Search

BackgroundCluster headache is commonly reported to follow an annual pattern with a peak in the spring and a second peak in autumn. Patients with headache frequently use search engines, such as Google, to look for terms related to their disease, creating trend data that can be analyzed with Google Trends. Indeed, Google Trends has been used for surveillance studies and can provide indirect estimates of the burden of diseases and symptoms. The present cross-sectional study investigated the seasonality of searches for "cluster headache" in the northern and southern hemispheres using 10 years of Google Trends data. MethodsThe term "cluster headache" or its translation in the 10 most spoken languages in the world was searched on Google Trends to obtain relative search volumes (from 0 to 100), in order to compare variations in searches across periods. Twenty-eight countries were selected according to the following criteria: (1) a relative search volume of >40 for the term for cluster headache; and (2) a population of at least 5 million inhabitants. For statistical purposes, countries were grouped in relation to hemisphere (northern or southern). Relative search volumes were extracted from January 2012 to January 2022 and analyzed according to two subgroups based on meteorological seasons (summer and winter vs. spring and autumn). ResultsA seasonal trend for in searches for cluster headache was found worldwide exhibiting higher relative search volumes in spring and autumn compared with summer and winter (17 [0, 39] vs. 13 [0, 37]; p = 0.016). ConclusionHigher search volumes for the term during the meteorological seasons of spring and autumn clearly reflect a circannual pattern of cluster headache occurrence, representing new evidence for its seasonality.

Aim: The aim of the present study is to investigate the relationship between both functional connectivity and brain networks with cognitive decline, in patients with Parkinson's disease (PD). Introduction: PD phenotype is not limited to motor impairment but, rather, a wide range of non-motor disturbances can occur, with cognitive impairment being one of the most common. However, how the large-scale organization of brain activity differs in cognitively impaired patients, as opposed to cognitively preserved ones, remains poorly understood. Methods: Starting from source-reconstructed resting-state magnetoencephalography data, we applied the phase linearity measurement (PLM) to estimate functional connectivity, globally and between brain areas, in PD patients with and without cognitive impairment (respectively PD-CI and PD-NC), as compared with healthy subjects (HS). Further, using graph analysis, we characterized the alterations in brain network topology and related these, as well as the functional connectivity, to cognitive performance. Results: We found reduced global and nodal PLM in several temporal (fusiform gyrus, Heschl's gyrus, and inferior temporal gyrus), parietal (postcentral gyrus), and occipital (lingual gyrus) areas within the left hemisphere, in the gamma band, in PD-CI patients, as compared with PD-NC and HS. With regard to the global topological features, PD-CI patients, as compared with HS and PD-NC patients, showed differences in multi-frequencies bands (delta, alpha, gamma) in the Leaf fraction, Tree hierarchy (Th) (both higher in PD-CI), and Diameter (lower in PD-CI). Finally, we found statistically significant correlations between the Montreal Cognitive Assessment test and both the Diameter in delta band and the Th in the alpha band. Conclusion: Our work points to specific large-scale rearrangements that occur selectively in cognitively compromised PD patients and are correlated to cognitive impairment. Impact statement In this article, we want to test the hypothesis that the cognitive decline observed in Parkinson's disease (PD) patients may be related to specific changes of both functional connectivity and brain network topology. Specifically, starting from magnetoencephalography signals and by applying the phase linearity measurement (PLM), a connectivity metric that measures the synchronization between brain regions, we were able to highlight differences in the global and nodal PLM values in PD patients with cognitive impairment as compared with both cognitively unimpaired patients and healthy subjects. Further, using graph analysis, we analyzed alterations in brain network topology that were related to cognitive functioning.

