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Despite beneficial cardiovascular effects, substantial long-term modulation of food pattern could only be achieved in a limited number of participants. The impact of attitude towards healthy nutrition (ATHN) on successful modulation of dietary behavior is unclear, especially in the elderly. We aimed to analyze whether the personal ATHN influences 12-month adherence to two different dietary intervention regimes within a 36-month randomized controlled trial., Methods: 502 subjects were randomized to an intervention group (IG; dietary pattern focused on high intake of unsaturated fatty acids (UFA), plant protein and fiber) or control group (CG; dietary recommendation in accordance with the German Society of Nutrition) within a 36-month dietary intervention trial. Sum scores for effectiveness, appreciation and practice of healthy nutrition were assessed using ATHN questionnaire during the trial ( n = 344). Linear regression models were used to investigate associations between ATHN and dietary patterns at baseline and at month 12., Results: Retirement, higher education level, age and lower body mass index (BMI) were associated with higher ATHN sum scores. ATHN was similar in CG and IG. Higher baseline intake of polyunsaturated fatty acids (PUFA) and fiber as well as lower intake in saturated fatty acids (SFA) were associated with higher scores in practice in both groups. The intervention resulted in a stronger increase of UFA, protein and fiber in the IG after 12 months, while intake of SFA declined ( p < 0.01). Higher scores in appreciation were significantly associated with higher intake of fiber and lower intake of SFA in the CG at month 12, whereas no associations between ATHN and macronutrient intake were observed in the IG after 12 months., Conclusions: While ATHN appeared to play a role in general dietary behavior, ATHN did not affect the success of the specific dietary intervention in the IG at month 12. Thus, the dietary intervention achieved a substantial modification of dietary pattern in the IG and was effective to override the impact of the individual ATHN on dietary behavior., Competing Interests: The authors declare no conflicts of interest.

We assessed the effect of a dietary pattern rich in unsaturated fatty acids (UFA), protein and fibers, without emphasizing energy restriction, on visceral adipose tissue (VAT) and cardiometabolic risk profile. Within the 36-months randomized controlled NutriAct trial, we randomly assigned 502 participants (50-80 years) to an intervention or control group (IG, CG). The dietary pattern of the IG includes high intake of mono-/polyunsaturated fatty acids (MUFA/PUFA 15-20% E/10-15% E), predominantly plant protein (15-25% E) and fiber (≥30 g/day). The CG followed usual care with intake of 30% E fat, 55% E carbohydrates and 15% E protein. Here, we analyzed VAT in a subgroup of 300 participants via MRI at baseline and after 12 months, and performed further metabolic phenotyping. A small but comparable BMI reduction was seen in both groups (mean difference IG vs. CG: -0.216 kg/m 2 [-0.477; 0.045], partial η 2 = 0.009, p = 0.105). VAT significantly decreased in the IG but remained unchanged in the CG (mean difference IG vs. CG: -0.162 L [-0.314; -0.011], partial η 2 = 0.015, p = 0.036). Change in VAT was mediated by an increase in PUFA intake (ß = -0.03, p = 0.005) and induced a decline in LDL cholesterol (ß = 0.11, p = 0.038). The NutriAct dietary pattern, particularly due to high PUFA content, effectively reduces VAT and cardiometabolic risk markers, independent of body weight loss.

Purpose: Neuro-endoscopic lavage (NEL) is an increasingly popular intervention for intraventricular haemorrhage (IVH) and post-haemorrhagic hydrocephalus (PHH), with considerable variation in technique dependent on clinician and clinical circumstances. Whilst efforts to standardise the technique are ongoing, this work describes a tertiary centre experience utilising NEL, highlighting potential caveats to standardisation., Methods: A retrospective review of electronic case notes for patients undergoing temporising surgical intervention for IVH between 2012 and 2021 at our centre was performed. Data collected included (i) gestational age, (ii) aetiology of hydrocephalus, (iii) age at time of intervention, (iv) intervention performed, (v) need for permanent CSF diversion, (vi) 'surgical burden', i.e. number of procedures following primary intervention, and (vii) wound failure and infection rate. Data was handled in Microsoft Excel and statistical analysis SPSS v27.0 RESULTS: 49 neonates (n = 25 males) were included. Overall mean gestational age was 27 weeks and at intervention 35 + 3 weeks. IVH was the predominant cause of hydrocephalus (93.8%) and primary surgical interventions included insertion of a ventriculosubgaleal shunt (VSGS) in n = 41 (83.6%) patients, NEL in n = 6 (12.2%) patients and insertion of an EVD in n = 2 (4.1%). N = 9 (18.4%) patients underwent NEL at some point during the time interval reviewed; n = 4 (8.2%) received NEL monotherapy and n = 5 (10.2%) also received a VSGS. Rate of conversion to definitive CSF diversion between NEL (n = 8, 88.9%) and VSGS cohorts (n = 37, 92.5%) was not significantly different (p = 0.57), nor between NEL alone (n = 3, 75%) and NEL + VSGS (n = 5, 100%) (p = 0.44). None of the patients that underwent NEL monotherapy had any wound issues or CNS infection as a result of the initial intervention, compared to n = 3 (60%) of those that underwent NEL and implantation of VSGS (p = 0.1)., Conclusion: Both NEL and VSGS are effective in temporising hydrocephalus in neonates, occasionally offering a definitive solution in and of themselves. The benefit of dual therapy however remains to be seen, with the addition of VSGS potentially increasing the risk of wound failure in an already vulnerable cohort., (© 2023. The Author(s).)

