Effect of Exercise Prior to Sedentary Behavior on Vascular Health Parameters: A Systematic Review and Meta-Analysis of Crossover Trials.

BACKGROUND: Sedentary behavior has been shown to negatively affect parameters of endothelial function and central hemodynamics, both of which are closely associated with vascular health. Exercise prior to sedentary behavior has demonstrated potential as a preventive strategy to mitigate these detrimental effects. To evaluate the impact of exercise prior to sedentary behavior on vascular health parameters in the adult population, a systematic review and meta-analysis were conducted, synthesizing the available body of knowledge. METHODS: A literature search was carried out in 6 databases. For each outcome, standard error and mean difference or standardized mean difference were calculated, as appropriate. An analysis was performed using a random effects model with a 95% confidence interval, using the inverse variance statistical method. Risk of bias assessment was performed using ROB2 and considerations for crossover trials. The quality of evidence was assessed using the GRADE system. RESULTS: Exercise performed prior to prolonged sedentary behavior resulted in increased flow-mediated vasodilation at the first and third hours of sedentary time, compared with the control condition of sedentary behavior without prior exercise [MD: 1.51% (95% CI: 0.57 to 2.45) and MD: 1.36% (95% CI: 0.56 to 2.16), respectively]. Moreover, prior exercise led to increased shear rate at the first and third hours of sedentary time [MD: 7.70 s^-1 (95% CI: 0.79 to 14.61) and MD: 5.21 s^-1 (95% CI: 1.77 to 8.43), respectively]. Furthermore, it increased blood flow at the third hour [SMD: 0.40 (95%CI: 0.07 to 0.72)], compared with the control condition of prolonged sedentary behavior without prior exercise. Regarding hemodynamic parameters, exercise prior to prolonged sedentary behavior decreased mean arterial pressure during the first and third hours of sedentary behavior [MD: -1.94 mmHg (95% CI: -2.77 to -1.11) and MD: -1.90 mmHg (95% CI: -3.27 to -0.53), respectively], and an increase in heart rate during the first hour [MD: 4.38 beats per minute (95%CI: 2.78 to 5.98)] compared with the control condition of prolonged sedentary behavior without prior exercise. CONCLUSIONS: The findings of this research suggest that prior exercise may prevent the impairment of vascular health parameters caused by sedentary behavior. However, the quality of the evidence was estimated as moderate. Therefore, further experimental studies and high-quality clinical trials are needed in this field to strengthen the results and conclusions drawn. PROSPERO REGISTRATION NUMBER: CRD42023393686.

Enhancing motor functional recovery in spinal cord injury through pharmacological inhibition of Dickkopf-1 with BHQ880 antibody.

BACKGROUND: Mounting experimental evidence has underscored the remarkable role played by the Wnt family of proteins in the spinal cord functioning and therapeutic potential in spinal cord injury (SCI). We aim to provide a therapeutic prospect associated with the modulation of canonical Wnt signaling, examining the spatio-temporal expression pattern of Dickkopf-1 (Dkk1) and its neutralization after SCI. We employ an intraparenchymal injection of the clinically validated Dkk1-blocking antibody, BHQ880, to elucidate its effects in SCI. METHODS: A rat model of contusion SCI was used. Histological analyses were performed, wherein Dkk1 protein was sought, and ELISA analyses were employed for Dkk1 detection in cerebrospinal fluid and serum. To ascertain the BHQ880 therapeutic effect, rats were subjected to SCI and then injected with the antibody in the lesion epicenter 24 hours post-injury (hpi). Subsequent evaluation of motor functional recovery extended up to 56 days post-injury (dpi). qRT-PCR and histological analyses were conducted. RESULTS: We demonstrate the presence of Dkk1 in the healthy rat spinal cord, with pronounced alterations observed following injury, primarily concentrated in the epicenter regions. Notably, a significative upregulation of Dkk1 was detected at 24 hpi, peaking at 3 dpi and remaining elevated until 42 dpi. Moreover, we revealed that early administration of BHQ880 considerably improved motor functional recovery, promoted preservation of myelinated tissue, and reduced astroglial and microglia/macrophage reactivity. Furthermore, there was a decrease in the acute expression of different inflammatory genes. CONCLUSIONS: Collectively, our findings highlight the therapeutic potential of BHQ880 treatment in the context of SCI.

