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Abstract Influenza vaccine effectiveness (VE) varies seasonally due to host, virus and vaccine characteristics. To investigate how antigenic matching and dosage impact VE, we developed a mechanistic knowledge-based mathematical model. Immunization with a split vaccine is modeled for exposure to A/H1N1 or A/H3N2 virus strains. The model accounts for cross-reactivity of immune cells elicited during previous immunizations with new antigens. We simulated vaccine effectiveness (sVE) of high dose (HD) versus standard dose (SD) vaccines in the older population, from 2011 to 2022. We find that sVE is highly dependent on antigenic matching and that higher dosage improves immunogenicity, activation and memory formation of immune cells. In alignment with clinical observations, the HD vaccine performs better than the SD vaccine in all simulations, supporting the use of the HD vaccine in the older population. This model could be adapted to predict the impact of alternative virus strain selection on clinical outcomes in future influenza seasons.

Background: Universities face increasing pressure to model healthy campuses in response to the ongoing mental health crisis, yet limited research explores ways to improve student wellness. Aim: This study explored strategies architecture and landscape architecture students adopt to overcome stress and solutions for promoting wellness in a school of architecture. Methods: The study utilized a convergent mixed methods research design. First, design students (n = 277) responded to an online wellness survey to explore how they lower stress during their academic studies. Second, semi-structured interviews (n = 37) uncovered students’ coping mechanisms to overcome stress during their academic studies and recommendations for creating a more healthful environment. Results: Strategies students most often adopted to lower stress were socializing, sleeping, exercising, taking personal time, spending time outdoors, and improving time management. Students recommended improving communication and time management, a sense of community, and building a health and wellness culture. Findings were translated into design considerations for creating healthier places on college campuses. Conclusions: Design students employ a variety of strategies to overcome the debilitating effects of mental distress. Policies and campus planning efforts should work toward student-informed solutions to promote wellness.

Background: College students are experiencing increasing levels of stress, anxiety, and depression, but little research exists on factors weakening the mental health of design students. Aim: This study investigates the prevalence and precursors of mental health challenges among architecture and landscape architecture students. Methods: This study used a convergent mixed-methods research design with three data collection methods: The Depression and Anxiety Stress Scale (DASS-21; n = 399 students), an online wellness survey (n = 269), and semi-structured interviews (n = 37). Results: Findings reveal that 33%, 46%, and 33% of students screened positive for moderate to extremely severe levels of depression, anxiety, and stress, respectively. The leading factors elevating stress included school deadlines and schedule, workload demands or amount of work outside of class, inadequate sleep, and time spent at work. Negative behaviors due to stress were discussed, including neglect of self-care (e.g., poor sleep patterns, eating habits, and physical inactivity), inability to focus, emotional instability, and social withdrawal. Conclusions: This study underscores mental health concerns among design students and identifies potential factors that contribute to unhealthy habits and compromise academic performance, including pedagogical approaches, learning and teaching culture, studio environment, and lifestyle choices.

Abstract Background Evidence indicating the optimal treatment protocol for dogs in adrenal crisis is lacking. Objectives Compare outcomes of dogs presented in adrenal crisis treated with either hydrocortisone (HC) continuous rate infusion (CRI) or intermittent dexamethasone (DEX) administration. Animals Thirty‐nine client‐owned dogs. Methods Multi‐institutional retrospective observational study (July 2016‐May 2022) including dogs diagnosed with adrenal crisis and with available sequential blood work during hospitalization. Dogs were excluded if already on treatment with exogenous corticosteroids. Outcomes assessed included duration of hospitalization, survival, number of repeat measurements of electrolyte concentrations, and time to normalization of electrolyte and acid‐base status. Results No significant difference was found between the groups for hospitalization time (P = .41; HC median [range] 48 h [19‐105 h]; DEX 57 h [17‐167 h]) nor case fatality rate 2/28 in the DEX group and 0/11 in the HC group (P = 1), nor in number of measurements of electrolyte concentrations (P = .90; HC 4 [2‐10]; DEX 4.5 [2‐15]). No significant differences were found between the 2 treatment groups in time to normalization of serum Na (P = .30; HC 33 h [7‐66 h]; DEX 16 h [1.5‐48 h]), K (P = .92; HC 17 h [4‐48 h]; DEX 16 h [1.25‐60 h]) or Na/K ratio (P = .08; HC 17 h [8‐48 h]; DEX 26 h [1.5‐60 h]). Conclusions This study detected no difference in outcomes for dogs in adrenal crisis treated with either DEX boluses or HC CRIs.

Abstract Background A recent study conducted at our tertiary hospital emergency department (ED) reviewed ED consultations and found that adolescents aged 16–18 years present significantly more often for trauma and psychiatric problems than adults over 18 years. Accidental injuries are one of the greatest health risks for children and adolescents. In view of the increased vulnerability of the adolescent population, this study aimed to further analyse trauma-related presentations in adolescents. Methods We conducted a single-centre, retrospective, cross-sectional study of all adolescent trauma patients aged 16 to 18 years presenting to the adult ED at the University Hospital (Inselspital) in Bern, Switzerland, from January 2013 to July 2017. We analysed presentation data as well as inpatient treatment and cost-related data. Data of female and male patients were compared by univariable analysis. A comparison group was formed consisting of 200 randomly chosen patients aged 19–25 years old with the same presentation characteristics. Predictive factors for surgical treatment were obtained by multivariable analysis. Results The study population included a total of 1,626 adolescent patients aged 16–18 years. The predominant causes for ED presentation were consistent within case and comparison groups for sex and age and were sports accidents, falls and violence. Male patients were more likely to need surgical treatment (OR 1.8 [95% CI: 1.2–2.5], p = 0.001) and consequently inpatient treatment (OR 1.5 [95% CI: 1.1–2.1], p = 0.01), associated with higher costs (median 792 Swiss francs [IQR: 491-1,598]). Other independent risk factors for surgical treatment were violence-related visits (OR 2.1 [95% CI: 1.3–3.5, p = 0.004]) and trauma to the upper extremities (OR 2.02 [95% CI: 1.5–2.8], p

Abstract We aimed to examine the concordance of type-2 diabetes, prediabetes and the metabolic syndrome in couples. In cross-sectional analyses, we used data from 1173 couples with index persons from the Heinz Nixdorf Recall Study (2011–2015), a population-based cohort study in Western Germany, and partners from the associated Heinz Nixdorf Multigeneration Study (2013–2016). Mean age (standard deviation) was 67.2 (6.6) years in index persons, and 67.8 (7.7) years in partners. The exposure was the presence of diabetes, prediabetes or metabolic syndrome in index persons, the outcome was the presence of the same health status in partners. Diabetes was defined by either self-reported diagnosis, intake of antidiabetic drugs or insulin, or HbA1c ≥ 6.5%. If the index person had prediabetes or diabetes, the partner was 1.46 (95% CI 1.07–2.00) times more likely to have diabetes than partners of index persons without the condition in the crude model (adjusted model: 1.33 (0.97–1.83)). For self-reported diabetes and for the metabolic syndrome, the corresponding prevalence ratios were 1.33 (0.90–1.97) and 1.17 (1.03–1.32), respectively (adjusted models: 1.23 (0.77–1.94), 1.04 (0.91–1.18)). In German couples, there was weak to moderate concordance of type-2 diabetes, prediabetes and the metabolic syndrome in crude, but poor concordance in adjusted models.

The new wide-bandgap power semiconductor devices, such as gallium nitride and silicon carbide, have encouraged the development of power electronic converters with better efficiency, higher switching frequency, and smaller packages. However, such fast power converters are characterized by steep pulse width modulation voltage waveforms that cause increased electrical stress on the insulation system of the electric machine windings, eventually leading to premature failure. This poses a serious problem for high-speed applications where high system reliability and safety are required. Therefore, this work aims to show the effects of electrical aging on the high-frequency characteristics of electrical machines and then to assess the damage caused to the windings of a motor by such steep PWM waveforms. Finally, using a high-frequency model of the machine windings, it is possible to identify the parameters that are most affected by electrical stresses and thus assess the aging status of the insulation system.