Background: Cannabidiol (CBD), a substance that belongs to the phytocannabinoids, appears to exert antioxidant, neuroprotective, antipsychotic, anticonvulsant, and anticancer properties. Recent evidence supports the immunoregulatory effect of CBD on autoimmune and/or inflammatory disease. Psoriasis is a chronic skin disease. The main immune cell population involved in the pathogenesis of the disease is the interleukin- (IL-) 17-producing T helper (Th) 17 subset. Other subpopulations, such as interferon-γ (IFNγ) -producing Th1 and T cytotoxic (Tc) 1, IL-17-producing Tc17, as well as natural killer (NK) and natural killer T cells (NKT) have been implicated in psoriasis development. Purpose: The aim of the present study was to evaluate the in vitro effect of CBD on the aforementioned subpopulations isolated from patients with psoriasis using flow cytometry. Methods: Cells were stimulated in the presence or absence of CBD, stained and examined using surface and intracellular markers. Results: CBD decreased IL-17 production within the CD3, Th, and NKT cell compartments and IFNγ production within the CD3 compartment in cells isolated from patients with psoriasis. Interestingly, CBD supplementation did not inhibit production of proinflammatory cytokines in cells isolated from healthy individuals. On the contrary, IFNγ-producing Th, Tc, and NK cells increased after CBD supplementation. Conclusion: CBD provides anti-inflammatory effects in T cells isolated from patients with psoriasis. Our results could be the impetus for future investigations regarding the immunomodulatory properties of CBD and its utilization for development of CBD-containing antipsoriatic agents.

Purpose: The aim of the study is to enhance understanding, raise awareness and inform prevention programmes regarding potential factors that lead to severe paediatric injuries caused by unintentional falls from windows., Methods: This is a retrospective review from a major Trauma Centre, covering the majority of North West England and North Wales and included children under the age of 16 that had sustained falls from windows and were hospitalised between April 2015 and June 2020., Results: Overall, 825 patients' records have been reviewed, 39% of which exhibited neurosurgical injuries (322 admissions). The most common cause of injury was falls (42%), out of which 19% was identified as falls from windows which was eventually the core focus of this review (25 patients). The records showed that 72% of the falls were not witnessed by another individual, suggesting that children were being left unattended. Average GCS recorded at presentation was 11.2 and 56% of cases were identified as severe major traumas. With a mean stay of 2.2 days in ICU, 1.6 days in HDU and 6 days in the neurosurgical clinic, average treatment costs per patient were £4,493, £651 and £4,156 respectively. Finally, 52% of patients were identified to require long-term physiotherapy/occupational therapy due to permanent disabilities, 20% long-term antiepileptic treatment for seizures and 44% long-term psychological services input., Conclusion: This study presents our experience at a major tertiary trauma centre in the UK over a 5-year period, from a paediatric neurosurgical injuries perspective due to fall from windows. We aim to raise awareness and highlight the importance of establishing prevention programmes which would hopefully decrease the incidence of paediatric window falls., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Target-dependent TCB activity can result in the strong and systemic release of cytokines that may develop into cytokine release syndrome (CRS), highlighting the need to understand and prevent this complex clinical syndrome., Experimental Design: We explored the cellular and molecular players involved in TCB-mediated cytokine release by single-cell RNA-sequencing of whole blood treated with CD20-TCB together with bulk RNA-sequencing of endothelial cells exposed to TCB-induced cytokine release. We used the in vitro whole blood assay and an in vivo DLBCL model in immunocompetent humanized mice to assess the effects of dexamethasone, anti-TNFα, anti-IL6R, anti-IL1R, and inflammasome inhibition, on TCB-mediated cytokine release and antitumor activity., Results: Activated T cells release TNFα, IFNγ, IL2, IL8, and MIP-1β, which rapidly activate monocytes, neutrophils, DCs, and NKs along with surrounding T cells to amplify the cascade further, leading to TNFα, IL8, IL6, IL1β, MCP-1, MIP-1α, MIP-1β, and IP-10 release. Endothelial cells contribute to IL6 and IL1β release and at the same time release several chemokines (MCP-1, IP-10, MIP-1α, and MIP-1β). Dexamethasone and TNFα blockade efficiently reduced CD20-TCB-mediated cytokine release whereas IL6R blockade, inflammasome inhibition, and IL1R blockade induced a less pronounced effect. Dexamethasone, IL6R blockade, IL1R blockade, and the inflammasome inhibitor did not interfere with CD20-TCB activity, in contrast to TNFα blockade, which partially inhibited antitumor activity., Conclusions: Our work sheds new light on the cellular and molecular players involved in cytokine release driven by TCBs and provides a rationale for the prevention of CRS in patients treated with TCBs. See related commentary by Luri-Rey et al., p. 4320., (©2023 The Authors; Published by the American Association for Cancer Research.)

Psoriasis is an inflammation of the skin mediated via the IL-23/Thl17/IL-17 pathway. We have previously demonstrated that the anthocyanin delphinidin diminishes in vitro the IL-17 and IFN-γ production of peripheral monocytes isolated by psoriasis patients (PBMCs). The degradation product of delphinidin is gallic acid (GA). This phenolic acid compound found in fruits, red wine, or green tea exerts pleiotropic antioxidant, anticarcinogenic, antimicrobial, and anti-inflammatory properties. Previous research has demonstrated the inhibitory effect of GA on pro-inflammatory transcription factors, such as STAT3, RORγt, and NF-κB, or cytokines as IL-1β and TNF, which contribute to psoriasis development. We investigated the effect of GA in vitro on PBMCs, which were stimulated ex vivo, from 40 individuals (28 diagnosed with psoriasis vulgaris and 12 healthy controls (HCs)). In our experiments, PBMCs were cultured untreated or were activated in the presence of phorbol 12-myristate 13-acetate/ionomycin with or without GA. We utilized multicolor flow cytometry to assess the production of inteleukin-17 (IL-17) and interferon-γ (IFN-γ) in T and NK cells. GA did not alter the fractions of IL-17- or IFN-γ-producing T and IFN-γ-producing NK cells in HCs. However, in psoriasis patients, the effect of GA on that cell population was significant. Specifically, GA decreased the frequency of IL-17-producing cells within the CD3 + (T) and CD3 + CD4 + (Th) compartment; the frequency of IFN-γ-producing cells within the CD3 + , CD3 + CD4 + , and CD3 + CD4 - (Tc) compartment, and the frequency of IFN-γ-producing cells within the CD3 - CD56 + (NK) compartment. Whether GA's effect also appears in vivo needs to be investigated in future., (© 2023. The Author(s).)

