Rejected

Cluster headache is uniquely rhythmic in its occurrence both diurnally and annually. This has implications for the clinical approach to the patient but also for our understanding of the role of central structures in its pathological basis. Many intrinsic and extrinsic factors seem to influence CH rhythmicity, including genetics. The proclivity for attacks to occur at night and the possible association with particular sleep phenomena, including sleep apnea, have motivated a number of studies which has improved our understanding but many questions remain unanswered. The sleep-headache interaction seems to be bidirectional and possibly both direct and indirect. The latter could involve more disperse networks of homeostatic regulation, which may better encompass recent observations. Treatment of the headache patient with concurrent sleep problems can be particularly challenging, especially considering side-effects and interactions of commonly used medications. While current treatment guidelines do not incorporate chronotherapeutic thinking, some evidence may suggest that application of such principles on an individual level may be beneficial.

Continuous epidural infusion (CEI) can provide analgesia during labor. The dural puncture epidural (DPE) technique is used to accelerate the onset of neuraxia anesthesia. The primary objective of this study was to compare the percentage of patients that received adequate labor analgesia following an injection of 0.08% epidural ropivacaine via the DPE and CEI techniques combined with the PIEB mode of maintenance.

Switching antiretroviral therapy (ART) in people with HIV (PWH) can influence their risk for drug-drug interactions (DDIs). The purpose of this study was to assess changes in the incidence and severity of DDIs among PWH who switched their ART to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF).

As a central nervous system disease, migraine often coexists with gastrointestinal disorders, which suggests a disruption of brain-gut regulation. Clinical studies have confirmed that acupuncture and flunarizine not only alleviate migraine attacks but also substantially inhibit accompanying gastrointestinal symptoms. However, it is still not clear how acupuncture and flunarizine regulate the interactions of brain, gut, and microbiome. Therefore, this study will combine neuroimaging technology and gut microbiota detection technology to explore and compare the effects and brain-gut modulating mechanisms of acupuncture and flunarizine for migraine.

We aimed to compare the efficacy and safety of laparoscopic pyelolithotomy (LPL) versus percutaneous nephrolithotomy (PCNL) for treating renal stones larger than 2 cm.

Various questionnaires have been validated as methods for screening of neuropathic pain, but none have been established for the orofacial region. Although chronic pain and depression are likely to comorbid, few studies have examined the relationship between orofacial chronic pain and depression. Therefore, we evaluated the potential of the Japanese Version of PainDETECT as an assessment tool for neuropathic pain associated with burning mouth syndrome (BMS) and persistent idiopathic facial pain (PIFP). We also evaluated the depression scale such as Beck's Depression Inventory (BDI: a subjective index) and Hamilton Depression Rating Scale (HDRS: an objective index) with BMS or PIFP.

The purpose of this investigation was to compare pain control and patient satisfaction for conventional postoperative opioid analgesia and nonopioid multimodal analgesia after elective open or endoscopic carpal tunnel release (CTR).

Prostate cancer is one of the most common causes of cancer incidence and death in men, with the mortality caused primarily by the late-stage and metastatic forms of the disease. The mechanisms and molecular markers for prostate cancer metastasis are not fully understood. Speckle type Poz Protein (SPOP) is an E3 ubiquitin ligase adaptor that is often mutated in prostate cancer. In this study, we sequenced the gene in 198 prostate cancer patients and found 16 mutations in the cohort. Multivariate analysis revealed that mutations correlated with the clinical stage of the disease and strongly with metastasis. We identified ITCH as a candidate protein for SPOP-mediated degradation mass spectrometry. We demonstrated the interaction between SPOP and ITCH, and found that the F133L mutation disrupted the SPOP-ITCH interaction, leading to a subsequent increase in the ITCH protein level. Further, we found that the SPOP knockdown led to higher levels of Epithelial- mesenchymal transition (EMT) proteins and increased cell invasion. Together, our results highlight the functional significance of the SPOP-ITCH pathway in prostate cancer metastasis.

