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Testicular large B-cell lymphoma (TLBCL) is an infrequent and aggressive lymphoma arising in an immune-privileged site and has recently been recognized as a distinct entity from diffuse large B-cell lymphoma (DLBCL). We describe the genetic features of TLBCL and compare them with published series of nodal DLBCL and primary large B-cell lymphomas of the CNS (PCNSL). We collected 61 patients with TLBCL. We performed targeted next-generation sequencing, copy number arrays, and fluorescent in situ hybridization to assess chromosomal rearrangements in 40 cases with available material. Seventy percent of the cases showed localized stages. BCL6 rearrangements were detected in 36% of cases, and no concomitant BCL2 and MYC rearrangements were found. TLBCL had fewer copy number alterations ( p  < 0.04) but more somatic variants ( p  < 0.02) than nodal DLBCL and had more frequent 18q21.32-q23 ( BCL2 ) gains and 6q and 9p21.3 ( CDKN2A/B ) deletions. PIM1 , MYD88 L265P , CD79B , TBL1XR1 , MEF2B , CIITA , EP300, and ETV6 mutations were more frequent in TLBCL, and BCL10 mutations in nodal DLBCL. There were no major genetic differences between TLBCL and PCNSL. Localized or disseminated TLBCL displayed similar genomic profiles. Using LymphGen, the majority of cases were classified as MCD. However, we observed a subgroup of patients classified as BN2, both in localized and disseminated TLBCL, suggesting a degree of genetic heterogeneity in the TLBCL genetic profile. TLBCL has a distinctive genetic profile similar to PCNSL, supporting its recognition as a separate entity from DLBCL and might provide information to devise targeted therapeutic approaches., Competing Interests: Ferran Nadeu has received honoraria from Janssen, AbbVie, AstraZeneca, and SOPHiA GENETICS for speaking at educational activities; has received research support from Gilead; and has licensed the use of the protected IgCaller algorithm to Diagnóstica Longwood. Tycho Baumann has received consulting fees or honoraria from Janssen, Roche, Novartis, Merck, Gilead/Kite, Incyte, Lilly, Abbvie, AstraZeneca, and BeiGene. Alejandro Martin García‐Sancho has received consulting fees or honoraria from Janssen, Roche, BMS/Celgene, Kyowa Kirin, Clinigen, EUSAPharma, Novartis, Gilead/Kite, Incyte, Lilly, Takeda, ADC Therapeutics America, Miltenyi, Ideogen, Abbvie, and BeiGene. Elías Campo has been a consultant for GenMab, and Takeda; has received research support from AstraZeneca; received honoraria from Janssen, EUSPharma, Takeda, and Roche for speaking at educational activities; and is an inventor on a Lymphoma and Leukemia Molecular Profiling Project patent “Method for subtyping lymphoma subtypes by means of expression profiling” (PCT/US2014/64161) and a bioinformatic tool (IgCaller) licensed to Diagnostic Longwood. Eva Giné has received honoraria or consulting fees from Gilead, Kite Pharma, Janssen, Genmab, Miltenyi, and Lilly; has received research support from Janssen and travel expenses from Gilead and Kite Pharma. Armando López Guillermo served on the advisory board of Roche, Celgene, Novartis, and Gilead/Kite, received grants from Celgene and Gilead/Kite, and travel expenses from Kite/Gilead. The remaining authors declare no competing interests., (© 2024 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.)

Amyotrophic lateral sclerosis (ALS) is characterised primarily by motor system degeneration, with clinical evidence of cognitive and behavioural change in up to 50% of cases. We have shown previously that resting-state EEG captures dysfunction in motor and cognitive networks in ALS. However, the longitudinal development of these dysfunctional patterns, especially in networks linked with cognitive-behavioural functions, remains unclear. Longitudinal studies on non-motor changes in ALS are essential to further develop our understanding of disease progression, improve care and enhance the evaluation of new treatments. To address this gap, we examined 124 ALS individuals with 128-channel resting-state EEG recordings, categorised by cognitive impairment (ALSci, n = 25), behavioural impairment (ALSbi, n = 58), or non-impaired (ALSncbi, n = 53), with 12 participants meeting the criteria for both ALSci and ALSbi. Using linear mixed-effects models, we characterised the general and phenotype-specific longitudinal changes in brain network, and their association with cognitive performance, behaviour changes, fine motor symptoms, and survival. Our findings revealed a significant decline in [Formula: see text]-band spectral power over time in the temporal region along with increased [Formula: see text]-band power in the fronto-temporal region in the ALS group. ALSncbi participants showed widespread β-band synchrony decrease, while ALSci participants exhibited increased co-modulation correlated with verbal fluency decline. Longitudinal network-level changes were specific of ALS subgroups and correlated with motor, cognitive, and behavioural decline, as well as with survival. Spectral EEG measures can longitudinally track abnormal network patterns, serving as a candidate stratification tool for clinical trials and personalised treatments in ALS., (© 2024. The Author(s).)