Adapting response to a measles outbreak in a context of high vaccination and breakthrough cases: an example from Vaud, Switzerland, January to March 2024.

A measles outbreak with 51 cases occurred in the canton of Vaud, Switzerland, between January and March 2024. The outbreak was triggered by an imported case, and 37 (72.5%) subsequent cases were previously vaccinated individuals. Epidemiological investigations showed that vaccinated measles cases were symptomatic and infectious. In a highly vaccinated population, it is important to raise awareness among healthcare professionals to suspect and test for measles virus when an outbreak is declared, irrespective of the vaccination status of the patients.

Asia-Pacific consensus on long-term and sequential therapy for osteoporosis.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Human olfactory neural progenitor cells reveal differences in IL-6, IL-8, thrombospondin-1, and MCP-1 in major depression disorder and borderline personality disorder.

Background: Discovering biological markers is essential for understanding and treating mental disorders. Despite the limitations of current non-invasive methods, neural progenitor cells from the olfactory epithelium (hNPCs-OE) have been emphasized as potential biomarker sources. This study measured soluble factors in these cells in Major Depressive Disorder (MDD), Borderline Personality Disorder (BPD), and healthy controls (HC). Methods: We assessed thirty-five participants divided into MDD (n=14), BPD (n=14), and HC (n=7). MDD was assessed using the Hamilton Depression Rating Scale. BPD was evaluated using the DSM-5 criteria and the Structured Clinical Interview for Personality Disorders. We isolated hNPCs-OE, collected intracellular proteins and conditioned medium, and quantified markers and soluble factors, including Interleukin-6, interleukin-8, and others. Analysis was conducted using one-way ANOVA or Kruskal-Wallis test and linear regression. Results: We found that hNPCs-OE of MDD and BPD decreased Sox2 and laminin receptor-67 kDa levels. MASH-1 decreased in BPD, while tubulin beta-III decreased in MDD compared to controls and BPD. Also, we found significant differences in IL-6, IL-8, MCP-1, and thrombospondin-1 levels between controls and MDD, or BPD, but not between MDD and BPD. Conclusions: Altered protein markers are evident in the nhNPCs-OE in MDD and BPD patients. These cells also secrete higher concentrations of inflammatory cytokines than HC cells. The results suggest the potential utility of hNPCs-OE as an in vitro model for researching biological protein markers in psychiatric disorders. However, more extensive validation studies are needed to confirm their effectiveness and specificity in neuropsychiatric disorders.

Identification of a measles variant displaying mutations impacting molecular diagnostics, Geneva, Switzerland, 2023.

Real-time PCR is one of the most widely used techniques to diagnose measles cases. Here we report measles virus variants with three genetic mutations in the reverse primer annealing site of a widely used PCR. The mutations result in a slight loss of the PCR sensitivity. Variants bearing the three mutations presently circulate in different countries since at least the end of 2021. Our findings highlight the usefulness of molecular surveillance in monitoring if oligonucleotides in diagnostic tests remain adequate.

Effect of Abiotic Treatments on Agricultural Plastic Waste: Efficiency of the Degradation Processes.

In this study, four different plastic materials usually used in the agricultural sector (polystyrene film (PS), polyethylene terephthalate film (PET), low-density polyethylene film (LDPE) and linear low-density polyethylene film (LLDPE)) were subjected to different abiotic treatments, including photo-oxidation (ultraviolet and e-beam radiation) and thermochemical treatments, to enhance polymer degradation. The extensive use of these polymers leads to large amounts of plastic waste generation, including small plastic pieces, known as microplastics, which affect the quality of the agricultural environment, including soil fertility and quality. Therefore, polymer degradation strategies are needed to effectively reduce plastic waste to protect the agricultural sector. The degree of polymer degradation was assessed by the use of thermal and spectroscopic analyses, such as TGA and FTIR. In addition, efficiency, cost-benefits, and potential side-effects were also evaluated to propose the optimal degradation strategy to reduce plastic waste from the point of view of efficiency. The results obtained showed that the pre-treatments based on photo-oxidation (ultraviolet B and C and e-beam radiation) were more efficient and had a better cost-benefit for the degradation of the polymers studied in relation to the thermochemical treatments. Specifically, ultraviolet photo-oxidation worked well for PS and PET, requiring low energy and medium times. However, e-beam radiation was recommended for PE (LDPE and LLDPE) degradation, since high energy and long times were needed when ultraviolet energy was applied to this polymer. Furthermore, the overall efficiency of the plastic degradation of pre-treatments should be studied using a multicriteria approach, since FTIR assessments, in some cases, only consider oxidation processes on the plastic surface and do not show the potential integrity changes on the plastic probes.