(1) Background: 3D printable materials with accurately defined iodine content enable the development and production of radiological phantoms that simulate human tissues, including lesions after contrast administration in medical imaging with X-rays. These phantoms provide accurate, stable and reproducible models with defined iodine concentrations, and 3D printing allows maximum flexibility and minimal development and production time, allowing the simulation of anatomically correct anthropomorphic replication of lesions and the production of calibration and QA standards in a typical medical research facility. (2) Methods: Standard printing resins were doped with an iodine contrast agent and printed using a consumer 3D printer, both (resins and printer) available from major online marketplaces, to produce printed specimens with iodine contents ranging from 0 to 3.0% by weight, equivalent to 0 to 3.85% elemental iodine per volume, covering the typical levels found in patients. The printed samples were scanned in a micro-CT scanner to measure the properties of the materials in the range of the iodine concentrations used. (3) Results: Both mass density and attenuation show a linear dependence on iodine concentration (R2 = 1.00), allowing highly accurate, stable, and predictable results. (4) Conclusions: Standard 3D printing resins can be doped with liquids, avoiding the problem of sedimentation, resulting in perfectly homogeneous prints with accurate dopant content. Iodine contrast agents are perfectly suited to dope resins with appropriate iodine concentrations to radiologically mimic tissues after iodine uptake. In combination with computer-aided design, this can be used to produce printed objects with precisely defined iodine concentrations in the range of up to a few percent of elemental iodine, with high precision and anthropomorphic shapes. Applications include radiographic phantoms for detectability studies and calibration standards in projective X-ray imaging modalities, such as contrast-enhanced dual energy mammography (abbreviated CEDEM, CEDM, TICEM, or CESM depending on the equipment manufacturer), and 3-dimensional modalities like CT, including spectral and dual energy CT (DECT), and breast tomosynthesis.

Abstract Background Patients undergoing cholecystectomy have not been reported previously to develop clinically relevant postoperative hypernatremia. Objectives Describe the frequency of postoperative hypernatremia in dogs undergoing cholecystectomy and its clinical relevance (duration of hospitalization and survival). Animals Thirty‐seven dogs undergoing cholecystectomy at 2 private referral hospitals. Methods Retrospective study of dogs undergoing cholecystectomy with available preoperative and postoperative serum sodium concentrations. Results Postoperative hypernatremia (>150 mEq/L) was common (56%; 95% confidence interval [CI], 40%‐70%) and was associated with significantly higher mortality compared to nonhypernatremic patients (52%; 95% CI, 30%‐70% vs 12.5%; 95% CI, 2%‐40%; P = .02). Nonsurvivors had higher mean postoperative peak serum sodium concentrations (155 mEq/L; range, 146‐172) than survivors (150 mEq/L; range, 142‐156; P = .01). Dogs developing hypernatremia within 6 hours after surgery had 7.7 higher odds of nonsurvival (odds ratio [OR], 7.7; 95% CI, 5.9‐9.4). A delta value (serum sodium concentration on admission [T0] − serum sodium concentration 6 hours postoperatively [T2]) of ≥10 mEq/L carried 3.3 higher odds of mortality (OR, 3.3; 95% CI, 1.6‐5.1). All dogs with a postoperative peak sodium concentration >160 mEq/L did not survive. Admission acute patient physiologic laboratory evaluation fast (APPLEfast) scores were not different between survivors and nonsurvivors or between postoperative hypernatremic and normonatremic patients. Hospitalization time was no different between hypernatremic and normonatremic patients (6 days vs 4.5 days; P = .15). Dogs with gallbladder mucocele were more likely to develop postoperative hypernatremia and have poorer outcomes. Conclusions Hypernatremia was a common and clinically relevant postoperative complication in dogs after cholecystectomy. Detection of hypernatremia within 6 hours after surgery may be associated with poorer outcomes.

Abstract Social participation, also termed stakeholder voice, is an important component of health system governance. Increased interactions between the community and policy makers could facilitate a more responsive health system that targets the needs of the community better. Recently, the World Health Organization (WHO) published a handbook on social participation that identified five key themes for ministries of health to consider when engaging the input of the community. In this rapid systematic literature review, we aimed to identify quantitative and qualitative measures that have been used to assess aspects of social participation involving people and policy makers. We identified 172 measures from 48 studies from countries in all six WHO regions. These measures were categorized by all five themes from the handbook on social participation and these measures are linked to 27 concepts. This rapid review found that the focus of measures is largely on the existence of participation—be it by the general population or specific vulnerable groups—rather than on the quality of their participation. The measures in this inventory may be useful for ministries of health and other key stakeholders to use when developing methods to assess and encourage social participation in their context.

Context: Diffuse idiopathic skeletal hyperostosis (DISH) or Forestier's syndrome may reduce vertebral mobility, thus affecting the stability of adjacent vertebral segments and promoting spinal stenosis, vertebral dislocation, and unstable fracture secondary to low-energy trauma. Aims: This study aimed to contribute with a case series of three patients affected by DISH undergone surgery with occipitocervical fixation for craniovertebral junction (CVJ) instability since the poor literature about CVJ instability and surgery in patients affected by DISH. Settings and Design: This was a multicentric case series. Subjects and Methods: Literature about CVJ instability and surgery in patients affected by DISH is poor. Thus, we present a case series of three patients affected by DISH, who underwent surgery with occipitocervical fixation with different clinical and radiological patterns. Results: CVJ represents one of the most mobile joints of the spine and is at greater risk for instability. Moreover, instability itself may act as primum movens for several degenerative conditions such as cervical spondylosis, ossification of the posterior longitudinal ligament, and cervical deformities. On the contrary, DISH itself may worsen CVJ instability because of subaxial spine stiffness. In case of DISH, the rigid unit formed by several ossified vertebral bodies acts as a long lever arm, increasing the forces applied to the hypermobile CVJ and reducing the dynamic buffer capability of ossified spine. On the other hand, vertebral instability increases the odds of fractures. In such cases, CVJ posterior instrumentation and fusion is an effective and feasible surgical technique, aimed to restore vertebral stability and to halt the progression of spinal stenosis. Conclusions: Due to the altered dynamics cervical spine along with the possible comorbidities, treatment indication and surgery for patients affected by DISH must be tailored case by case.

Introduction The need of a regional healthcare monitoring in order to evaluate quality and utilisation of health services in smaller scale is internationally and in Germany well established. Little is known about variation in healthcare in rural German areas, especially for women’s health. In particular, endometriosis is highly prevalent and known to be unsatisfactorily treated. Thus, this study aims to investigate utilisation and quality of care, the influence of structural determinants on quality and the patient’s experiences on endometriosis healthcare in rural Hesse.Methods and analysis We will use a mixed methods approach to ensure reliable mapping of the care situation for endometriosis patients in seven counties in Central and Eastern Hesse. First, retrospective secondary utilisation data and quality indicators will be used to describe possible regional variation in the treatment of endometriosis in the outpatient and inpatient sector. Second, we compare structural determinants of regions with quality of care. Third, we conduct qualitative, semistructured interviews with endometriosis patients on their perspective and experiences in those chosen rural regions. Data will then be analysed using descriptive statistics, small area variation analyses and multifactorial analyses of variance (ANOVAs). The interview will be interpreted using the experience-focused phenomenological approach.Ethics and dissemination The study has been approved by the ethics committee of Philipps-University Marburg. Utilisation data and structural determinants are anonymised and partly aggregated. The interview will use tokens for pseudonymisation to prevent the collected data from being assigned to an individual person. Also, informed consent will be obtained from patients.The results of this study will be reported to the scientific community in peer-reviewed journals and at conferences. A summary of the key findings will be provided to the interviewed patients and the Endometriosis Association Germany.