Objective: To explore the lived experience of informal dementia caregivers during the COVID-19 pandemic., Methods: Interpretative Phenomenological Analysis (IPA) was employed. Eight primary informal caregivers were recruited from a community mental health service for older people when attending in their role as caregiver of a service-user. Semi-structured interviews were conducted at home or in the clinic based on the participants' convenience and preference. IPA was completed following Smith and colleagues framework for analysis., Results: Six group experiential themes, each with a number of subthemes, emerged from the cross-case interpretative analysis: the ambivalent experience of caregiving (subtheme: those complex emotional experiences ); navigating lockdown: lived challenges and opportunities (subthemes: the pervasive fear , intensification of existing struggles , being prevented from caring for a loved one , and lockdown as a time for opportunity ); transitioning out of lockdown (subthemes: regaining freedom, but restricted freedom after all and being in a lockdown of one's own ); the present with COVID-19, but mostly with dementia (subthemes: dementia, a disease that does not pause , and 'takeaways' from the journey ); looking into the future (subthemes: embracing COVID-19 and the true needs ); and a word on coping (subtheme: managing it all as best one can )., Conclusion: Findings demonstrate the significance of the meaning caregivers ascribed to their experiences on their wellbeing and ability to cope in times of COVID-19 and thereafter. Gaining an understanding of the caregivers' unique experiences is crucial to appreciate how to best support them.

The t(14;19)(q32;q13) often juxtaposes BCL3 with immunoglobulin heavy chain (IGH) resulting in overexpression of the gene. In contrast to other oncogenic translocations, BCL3 rearrangement (BCL3-R) has been associated with a broad spectrum of lymphoid neoplasms. Here we report an integrative whole-genome sequence, transcriptomic, and DNA methylation analysis of 13 lymphoid neoplasms with BCL3-R. The resolution of the breakpoints at single base-pair revealed that they occur in two clusters at 5' (n=9) and 3' (n=4) regions of BCL3 associated with two different biological and clinical entities. Both breakpoints were mediated by aberrant class switch recombination of the IGH locus. However, the 5' breakpoints (upstream) juxtaposed BCL3 next to an IGH enhancer leading to overexpression of the gene whereas the 3' breakpoints (downstream) positioned BCL3 outside the influence of the IGH and were not associated with its expression. Upstream BCL3-R tumors had unmutated IGHV, trisomy 12, and mutated genes frequently seen in chronic lymphocytic leukemia (CLL) but had an atypical CLL morphology, immunophenotype, DNA methylome, and expression profile that differ from conventional CLL. In contrast, downstream BCL3-R neoplasms were atypical splenic or nodal marginal zone lymphomas (MZL) with mutated IGHV, complex karyotypes and mutated genes typical of MZL. Two of the latter four tumors transformed to a large B-cell lymphoma. We designed a novel fluorescence in situ hybridization assay that recognizes the two different breakpoints and validated these findings in 17 independent tumors. Overall, upstream or downstream breakpoints of BCL3-R are mainly associated with two subtypes of lymphoid neoplasms with different (epi)genomic, expression, and clinicopathological features resembling atypical CLL and MZL, respectively.