Background: Short-term trials indicate improvement of intrahepatic lipids (IHLs) and metabolism by dietary protein or unsaturated fatty acids (UFAs) beyond weight loss., Objectives: We aimed to assess the effect of a dietary intervention high in protein and UFAs on IHLs and metabolic outcome after 12 mo, as long-term effects of such a combined intervention are unknown., Methods: Within a 36-mo randomized controlled trial, eligible subjects (aged 50 to 80 y, ≥1 risk factor for unhealthy aging) were randomly assigned to either intervention group (IG) with high intake of mono-/poly-UFAs [15-20 percent of total energy (%E)/10%-15%E, respectively], plant protein (15%-25%E), and fiber (≥30 g/d), or control group [CG, usual care, dietary recommendations of the German Nutrition Society (fat 30%E/carbohydrates 55%E/protein 15%E)]. Stratification criteria were sex, known cardiovascular disease, heart failure, arterial hypertension, type 2 diabetes, and cognitive or physical impairment. Nutritional counseling and supplementation of foods mirroring the intended dietary pattern were performed in the IG. Diet-induced effects on IHLs, analyzed by magnetic resonance spectroscopy, as well as on lipid and glucose metabolism were predefined secondary endpoints., Results: IHL content was analyzed in 346 subjects without significant alcohol consumption at baseline and in 258 subjects after 12 mo. Adjusted for weight loss, sex, and age, we observed a comparable decline of IHLs in IG and CG (-33.3%; 95% CI: -49.3, -12.3%; n = 128 compared with -21.8%; 95% CI: -39.7, 1.5%; n = 130; P = 0.179), an effect that became significant by comparing adherent IG subjects to adherent CG subjects (-42.1%; 95% CI: -58.1, -20.1%; n = 88 compared with -22.2%; 95% CI: -40.7, 2.0%; n = 121; P = 0.013). Compared with the CG, decline of LDL cholesterol (LDL-C) and total cholesterol (TC) was stronger in the IG (for LDL-C P = 0.019, for TC P = 0.010). Both groups decreased in triglycerides and insulin resistance (P for difference between groups P = 0.799 and P = 0.124, respectively)., Conclusions: Diets enriched with protein and UFAs have beneficial long-term effects on liver fat and lipid metabolism in adherent older subjects. This study was registered at the German Clinical Trials Register, https://www.drks.de/drks&#95;web/setLocale&#95;EN.do, DRKS00010049. Am J Clin Nutr 20XX;xx:xx-xx., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Introduction: We present the largest series of paediatric intracranial empyemas occurring after COVID-19 infection to date, and discuss the potential implications of the pandemic on this neurosurgical pathology., Methods: Patients admitted to our centre between January 2016 and December 2021 with a confirmed radiological diagnosis of intracranial empyema were retrospectively reviewed, excluding non-otorhinological source cases. Patients were grouped according to onset before or after onset of the COVID-19 pandemic and COVID-19 status. A literature review of all post-COVID-19 intracranial empyemas was performed. SPSS v27 was used for statistical analysis., Results: Sixteen patients were diagnosed with intracranial empyema: n = 5 prior to 2020 and n = 11 after, resulting in an average annual incidence of 0.3% prior to onset of the pandemic and 1.2% thereafter. Of those diagnosed since the pandemic, 4 (25%) were confirmed to have COVID-19 on recent PCR test. Time from COVID-19 infection until empyema diagnosis ranged from 15 days to 8 weeks. Mean age for post-COVID-19 cases was 8.5 years (range: 7-10 years) compared to 11 years in non-COVID cases (range: 3-14 years). Streptococcus intermedius was grown in all cases of post-COVID-19 empyema, and 3 of 4 (75%) post-COVID-19 cases developed cerebral sinus thromboses, compared to 3 of 12 (25%) non-COVID-19 cases. All cases were discharged home with no residual deficit., Conclusion: Our post-COVID-19 intracranial empyema series demonstrates a greater proportion of cerebral sinus thromboses than non-COVID-19 cases, potentially reflecting the thrombogenic effects of COVID-19. Incidence of intracranial empyema at our centre has increased since the start of the pandemic, causes of which require further investigation and multicentre collaboration., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Purpose: The aim of the study was to evaluate the role of telephone consultations due to the pandemic in the management of paediatric neurosurgical patients and, furthermore, to examine the proportion of patients who eventually needed a face-to-face appointment and assess the underline reasons for that., Methods: This retrospective study included all the paediatric neurosurgical patients who had a telephone appointment during a 3-month lockdown period. Overall, 319 patients (186 males and 133 females) aged 8.36 ± 4.88 (mean ± SD) had a consultation via telephone. Two hundred fifty-one (78.7%) patients had a follow-up assessment and 68 (21.3%) were new appointments., Results: Patients were divided between two main groups. Group A included 263 patients (82.4%) whose consultation was adequate via telephone, and Group B included 56 patients (17.6%) who required a complementary face-to-face appointment. Patients who were more likely to require a supplementary appointment were patients with either dysraphism or ventriculomegaly and benign enlarged subarachnoid spaces (BESS) (43.3% and 36.4%, respectively). Interestingly, most children with hydrocephalus who underwent a cerebrospinal fluid (CSF) diversion procedure and children with Chiari I malformation were appropriately assessed via telephone (85.1% and 83.3%, respectively). Finally, children aged < 2 years (55.2%) were better managed with face-to-face appointments. No difference was noticed regarding follow-up and new appointments., Conclusion: Although telemedicine was not unknown to neurosurgical services, the actual application of telephone or video consultations remained quite limited. It was COVID-19 pandemic who reinforced the use of telemedicine, and taking into consideration its promising results, we can safely assume that it can be incorporated into neurosurgical health care even once the pandemic crisis has resolved., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background & Aims: NutriAct is a 36-month randomized controlled multi-center trial designed to analyze the effects of a food pattern focusing on a high-protein and high-unsaturated fatty acids (UFA) intake on healthy aging. We aimed to determine factors associated with a successful modulation of dietary pattern after 12 months in elderly participants., Methods: 502 participants were randomized into either usual care control group including dietary recommendations of the German Nutrition Society (DGE) or an intervention group, which used supplementation of rapeseed oil and specifically designed foods as well as repetitive advices to implement a food pattern based on high intake of predominantly plant proteins, UFA and fiber (NutriAct pattern). Food intake was repeatedly assessed by 3-day food records at months 0, 3, 6 and 12. Linear regression models were used to investigate determinants of basal food intake and modulation of dietary pattern during the intervention., Results: Food records of 242 intervention and 246 control participants (median age 66 y, 37% males) were available at baseline and were included. At baseline, high BMI was related to higher protein and saturated fatty acids and lower fiber intake. The intervention resulted in higher intake of protein, mono- and polyunsaturated fatty acids (MUFA and PUFA) and fiber, and lower carbohydrate and saturated fatty acid consumption (all p < 0.001). While individuals who were already at baseline closer to the NutriAct pattern also achieved a diet closer to the proposed pattern at month 12, the strongest absolute changes (%E) of dietary behavior were seen in those with dietary patterns further away from the proposed pattern at baseline. Attendance to nutritional sessions was crucial to change MUFA, PUFA, fiber and carbohydrate intake., Conclusions: A successful modification of dietary pattern was achieved by the performed intervention within 12 months. Baseline dietary habits and attendance to nutritional sessions were substantial determinants predicting changes in dietary pattern., Clinical Trial Registration: The trial was registered at German Clinical Trials Register (drks.de) as DRKS00010049., Competing Interests: Conflict of interest All authors declare no conflicts of interest., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Dysraphic entities like diastematomyelia are not uncommon. However, the co-existence of split cord malformation with two pathologically different lesions on the same hemicord is extremely rare. We report a case of a young child who presented with an unusual combination of diastematomyelia, intramedullary lipoma, and dermoid cyst., (© 2021. Crown.)

