Rejected

Patients with essential thrombocythemia (ET) can experience hemorrhagic or ischemic vascular events. The prevention of these complications is challenging, and the overall risk of vascular events caused by ET is often overlooked. A 34-year-old man was admitted for a 10-day history of weakness and numbness in his right limbs. He had been diagnosed with ET in 2008 but had stopped receiving treatment half a year before admission. Physical examination showed a superficial sense of disturbance in the right limbs and decreased muscle strength in the right upper and lower limbs (4/5). His platelet count (459 × 10/L) was elevated. Magnetic resonance imaging showed acute watershed infarction, and he was treated successfully. However, he was readmitted for headache and left limb weakness 14 months later. A head computed tomography scan revealed spontaneous subdural hemorrhage. He underwent subdural hematoma removal and decompressive craniectomy. Surgery and pathological investigation revealed no venous sinus thrombosis or vascular malformation. His condition improved, and he exhibited a stable condition 1 year after discharge. Successive development of ischemic stroke and spontaneous subdural hemorrhage is rare in a patient with ET. This case suggests that ET is not only a risk factor for stroke but can also cause highly heterogeneous strokes.

Communication is key to understanding the emotional state of critical care patients.

Conventional neuroimaging techniques cannot truly reflect the change of regional cerebral blood flow in patients with carpal tunnel syndrome. Pseudo-continuous arterial spinning labeling (pCASL) as an efficient non-invasive neuroimaging technique can be applied to directly quantify the neuronal activities of individual brain regions that show the persistent symptoms owing to its better spatial resolution and increased signal-to-noise ratio. Therefore, this prospective observational study was conducted in 27 eligible female carpal tunnel syndrome, aged 57.7 ± 6.51 years. Psychometric tests, nerve conduction studies and pCASL neuroimaging assessment were performed. The results showed that the relevant activated brain regions in the cortical, subcrotical, and cerebral regions were correlated with numbness, pain, functionality, median nerve status and motor amplitude of median nerve (K = 21-2849, r = -0.77-0.76, P < 0.05). There was a tendency of pain processing which shifted from the nociceptive circuitry to the emotional and cognitive one during the process of chronic pain caused by carpal tunnel syndrome. It suggests the necessity of addressing the ignored cognitive or emotional state when managing patients with carpal tunnel syndrome. Approval for this study was obtained from the Institutional Review Board of The University of Hong Kong/Hospital Authority Hong Kong West, China (HKU/HA HKW IRB, approval No. UW17-129) on April 11, 2017. This study was registered in Clinical Trial Registry of The University of Hong Kong, China (registration number: HKUCTR-2220) on April 24, 2017.

Differences in movement asymmetry between surfaces and with increasing speed increase the complexity of incorporating gait analysis measurements from lunging into clinical decision making. This observational study sets out to quantify by means of quantitative gait analysis the influence of surface and speed on individual-rein movement asymmetry measurements and their averages across reins (average-rein measurements). Head, withers, and pelvic movement asymmetry was quantified in 27 horses, identified previously as presenting with considerable movement asymmetries on the straight, during trot in hand and on the lunge on two surfaces at two speeds. Mixed linear models ( < 0.05) with horse as the random factor and surface and speed category (and direction) as fixed factors analyzed the effects on 11 individual-rein and average-rein asymmetry measures. Limits of agreement quantified differences between individual-rein and average-rein measurements. A higher number of individual-rein asymmetry variables-particularly when the limb that contributed to movement asymmetry on the straight was on the inside of the circle-were affected by speed (nine variables, all ≤ 0.047) and surface (three variables, all ≤ 0.037) compared with average-rein asymmetry variables (two for speed, all ≤ 0.003; two for surface, all ≤ 0.046). Six variables were significantly different between straight-line and average-rein assessments (all ≤ 0.031), and asymmetry values were smaller for average-rein assessments. Limits of agreement bias varied between +0.4 and +4.0 mm with standard deviations between 3.2 and 12.9 mm. Fewer average-rein variables were affected by speed highlighting the benefit of comparing left and right rein measurements. Only one asymmetry variable showed a surface difference for individual-rein and average-rein data, emphasizing the benefit of assessing surface differences on each rein individually. Variability in straight-line vs. average-rein measurements across horses and exercise conditions highlight the potential for average-rein measurements during the diagnostic process; further studies after diagnostic analgesia are needed.

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.

There is vast published literature proposing repetitive transcranial magnetic stimulation (rTMS) technology on the motor cortex (M1) for the treatment of neuropathic pain (NP). Systematic reviews (SRs) focus on a specific problem and do not provide a comprehensive overview of a research area. This study aimed to summarize and analyze the evidence of rTMS on the M1 for NP treatment through a new synthesis method called evidence mapping.

