Topological cascade laser for frequency comb generation in PT\mathcal{PT}-symmetric structures

The cascade of resonant topological structures with $\mathcal{PT}$-symmetry breaking is shown to emit laser light with a frequency-comb spectrum. We consider optically active topological Aubry-Andr\'e-Harper lattices supporting edge-modes at regularly spaced frequencies. When the amplified resonances in the $\mathcal{PT}$-broken regime match the edge modes of the topological gratings, we predict the emission of discrete laser lines. A proper design enables to engineer the spectral features for specific applications. The robustness of the topological protection makes the system very well suited for a novel generation of compact frequency comb emitters for spectroscopy, metrology, and quantum information.Comment: 6 pages, 6 figure

Topological lasing and self-induced transparency in two level systems

The use of virtually lossless topologically isolated edge states may lead to a novel class of thresholdless lasers operating without inversion. One needs however to understand if topological states may be coupled to external radiation and act as active cavities. We study a two-level topological insulator and show that self-induced transparency pulses can directly excite edge states. We simulate laser emission by a suitable designed topological cavity, and show that it can emit tunable radiation. For a configuration of sites following the off-diagonal Aubry-Andre-Harper model we solve the Maxwell-Bloch equations in the time domain and provide a first principle confirmation of topological lasers. Our results open the road to a new class of light emitters with topological protection for applications ranging from low-cost energetically-effective integrated lasers sources, also including silicon photonics, to strong coupling devices for studying ultrafast quantum processes with engineered vacuum

Risk factors associated with the occurrence of autoimmune diseases in adult coeliac patients

Objectives. Autoimmune diseases (AD) may be associated with coeliac disease (CD), but specific risk factors have been poorly investigated. The aim of this study was to assess the spectrum of AD and its specific risk factors associated in a series of adult coeliac patients. Materials and Methods. We performed a single-center case-control study including adult newly diagnosed CD patients. To evaluate the risk factors of the association between AD and CD, 341 coeliac patients included were categorized on the basis of AD presence: 91 cases with at least one AD and 250 controls without AD were compared for clinical, serological, and histological features. Eighty-seven cases were age-gender-matched with 87 controls. Results. Among 341 CD patients, 26.6% of CD patients had at least one AD. Endocrine and dermatological diseases were the most prevalent AD encountered: autoimmune thyroiditis was present in 48.4% of cases, psoriasis in 17.6%, and type I diabetes and dermatitis herpetiformis in 11%, respectively. At logistic regression, factors associated with AD were a positive 1st-degree family history of AD (OR 3.7, 95% CI 1.93–7), a body mass index ≥ 25 kg/m2 at CD diagnosis (OR 2.95%, CI 1.1–3.8), and long standing presentation signs/symptoms before CD diagnosis (>10 years) (OR 2.1, 95% CI 1.1–3.7). Analysis on age-gender-matched patients confirmed these results. Conclusions. CD patients with family history of AD, overweight at CD diagnosis, and a delay of CD diagnosis had an increased risk of having another AD. The benefit of CD screening in these specific subsets of patients with AD awaits further investigation

Cognitive dysfunction improves in systemic lupus erythematosus: Results of a 10 years prospective study

Objective Cognitive impairment (CI) has been described in 3–80% of Systemic lupus erythematosus (SLE) patients but only short-term studies evaluated its over-time changes, suggesting that CI is usually a stable finding. We aimed at evaluating the changes of SLE-related CI in a 10-years prospective single center cohort study. Methods We evaluated 43 patients (M/F 5/38; mean age = 45.7±10.1 years; mean disease duration = 230.8±74.3 months) at baseline (T0) and after 10 years (T1). A test battery designed to detect fronto-subcortical dysfunction across five domains (memory, attention, abstract reasoning, executive and visuospatial function) was administered. A global cognitive dysfunction score (GCD) was obtained and associated with clinical and laboratory features. Results Prevalence of CI was 20.9% at T0 and 13.9% at T1 (P = NS). This impairment was prevalently mild at T0 (55.5%) and mild or moderate at T1 (36.3% for both degrees). After 10 years, CI improved in 50% of patients, while 10% worsened. Impaired memory (P = 0.02), executive functions (P = 0.02) and abstract reasoning (P = 0.03) were associated with dyslipidemia at T0. Worsening of visuospatial functions was significantly associated with dyslipidemia and Lupus Anticoagulant (P = 0.04 for both parameters). Finally, GCD significantly correlated with chronic damage measured by SLICC/damage index at T0 (r = 0.3; P = 0.04) and T1 (r = 0.3; P = 0.03). Conclusions For the first time, we assessed CI changes over 10-years in SLE. CI improved in the majority of the patients. Furthermore, we observed an improvement of the overall cognitive functions. These results could suggest that an appropriate management of the disease during the follow-up could be able to control SLE-related CI