Character variation in separate body regions of Gerreidae (Osteichthyes: Teleostei) fishes inferred from geometric morphometrics.

Body morphology is a valuable feature for distinguishing teleostean fishes. However, the utility of character variation in separate body regions has yet to be tested. The taxonomy of the Gerreidae family is controversial due to character overlapping among its fish species. This work aims to analyze and compare the body shape variation in three regions, cephalic, trunk, and caudal peduncle, using landmark data and geometric morphometric methods in 17 species and five genera of the family Gerreidae. The pattern of shape variation for the cephalic region consisted of well-defined character states exclusive of each species analyzed. Shape variation in the trunk and caudal peduncle regions does not distinguish all species in this study. This study showed that the dorsal cephalic profile is highly variable among the species, therefore, shape variation in this region is useful for distinguishing Gerreidae species. In contrast, some species within the same genus share similar shape states in the trunk and caudal peduncle regions, with the most shape variation in the dorsal profile and anal fin for the trunk and in the middle of the caudal peduncle.

Assessment of Classical and Non-Classical Quantitative Electroencephalographic Measures in Patients with Substance Use Disorders.

Background: People diagnosed with substance use disorders (SUDs) are at risk for impairment of brain function and structure. However, physicians still do not have any clinical biomarker of brain impairment that helps diagnose or treat these patients when needed. The most common method to study these patients is the classical electroencephalographic (EEG) analyses of absolute and relative powers, but this has limited individual clinical applicability. Other non-classical measures such as frequency band ratios and entropy show promise in these patients. Therefore, there is a need to expand the use of quantitative (q)EEG beyond classical measures in clinical populations. Our aim is to assess a group of classical and non-classical qEEG measures in a population with SUDs. Methods: We selected 56 non-medicated and drug-free adult patients (30 males) diagnosed with SUDs and admitted to Rehabilitation Clinics. According to qualitative EEG findings, patients were divided into four groups. We estimated the absolute and relative powers and calculated the entropy, and the alpha/(delta + theta) ratio. Results: Our findings showed a significant variability of absolute and relative powers among patients with SUDs. We also observed a decrease in the EEG-based entropy index and alpha/(theta + delta) ratio, mainly in posterior regions, in the patients with abnormal qualitative EEG. Conclusions: Our findings support the view that the power spectrum is not a reliable biomarker on an individual level. Thus, we suggest shifting the approach from the power spectrum toward other potential methods and designs that may offer greater clinical possibilities.

Direct Dengue Virus Genome Sequencing from Antigen NS1 Rapid Diagnostic Tests: A Proof-of-Concept with the Standard Q Dengue Duo Assay.

With nearly half of the world's population being at risk of infection, dengue virus represents a major global health issue. The use of dengue antigen rapid diagnostic tests (Ag-RDTs) represents an alternative to PCR methods for the diagnosis of acute infections since they display excellent sensitivities and specificities and can be performed outside the laboratory. The high genetic diversity of the dengue virus genome represents a challenge for vaccine development, and the progressive expansion of this virus into previously nonendemic regions justifies the implementation of a genomic surveillance program. In this proof-of-concept study, we show the feasibility of sequencing dengue virus genomes directly from positive Ag-RDT (Standard Q Dengue Duo Test assay, n = 7) cassettes stored up to 31 days at room temperature after testing. For 5 of the 7 samples, a high number of reads were obtained allowing phylogenetic analyses to be carried out to determine not only the serotypes (dengue 1, 2, 3 and 4 were detected) but also the genotypes. Furthermore, in one sample, our unbiased metagenomic next-generation sequencing approach made it possible to detect epizootic hemorrhagic disease virus sequences, an arthropod-transmitted virus in ruminants. To conclude, as such an approach requires no cold storage or freezing of samples, dengue Ag-RDTs represent a very pragmatic and robust alternative for the genomic surveillance of dengue virus.

Benefits of Adaptive Sport on Physical and Mental Quality of Life in People with Physical Disabilities: A Meta-Analysis.

