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BackgroundSystemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by a variety of both signs and symptoms; it mainly affects women of childbearing age, with an estimated prevalence of 24/100,000 people in Europe and North America. SLE is often described as an antibodies-driven disease as its clinical manifestations are usually associated with the presence or the absence of specific antibodies.ObjectivesTo evaluate clinical manifestations in patients with SLE and to assess the relationship with the presence of specific antibodies by using real-world data.MethodsA retrospective study was performed; the 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus were used to classify patients with SLE. Data concerning serological profiles (which included Antinuclear antibodies – ANA, anti dsDNA, anti-Ro/SS-A, anti-La/SS-B, anti-Smith) were gathered along with medical records of clinical manifestations. Complement levels were also tested for possible clinical correlations. χ² or Fisher’s exact tests were utilized to establish associations between autoantibodies and symptoms. The odds ratios (OR) and their 95% confidence intervals (CI) were computed. No correction was made for multiple testing; only a p-value 0.01 ≤ was considered significant.ResultsOne-hundred and twenty-seven patients (n=127, mean age 53.43 ± 14.02) were enrolled in this study. Anti-dsDNA antibodies were found to be statistically significant for both malar rash and proteinuria; anti-Ro/SSA antibodies showed an association with photosensitivity and pericarditis; furthermore, a strong association was found between anti-Ro antibodies and proteinuria, but only if anti-dsDNA antibodies were present as well. Patients who tested positive for anti-La/SSB antibodies correlated with a threefold increase in the risk of developing pericarditis. Lastly, anti-Smith appeared to be associated with NPSLE as well as an increased risk for both autoimmune hemolytic anemia and thrombocytopenia.ConclusionsIn our study, many associations confirmed those found in previous studies; however, new relationships between antibodies and clinical manifestations were found thus indicating the need for additional evaluations to assess these correlations further.

Background: The extensor apparatus of the knee can be thought of a chain that transmits the muscular strength developed by the quadriceps muscles to the proximal tibia. This complex is essential to allow the extension of the tibia over the femur, being essential to provide knee mobility and stability. In case of lesions which irreparably damage the patella, such as a locally aggressive bone tumor, it is necessary to restore both the apparatus’ anatomical continuity and its strength.Case report: A 39-years-old Caucasian man with a history of lung carcinoma developed atraumatic swelling and soreness in his left knee. Imaging evidence reported a degeneration of the left patella. We performed an en bloc resection of the patella and the nearby soft tissues of the extensor apparatus. The resulting gap was fulfilled with a massive allograft consisting of a quadriceps tendon, a patella and a patellar ligament. No complication or local recurrences were observed. At the patient’s latest follow-up, he did not have any extension lag and quadriceps strength was completely restored.Conclusion: Massive allografts can represent a reliable alternative for the reconstruction of the patella and the knee extensor apparatus in orthopedic oncology.

Myxoid liposarcomas are malignant soft-tissue sarcomas whose treatment represents a challenge, even for the most experienced surgeon. In this study, we report on our experience with the treatment of myxoid liposarcomas of the thigh. Our retrospective analysis included myxoid liposarcomas of the thigh treated with surgical resection between 2016 and 2022. Resection margins, complications, local recurrences, and metastases were recorded. The oncological outcome of each case was evaluated at their latest follow-up. Adjuvant therapies were administered according to the ESMO guidelines. Functionality was assessed with the MSTS score before surgery and at the patients’ latest follow-up. Thirty cases (ten high-grade and 20 low-grade) were included. The mean diameter was 11.8 cm. Twenty-four cases had wide margins (80%) and six (20%) were marginal. Five cases (60% marginal) had local recurrences (17%). Marginal resection was associated with a higher risk of local recurrence (p = 0.041). Three cases with high-grade tumors (10%) developed metastases. At the patients’ latest follow-up, their mean MSTS score had risen from 22.9 to 27.3. While tumor grade influences the risk of metastases, the quality of resection margins can determine the local recurrence rate. An adequate surgery can lead to good post-operative functional outcomes.

