Blue Gravity Waves from BICEP2 ?

We present new constraints on the spectral index n_T of tensor fluctuations from the recent data obtained by the BICEP2 experiment. We found that the BICEP2 data alone slightly prefers a positive, "blue", spectral index with n_T=1.36\pm0.83 at 68 % c.l.. However, when a TT prior on the tensor amplitude coming from temperature anisotropy measurements is assumed we get n_T=1.67\pm0.53 at 68 % c.l., ruling out a scale invariant $n_T=0$ spectrum at more than three standard deviations. These results are at odds with current bounds on the tensor spectral index coming from pulsar timing, Big Bang Nucleosynthesis, and direct measurements from the LIGO experiment. Considering only the possibility of a "red", n_T<0 spectral index we obtain the lower limit n_T > -0.76 at 68 % c.l. (n_T>-0.09 when a TT prior is included).Comment: 3 Pages, 4 Figure

A Stage-Based Approach to Therapy in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder that features progressive, disabling motor symptoms, such as bradykinesia, rigidity, and resting tremor. Nevertheless, some non-motor symptoms, including depression, REM sleep behavior disorder, and olfactive impairment, are even earlier features of PD. At later stages, apathy, impulse control disorder, neuropsychiatric disturbances, and cognitive impairment can present, and they often become a heavy burden for both patients and caregivers. Indeed, PD increasingly compromises activities of daily life, even though a high variability in clinical presentation can be observed among people affected. Nowadays, symptomatic drugs and non-pharmaceutical treatments represent the best therapeutic options to improve quality of life in PD patients. The aim of the present review is to provide a practical, stage-based guide to pharmacological management of both motor and non-motor symptoms of PD. Furthermore, warning about drug side effects, contraindications, as well as dosage and methods of administration, are highlighted here, to help the physician in yielding the best therapeutic strategies for each symptom and condition in patients with PD

Epididymal adrenal rest in an orchiectomy specimen with seminoma

Ectopic adrenal tissue is rare but is reported in various locations within the urogenital tract and abdominal structures. The vast majority of adrenal rests represent incidental findings in surgical specimens; thus, their incidence is unknown.1&nbsp;Notwithstanding, the results of reports on their higher frequency in infants than adults and sex distribution are conflicting.1,2&nbsp;In male subjects, the paratesticular and inguinal regions represent common sites of ectopic adrenal tissue, given the intimate embryologic relationship between the gonad and the adrenal cortex.3&nbsp;In testis and paratestis, they are also known as Marchand rest and are most commonly found in the spermatic cord,3&nbsp;followed by testis4&nbsp;and epididymis.5,6&nbsp;In these anatomic locations, ectopic adrenals may be associated with undescended testis, inguinal hernia, epididymal abnormality, and spermatic cord torsion, but none represent a predisposing factor. Also, the association with malignant testicular neoplasms merely represents a matter of chance. As a rule, adrenal rests do not show significant clinical implications. However, they may undergo hyperplasia when the function of the main adrenals is deficient or in congenital adrenal hyperplasia (CAH), an autosomal recessive disease with increased ACTH levels.5,6&nbsp;Also, adrenal rests may be accidentally removed during surgery, leading to adrenal insufficiency. Finally, ectopic adrenal may harbor benign or malignant tumors resulting in clinically evident dysfunctions.3&nbsp;The adrenal rests comprise nodules ranging between 1 mm and 1 cm, appearing as encapsulated or well-circumscribed round yellowish masses that may be multiple or bilateral. Microscopic appearance reminds normal adrenal cortex, often arranged in different zones, without medullary tissue.Figure 1&nbsp;refers to a case of a tiny adrenal rest nodule incidentally observed in an orchiectomy specimen obtained from a 40-year-old man affected by a suspect germ cell tumor of the right testis. The surgical specimen´s gross examination depicted a yellowish-brown nodule measuring 2 mm in its longest axis, located under the visceral mesothelium of the tunica vaginalis near the head of the epididymis (Figure 1A).Figure 1A -&nbsp;Gross orchiectomy specimen displaying a tiny nodule yellowish-brown in color (arrowhead) below the visceral layer of the tunica vaginalis and close to the head of the epididymis (scale bar= 3 cm);&nbsp;B -&nbsp;Encapsulated adrenal rest located between epididymis and rete testis;&nbsp;C -&nbsp;Encapsulated adrenal cortical tissue;&nbsp;D -&nbsp;Immunohistochemical positivity for Melan-A.:&nbsp;Microscopical examination diagnosed a pure testicular seminoma infiltrating the albuginea and the visceral part of the tunica vaginalis (pT2). Histology showed a well-encapsulated nodule between the epididymis head and the rete testis (Figure 1B). The nodule was composed of epithelial cells arranged into an organoid pattern consistent with the adrenal cortex (Figure 1C). No adrenal medullary tissue was present. The cells were immunohistochemically positive for Melan-A monoclonal antibody (clone A103) (Figure 1D). No immunostaining was observed for inhibin α (clone R1), calretinin (clone DAK-Calret 1), and BCL2 oncoprotein (clone 124)

Motor, epileptic, and developmental phenotypes in genetic disorders affecting G protein coupled receptors-cAMP signaling

