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Non-specific chronic low back pain (cLBP) represents a common musculoskeletal condition with no identifiable cause. It cannot be diagnosed with conventional neuroimaging techniques such as computerized tomography (CT). The diagnostic uncertainty that characterizes non-specific cLBP can lead to stigmatizing responses from others that can become internalized Among individuals with non-specific cLBP, internalized stigma is associated with greater pain intensity and disability. Yet, no study has examined the biological mechanism linking high internalized stigma to worse outcomes in individuals with non-specific cLBP. We aimed to identify differentially methylated loci (DML), enrichment pathways, and associated network interactions among individuals with non-specific cLBP experiencing low vs. high internalized stigma. We examined DNA methylation in whole blood samples from 48 adults, ages 19-85, using reduced representation bisulfite sequencing (RRBS). After controlling for age, sex, race, and multiple testing, differentially methylated loci (DML) differed in adults with low vs. high internalized stigma by at least 10% and  < 0.01 in 3,665 CpG sites: 2,280 hypomethylated and 1,385 hypermethylated. Gene ontology (GO) analyses of the annotated genes from these sites revealed significant enrichment of 274 biological processes, 29 cellular components, and 24 molecular functions (adjusted  < 0.05). The top enriched molecular functions regulate protein binding and DNA binding of transcription factor activity. Pathway analyses indicated that many functional genomic pathways, including Hippo Signaling, Melanogenesis, and Pathways in Cancer, were enriched with differentially methylated genes. Also, there was a significant interaction between relevance pathways such as , , , and pathways. These pathways have previously been associated with neuroinflammation, neurodegeneration, and stress-related conditions. Thus, findings point to possible stress-induced DNAm changes as the link between high levels of internalized stigma and worse outcomes in adults with non-specific cLBP.

We report a very rare case of referred pain associated with entrapment of the greater occipital nerve (GON) occurring not only in the ipsilateral hemiface but also in the ipsilateral limb. There is an extensive convergence of cutaneous, tooth pulp, visceral, neck, and muscle afferents onto nociceptive and nonnociceptive neurons in the trigeminal nucleus caudalis (medullary dorsal horn). In addition, nociceptive input from trigeminal, meningeal afferents projects into trigeminal nucleus caudalis and dorsal horn of C1 and C2. Together, they form a functional unit, the trigeminocervical complex (TCC). The nociceptive inflow from suboccipital and high cervical structures is mediated with small-diameter afferent fibers in the upper cervical roots terminating in the dorsal horn of the cervical cord extending from the C2 segment up to the medullary dorsal horn. The major afferent contribution is mediated by the spinal root C2 that is peripherally represented by the greater occipital nerve (GON). Convergence of afferent signals from the trigeminal nerve and the GON onto the TCC is regarded as an anatomical basis of pain referral in craniofacial pain and primary headache syndrome. Ipsilateral limb pain occurs long before the onset of the referred facial pain. The subsequent severe hemifacial pain suggested GON entrapment. The occipital nerve block provided temporary relief from facial and extremity pain. Imaging studies found a benign osteoma in the ipsilateral suboccipital bone, but no direct contact with GON was identified. During GON decompression, severe entrapment of the GON was observed by the tendinous aponeurotic edge of the trapezius muscle, but the osteoma had no contact with the nerve. Following GON decompression, the referred trigeminal and extremity pain completely disappeared. The pain referral from GON entrapment seems to be attributed to the sensitization and hypersensitivity of the trigeminocervical complex (TCC). The clinical manifestations of TCC hypersensitivity induced by chronic entrapment of GONs are diverse when considering the occurrence of extremity pain as well as facial pain.

Diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI) were applied to speculate the altered structural and functional abnormalities within the hippocampus in classical trigeminal neuralgia (CTN) patients by detecting the alteration of apparent diffusion coefficient (ADC), fractional anisotropy (FA), and regional homogeneity (ReHo). . Multimodal MRI dataset (DTI and fMRI) and clinical indices (pain and neuropsychological scores) were collected in 27 CTN patients and 27 age- and gender-matched healthy controls (HC). Two independent-sample -tests were performed to compare the ADC, FA, and ReHo values in hippocampus areas between CTN patients and HC. Correlation analyses were applied between all the DTI and fMRI parameters within the hippocampus and the VAS (visual analog scale), MoCA (Montreal cognitive assessment), and CDR (clinical dementia rating) scores.