The structural connectivity from the primary olfactory cortex to the main secondary olfactory areas was previously reported as relatively increased in the medial orbitofrontal cortex in a cohort of 27 recently SARS-CoV-2-infected (COV+) subjects, of which 23/27 had clinically confirmed olfactory loss, compared to 18 control (COV-) normosmic subjects, who were not previously infected. To complement this finding, here we report the outcome of an identical high angular resolution diffusion MRI analysis on follow-up data sets collected in 18/27 COV+ subjects (10 males, mean age ± SD : 38.7 ± 8.1 years) and 10/18 COV- subjects (5 males, mean age ± SD : 33.1 ± 3.6 years) from the previous samples who repeated both the olfactory functional assessment and the MRI examination after ~1 year. By comparing the newly derived subgroups, we observed that the increase in the structural connectivity index of the medial orbitofrontal cortex was not significant at follow-up, despite 10/18 COV+ subjects were still found hyposmic after ~1 year from SARS-CoV-2 infection. We concluded that the relative hyperconnectivity of the olfactory cortex to the medial orbitofrontal cortex could be, at least in some cases, an acute or reversible phenomenon linked to the recent SARS-CoV-2 infection with associated olfactory loss.

Multiple system atrophy (MSA) is characterized by accumulation of phosphorylated α-synuclein (p-syn) as glial cytoplasmic inclusions in the brain and a specific biomarker for this disorder is urgently needed. We aimed at investigating if p-syn can also be detected in skin Remak non-myelinating Schwann cells (RSCs) as Schwann cell cytoplasmic inclusions (SCCi) and may represent a reliable clinical biomarker for MSA. This cross-sectional diagnostic study evaluated skin p-syn in 96 patients: 46 with probable MSA (29 with parkinsonism type MSA and 17 with cerebellar type MSA), 34 with Parkinson's disease (PD) and 16 with dementia with Lewy bodies (DLB). We also included 50 healthy control subjects. Patients were recruited from five different medical centres. P-syn aggregates in skin sections were stained by immunofluorescence, followed by analyses with confocal microscopy and immuno-electron microscopy. All analyses were performed in a blinded fashion. Overall, p-syn aggregates were found in 78% of MSA patients and 100% of patients with PD/DLB, whereas they could not be detected in controls. As for neuronal aggregates 78% of MSA patients were positive for p-syn in somatic neurons, whereas all PD/DLB patients were positive in autonomic neurons. When analysing the presence of p-syn in RSCs, 74% of MSA patients were positive, whereas no such SCCi could be observed in PD/DLB patients. Analyses by immuno-electron microscopy confirmed that SCCi were only found in cases with MSA and thus absent in those with PD/DLB. In conclusion, our findings demonstrate that (i) fibrillar p-syn in RSCs is a pathological hallmark of MSA and may be used as a specific and sensitive disease biomarker; (ii) in Lewy body synucleinopathies (PD/DLB) only neurons contain p-syn deposits; and (iii) the cell-specific deposition of p-syn in the skin thus mirrors that of the brain in many aspects and suggests that non-myelinated glial cells are also involved in the MSA pathogenesis.

Background: Differentiating progressive supranuclear palsy-parkinsonism (PSP-P) from Parkinson's disease (PD) is clinically challenging. Objective: This study aimed to develop an automated Magnetic Resonance Parkinsonism Index 2.0 (MRPI 2.0) algorithm to distinguish PSP-P from PD and to validate its diagnostic performance in two large independent cohorts. Methods: We enrolled 676 participants: a training cohort (n=346; 43 PSP-P, 194 PD, and 109 control subjects) from our center and an independent testing cohort (n=330; 62 PSP-P, 171 PD, and 97 control subjects) from an international research group. We developed a new in-house algorithm for MRPI 2.0 calculation and assessed its performance in distinguishing PSP-P from PD and control subjects in both cohorts using receiver operating characteristic curves. Results: The automated MRPI 2.0 showed excellent performance in differentiating patients with PSP-P from patients with PD and control subjects both in the training cohort (area under the receiver operating characteristic curve [AUC]=0.93 [95% confidence interval, 0.89–0.98] and AUC=0.97 [0.93–1.00], respectively) and in the international testing cohort (PSP-P versus PD, AUC=0.92 [0.87–0.97]; PSP-P versus controls, AUC=0.94 [0.90–0.98]), suggesting the generalizability of the results. The automated MRPI 2.0 also accurately distinguished between PSP-P and PD in the early stage of the diseases (AUC=0.91 [0.84–0.97]). A strong correlation (r=0.91, P < 0.001) was found between automated and manual MRPI 2.0 values. Conclusions: Our study provides an automated, validated, and generalizable magnetic resonance biomarker to distinguish PSP-P from PD. The use of the automated MRPI 2.0 algorithm rather than manual measurements could be important to standardize measures in patients with PSP-P across centers, with a positive impact on multicenter studies and clinical trials involving patients from different geographic regions. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Periods of intensified training may increase athletes’ fatigue and impair their recovery status. Therefore, understanding internal and external load markers-related to fatigue is crucial to optimize their weekly training loads. The current investigation aimed to adopt machine learning (ML) techniques to understand the impact of training load parameters on the recovery status of athletes. Twenty-six adult soccer players were monitored for six months, during which internal and external load parameters were daily collected. Players’ recovery status was assessed through the 10-point total quality recovery (TQR) scale. Then, different ML algorithms were employed to predict players’ recovery status in the subsequent training session (S-TQR). The goodness of the models was evaluated through the root mean squared error (RMSE), mean absolute error (MAE), and Pearson’s Correlation Coefficient (r). Random forest regression model produced the best performance (RMSE=1.32, MAE=1.04, r = 0.52). TQR, age of players, total decelerations, average speed, and S-RPE recorded in the previous training were recognized by the model as the most relevant features. Thus, ML techniques may help coaches and physical trainers to identify those factors connected to players’ recovery status and, consequently, driving them toward a correct management of the weekly training loads.