(1) Background: Gangliogliomas are rare tumors accounting for about 0.4% of all central nervous system tumors. They are usually located in the temporal lobes of children and young adults, though such tumors in the infratentorial region and adult-age patients rarely reported. (2) Methods: A systematic review on ganglioglioma with infratentorial location in the adult population was conducted in accordance with the PRISMA guidelines. A total of 275 articles were found, and 23 were included. Demographic data, the location and histology of the lesion, pre-operative neurological status, the type of surgery, recurrence, radiotherapy/chemotherapy adjuvant treatments, neurological outcomes and follow-up information were collected. We also presented an illustrative case. (3) Results: A total of 27 patients were included. In 51%, the location was the cerebellum; in 40%, it was the fourth ventricle; in 11%, it was brainstem; and in 4%, it was the cerebellopontine angle. STR was performed in 44%, GTR in 26% and biopsy in 15% of the cases. Adjuvant radiotherapy was found in 22% of cases. Disease recurrence occurred in 15% of patients between 1 and 12 months after surgery with a diagnosis of high-grade ganglioglioma, while in six cases, no disease recurrence was documented. (4) Conclusions: Infratentorial glioneuronal tumors are rare findings in the adult population. Histopathological characterization does not seem to fully reflect their true behavior. Future studies are warranted for better characterizing histopathological findings and treatment.

Surgical treatment of neurovascular lesions like intracranial aneurysms, arteriovenous malformations and arteriovenous dural fistulas is still associated with high morbidity. Several recent studies are providing increasing insights into reliable tools to improve surgery and reduce complications. Inadvertent vessel compromise and incomplete occlusion of the lesion represent the most possible complications in neurovascular surgery. It is clear that direct visual examination alone does not allow to identify all instances of vessel compromise. Various modalities, including angiography, microvascular Doppler and neurophysiological studies, have been utilized for hemodynamics of flow vessels in proper clipping of the aneurysm or complete obliteration of the lesion. We intended to review the current knowledge about the intraoperative microvascular Doppler (iMDS) employment in the most updated literature, and explore the most recent implications not only in intracranial aneurysms but also in neurovascular lesions like arteriovenous malformations (AVMs) and arteriovenous dural fistulas (AVDFs). According to the PRISMA guidelines, systematic research in the most updated platform was performed in order to provide a complete overview about iMDS employment in neurovascular surgery. Twelve articles were included in the present paper and analyzed according to specific research areas. iMDS employment could represent a crucial tool to improve surgery in neurovascular lesions. The safety and effectiveness of the surgical treatment of neurovascular lesions like intracranial aneurysm and other neurovascular lesions like AVMs and AVDFs requires careful and accurate consideration regarding the assessment of anatomy and blood flow. Prognosis may depend on suboptimal or incomplete exclusion of the lesion.

In the field of minimally invasive neurosurgery, microscopic transsphenoidal surgery (MTS) and endoscopic transsphenoidal surgery (ETS) have been widely accepted as a safe approach for pituitary lesions and, more recently, their indications have been extended to lesions at various skull base regions. It is mandatory during transsphenoidal surgery (TS) to identify key anatomical landmarks in the sphenoid sinus and distinguish them from the lesion. Over the years, many intraoperative tools have been introduced to improve the neuronavigation systems aiming to achieve safer and more accurate neurosurgical interventions. However, traditional neuronavigation systems may lose the accuracy of real-time location due to the discrepancy between the actual surgical field and the preoperative 2D images. To deal with this, augmented reality (AR)—a new sophisticated 3D technology that superimposes computer-generated virtual objects onto the user’s view of the real world—has been considered a promising tool. Particularly, in the field of TS, AR can minimize the anatomic challenges of traditional endoscopic or microscopic surgery, aiding in surgical training, preoperative planning and intra-operative orientation. The aim of this systematic review is to analyze the potential future role of augmented reality, both in endoscopic and microscopic transsphenoidal surgeries.

Spinal cord injury (SCI) is a devastating neurological disorder that has a substantial detrimental impact on a person’s quality of life. The estimated global incidence of SCI is 40 to 80 cases per million people and around 90% of cases are traumatic. Various etiologies can be recognized for SCI, and post-traumatic SCI represents the most common of these. Patients worldwide with SCI suffer from a persistent loss of motor and sensory function, which affects every aspect of their personal and social lives. Given the lack of effective treatments, many efforts have been made to seek a cure for this condition. In recent years, thanks to their ability to regenerate tissue and repair lost or damaged cells, much attention has been directed toward the use of stem cells (embryonic, induced pluripotent, mesenchymal, hematopoietic), aimed at restoring the functional integrity of the damaged spinal cord and improving a functional recovery including sensory and motor function. In this paper, we offer an overview of the benefits and drawbacks of stem cell therapy for SCI based on clinical evidence. This report also addresses the characteristics of various stem cell treatments, as well as the field’s likely future. Each cell type targets specific pathological characteristics associated with SCI and demonstrates therapeutic effects via cell replacement, nutritional support, scaffolds, and immunomodulation pathways. SCI accompanied by complex pathological processes cannot be resolved by single treatment measures. Stem cells are associated with the adjustment of the expression of neurotrophic factors that help to achieve better nutrition to damaged tissue. Single-cell treatments have been shown in some studies to provide very minor benefits for SCI in multiple preclinical studies and a growing number of clinical trials. However, SCI damage is complex, and many studies are increasingly recognizing a combination approach such as physical therapy, electrical stimulation, or medication therapy to treatment.

(1) Background: Innovation and continuous demand in the field of visual enhancing technologies and video streaming have led to the discovery of new systems capable of improving visualization and illumination of the surgical field. The exoscope was brought into neurosurgical routine, and nearly ten years later, modern 3D systems have been introduced and tested, giving encouraging results. (2) Methods: In order to evaluate the surgeon’s confidence with the exoscope and their increasing ability in terms of time spent and quality of the final achievement since their first encounter with the technique, an experimental trial on 18 neurosurgeons from a single Institution was performed to evaluate the learning curve for the use of the VITOM-3D exoscope in neurosurgical practice on a model of brain and dura mater. (3) Results: A significant improvement in the quality of the performance, number of errors made, and reduction in the time was found after the third iteration of the task, by when almost all the participants felt more comfortable and confident. No significant differences between senior neurosurgeons and resident neurosurgeons were reported. (4) Conclusions: Our results show that three iterations are enough to gain confidence with the exoscope from its first use, regardless of previous experience and training with an operating microscope.

Abstract Background Secondary adrenal insufficiency is a frequent issue in patients with renal replacement therapy. There are concerns about metabolism and clearance for adrenocorticotropic hormone (ACTH) and cortisol in addition to hemoconcentration as confounding factors during hemodialysis (HD). Therefore, ACTH testing is currently performed before or in between HD sessions. This review of the literature aims to evaluate the current evidence for validity of testing for adrenal insufficiency in patients on chronic renal replacement therapy. Methods A literature search of PubMed database for interventional and observational clinical trials was performed. Case reports and reviews were excluded. The search included all articles published until July 2020. Results Of 218 potentially eligible articles, 16 studies involving 381 participants were included. Seven studies performed an ACTH test before HD or in between HD sessions. There was no data available regarding ACTH testing during HD. But there was evidence of decreased cortisol levels during HD as compared to afterwards. All included 16 studies measured basal cortisol, and seven studies performed an ACTH test. Seven trials had comparable data of baseline cortisol for a quantitative analysis. Standardized mean difference of overall cortisol was 0.18 nmol/l (95%CI − 0.08 to 0.44) in the case group. Conclusions In patients undergoing renal replacement therapy, basal serum cortisol values are comparable to healthy volunteers. There is limited data on the validity of stimulated cortisol in these patients, especially during HD. Trial registration Registration no. CRD42020199245 .

Objetiva-se com este trabalho analisar as representações sociais no ciberespaço da Rede de Grupos de Agroecologia do Brasil (REGA Brasil), considerando as informações sobre os movimentos de agroecologia brasileira entre jovens acadêmicos, a partir da Teoria das Representações Sociais e da articulação de redes e/ou grupos de agroecologia nas universidades. Para tanto, realizou-se análise netnográfica no site da Rede, análise de conteúdo das cartas agroecológicas redigidas nos encontros nacionais dos grupos de agroecologia (ENGAs) e uma breve discussão das campanhas de comunicação digital. Do ponto de vista representativo, apresentam-se muitos significados ancorados em uma base definida entre o sujeito (agroecologia) e o objeto (juventude). Observaram-se indícios representativos fundamentados na agricultura familiar, trabalho coletivo, gênero, universidades, ações extensionistas e recursos midiáticos. Os resultados demonstraram que para a juventude o uso das representações sociais é importante, sendo uma formação alternativa em favor da sustentabilidade, cooptando grupos universitários de agroecologia e outros setores sociais a aderirem à causa.