Abstract In this manuscript, we report on a novel architecture for the fabrication of highly sensitive multimodal tactile transducers, for the simultaneous detection of temperature and force. Such devices are based on a flexible Organic Charge Modulated Field Effect Transistor (OCMFET) coupled with a pyro/piezoelectric element, namely a commercial film of poly-vinylene difluoride (PVDF). The reduction of the channel length, obtained by employing a low-resolution vertical channel architecture, allowed to maximize the ratio between the sensing area and the transistor’s channel area, a technological approach that allows to considerably enhance both temperature and force sensitivity, while at the same time minimize the sensor’s dimensions. Thanks to the employment of a straightforward, up-scalable, and highly reproducible fabrication process, this solution represents an interesting alternative for all those applications requiring high-density, high-sensitivity sensors such as robotics and biomedical applications.

New diagnostic methods have been developed for the early diagnosis of Alzheimer’s disease (AD) with the primary purpose of intercepting the transition-phase (mild cognitive impairment, MCI) between normal aging and dementia. We aimed to explore whether the five-word test (FWT) and the mini-mental state examination (MMSE) are predictive for the early diagnosis of MCI due to AD (AD-MCI). We computed ROC analyses to evaluate the sensitivity and specificity of MMSE and FWT in predicting abnormal CSF (t-Tau, p-Tau181, Aβ1–42) and amyloid-PET biomarkers. AD-MCI patients showed lower MMSE and FWT scores (all p < 0.001) than non-AD-MCI. The best predictor of amyloid plaques’ presence at amyloid-PET imaging was the encoding sub-score of the FWT (AUC = 0.84). Both FWT and MMSE had low/moderate accuracy for the detection of pathological CSF Aβ42, t-Tau and p-Tau181 values, with higher accuracy for the t-Tau/Aβ1–42 ratio. In conclusion, the FWT, as a single-domain cognitive screening test, seems to be prompt and moderately accurate tool for the identification of an underlying AD neuropathological process in patients with MCI, supporting the importance of associating biomarkers evaluation in the work-up of patients with dementing neurodegenerative disorders.

Giant Cell Tumor of Bone is a benign tumor with high local aggressive expansion, which, in rare cases, spreads metastasis. Surgical treatment, which often consists of wide curettage to reduce recurrence risk, can lower the quality of life for those affected. Along with aggressive surgery, adjuvant intraoperative techniques have been implemented such as PMMA and cryotherapy. One of the most widely used cryotherapy techniques involves the use of probes to generate ice balls, which have been scientifically shown to have various impacts on the tumor. Although this has been acknowledged, no one has yet tested a way to accurately plan the positioning of cryotherapy probes before surgery, according to the research conducted by the authors. CRIO2AR is a randomized clinical prospective ongoing study by which it will be experimented via preoperative planning of ice probes placement using AR and 3D printing technologies. By studying a single clinical case with these technologies, the surgeon gains better awareness of patient’s anatomy and tumor localization. Preliminary results are shown in the article. The first results are confirming that these technologies are applicable in clinical practice. Secondly, preoperative planning is proving to be reliable, easily replicable, and useful for the surgeon.

ObjectiveTo determine whether exosomal microRNAs (miRNAs) in cerebrospinal fluid (CSF) of patients with frontotemporal dementia (FTD) can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic Frontotemporal Dementia Initiative (GENFI) cohort and in sporadic FTD.MethodsGENFI participants were either carriers of a pathogenic mutation in progranulin, chromosome 9 open reading frame 72 or microtubule-associated protein tau or were at risk of carrying a mutation because a first-degree relative was a known symptomatic mutation carrier. Exosomes were isolated from CSF of 23 presymptomatic and 15 symptomatic mutation carriers and 11 healthy non-mutation carriers. Expression of 752 miRNAs was measured using quantitative PCR (qPCR) arrays and validated by qPCR using individual primers. MiRNAs found differentially expressed in symptomatic compared with presymptomatic mutation carriers were further evaluated in a cohort of 17 patients with sporadic FTD, 13 patients with sporadic Alzheimer's disease (AD) and 10 healthy controls (HCs) of similar age.ResultsIn the GENFI cohort, miR-204-5p and miR-632 were significantly decreased in symptomatic compared with presymptomatic mutation carriers. Decrease of miR-204-5p and miR-632 revealed receiver operator characteristics with an area of 0.89 (90% CI 0.79 to 0.98) and 0.81 (90% CI 0.68 to 0.93), respectively, and when combined an area of 0.93 (90% CI 0.87 to 0.99). In sporadic FTD, only miR-632 was significantly decreased compared with AD and HCs. Decrease of miR-632 revealed an area of 0.90 (90% CI 0.81 to 0.98).ConclusionsExosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD.

