Rejected

Chronic musculoskeletal pain and disability dramatically reduce quality and quantity of life worldwide, disproportionately so in low- and middle-income countries. Complementary therapies not typically learned in conventional medical training have much to offer but are under-utilized. Prolotherapy is an injection-based complementary therapy supported by high-quality evidence for osteoarthritis, tendinopathy, and low back pain. Prolotherapy addresses causes of pain and disability at the tissue level, is straightforward to learn, and relies on common, inexpensive material, and requires no refrigeration. Not-for-profit organizations are delivering prolotherapy to underserved patients in low- and middle-income countries through service-learning projects.

To review the efficacy, safety, and pharmacology of brexanolone (Zulresso), a new antidepressant with a novel mechanism of action, in the treatment of postpartum depression (PPD).

Thromboses and phenotypic evolutions (leukemia, myelofibrosis) are the most frequent complications in Polycythemia vera (PV) and essential thrombocythemia (ET). Aquagenic pruritus (AP) is not only PV symptom, but is also present in ET. The presence of pruritus in PV is associated with a lower risk of arterial thrombosis. Among 396 ET patients, presence of AP characterizes patients with higher risk of morbidity: more proliferative, more symptomatic at diagnosis and higher risk of thromboses and evolutions. The systematic determination of the presence of AP in ET patients should permit to better identify these high-risk patients for better management and follow-up. This article is protected by copyright. All rights reserved.

Sickle cell disease (SCD) is among the most common genetic diseases in the United States, affecting approximately 100,000 people. In the United States, SCD is characterized by a shortened life expectancy of only about 50 years in severe subtypes, significant quality-of-life impairments, and increased healthcare utilization and spending. SCD is characterized by chronic hemolytic anemia, vaso-occlusion, and progressive vascular injury affecting multiple organ systems. The pathophysiology is directly related to polymerization of deoxygenated hemoglobin, leading to a cascade of pathologic events including erythrocyte sickling, vaso-occlusion, tissue ischemia, and reperfusion injury as well as hemolysis, abnormal activation of inflammatory and oxidative pathways, endothelial dysfunction, increased oxidative stress, and activation of coagulation pathways. These multifactorial abnormalities have both acute and chronic clinical consequences across multiple organ systems, including acute pain episodes, chronic pain syndromes, acute chest syndrome, anemia, stroke and silent cerebral infarcts, cognitive dysfunction, pulmonary hypertension, and a wide range of other clinical consequences. Hydroxyurea was the only approved treatment for SCD for nearly 2 decades; in 2017, L-glutamine oral powder was approved for the prevention of the acute complications of SCD. During the last several years there has been a dramatic increase in research into treatments that address distinct elements of SCD pathophysiology and even new curative approaches that provide new hope to patients and physicians for a clinically consequential disease that has long been neglected.

Neuroplasty, also known as percutaneous adhesiolysis, is an effective treatment for persistent axial and radicular pain.

This PubMed-based review discusses primary and secondary sleep disorders associated with rheumatological diseases. It presents the pathophysiological interaction of sleep-related diseases and rheumatological disorders and summarises clinical symptoms, diagnostic investigation and therapies from a somnological perspective.

Primary care physicians can help their patients with migraine modify their triggers, and thereby mitigate the severity and frequency of their symptoms, by offering lifestyle modification counseling based on the mnemonic SEEDS (sleep, exercise, eat, diary, and stress). The authors review evidence associated with each of these factors and provide best-practice recommendations.

Osteoarthritis (OA) is a degenerative chronic disease affecting the whole joint structures. With the increment in life expectancy and aging population, OA has become one of the largest socioeconomic burdens, associated with pain and loss of joint function. However, early laboratory tests of OA are still lacking. Therefore, new diagnostic tests for this disease are urgently needed. In this study, to gain an insight into the pathogenesis and the potential biomarkers of OA, we implemented a comparative urine proteomics study on OA patients and health people using iTRAQ-based mass spectrometry technology. Western blotting was used to validate the relative changes in urine protein levels for four of the identified proteins. We constructed a comprehensive urine proteome profile of the OA patients and identified 102 proteins differently changed in abundance. Forty-six proteins were upregulated and 56 proteins were significantly downregulated in OA patients. Furthermore, the proteins, COL-4, MMP9, adiponectin, and BBOX1 were validated through Western blots, which can serve as valuable candidate biomarkers and help to illustrate the pathogenesis of OA. These findings may provide clues for promising biomarkers for the early diagnosis and also offer a theoretical basis for the early treatment of OA.

Polymicrogyria is a heterogeneous malformation of cortical development microscopically defined by an excessive folding of the cortical mantle resulting in small gyri with a fused surface. Polymicrogyria is responsible for a wide range of neurological symptoms (e.g. epilepsy, intellectual disability, motor dysfunction). Most cases have a supposed environmental clastic vascular or infectious origin but progress in genomics has revealed new monogenic entities. We report four cases from two independent families sharing a common recognizable lethal syndromic polymicrogyria of autosomal recessive inheritance. Beyond diffuse polymicrogyria detected prenatally, pathological examination revealed a common pattern associating meningeal arterial calcifications, necrotic and calcified areas in basal ganglia, dentato-olivary dysplasia and severe hypoplasia/agenesis of the pyramidal tracts. In all affected cases, exome sequencing showed a pathogenic homozygous nonsense ATP1A2 variant. This resulted in absence of immunodetectable ATP1A2 protein in two brains analysed. ATP1A2 encodes the alpha-2 isoform of the Na+/K+-ATPase, which is highly expressed in brain tissues and has previously been related to familial hemiplegic migraine (MIM#602481) and alternating hemiplegia of childhood (MIM#104290). Through the description of this genetic entity, we emphasize the possibility of dual mode of transmission for disease-causing genes and provide the key neuropathological features that should prompt geneticists to test for mutations in the ATP1A2 gene.

Previous studies have shown that α7 nicotinic acetylcholine receptor (nAChR) has a critical role in the regulation of pain sensitivity and neuroinflammation. However, pharmacological effects of α7 nAChR activation in the hippocampus on neuroinflammatory mechanisms associated with allodynia and hyperalgesia remain unknown. We have determined the effects of 3a,4,5,9b-tetrahydro-4-(l-naphthalenyl)-3H-cyclopentan[c]quinoline-8-sulfonamide (TQS), an α7 nAChR positive allosteric modulator, on lipopolysaccharide (LPS)-induced allodynia and hyperalgesia in mice. We also evaluated the effects of TQS on immunoreactivity of microglial marker ionized-calcium binding adaptor molecule 1 (Iba-1), phospho-nuclear factor-KB (p-NF-KB p), tumor necrosis factor-alpha (TNF-α), and norepinephrine (NE) level.