Age-induced cellular senescence leads to a decline in efficacy of immune response and an increase in morbidity and mortality. Physical activity may be an intervention to slow down or reverse this process for elderly individuals or even delay it via enhanced activity over their lifespan. The aim of this systematic review was to analyze and discuss the current evidence of the effects of physical activity on senescence in leukocyte subpopulations. Two electronic databases (PubMed, Web of Science) were scanned in July 2020. Studies performing endurance or resistance exercise programs and investigating leukocytes of healthy, particularly elderly subjects were included. Nine human studies were identified, including a total of 440 participants, of which two studies examined different types of exercise training retrospectively, three conducted resistance exercise, three endurance exercise, and one endurance vs. resistance training. Results revealed that exercise training increased the naïve subsets of peripheral T-helper cells and cytotoxic T-cells, whereas the senescent and effector memory T-cells re-expresses CD45RA (TEMRA) subsets decreased. Moreover, the percentage of T-helper- compared to cytotoxic T-cells increased. The results suggest that physical activity reduces or slows down cellular immunosenescence. Endurance exercise seems to affect cellular senescence in a more positive way than resistance training. However, training contents and sex also influence senescent cells. Explicit mechanisms need to be clarified.

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor with roles in inflammation and tumorigenicity. A fraction of STAT3 localizes in mitochondria, where it augments tumorigenesis via regulation of mitochondrial functions, including modulation of respiration and redox status. We show a novel mechanism for mitochondrial STAT3 regulation of redox homeostasis in triple‐negative breast cancer cells. Loss of STAT3 diminished complex I dehydrogenase activity and impaired NAD+ regeneration, leading to impaired expression of glutathione biosynthetic genes and other antioxidant genes. Expressing mitochondrially restricted STAT3 or replenishment of the cellular NAD pool restored antioxidant gene expression, as did complementation of the NADH dehydrogenase activity by expression of the STAT3‐independent yeast dehydrogenase, NDI1. These NAD‐regulated processes contributed to malignant phenotypes by promoting clonal cell growth and migration. Proximity interaction and protein pull‐down assays identified three components of complex I that associated with mitochondrial STAT3, providing a potential mechanistic basis for how mitochondrial STAT3 affects complex I activity. Our data document a novel mechanism through which mitochondrial STAT3 indirectly controls antioxidant gene regulation through a retrograde NAD+ signal that is modulated by complex I dehydrogenase activity.

Abstract Background Transcriptomic studies combined with a well annotated genome have laid the foundations for new understanding of molecular processes. Tools which visualise gene expression patterns have further added to these resources. The manual annotation of the Actinidia chinensis (kiwifruit) genome has resulted in a high quality set of 33,044 genes. Here we investigate gene expression patterns in diverse tissues, visualised in an Electronic Fluorescent Pictograph (eFP) browser, to study the relationship of transcription factor (TF) expression using network analysis. Results Sixty-one samples covering diverse tissues at different developmental time points were selected for RNA-seq analysis and an eFP browser was generated to visualise this dataset. 2839 TFs representing 57 different classes were identified and named. Network analysis of the TF expression patterns separated TFs into 14 different modules. Two modules consisting of 237 TFs were correlated with floral bud and flower development, a further two modules containing 160 TFs were associated with fruit development and maturation. A single module of 480 TFs was associated with ethylene-induced fruit ripening. Three “hub” genes correlated with flower and fruit development consisted of a HAF-like gene central to gynoecium development, an ERF and a DOF gene. Maturing and ripening hub genes included a KNOX gene that was associated with seed maturation, and a GRAS-like TF. Conclusions This study provides an insight into the complexity of the transcriptional control of flower and fruit development, as well as providing a new resource to the plant community. The Actinidia eFP browser is provided in an accessible format that allows researchers to download and work internally.

Abstract Background Streptococcal infections are associated with life-threatening pneumonia and sepsis. The rise in antibiotic resistance calls for novel approaches to treat bacterial diseases. Anti-virulence strategies promote a natural way of pathogen clearance by eliminating the advantage provided to bacteria by their virulence factors. In contrast to antibiotics, anti-virulence agents are less likely to exert selective evolutionary pressure, which is a prerequisite for the development of drug resistance. As part of their virulence mechanism, many bacterial pathogens secrete cytolytic exotoxins (hemolysins) that destroy the host cell by destabilizing their plasma membrane. Liposomal nanotraps, mimicking plasmalemmal structures of host cells that are specifically targeted by bacterial toxins are being developed in order to neutralize-by competitive sequestration-numerous exotoxins. Results In this study, the liposomal nanotrap technology is further developed to simultaneously neutralize the whole palette of cytolysins produced by Streptococcus pneumoniae, Streptococcus pyogenes and Streptococcus dysgalactiae subspecies equisimilis-pathogens that can cause life-threatening streptococcal toxic shock syndrome. We show that the mixture of liposomes containing high amounts of cholesterol and liposomes composed exclusively of choline-containing phospholipids is fully protective against the combined action of exotoxins secreted by these pathogens. Conclusions Unravelling the universal mechanisms that define targeting of host cells by streptococcal cytolysins paves the way for a broad-spectrum anti-toxin therapy that can be applied without a diagnostic delay for the treatment of bacterial infections including those caused by antibiotic-resistant pathogens.

Transplantation of hematopoietic material into recipient mice is an assay routinely used to determine the presence and function of hematopoietic stem and progenitor cells (HSPCs) in vivo. The principle of the method is to transplant donor cells being tested for HSPCs into a recipient mouse following bone marrow ablation and testing for reconstitution of hematopoiesis. Congenic mouse strains where donor and recipient differ by a distinct cell surface antigen (commonly CD45.1 versus CD45.2) are used to distinguish between cells derived from the donor and any residual recipient cells. Typically, the transplantation is performed using bone marrow cells, which are enriched for HSPCs. Here, we describe an analogous procedure using hematopoietic material from spleen, allowing detection of functional progenitors and/or stem cells in the spleen that can occur under certain pathologies. Key to the success of this procedure is the prior removal of mature T cells from the donor sample, to minimize graft versus host reactions. As such, this protocol is highly analogous to standard bone marrow transplant procedures, differing mainly only in the source of stem cells (spleen rather than bone marrow) and the recommendation for T cell depletion to avoid potential immune incompatibilities.Graphical abstract: Schematic overview for assessment of stem cells in spleen by transplantation. Single cell suspensions from spleens are depleted of potentially pathogenic mature T lymphocytes by magnetic bead immunoselection using biotinylated antibodies against CD4 and CD8, followed by streptavidin magnetic beads, which are subsequently removed by using a magnet (MojoSort, Biolegend). Successful T cell depletion is then evaluated by Fluorescence Activated Cell Sorting (FACS). T-cell depleted cell suspension is injected intravenously through the retro-orbital sinus into lethally irradiated recipients. Recipients are analyzed for successful engraftment by FACS analysis for the presence of donor-derived mature hematopoietic lineages in the peripheral blood. A second serial transplantation can be used to document the presence of long-term reconstituting stem cells in the periphery of the original donor mice.

BackgroundDespite various existing scores that predict morbidity and mortality of patients with cirrhotic liver disease (CLD), data on specific risk stratification of patients with CLD undergoing colorectal surgery (CRS) are rare. The aim of this study was to assess in-hospital morbidity and mortality of patients with liver cirrhosis scheduled for CRS, with specific focus on possible pitfalls of surgery in this special cohort.MethodsBetween 1996 and 2018, 54 patients with CLD undergoing CRS were identified and included in this study cohort. Postoperative morbidity and mortality were assessed using the Clavien/Dindo (C/D) classification as well as by type of complication. Univariate and multivariate analyses were performed to analyze the predictive factors for increased postoperative morbidity.ResultsOf the patients, 37% patients died during the procedure or postoperatively. Major complications were seen in 23.1% of patients (>C/D IIIb). Patients with Child B or C cirrhosis as well as patients undergoing emergency surgery experienced significantly more major complications (p = 0.04 and p = 0.023, respectively). The most common complications were bleeding requiring blood transfusion (51.1%) and cardiocirculatory instability due to bleeding or sepsis (44.4%). In 53.7% of patients, an anastomosis was created without a protective ostomy. Anastomotic leakage occurred in 20.7% of these patients. Multivariate analysis showed that a primary anastomosis without a protective ostomy was the strongest risk factor for major complications (p = 0.042).DiscussionMorbidity and mortality after CRS in patients with CLD remains high and is not only influenced by liver function but also by surgical variables. Considering the high rate of anastomotic leakage, creating a protective or definitive ostomy must be considered with regard to the underlying pathology, the extent of CLD, and the patient's condition. Moreover, our data suggest that surgery in these most fragile patients should be performed only in experienced centers with immediate contact to hepatologists and experts in hemostasis.