Amyotrophic lateral sclerosis is a devastating disease characterized primarily by motor system degeneration, with clinical evidence of cognitive and behavioural change in up to 50% of cases. Amyotrophic lateral sclerosis is both clinically and biologically heterogeneous. Subgrouping is currently undertaken using clinical parameters, such as site of symptom onset (bulbar or spinal), burden of disease (based on the modified El Escorial Research Criteria) and genomics in those with familial disease. However, with the exception of genomics, these subcategories do not take into account underlying disease pathobiology, and are not fully predictive of disease course or prognosis. Recently, we have shown that resting-state EEG can reliably and quantitatively capture abnormal patterns of motor and cognitive network disruption in amyotrophic lateral sclerosis. These network disruptions have been identified across multiple frequency bands, and using measures of neural activity (spectral power) and connectivity (comodulation of activity by amplitude envelope correlation and synchrony by imaginary coherence) on source-localized brain oscillations from high-density EEG. Using data-driven methods (similarity network fusion and spectral clustering), we have now undertaken a clustering analysis to identify disease subphenotypes and to determine whether different patterns of disruption are predictive of disease outcome. We show that amyotrophic lateral sclerosis patients (n = 95) can be subgrouped into four phenotypes with distinct neurophysiological profiles. These clusters are characterized by varying degrees of disruption in the somatomotor (α-band synchrony), frontotemporal (β-band neural activity and γl-band synchrony) and frontoparietal (γl-band comodulation) networks, which reliably correlate with distinct clinical profiles and different disease trajectories. Using an in-depth stability analysis, we show that these clusters are statistically reproducible and robust, remain stable after reassessment using a follow-up EEG session, and continue to predict the clinical trajectory and disease outcome. Our data demonstrate that novel phenotyping using neuroelectric signal analysis can distinguish disease subtypes based exclusively on different patterns of network disturbances. These patterns may reflect underlying disease neurobiology. The identification of amyotrophic lateral sclerosis subtypes based on profiles of differential impairment in neuronal networks has clear potential in future stratification for clinical trials. Advanced network profiling in amyotrophic lateral sclerosis can also underpin new therapeutic strategies that are based on principles of neurobiology and designed to modulate network disruption., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Aim: To describe epidemiological aspects, clinical findings, and visual results in eye trauma patients requiring urgent surgery at a tertiary hospital., Methods: Retrospective review of adult patients requiring urgent surgery for trauma to the eyeball from January 2010 and April 2020. Data was collected relative to age, gender, mechanism of the injury, type of wound, initial and final visual acuity, number and type of surgeries carried out. Injuries were classed according to the Birmingham Eye Trauma Terminology (BETT) and the Ocular Trauma Score (OTS) categories., Results: The survey included 92 eyes. Mean age was 54.76±22.18y. The most frequent cause was domestic accidents (44.6%), followed by aggression (22.80%) and occupational accidents (17.4%). Trauma from aggression was more frequent in men ( P =0.006) and accidents in the home more common in women ( P =0.011). Patients over 65y presented an odds ratio (OR) of 10.71 for suffering a domestic accident. Patients between 15-45 and 46-65y were at higher risk of trauma from aggression (OR=17.52 and OR=10.94, respectively). As for the type of injury, 63.04% were open-globe lesions, Zone II being the most frequently affected (27.2%). In Logistic regression analysis, old age ( P =0.05) and retinal involvement ( P =0.001) were found to be associated with higher rate of unfavourable visual outcome., Conclusion: The epidemiological aspects of eye trauma are highly dependent on the area of population studied. Domestic accidents are more relevant than workplace accidents in older urban areas with high socio-economic status. A better knowledge of the epidemiological characteristics is useful for implementing specific prevention measures and appropriate treatment strategies., (International Journal of Ophthalmology Press.)

