Central and peripheral mechanisms of pain in fibromyalgia: scoping review protocol.

Fibromyalgia is characterised by widespread musculoskeletal pain, which may present with fatigue, depression, anxiety, sleep and cognitive disturbances. It is the second most prevalent rheumatic disease. An accurate diagnosis is challenging, since its symptoms may resemble diverse conditions such as carpal tunnel syndrome, Raynaud syndrome, Sjögren syndrome, amongst others. Neuropathic pain and autonomic dysfunction in fibromyalgia suggest the involvement of the nervous system. Ion channels, neurotransmitters and neuromodulators may play a role. Small fibre neuropathy (SFN) may also cause chronic widespread pain. SFN may occur in 50% of fibromyalgia patients, but its role in the disease is unknown. Despite several efforts to synthesise the evidence on the mechanisms for pain in fibromyalgia, there are few studies applying an integrative perspective of neurochemical, immunological, and neuroanatomical characteristics, and their relevance to the disease. This protocol aims to clarify the mechanisms of the central and peripheral nervous system associated with pain in fibromyalgia. We will retrieve published studies from Web of Science, MEDLINE, Scopus, EBSCOhost, Ovid and Google Scholar. All clinical studies or experimental models of fibromyalgia reporting imaging, neurophysiological, anatomical, structural, neurochemical, or immunological characteristics of the central or peripheral nervous systems associated with pain will be included. Exclusion criteria will eliminate studies evaluating pain without a standardised measure, studies written in languages different from Spanish or English that could not be appropriately translated, and studies whose full-text files could not be retrieved after all efforts made. A narrative synthesis will be performed.

Adherence to literature search reporting guidelines in leading rheumatology journals' systematic reviews: umbrella review protocol.

Literature searches are important components of systematic reviews. They are not only informative of the retrieval process, but they also set the data to be analyzed and influence additional components of systematic reviews. Despite the available guidelines, several studies have shown that the quality of reporting in systematic reviews is deficient in several medical fields. Systematic reviews may not comply completely with those guidelines despite explicitly stating they do. This protocol intends to answer to what extent systematic reviews published in rheumatology journals have complied with the PRISMA's search strategy guidelines published in 2009. The objective of the study is to analyze the compliance with the PRISMA (2009) search strategy guidelines among systematic reviews published in leading rheumatology journals. Inclusion criteria for this umbrella review protocol are systematic reviews (with or without meta-analyses) that mention having followed the PRISMA statement (2009) in their methods section, and published in journals listed in the Rheumatology category of the Journal of Citations Report 2020. Exclusion criteria are articles published before 2009; retraction letters, notes, expressions of concern; systematic reviews using PRISMA 2020. Databases to be consulted are Web of Science, PubMed and Scopus, from inception to present. Data summaries will be presented in graphs, figures, tables and network maps. A narrative synthesis will be described. This protocol complies with guidelines such as PRISMA 2020, PRISMA-A, PRISMA-P, PRISMA-S, PRESS, and JBI Manual for evidence synthesis, as long as it is suitable for umbrella review protocols. Articles in any language will be considered.

Advances in imaging technologies for the assessment of peripheral neuropathies in rheumatoid arthritis.

Peripheral neuropathy in patients with rheumatoid arthritis is associated with a maladaptive autoimmune response that may cause chronic pain and disability. Nerve conduction studies are the routine method performed when rheumatologists presume its presence. However, this approach is invasive, may not reveal subtle malfunctions in the early stages of the disease, and does not expose abnormalities in structures surrounding the nerves and muscles, limiting the possibility of a timely diagnosis. This work aims to present a narrative review of new technologies for the clinical assessment of peripheral neuropathy in Rheumatoid Arthritis. Through a bibliographic search carried out in five repositories, from 1990 to 2020, we identified three technologies that could detect peripheral nerve lesions and perform quantitative evaluations: (1) magnetic resonance neurography, (2) functional magnetic resonance imaging, and (3) high-resolution ultrasonography of peripheral nerves. We found these tools can overcome the main constraints imposed by the previous electrophysiologic methods, enabling early diagnosis.

Essential fatty acid-rich diets protect against striatal oxidative damage induced by quinolinic acid in rats.