BackgroundArterial vasospasm has been ascribed as the responsible etiology of delayed cerebral infarction in patients with aneurysmal subarachnoid hemorrhage (aSAH), but other neurovascular structures may be involved. We present the protocol for a multicenter, prospective, observational study focused on analyzing morphological changes in cerebral veins of patients with aSAH.Methods and AnalysisIn a retrospective arm, we will collect head arterial and venous CT angiograms (CTA) of 50 patients with aSAH and 50 matching healthy controls at days 0–2 and 7–10, comparing morphological venous changes. A multicenter prospective observational study will follow. Patients aged ≥18 years of any gender with aSAH will be enrolled at 9 participating centers based on the predetermined eligibility criteria. A sample size of 52 aSAH patients is expected, and 52 healthy controls matched per age, gender, and comorbidities will be identified. For each patient, sequential CTA will be conducted upon admission (day 0–2), at 7–10 days, and at 14–21 days after aSAH, evaluating volumes and morphology of the cerebral deep veins and main cortical veins. One specialized image collecting center will analyze all anonymized CTA scans, performing volumetric calculation of targeted veins. Morphological venous changes over time will be evaluated using the Dice coefficient and the Jaccard index and scored using the Boeckh–Behrens system. Morphological venous changes will be correlated to clinical outcomes and compared between patients with aSAH and healthy-controls, and among groups based on surgical/endovascular treatments for aSAH.Ethics and DisseminationThis protocol has been approved by the ethics committee and institutional review board of Ethikkommission, SALK, Salzburg, Austria, and will be approved at all participating sites. The study will comply with the Declaration of Helsinki. Written informed consent will be obtained from all enrolled patients or their legal tutors. We will present our findings at academic conferences and peer-reviewed journals.Approved Protocol Version and RegistrationVersion 2, 09 June 2021.

Resumen: La oxigenoterapia crónica domiciliaria (OCD) consiste en el uso terapéutico del oxígeno a concentraciones mayores de las que se encuentran en el aire ambiente, con la intención de tratar o prevenir las manifestaciones a largo plazo de la hipoxia. Esta terapia ha demostrado aumentar la supervivencia en los enfermos con enfermedad pulmonar obstructiva crónica (EPOC) e insuficiencia respiratoria crónica (IRC). Este concepto se ha extendido por analogía a la IRC originada por otras enfermedades respiratorias y no respiratorias, sin que su efectividad haya podido ser demostrada. La OCD no se ha demostrado efectiva en mejorar la supervivencia de pacientes con EPOC e hipoxemia moderada. Tampoco hay consenso sobre su empleo durante las desaturaciones nocturnas en EPOC y durante las desaturaciones al esfuerzo. La OCD actual debe valorar la situación clínica y social, adecuando las fuentes de administración de oxígeno al perfil de movilidad de los pacientes, conseguir la adecuada selección de paciente y fuente de oxígeno y es imprescindible titular la oxigenoterapia para asegurar la corrección de la hipoxemia. La búsqueda del equipo de oxígeno ideal, mejorar los sistemas de regulación e información de las terapias, avanzar en la educación de los pacientes y potenciar la investigación, son líneas de trabajo que nos marcan el futuro de la OCD. Abstract: Continuous home oxygen therapy (HOT) is the therapeutic use of oxygen at higher concentrations than those found in ambient air for treating or preventing long-term manifestations of hypoxia, and has been shown to increase survival in patients with chronic obstructive pulmonary disease (COPD) and chronic respiratory failure (CRF). This concept has been extended by analogy to CRF originating from other respiratory and non-respiratory diseases, but its effectiveness has not been demonstrated. HOT has not been shown to be effective in improving the survival of patients with COPD and moderate hypoxemia, nor is there any consensus on its use during nocturnal desaturations in COPD and desaturations caused by exertion. In the current use of HOT, the patient's clinical and social situation should be assessed, oxygen supply sources must be adapted to the patient's mobility profile, the appropriate oxygen source must be selected for each patient, and oxygen therapy must be titrated to ensure that hypoxemia is corrected. Lines of research that will shape the future of HOT include investigating the ideal equipment, improving regulation systems and information about treatments, educating patients, and promoting research.

Intraoperative ultrasound (IOUS) is becoming progressively more common during brain tumor surgery. We present data from our case series of brain tumor surgery performed with the aid of IOUS in order to identify IOUS advantages and crucial aspects that may improve the management of neurosurgical procedures for brain tumors. From January 2021 to September 2021, 17 patients with different brain tumors underwent brain tumor surgery aided by the use of IOUS. During surgery, the procedure was supported by the use of multiples ultrasonographic modalities in addition to standard B-mode: Doppler, color Doppler, elastosonography, and contrast-enhanced intraoperative ultrasound (CEUS). In selected cases, the use of IOUS during surgical procedure was combined with neuronavigation and the use of intraoperative fluorescence by the use of 5-aminolevulinic acid (5-ALA). In one patient, a preoperative ultrasound evaluation was performed through a former iatrogenic skull defect. This study confirms the role of IOUS in maximizing the EOR, which is strictly associated with postoperative outcome, overall survival (OS), and patient’s quality of life (QoL). The combination of ultrasound advanced techniques such as Doppler, color Doppler, elastosonography, and contrast-enhanced intraoperative ultrasound (CEUS) is crucial to improve surgical effectiveness and patient’s safety while expanding surgeon’s view.

Between-subject variability in cognitive performance has been related to inter-individual differences in functional brain networks. Targeting the dorsal attention network (DAN) we questioned (i) whether resting-state functional connectivity (FC) within the DAN can predict individual performance in spatial attention tasks and (ii) whether there is short-term adaptation of DAN-FC in response to task engagement. Twenty-seven participants first underwent resting-state fMRI (PRE run), they subsequently performed different tasks of spatial attention [including visual search (VS)] and immediately afterwards received another rs-fMRI (POST run). Intra- and inter-hemispheric FC between core hubs of the DAN, bilateral intraparietal sulcus (IPS) and frontal eye field (FEF), was analyzed and compared between PRE and POST. Furthermore, we investigated rs-fMRI-behavior correlations between the DAN-FC in PRE/POST and task performance parameters. The absolute DAN-FC did not change from PRE to POST. However, different significant rs-fMRI-behavior correlations were revealed for intra-/inter-hemispheric connections in the PRE and POST run. The stronger the FC between left FEF and IPS before task engagement, the better was the learning effect (improvement of reaction times) in VS (r = 0.521, p = 0.024). And the faster the VS (mean RT), the stronger was the FC between right FEF and IPS after task engagement (r = −0.502, p = 0.032). To conclude, DAN-FC relates to the individual performance in spatial attention tasks supporting the view of functional brain networks as priors for cognitive ability. Despite a high inter- and intra-individual stability of DAN-FC, the change of FC-behavior correlations after task performance possibly indicates task-related adaptation of the DAN, underlining that behavioral experiences may shape intrinsic brain activity. However, spontaneous state fluctuations of the DAN-FC over time cannot be fully ruled out as an alternative explanation.