Introduction and Objectives: Paget's disease of bone (PDB) may lead to hearing loss. The present study was conducted with the aim of measuring, characterizing and determining the risk factors for hearing loss in a group of subjects with PDB., Methods: An observational, transversal, case-control study was conducted, a cohort of 76 subjects diagnosed with PDB in the case group and a control group of 134 subjects were included. Clinical, demographic and audiometric data were analysed., Results: The comparative analysis between the subjects in the PDB group and the control group found that the case group showed higher hearing thresholds (39,51dB) compared with the control group (37.28dB) (P=.069) and presented a greater rate of conductive hearing loss (22.76%) than the control group (12.05%) (P=.0062). The study of risk factors for hearing loss found that skull involvement in bone scintigraphy, age and high blood pressure were risk factors for higher impairment in PDB., Conclusions: The subjects with PDB showed more profound and a higher proportion of conductive hearing loss than the control group. The patients with PDB and skull involvement presented a more severe hearing loss compared with the subjects without skull involvement. Skull involvement and age were found to be risk factors for hearing loss., (Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: To elucidate the relationship between disease stage in amyotrophic lateral sclerosis (ALS), as measured with the King's Clinical Staging System, and cognitive and behavioral change, measured with the Edinburgh Cognitive and Behavioural ALS Screen (ECAS)., Methods: A large multicenter observational cohort of 161 cross-sectional patients with ALS and 80 healthy matched controls were recruited across 3 research sites (Dublin, Edinburgh, and London). Participants were administered the ECAS and categorized into independent groups based on their King's clinical disease stage at time of testing., Results: Significant differences were observed between patients and controls on all subtests of the ECAS except for visuospatial functioning. A significant cross-sectional effect was observed across disease stages for ALS-specific functions (executive, language, letter fluency) and ECAS total score but not for ALS-nonspecific functions (memory, visuospatial). Rates of ALS-specific impairment and behavioral change were also related to disease stage. The relationship between cognitive function and disease stage may be due to letter fluency impairment, whereas higher rates of all behavioral domains were seen in later King's stage. The presence of bulbar signs, but not site of onset, was significantly related to ALS-specific, ECAS total, and behavioral scores., Conclusion: ALS-specific cognitive deficits and behavioral impairment are more frequent with more severe disease stage. By end-stage disease, only a small percentage of patients are free of neuropsychological impairment. The presence of bulbar symptoms exaggerates the differences observed between disease stages. These findings suggest that cognitive and behavioral change should be incorporated into ALS diagnostic criteria and should be included in future staging systems., (Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) landscape in 1699 colorectal cancers, 256 of which have been whole-genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge. Unbiased CRISPR-Cas9 knockout and activation screens identified in total 79 genes within AI peaks regulating cell growth. Genetic and functional data implicate loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point mutations. Importantly, the data reveal several associations between AI target genes, suggesting a role for a network of lineage-determining transcription factors in colorectal tumorigenesis. Overall, the results unravel the contribution of AI in colorectal cancer and provide a plausible explanation why so few genes are commonly affected by point mutations in cancers.

Amyotrophic Lateral Sclerosis is a neurodegenerative disorder characterized primarily by motor network disruption. Extra-motor manifestations including executive functions, social cognition, and behavioral changes are now well recognized as important features of ALS, and are associated with frontotemporal and frontostriatal network disruption. However, the presence and characterization of language changes has received less attention. This systematic review characterizes the profile of reported language dysfunction in ALS. PRISMA guidelines were implemented to carry out and report the review. Current evidence suggests that areas of neuroanatomical disruption in ALS spread to language centers such as posterior, inferior frontal and superior temporal areas leading to deficits in word retrieval, syntactic and grammatical processing, and spelling. However, the majority of studies of language in ALS have been limited by the recruitment of small clinic-based prevalent samples and important questions remain regarding the incidence and progression of language impairment in ALS. Further studies from population-based incident cohorts will help to determine the range of language deficits in ALS, and how these relate to previously defined executive and behavioral sub-phenotypes.