This study provides a culturally sensitive quantitative investigation aimed at assessing the post-traumatic symptomatology, post-migratory difficulties, and resilience of 36 Nigerian male asylum seekers hosted in the province of Caserta, South Italy. A survey composed by the Harvard Trauma Questionnaire-Revised (HTQ-R), the Post-Migratory Checklist (PLMD), and the Connor-Davidson Resilience Scale (CD-RISC) was administered to participants. Descriptive and correlation analyses were made in order to describe the mental health risk and protective factors and understand the relation between these. A linear regression analysis was used to evaluate the influence of post-migratory difficulties and resilience on PTSD. Stratified bivariate analyses were also computed to detect PTSD group and no-PTSD group differences about post-migration difficulties and resilience levels. Regression analysis showed that PMLD numbers significantly increased the risk of having PTSD. No significant effect emerged for the level of resilience. Statistically significant differences between the PTSD group and non-PTSD group in relation to post-migratory difficulties were also found. No differences in the resilience factors emerged. The results offer a glimpse into a specific ethnic group of asylum seekers and its mental health risks and protective factors, taking into consideration the specificities of their past and current life-story experiences. Clinical implications for professionals working in the field of forced migration will be outlined.

Background: Professionals working with refugees are vicariously exposed to complex traumatic experiences lived by forced migrants, which can lead to the risk of developing secondary traumatic stress, burnout, and a poor compassion satisfaction. The current study aimed to explore the effects of secondary traumatic stress on burnout and compassion satisfaction in 264 Italian professionals working with refugees and forced migrants. Moreover, it examined the mediating role of emotion regulation between secondary traumatic stress and both burnout and compassion satisfaction. Methods: A structural equation modeling (SEM) was performed to test the hypothesis. Results: The results showed that increased levels of secondary traumatic stress were associated with an increase of burnout both directly and indirectly through the mediation of emotion regulation. Emotion regulation also totally mediated the relationship between secondary traumatic stress and compassion satisfaction. Conclusions: The results suggested that prevention or interventions programs targeting emotion regulation might be important to improve the professional quality of life of operators working with refugees and forced migrants.

Background The aims of this study were: to investigate the capacity of the rare disease healthcare network in Campania to diagnose patients with rare diseases during the outbreak of Covid-19; and to shed light on problematic diagnoses during this period. Methods To describe the impact of the Covid-19 pandemic on the diagnosis of patients with rare diseases, a retrospective analysis of the Campania Region Rare Disease Registry was performed. A tailored questionnaire was sent to rare disease experts to investigate major issues during the emergency period. Results Prevalence of new diagnoses of rare disease in March and April 2020 was significantly lower than in 2019 (117 versus 317, P Conclusions This study describes the effects of the Covid-19 outbreak on the diagnosis of rare disease in a single Italian region and investigates potential issues of diagnosis and management during this period.

