Rejected

This study investigates the relationship between headache and the occurrence of signs associated with intracranial hypertension (ICH) such as ophthalmic signs, restricted skull growth and a vertex bulge in children who were operated for sagittal synostosis.

Transcription factor GLI1 is an effecter of Hedgehog (HH) signalling and activated in a broad spectrum of cancers. However, the role of the HH-GLI1 pathway in cancer and the activation mechanism of GLI1 in HH signalling after dissociation from its inhibitor, SUFU, are not fully understood. Here, we found that GLI1 associated with the methylosome protein 50 (MEP50)/protein arginine methyltransferase 5 (PRMT5) complex and was methylated. Association of MEP50/PRMT5 with GLI1 was enhanced and expression of MEP50 and PRMT5 was activated by HH signals, suggesting their role in positive feedback regulation. Methylated GLI1 lost its ability to bind ubiquitin ligase ITCH/NUMB, resulting in nuclear accumulation and activation of GLI1. Moreover, protein expression of GLI1 was enhanced by MEP50/PRMT5 and expression of MEP50, PRMT5, and GLI1 target genes was upregulated in HH-expressing cancers. These results suggest that MEP50/PRMT5 is important for HH signal-induced GLI1 activation, especially in cancers.

Executive functions are high-level cognitive processes that allow a person to success-fully engage in an independent and self-fulfilling life. Previous literature indicates that chronic pain can affect executive function, but there are limited studies that investigate the effect of acute pain on executive function. The purpose of this study was to determine if acute pain affects executive function in recreationally active indi-viduals who sustained a musculoskeletal injury.

Thrombolysis and late thrombectomy can be performed in case of compatible radiological imaging. Anti-CGRP monoclonal antibodies seem more effective for the treatment of migraine. Siponimod can reduce significantly disability progression in secondarily progressive MS. Brand-to-generic levetiracetam switching does not cause recrudescence of epileptic seizures. A new definition of Alzheimer's disease using biomarkers of cerebrospinal fluid (CSF) and imaging provides a better understanding of the underlying mechanisms. The use of levodopa-carbidopa intestinal gel and a subcutaneous apomorphine infusion allow a reduction of motor fluctuations in Parkinson's disease. Eculizumab appears as an alternative treatment in severe forms of myasthenia gravis.

Pain nanomedicine is an emerging field in response to current needs of addressing the opioid crisis in the USA and around the world. Our group has focused on the development of macrophage-targeted perfluorocarbon nanoemulsions as inflammatory pain nanomedicines over the past several years. We present here, for the first time, a quality by design approach used to design pain nanomedicine. Specifically, we used failure mode, effects, and criticality analysis (FMECA) which identified the process and composition parameters that were most likely to impact nanoemulsion critical quality attributes (CQAs). From here, we applied a unique combination approach that compared multiple linear regression, boosted decision tree regression, and partial least squares regression methods in combination with correlation plots. The presented combination approach allowed for in-depth analyses of which formulation steps in the nanoemulsification processes control nanoemulsion droplet diameter, stability, and drug loading. We identified that increase in solubilizer (transcutol) content increased drug loading and decreased nanoemulsion stability. This was mitigated by inclusion of perfluorocarbon oil in the internal phase. We observed negative correlation (R = 0.4357, p value 0.0054) between the amount of PCE and the percent diameter increase (destabilization), and no correlation between processing parameters and percent diameter increase over time. Further, we identified that increased sonication time decreases nanoemulsion drug loading but does not significantly impact droplet diameter or stability. We believe the methods presented here can be useful in the development of various nanomedicines to produce higher-quality products with enhanced manufacturing and design control.