Introduction: The mean age of the German population increased over the last years, which resulted in a higher prevalence of cardiovascular diseases, type 2 diabetes, cognitive impairment, sarcopenia and bone fractures. Current evidence indicates a preservation of human wellbeing in the elderly by a healthy diet, although the recommended macronutrient composition and quality remains unclear and needs further long-term investigation. In this context we investigate the effect of a specific dietary pattern on age-related disorders in a randomized controlled multi-center trial (RCT)., Methods: We assess the effect of a specific dietary pattern (NutriAct) with a high proportion of unsaturated fat, plant proteins and fibres (fat 35%-40% of total energy (%E) of which 15%E-20%E monounsaturated fatty acids (MUFA) and 10%E-15%E polyunsaturated fatty acids (PUFA), 15%E-25%E proteins, ≥30 g fibres per day and 35%E-45%E carbohydrates) on age-related impairment of health within a 36-months RCT conducted in the region of Berlin and Potsdam. 502 eligible men (n = 183) and women (n = 319), aged 50 to 80 years, with an increased risk to develop age-related diseases were randomly assigned to either an intervention group focusing on NutriAct dietary pattern or a control group focusing on usual care and dietary recommendations in accordance to the German Nutrition Society (DGE). In the intervention group, 21 nutrition counsellings as well as supplementation of rapeseed oil, oil cake and specific designed foods are used to achieve the intended NutriAct dietary pattern.The primary outcome is a composite endpoint of age-related disorders, including cardiovascular morbidity, decline of cognitive function as well as clinical features of sarcopenia. Secondary outcomes include diet-induced effects on quality of life, depression, frailty, cardiovascular function, bone density, fat distribution pattern, glucose, lipid and energy metabolism, as well as the identification of biomarkers linked with age-related disorders., Discussion: The findings of this trial will provide clinically relevant information regarding dietary effects on age-related impairment of health and will contribute to the definition of the optimal macronutrient composition in the context of healthy aging in the German population.

Background: Intracerebral hemorrhage (ICH)1 is characterized by the pathological accumulation of blood within the brain parenchyma, most commonly associated with hypertension, arteriovenous malformations, or trauma. However, it can also present in patients receiving antithrombotic drugs, either anticoagulants such as acenocoumarol/warfarin-novel oral anticoagulants or antiplatelets, for the prevention and treatment of thromboembolic disease., Objective: The purpose of this review is to present current bibliographic data regarding ICH irrespective of the cause, as well as post-hemorrhage use of antithrombotic agents. Moreover, this review attempts to provide guidelines concerning the termination, inversion, and of course resumption of antithrombotic therapy., Methods and Materials: We reviewed the most recently presented available data for patients who dealt with intracerebral hemorrhagic events while on antithrombotic agents (due to atrial fibrillation, prosthetic mechanical valves or recent/recurrent deep vein thrombosis). Furthermore, we examined and compared the thromboembolic risk, the bleeding risk, as well as the re-bleeding risk in two groups: patients receiving antithrombotic therapy versus patients not on antithrombotic therapy., Conclusion: Antithrombotic therapy is of great importance when indicated, though it does not come without crucial side-effects, such as ICH. Optimal timing of withdrawal, reversal, and resumption of antithrombotic treatment should be determined by a multidisciplinary team consisting of a stroke specialist, a cardiologist, and a neurosurgeon, who will individually approach the needs and risks of each patient., Competing Interests: The authors declare no conflicts of interest., (© 2020 Journal of Population Therapeutics and Clinical Pharmacology. All rights reserved.)