Abstract Background First metatarsophalangeal joint (MTPJ) fusion is the most effective technique for the treatment of MTPJ primary arthritis, severe hallux valgus and failure of primary corrective surgery of these conditions. It can be achieved through different techniques. We evaluated the outcomes in a cohort of patients treated with dorsal plate arthrodesis. Materials and methods We treated 30 feet for 28 patients; the mean follow-up was 35 months. For each foot, we collected radiological and clinical assessment, with the visual analogue scale (VAS) for pain and the Manchester and Oxford Foot questionnaire (MOFQ). The technique consisted in a cup and cone arthrodesis with the application of a low profile dorsal plate. Patients were allowed for immediate weight bearing. Results Consolidation was achieved in all cases; in 29 cases, radiographic union was recorded within 6 months from surgery, in one case after 9 months. Comparison between the preoperative and postoperative of VAS and MOXFQ values showed a statistically significant difference (p

In orthopedic oncology, total scapulectomy is necessary to allow a wide resection of extended malignancies of the scapula and scapular girdle. Scapular reconstruction is challenging even for the most experienced surgeon. This paper reports our experience with total scapular resections, followed by humeral suspension or custom-made prostheses. In this retrospective study, we evaluated all the oncologic patients treated in our institution between 2016 and 2023 with total scapulectomy and consequential reconstruction using humeral suspension or a custom-made prosthesis. Only cases suffering from malignant bone tumors were included. The postoperative functionality of the treated limbs was assessed using the Musculoskeletal Tumor Society (MSTS) scoring scale. Complications and local recurrences were also recorded. Nine patients were enrolled. Five had custom-made implants, and four had humeral suspensions. The mean postoperative MSTS score of patients treated with custom-made prostheses was 24.0 (22–26). Globally, our cohort's mean MSTS score was 19.1 (9–26). Patients with custom-made prostheses had significantly better functional outcomes (MSTS 24 vs 13) and similar complication rates (40% vs 50%) than those who received humeral suspensions. Our outcomes suggest that, when feasible, custom-made scapular prostheses can represent a reliable reconstructive option after total scapulectomy for malignant scapular tumors. [ABSTRACT FROM AUTHOR]

A breathable tattoo electrode for bio-potential recording based on a Parylene C nanofilm is presented in this study. The proposed approach allows for the fabrication of micro-perforated epidermal submicrometer-thick electrodes that conjugate the unobtrusiveness of Parylene C nanofilms and the very important feature of breathability. The electrodes were fully validated for electrocardiography (ECG) measurements showing performance comparable to that of conventional disposable gelled Ag/AgCl electrodes, with no visible negative effect on the skin even many hours after their application. This result introduces interesting perspectives in the field of epidermal electronics, particularly in applications where critical on-body measurements are involved.

Objective: To evaluate if transcranial magnetic stimulation (TMS) measures correlate with disease severity and predict functional decline in frontotemporal dementia (FTD) phenotypes. Methods: Paired-pulse TMS was used to investigate the activity of different intracortical circuits in 171 FTD patients (122 bvFTD, 31 avPPA, 18 svPPA) and 74 healthy controls. Pearson’s correlations were used to analyze the association between TMS measures and disease severity, while multiple regression analysis was used to identify the best clinical or neurophysiological measure to predict functional decline at 12 months. Results: We observed significant strong correlations between TMS measures [short interval intracortical inhibition-facilitation (SICI-ICF) and long interval intracortical inhibition (LICI)], and disease severity (evaluated with the FTLD-CDR) (all r > 0.5, p

In an increasingly interconnected world, where electronic devices permeate every aspect of our lives, wearable systems aimed at monitoring physiological signals are rapidly taking over the sport and fitness domain, as well as biomedical fields such as rehabilitation and prosthetics. With the intent of providing a novel approach to the field, in this paper we discuss the development of a wearable system for the acquisition of EEG signals based on a portable, low-power custom PCB specifically designed to be used in combination with non-conventional ultra-conformable and imperceptible Parylene-C tattoo electrodes. The proposed system has been tested in a standard rest-state experiment, and its performance in terms of discrimination of two different states has been compared to that of a commercial wearable device for EEG signal acquisition (i.e., the Muse headset), showing comparable results. This first preliminary validation demonstrates the possibility of conveniently employing ultra-conformable tattoo-electrodes integrated portable systems for the unobtrusive acquisition of brain activity.