The haemolytic crisis is a sudden reduction in the half-life of red blood cells. Consequently, it leads to massive destruction of red blood cells (haemolysis), which is more significant than the compensatory capacity of the bone marrow and results in the reduction of haemoglobin levels in the peripheral blood (anaemia). The management of acute haemolytic crisis represents a challenge for the paediatrician in the emergency room and one of the few true haematological emergencies. In particular, autoimmune haemolytic anaemia must be promptly identified to ensure a correct therapeutic approach from the start of treatment in the emergency room.

Hemostasis in neurosurgery is of utmost importance. Bleeding management is one of the crucial steps of each neurosurgical procedure. Several strategies, namely thermal, mechanical, electric, and chemical, have been advocated to face blood loss within the surgical field. Over time, countless hemostatic agents and devices have been proposed. Furthermore, the ever-growing recent technological innovation has made available several novel and interesting tools. Pursuant to their impact on surgical practice, we perceived the imperative to update our previous disclosure paper. Therefore, we reviewed the literature and analyzed technical data sheets of each product in order to provide an updated and comprehensive overview in regard to chemical properties, mechanisms of action, use, complications, tricks, and pitfalls of topical hemostatic agents.

Heart failure (HF) is an important health care issue in children because of its considerable morbidity and mortality. Advanced HF encompasses patients who remained symptomatic despite optimal medical treatment and includes patients who require special management, such as continuous inotropic therapy, mechanical circulatory support, or heart transplantation (HT). HT is the gold standard for children with advanced HF; nonetheless, the number of suitable donors has not increased for decades, leading to prolonged waitlist times and increased mortality rates. Therefore, the role of pediatric mechanic circulatory support has been assessed as an alternative treatment in patients in whom heart transplant could not be performed. The authors discuss the epidemiology, causes, pathophysiology, clinical manifestation, medical treatment, device therapy, and HT in pediatric HF, and a particular emphasis was posed on patients with advanced HF.

The naked mole rat (NMR), Heterocephalus glaber, the longest-living rodent1, provides a unique opportunity to explore how evolution has shaped adult stem cell (ASC) activity with increasing lifespan. Using cumulative BrdU labelling and a quantitative imaging approach to track intestinal ASCs (Lgr5+) in NMRs over time in their native in vivo state, we show adaptations to living in near-anaerobic2, food-deprived3 subterranean environment, has necessitated an expanded pool of Lgr5+ cells, which exhibit slower division rates compared to short-lived mice, but have similar turnover as humans. Unlike human LGR5+ cells at the crypt base (LGR5+CBC) that slow down their division rates by entering quiescence(G0) 4, NMR Lgr5+CBC cells in both the small intestine and the colon transit slowly through the active cell cycle (G1 to M) by prolonging arrest at G1 and/or G2. The inverse correlation between ASC division rates and lifespan appears to be specific to Lgr5+CBC/LGR5+CBC cells as this relationship is not seen for cells outside the crypt base. Our data provide an explanation for the observed anticorrelation between somatic mutation rates and longevity in mammals5, with ASC lineages in longer-lived organisms turning over slowly to possibly mitigate ASC exhaustion and reduce mutation rates for long-term tissue maintenance. Finally, we also observe an expanded pool of differentiated cells in NMRs that confer enhanced protection and function to the intestinal mucosa which is able to detect any chemical imbalance in the luminal environment efficiently, triggering a robust anti-proliferative, pro-apoptotic response within the stem cell zone.

Although enhancing change of direction (COD) performance is a crucial factor for improving athletic performance in many sports, few studies have explored its effective methods.This study aimed to investigate the effects of inclined-adaptive footwear (IAF) on force-time characteristics during a COD task.Thirteen male team sport athletes were randomly assigned to wear IAF or footwear without adaptive technology to perform a COD60° task at their best effort. A three-dimensional force plate was used to obtain the force-time curve and related parameters at the turning step (plant foot).IAF led to a significantly higher resultant ground reaction force (GRF), horizontal GRF, vertical GRF, and horizontal/vertical ratio during the braking phase, followed by a significantly shorter contact time and higher resultant horizontal GRF and vertical GRF during the propulsive phase.This indicated that a greater GRF output, redistributed GRF, and shorter contact time occurred with the IAF. Therefore, IAF has the potential to enhance COD performance for sports involving multi-directional footwork and contribute to the development of new functional footwear.