Over the last years, a constantly increasing number of genetic diseases associated with epilepsy and movement disorders have been recognized. An emerging group of conditions in this field is represented by genetic disorders affecting G-protein-coupled receptors (GPCRs)-cAMP signaling. This group of postsynaptic disorders includes genes encoding for proteins highly expressed in the central nervous system and involved in GPCR signal transduction and cAMP production (e.g., GNAO1, GNB1, ADCY5, GNAL, PDE2A, PDE10A, and HPCA genes). While the clinical phenotype associated with ADCY5 and GNAL is characterized by movement disorder in the absence of epilepsy, GNAO1, GNB1, PDE2A, PDE10A, and HPCA have a broader clinical phenotype, encompassing movement disorder, epilepsy, and neurodevelopmental disorders. We aimed to provide a comprehensive phenotypical characterization of genetic disorders affecting the cAMP signaling pathway, presenting with both movement disorders and epilepsy. Thus, we reviewed clinical features and genetic data of 203 patients from the literature with GNAO1, GNB1, PDE2A, PDE10A, and HPCA deficiencies. Furthermore, we delineated genotype-phenotype correlation in GNAO1 and GNB1 deficiency. This group of disorders presents with a highly recognizable clinical phenotype combining distinctive motor, epileptic, and neurodevelopmental features. A severe hyperkinetic movement disorder with potential life-threatening exacerbations and high susceptibility to a wide range of triggers is the clinical signature of the whole group of disorders. The existence of a distinctive clinical phenotype prompting diagnostic suspicion and early detection has relevant implications for clinical and therapeutic management. Studies are ongoing to clarify the pathophysiology of these rare postsynaptic disorders and start to design disease-specific treatments

Hypergraphx: a library for higher-order network analysis

From social to biological systems, many real-world systems are characterized by higher-order, non-dyadic interactions. Such systems are conveniently described by hypergraphs, where hyperedges encode interactions among an arbitrary number of units. Here, we present an open-source python library, hypergraphx (HGX), providing a comprehensive collection of algorithms and functions for the analysis of higher-order networks. These include different ways to convert data across distinct higher-order representations, a large variety of measures of higher-order organization at the local and the mesoscale, statistical filters to sparsify higher-order data, a wide array of static and dynamic generative models, and an implementation of different dynamical processes with higher-order interactions. Our computational framework is general, and allows to analyse hypergraphs with weighted, directed, signed, temporal and multiplex group interactions. We provide visual insights on higher-order data through a variety of different visualization tools. We accompany our code with an extended higher-order data repository, and demonstrate the ability of HGX to analyse real-world systems through a systematic analysis of a social network with higher-order interactions. The library is conceived as an evolving, community-based effort, which will further extend its functionalities over the years. Our software is available at https://github.com/HGX-Team/hypergraph

Artificial neural networks allow the use of simultaneous measurements of Alzheimer Disease markers for early detection of the disease

BACKGROUND: Previous studies have shown that in platelets of mild Alzheimer Disease (AD) patients there are alterations of specific APP forms, paralleled by alteration in expression level of both ADAM 10 and BACE when compared to control subjects. Due to the poor linear relation among each key-element of beta-amyloid cascade and the target diagnosis, the use of systems able to afford non linear tasks, like artificial neural networks (ANNs), should allow a better discriminating capacity in comparison with classical statistics. OBJECTIVE: To evaluate the accuracy of ANNs in AD diagnosis. METHODS: 37 mild-AD patients and 25 control subjects were enrolled, and APP, ADM10 and BACE measures were performed. Fifteen different models of feed-forward and complex-recurrent ANNs (provided by Semeion Research Centre), based on different learning laws (back propagation, sine-net, bi-modal) were compared with the linear discriminant analysis (LDA). RESULTS: The best ANN model correctly identified mild AD patients in the 94% of cases and the control subjects in the 92%. The corresponding diagnostic performance obtained with LDA was 90% and 73%. CONCLUSION: This preliminary study suggests that the processing of biochemical tests related to beta-amyloid cascade with ANNs allows a very good discrimination of AD in early stages, higher than that obtainable with classical statistics methods

Inflammation, underweight, malignancy and a marked catabolic state as predictors for worse outcomes in COVID-19 patients with moderate-to-severe disease admitted to Internal Medicine Unit

Introduction: During COVID-19 pandemic, Internal Medicine Units (IMUs) accounted for about 70% of patients hospitalized. Although a large body of data has been published regarding the so-called first wave of the pandemic, little is known about the characteristics and predictors of worse outcomes of patients managed in IMUs during the second wave. Methods: We prospectively assessed demographics, comorbidities, treatment and outcomes, including ventilation support (VS) and death, in patients admitted to our IMU for SARS-CoV-2 between October 13th, 2020 and January 21st, 2021. Clinical evolution and biochemical testing 1, 7 and 14 days after COVID-19 diagnosis were recorded. Results: We studied 120 patients (M/F 56/64, age 71±14.5 years) admitted to our IMU. Most of them had at least one comorbidity (80%). Patients who died were older, more frequently underweight, affected by malignant neoplasms and on statin therapy compared to patients eventually discharged. Both worse outcome groups (VS and death) presented higher neutrophils, ferritin, IL-6 and lower total proteins levels than controls. Age was significantly associated with mortality but not with VS need. The multivariate analysis showed age and gender independent association of mortality with underweight, malignancy and antibiotics use at the admission. With regard to biochemical parameters, both unfavourable outcomes were positively associated with high WBC count, neutrophils, blood urea nitrogen and low serum total proteins. Conclusions: Our study identified inflammation, underweight, malignancy and a marked catabolic state as the main predictors for worse outcomes in COVID-19 patients admitted to IMU during the so-called second wave of the pandemic