The introduction of the Eastern grey squirrel (Sciurus carolinensis) in Europe is one of the best-known cases of invasive alien species (IAS) colonisation, that poses a severe risk to the conservation of biodiversity. In 2003, it was released in a private wildlife park near the city of Perugia (Italy), where it is replacing the native Eurasian red squirrel (Sciurus vulgaris). The LIFE13 BIO/IT/000204 Project (U-SAVEREDS) was set up for the Sciurus vulgaris conservation in Umbria through an eradication campaign of grey squirrels. One hundred and fifty-four animals were analysed for bacteriological, mycological, virological, and serological investigations (C4 action). Sanitary screening showed that Sciurus carolinensis is a dermatophyte carrier, and therefore, it could cause public health issues for humans, considering its confident behaviour. Moreover, it has been marginally responsible for the spreading of Candida albicans, Coxiella burnetii, and Borrelia lusitaniae. Health status evaluation conducted on the Sciurus carolinensis population indicated that it is necessary to raise awareness of its impacts on biodiversity and human health. Moreover, the health status and behaviours of the IAS must be considered when control or eradication campaigns are planned.

The clinical significance of antiphospholipid antibodies (aPL) in the context of infections has attracted attention since their first discovery in patients with syphilis. In fact, the recognition of aPL in patients with infections has been described in parallel to the understating of the syndrome. Since the first description of aPL-positive tests in three patients with COVID-19 diagnosed in January 2020 in Wuhan, China, a large number of studies took part in the ongoing debate on SARS-2-Cov 2 induced coagulopathy, and many following reports speculated a potential role for aPL. In order to get further insights on the effective role of detectable aPL in the pro-thrombotic status observed in COVID-19 patients, we performed an observational age-sex controlled study to compare the aPL profile of hospitalized patients with COVID with those observed in a) patients with thrombotic APS and b) patients with cultural/serologically-proved infections. Our data showed positive aPL testing in about half of the patients (53%) with COVID-19 and patients with other viral/bacterial infections (49%). However, aPL profile was different when comparing patients with overt APS and patients with aPL detected in the contest of infections. Caution is therefore required in the interpretation and generalization of the role of aPL s in the management of patients with COVID-19. Before introducing aPL testing as a part of the routine testing in patients with COVID-19, larger well-designed clinical studies are required. While the pro-thrombotic status in patients with COVID-19 is now unquestionable, different mechanisms other than aPL should be further investigated.

Urine citrate analysis is relevant in the screening and monitoring of patients with calcium nephrolithiasis. A sensitive, fast, easy, and low-maintenance ion chromatographic (IC) method with conductivity detection for the analysis of urine citrate is developed and validated. Its application on true samples is also reported. Sample urine is diluted with a water solution containing internal standard (IS) before the chromatographic assay. The isocratic chromatographic run time is twenty-five minutes, using sodium hydroxide aqueous solution as the mobile phase. The method is fully validated as a quantitative method to objectively demonstrate its applicability for the intended use. The analytical response is linear in the 0.08–10.4 mmol/L concentration range. Precision and accuracy studies carried out on spiked urine and internal quality control samples reveal an imprecision CV% lower than 11% and an accuracy between 85 and 103%. The stability of citrate in urine samples is also evaluated. An easy, rapid, and low-maintenance, cost-effective IC method for urinary citrate determination is developed and validated. Internal standardization improves reliability and precision. The method has been currently used in our laboratory over recent years to analyze more than 1000 samples per year.