Essential fatty acids have an important effect on oxidative stress-related diseases. The Huntington's disease (HD) is a hereditary neurologic disorder in which oxidative stress caused by free radicals is an important damage mechanism. The HD experimental model induced by quinolinic acid (QUIN) has been widely used to evaluate therapeutic effects of antioxidant compounds. The aim of this study was to test whether the fatty acid content in olive- or fish-oil-rich diet prevents against QUIN-related oxidative damage in rats. Rats were fed during 20 days with an olive- or a fish-oil-rich diet (15% w/w). Posterior to diet period, rats were striatally microinjected with QUIN (240 nmol/µl) or saline solution. Then, we evaluated the neurological damage, oxidative status, and gamma isoform of the peroxisome proliferator-activated receptor (PPARγ) expression. Results showed that fatty acid-rich diet, mainly by fish oil, reduced circling behavior, prevented the fall in GABA levels, increased PPARγ expression, and prevented oxidative damage in striatal tissue. In addition none of the enriched diets exerted changes neither on triglycerides or cholesterol blood levels, nor or hepatic function. This study suggests that olive- and fish-oil-rich diets exert neuroprotective effects.

Disability in Mexico: a comparative analysis between descriptive models and historical periods using a timeline.

Some interpretations frequently argue that three Disability Models (DM) (Charity, Medical/Rehabilitation, and Social) correspond to historical periods in terms of chronological succession. These views permeate a priori within major official documents on the subject in Mexico. This paper intends to test whether this association is plausible by applying a timeline method. A document search was made with inclusion and exclusion criteria in databases to select representative studies with which to depict milestones in the timelines for each period. The following is demonstrated: 1) models should be considered as categories of analysis and not as historical periods, in that the prevalence of elements of the three models is present to date, and 2) the association between disability models and historical periods results in teleological interpretations of the history of disability in Mexico.

Neurotransmitter systems, neuroanatomical pathology and cell death in schizophrenia: update and perspectives.

Schizophrenia is a thought disorder characterized by delusional thinking which may be accompanied by hallucinations involving any sensory modality. Schizophrenia may be associated with several neurologic and psychiatric disorders. Also, it may be induced by drugs. In spite of the similarity in psychoses symptomatology, it is unknown if it involves the same underlying neurobiologic mechanisms in those cases. Schizophrenic patients exhibit not only neuroanatomical alterations, but also, distortion of several neurotransmitter systems. Nowadays, the main theories in this regard involve dopaminergic hyperfunction and glutama- tergic hypofunction. Additionally, other systems involved in the schizophrenia pathophysiology are the nitric oxide pathway as well as GABAergic, glycinergic and serotonergic systems. Fur- thermore, those systems interact with each other to modulate nervous system development and cell survival. The alterations described in this paper may be part of a single cascade of events. Research in this field should focus on the elucidation of this chain to find its limits, the initial stage that originates it, and the final stage that has therapeutic implications.

[Neuroprotective mechanisms of cannabinoids in brain ischemia and neurodegenerative disorders]. / Mecanismos neuroprotectores de los canabinoides en la isquemia cerebral y las enfermedades neurodegenerativas.

One of the most important causes of morbidity and mortality is neurologic dysfunction; its high incidence has led to an intense research of the mechanisms that protect the central nervous system from hypoxia and ischemia. The mayor challenge is to block the biochemical events leading to neuronal death. This may be achieved by neuroprotective mechanisms that avoid the metabolic and immunologic cascades that follow a neurological damage. When it occurs, several pathophysiological events develop including cytokine release, oxidative stress and excitotoxicity. Neuroprotective effects of cannabinoids to all those mechanisms have been reported in animal models of brain ischemia, excitotoxicity, brain trauma and neurodegenerative disorders. Some endocannabinoid analogs are being tested in clinical studies (I-III phase) for acute disorders involving neuronal death (brain trauma and ischemia). The study of the cannabinoid system may allow the discovery of effective neuroprotective drugs for the treatment of neurological disorders.

[Relevance of hyperglycemia on the course and outcome of aneurysmal subarachnoid hemorrhage: evidence and mechanisms]. / Relevancia de la hiperglucemia para la evolución y el desenlace de la hemorragia subaracnoidea aneurismática: evidencias y mecanismos.