Pruritus is a key symptom in allergology and dermatology, contributing to the global and huge impact on quality of life related to skin disorders, both those which are not related to a primary dermatosis (illness) and those which are linked with primary skin lesions (disease). This is particularly evident within psychophysiological dermatoses, a group of psychodermatological diseases where there is a primary dermatosis, where psychological stress plays a role, and where pruritus may represent a major and shared symptom. The etiopathogenesis of pruritus in those disorders sheds light on the link among psychopathological features, psychological stress and the subtle interface between allergic and autoimmune mechanisms, where mast cells play a pivotal role. Allergy has long been recognised as an altered reactivity to exogenous antigens (allergens), defined as an immediate hypersensitivity mediated by immunoglobulin E (IgE). In turn, the immunological understanding of atopy is related to an immediate hypersensitivity reaction to environmental antigens involving T-helper 2 (Th2) responses and the IgE production. Mast cells are major cells in the early phase of allergy, releasing the mediators involved in the symptoms associated with the allergic disease, including pruritus, when the allergen cross-links with IgE, whose mechanisms can be observed in acute urticaria and atopy. Some allergic reactions may persist and allergy may eventually lead to autoimmunity, with the development of a T-helper 1 (Th1) and then IgE-independent inflammation. For instance, in chronic spontaneous urticaria, the mast cell activation may include autoimmune mechanisms, where autoantibodies against the extracellular α subunit of the high-affinity IgE receptor (FcεRIα) and to IgE are observed, with the involvement of Th1 lymphocytes and the production of interferon-γ (INF-γ). The role of autoimmunity is also suggested in the etiopathogenesis of other psychophysiological dermatoses, namely psoriasis, atopic dermatitis and alopecia areata. In the latter, for example, mast cells were reported to be linked with the loss of immune privilege and they are the key cells involved in the experience of pruritus, whose intensity was reported to precede and be correlated with the onset of the hair loss. Furthermore, considering that the role of hair and skin is wide, from psychosocial aspects (communication and social interaction) to vital functions (such as, temperature control), it is straightforward that they are central in our interactions and synchronization with others and the world; thereby, we may admit that the psychophysiological dermatoses could represent a loss of such synchronization. Furthermore, they are often linked with psychopathology which strongly connects with the concept of desynchronization, namely, sleep disorders and depressive symptoms, the clinical expression of a dysfunction in the interplay among mast cells, pineal gland and melatonin, thus the circadian rhythm, as well as their connection with the hypothalamic corticotrophin-releasing hormone (CRH), well-known for its key role in stress response. Moreover, increasing evidence has supported the existence of cutaneous equivalents for these mechanisms, connecting with those central pathways. Thereby, taking all these concepts into consideration, this review intends to look into the updated evidence on the shared biological mechanisms between allergy and autoimmunity, underlining pruritus as a core element, then revisiting the key role of mast cells and discussing the connection with melatonin and immune-inflammatory pathways in the physiopathology of psychophysiological dermatoses, thus paving the way for the understanding of their psychosomatic correlates and a comprehensive psychodermatological approach.

The existence of "sex phenotype" in migraine is a long-standing scientific question. Fluctuations of female sex hormones contribute to migraine attacks, and women also have enhanced brain activity during emotional processing and their functional brain networks seem to be more vulnerable to migraine-induced disruption compared to men. Periaqueductal grey matter (PAG) is a core region of pain processing and modulation networks with possible sex-related implications in migraine. In our study, sex differences of PAG functional resting-state connectivity were investigated in the interictal state in 32 episodic migraines without aura patients (16 women and 16 men). A significant main effect of sex was detected in PAG connectivity with postcentral, precentral, and inferior parietal gyri, and further differences were found between right PAG and visual areas (superior occipital gyrus, calcarine, and cuneus), supplementary motor area, and mid-cingulum connectivity. In all cases, PAG functional connectivity was stronger in female migraineurs compared to males. However, higher average pain intensity of migraine attacks correlated with stronger connectivity of PAG and middle temporal, superior occipital, and parietal gyri in male migraineurs compared to females. Migraine-related disability is also associated with PAG connectivity but without sex differences. Our results indicate that sex differences in PAG connectivity with brain regions involved in sensory and emotional aspects of pain might contribute to the "sex-phenotype" in migraine. The stronger functional connectivity between PAG and pain processing areas may be a sign of increased excitability of pain pathways even in resting-state in females compared to male migraineurs, which could contribute to female vulnerability for migraine. However, pain intensity experienced by male migraineurs correlated with increased connectivity between PAG and regions involved in the subjective experience of pain and pain-related unpleasantness. The demonstrated sex differences of PAG functional connectivity may support the notion that the female and male brain is differently affected by migraine.