Spine is a frequent site of bone metastases, with a 8.5 months median survival time after diagnosis. In most cases treatment is only palliative. Several advanced techniques can ensure a better Quality of Life (QoL) and increase life expectancy. Radiofrequency ablation (RFA) uses alternating current to produce local heating and necrosis of the spinal lesion, preserving the healthy bone. RFA is supported by vertebral reinforcement through kyphoplasty and vertebroplasty in order to stabilize the fracture with polymethylmethacrylate (PMMA) injection, restoring vertebral body height and reducing the weakness of healthy bone. The aim of this study is to demonstrate the efficacy and advantages of RFA plus vertebral reinforcement through PMMA vertebroplasty and fixation in patients affected by bone spinal metastases. We retrospectively analyzed 54 patients with thoraco-lumbar metastatic vertebral fractures admitted to our Unit between January 2014 and June 2020. Each patient underwent RFA followed by PMMA vertebroplasty and transpedicle fixation. We evaluated pain relief through the Visual Analogue Scale (VAS) Score and PMMA vertebral filling based on the mean Saliou filling score. Analysis of variance (ANOVA) was used to test pain relief with statistical significance for p

(1) Background: The “snake-eyes” sign represents a unique finding characterized by bilateral hyperintense symmetric, circular, or ovoid foci on T2-weighted MRI sequences in the anterior horn cells of the spinal cord. There are conflicting opinions as some authors affirm that it does not affect the prognosis of cervical myelopathy while other papers emphasize the opposite, stating how the “snake-eyes” sign constitutes an irreversible lesion and a predictor of poor prognosis. This systematic review evaluates the correlation between the “snake-eyes” sign and the prognosis of cervical myelopathy after surgery including anterior and/or posterior approaches; (2) Methods: A systematic literature review was conducted following the PRISMA statement and a total of seven papers were included; (3) Results: A total of 419 patients were evaluated, with a mean age of 55.72 ± 14.38 years. After surgery, 26.01% of patients experienced a significant clinical improvement, while in 61.81%, there was no significant improvement. In particular, 144 of 196 patients (73.5%) treated through an anterior approach and 114 of 223 (51.1%) that underwent a posterior approach, did not present a significant improvement. Furthermore, in 12.17% of patients, the postoperative outcome was not reported, leading to a high risk of bias in the assessment of the prognostic significance of the “snake-eyes” appearance; (4) Conclusions: The “snake-eyes” sign is usually considered as an unfavorable predictive marker for myelopathic surgical patients, but the pathophysiology is still unclear, and the results have not yet reached unified levels of evidence.

Background: ACDF has become one of the established procedures for the surgical treatment of symptomatic cervical spondylosis, showing excellent clinical results and effective improvements in neural functions and neck pain relief. The main purpose of ACDF is neural decompression, and it is considered by some authors as an indirect result of the intervertebral distraction and cage insertion and the consequent restoration of the disc space and foramen height. Methods: Radiological data from 28 patients who underwent single-level ACDF were retrospectively collected and evaluated. For neural foramen evaluation, antero-posterior (A-P) and cranio-caudal (C-C) diameters were manually calculated; for intervertebral disc height the anterior, centrum and posterior measurement were calculated. All measurements were performed at surgical and adjacent (above and below) segments. NRS, NDI and also the mJOA and Nurick scale were collected for clinical examination and complete evaluation of patients’ postoperative outcome. Results: The intervertebral disc height in all its measurements, in addition to the height (C-C diameter) of the foramen (both right and left) increase at the surgical segment when comparing pre and postop results (p < 0.001, and p = 0.033 and p = 0.001). NRS and NDI radiculopathy scores showed improved results from pre- to post-op evaluation (p < 0.001), and a negative statistical correlation with the improved disc height at the surgical level. Conclusions: The restoration of posterior disc height through cage insertion appears to be effective in increasing foraminal height in patients with symptomatic preoperative cervical foraminal stenosis.

Mucopolysaccharidoses (MPSs) are a rare group of heterogeneous genetic and metabolic disorders, caused by loss of functions of several enzymes that are involved in glycosaminoglycan catabolism. Their progressive accumulations in cells, tissues, and consequently, organs lead to several clinical manifestations, such as musculoskeletal involvement. Indeed, the most common manifestation in the central nervous system is represented by cervical spinal stenosis due to bony alterations or dural thickening. Cervical involvement can commonly cause myelopathy and instability exerting severe symptoms. A prompt diagnosis and treatment of the aforementioned conditions is mandatory to ensure a better quality of life in patients with such debilitating disorders. Nevertheless, a clear consensus about their management (i.e., surgical or not) is still lacking, leading to an inevitable delay. This review aims to investigate and discuss the main causes of myelopathy in patients with mucopolysaccharidoses, available therapeutic strategies, and the impact and role of surgery on the neurological outcome.

Glial tumors alone account for 40% of all CNS tumors and present a low survival rate. The tumor microenvironment is a critical regulator of tumor progression and therapeutic effectiveness in glioma. Growing evidence from numerous studies of human solid tumor-infiltrating CD8+ T cells indicates that tissue-resident memory T cells (TRM) represent a substantial subpopulation of tumor-infiltrating lymphocytes (TILs). Although it is reported that some types of cancer patients with high immune infiltration tend to have better outcomes than patients with low immune infiltration, it seems this does not happen in gliomas. This study aimed to characterize TRMs cells in the glioma tumor microenvironment to identify their potential predictive and prognostic role and the possible therapeutic applications. Fluorescence activated cell sorting (FACS) analysis and immunofluorescence staining highlighted a statistically significant increase in CD8+ TRM cells (CD103+ and CD69+ CD8+ T cells) in gliomas compared to control samples (meningioma). In-silico analysis of a dataset of n = 153 stage IV glioma patients confirmed our data. Moreover, the gene expression analysis showed an increase in the expression of TRM-related genes in tumor tissues compared to normal tissues. This analysis also highlighted the positive correlation between genes associated with CD8+ TRM and TILs, indicating that CD8+ TRMs cells are present among the infiltrating T cells. Finally, high expression of Integrin subunit alpha E (ITGAE), the gene coding for the integrin CD103, and high CD8+ TILs abundance were associated with more prolonged survival, whereas high ITGAE expression but low CD8+ TILs abundance were associated with lower survival.

Maintenance of immune homeostasis involves a synergistic relationship between the host and the microbiome. Canonical interferon (IFN) signaling controls responses to acute microbial infection, through engagement of the STAT1 transcription factor. However, the contribution of tonic levels of IFN to immune homeostasis in the absence of acute infection remains largely unexplored. We report that STAT1 KO mice spontaneously developed an inflammatory disease marked by myeloid hyperplasia and splenic accumulation of hematopoietic stem cells. Moreover, these animals developed inflammatory bowel disease. Profiling gut bacteria revealed a profound dysbiosis in the absence of tonic IFN signaling, which triggered expansion of TH17 cells and loss of splenic Treg cells. Reduction of bacterial load by antibiotic treatment averted the TH17 bias and blocking IL17 signaling prevented myeloid expansion and splenic stem cell accumulation. Thus, tonic IFNs regulate gut microbial ecology, which is crucial for maintaining physiologic immune homeostasis and preventing inflammation.

Disruption of resting-state functional connectivity (RSFC) between core regions of the dorsal attention network (DAN), including the bilateral superior parietal lobule (SPL), and structural damage of the right-lateralized ventral attention network (VAN), including the temporo-parietal junction (TPJ), have been described as neural basis for hemispatial neglect.Pursuing a virtual lesion model, we aimed to perturbate the attention networks of 22 healthy subjects by applying continuous theta burst stimulation (cTBS) to the right SPL or TPJ. We first created network masks of the DAN and VAN based on RSFC analyses from a RS-fMRI baseline session and determined the SPL and TPJ stimulation site within the respective mask. We then performed RS-fMRI immediately after cTBS of the SPL, TPJ (active sites) or vertex (control site). RSFC between SPL/TPJ and whole brain as well as between predefined regions of interest (ROI) in the attention networks was analyzed in a within-subject design.Contrary to our hypothesis, seed-based RSFC did not differ between the four experimental conditions. The individual change in ROI-to-ROI RSFC from baseline to post-stimulation did also not differ between active (SPL, TPJ) and control (vertex) cTBS.In our study, a single session offline cTBS over the right SPL or TPJ could not alter RSFC in the attention networks as compared to a control stimulation, maybe because effects wore off too early. Future studies should consider a modified cTBS protocol, concurrent TMS-fMRI or transcranial direct current stimulation.