Background: Complex spinal deformities are a common issue in pediatric patients with an underlying neurologic diagnosis or syndrome. Management of neuromuscular scoliosis is an awesome responsibility, because these patients present with the most challenging pathologies of the deformed spine. Along with surgical correction of the underlying deformity, an intrathecal baclofen (ITB) pump is considered effective in managing the associated spasticity., Case Description: We present the case of an 11-year-old female who sustained an episode of severe ischemic encephalopathy accompanied by hydrocephalus and severe spastic quadriplegia. An ITB pump was inserted to manage spasticity. Two years later, a very severe decompensated spinal curvature developed. In addition, malfunction of the pump was noted, and the decision was made to perform revision along with open hemilaminectomy at the L3-4 level. The inability of cerebrospinal fluid (CSF) to access the pump was verified intraoperatively, with the absence of CSF glow through the intrathecal space demonstrating blockage of CSF flow., Conclusions: The association of cerebral palsy and relevant disorders with the relentless progression of scoliosis is analyzed, along with the possible offending mechanisms. The efficacy of an ITB pump in controlling intractable spasticity associated with neuromuscular scoliosis is reviewed, as well as its potential to accentuate the clinical progression of neuromuscular scoliosis. Although this is an extremely infrequent situation, we must always bear in mind the possibility that malfunction of an ITB pump could be related to obstruction of CSF flow, owing to the extreme severity of the curves established during the course of, most likely untreated, neuromuscular scoliosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Premature ovarian failure (POF), which may be undetectable for a long time, is associated with impaired fertility. The mechanisms involved in the pathogenesis of POF as well as the concomitant treatments are still unclear. Although many data exist, mainly produced by the study of transgenic animals under various experimental conditions, they remain fragmented. A systematic review of the pathways involved in premature ovarian failure was conducted. Data extraction was performed from experimental studies until 2019. The molecular processes and their correlation with the follicular developmental stage have been described. Furthermore, the effects in other cells, such as oocytes, granulosa and theca cells have been reported. An overall estimation was conducted., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

BACKGROUND The ventriculoperitoneal shunt remains, despite recent advances, the mainstay of treatment for hydrocephalus. Although it is used as a routine practice, and besides its recorded and documented safety, it often malfunctions due to a variety of reasons, most commonly referred to as obstruction, breakage, migration and infection. A usual finding of those children suspected to magnetic resonance imaging is the detection of a rim of hyperintensity in the periventricular white matter (halo). CASE REPORT We describe the case of a 7-year-old male patient, treated 4 years ago for an infratentorial ependymoma, who developed hydrocephalus at the time of clinical presentation. During his previous follow-up, he was disease-free but developed clinically evident acute shunt malfunction, accompanied by imaging findings on magnetic resonance imaging (MRI) consisting of interstitial edema surrounding the supratentorial ventricular system, with additional involvement of the floor of the fourth ventricle. This peculiar and novel imaging finding subsided after successful management of hydrocephalus. CONCLUSIONS At present, contemporary computed tomography and MRI modalities constitute the gold standard in order to assess and follow-up patients with established hydrocephalus. Periventricular interstitial edema is a well-established imaging feature of acute hydrocephalus and, in cases of ventriculoperitoneal shunt, of shunt malfunction. Besides that, a newly described, to the best of our knowledge, imaging feature could be the distinction of that signal alteration at the floor of the fourth ventricle. It seems to have prognostic significance regarding the adequacy of management of hydrocephalus, as it disappeared after its successful treatment.

Background: Primary Ewing sarcoma arising from the calvarial bone and/or underlying dura matter are relatively rarely reported in the literature. Even rarer are considered to be those that originate from the dura and proliferate in both directions, toward the brain parenchyma and through the dura invading the overlying bone., Case Description: We report the case of a girl aged 11 years who presented with an ictus of generalized tonic-clonic seizures, without known focal neurologic deficit. Neuroradiologic work-up verified the existence of a tumor in the right fronto-parietal area of the brain, invading both the bone and brain parenchyma and emanating from the dura. No other tumor location was discovered after radiologic work-up, and gross total resection was undertaken followed by adjuvant radiation therapy and chemotherapy., Conclusions: The patient had an uneventful neurologic recovery without persistent neurologic deficit. One year after the operation, with the patient under close clinical and radiologic surveillance, no recurrence of the disease was detected. This case illustrates an extremely uncommon location of primary Ewing sarcoma, along with a constellation of clinical signs and symptoms that are fairly uncommon for this location of this rare disease entity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Herpes simplex encephalitis caused by herpes simplex has an estimated annual prevalence in the order of 1 in 250,000 to 500,000 patients and is considered to be the most usually encountered nonendemic pathogenic cause of lethal encephalitis in well-developed countries. There are a few cases reported in the literature in which a diagnostic dilemma between was raised between herpes simplex encephalitis and brain glioma and a definitive diagnosis was difficult to obtain., Case Description: We report the case of a 5-year-old girl with a previous medical history of premature thelarche. As a part of her investigation, magnetic resonance imaging of the brain was performed, which revealed a space-occupying lesion of the posterior fossa. Magnetic resonance spectroscopy was performed, which advocated for the diagnosis of glioma. She was operated on, but the histopathologic analysis failed to verify the imaging findings. Herpes simplex virus (HSV) 1 was detected in cerebrospinal fluid (CSF) samples. Follow-up magnetic resonance imaging scans illustrated the progression of the disease., Conclusions: The accumulation of data regarding CSF sample analysis, electroencephalography, brain biopsy, and imaging findings, along with the progression of the clinical picture of our patient, verified the diagnosis of HSV encephalitis. When confronted with confounding data that can pose a diagnostic dilemma between HSV encephalitis and glioma, brain biopsy and polymerase chain reaction of CSF samples could be able to verify the definitive diagnosis. When interpreting our results, we always have to consider the evolution of the clinical picture., (Copyright © 2019 Elsevier Inc. All rights reserved.)