Systemic Lupus Erythematosus with and without Anti-dsDNA Antibodies: Analysis from a Large Monocentric Cohort

Objectives. The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70–98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the antidsDNA status. Methods. We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA − (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM). Results. We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA −: 24.4%). The renal involvement was signifiantly more frequent in anti-dsDNA + (30.2%), compared with antidsDNA ± and anti-dsDNA − (21.1% and 18.7%, resp.; = 0.001). Serositis resulted signifiantly more frequent in anti-dsDNA − (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.; < 0.0001). Th reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with antidsDNA − (21.8%, = 0.005). We did not identify significant differences in the mean ECLAM values before and after modifiation of anti-dsDNA status ( = 0.7). Conclusion. Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity

Low expression of estrogen receptor β in T lymphocytes and high serum levels of anti-estrogen receptor α antibodies impact disease activity in female patients with systemic lupus erythematosus

BACKGROUND: Current evidence indicates that estrogens, in particular 17β-estradiol (E2), play a crucial role in the gender bias of autoimmune diseases although the underlying molecular mechanisms have not yet been fully elucidated. Immune cells have estrogen receptors (ERs), i.e., ERα and ERβ, that play pro- and anti-inflammatory functions, respectively, and the presence of one estrogen receptor (ER) subtype over the other might change estrogen effects, promoting or dampening inflammation. In this study, we contributed to define the influences of E2 on T cells from female patients with systemic lupus erythematosus (SLE), a representative autoimmune disease characterized by a higher prevalence in women than in men (female/male ratio 9:1). Particularly, our aim was to evaluate whether alterations of ERα and ERβ expression in T cells from female SLE patients may impact lymphocyte sensitivity to E2 and anti-ERα antibody (anti-ERα Ab) stimulation interfering with cell signaling and display a direct clinical effect. METHODS: Sixty-one premenopausal female patients with SLE and 40 age-matched healthy donors were recruited. Patients were divided into two groups based on the SLE Disease Activity Index 2000 (SLEDAI-2K) (i.e., <6 and ≥6). ER expression was evaluated in T lymphocytes by flow cytometry, immunofluorescence, and Western blot analyses. Serum anti-ERα Ab levels were analyzed by enzyme-linked immunosorbent assay (ELISA). ER-dependent signaling pathways were measured by a phosphoprotein detection kit. RESULTS: Intracellular ERβ expression was significantly lower in T cells from patients with SLEDAI-2K ≥6 as compared with healthy donors and patients with SLEDAI-2K <6 and negatively correlated with disease activity. The expression of intracellular and membrane-associated-ERα was similar in SLE and control T cells. ER-dependent signaling pathways were activated in T cells from SLE patients with SLEDAI-2K ≥6, but not with SLEDAI-2K <6, when both membrane and intracellular ERs were stimulated by co-treatment with E2 and anti-ERα Abs. CONCLUSIONS: Our results demonstrate an altered ER profile in SLE patients, possibly contributing to SLE pathogenesis and interfering with clinical activity, and highlight the potential exploitation of T cell-associated ERβ as a biomarker of disease activity