Interfacing ultrathin functional films for epidermal applications with external recording instruments or readout electronics still represents one of the biggest challenges in the field of tattoo electronics. With the aim of providing a convenient solution to this ever-present limitation, in this work we propose an innovative free-standing electrode made of a composite thin film based on the combination of the conductive polymer PEDOT:PSS and ferrimagnetic powder. The proposed epidermal electrode can be directly transferred onto the skin and is structured in two parts, namely a conformal conductive part with a thickness of 3 μm and a ferrimagnetic-conductive part that can be conveniently connected using magnetic connections. The films were characterized for ECG recordings, revealing a performance comparable to that of commercial pre-gelled electrodes in terms of cross-spectral coherence, signal-to-noise ratio, and baseline wandering. These new, conductive, magnetically interfaceable, and free-standing conformal films introduce a novel concept in the domain of tattoo electronics and can set the basis for the development of a future family of epidermal devices and electrodes.

Mutations in the granulin gene (GRN) cause familial frontotemporal dementia. Understanding the structural brain changes in presymptomatic GRN carriers would enforce the use of neuroimaging biomarkers for early diagnosis and monitoring. We studied 100 presymptomatic GRN mutation carriers and 94 noncarriers from the Genetic Frontotemporal dementia initiative (GENFI), with MRI structural images. We analyzed 3T MRI structural images using the FreeSurfer pipeline to calculate the whole brain cortical thickness (CTh) for each subject. We also perform a vertex-wise general linear model to assess differences between groups in the relationship between CTh and diverse covariables as gender, age, the estimated years to onset and education. We also explored differences according to TMEM106B genotype, a possible disease modifier. Whole brain CTh did not differ between carriers and noncarriers. Both groups showed age-related cortical thinning. The group-by-age interaction analysis showed that this age-related cortical thinning was significantly greater in GRN carriers in the left superior frontal cortex. TMEM106B did not significantly influence the age-related cortical thinning. Our results validate and expand previous findings suggesting an increased CTh loss associated with age and estimated proximity to symptoms onset in GRN carriers, even before the disease onset.

The aim of this study is to assess direct X-ray detectors based on organic thin films, fabricated onto flexible plastic substrates, and operating at ultra-low bias (

Introduction. A recent attractive option regarding mesenchymal stem cells (MSC) application is the treatment of bone cystic lesions and in particular aneurysmal bone cysts (ABC), in order to stimulate intrinsic healing. We performed a retrospective evaluation of the results obtained at our institution. Methods. The study group consisted of 46 cases with an average follow-up of 33 months. Forty-two patients underwent percutaneous treatment as the first approach; four patients had curettage as first treatment. In all cases, autologous bone marrow concentrate (BMC) was associated too. The healing status was followed up through a plain radiograph 45 days and 2 months after the procedure. Results and Conclusions. At the final follow-up, thirty-six patients healed with a Neer type II aspect, nine healed with a type I aspect, and one patient was not classified having total hip arthroplasty. Bone marrow concentrate is easy to obtain and to manipulate and can be immediately available in a clinical setting. We can assert that the use of BMC must be encouraged being harmless and having an unquestionable high osteogenic and healing potential in bone defects.

Abstract Introduction Frontotemporal dementia (FTD) is a progressive disease for which no curative treatment is currently available. We aimed to determine whether transcranial direct current stimulation (tDCS) can modulate intracortical connectivity and improve cognition in symptomatic FTD patients and presymptomatic FTD subjects. Methods We performed a double‐blind, randomized, sham‐controlled trial with anodal tDCS or sham stimulation over the left prefrontal cortex in 70 participants (15 presymptomatic and 55 symptomatic FTD). Results We observed a significant increase of intracortical connectivity (short interval intracortical inhibition and facilitation) and improvement in clinical scores and behavioral disturbances in both symptomatic FTD patients and presymptomatic carriers after real tDCS but not after sham stimulation. Discussion A 2‐weeks’ treatment with anodal left prefrontal tDCS improves symptoms and restores intracortical inhibitory and excitatory circuits in both symptomatic FTD patients and presymptomatic carriers. tDCS might represent a promising future therapeutic and rehabilitative approach in patients with FTD.