An ischemia/reperfusion injury of rat's sciatic nerve was experimentally developed. In this model, we measured the in vivo production of superoxide radical, as a marker of oxidative stress and the occludin expression as an indicator of blood-nerve barrier function and we examined potential protective innervations against these abnormalities. Right sciatic nerves of the animals underwent 3 h of ischemia followed by 7 days of reperfusion and were divided into three groups: ischemic, pretreated with vitamin C in conjunction with vitamin E and treated with tissue plasminogen activator. Compared to measurements from left sciatic nerves used as sham, the ischemic group showed significantly increased superoxide radical and reduced expression of occludin in western blot and immunohistochemistry. No such differences were detected between sham and nerves in the vitamin or tissue plasminogen activator groups. It is suggested that the experimental ischemia/reperfusion model was suitable for studying the relationship between oxidative state and blood-nerve barrier. The reversion of abnormalities by the applied neuroprotective agents might prove to be a clinically important finding in view of the implication of vascular supply derangement in various neuropathies in humans.

Spinal cord intramedullary lipomas are rare, comprising 2% of intramedullary tumours. They are more often associated with spinal dysraphism, while lipomas not associated with spinal dysraphism are even less frequent, accounting for 1% of cases. The pathogenesis of spinal cord intramedullary lipomas remains unclear. MRI is the gold standard for the evaluation of these lesions. We hereby present a case of a 37-year-old male, who underwent MRI due to spastic paraparesis. MRI revealed a bilocular, spinal cord intramedullary lesion at the level of T 2 - T 5 , with dilatation of the spinal canal and signal characteristics compatible with lipoma. There was no clear imaging evidence of spinal dysraphism. The patient underwent surgery and diagnosis was confirmed histopathologically.

Background: To assess the role of somatostatin receptor (SR) PET/CT using Ga-68 DOTATOC or DOTATATE in staging and restaging of typical (TC) and atypical (AC) lung carcinoids., Methods: Clinical and PET/CT data were retrospectively analyzed in 27 patients referred for staging (N = 5; TC, N = 4; AC, N = 1) or restaging (N = 22; TC, N = 8; AC, N = 14). Maximum standardized uptake value (SUVmax) of SR-positive lesions was normalized to the SUVmax of the liver to generate SUVratio; SR PET was compared to contrast-enhanced (ce) CT. The classification system proposed by Rindi et al. (Endocr Relat Cancer. 2014;21(1):1-16, 2014) was used for classification of patients in TC and AC groups., Results: Only 18/27 patients were found to have metastases on PET/CT. Of the 186 lesions, 101 (54.3 %) were depicted on both PET and CT, 53 (28.5 %) lesions only on CT, and 32 (17.2 %) only on PET. SUVratio of lesions was significantly higher in AC as compared to TC (p < 0.001). In patients referred for restaging, additional findings on PET lead to upstaging with change in management strategy in 5/22 (22.7 %) patients (AC, N = 5; TC, N = 1). In four patients (all AC) referred for restaging and in one patient (TC) referred for staging, additional findings on CT missed on PET lead to correct staging., Conclusions: Typical and atypical carcinoid patients have complex patterns of metastases which make it necessary to combine functional SR PET and contrast-enhanced CT for appropriate restaging. In patients referred for restaging SR, PET may have a relevant impact on treatment strategy in up to 22.7 of patients with typical and atypical lung carcinoids.

Objective: The renin-angiotensin-aldosterone-system (RAAS) has gained increasing attention in the investigation of the pathogenesis of depression. Primary hyperaldosteronism (PA) is associated with a marked aldosterone excess. Prior studies on PA describe an increased prevalence of anxiety and sub-threshold depressive symptoms in these patients., Methods: In a cross-sectional exploratory study we investigated 132 patients with PA. Twenty-seven patients were studied before initiation of specific treatment (U = untreated), 56 were studied 5.4 years after initiation of mineralocorticoid antagonist treatment (MRA) and 49 patients were studied 4.3 years after unilateral adrenalectomy (ADX). GAD-7 and PHQD self-rating questionnaires were used to assess symptoms for anxiety and depression., Results: No significant difference was found between the three investigated groups. A higher prevalence for depression and anxiety compared to the normal population was found. Women of all groups had higher mean values compared to men, for depression in untreated patients this difference was found to be significant. Correlations between the psychopathology and hormones were only found for renin. Plasma renin concentration correlated significantly with anxious symptoms of untreated females., Conclusions: This study supports the RAAS to be involved in the pathogenesis of depression as patients with PA seem to be more depressive and anxious compared to the normal population. Gender differences in the regulation of the RAAS seem to be apparent, as females were more affected by the dysregulation than males.