African tick-bite fever (ATBF), caused by , is the main tick-borne rickettsiosis and the second most frequent cause of fever after malaria in travelers returning from sub-Saharan Africa. General descriptions on ATBF were made in the first two decades after recognized as a new infectious entity, and since then, many authors have contributed to the knowledge of the disease by reporting clinical cases in scientific literature. We developed a systematic review that evaluated all available evidence in the literature regarding clinical, epidemiological, and laboratory features of confirmed rickettsiosis cases. We followed the recommendations made by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guide. A total of 48 scientific publications (108 confirmed cases) were analyzed in order to extract data for developing this review. Overall, our results show that rickettsiosis is more frequent in males in the age group of 18-64 years, more than 80% of the cases occurred in European travelers, South Africa was the country where most infections were acquired, and almost 40% of cases occurred in clusters. Clinically, more than 80% of the cases had fever and eschar (55% developed multiple eschars), rash was present in less than the half of cases, and lymphangitis was not a common sign (11%). Headache, myalgia and regional lymphadenopathy were predominant nonspecific clinical manifestation (mean of 60%, 49% and 51%, respectively). Our results show that at least 70% of cases had altered laboratory parameters, most often showing an increase in transaminases and C-reactive protein. Tetracycline-class antibiotics, as monotherapy, were used in most (>90%) of the patients. Overall, only 4% of cases had complications, 12% required hospitalization, and there was a 100% rate of clinical recovery.

Crocin, the main biologically active carotenoid of saffron, generally is derived from the dried trifid stigma of L. Many studies have demonstrated that crocin has several therapeutic effects on biological systems through its anti-oxidant and anti-inflammatory properties. The wide range of crocin activities is believed to be because of its ability to anchor to many proteins, triggering some cellular pathways responsible for cell proliferation and differentiation. It also has therapeutic potentials in arthritis, osteoarthritis, rheumatoid arthritis, and articular pain probably due to its anti-inflammatory properties. Anti-apoptotic effects, as well as osteoclast inhibition effects of crocin, have suggested it as a natural substance to treat osteoporosis and degenerative disease of bone and cartilage. Different mechanisms underlying crocin effects on bone and cartilage repair have been investigated, but remain to be fully elucidated. The present review aims to undertake current knowledge on the effects of crocin on bone and cartilage degenerative diseases with an emphasis on its proliferative and differentiative properties in mesenchymal stem cells.

Perioperative neurocognitive disorders (PNDs) occur commonly in older patients after anesthesia and surgery. Treating astrocytes with general anesthetic drugs stimulates the release of soluble factors that increase the cell-surface expression and function of GABA receptors in neurons. Such crosstalk may contribute to PNDs; however, the receptor targets in astrocytes for anesthetic drugs have not been identified. GABA receptors, which are the major targets of general anesthetic drugs in neurons, are also expressed in astrocytes, raising the possibility that these drugs act on GABA receptors in astrocytes to trigger the release of soluble factors. To date, no study has directly examined the sensitivity of GABA receptors in astrocytes to general anesthetic drugs that are frequently used in clinical practice. Thus, the goal of this study was to determine whether the function of GABA receptors in astrocytes was modulated by the intravenous anesthetic etomidate and the inhaled anesthetic sevoflurane. Whole-cell voltage-clamp recordings were performed in astrocytes in the stratum radiatum of the CA1 region of hippocampal slices isolated from C57BL/6 male mice. Astrocytes were identified by their morphologic and electrophysiologic properties. Focal puff application of GABA (300 μM) was applied with a Picospritzer system to evoke GABA responses. Currents were studied before and during the application of the non-competitive GABA receptor antagonist picrotoxin (0.5 mM), or etomidate (100 μM) or sevoflurane (532 μM). GABA consistently evoked inward currents that were inhibited by picrotoxin. Etomidate increased the amplitude of the peak current by 35.0 ± 24.4% and prolonged the decay time by 27.2 ± 24.3% ( = 7, < 0.05). Sevoflurane prolonged current decay by 28.3 ± 23.1% ( = 7, < 0.05) but did not alter the peak amplitude. Etomidate and sevoflurane increased charge transfer (area) by 71.2 ± 45.9% and 51.8 ± 48.9% ( = 7, < 0.05), respectively. The function of astrocytic GABA receptors in the hippocampus was increased by etomidate and sevoflurane. Future studies will determine whether these general anesthetic drugs act on astrocytic GABA receptors to stimulate the release of soluble factors that may contribute to PNDs.