Background: Glycogenin-interacting protein 1 (GNIP1) is a tripartite motif (TRIM) protein with E3 ubiquitin ligase activity that interacts with glycogenin. These data suggest that GNIP1 could play a major role in the control of glycogen metabolism. However, direct evidence based on functional analysis remains to be obtained., Objectives: The aim of this study was 1) to define the expression pattern of glycogenin-interacting protein/Tripartite motif containing protein 7 (GNIP/TRIM7) isoforms in humans, 2) to test their ubiquitin E3 ligase activity, and 3) to analyze the functional effects of GNIP1 on muscle glucose/glycogen metabolism both in human cultured cells and in vivo in mice., Results: We show that GNIP1 was the most abundant GNIP/TRIM7 isoform in human skeletal muscle, whereas in cardiac muscle only TRIM7 was expressed. GNIP1 and TRIM7 had autoubiquitination activity in vitro and were localized in the Golgi apparatus and cytosol respectively in LHCN-M2 myoblasts. GNIP1 overexpression increased glucose uptake in LHCN-M2 myotubes. Overexpression of GNIP1 in mouse muscle in vivo increased glycogen content, glycogen synthase (GS) activity and phospho-GSK-3α/β (Ser21/9) and phospho-Akt (Ser473) content, whereas decreased GS phosphorylation in Ser640. These modifications led to decreased blood glucose levels, lactate levels and body weight, without changing whole-body insulin or glucose tolerance in mouse., Conclusion: GNIP1 is an ubiquitin ligase with a markedly glycogenic effect in skeletal muscle., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Caregiver burden is a recognised consequence of caring for a patient with neurodegeneration. Amyotrophic lateral sclerosis (ALS) differs from other neurodegenerations by its rapid progression and impairment of motor, cognitive, and behavioural function, which contribute to caregiver burden. However, longitudinal factors that determine the extent of caregiver burden, and in particular the impact of psychological distress among caregivers, have not been fully established., Methods: Patients with ALS (n = 85) and their primary caregivers (n = 85) completed three serial evaluations. Caregiver burden was measured using the Zarit Burden Interview (ZBI). Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale (HADS). The Edinburgh Cognitive-Behavioural ALS Screen (ECAS) was used to determine cognitive function in patients. The ALS Functional Rating Scale (ALSFRS-R) measured disease progression., Results: Using the ZBI, caregivers were categorised as high or low burden. In the low burden group, anxiety scores from the HADS predicted caregiver burden (r = 0.410, F = 3.73, p = 0.033), whereas the depression sub-score from the HADS was predictive of caregiver burden in the high burden group (r = 0.501, F = 5.87, p = 0.006) for cross-sectional analyses. Longitudinally, an elevated score on the HADS at Time 1 was the largest predictor of caregiver burden across serial assessments., Conclusion: In a patient cohort with relatively preserved cognitive function (65%), anxiety and depression at Time 1, as measured by the HADS, were the best predictors of caregiver burden at Time 3. This observation provides a mechanism by which caregiver burden can be identified by health-care professionals and a stepped care programme of intervention initiated.

The Beaumont Behavioural Inventory (BBI) is a behavioural proxy report for the assessment of behavioural changes in ALS. This tool has been validated against the FrSBe, a non-ALS-specific behavioural assessment, and further comparison of the BBI against a disease-specific tool was considered. This study cross-validates the BBI against the ALS-FTD-Q. Sixty ALS patients, 8% also meeting criteria for FTD, were recruited. All patients were evaluated using the BBI and the ALS-FTD-Q, completed by a carer. Correlational analysis was performed to assess construct validity. Precision, sensitivity, specificity, and overall accuracy of the BBI when compared to the ALS-FTD-Q, were obtained. The mean score of the whole sample on the BBI was 11.45 ± 13.06. ALS-FTD patients scored significantly higher than non-demented ALS patients (31.6 ± 14.64, 9.62 ± 11.38; p < 0.0001). A significant large positive correlation between the BBI and the ALS-FTD-Q was observed (r = 0.807, p < 0.0001), and no significant correlations between the BBI and other clinical/demographic characteristics indicate good convergent and discriminant validity, respectively. 72% of overall concordance was observed. Precision, sensitivity, and specificity for the classification of severely impaired patients were adequate. However, lower concordance in the classification of mild behavioural changes was observed, with higher sensitivity using the BBI, most likely secondary to BBI items which endorsed behavioural aspects not measured by the ALS-FTD-Q. Good construct validity has been further confirmed when the BBI is compared to an ALS-specific tool. Furthermore, the BBI is a more comprehensive behavioural assessment for ALS, as it measures the whole behavioural spectrum in this condition.

Few studies in amyotrophic lateral sclerosis (ALS) have profiled disease-specific features of the condition in conjunction with assessment of caregivers' burden, distress, quality of life, and investigated patient survival. Eighty-four ALS patients and their primary caregivers were enrolled. Patients completed ALS-specific measures of physical and cognitive function, while caregivers completed measures of anxiety, depression, caregiver burden, and quality of life. Patient-caregiver dyads were interviewed about their health-service utilisation. Survival data were obtained through the Irish register for ALS. Participants were dichotomised into low/high groups according to the severity of self-reported caregiver burden, based on statistically derived cut-off scores. High-burdened caregivers (n = 43) did not significantly differ from low-burdened caregivers (n = 41) with respect to disease-specific characteristics, i.e., ALSFRS-R, bulbar- or spinal-onset ALS, disease duration, or survival data. However, significant differences were reported on subjective measures of anxiety (p < 0.000), depression (p < 0.001), distress (p < 0.000), and quality of life (p < 0.000). These data demonstrate the limited impact of ALS patient-related variables, i.e., ALSFRS-R and onset, on caregiver burden in ALS, and identify the importance of the psychological composition of caregivers. This study suggests that the subjective experience of individual caregivers is an important factor influencing the severity of experienced caregiver burden.