Adaptive sports could produce multiple health benefits in people with physical disabilities. The aim is to evaluate if adaptive sports practice has an influence on physical and mental quality of life. A meta-analysis was performed using electronic databases and other sources. A within- and between-group analysis for physical and mental quality of life was conducted. Standardized mean difference (SMD) was used as a measure of the mean size effect. The statistical heterogeneity, the risk of bias, and the quality of evidence were evaluated. Eight studies met the inclusion criteria and four of them were included in the meta-analysis. In mental quality of life, significant differences were observed in the within-group analysis (SMD = 0.71, p < 0.001) and between people practicing adaptive sports and those not engaging in them (SMD = 0.62, p = 0.009). In physical quality of life, significant differences were also found between pre- and post-practice of adaptive sports (SMD = 1.03, p = 0.007). The engagement in adaptive sports showed a positive impact on the mental quality of life among adults with physical disabilities. However, the positive effect of adaptive sports practice on physical quality of life was shown only in the pre-post-test analysis. Further studies are required to validate the obtained findings.

Hospital de día psiquiátrico en tiempos de COVID: grupos y telemedicina / Psychiatric day hospital in times of covid: Groups and telemedicine

Tras decretarse el estado de alarma y el confinamiento por la amenaza del COVID-19, el acceso a los servicios de salud mental y recursos psicosociales se vio obstaculizado, incluso interrumpido.Un colectivo especialmente en riesgo es el de pacientes diag-nosticados de Trastorno Mental Grave. Estos presentan una serie de características que los hace más vulnerables a padecer un em-peoramiento en su salud mental.Desde el Hospital de Día para primeros brotes psicóticos de Pontones se intentó mantener la atención y el seguimiento estre-cho de los pacientes mediante la reestructuración del programa de tratamiento, optando por una intervención terapéutica alternativa mixto (con atención individual presencial y telefónica y terapias grupales por videoconferencia).El objetivo de este trabajo es dar a conocer la experiencia de la implementación de la telemedicina en nuestro HD como res-puesta a la emergencia sanitaria que ocasionó la pandemia, así como recoger el programa de actividades que se desarrollaron y el nivel de satisfacción con el tratamiento recibido de los pacientes que participaron.(AU)

Following the state of alarm and containment due to the CO-VID-19 threat, access to mental health services and psychosocial resources was hampered, even interrupted.A particularly at-risk group is that of patients diagnosed with Severe Mental Disorder. They present a series of characteristics that make them more vulnerable to a worsening of their mental health.From the Day Hospital for first psychotic outbreaks in Pontones we tried to maintain the attention and close monitoring of patients by restructuring the treatment programme, opting for a mixed al-ternative therapeutic intervention (with individual face-to-face and telephone attention and group therapies by videoconference).The aim of this paper is to report on the experience of implemen-ting telemedicine in our HD as a response to the health emergency caused by the pandemic, as well as to record the programme of activities that were developed and the level of satisfaction with the treatment received by the patients who participated.(AU)

Legionella and mitochondria, an intriguing relationship.

Legionella pneumophila is the causative agent of Legionnaires' disease, a severe pneumonia. L. pneumophila injects via a type-IV-secretion-system (T4SS) more than 300 bacterial proteins into macrophages, its main host cell in humans. Certain of these bacterial effectors target organelles in the infected cell and hijack multiple processes to facilitate all steps of the intracellular life cycle of this pathogen. In this review, we discuss the interplay between L. pneumophila, an intracellular bacterium fully armed with virulence tools, and mitochondria, the extraordinary eukaryotic organelles playing prominent roles in cellular bioenergetics, cell-autonomous immunity and cell death. We present and discuss key findings concerning the multiple interactions of L. pneumophila with mitochondria during infection and the mechanisms employed by T4SS effectors that target mitochondrial functions to subvert infected cells.

High-content assay to measure mitochondrial function and bacterial vacuole size in infected human primary macrophages.

Regulation of bioenergetics and cell death are pivotal mitochondrial functions determining the responses of macrophages to infection. Here, we provide a protocol to investigate mitochondrial functions during infection of macrophages by intracellular bacteria. We describe steps for quantifying mitochondrial polarization, cell death, and bacterial infection in infected, living, human primary macrophages at the single-cell level. We also detail the use of the pathogen Legionella pneumophila as model. This protocol can be adapted to investigate mitochondrial functions in other settings. For complete details on the use and execution of this protocol, please refer to Escoll et al. (2021).1.

Altered cell function and increased replication of rhinoviruses and EV-D68 in airway epithelia of asthma patients.