Aneurysmal subarachnoid hemorrhage (aSAH) may have a fatal outcome after a few weeks from ictus, due to its complications, like cerebral vasospasm and edema along with hyperglycemia. Hyperglycemia may be involved in the development of brain vasospasm and edema. It is possible that hyperglycemia plays a central role in the outcome of aSAH. Several mechanisms may explain this relationship; they include ion balance, excitatory amino acid release, stimulation of vasoconstrictor molecules and reduced synthesis of vasorelaxants. However, some studies do not support this hypothesis regarding the role of hyperglycemia in aSAH. Taken together, the evidence suggests that the control of glucose levels may influence the aSAH outcome depending on the complications that may develop.

[Early analgesia does not block labor in first pregnancies]. / La aplicación temprana de analgesia no detiene el trabajo de parto en mujeres primigestas.

Pain during labor alters the well-being of the mother and fetus. Peridural analgesia may prevent pain, but some physicians prefer to administrate this until labor has progressed in order to avoid blocking labor so a cesarean surgery would be required. In this case, the mother suffers pain until labor has progressed enough to apply analgesia. Thus, the mother suffers pain while labor has progressed enough. Cesarean surgery increases maternal morbidity, thus it is important to evaluate labor progression when analgesia is applied at an early or advanced stage of labor. This study evaluated the effect of early analgesia on labor progression. First pregnancies at a latent or active stage of labor were included. Ropivacaine peridural analgesia was applied. All the patients completed labor (latent labor: final dilation 10 cm (10-10 cm); active labor: final dilation 10 cm (10-10 cm); p = 0.812). The proportion of patients undergoing cesarean surgery was not different between the groups (four in latent labor (7%), eight in active labor (12%); p = 0.545). Our results suggest that early analgesia may be applied without compromising labor progression.

Threats to scholarly research integrity arising from paper mills: a rapid scoping review.

"Paper mills" are unethical outsourcing agencies proficient in fabricating fraudulent manuscripts submitted to scholarly journals. In earlier years, the activity of such companies involved plagiarism, but their processes have gained complexity, involving the fabrication of images and fake results. The objective of this study is to examine the main features of retracted paper mills' articles registered in the Retraction Watch database, from inception to the present, analyzing the number of articles per year, their number of citations, and their authorship network. Eligibility criteria for inclusion: retracted articles in any language due to paper mill activity. Retraction letters, notes, and notices, for exclusion. We collected the associated citations and the journals' impact factors of the retracted papers from Web of Science (Clarivate) and performed a data network analysis using VOSviewer software. This scoping review complies with PRISMA 2020 statement and main extensions. After a thorough analysis of the data, we identified 325 retracted articles due to suspected operations published in 31 journals (with a mean impact factor of 3.1). These retractions have produced 3708 citations. Nearly all retracted papers have come from China. Journal's impact factor lower than 7, life sciences journals, cancer, and molecular biology topics were common among retracted studies. The rapid increase of retractions is highly challenging. Paper mills damage scientific research integrity, exacerbating fraud, plagiarism, fake images, and simulated results. Rheumatologists should be fully aware of this growing phenomenon.

Therapeutic Potential of Ultrasound Neuromodulation in Decreasing Neuropathic Pain: Clinical and Experimental Evidence.

BACKGROUND: For more than seven decades, ultrasound has been used as an imaging and diagnostic tool. Today, new technologies, such as focused ultrasound (FUS) neuromodulation, have revealed some innovative, potential applications. However, those applications have been barely studied to deal with neuropathic pain (NP), a cluster of chronic pain syndromes with a restricted response to conventional pharmaceuticals. OBJECTIVE: To analyze the therapeutic potential of low-intensity (LIFUS) and high-intensity (HIFUS) FUS for managing NP. METHODS: We performed a narrative review, including clinical and experimental ultrasound neuromodulation studies published in three main database repositories. DISCUSSION: Evidence shows that FUS may influence several mechanisms relevant for neuropathic pain management such as modulation of ion channels, glutamatergic neurotransmission, cerebral blood flow, inflammation and neurotoxicity, neuronal morphology and survival, nerve regeneration, and remyelination. Some experimental models have shown that LIFUS may reduce allodynia after peripheral nerve damage. At the same time, a few clinical studies support its beneficial effect on reducing pain in nerve compression syndromes. In turn, Thalamic HIFUS ablation can reduce NP from several etiologies with minor side-effects, but some neurological sequelae might be permanent. HIFUS is also useful in lowering non-neuropathic pain in several disorders. CONCLUSION: Although an emerging set of studies brings new evidence on the therapeutic potential of both LIFUS and HIFUS for managing NP with minor side-effects, we need more controlled clinical trials to conclude about its safety and efficacy.