Metacognition as a predictor of improvements in personality disorders

Personality Disorders (PDs) are particularly hard to treat and treatment drop-out rates are high. Several authors have agreed that psychotherapy is more successful when it focuses on the core of personality pathology. For this reason, therapists dealing with PDs need to understand the psychopathological variables that characterize this pathology and exactly what contributes to maintaining psychopathological processes. Moreover, several authors have noted that one key problem that characterizes all PDs is an impairment in understanding mental states - here termed metacognition - which could also be responsible for therapy failures. Unfortunately, a limited number of studies have investigated the role of mentalization in the process of change during psychotherapy. In this paper, we assume that poor metacognition corresponds to a core element of the general pathology of personality, impacts a series of clinical variables, generates symptoms and interpersonal problems, and causes treatment to be slower and less effective. We explored whether changes in metacognition predicted an improvement among different psychopathological variables characterizing PDs; 193 outpatients were treated at the Third Center of Cognitive Psychotherapy in Rome, Italy, and followed a structured path tailored for the different psychopathological variables that emerged from a comprehensive psychodiagnostic assessment that considered patients' symptoms, metacognitive abilities, interpersonal relationships, personality psychopathology, and global functioning. The measurements were repeated after a year of treatment. The results showed that changes in metacognitive abilities predicted improvements in the analyzed variable

TDP-43 affects splicing profiles and isoform production of genes involved in the apoptotic and mitotic cellular pathways

In recent times, high-throughput screening analyses have broadly defined the RNA cellular targets of TDP-43, a nuclear factor involved in neurodegeneration. A common outcome of all these studies is that changing the expression levels of this protein can alter the expression of several hundred RNAs within cells. What still remains to be clarified is which changes represent direct cellular targets of TDP-43 or just secondary variations due to the general role played by this protein in RNA metabolism. Using an HTS-based splicing junction analysis we identified at least six bona fide splicing events that are consistent with being controlled by TDP-43. Validation of the data, both in neuronal and non-neuronal cell lines demonstrated that TDP-43 substantially alters the levels of isoform expression in four genes potentially important for neuropathology: MADD/IG20, STAG2, FNIP1 and BRD8. For MADD/IG20 and STAG2, these changes could also be confirmed at the protein level. These alterations were also observed in a cellular model that successfully mimics TDP-43 loss of function effects following its aggregation. Most importantly, our study demonstrates that cell cycle alterations induced by TDP-43 knockdown can be recovered by restoring the STAG2, an important component of the cohesin complex, normal splicing profile

Impaired Ethanol-Induced Sensitization and Decreased Cannabinoid Receptor-1 in a Model of Posttraumatic Stress Disorder

Background and Purpose Impaired striatal neuroplasticity may underlie increased alcoholism documented in those with posttraumatic stress disorder (PTSD). Cannabinoid receptor-1 (CB1) is sensitive to the effects of ethanol (EtOH) and traumatic stress, and is a critical regulator of striatal plasticity. To investigate CB1 involvement in the PTSD-alcohol interaction, this study measured the effects of traumatic stress using a model of PTSD, mouse single-prolonged stress (mSPS), on EtOH-induced locomotor sensitization and striatal CB1 levels. Methods Mice were exposed to mSPS, which includes: 2-h restraint, 10-min group forced swim, 15-min exposure to rat bedding odor, and diethyl ether exposure until unconsciousness or control conditions. Seven days following mSPS exposure, the locomotor sensitizing effects of EtOH were assessed. CB1, post-synaptic density-95 (PSD95), and dopamine-2 receptor (D2) protein levels were then quantified in the dorsal striatum using standard immunoblotting techniques. Results Mice exposed to mSPS-EtOH demonstrated impaired EtOH-induced locomotor sensitization compared to Control-EtOH mice, which was accompanied by reduced striatal CB1 levels. EtOH increased striatal PSD95 in control and mSPS-exposed mice. Additionally, mSPS-Saline exposure increased striatal PSD95 and decreased D2 protein expression, with mSPS-EtOH exposure alleviating these changes. Conclusions These data indicate that the mSPS model of PTSD blunts the behavioral sensitizing effects of EtOH, a response that suggests impaired striatal neuroplasticity. Additionally, this study demonstrates that mice exposed to mSPS and repeated EtOH exposure decreases CB1 in the striatum, providing a mechanism of interest for understanding the effects of EtOH following severe, multimodal stress exposure