YokoCo

Preventive treatment for refractory chronic cluster headache (rCCH) is challenging and many therapies have been tried.

Recent studies have indicated that long-term neurological sequelae after COVID-19 are not accompanied by an increase of canonical biomarkers of central nervous system injury in blood, but subgroup stratifications are lacking. This is a particular concern in chronic headache, which can be a leading symptom of Post-COVID diseases associated with neuronal damage such as vasculitis or autoimmune encephalitis. We here compared patients with mild Post-COVID-19 syndrome and persistent headache (persistent Post-COVID-19 headache) lasting longer than 12 weeks after the initial serological diagnosis, to patients with mild and severe COVID-19 and COVID-19-negative controls. Levels of neurofilament light chain and glial fibrillary astrocytic protein, i.e. markers of neuronal damage and reactive astrogliosis, were lower in blood from patients with persistent Post-COVID-19 headache compared to patients with severe COVID-19. Hence, our pilot serological study indicates that long-term Post-COVID-19 headache may not be a sign of underlying neuronal damage or neuroinflammation.

Opioid analgesics exert their therapeutic and adverse effects by activating mu opioid receptors (MOPR), however functional responses to MOPR activation are modulated by distinct signal transduction complexes within the brain. The ventrolateral periaqueductal gray (vlPAG) plays a critical role in modulation of nociception and analgesia, but the exact intracellular pathways associated with opioid responses in this region are not fully understood. We previously showed that knockout of the signal transduction modulator RGSz1 (RGSZ1KO) enhanced analgesic responses to opioids, while it decreased the rewarding efficacy of morphine. Here, we applied viral mediated gene transfer and delivered AAV-Cre viruses to the vlPAG of RGSz1 mice to demonstrate that downregulation of RGSz1 in this region decreases sensitivity to morphine in the place preference paradigm, under pain-free as well as neuropathic pain states. We also utilized retrograde viral vectors along with flipase-dependent Cre vectors to conditionally downregulate RGSz1 in vlPAG projections to the ventral tegmental area (VTA) and show that downregulation of RGSz1 prevents the development of place conditioning to low morphine doses. Consistent with the role for RGSz1 as a negative modulator of MOPR activity, RGSz1KO enhances opioid-induced cAMP inhibition in PAG membranes. Furthermore, using a new generation of BRET sensors, we demonstrate that RGSz1 modulates Galphaz but not other Gai subunits, and selectively impedes MOPR-mediated Galphaz signaling events invoked by morphine and other opioids. Our work highlights a regional and circuit-specific role of the G protein signaling modulator RGSz1 in morphine reward, providing insights on midbrain intracellular pathways that control addiction-related behaviors. In this study we used advanced genetic mouse models to highlight the role of the signal transduction modulator named RGSz1 in responses to clinically used opioid analgesics. We show that RGSz1 controls the rewarding efficacy of opioids by actions in vlPAG projections to the ventral tegmental area, a key component of the midbrain dopamine pathway. These studies highlight novel mechanisms by which pain-modulating structures control the rewarding efficacy of opioids.

Osteoarthritis (OA) is a degenerative disease that leads to the progressive destruction of articular cartilage. Current clinical therapeutic strategies are moderately effective at relieving OA-associated pain but cannot induce chondrocyte differentiation or achieve cartilage regeneration. We investigated the ability of wedelolactone, a biologically active natural product that occurs in Eclipta alba (false daisy), to promote chondrogenic differentiation.

Prevalence of intracranial aneurysms in children with Apert syndrome has not been described, and development of an aneurysm as a complication secondary to craniofacial surgery has never been reported.

Homozygous familial hypercholesterolaemia (HoFH) is a disorder affecting low-density lipoprotein (LDL) receptor genes. Patients typically have a triad of elevated LDL-cholesterol (LDL-C), xanthomatosis and premature atherosclerotic cardiovascular disease. Our patient, a preteen boy, presented with signs of hypertensive encephalopathy. Physical examination showed arcus cornealis, planar xanthomas and tuberous xanthomas. After appropriate investigations, a direct aetiology of the hypertension could not be elucidated; however, our patient's hypertension resolved with the reduction in serum lipid levels. β-hydroxy β-methylglutaryl coenzyme A reductase and cholesterol absorption inhibitors were administered as first-line treatment. A significant proportion of patients with HoFH continue to have elevated LDL-C levels, thereby requiring second-line agents, such as proprotein convertase subtilisin/kexin type inhibitors (evolocumab), microsomal triglyceride transfer protein inhibitors (lomitapide) and angiopoietin-like protein inhibitors (evinacumab). This case report aimed to raise awareness among paediatricians to consider HoFH as a possible aetiology in a child presenting with hypertension and suggestive physical findings.

