A Multidisciplinary Approach to the First Autochthonous Case of Tularemia Reported in Portugal

Francisella tularensis, a Gram-negative coccobacillus, is a highly virulent pathogen responsible for several zoonotic outbreaks in Europe in the last few decades. The authors report the case of a 46-year-old male who developed fever, myalgias and headache a week after having contact with animal feed contaminated by rodents. Serological tests were positive for Francisella tularensis. This first case of autochthonous tularemia in Portugal led to an intensive investigation involving several healthcare services and national governmental authorities. The authors address the possible underdiagnosis of this infection in the country.

Fanconi Anemia: Examining Guidelines for Testing All Patients with Hand Anomalies Using a Machine Learning Approach

Background: This study investigated the questionable necessity of genetic testing for Fanconi anemia in children with hand anomalies. The current UK guidelines suggest that every child with radial ray dysplasia or a thumb anomaly should undergo further cost intensive investigation for Fanconi anemia. In this study we reviewed the numbers of patients and referral patterns, as well as the financial and service provision implications UK guidelines provide. Methods: Over three years, every patient with thumb or radial ray anomaly referred to our service was tested for Fanconi Anemia. CART Analysis and machine learning techniques using Waikato Environment for Knowledge Analysis were applied to evaluate single clinical features predicting Fanconi anemia. Results: Youden Index and Predictive Summary Index (PSI) scores suggested no clinical significance of hand anomalies associated with Fanconi anemia. CART Analysis and attribute evaluation with Waikato Environment for Knowledge Analysis (WEKA) showed no single feature predictive for Fanconi anemia. Furthermore, none of the positive Fanconi anemia patients in this study had an isolated upper limb anomaly without presenting other features of Fanconi anemia. Conclusion: As a conclusion, this study does not support Fanconi anemia testing for isolated hand abnormalities in the absence of other features associated with this blood disease.

Lifetime prevention of cardiovascular disease. Part III: young, middle, elderly and senile age

Intensive investigation of cardiovascular disease (CVD) risk factors (RFs), both traditional (smoking, dyslipidemia, diabetes, etc.) and non-traditional, which are a component of the so-called exposome, as well as their non-drug and drug correction provide wide prospects for effective cardiovascular prevention. Prevention becomes the dominant trend in cardiology and in medicine in general. The aim of the article was to describe cardiovascular prevention in young, middle, elderly and senile age. Due to the multifaceted nature of cardiovascular RFs, an integrated biopsychosocial approach, individual and population-based prevention, cumulative risk assessment of all CVDs, intersectoral collaboration and the involvement of decision-makers, are key to the success and effectiveness of prevention measures. It is important to note that, on the one hand, preventive measures should be started as early as possible due to cumulative effect of RFs, on the other hand, most of the preventive interventions for CVD are extremely relevant at all life stages.

Impact of rheological properties on bacterial streamer formation

Bacterial biofilms, which can be found wherever there is water and a substrate, can cause chronic infections and clogging of industrial flow systems. Despite intensive investigation of the dynamics and rheological properties of biofilms, the impact of their rheological properties on streamer growth remains unknown. We numerically simulated biofilm growth in a pillar-flow and investigated the effects of rheological properties of a filamentous flow-shaped biofilm, called a ‘streamer’, on its formation by varying the viscoelasticity. The flow-field is assumed to be a Stokes flow and is solved by a boundary element method. A Maxwell model is used for extracellular matrix-mediated streamer growth to express the fluidity of streamer formations. Both high elastic modulus and viscosity are needed for streamer formation, and high viscosity promotes streamer growth at low cell concentrations. Our findings are consistent with experimental observations and can explain the relationship between the cell concentrations and viscosity at which streamers form.

Progranulin deficiency results in reduced bis(monoacylglycero)phosphate (BMP) levels and gangliosidosis

Homozygous mutations of granulin precursor (GRN) lead to neuronal ceroid lipofuscinosis, a severe neurodevelopmental disease, in humans and neuroinflammation in mice. Haploinsufficiency of GRN almost invariably causes frontotemporal dementia (FTD). The GRN locus produces progranulin (PGRN), a lysosomal precursor protein that is cleaved to granulin peptides. Despite intensive investigation, the function of granulins and the reason why their absence causes neurodegeneration remain unclear. Here, we investigated PGRN function in lipid degradation, a major function of lysosomes. We show that PGRN knockout human cells, PGRN-deficient murine brain, and frontal lobes of human brains from subjects with PGRN deficient FTD have increased levels of gangliosides, highly abundant sialic acid containing glycosphingolipids (GSL) that are degraded in lysosomes. Probing how PGRN deficiency causes these changes, we found normal levels and activities of enzymes that catabolize gangliosides. However, levels of bis(monoacylglycero)phosphate (BMP), a lysosomal lipid required for ganglioside catabolism, were markedly reduced in PGRN deficient cells and brain tissues. These data indicate that granulins are required to maintain BMP levels, which regulate ganglioside catabolism, and that PGRN deficiency in lysosomes leads to gangliosidosis. This aberrant accumulation of gangliosides may contribute to neuroinflammation and neurodegeneration susceptibility.

