antagonists. The rats were divided into vehicle-treated control (C), sham-surgery (SS), and CCI-ION groups, and then subdivided into the vehicle (V)-treated SS-V and CCI-ION-V groups, SS-MK801 and CCI-ION-MK801, treated with the N-methyl-D-aspartate receptor selective antagonist MK801; SS-PB and CCI-ION-PB, treated with phenobarbital; SS-BZD and CCI-ION-BZD, treated with diazepam; SS-MOR and CCI-ION-MOR, treated with morphine. BDNF levels were evaluated in the cerebral cortex, brainstem, trigeminal ganglion, infraorbital branch of the trigeminal nerve, and serum. CCI-ION induced facial mechanical hyperalgesia. Phenobarbital and morphine reversed the hyperalgesia induced by CCI-ION, and the CCI-BZD group had an increased nociceptive threshold until 60 min. CCI-ION-GLU increased the nociceptive threshold at 60 min. Cerebral cortex and brainstem BDNF levels increased in the CCI-ION and SS groups. Only the CCI group presented high levels of BDNF in the trigeminal ganglion. Our data suggest the involvement of GABAergic, glutamatergic, and opioidergic systems and peripheral BDNF in the TNP process.

Fibromyalgia is a complex pain syndrome without a precise etiology. Reduced monoamines levels in serum and cerebrospinal fluid in fibromyalgia patients has been reported and could lead to a dysfunction of descending pain modulatory system producing the painful syndrome. This study evaluated the role of D-like dopamine receptors in the reserpine-induced fibromyalgia-like pain model in female Wistar rats. Reserpine-treated animals were intrathecally injected with different dopamine receptors agonists and antagonists, and small interfering RNAs (siRNAs) against D and D receptor subtypes. Withdrawal and muscle pressure thresholds were assessed with von Frey filaments and the Randall-Selitto test, respectively. Expression of D-like receptors in lumbar spinal cord and dorsal root ganglion was determined using real time polymerase chain reaction (qPCR). Reserpine induced tactile allodynia and muscle hyperalgesia. Intrathecal dopamine and D-like receptor agonist SKF-38393 induced nociceptive hypersensitivity in naïve rats, whilst this effect was prevented by the D-like receptor antagonist SCH-23390. Moreover, SCH-23390 induced a sex-dependent antiallodynic effect in reserpine-treated rats. Furthermore, transient silencing of D and D receptors significantly reduced reserpine-induced hypersensitivity in female rats. Reserpine slightly increased mRNA D receptor expression in dorsal spinal cord, but not in DRG. This work provides new insights about the involvement of the spinal dopaminergic D/D receptors in reserpine-induced hypersensitivity in rats.

Ponatinib and blinatumomab are effective therapies in patients with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukaemia, and their combination might be a promising treatment option. In this study, we aimed to evaluate this chemotherapy-free strategy.

In developing countries delayed presentation following major vascular injury is common due to limited vascular trauma units; delay in diagnosis and time lost in transit which pose a major challenge for limb salvage. Aim of this study was to assess limb survival and complications after delayed revascularization of extremity following major vascular injury.

In clinically node-negative breast cancer patients, the INSEMA trial (NCT02466737) assessed the non-inferiority of avoiding sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). Here we present patient-reported outcomes (PROs) as a secondary endpoint.

Clinicians must individualize pharmacotherapy for patients with acute neurological injury based on multiple factors, including age, comorbidities, and chronic medication use. Many pharmacokinetic and pharmacodynamic properties are altered during acute illness, particularly absorption, distribution, metabolism, and elimination, which may result in loss of drug effect or toxicity. This article provides clinicians with general pharmacologic knowledge of the following drug regimens commonly prescribed to neurocritically ill adults: sedatives, analgesics, osmotherapy, antiseizure medications, antishivering agents, vasoactive agents, and antithrombotic reversal agents.

Back pain is a common health complaint that contributes globally to medical burden and costs, particularly in elderly populations. Nuclear medicine techniques using PET tracers offer diagnostic information about various spine disorders, including malignant, degenerative, inflammatory, and infectious diseases. Herein, the authors briefly review applications of PET in the evaluation of spine disorders in elderly patients.

Previous studies suggested that autoimmune limbic encephalitis with antibodies against contactin-associated protein-like 2 (CASPR2-encephalitis) is clinically heterogeneous and progresses slowly, preventing its early recognition. We aimed to describe the onset and progression of CASPR2-encephalitis and to assess long-term outcomes.

Advancing age significantly affects the structural and functional characteristics of organs and tissues, including the peripheral nervous system (PNS) and musculoskeletal system. PET molecular imaging systems offer the ability to assess the metabolic and quantitative effects due to nerve and muscle injuries, which has the potential to impact clinical management of aged subjects. Here, we aim to describe some features of molecular imaging PET systems using different tracers and methods of imaging in musculoskeletal disorders and peripheral neuropathies commonly seen in elderly patients.