Psychopathological symptoms in patients with primary aldosteronism (PA) have been reported. In a cross-sectional design the self-reported physical and mental condition among patients with PA of the German Conn's Registry differently treated during the course of the disease were analysed. 27 patients were investigated before initiation of specific therapy (U), 56 patients were on chronic mineralocorticoid antagonist treatment (MRA) and 49 patients had undergone adrenalectomy (ADX). Patient's quality of life was analysed with the SF-12 for a Physical (PCS) and a Mental Component (MCS). Statistically significant lower scores for PCS were found for female PA patients treated with MRA in comparison to ADX patients and the German reference population (36.4 ± 11.1 vs. 49.1 ± 10.9 (p = 0.024) vs. 47.9 ± 9.7 (p = 0.001)), respectively. Concerning MCS, untreated female patients scored significantly lower (36.5 ± 7.4) than females from the German population (51.3 ± 8.4, p = 0.000). Furthermore, untreated females appear to differ significantly from MRA and ADX females, scoring the lowest reading (U vs. MRA: p = 0.029; U vs. ADX: p = 0.005). Significant correlations were found between plasma aldosterone (r = -0.819, p = 0.013) and the MCS and between plasma renin concentration and MCS (r = -0.938, p = 0.001) in female MRA patients. In summary, PA patients report a worse physical and mental condition than the one reported for the German reference population. Untreated and mineralocorticoid antagonist treated patients report the lowest readings. Females were found to be more impaired than males in QoL. MRA treatment seems to affect the MCS of female patients., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The prevalence of postconcussion syndrome (PCS) in the first weeks after mild traumatic brain injury varies from 40% to 80%. However, as many as 50% of patients report symptoms for up to 3 months and 10% to 15% for more than a year. The objective of this study is to analyze the characteristics and estimate the prevalence of PCS in an adult Greek population., Methods: This prospective study was performed in the University Hospital of Patras in Western Greece. Patients with mild traumatic brain injury (n = 539) were randomly recruited on admission between May 2006 and May 2008. Overall, 223 patients (223 of 539, 41.5%) met the Colorado Medical Society guidelines for concussion; 141 men (63%) and 82 women (37%) with a median age of 30 years (range, 18.5-57.5 years) were included in the study. Patient follow-up consisted of telephone interviews at 1 month, 3 months, and 6 months postinjury, when they were asked about experiencing common postconcussion symptoms (International Classification of Diseases-10th revision criteria)., Results: The rate of PCS at 1 month, 3 months, and 6 months postinjury was estimated to be 10.3%, 6%, and 0.9%, respectively. The syndrome was more frequent among women (17%) and individuals with bleeding diathesis (26%) compared with men (6.4%) and patients without clotting disorders (8.5%), respectively. In addition, higher rates of PCS affected patients who sustained assaults compared with other types of accidents., Conclusions: The prevalence of PCS was remarkably higher in previous studies. Cultural differences regarding symptom expectation and the lack of compensation might explain the low rate of chronic symptoms in Greeks.

p57(KIP2) is an imprinted gene located at the chromosomal locus 11p15.5. It is a cyclin-dependent kinase inhibitor belonging to the CIP/KIP family, which includes additionally p21(CIP1/WAF1) and p27(KIP1). It is the least studied CIP/KIP member and has a unique role in embryogenesis. p57(KIP2) regulates the cell cycle, although novel functions have been attributed to this protein including cytoskeletal organization. Molecular analysis of animal models and patients with Beckwith-Wiedemann Syndrome have shown its nodal implication in the pathogenesis of this syndrome. p57(KIP2) is frequently down-regulated in many common human malignancies through several mechanisms, denoting its anti-oncogenic function. This review is a thorough analysis of data available on p57(KIP2), in relation to p21(CIP1/WAF1) and p27(KIP1), on gene and protein structure, its transcriptional and translational regulation, and its role in human physiology and pathology, focusing on cancer development.

Osteosarcoma is the most common primary bone cancer. Mutations of the RB gene represent the most frequent molecular defect in this malignancy. A major consequence of this alteration is that the activity of the key cell cycle regulator E2F1 is unleashed from the inhibitory effects of pRb. Studies in animal models and in human cancers have shown that deregulated E2F1 overexpression possesses either "oncogenic" or "oncosuppressor" properties, depending on the cellular context. To address this issue in osteosarcomas, we examined the status of E2F1 relative to cell proliferation and apoptosis in a clinical setting of human primary osteosarcomas and in E2F1-inducible osteosarcoma cell line models that are wild-type and deficient for p53. Collectively, our data demonstrated that high E2F1 levels exerted a growth-suppressing effect that relied on the integrity of the DNA damage response network. Surprisingly, induction of p73, an established E2F1 target, was also DNA damage response-dependent. Furthermore, a global proteome analysis associated with bioinformatics revealed novel E2F1-regulated genes and potential E2F1-driven signaling networks that could provide useful targets in challenging this aggressive neoplasm by innovative therapies.