Abstract In this study, a novel approach to the fabrication of a multimodal temperature and force sensor on ultrathin, conformable and flexible substrates is presented. This process involves coupling a charge-modulated organic field-effect transistor (OCMFET) with a pyro/piezoelectric element, namely a commercial film of poly-vinylene difluoride (PVDF). The proposed device is able to respond to both pressure stimuli and temperature variations, demonstrating the feasibility of the approach for the development of low-cost, highly sensitive and conformable multimodal sensors. The overall thickness of the device is 1.2 μm, being thus able to conform to any surface (including the human body), while keeping its electrical performance. Furthermore, it is possible to discriminate between simultaneously applied temperature and pressure stimuli by coupling sensing surfaces made of poled and unpoled spin-coated PVDF-trifluoroethylene (PVDF-TrFE, a PVDF copolymer) with OCMFETs. This demonstrates the possibility of creating multimodal sensors that can be employed for applications in several fields, ranging from robotics to wearable electronics.

Abstract To explore the effects of PD pathology on brain connectivity, we characterized with an emergent computational approach the brain metabolic connectome using [18F]FDG-PET in early idiopathic PD patients. We applied whole-brain and pathology-based connectivity analyses, using sparse-inverse covariance estimation in thirty-four cognitively normal PD cases and thirty-four age-matched healthy subjects for comparisons. Further, we assessed high-order resting state networks by interregional correlation analysis. Whole-brain analysis revealed altered metabolic connectivity in PD, with local decreases in frontolateral cortex and cerebellum and increases in the basal ganglia. Widespread long-distance decreases were present within the frontolateral cortex as opposed to connectivity increases in posterior cortical regions, all suggestive of a global-scale connectivity reconfiguration. The pathology-based analyses revealed significant connectivity impairment in the nigrostriatal dopaminergic pathway and in the regions early affected by α-synuclein pathology. Notably, significant connectivity changes were present in several resting state networks especially in frontal regions. These findings expand previous imaging evidence of altered connectivity in cognitively stable PD patients by showing pathology-based connectivity changes and disease-specific metabolic architecture reconfiguration at multiple scale levels, from the earliest PD phases. These alterations go well beyond the known striato-cortical connectivity derangement supporting in vivo an extended neural vulnerability in the PD synucleinopathy.

Genetic frontotemporal dementia is most commonly caused by mutations in the progranulin (GRN), microtubule-associated protein tau (MAPT) and chromosome 9 open reading frame 72 (C9orf72) genes. Previous small studies have reported the presence of cerebral white matter hyperintensities (WMH) in genetic FTD but this has not been systematically studied across the different mutations. In this study WMH were assessed in 180 participants from the Genetic FTD Initiative (GENFI) with 3D T1- and T2-weighed magnetic resonance images: 43 symptomatic (7 GRN, 13 MAPT and 23 C9orf72), 61 presymptomatic mutation carriers (25 GRN, 8 MAPT and 28 C9orf72) and 76 mutation negative non-carrier family members. An automatic detection and quantification algorithm was developed for determining load, location and appearance of WMH. Significant differences were seen only in the symptomatic GRN group compared with the other groups with no differences in the MAPT or C9orf72 groups: increased global load of WMH was seen, with WMH located in the frontal and occipital lobes more so than the parietal lobes, and nearer to the ventricles rather than juxtacortical. Although no differences were seen in the presymptomatic group as a whole, in the GRN cohort only there was an association of increased WMH volume with expected years from symptom onset. The appearance of the WMH was also different in the GRN group compared with the other groups, with the lesions in the GRN group being more similar to each other. The presence of WMH in those with progranulin deficiency may be related to the known role of progranulin in neuroinflammation, although other roles are also proposed including an effect on blood-brain barrier permeability and the cerebral vasculature. Future studies will be useful to investigate the longitudinal evolution of WMH and their potential use as a biomarker as well as post-mortem studies investigating the histopathological nature of the lesions.

The complicated patterns of the single-channel currents in potassium ion channel KcsA are governed by the structural variability of the selectivity filter. A comparative analysis of the dynamics of the wild type KcsA channel and several of its mutants showing different conducting patterns was performed. A strongly correlated dynamical network of interacting residues is found to play a key role in regulating the state of the wild type channel. The network is centered on the aspartate D80 which plays the role of a hub by strong interacting via hydrogen bonds with residues E71, R64, R89, and W67. Residue D80 also affects the selectivity filter via its backbones. This network further compromises ions and water molecules located inside the channel that results in the mutual influence: the permeation depends on the configuration of residues in the network, and the dynamics of network’s residues depends on locations of ions and water molecules inside the selectivity filter. Some features of the network provide a further understanding of experimental results describing the KcsA activity. In particular, the necessity of anionic lipids to be present for functioning the channel is explained by the interaction between the lipids and the arginine residues R64 and R89 that prevents destabilizing the structure of the selectivity filter.