Objective: Glycogen metabolism has emerged as a mediator in the control of energy homeostasis and studies in murine models reveal that adipose tissue might contain glycogen stores. Here we investigated the physio(patho)logical role of glycogen in human adipose tissue in the context of obesity and insulin resistance., Methods: We studied glucose metabolic flux of hypoxic human adipoctyes by nuclear magnetic resonance and mass spectrometry-based metabolic approaches. Glycogen synthesis and glycogen content in response to hypoxia was analyzed in human adipocytes and macrophages. To explore the metabolic effects of enforced glycogen deposition in adipocytes and macrophages, we overexpressed PTG, the only glycogen-associated regulatory subunit (PP1-GTS) reported in murine adipocytes. Adipose tissue gene expression analysis was performed on wild type and homozygous PTG KO male mice. Finally, glycogen metabolism gene expression and glycogen accumulation was analyzed in adipose tissue, mature adipocytes and resident macrophages from lean and obese subjects with different degrees of insulin resistance in 2 independent cohorts., Results: We show that hypoxia modulates glucose metabolic flux in human adipocytes and macrophages and promotes glycogenesis. Enforced glycogen deposition by overexpression of PTG re-orients adipocyte secretion to a pro-inflammatory response linked to insulin resistance and monocyte/lymphocyte migration. Furthermore, glycogen accumulation is associated with inhibition of mTORC1 signaling and increased basal autophagy flux, correlating with greater leptin release in glycogen-loaded adipocytes. PTG-KO mice have reduced expression of key inflammatory genes in adipose tissue and PTG overexpression in M0 macrophages induces a pro-inflammatory and glycolytic M1 phenotype. Increased glycogen synthase expression correlates with glycogen deposition in subcutaneous adipose tissue of obese patients. Glycogen content in subcutaneous mature adipocytes is associated with BMI and leptin expression., Conclusion: Our data establish glycogen mishandling in adipose tissue as a potential key feature of inflammatory-related metabolic stress in human obesity.

Introduction and Objectives: Facial nerve monitoring is fundamental in the preservation of the facial nerve in vestibular schwannoma surgery. Our objective was to analyse the usefulness of facial nerve monitoring under partial neuromuscular blockade., Methods: This was a retrospective analysis of 69 patients operated in a tertiary hospital., Results: We monitored 100% of the cases. In 75% of the cases, we could measure an electromyographic response after tumour resection. In 17 cases, there was an absence of electromyographic response. Fifteen of them had an anatomic lesion with loss of continuity of the facial nerve and, in 2 cases, there was a lesion with preservation of the nerve. Preoperative facial palsy (29% 7%; P=.0349), large tumour size (88 vs. 38%; P=.0276), and a non-functional audition (88 vs. 51%; P=.0276) were significantly related with an absence of electromyographic response., Conclusions: Facial nerve monitoring under neuromuscular blockade is possible and safe in patients without previous facial palsy. If the patient had an electromyographic response after tumour excision, they developed better facial function in the postoperative period and after a year of follow up., (Copyright © 2014 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.)

Calorie restriction's (CR) effects on age-associated changes in glycogen-metabolizing enzymes were studied in rat soleus (SOL) and tibialis anterior (TA) muscles. Old (24 months) compared to young (6 months) rats maintained ad libitum on a standard diet had reduced glycogen synthase (GS) activity, lower muscle GS protein levels, increased phosphorylation of GS at site 3a with less activation in SOL. Age-associated impairments in GS protein and activation-phosphorylation were also shown in TA. There was an age-associated reduction in glycogen phosphorylase (GP) activity level in SOL, while brain/muscle isoforms (B/M) of GP protein levels were higher. GP activity and protein levels were preserved, but GP was inactivated in TA with age. Glycogen content was unchanged in both muscles. CR did not alter GS or GP activity/protein levels in young rats. CR hindered age-related decreases in GS activity/protein, unrelated to GS mRNA levels, and GS inactivation-phosphorylation; not on GP. In older rats, CR enhanced glycogen accumulation in SOL. Short-term fasting did not recapitulate CR effects in old rats. Thus, the predominant age-associated impairments on skeletal muscle GS and GP activities occur in the oxidative SOL muscle of rats, and CR can attenuate the loss of GS activity/activation and stimulate glycogen accumulation.