BackgroundThere is no consensus on the most effective endovascular technique to use in patients with acute ischemic stroke due to terminal internal carotid artery (ICA) occlusion. The aim of this study was to compare safety and efficacy of the aspiration technique (AT) and combined technique (CT) as first-line approach in terminal ICA occlusions.MethodsWe performed a retrospective analysis of prospectively collected databases from seven Italian stroke centers. Patients were divided into two subgroups according to the first-line approach: AT group or CT group. We followed the STROBE guidelines for cohort studies. We used Chi-square test, one-way and multivariate ANOVA analysis, together with contrast analysis and post hoc tests, logistic regression and Pearson’s bivariate correlation for the statistical analyses.ResultsBetween January 2018 and August 2020, 353 patients were treated for a terminal ICA occlusion, with either AT or CT. CT was associated with a higher Thrombolysis in Cerebral Infarction (TICI) 2B-3 after the first pass (51.0% vs 26.9%) and at the end of the procedure (84% vs 73.3%) and with an improved clinical outcome at discharge (modified Rankin Scale (mRs) 0–2 of 47.8% vs 34.0%) and at 3 months’ follow-up (mRs 0–2 of 56.5% vs 38.9%) compared with AT.ConclusionThrombectomy of terminal ICA occlusions obtained using CT as first-line approach demonstrated better technical and functional outcomes in comparison with AT.

According to the Italian national statistical institute, severe bacterial infections (SBI) in Italy are responsible for 1.7% of mortality under 5 years of age and their recognition is often challenging, especially in the first stages of the disease. We tried to estimate the prevalence of SBI in our target population and to identify signs and symptoms that could guide in the initial evaluation of a child with a possible SBI.We designed a prospective, multicentre study and enrolled patients aged 0-14 years at the first evaluation to the emergency department with an acute illness lasting a maximum of 5 days. The presence of variables suggestive of SBI was collected for every enrolled patient. One week after the enrolment, every patient was followed up by telephone.SBI is more likely to be detected with the 'gut feeling' in both univariate and multivariate models (univariate OR: 7.16, 95% CI: 4.08-12.56; multivariate OR: 5.34, 95% CI: 2.78-10.25), while abnormal breathing pattern resulted significative only in univariate model (OR 3.83, 95% CI: 1.98-7.40). Nevertheless, their associated sensitivity is low.SBI is uncommon in the absence of paediatricians' gut feeling and abnormal respiratory pattern.

BackgroundLeft ventricular non-compaction (LVNC) is an abnormality of the myocardium, characterized by prominent left ventricular trabeculae and deep inter-trabecular recesses. Long QT syndrome (LQTS) is a cardiac ion channelopathy presenting with a prolonged QT interval on resting electrocardiogram and is associated with increased susceptibility to sudden death. The association between LVNC and LQTS is uncommon.Case presentationWe report an Italian family with a novel pathogenic KCNH2 variant who presented with clinical features of LVNC and LQTS. The proband came to our attention after two syncopal episodes without prodromal symptoms. His ECG showed QTc prolongation and deep T wave inversion in anterior leads, and the echocardiogram fulfilled LVNC criteria. After that, also his sister was found to have LQTS and LVNC, while his father only presented LQTS.ConclusionsPhysicians should be aware of the possible association between LVNC and LQTS. Even if this association is rare, patients with LVNC should be investigated for LQTS to prevent possible severe or even life-threatening arrhythmic episodes.