Outbreaks of Rift Valley fever (RVF) occurred in Namibia in 2010 and 2011. Complete genome characterization was obtained from virus isolates collected during disease outbreaks in southern Namibia in 2010 and from wildlife in Etosha National Park in 2011, close to the area where RVF outbreaks occurred in domestic livestock. The virus strains were sequenced using Sanger sequencing (Namibia_2010) or next generation sequencing (Namibia_2011). A sequence-independent, single-primer amplification (SISPA) protocol was used in combination with the Illumina Next 500 sequencer. Phylogenetic analysis of the sequences of the small (S), medium (M), and large (L) genome segments of RVF virus (RVFV) provided evidence that two distinct RVFV strains circulated in the country. The strain collected in Namibia in 2010 is genetically similar to RVFV strains circulating in South Africa in 2009 and 2010, confirming that the outbreaks reported in the southern part of Namibia in 2010 were caused by possible dissemination of the infection from South Africa. Isolates collected in 2011 were close to RVFV isolates from 2010 collected in humans in Sudan and which belong to the large lineage containing RVFV strains that caused an outbreak in 2006–2008 in eastern Africa. This investigation showed that the RVFV strains circulating in Namibia in 2010 and 2011 were from two different introductions and that RVFV has the ability to move across regions. This supports the need for risk-based surveillance and monitoring.

Organic electronics show advantages in easy processing, mechanical flexibility and low costs compared to their inorganic counterparts, yet there are not many proofs for the sake of X-ray detection. Here, Basiricò et al. build a flexible X-ray detector operated at sub-1 V using pentacene-based thin films.

The development of electronic devices with enhanced properties of transparency and conformability is of high interest for the development of novel applications in the field of bioelectronics and biomedical sensing. Here, a fabrication process for all organic Organic Field-Effect Transistors (OFETs) by means of large-area, cost-effective techniques such as inkjet printing and chemical vapor deposition is reported. The fabricated device can operate at low voltages (as high as 4 V) with ideal electronic characteristics, including low threshold voltage, relatively high mobility and low subthreshold voltages. The employment of organic materials such as Parylene C, PEDOT:PSS and 6,13-Bis(triisopropylsilylethynyl)pentacene (TIPS pentacene) helps to obtain highly transparent transistors, with a relative transmittance exceeding 80%. Interestingly enough, the proposed process can be reliably employed for OFET fabrication over different kind of substrates, ranging from transparent, flexible but relatively thick polyethylene terephthalate (PET) substrates to transparent, 700-nm-thick, compliant Parylene C films. OFETs fabricated on such sub-micrometrical substrates maintain their functionality after being transferred onto complex surfaces, such as human skin and wearable items. To this aim, the electrical and electromechanical stability of proposed devices will be discussed.

Taste buds containing receptor cells that primarily detect one taste quality provide the basis for discrimination across taste qualities. The molecular receptor multiplicity and the interactions occurring between bud cells encode information about the chemical identity, nutritional value, and potential toxicity of stimuli before transmitting signals to the hindbrain. PROP (6-n-propylthiouracil) tasting is widely considered a marker for individual variations of taste perception, dietary preferences, and health. However, controversial data have been reported. We present measures of the peripheral gustatory system activation in response to taste qualities by electrophysiological recordings from the tongue of 39 subjects classified for PROP taster status. The waveform of the potential variation evoked depended on the taste quality of the stimulus. Direct relationships between PROP sensitivity and electrophysiological responses to taste qualities were found. The largest and fastest responses were recorded in PROP super-tasters, who had the highest papilla density, whilst smaller and slower responses were found in medium tasters and non-tasters with lower papilla densities. The intensities perceived by subjects of the three taster groups correspond to their electrophysiological responses for all stimuli except NaCl. Our results show that each taste quality can generate its own electrophysiological fingerprint on the tongue and provide direct evidence of the relationship between general taste perception and PROP phenotype.

[This corrects the article DOI: 10.1371/journal.pone.0177246.].