Introduction: Rhinovirus (RV) infections constitute one of the main triggers of asthma exacerbations and an important burden in pediatric yard. However, the mechanisms underlying this association remain poorly understood. Methods: In the present study, we compared infections of in vitro reconstituted airway epithelia originating from asthmatic versus healthy donors with representative strains of RV-A major group and minor groups, RV-C, RV-B, and the respiratory enterovirus EV-D68. Results: We found that viral replication was higher in tissues derived from asthmatic donors for all tested viruses. Viral receptor expression was comparable in non-infected tissues from both groups. After infection, ICAM1 and LDLR were upregulated, while CDHR3 was downregulated. Overall, these variations were related to viral replication levels. The presence of the CDHR3 asthma susceptibility allele (rs6967330) was not associated with increased RV-C replication. Regarding the tissue response, a significantly higher interferon (IFN) induction was demonstrated in infected tissues derived from asthmatic donors, which excludes a defect in IFN-response. Unbiased transcriptomic comparison of asthmatic versus control tissues revealed significant modifications, such as alterations of cilia structure and motility, in both infected and non-infected tissues. These observations were supported by a reduced mucociliary clearance and increased mucus secretion in non-infected tissues from asthmatic donors. Discussion: Altogether, we demonstrated an increased permissiveness and susceptibility to RV and respiratory EV infections in HAE derived from asthmatic patients, which was associated with a global alteration in epithelial cell functions. These results unveil the mechanisms underlying the pathogenesis of asthma exacerbation and suggest interesting therapeutic targets.

Reduction of natural radioactivity in groundwater with different salinity through adsorption of uranium and radium in filter materials.

In many small communities in the Mediterranean area, groundwater is usually the only water body available. Depending mainly on the surrounding geology, their concentration of naturally occurring radionuclides may pose a radiological hazard. Removal of uranium and radium from drinking water is the best way to avoid it, i.e., reverse osmosis (RO), but consuming a lot of energy. Thus, two modified drinking water treatment plants (DWTPs) using zeolites coated with manganese dioxide as adsorbent material were analyzed as an alternative to RO. Groundwater salinity can negatively affect this process. Radium removal decreased as water salinity increased; but it had a major impact on uranium, rendering the adsorption effectless in one DWTP. Waste management and how to avoid it from becoming radioactive are of major concern. Radium and uranium were associated to the reducible fraction in the filter material and also to the carbonate fraction in the case of uranium. Regeneration of the filter material using KCl solutions was able to remove 81% and 63% of uranium and radium, respectively.

Silk-Elastin-like Polymers for Acute Intraparenchymal Treatment of the Traumatically Injured Spinal Cord: A First Systematic Experimental Approach.

Despite the promising potential of hydrogel-based therapeutic approaches for spinal cord injury (SCI), the need for new biomaterials to design effective strategies for SCI treatment and the outstanding properties of silk-elastin-like polymers (SELP), the potential use of SELPs in SCI is currently unknown. In this context, we assessed the effects elicited by the in vivo acute intraparenchymal injection of an SELP named (EIS)2-RGD6 in a clinically relevant model of SCI. After optimization of the injection system, the distribution, structure, biodegradability, and cell infiltration capacity of (EIS)2-RGD6 were assessed. Finally, the effects exerted by the (EIS)2-RGD6 injection-in terms of motor function, myelin preservation, astroglial and microglia/macrophage reactivity, and fibrosis-were evaluated. We found that (EIS)2-RGD6 can be acutely injected in the lesioned spinal cord without inducing further damage, showing a widespread distribution covering all lesioned areas with a single injection and facilitating the formation of a slow-degrading porous scaffold at the lesion site that allows for the infiltration and/or proliferation of endogenous cells with no signs of collapse and without inducing further microglial and astroglial reactivity, as well as even reducing SCI-associated fibrosis. Altogether, these observations suggest that (EIS)2-RGD6-and, by extension, SELPs-could be promising polymers for the design of therapeutic strategies for SCI treatment.