Although remarkable progress has been achieved in understanding cluster headache (CH) pathophysiology, there are still several gaps about the mechanisms through which independent subcortical and cortical brain structures interact with each other. These gaps could be partially elucidated by structural and functional advanced neuroimaging investigations.Although we are aware that substantial achievements have come from preclinical, neurophysiological, and biochemical experiments, the present narrative review aims to summarize the most significant findings from structural, microstructural, and functional neuroimaging investigations, as well as the consequent progresses in understanding CH pathophysiological mechanisms, to achieve a comprehensive and unifying model.Advanced neuroimaging techniques have contributed to overcoming the peripheral hypothesis that CH is of cavernous sinus pathology, in transitioning from the pure vascular hypothesis to a more comprehensive trigeminovascular model, and, above all, in clarifying the role of the hypothalamus and its connections in the genesis of CH.Altogether, neuroimaging findings strongly suggest that, beyond the theoretical model of the "pain matrix," the model of the "neurolimbic pain network" that is accepted in migraine research could also be extended to CH. Indeed, although the hypothalamus' role is undeniable, the genesis of CH attacks is complex and seems to not be just the result of a single "generator." Cortical-hypothalamic-brainstem functional interconnections that can switch between out-of-bout and in-bout periods, igniting the trigeminovascular system (probably by means of top-down mechanisms) and the consensual trigeminal autonomic reflexes, may represent the "neuronal background" of CH.

Osteogenesis imperfecta (OI) is a rare bone disease due to an abnormal synthesis of 1-type collagen. OI is frequently associated with basilar impression (BI), defined by the elevation of the clivus and floor of the posterior fossa with subsequent migration of the upper cervical spine and the odontoid peg into the base of the skull. Bone intrinsic fragility leading to fractures and deformity, brainstem compression and impaired CSF circulation at cranio-vertebral junction (CVJ) makes the management of these conditions particularly challenging. Different surgical strategies, including posterior fossa decompression with or without instrumentation, transoral or endonasal decompression with posterior occipito-cervical fusion, or halo gravity traction with posterior instrumentation have been reported, but evidence about best modalities treatment is still debated. In this technical note, we present a case of a 16-years-old patient, diagnosed with OI and BI, treated with halo traction, occipito-cervico-thoracic fixation, foramen magnum and upper cervical decompression, and expansive duroplasty. We focus on technical aspects, preoperative work up and postoperative follow up. We also discuss advantages and limitations of this strategy compared to other surgical techniques.

Study Design: Narrative review. Objectives: To discuss the current understanding of the natural history of degenerative cervical myelopathy (DCM). Methods: Literature review summarizing current evidence pertaining to the natural history and risk factors of DCM. Results: DCM is a common condition in which progressive arthritic disease of the cervical spine leads to spinal cord compression resulting in a constellation of neurological symptoms, in particular upper extremity dysfunction and gait impairment. Anatomical factors including cord-canal mismatch, congenitally fused vertebrae and genetic factors may increase individuals’ risk for DCM development. Non-myelopathic spinal cord compression (NMSCC) is a common phenomenon with a prevalence of 24.2% in the healthy population, and 35.3% among individuals >60 years of age. Clinical radiculopathy and/or electrophysiological signs of cervical cord dysfunction appear to be risk factors for myelopathy development. Radiological progression of incidental Ossification of the Posterior Longitudinal Ligament (OPLL) is estimated at 18.3% over 81-months and development of myelopathy ranges between 0-61.5% (follow-up ranging from 40 to 124 months between studies) among studies. In patients with symptomatic DCM undergoing non-operative treatment, 20-62% will experience neurological deterioration within 3-6 years. Conclusion: Current estimates surrounding the natural history of DCM, particularly those individuals with mild or minimal impairment, lack precision. Clear predictors of clinical deterioration for those treated with non-operative care are yet to be identified. Future studies are needed on this topic to help improve treatment counseling and clinical prognostication.