The 2020 research pandemic: A bibliometric analysis of publications on COVID-19 and their scientific impact during the first months.

BACKGROUND: The outbreak of COVID-19 has created a landslide of publications, from different sources and unequal impact. We considered that the first 3 months are crucial to understand how knowledge has been generated by performing a bibliometric analysis, including the citations to these articles to guide researchers in exploring this field, and to evaluate the relationship between confirmed COVID-19 cases and deaths with the number of papers per country. METHODS: Scientific publications were obtained from PubMed (January-March 2020) and their citations during the first 6 months retrieved from the Scopus database. An analysis of the number of papers by country, approach (type and category of publication), and impact was made. A multiple linear regression model was implemented to analyze the correlation between the number of publications and confirmed cases and deaths. RESULTS: A total of 2,530 publications were analyzed with 59,104 citations (23.4 citations/article), written by authors from 67 countries. China was the country with more publications (988, 39%) and more citations (36,416, 63%) followed by the United States with 423 articles (16.7%) and 7,458 citations (12.6%). The coauthorship network identified 10,756 authors. According to the multivariate analysis, both confirmed cases and deaths were significantly correlated with the number of publications per country (corrected by population size and gross domestic product). CONCLUSION: The correlation with the number of publications suggests that cases and deaths had some impact on the medical literature, reflecting how rapidly the scientific community has been on the frontline in the fight against COVID-19.

Dehydroepiandrosterone increases tonic and phasic dopamine release in the striatum.

Dehydroepiandrosterone (DHEA) modulates dopaminergic neurotransmission. It takes part in neurologic and psychiatric diseases involving monoamine neurotransmitters. Earlier results show that DHEA (120-min treatment) reduced striatal dopamine (DA) turnover in rats, suggesting a reduced DA release. Some investigations report that DHEA increases DA release but inhibits motor activity, which seems contradictory. This research examines the effect of DHEA on striatal DA release, its metabolism and motor activity. Male Wistar rats were implanted in the striatum with a cannula for in vivo microdialysis. DHEA was administered (120 mg/kg) and dialysates were collected for 280 min. A depolarizing stimulus was applied at 120 min. Samples were analyzed by HPLC-ED to determine the concentration of DA and its metabolites. The effect of DHEA on motor activity was also evaluated during 120 min. Extracellular DA concentration was greater in treated animals both before and after depolarization. In contrast, DHEA reduced the areas below the curves for DA metabolites and DA/metabolite ratios. DHEA also reduced motor activity, remarkably in the first 20 min after treatment. In summary, DHEA yielded a stimulatory effect on striatal DA release that was not reflected in neither DA metabolism nor motor activity. Thus, DHEA resembles the effect of typical antipsychotics, increasing DA release but reducing behavioral activation.

Multidrug-resistant Klebsiella oxytoca ventriculitis, successfully treated with intraventricular tigecycline: A case report.

A 38-year-old male presented to the hospital with headache, fever, and meningeal signs. He had undergone a surgical review of a ventriculoperitoneal shunt system one month earlier. A head computed tomography scan showed hydrocephalus. His medical history included a human immunodeficiency virus infection identified four years before and resolved cryptococcal meningitis, which had necessitated the implantation of the shunt system. Ventricular cerebrospinal fluid (CSF) was obtained, which showed inflammation and, in culture, grew a Gram-negative bacillus identified as multidrug-resistant Klebsiella oxytoca. The shunt was removed and a ventricular drain was installed. Treatment with meropenem and amikacin was established without a response; the CSF white blood cell count continued to increase, with cultures remaining positive. The patient's clinical condition deteriorated to stupor. With informed consent, intraventricular (ITV) treatment with tigecycline was initiated at a dose of 5 mg every 24 h and, three days later, the CSF cultures were negativized. Tigecycline levels in the CSF were quantified by liquid chromatography with ultraviolet detection and showed peak concentrations achieved at two hours after the dose of between 178 and 310 µg/mL. After 11 days of treatment with ITV tigecycline and eight negative CSF cultures, a new CSF shunt was installed. During follow-up review 10 months later, the patient reported he was working. The dose of tigecycline used in this study produced levels 15 to 20 times the minimum inhibitory concentration of the bacteria for up to six hours with adequate tolerance.