Relying on anthropomorphism research, Illness Personification Theory (ILL-PERF) posits that individuals living with a chronic illness ascribe human-like characteristics to their illness. Herein we examine the personification of chronic pain using a new measure: the Ben-Gurion University Illness Personification Scale (BGU-IPS). Three samples of chronic pain patients (Sample 1 and 2 are distinct samples sharing similar characteristics, collected in the context of a cross-sectional design, Ns = 259, 263; Sample 3: a 2-waves longitudinal, N =163) completed the 12-item BGU-IPS, and measures of pain and related factors. An orthogonal, two-factor structure was revealed for the BGU-IPS pertaining to negative vs. positive personifications. Negative personification was associated with pain intensity and illness-related distress (e.g., depression and low adjustment to pain). Positive personification was correlated with hope, pain-related sense of control, and low depression. However, positive personification also augmented the associations between negative personification and several risk factors. : Pain personification, particularly as assessed via the BGU-IPS, plays a major role in (mal)adaptation to chronic pain.

Treatment of articular cartilage, tendon and soft tissue damage remains a challenge for the practicing orthopaedic surgeon. Due to the multifactorial aetiology of these lesions, there is a narrow therapeutic window within which they can be treated successfully, thus preventing progression to other musculoskeletal tissues. Recently, a new material that combines platelet-rich fibrin with collagen and is applied as a gel scaffold (ArthroZheal®, Vivostat A/S, Allerød, Denmark) has been shown to provide unique results in these patients. We arthroscopically treated 210 patients (114 knees, 32 hips, 52 shoulders, 12 ankle joints) with ArthroZheal®. The basic idea was to adjust treatment to the individual patient and to repair related and/or contributing problems before or along with treatment of chondral/tendon/ligament injuries. Arthroscopy was our preferred surgical method; the goal was to restore and preserve function, alleviate pain and minimise progression to osteoarthritis. We excluded cases of inflammatory arthropathy, unstable or malaligned joint, "kissing lesions" (bipolar), infection, obesity, massive rotator cuff rupture and multiligament instability. Our results were more than promising. We observed improved mobility in 93%, reduced pain in 95% at 3 months and further improvement at 6 months, with near-normal ROM (97% ) and pain-free status (98%). The MRI at 12 months post application showed cartilage restoration/reformation in 94% of patients, improved cartilage quality (84% )-by 2nd-look arthroscopic confirmationand normal tendon or ligament reconstruction (without stitching of the affected area)(95%). We were concerned about bone marrow oedema and rehab compliance among elderly patients. For successful regeneration of tissue lesions and osteochondral defects, natural gel bioscaffolds, combined with platelet rich fibrin (PRF) with chondroinductive and osteoinductive growth factor stimulators (ArthroZheal®) are required. There is no "gold standard" in the treatment of cartilage defect/tissue lesions or preferred treatment option. Many algorithms are used, which mostly rely on the surface area of the defect/site of lesion and on surgeon experience. An important issue is that rehabilitation depends on the treatment mode used and on the defect/lesion characteristics (classification and qualification). While a return to functional work and sports is possible with all procedures, different lengths of time are needed.

This survey investigated on adverse events after vaccination with mRNA BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine in children aged 5-11 years in central Italy through active surveillance reporting. During December 2021-January 2022, parents of children who undergone vaccination were interviewed using a structured questionnaire. 197 out of 208 contacted parents participated (94.7% response rate), of whom 166 (84.3%) had one child. Of the 229 children, the mean age was 8.9 years, 50.7% were female. 193 (84.3%) had at least one adverse event after the first dose (mean age 9.1 years; 54.4% female), and 146 (73.4%) of 199 after the second (mean age 8.9 years; 54.8% female), which was not administered to 30 children due to previous COVID-19 history. Local symptoms after the first and second dose occurred in 183 (94.8%) and 141 (96.6%) recipients (p = .435), respectively, while systemic reactions in 62 (32.1%) and 34 (23.3%) ( = .074). Mild events were reported by 81.7% and 69.8% children after the first and second dose, followed by moderate (3.9% and 10.6%) and severe (1.3% and 0.5%). After each dose, injection site reactions (79.5% and 68.8%) were the most frequent, followed by headache (13.1%) and lymphadenopathy (8.5%) after the first and second dose, respectively. The adverse events were reported to pediatricians only for 5.7% and 3.9% of children and treated for 17.6% and 15.8%. This is the first report about safety profile through active surveillance of mRNA BNT162b2 among children in Italy, revealing temporary and mild-to-moderate symptoms with no serious events after each vaccine dose.

Examine SCAT5 baseline and acute symptom subscales in professional hockey players.