A high training load could increase the risk of injury in soccer players. However, there is still a lack of knowledge regarding the effect on young athletes, in whom a different maturity status could lead to different physiological responses to training. Therefore, the aim of this study was to investigate the association of internal load markers and recovery status with risk of illnesses and non-contact injuries in young soccer players characterised by different maturity status. Twenty-three U14 soccer players were monitored during a full season and categorised according to years from peak height velocity (PHV). Based on the estimated values, athletes were divided into three different groups: Pre-PHV, Circa-PHV and Post-PHV players. The following internal load markers were monitored: rating of perceived exertion (RPE), session rating of perceived exertion (S-RPE), weekly load (WL), cumulative loads for 2, 3, and 4 weeks (WL2, WL3, WL4), acute to chronic workload ratio for 2, 3 and 4 weeks (A:C2, A:C3, A:C4) and week-to-week percentage variation (%WL). Recovery status was quantified using the total quality recovery (TQR) scale. Z-score transformation was adopted for TQR and RPE values and the difference between the parameters was calculated (Z-TQR-RPE). The Kruskal-Wallis test was adopted to evaluate differences in TQR and RPE with respect to maturity offset. A multinomial regression analysis was performed to evaluate the association between internal load markers and risk of illness and non-contact injuries. The variables that showed a significant association were included in the receiver operating characteristic (ROC) curve analysis. The results revealed that RPE was significantly higher (

Dye sensitization is a promising route to enhance luminescence from lanthanide-doped upconverting nanoparticles (LnUCNPs) by improving the photon harvesting capability of LnUCNPs through the use of dye molecules, characterized by higher absorption coefficients. The literature does not fully address the poor photostability of NIR dyes, hindering solution-based applications. The improvements achieved by dye-sensitized LnUCNPs are usually obtained by comparison with non-dye sensitized LnUCNPs. This comparison results in exciting the LnUCNPs at different wavelengths with respect to the dye-sensitized LnUCNPs or at the same wavelengths, where, however, the non-dye sensitized LnUCNPs do not absorb. Both these comparisons are hardly conclusive for a quantification of the improvements achieved by dye-sensitization. Both shortcomings were addressed by studying the photodegradation

Supplementary Fig. S1 from Autophagy inhibition enhances anthocyanin-induced apoptosis in hepatocellular carcinoma

Purpose Tau/MAPT (microtubule associated protein tau) protein is actively studied for the pathologic consequences of its aberrant proteostasis in central nervous system leading to neurodegenerative diseases. Besides its ability to generate insoluble toxic oligomers, Tau homeostasis has attracted attention for its involvement in the formation of the mitotic spindle. This evidence, in association with the description of Tau expression in extra-neuronal tissues, and mainly in cancer tissues, constitutes the rationale for a more in-depth investigation of Tau role also in neoplastic diseases. Methods In our study, we investigated the expression of phosphorylated Tau in prostate cancer cell lines with particular focus on the residue Thr231 present in microtubule binding domain. Results The analysis of prostate cancer cells synchronized with nocodazole demonstrated that the expression of Tau protein phosphorylated at residue Thr231 is restricted to G2/M cell cycle phase. The phosphorylated form was unable to bind tubulin and it does not localize on mitotic spindle. As demonstrated by the use of specific inhibitors, the phosphorylation status of Tau is under the direct control of cdk5 and PP2A, while cdk1 activation was able to exert an indirect control. These mechanisms were also active in cells treated with docetaxel, where counteracting the expression of the dephosphorylated form, by kinase inhibition or protein silencing, determined resistance to drug toxicity. Conclusions We hypothesize that phosphorylation status of Tau is a key marker for G2/M phase in prostate cancer cells and that the forced modulation of Tau phosphorylation can interfere with the capacity of cell to efficiently progress through G2/M phase.