Internal jugular agenesis is a vascular malformation that is often associated with a history of recurrent headache. Due to the resulting abnormalities in intracranial venous drainage, it may be complicated by neurological dysfunction, such as intracranial hypertension, intracranial micro-thromboses, and neurodegenerative diseases such as multiple sclerosis. The simultaneous presence of jugular vein agenesis and thrombosis is possible in cases of acute illness, hormonal treatment, pregnancy, hypomobility, or venous drainage abnormalities (VDA) (e.g., May-Thurner syndrome). In particular, the literature still lacks data on thromboprophylaxis in pregnant women with jugular vein agenesis. Here, we report a positive experience with prophylaxis using enoxaparin during pregnancy in a patient with internal jugular agenesis.

Migraine is a highly prevalent disorder with an enormous burden on societies. Different types of medications are used for controlling both acute attacks and prevention. This article reviews some non-pharmacological recommendations aiming to manage migraine disorder better and prevent headache attacks. Different triggers of migraine headache attacks, including environmental factors, sleep pattern changes, diet, physical activity, stress and anxiety, some medications, and hormonal changes, are discussed. It is advised that they be identified and managed. Patients should learn the skills to cope with the trigger factors that are difficult to avoid. In addition, weight control, management of migraine comorbidities, lifestyle modification, behavioural treatment and biofeedback, patient education, using headache diaries, and improving patients' knowledge about the disease are recommended to be parts of migraine management. In addition, using neuromodulation techniques, dietary supplements such as riboflavin, coenzyme Q10 and magnesium, and acupuncture can be helpful. Non-pharmacological approaches should be considered in migraine management. Furthermore, the combination of pharmacological and non-pharmacological approaches is more effective than using each separately.

Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome is an acronym for synovitis, pustulosis, acne, hyperostosis, and osteitis, and clinically manifests as dermatological and musculoskeletal damage. Two major manifestations that co-occur in a single patient are rare.

A 50-year-old man was admitted to our hospital for vomit, nausea, diplopia, and headache resistant to analgesic drugs. Symptoms started the day after his third COVID-19 mRNA vaccine (Moderna) whereas SARS-CoV-2 nasal swab was negative. Pituitary MRI showed recent bleeding in macroadenoma, consistent with pituitary apoplexy. Adverse Drug Reaction was reported to AIFA (Italian Medicines Agency).A stress dexamethasone dose was administered due to the risk of adrenal insufficiency and to reduce oedema. Biochemistry showed secondary hypogonadism; inflammatory markers were elevated as well as white blood cells count, fibrinogen and D-dimer. Pituitary tumour transsphenoidal resection was performed and pathology report was consistent with pituitary adenoma with focal haemorrhage and necrosis; we found immunohistochemical evidence for SARS-CoV-2 proteins next to pituitary capillaries, in the presence of an evident lymphocyte infiltrate.Few cases of pituitary apoplexy after COVID-19 vaccination and infection have been reported. Several hypotheses have been suggested to explain this clinical picture, including cross-reactivity between SARS-CoV-2 and pituitary proteins, COVID-19-associated coagulopathy, infection-driven acutely increased pituitary blood demand, anti-Platelet Factor 4/heparin antibodies development after vaccine administration. Ours is the first case of SARS-CoV-2 evidence in pituitary tissue, suggesting that endothelial infection of pituitary capillaries could be present before vaccination, possibly due to a previous asymptomatic SARS-CoV-2 infection. Our case underlines that SARS-CoV-2 can associate with apoplexy by penetrating the central nervous system, even in cases of negative nasal swab. Patients with pituitary tumours may develop pituitary apoplexy after exposure to SARS-CoV-2, therefore clinicians should be aware of this risk.