Leptin Levels and Q223R Leptin Receptor Gene Polymorphism in Obese Mexican Young Adults.

INTRODUCTION: The Q223R polymorphism of the leptin receptor (LEPR) gene is one of the most common polymorphisms and it is believed to be associated with a damaged capacity of LEPR signaling and with high circulating leptin levels. METHODS: An observational, cross-sectional, analytical study was carried out in the Autonomous University of Ciudad Juarez, Mexico, where a sample of young adult participants (ranging from 18 to 30 years of age) was obtained. They were classified based on the results of body mass index: non-obese, and overweight/obese. The polymorphic variant was determined by Polymerase Chain Reaction (PCR) from the DNA sample and serum leptin levels were measured by Enzyme-Linked Immuno Sorbent Assay. RESULTS: A total of 159 participants were included (non-obese, n=103; overweight/obese, n=56). Leptin levels were 15.14±12.3 ng/mL in the non-obese group and 26.13±19.0 ng/mL in the overweight/obese group (p≤0.001). The allelic frequencies of the Q and R alleles of the LEPR gene in the studied subjects were as follows: non-obese, Q=0.56, R=0.44; overweight/obese, Q=0.62, R=0.38. The relative risk for the Q/Q genotype was 1.18 (Cl 0.53-2.34), for Q/R was 1.14 (Cl 0.59-2.18) and for R/R was 0.59 (Cl 0.23-1.50). CONCLUSIONS: This study shows that leptin levels are associated with overweight/obesity in Mexican young adults, but this is not related to the presence of the Q223R polymorphism in the LEPR gene, so the underlying mechanisms for a possible disturbance in leptin signaling in obese Mexican young adults await further studies.

Miller fisher syndrome: 10 years' experience in a third-level center.

INTRODUCTION: There are few studies regarding the clinical characteristics of Miller Fisher syndrome (MFS) in the Latin-American population. METHODS: A retrospective analysis was made of the clinical characteristics, neurophysiology, treatment and prognosis of MFS patients between 1995 and 2005. RESULTS: Nineteen MFS cases were documented, 12 of which did not receive immunosuppressive therapy. In both groups, the mean age was 36 years, 84% were male; onset in spring and fall was also predominant (73%), and antecedents of respiratory disease were found (79%). The mean duration of infectious symptoms was 7 days (1-11 days), and the mean interval between the onset of the infection and neurological symptoms was 7 days (1-30 days). The principal sign of onset was diplopia (63%). The mean delay between the onset of neurological symptoms and the beginning of recovery from ataxia, ophthalmoplegia and areflexia was 10 (1-30 days), 11 (1-30 days) and 14 (4-45 days) days, respectively, and the mean delay of the disappearance of ataxia, ophthalmoplegia and areflexia was 35 (10-121 days), 93 (18-244 days) and 64 (10-650 days) days, respectively. There was no significant difference between the group that received immunosuppression and the one that did not. DISCUSSION: The natural course of MSF is characterized by excellent recovery; there were no differences between the two groups.

Challenges for social media editors in rheumatology journals: an outlook.

Social media has become a key component of contemporary medicine, and the rheumatology subspecialty is not an exemption. We found that just six of the 40 key peer-reviewed rheumatology journals have found it sensible to incorporate the new appointment of a Social Media Editor-or a similar designation-into their Editorial Boards. We propose that the role of a social media editor is a trinomial: not only a technological work to promote digital engagement but also an activity of ethical guidance and a cultural challenge dealing with worldwide cultural and mindset diversity.

Calcium pyrophosphate deposition disease: historical overview and potential gaps.