Brain gliomas require a deep knowledge of their effects on brain connectivity. Understanding the complex relationship between tumor and functional brain is the preliminary and fundamental step for the subsequent surgery. The extent of resection (EOR) is an independent variable of surgical effectiveness and it correlates with the overall survival. Until now, great efforts have been made to achieve gross total resection (GTR) as the standard of care of brain tumor patients. However, high and low-grade gliomas have an infiltrative behavior and peritumoral white matter is often infiltrated by tumoral cells. According to these evidences, many efforts have been made to push the boundary of the resection beyond the contrast-enhanced lesion core on T1w MRI, in the so called supratotal resection (SpTR). SpTR is aimed to maximize the extent of resection and thus the overall survival. SpTR of primary brain tumors is a feasible technique and its safety is improved by intraoperative neuromonitoring and advanced neuroimaging. Only transient cognitive impairments have been reported in SpTR patients compared to GTR patients. Moreover, SpTR is related to a longer overall and progression-free survival along with preserving neuro-cognitive functions and quality of life.

Background: The surgical strategy for brain glioma has changed, shifting from tumor debulking to a more careful tumor dissection with the aim of a gross-total resection, extended beyond the contrast-enhancement MRI, including the hyperintensity on FLAIR MR images and defined as supratotal resection. It is possible to pursue this goal thanks to the refinement of several technological tools for pre and intraoperative planning including intraoperative neurophysiological monitoring (IONM), cortico-subcortical mapping, functional MRI (fMRI), navigated transcranial magnetic stimulation (nTMS), intraoperative CT or MRI (iCT, iMR), and intraoperative contrast-enhanced ultrasound. This systematic review provides an overview of the state of the art techniques in the application of nTMS and nTMS-based DTI-FT during brain tumor surgery.Materials and Methods: A systematic literature review was performed according to the PRISMA statement. The authors searched the PubMed and Scopus databases until July 2020 for published articles with the following Mesh terms: (Brain surgery OR surgery OR craniotomy) AND (brain mapping OR functional planning) AND (TMS OR transcranial magnetic stimulation OR rTMS OR repetitive transcranial stimulation). We only included studies regarding motor mapping in craniotomy for brain tumors, which reported data about CTS sparing.Results: A total of 335 published studies were identified through the PubMed and Scopus databases. After a detailed examination of these studies, 325 were excluded from our review because of a lack of data object in this search. TMS reported an accuracy range of 0.4–14.8 mm between the APB hotspot (n1/4 8) in nTMS and DES from the DES spot; nTMS influenced the surgical indications in 34.3–68.5%.Conclusion: We found that nTMS can be defined as a safe and non-invasive technique and in association with DES, fMRI, and IONM, improves brain mapping and the extent of resection favoring a better postoperative outcome.

PICO question In dogs presenting with gastrointestinal (GI) hypomotility is ranitidine administration (any route) beneficial in improving GI motility? Clinical bottom line Category of research question Treatment The number and type of study designs reviewed One prospective controlled clinical trial and five experimental crossover studies Strength of evidence Weak Outcomes reported The vast majority of the evidence investigating ranitidine as a prokinetic has been carried out in experimental settings both in vivo with healthy conscious and anaesthetised dogs and in vitro. Under these circumstances ranitidine has shown some prokinetic properties. However, it is difficult to translate these results into reliable clinical recommendations, as the doses mentioned in these studies are often higher than the ones clinically recommended and healthy canine patients might respond differently to clinically affected ones Conclusion Although in experimental settings ranitidine has shown some prokinetic activities, no reliable clinical recommendations can be drawn from the appraised studies. There is a need of prospective clinical trials evaluating the administration of ranitidine to dogs presenting with GI hypomotility. Until further relevant studies become available, the efficacy of ranitidine administration as a prokinetic agent in dogs with GI hypomotility remains uncertain How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Free fatty acids (FFA), hyperglycemia, and inflammatory cytokines are major mediators of β-cell toxicity in type 2 diabetes mellitus, impairing mitochondrial metabolism. Glutaredoxin 5 (Glrx5) is a mitochondrial protein involved in the assembly of iron–sulfur clusters required for complexes of the respiratory chain. We have provided evidence that islet cells are deprived of Glrx5, correlating with impaired insulin secretion during diabetes in genetically obese mice. In this study, we induced diabesity in C57BL/6J mice in vivo by feeding the mice a high-fat diet (HFD) and modelled the diabetic metabolism in MIN6 cells through exposure to FFA, glucose, or inflammatory cytokines in vitro. qRT-PCR, ELISA, immunohisto-/cytochemistry, bioluminescence, and respirometry were employed to study Glrx5, insulin secretion, and mitochondrial biomarkers. The HFD induced a depletion of islet Glrx5 concomitant with an obese phenotype, elevated FFA in serum and reactive oxygen species in islets, and impaired glucose tolerance. Exposure of MIN6 cells to FFA led to a loss of Glrx5 in vitro. The FFA-induced depletion of Glrx5 coincided with significantly altered mitochondrial biomarkers. In summary, we provide evidence that Glrx5 is regulated by FFA in type 2 diabetes mellitus and is linked to mitochondrial dysfunction and blunted insulin secretion.

(1) Background: Treatment of cancer-related pain is still challenging, and it can be managed by both medical and interventional therapies. Spinal Cord Stimulation (SCS) is a minimally invasive technique, and its use is rapidly increasing in the treatment of chronic pain. (2) Materials and Methods: Our study aims to perform a review of the pertinent literature about current evidences in cancer pain treatment by Spinal Cord Stimulation. Moreover, we created a database based on case reports or case series (18 studies) in the literature. We analyzed a clinical group of oncological patients affected by intractable pain undergoing SCS implantation, focusing on outcome. (3) Results: The analysis of the 18 included studies in our series has shown a reduction in painful symptoms in 48 out of 56 treated patients (87.51%); also 53 out of 56 patients (96.64%) have shown an improvement in their Quality of Life (QoL). (4) Conclusions: Spinal Cord Stimulation can be considered an efficient method in the treatment of cancer-related pain. However, literature regarding SCS for the treatment of cancer-related pain is largely represented by case reports and small case series, with no effective population studies or Randomized Controlled Trials demonstrating the efficacy and the level of evidence. Further prospective studies are needed.

Background: In recent decades, the application of machine learning technologies to medical imaging has opened up new perspectives in neuro-oncology, in the so-called radiomics field. Radiomics offer new insight into glioma, aiding in clinical decision-making and patients’ prognosis evaluation. Although meningiomas represent the most common primary CNS tumor and the majority of them are benign and slow-growing tumors, a minor part of them show a more aggressive behavior with an increased proliferation rate and a tendency to recur. Therefore, their treatment may represent a challenge. Methods: According to PRISMA guidelines, a systematic literature review was performed. We included selected articles (meta-analysis, review, retrospective study, and case–control study) concerning the application of radiomics method in the preoperative diagnostic and prognostic algorithm, and planning for intracranial meningiomas. We also analyzed the contribution of radiomics in differentiating meningiomas from other CNS tumors with similar radiological features. Results: In the first research stage, 273 papers were identified. After a careful screening according to inclusion/exclusion criteria, 39 articles were included in this systematic review. Conclusions: Several preoperative features have been identified to increase preoperative intracranial meningioma assessment for guiding decision-making processes. The development of valid and reliable non-invasive diagnostic and prognostic modalities could have a significant clinical impact on meningioma treatment.

Spine represents the most common site for metastatic disease involvement. Due to the close relationship between the spinal cord and critical structures, therapeutic management of spinal metastases remains challenging. Spinal localization can lead to neurological sequelae, which can significantly affect the quality of life in patients with a limited life expectancy. The authors conducted a systematic literature review according to PRISMA guidelines in order to determine the impact of the most updated palliative care on spinal metastases. The initial literature search retrieved 2526 articles, manually screened based on detailed exclusion criteria. Finally, 65 studies met the inclusion criteria and were finally included in the systematic review. In the wide scenario of palliative care, nowadays, recent medical or surgical treatments represent valuable options for ameliorating pain and improving patients QoL in such this condition.