Obesity-induced metabolic syndrome is a rapidly growing conundrum, reaching epidemic proportions globally. Chronic inflammation in obese adipose tissue plays a key role in metabolic syndrome with a series of local and systemic effects such as inflammatory cell infiltration and inflammatory cytokine secretion. Adipose tissue macrophages (ATM), as one of the main regulators in this process, are particularly crucial for pharmacological studies on obesity-related metabolic syndrome. Ponatinib, a multi-targeted tyrosine kinase inhibitor originally used to treat leukemia, has recently been found to improve dyslipidemia and atherosclerosis, suggesting that it may have profound effect on metabolic syndrome, although the mechanisms underlying have not yet been revealed. Here we discovered that ponatinib significantly improved insulin sensitivity in leptin deficient obese mice. In addition to that, ponatinib treatment remarkably ameliorated high fat diet-induced hyperlipidemia and inhibited ectopic lipid deposition in the liver. Interestingly, although ponatinib did not reduce but increase the weight of white adipose tissue (WAT), it remarkably suppressed the inflammatory response in WAT and preserved its function. Mechanistically, we showed that ponatinib had no direct effect on hepatocyte or adipocyte but attenuated free fatty acid (FFA) induced macrophage transformation from pro-inflammatory to anti-inflammatory phenotype. Moreover, adipocytes co-cultured with FFA-treated macrophages exhibited insulin resistance, while pre-treat these macrophages with ponatinib can ameliorate this process. These results suggested that the beneficial effects of ponatinib on metabolic disorders are achieved by inhibiting the inflammatory phenotypic transformation of ATMs, thereby maintaining the physiological function of adipose tissue under excessive obesity. The data here not only revealed the novel therapeutic function of ponatinib, but also provided a theoretical basis for the application of multi-target tyrosine kinase inhibitors in metabolic diseases.

Little is known on the sex-specific healing responses after an anterior cruciate ligament (ACL) rupture. To address this, we compared male and female Sprague-Dawley rats following non-surgical ACL rupture. Hematology, inflammation, joint swelling, range of motion, and pain-sensitivity were analyzed at various times over 31-days. Healing was assessed by histopathology and gene expression changes in the ACL remnant and adjacent joint tissues. In the first few days, males and females showed similar functional responses after rupture, despite contrasting hematology and systemic inflammatory profiles. Sex-specific differences were found in inflammatory, immune and angiogenic potential in the synovial fluid. Histopathology and increased collagen and fibronectin gene expression revealed significant tissue remodeling in both sexes. In the ACL remnant, however, Acta2 gene expression (α-SMA production) was 4-fold higher in males, with no change in females, indicating increased fibroblast-to-myofibroblast transition with higher contractile elements (stiffness) in males. Females had 80% lower Pparg expression, which further suggests reduced cellular differentiation potential in females than males. Sex differences were also apparent in the infrapatellar fat pad and articular cartilage. We conclude females and males showed different patterns of healing post-ACL rupture over 31-days, which may impact timing of reconstruction surgery, and possibly clinical outcome.

Colon capsule endoscopy (CCE) has been available for nearly two decades but has grappled with being an equal diagnostic alternative to optical colonoscopy (OC). Due to the COVID-19 pandemic, CCE has gained more foothold in clinical practice. In this cutting-edge review, we aim to present the existing knowledge on the pros and cons of CCE and discuss whether the modality is ready for a larger roll-out in clinical settings. We have included clinical trials and reviews with the most significant impact on the current position of CCE in clinical practice and discuss the challenges that persist and how they could be addressed to make CCE a more sustainable imaging modality with an adenoma detection rate equal to OC and a low re-investigation rate by a proper preselection of suitable populations. CCE is embedded with a very low risk of severe complications and can be performed in the patient's home as a pain-free procedure. The diagnostic accuracy is found to be equal to OC. However, a significant drawback is low completion rates eliciting a high re-investigation rate. Furthermore, the bowel preparation before CCE is extensive due to the high demand for clean mucosa. CCE is currently not suitable for large-scale implementation in clinical practice mainly due to high re-investigation rates. By a better preselection before CCE and the implantation of artificial intelligence for picture and video analysis, CCE could be the alternative to OC needed to move away from in-hospital services and relieve long-waiting lists for OC.