Strengthening Primary Health Care for Epidemic and Pandemic Response: A Scoping Review.

Aims: Epidemics strain healthcare systems and reduce care quality, making primary healthcare a crucial frontline component in combating pandemics. The aim of this paper was to explore the experiences of countries in strengthening primary health care to address epidemics and pandemics of infectious diseases.

Design: It was a scoping review conducted in 2024.

Patient dissatisfaction following rhinoplasty: a 10-year experience in Iran.

Background: The nose is one of the most prominent parts of the face and plays a significant role in peoples' self-satisfaction as well as quality of life. Rhinoplasty is considered as one of the most numerous and delicate cosmetic surgeries all around the world that can be performed for functional issues, esthetic issues, or both. In this study, we aimed to evaluate the dissatisfaction of patients who had undergone rhinoplasty surgery and inform the surgeons to improve the surgical techniques to prevent probable future complaints.

Utilization and safety of onabotulinumtoxinA for the prophylactic treatment of chronic migraine from an observational study in Europe.

Objective To examine treatment utilization patterns and safety of onabotulinumtoxinA for the prophylactic treatment of chronic migraine in routine clinical practice. Background Clinical trials support onabotulinumtoxinA for the prophylaxis of headache in patients with chronic migraine, but real-world data are limited. Design/methods A prospective, observational, post-authorization study in adult patients with chronic migraine treated with onabotulinumtoxinA.

A novel PEGylated interferon beta-1a for multiple sclerosis: safety, pharmacology, and biology.

This study clinically evaluated a novel PEGylated form of interferon beta-1a (PEG-IFN beta-1a), a potential first-line treatment for relapsing multiple sclerosis, in healthy volunteers. Two randomized, blinded phase I studies were conducted: a single-dose study (n = 60) comparing subcutaneous or intramuscular PEG-IFN beta-1a (63, 125, or 188 µg) with intramuscular unmodified IFN beta-1a 30 µg and a multiple-dose study (n = 69) comparing subcutaneous PEG-IFN beta-1a dosed once every 2 or 4 weeks with placebo. Assessments included pharmacokinetic and pharmacodynamic (serum neopterin and 2',5'-OAS) measures, exploratory immune assessments, safety, and tolerability.

PEGylated interferon beta-1a: meeting an unmet medical need in the treatment of relapsing multiple sclerosis.

Multiple sclerosis is a chronic autoimmune disease of the central nervous system for which a number of disease-modifying therapies are available, including interferon beta (Avonex®, Rebif®, and Betaseron/Betaferon®), glatiramer acetate (Copaxone®), and an anti-VLA4 monoclonal antibody (Tysabri®). Despite the availability and efficacy of these protein and peptide drugs, there remains a significant number of patients who are untreated, including those with relatively mild disease who choose not to initiate therapy, those wary of injections or potential adverse events associated with therapy, and those who have stopped therapy due to perceived lack of efficacy. Since these drugs have side effects that may affect a patient's decision to initiate and to remain on treatment, there is a need to provide a therapy that is safe and efficacious but that requires a reduced dosing frequency and hence a concomitant reduction in the frequency of side effects.

Intramuscular interferon beta-1a in chronic inflammatory demyelinating polyradiculoneuropathy.

Objective: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) shares immunologic features with multiple sclerosis (MS). Because IM interferon beta-1a (IM IFNbeta-1a) is an effective and safe treatment for MS, we conducted a dose-ranging efficacy study of IFNbeta-1a in patients with CIDP.

Methods: Adults with IV immunoglobulin (IVIg)-dependent CIDP (n = 67) were enrolled in this 32-week double-blind trial and randomized to IM IFNbeta-1a.

Dual Roles for Endothelin-B Receptors in Modulating Adjuvant-Induced Inflammatory Hyperalgesia in Rats.

Injection of endothelin-1 (ET-1) into the plantar rat hindpaw causes acute pain at high concentrations and tactile sensitization at low concentrations. The pro-nociceptive actions are driven through ET(A) receptors for both levels of [ET-1], but the ET(B) receptors are only pro-nociceptive for allodynia from low [ET-1] and anti-nociceptive for pain from high [ET-1]. The goal of the present work was to discriminate the roles of the ET receptors in the acute hyperalgesia from inflammation by complete Freund's adjuvant (CFA, 20 mg/paw) into the rat hindpaw.

Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans.

The vanilloid receptor TRPV1 has been identified as a molecular target for the treatment of pain associated with inflammatory diseases and cancer. Hence, TRPV1 antagonists have been considered for therapeutic evaluation in such diseases. During Phase I clinical trials with AMG 517, a highly selective TRPV1 antagonist, we found that TRPV1 blockade elicited marked, but reversible, and generally plasma concentration-dependent hyperthermia.

The association between psychopathology and placebo analgesia in patients with discogenic low back pain.

Background: Chronic low back pain patients have a high rate of psychopathology, comprised mainly of depression, anxiety, and high levels of neuroticism. We previously found that psychopathology is associated with increased placebo analgesia in this patient group.

Objective: To better understand this finding in the context of other known predictors of placebo response (such as expectations for relief), we performed a detailed analysis of expectations and other possible covariates.

Pathologic alterations of cutaneous innervation and vasculature in affected limbs from patients with complex regional pain syndrome.

Complex regional pain syndromes (CRPS, type I and type II) are devastating conditions that can occur following soft tissue (CRPS type I) or nerve (CRPS type II) injury. CRPS type I, also known as reflex sympathetic dystrophy, presents in patients lacking a well-defined nerve lesion, and has been questioned as to whether or not it is a true neuropathic condition with an organic basis. As described here, glabrous and hairy skin samples from the amputated upper and lower extremity from two CRPS type I diagnosed patients were processed for double-label immunofluorescence using a battery of antibodies directed against neural-related proteins and mediators of nociceptive sensory function.

The association between negative affect and opioid analgesia in patients with discogenic low back pain.

Comprised mainly of depression, anxiety, and high neuroticism, psychopathology diminishes the effectiveness of many chronic pain treatments. But, it is not known if it is associated with diminished opioid analgesia in patients with chronic, noncancer pain. We tested the hypothesis that psychopathology diminishes opioid analgesia in patients with discogenic low back pain in 60 patients not on opioids in a double blind, placebo controlled, random crossover designed trial.

CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids.

CB(2) cannabinoid receptor-selective agonists are promising candidates for the treatment of pain. CB(2) receptor activation inhibits acute, inflammatory, and neuropathic pain responses but does not cause central nervous system (CNS) effects, consistent with the lack of CB(2) receptors in the normal CNS. To date, there has been virtually no information regarding the mechanism of CB(2) receptor-mediated inhibition of pain responses.

Sensory fibers resistant to the actions of tetrodotoxin mediate nocifensive responses to local administration of endothelin-1 in rats.

Endothelin-1 (ET-1) applied to the sciatic nerve or injected into the plantar hindpaw of rats induces pain behavior (ipsilateral hindpaw flinching) and selective excitation of nociceptors by activation of endothelin-A (ET(A)) receptors. To determine the pharmacological profile of the sensory fibers that mediate this pain behavior, we administered lidocaine (LID, a non-selective conduction blocker) or tetrodotoxin (TTX) prior to ET-1. LID (1 or 2%, 0.

Endothelin-1 and metastatic cancer pain.

Pain in patients with metastatic cancer contributes to increased suffering in those already burdened by their advancing illness. The causes of this pain are unknown but likely to involve the action of tumor-associated mediators and their receptors. One such mediator, endothelin-1 (ET-1), can induce both pain-like behavior in animals and pain in humans that is endothelin-A (ET(A)) receptor-dependent, and that appears to be due to the selective excitation of pain fibers.

Identification of a novel gene (HSN2) causing hereditary sensory and autonomic neuropathy type II through the Study of Canadian Genetic Isolates.

Hereditary sensory and autonomic neuropathy (HSAN) type II is an autosomal recessive disorder characterized by impairment of pain, temperature, and touch sensation owing to reduction or absence of peripheral sensory neurons. We identified two large pedigrees segregating the disorder in an isolated population living in Newfoundland and performed a 5-cM genome scan. Linkage analysis identified a locus mapping to 12p13.

Endothelin-B receptor activation triggers an endogenous analgesic cascade at sites of peripheral injury.