In several neoplastic diseases, including hepatocellular carcinoma, the expression of P-glycoprotein and cyclooxygenase-2 (COX-2) are often increased and involved in drug resistance and poor prognosis. P-glycoprotein, in addition to drug resistance, blocks cytochrome c release, preventing apoptosis in tumor cells. Because COX-2 induces P-glycoprotein expression, we evaluated the effect of celecoxib, a specific inhibitor of COX-2 activity, on P-glycoprotein–mediated resistance to apoptosis in cell lines expressing multidrug resistant (MDR) phenotype. Experiments were done using MDR-positive and parental cell lines at basal conditions and after exposure to 10 or 50 μmol/L celecoxib. We found that 10 μmol/L celecoxib reduced P-glycoprotein, Bcl-xL, and Bcl-2 expression, and induced translocation of Bax from cytosol to mitochondria and cytochrome c release into cytosol in MDR-positive hepatocellular carcinoma cells. This causes the activation of caspase-3 and increases the number of cells going into apoptosis. No effect was shown on parental drug-sensitive or on MDR-positive hepatocellular carcinoma cells after transfection with MDR1 small interfering RNA. Interestingly, although inhibiting COX-2 activity, 50 μmol/L celecoxib weakly increased the expression of COX-2 and P-glycoprotein and did not alter Bcl-xL and Bcl-2 expression. In conclusion, these results show that relatively low concentrations of celecoxib induce cell apoptosis in MDR cell lines. This effect is mediated by P-glycoprotein and suggests that the efficacy of celecoxib in the treatment of different types of cancer may depend on celecoxib concentration and P-glycoprotein expression. [Cancer Res 2007;67(10):4915–23]

Supplementary Figure Legends 1-2 from P-Glycoprotein Mediates Celecoxib-Induced Apoptosis in Multiple Drug-Resistant Cell Lines

Supplementary Figure 2 from P-Glycoprotein Mediates Celecoxib-Induced Apoptosis in Multiple Drug-Resistant Cell Lines

Supplementary Figure 1 from P-Glycoprotein Mediates Celecoxib-Induced Apoptosis in Multiple Drug-Resistant Cell Lines

Introduction: Neurological manifestations related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may involve both peripheral and central nervous system, including acute ischemic stroke and cerebral venous sinus thrombosis (CVST). Case Presentation: Hereby, we present an adult patient with post-vaccination breakthrough COVID-19 infection and CVST, treated with venous mechanical thrombectomy (MT). The patient manifested continuous tonic-clonic seizures, after an insidious presentation with headache and left-sided weakness. SARS-CoV-2 testing was positive, despite fully vaccination, using two approved mRNA platforms. Factor V Leiden polymorphism was detected. The patient was initially managed with anticoagulation, followed by MT with a positive response. We provided a comparison to similar cases of COVID-19 associated CVST undergoing mechanical thrombectomy. Conclusions: High index of suspicion and prompt diagnosis are extremely important to ensure immediate hospitalization and therapy, since CVST associated with either vaccines or COVID-19 seems to evolve rapidly and with a high mortality rate. Even a breakthrough infection may present severe vascular complications. In addition, evaluation of acquired and hereditary thrombophilia may be beneficial in acute phase, also without a previous history of thrombosis. Clinicians should start early medical treatment, and additionally consider the endovascular approach as an optimistic choice in refractory CVST related to SARS-CoV-2 infection.

This study quantified average and peak external intensities of various basketball training drills. Thirteen youth male basketball players (age: 15.2±0.3 years) were monitored (BioHarness-3 devices) to obtain average and peak external load per minute (EL·min−1; peak EL·min−1) during team-based training sessions. Researchers coded the training sessions by analysing the drill type (skills, 1vs1, 2vs2, 3vs0, 3vs3, 4vs0, 4vs4, 5vs5, 5vs5-scrimmage), court area per player, player’s involvement in the drill (in percentage), playing positions (backcourt; frontcourt) and competition rotation status (starter; rotation; bench). Separate linear mixed models were run to assess the influence of training and individual constraints on average and peak EL·min−1. Drill type influenced average and peak EL·min−1 (p < 0.05), but with different directions of effects. EL·min−1 was higher in skills and 4vs0 drills, while higher peak EL·min−1 values were obtained in 5vs5 and 5vs5-scrimmage. Similarly, EL·min−1 was higher when involvement % increased (p = 0.001), while there was an opposite trend for peak EL·min−1 (lower with higher involvement %). Court area per player influenced peak (p = 0.025) but not average demands. No effects were found for playing position or competition rotation status (all p > 0.05), except for a moderately higher EL·min−1 in starters compared to bench players. The external load intensities of basketball training drills substantially vary depending on the load indicator chosen, the training content, and task and individual constraints. Practitioners should not interchangeably use average and peak external intensity indicators to design training but considering them as separate constructs could help to gain a better understanding of basketball training and competition demands.