Afterword

The sensory turn and the affective turn in contemporary scholarship both crystalised at roughly the same time but then diverged. This special issue reintegrates them. Conjointly, these twin approaches direct attention to the multiplicity, agency, and interactivity of the full spectrum of human faculties (i.e., how the senses and affects intersect with and may also disrupt the rule of reason) in addition to highlighting the extent to which ‘the perceptual is political.’ The resulting paradigm has precipitated a shift from the study of communities as ‘imagined’ to how they are sensed and/or felt, and from a focus on ‘the human condition’ to the intensive investigation of the multiple ‘national post-revolutionary conditions’ that define the current conjuncture. By foregrounding the aesthetics of politics, and tracking the eruption of dis-sensus (laughter, graffiti, dissent) within the con-sensus that states seek to foster in their citizenry, this special issue sounds a much-needed wake-up call.

Facile Synthesis of Holmium-Based Nanoparticles as a CT and MRI Dual-Modal Imaging for Cancer Diagnosis

The rapid development of medical imaging has boosted the abilities of modern medicine. As single modality imaging limits complex cancer diagnostics, dual-modal imaging has come into the spotlight in clinical settings. The rare earth element Holmium (Ho) has intrinsic paramagnetism and great X-ray attenuation due to its high atomic number. These features endow Ho with good potential to be a nanoprobe in combined x-ray computed tomography (CT) and T2-weighted magnetic resonance imaging (MRI). Herein, we present a facile strategy for preparing HoF3 nanoparticles (HoF3 NPs) with modification by PEG 4000. The functional PEG-HoF3 NPs have good water solubility, low cytotoxicity, and biocompatibility as a dual-modal contrast agent. Currently, there is limited systematic and intensive investigation of Ho-based nanomaterials for dual-modal imaging. Our PEG-HoF3 NPs provide a new direction to realize in vitro and vivo CT/MRI imaging, as well as validation of Ho-based nanomaterials will verify their potential for biomedical applications.

Parkinson’s Disease Associated with GBA Gene Mutations: Molecular Aspects and Potential Treatment Approaches

Parkinsons disease (PD) is a multifactorial neurodegenerative disease. To date, genome-wide association studies have identified more than 70 loci associated with the risk of PD. Variants in the GBA gene encoding glucocerebrosidase are quite often found in PD patients in all populations across the world, which justifies intensive investigation of this gene. A number of biochemical features have been identified in patients with GBA-associated Parkinsons disease (GBA-PD). In particular, these include decreased activity of glucocerebrosidase and accumulation of the glucosylceramide substrate. These features were the basis for putting forward a hypothesis about treatment of GBA-PD using new strategies aimed at restoring glucocerebrosidase activity and reducing the substrate concentration. This paper discusses the molecular and genetic mechanisms of GBA-PD pathogenesis and potential approaches to the treatment of this form of the disease.

Hypertrophy of Rat Skeletal Muscle Is Associated with Increased SIRT1/Akt/mTOR/S6 and Suppressed Sestrin2/SIRT3/FOXO1 Levels

Despite the intensive investigation of the molecular mechanism of skeletal muscle hypertrophy, the underlying signaling processes are not completely understood. Therefore, we used an overload model, in which the main synergist muscles (gastrocnemius, soleus) of the plantaris muscle were surgically removed, to cause a significant overload in the remaining plantaris muscle of 8-month-old Wistar male rats. SIRT1-associated pro-anabolic, pro-catabolic molecular signaling pathways, NAD and H2S levels of this overload-induced hypertrophy were studied. Fourteen days of overload resulted in a significant 43% (p < 0.01) increase in the mass of plantaris muscle compared to sham operated animals. Cystathionine-β-synthase (CBS) activities and bioavailable H2S levels were not modified by overload. On the other hand, overload-induced hypertrophy of skeletal muscle was associated with increased SIRT1 (p < 0.01), Akt (p < 0.01), mTOR, S6 (p < 0.01) and suppressed sestrin 2 levels (p < 0.01), which are mostly responsible for anabolic signaling. Decreased FOXO1 and SIRT3 signaling (p < 0.01) suggest downregulation of protein breakdown and mitophagy. Decreased levels of NAD+, sestrin2, OGG1 (p < 0.01) indicate that the redox milieu of skeletal muscle after 14 days of overloading is reduced. The present investigation revealed novel cellular interactions that regulate anabolic and catabolic processes in the hypertrophy of skeletal muscle.

VMH neurons under the magnifying glass

The ventromedial nucleus of the hypothalamus (VMH) is a complex brain structure that is integral to many neuroendocrine functions, including glucose regulation, thermogenesis, appetitive, social and sexual behaviours. As such, it is of little surprise that the nucleus is under intensive investigation to decipher the mechanisms which underlie these diverse roles. Developments in genetic and investigative tools, for example the targeting of steroidogenic factor-1-expressing neurons, have allowed us to take a closer look at the VMH, its connections and how it affects competing behaviours. In the current review, we aim to integrate recent findings into the literature and contemplate the conclusions that can be drawn.