ZBTB7A (Pokemon) is a member of the POK family of transcriptional repressors. Its main function is the suppression of the p14ARF tumour suppressor gene. Although ZBTB7A expression has been found to be increased in various types of lymphoma, there are no reports dealing with its expression in solid tumours. Given that p14(ARF) inhibits MDM2, the main negative regulator of p53, we hypothesized that overexpression of ZBTB7A could lead indirectly to p53 inactivation. To this end, we examined the status of ZBTB7A and its relationship with tumour kinetics (proliferation and apoptosis) and nodal members of the p53 network in a panel of 83 non-small cell lung carcinomas (NSCLCs). We observed, in the majority of the samples, prominent expression of ZBTB7A in the cancerous areas compared to negligible presence in the adjacent normal tissue elements. Gene amplification (two- to five-fold) was found in 27.7% of the cases, denoting its significance as a mechanism driving ZBTB7A overproduction in NSCLCs. In the remaining non-amplified group of carcinomas, analysis of the mRNA and protein expression patterns suggested that deregulation at the transcriptional and post-translational level accounts for ZBTB7A overexpression. Proliferation was associated with ZBTB7A expression (p = 0.033) but not apoptosis. The association with proliferation was reflected in the positive correlation between ZBTB7A expression and tumour size (p = 0.018). The overexpression of ZBTB7A in both p53 mutant and p53 wild-type cases, implies either a synergistic effect or that ZBTB7A exerts its oncogenic properties independently of the p14(ARF)-MDM2-p53 axis. The concomitant expression of ZBTB7A with p14(ARF) (p = 0.039), instead of the anticipated inverse relation, supports the latter notion. In conclusion, regardless of the pathway followed, the distinct expression of ZBTB7A in cancerous areas and the association with proliferation and tumour size pinpoints a role for this novel cell cycle regulator in the pathogenesis of lung cancer., (Copyright 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Knowing the status of molecules involved in cell cycle control in cancer is vital for therapeutic approaches aiming at their restoration. The p27(KIP1) and p57(KIP2) cyclin-dependent kinase inhibitors are nodal factors controlling normal cell cycle. Their expression in normal lung raises the question whether they have a mutual exclusive or redundant role in nonsmall cell lung cancer (NSCLC). A comparative comprehensive analysis was performed in a series of 70 NSCLCs. The majority of cases showed significantly reduced expression of both members compared to normal counterparts. Low KIP protein levels correlated with increased proliferation, which seems to be histological subtype preponderant. At mechanistic level, degradation by SKP2 was demonstrated, in vivo and in vitro, by siRNA-methodology, to be the most important downregulating mechanism of both KIPs in NSCLC. Decreased p57(KIP) (2)-transcription complements the above procedure in lowering p57(KIP2)-protein levels. Methylation was the main cause of decreased p57(KIP) (2)-mRNA levels. Allelic loss and imprinting from LIT1 mRNA contribute also to decreased p57(KIP2) transcription. In vitro recapitulation of the in vivo findings, in A549 lung cells (INK4A-B((-/-))), suggested that inhibition of the SKP2-degradation mechanism restores p27(KIP1) and p57(KIP2) expression. Double siRNA treatments demonstrated that each KIP is independently capable of restraining cell growth. An additional demethylation step is required for complete reconstitution of p57(KIP2) expression in NSCLC.

Centrosome abnormalities are observed in human cancers and have been associated with aneuploidy, a driving force in tumour progression. However, the exact pathways that tend to cause centrosome abnormalities have not been fully elucidated in human tumours. Using a series of 68 non-small-cell lung carcinomas and an array of in vitro experiments, the relationship between centrosome abnormalities, aneuploidy, and the status of key G1 to S-phase transition cell-cycle molecules, involved in the regulation of centrosome duplication, was investigated. Centrosome amplification and structural abnormalities were common (53%), were strongly related to aneuploidy, and, surprisingly, were even seen in adjacent hyperplastic regions, suggesting the possibility that these are early lesions in lung carcinogenesis. Cyclin E and E2F1 overexpression, but not p53 mutation, was observed to correlate with centrosome abnormalities in vivo (p = 0.029 and p = 0.015, respectively). This was further strengthened by the observation that cyclin E was specifically present in the nucleus and/or cytoplasm of the cells that contained centrosome aberrations. The cytoplasmic cyclin E signal may be attributed, in part, to the presence of truncated low-molecular-weight isoforms of cyclin E. In order to isolate the effect of cyclin E on the appearance of centrosome abnormalities, a U2OS tetracycline-repressible cyclin E cell line that has a normal centrosome profile by default was used. With this system, it was confirmed in vitro that persistent cyclin E overexpression is sufficient to cause the appearance of centrosome abnormalities., (Copyright 2006 Pathological Society of Great Britain and Ireland.)

Pyoderma gangrenosum is an extraintestinal manifestation of inflammatory bowel disease requiring meticulous medical and/or surgical treatment. We describe a 46-year-old patient who developed harsh pyoderma gangrenosum during a severe flare-up of the underlying Crohn disease of the terminal ileum. The patient responded favorably to treatment with infliximab-the chimeric antibody against tumor necrosis factor-alpha. The drug was administered intravenously at a dose 5 mg/kg/BW at baseline and weeks 2 and 6. Abdominal signs and symptoms as well as the skin lesions improved markedly before the second infusion. The patient is presently on infliximab maintenance regimen at a dose of 5 mg/kg/BW being administered as a 3 dose loading regimen at 0, 2 and 6 weeks with a treatment-free interval of 10 weeks until the next loading dose. The skin lesions remained in remission. Infliximab is a promising therapeutic modality for patients with Crohn disease and pyoderma gangrenosum.

There is evidence from in vitro experiments that spironolactone not only antagonises the peripheral effects of aldosterone but also inhibits the production of corticosteroids by the adrenals. However relevant data from clinical studies are contradictory probably because spironolactone action on the kidneys also activates other mechanisms, such as renin secretion and potassium retention, which are potent stimulants of the adrenal cortex and thus tend to compensate for the inhibition. To determine the inhibitory effect of spironolactone on the adrenals in isolation, three groups of nephrectomized dogs were studied. Steroidogenesis was stimulated either by angiotensin II, potassium, or ACTH infusion. Potassium canrenoate was administered i.v. bolus at the beginning of the experiment. All the groups showed a similar marked decrease in plasma renin activity (PRA). Plasma aldosterone and cortisol were stimulated by the appropriate stimulus but their increase was blunted after the canrenoate K administration. The altered response between the subgroups was statistically significant (P less than 0.05). Plasma progesterone increased after the administration of canrenoate K. The response difference between the respective subgroups was again statistically significant (P less than 0.05). Canrenoate K was rapidly eliminated from the systemic circulation. These data indicate that canrenoate K causes a partial inhibition of aldosterone and cortisol stimulated secretion but augments the plasma levels of the precursor progesterone, as would be expected following inhibition of specific steps of corticosteroid biosynthesis.