Calidad de vida, nivel de actividad física y pruebas funcionales en personas adultas y mayores laboralmente activas / Quality of life, level of physical activity and functional tests in actively working adults and older people

BACKGROUND: The population of actively working older people is growing rapidly. The relationship between quality of life, levels of physical activity and functionality in this population is not entirely clear. AIM: To determine the association between quality of life, levels of physical activity and functional tests in actively working adults and older people. MATERIAL AND METHODS: Cross sectional assessment of 138 adults aged 40 to 50 years (53% women) and 119 older people aged 60 to 75 years (53% women) who were actively working in two public services. Quality of life was measured with the SF-36 questionnaire and usual physical activity was assessed with the International Physical Activity Questionnaire (IPAQ-short). Handgrip strength, the timed up and go (TUG) and chair stand test (CST) were used as functional tests. RESULTS: Compared to older people, adults had better physical functional tests (P < 0.01). Older people had better scores in the mental health component (MHC) of quality of life (p < 0.05). In adults, the physical health component of quality of life (CSF) had a positive association with physical activity (Spearman Rho (rs)= 0.270; p = 0.01), grip strength (rs = 0.330; p < 0.01) and the TUG (rs = −0.229; p < 0.01). In older patients, CSM and CST were positively correlated (rs = 0.201; P = 0.029). In both groups, a correlation was observed between CSM, grip strength (adults rs = 0.283; p < 0.01; older people rs = 0.211; P = 0.02) and with TUG (adults rs = −0.197; P = 0.021; older people rs = - 0.212; p = 0.02). CONCLUSIONS: There is a positive correlation between quality of life and level of physical activity in working adults, which is not observed in older people. Adequate performance in physical functional tests is positively correlated with better quality of life (CSF and CSM) in adults and only with the mental health component in older people.

2-deoxyglucose transiently inhibits yeast AMPK signaling and triggers glucose transporter endocytosis, potentiating the drug toxicity.

2-deoxyglucose is a glucose analog that impacts many aspects of cellular physiology. After its uptake and its phosphorylation into 2-deoxyglucose-6-phosphate (2DG6P), it interferes with several metabolic pathways including glycolysis and protein N-glycosylation. Despite this systemic effect, resistance can arise through strategies that are only partially understood. In yeast, 2DG resistance is often associated with mutations causing increased activity of the yeast 5'-AMP activated protein kinase (AMPK), Snf1. Here we focus on the contribution of a Snf1 substrate in 2DG resistance, namely the alpha-arrestin Rod1 involved in nutrient transporter endocytosis. We report that 2DG triggers the endocytosis of many plasma membrane proteins, mostly in a Rod1-dependent manner. Rod1 participates in 2DG-induced endocytosis because 2DG, following its phosphorylation by hexokinase Hxk2, triggers changes in Rod1 post-translational modifications and promotes its function in endocytosis. Mechanistically, this is explained by a transient, 2DG-induced inactivation of Snf1/AMPK by protein phosphatase 1 (PP1). We show that 2DG-induced endocytosis is detrimental to cells, and the lack of Rod1 counteracts this process by stabilizing glucose transporters at the plasma membrane. This facilitates glucose uptake, which may help override the metabolic blockade caused by 2DG, and 2DG export-thus terminating the process of 2DG detoxification. Altogether, these results shed a new light on the regulation of AMPK signaling in yeast and highlight a remarkable strategy to bypass 2DG toxicity involving glucose transporter regulation.

Efficacy of cabergoline therapy in patients with non-functioning pituitary adenomas: A single center clinical experience

ABSTRACT Objective: To evaluate the response to cabergoline (CBG) treatment in patients with non-functioning pituitary adenomas (NFPA). Subjects and methods: Retrospective, single tertiary care center study. A total of 44 patients were treated with 3 mg/week of CBG, 32 after surgical treatment (transsphenoidal surgery [TSS] in 27 and TC in 5 patients) and 12 as primary therapy. Mean age was 59.2 ± 12 years and 23 (52.2%) were women. Response to therapy was ascertained by serial magnetic resonance imaging. The median duration of CBG therapy was 30 months (IQR 24-48). Response to CBG therapy was defined as a greater than 20% reduction in tumor size and volume. Results: A significant reduction in tumor size was documented in 29 patients (66%), whereas in 11 patients (25%) the tumor increased in size and in 4 (9%), it remained stable. Significant tumor shrinkage was documented in 4 (33.3%) of 12 patients treated primarily and in 23 (71.8%) of those treated secondarily. The three-year progression-free survival was 0.61. Conclusion: Cabergoline therapy is effective in reducing tumor growth in over two thirds of patients with NFPA, however 16% of patients will escape to this beneficial effect and will require alternative forms of treatment to halt tumor progression.