Endometriosis is a disease in which tissue that normally grows inside the uterus grows outside the uterus and causes chronic pelvic pain and infertility. However, the exact mechanisms of the pathogenesis of endometriosis-associated infertility are unknown. Epigenetic dysregulation has recently been implicated in infertility. Here, we report a reduction of histone deacetylase 3 (HDAC3) protein amounts in eutopic endometrium of infertile women with endometriosis compared to a control group. To investigate the effect of HDAC3 loss in the uterus, we generated mice with conditional ablation of in progesterone receptor (PGR)-positive cells ( ; ). Loss of in the uterus of mice results in infertility due to implantation failure and decidualization defect. Expression microarray and ChIP-seq analyses identified and as direct targets of HDAC3 in both mice and humans. Reduction of abrogated decidualization in a primary culture of human endometrial stromal cells (hESCs) similar to that observed in infertile patients with endometriosis. Whereas attenuation of resulted in p300 recruitment to and genes in the uterus of mice as well as hESCs, inhibition of p300 permitted hESCs to undergo decidualization. Collectively, we found attenuation of HDAC3 and overexpression of collagen type I in the eutopic endometrium of infertile patients with endometriosis. HDAC3 loss caused a defect of decidualization through the aberrant transcriptional activation of and genes in mice and and genes in humans. Our results suggest that HDAC3 is critical for endometrial receptivity and decidualization.

Patients suffering from chronic, subjective tinnitus are on a quest to find a cure or any form of alleviation for their persistent complaint. Current recommended therapy forms provide psychotherapeutic interventions that are intended to train the patient how to deal with the tinnitus sound. Pharmaceutical managements are used to reduce secondary effects of the tinnitus sound such as sleep deprivation, emotional and concentration difficulties, but these treatments do not cure the tinnitus. Recent studies have shown that Tinnitus Retraining Therapy (TRT) significantly improves the quality of life for tinnitus patients. Furthermore, several studies have reported that cognitive behavioral therapy (CBT) relieves a substantial amount of distress by changing dysfunctional cognitions. However, when the tinnitus causes great interference with daily functioning, these treatment methods are not always sufficiently effective. Recent insights show that Eye Movement Desensitization Reprocessing (EMDR) is a highly effective therapy for medically unexplained symptoms such as chronic pain and phantom pain. In scientific research, tinnitus is compared to phantom limb pain. Starting from tinnitus as a phantom percept we therefore aim to demonstrate that the operating mechanisms of EMDR may also be an effective treatment method for patients with subjective tinnitus. The aim of this randomized controlled study with blind evaluator is to examine the effect of EMDR compared to CBT in chronic tinnitus patients. To our knowledge, there are no other studies that evaluate both methods simultaneously.

Cystic echinococcosis (CE) is a worldwide zoonosis and the liver is the most commonly affected organ. Clinical manifestations range from completely asymptomatic cysts to a potential lethal cyst rupture and anaphylaxis.

Dysmenorrhea (pain during menstruation) is one of the most common medical conditions among women of reproductive age. Dysmenorrhea has been studied around the world but not yet in Greece. The aim of the present study was to investigate the prevalence, characteristics, and impact of dysmenorrhea on the wellbeing (exercising, and social and academic functioning) among nursing students in Greece. A cross-sectional study of 637 nursing students was conducted by administering a questionnaire at a university in Athens. The prevalence of dysmenorrhea was 89.2% and the rate of severe intensity was 52.5%. Factors that were associated with severe dysmenorrhea were family history ( = 0.02), early menarche ( = 0.05) and menstruation duration ( = 0.05). Women with moderate and severe pain reported using pain relievers (non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol etc., 0.0005). Finally, activities affected by severe pain were class attendance ( = 0.01), personal studying ( < 0.0005), exercising ( < 0.0005), and socializing ( < 0.0005). Exam attendance ( = 0.27) and clinical placement attendance ( = 0.48) were not affected by severe dysmenorrhea. Dysmenorrhea has a high prevalence among nursing students and seems to affect important aspects of wellbeing and academic performance when the pain intensity is severe. The present findings lay the foundation for further investigation of dysmenorrhea both in the Greek population and cross-culturally.

Uterine artery embolisation (UAE) is an established treatment option for women with symptomatic uterine fibroids who wish to avoid surgery. However the most efficacious embolic agent remains uncertain.