Summary: STAT3 is a transcription factor involved in several cellular activities including inflammation, proliferation, and survival, but it also plays a non-transcriptional role in modulating mitochondrial metabolism. Given its diverse functions in human cancers, it is an emerging therapeutic target. Here we show that OPB-51602, a small molecule inhibitor of STAT3, is highly toxic in a STAT3-dependent manner. Specifically, drug toxicity depends on mitochondrial STAT3 as tumor cells expressing only a mitochondrially restricted form of STAT3 are sensitive to the compound, whereas STAT3-null cells are protected. OPB-51602 inhibited complex I activity and led to increased ROS production, which in turn induced mitophagy, actin rearrangements, and cell death. Cells undergoing reduced oxidative phosphorylation or expressing NDI1 NADH dehydrogenase from Saccharomyces cerevisiae, which bypasses mammalian complex I, were resistant to OPB-51602 toxicity. These results show that targeting mitochondrial STAT3 function causes synthetic lethality through complex I inhibition that could be exploited for cancer chemotherapy.

Children and adolescents with developmental problems are at increased risk of experiencing mental health problems. The Strengths and Difficulties Questionnaire (SDQ) is widely used as a screener for detecting mental health difficulties in these populations, but its use thus far has been restricted to groups of children with diagnosed disorders (e.g., ADHD). Transdiagnostic approaches, which focus on symptoms and soften or remove the boundaries between traditional categorical disorders, are increasingly adopted in research and practice. The aim of this study was to assess the potential of the SDQ to detect concurrent mental health problems in a transdiagnostic sample of children. The sample were referred by health and educational professionals for difficulties related to learning (N = 389). Some had one diagnosis, others had multiple, but many had no diagnoses. Parent-rated SDQ scores were significantly positively correlated with parent ratings of mental health difficulties on the Revised Child Anxiety and Depression Scale (RCADS). Ratings on the SDQ Emotion subscale significantly predicted the likelihood of having concurrent clinical anxiety and depression scores. Ratings on the Hyperactivity subscale predicted concurrent anxiety levels. These findings suggest the SDQ could be a valuable screening tool for identifying existing mental health difficulties in children recognized as struggling, as it can be in typically developing children and those with specific diagnoses.

Gliomas, particularly high-grade gliomas, represent the most common and aggressive tumors of the CNS and are still burdened by high mortality and a very poor prognosis, regardless of the type of therapy. Their diagnosis and monitoring rely on imaging techniques and direct biopsy of the pathological tissue; however, both procedures have inherent limitations. To address these limitations, liquid biopsies have been proposed in this field. They could represent an innovative tool that could help clinicians in the early diagnosis, monitoring, and prognosis of these tumors. Furthermore, the rapid development of next-generation sequencing (NGS) technologies has led to a significant reduction in sequencing cost, with improved accuracy, providing a molecular profile of cancer and leading to better survival results and less disease burden. This paper focuses on the current clinical application of liquid biopsy in the early diagnosis and prognosis of cancer, introduces NGS-related methods, reviews recent progress, and summarizes challenges and future perspectives.

In spinal surgery, 3D prothesis represents a useful instrument for spinal reconstruction after the removal of spinal tumors that require an “en bloc” resection. This represents a complex and demanding procedure, aiming to restore spinal length, alignment and weight-bearing capacity and to provide immediate stability. Thus, in this systematic review the authors searched the literature to investigate and discuss the advantages and limitations of using 3D-printed custom-made vertebral bodies in the treatment of spinal tumors. A systematic literature review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, with no limits in terms of date of publication. The collected studies were exported to Mendeley. The articles were selected according to the following inclusion criteria: availability of full articles, full articles in English, studies regarding the implant of 3D custom-made prothesis after total or partial vertebral resection, studies regarding patients with a histologically confirmed diagnosis of primary spinal tumor or solitary bone metastasis; studies evaluating the implant of 3d custom-made prothesis in the cervical, thoracic, and lumbar spine. Nineteen published studies were included in this literature review, and include a total of 87 patients, 49 males (56.3%) and 38 females (43.7%). The main tumoral location and primary tumor diagnosis were evaluated. The 3D custom-made prothesis represents a feasible tool after tumor en-bloc resection in spinal reconstruction. This procedure is still evolving, and long-term follow-ups are mandatory to assess its safeness and usefulness.

Abstract Background Pseudomonas syringae is a widespread bacterial species complex that includes a number of significant plant pathogens. Amongst these, P. syringae pv. actinidiae (Psa) initiated a worldwide pandemic in 2008 on cultivars of Actinidia chinensis var. chinensis. To gain information about the expression of genes involved in pathogenicity we have carried out transcriptome analysis of Psa during the early stages of kiwifruit infection. Results Gene expression in Psa was investigated during the first five days after infection of kiwifruit plantlets, using RNA-seq. Principal component and heatmap analyses showed distinct phases of gene expression during the time course of infection. The first phase was an immediate transient peak of induction around three hours post inoculation (HPI) that included genes that code for a Type VI Secretion System and nutrient acquisition (particularly phosphate). This was followed by a significant commitment, between 3 and 24 HPI, to the induction of genes encoding the Type III Secretion System (T3SS) and Type III Secreted Effectors (T3SE). Expression of these genes collectively accounted for 6.3% of the bacterial transcriptome at this stage. There was considerable variation in the expression levels of individual T3SEs but all followed the same temporal expression pattern, with the exception of hopAS1, which peaked later in expression at 48 HPI. As infection progressed over the time course of five days, there was an increase in the expression of genes with roles in sugar, amino acid and sulfur transport and the production of alginate and colanic acid. These are both polymers that are major constituents of extracellular polysaccharide substances (EPS) and are involved in biofilm production. Reverse transcription-quantitative PCR (RT-qPCR) on an independent infection time course experiment showed that the expression profile of selected bacterial genes at each infection phase correlated well with the RNA-seq data. Conclusions The results from this study indicate that there is a complex remodeling of the transcriptome during the early stages of infection, with at least three distinct phases of coordinated gene expression. These include genes induced during the immediate contact with the host, those involved in the initiation of infection, and finally those responsible for nutrient acquisition.

Abstract Background Most published genome sequences are drafts, and most are dominated by computational gene prediction. Draft genomes typically incorporate considerable sequence data that are not assigned to chromosomes, and predicted genes without quality confidence measures. The current Actinidia chinensis (kiwifruit) ‘Hongyang’ draft genome has 164 Mb of sequences unassigned to pseudo-chromosomes, and omissions have been identified in the gene models. Results A second genome of an A. chinensis (genotype Red5) was fully sequenced. This new sequence resulted in a 554.0 Mb assembly with all but 6 Mb assigned to pseudo-chromosomes. Pseudo-chromosomal comparisons showed a considerable number of translocation events have occurred following a whole genome duplication (WGD) event some consistent with centromeric Robertsonian-like translocations. RNA sequencing data from 12 tissues and ab initio analysis informed a genome-wide manual annotation, using the WebApollo tool. In total, 33,044 gene loci represented by 33,123 isoforms were identified, named and tagged for quality of evidential support. Of these 3114 (9.4%) were identical to a protein within ‘Hongyang’ The Kiwifruit Information Resource (KIR v2). Some proportion of the differences will be varietal polymorphisms. However, as most computationally predicted Red5 models required manual re-annotation this proportion is expected to be small. The quality of the new gene models was tested by fully sequencing 550 cloned ‘Hort16A’ cDNAs and comparing with the predicted protein models for Red5 and both the original ‘Hongyang’ assembly and the revised annotation from KIR v2. Only 48.9% and 63.5% of the cDNAs had a match with 90% identity or better to the original and revised ‘Hongyang’ annotation, respectively, compared with 90.9% to the Red5 models. Conclusions Our study highlights the need to take a cautious approach to draft genomes and computationally predicted genes. Our use of the manual annotation tool WebApollo facilitated manual checking and correction of gene models enabling improvement of computational prediction. This utility was especially relevant for certain types of gene families such as the EXPANSIN like genes. Finally, this high quality gene set will supply the kiwifruit and general plant community with a new tool for genomics and other comparative analysis.