The goal of this work is to develop an automatic system for the evaluation of the gustatory sensitivity of patients using an electrophysiological recording of the response of bud cells to taste stimuli. In particular, the study aims to evaluate the effectiveness and limitations of supervised classifiers in the discrimination between subjects belonging to the three 6-n-propylthiouracil (PROP) taster categories (supertasters, medium tasters, and non-tasters), exploiting features extracted from electrophysiological recordings of the tongue. Thirty-nine subjects (equally divided into the three PROP status classes by standard non-objective scaling methods) underwent a non-invasive, differential, biopotential recording of their tongues during stimulation with PROP by using a custom-made, flexible, silver electrode. Two different classifiers were trained to recognize up to seven different features extracted from the recorded depolarization signal. The classification results indicate that the identified set of features allows to distinguish between PROP tasters and non-tasters (average accuracy of 80% ± 18% and up to 94% ± 15% when only supertasters and non-tasters are considered), but medium tasters were difficult to identify. However, these apparent classification errors are related to uncertainty in the labeling procedures, which are based on non-objective tests, in which the subjects provided borderline evaluations. Thus, using the proposed method, it is possible, for the first time, to automatically achieve objective PROP taster status identification with high accuracy. The simplicity of the recording technique allows for easy reproduction of the experimental setting; thus the technique can be used in future studies to evaluate other gustatory stimuli. The proposed approach represents the first objective and automatic method to directly measure human gustatory responses and a milestone for physiological taste studies, with applications ranging from basic science to food tasting evaluations.

It is widely known that prion strains can mutate in response to modification of the replication environment and we have recently reported that prion mutations can occur in vitro during amplification of vole-adapted prions by Protein Misfolding Cyclic Amplification on bank vole substrate (bvPMCA). Here we exploited the high efficiency of prion replication by bvPMCA to study the in vitro propagation of natural scrapie isolates. Although in vitro vole-adapted PrPSc conformers were usually similar to the sheep counterpart, we repeatedly isolated a PrPSc mutant exclusively when starting from extremely diluted seeds of a single sheep isolate. The mutant and faithful PrPSc conformers showed to be efficiently autocatalytic in vitro and were characterized by different PrP protease resistant cores, spanning aa ∼155-231 and ∼80-231 respectively, and by different conformational stabilities. The two conformers could thus be seen as different bona fide PrPSc types, putatively accounting for prion populations with different biological properties. Indeed, once inoculated in bank vole the faithful conformer was competent for in vivo replication while the mutant was unable to infect voles, de facto behaving like a defective prion mutant. Overall, our findings confirm that prions can adapt and evolve in the new replication environments and that the starting population size can affect their evolutionary landscape, at least in vitro. Furthermore, we report the first example of "authentic" defective prion mutant, composed of brain-derived PrPC and originating from a natural scrapie isolate. Our results clearly indicate that the defective mutant lacks of some structural characteristics, that presumably involve the central region ∼90-155, critical for infectivity but not for in vitro replication. Finally, we propose a molecular mechanism able to account for the discordant in vitro and in vivo behavior, suggesting possible new paths for investigating the molecular bases of prion infectivity.

The perception of fat varies among individuals and has also been associated with CD36 rs1761667 polymorphism and genetic ability to perceive oral marker 6-n-propylthiouracil (PROP). Nevertheless, data in the literature are controversial. We present direct measures for the activation of the peripheral taste system in response to oleic acid by electrophysiological recordings from the tongue of 35 volunteers classified for PROP taster status and genotyped for CD36. The waveform of biopotentials was analyzed and values of amplitude and rate of potential variation were measured. Oleic acid stimulations evoked positive monophasic potentials, which represent the summated voltage change consequent to the response of the stimulated taste cells. Bio-electrical measurements were fully consistent with the perceived intensity during stimulation, which was verbally reported by the volunteers. ANOVA revealed that the amplitude of signals was directly associated, mostly in the last part of the response, with the CD36 genotypes and PROP taster status (which was directly associated with the density of papillae). The rate of potential variation was associated only with CD36, primarily in the first part of the response. In conclusion, our results provide direct evidence of the relationship between fat perception and rs1761667 polymorphism of the CD36 gene and PROP phenotype.