Endothelin-1 (ET-1) is a newly described pain mediator that is involved in the pathogenesis of pain states ranging from trauma to cancer. ET-1 is synthesized by keratinocytes in normal skin and is locally released after cutaneous injury. While it is able to trigger pain through its actions on endothelin-A (ET(A)) receptors of local nociceptors, it can coincidentally produce analgesia through endothelin-B (ET(B)) receptors.

Local injection of a selective endothelin-B receptor agonist inhibits endothelin-1-induced pain-like behavior and excitation of nociceptors in a naloxone-sensitive manner.

We showed previously that subcutaneous injection of the injury-associated peptide mediator endothelin-1 (ET-1) into the rat plantar hindpaw produces pain behavior and selective excitation of nociceptors, both through activation of ET(A) receptors likely on nociceptive terminals. The potential role of ET(B) receptor activation in these actions of ET-1-has not been examined. Therefore, in these experiments, we studied the effect of blocking or activating ET(B) receptors on ET-1-induced hindpaw flinching and excitation of nociceptors in rats.

Endothelin-1 (ET-1) selectively enhances the activation gating of slowly inactivating tetrodotoxin-resistant sodium currents in rat sensory neurons: a mechanism for the pain-inducing actions of ET-1.

Endothelin-1 (ET-1) causes pain through activation of nociceptors, by either direct depolarization or increased excitability. Here we examined the effect of ET-1 on nociceptor-associated tetrodotoxin-resistant (TTX-R) sodium currents using whole-cell voltage clamp of acutely dissociated rat dorsal root ganglion (DRG) neurons. DRG neurons that responded had enhanced activation gating when exposed to 10 nm ET-1, as determined by significant shifts in their average activation midpoint potentials (DeltaE(0.

Endothelin-1 activates ET(A) receptors to increase intracellular calcium in model sensory neurons.

Endothelin-1 (ET-1) induces endothelin-A (ETA) receptor-mediated pain and selective excitation of nociceptors. Here we studied ET-1-induced changes in intracellular calcium (Ca2+in) in Fura-2 loaded mouse neuroblastoma-rat dorsal root ganglion hybrid cells (ND7/104). ET-1 (1-400 nM) induced concentration-dependent, transient increases in Ca2+in, probably of intracellular source.

Local injection of endothelin-1 produces pain-like behavior and excitation of nociceptors in rats.

Neurobehavioral and neurophysiological actions of the peptide endothelin-1 (ET-1) were investigated after subcutaneous plantar hindpaw injections in adult male Sprague Dawley rats. Hindpaw flinching developed within minutes after ET-1 (8-16 nmol) injection, peaked at 30 min, lasted for 60 min, and was strongly inhibited by the endothelin-A (ET(A)) receptor antagonist, BQ-123 (3.2 m).

Recent advances in the pharmacology of nerve-injury pain.

Nerve injury pain remains a complex clinical challenge. Although the development of animal models of nerve injury pain has aided our understanding of potential pathophysiologic mechanisms for this condition, effective treatment still remains beyond our reach. Several classes of agents appear to block pain behavior in these animal models and humans, but they are often limited in their use by low efficacy, or undesirable side-effects.

Behavioral signs of acute pain produced by application of endothelin-1 to rat sciatic nerve.

We examined whether endothelin-1 (ET-1), a potent vasoconstrictive peptide secreted in high concentration by metastatic prostate cancer cells, produces endothelin receptor-dependent pain behavior when applied to rat sciatic nerve. ET-1 (200-800 microM) applied to the epineurial surface of rat sciatic nerve produced reliable, robust, unilateral hindpaw flinching lasting 60 min. Pre-emptive systemic morphine completely blocked this effect in a naloxone-reversible manner, suggesting that this behavior was pain-related.

Exclusion of p75NGFR and other candidate genes in a family with hereditary sensory neuropathy type II.

Hereditary sensory neuropathy Type II (HSN II) is an autosomal recessive disorder characterized by the loss of peripheral sensory modalities in individuals with otherwise normal development. Patients with HSN II often have chronic ulceration of the fingers and toes, autoamputation of the distal phalanges, and neuropathic joint degeneration associated with loss of pain sensation. Recent descriptions of a similar phenotype in mice carrying a targeted mutation in the low affinity nerve growth factor receptor, p75NGFR, suggested the possibility that mutations in this gene or other members of the nerve growth factor (NGF) family of genes and their receptors might be responsible for this human disorder.