CPPD disease can affect patients' quality of life through its various clinical presentations. This mini-review discusses the evolution of CPPD from its discovery to current knowledge of its pathogenesis, genetic associations, diagnostics, and treatment options. Despite extensive research, the exact mechanisms of CPPD are not well understood, and there is a notable lack of knowledge about psychosocial impacts and patient experiences. This study aims to present a CPPD Disease Timeline identifying gaps in current knowledge and potential directions for future research. These findings contribute to a broader understanding of CPPD disease and emphasize the importance of continued research and innovation in this field.

Histamine H3 receptor activation reduces the impairment in prepulse inhibition (PPI) of the acoustic startle response and Akt phosphorylation induced by MK-801 (dizocilpine), antagonist at N-Methyl-d-Aspartate (NMDA) receptors.

We have investigated the effect of the local activation of histamine H3 receptors (H3Rs) in the rat prefrontal cortex (PFCx) on the impairment of pre-pulse inhibition (PPI) of the startle response induced by the systemic administration of MK-801, antagonist at glutamate N-Methyl-d-Aspartate (NMDA) receptors, and the possible functional interaction between H3Rs and MK-801 on PFCx dopaminergic transmission. Infusion of the H3R agonist RAMH (19.8 ng/1 µl) into the PFCx reduced or prevented the inhibition by MK-801 (0.15 mg/kg, ip) of PPI evoked by different auditory stimulus intensities (5, 10 and 15 dB), and the RAMH effect was blocked by the H3R antagonist/inverse agonist ciproxifan (30.6 ng/1 µl). MK-801 inhibited [3H]-dopamine uptake (-45.4 ±â€¯2.1%) and release (-32.8 ±â€¯2.6%) in PFCx synaptosomes or slices, respectively, and molecular modeling indicated that MK-801 binds to and blocks the rat and human dopamine transporters. However, H3R activation had no effect on the inhibitory action of MK-801 on dopamine uptake and release. In PFCx slices, MK-801 and the activation of H3Rs or dopamine D1 receptors (D1Rs) stimulated ERK-1/2 and Akt phosphorylation. The co-activation of D1Rs and H3Rs prevented ERK-1/2 and Akt phosphorylation, and H3R activation or D1R blockade prevented the effect of MK-801. In ex vivo experiments, the intracortical infusion of the D1R agonist SKF-81297 (37 ng/1 µl) or the H3R agonist RAMH increased Akt phosphorylation, prevented by D1R/H3R co-activation. These results indicate that MK-801 enhances dopaminergic transmission in the PFCx, and that H3R activation counteracts the post-synaptic actions of dopamine.

Dopaminergic Hyperactivity in Neurological Patients with Delirium.

BACKGROUND: Delirium has important etiological, prognostic, and therapeutic implications. The study of neurochemical markers in this condition is relevant to the understanding of its pathophysiology. The assessment of the dopamine system is particularly relevant, as dopamine antagonists are the most used drugs in delirium. AIM: To analyze neurotransmission markers in patients with delirium, focusing in the dopamine metabolite, homovanillic acid. METHODS: A case-control study was performed at the National Institute of Neurology and Neurosurgery, Mexico, including hospitalized patients in which lumbar puncture was obtained for diagnostic purposes. Cases were selected if they fulfilled DSM-5 criteria for delirium. Age-paired controls were patients in which delirium was ruled out, selected at the same clinical scenario, during the same period. Neurological and systemic diagnoses were registered. Delirium was assessed using the DRS-98-R instrument. The dopamine metabolite, homovanillic acid (HVA), was measured by means of high-performance liquid chromatography. Other neurotransmission markers were also measured (5-hydroxyindoleacetic acid, glutamate, aspartate, GABA, glycine, arginine, citrulline, nitrites, and nitrates). A logistic regression model was used to determine pathogenic factors associated with the presence of delirium. RESULTS: 68 neurological patients with delirium and 68 patients without delirium were included. Higher homovanillic acid levels in cerebrospinal fluid were significantly associated with delirium. This result was significant after a subanalysis in patients without exposure to antipsychotics. Male gender and autoimmune limbic encephalitis were also associated with the presence of delirium. CONCLUSIONS: In hospitalized neurological patients, dopaminergic hyperactivity and autoimmune limbic encephalitis are pathogenic factors associated with the presence of delirium.