Recovery from repeated sudden hearing loss in a patient with Takayasu’s arteritis treated with hyperbaric oxygen therapy: the first report in the literature

Hearing loss has been rarely reported in Takayasu's arteritis, presents as sudden sensorineural hearing loss and usually responds well to corticosteroid therapy. Hyperbaric Oxygen Therapy is commonly used as a supplementary treatment to corticosteroids for sudden hearing loss. We present the case of a woman with Takayasu's arteritis who had two episodes of hearing loss involving one ear at a time with a 11-month delay between each episode. During the first episode, the patient was treated with high-dose intramuscular corticosteroids with a temporary improvement of auditory threshold, that deteriorated close to previous level 14 days after cessation of therapy. In the second episode, Hyperbaric Oxygen Therapy was associated to corticosteroids, with a significant, longer term improvement in both ears, including the one that had shown to be unresponsive to previous pharmacologic therapy. Oxygen therapy could have played a role in hearing restoration in this patient, as it could have acted synergically with corticosteroids amplifying their effect

Sensitivity-Based Model of Low Voltage Distribution Systems with Distributed Energy Resources

A key issue in Low Voltage(LV) distribution systems is to identify strategies for the optimal management and control in the presence of Distributed Energy Resources (DERs). To reduce the number of variables to be monitored and controlled, virtual levels of aggregation, called Virtual Microgrids (VMs), are introduced and identified by using new models of the distribution system. To this aim, this paper, revisiting and improving the approach outlined in a conference paper, presents a sensitivity-based model of an LV distribution system, supplied by a Medium/Low Voltage (MV/LV) substation and composed by several feeders, which is suitable for the optimal management and control of the grid and for VM definition. The main features of the proposed method are: it evaluates the sensitivity coefficients in a closed form; it provides an overview of the sensitivity of the network to the variations of each DER connected to the grid; and it presents a limited computational burden. A comparison of the proposed method with both the exact load flow solutions and a perturb-and-observe method is discussed in a case study. Finally, the method is used to evaluate the impact of the DERs on the nodal voltages of the network

Nuclear Inositides and Inositide-Dependent Signaling Pathways in Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies characterized by peripheral blood cytopenia and abnormal myeloproliferation, as well as a variable risk of evolution into acute myeloid leukemia (AML). The nucleus is a highly organized organelle with several distinct domains where nuclear inositides localize to mediate essential cellular events. Nuclear inositides play a critical role in the modulation of erythropoiesis or myelopoiesis. Here, we briefly review the nuclear structure, the localization of inositides and their metabolic enzymes in subnuclear compartments, and the molecular aspects of nuclear inositides in MDS

Compartmental tongue surgery for intermediate-advanced squamous cell carcinoma: A multicentric study

Background: A multicentric study was conducted on technical reproducibility of compartmental tongue surgery (CTS) in advanced tongue cancers (OTSCC) and comparison to standard wide margin surgery (SWMS). Methods: We studied 551 patients with OTSCC treated by CTS and 50 by SWMS. Oncological outcomes were analyzed. A propensity score was performed to compare survival endpoints for the two cohorts. Results: In the CTS group, survival and prognosis were significantly associated with positive lymph-nodes, extranodal extension, depth of invasion and involvement of the soft tissue connecting the tongue primary tumor to neck lymph nodes (T-N tract), independently from the center performing the surgery. SWMS versus CTS showed a HR Cause-Specific Survival (CSS) of 3.24 (95% CI: 1.71-6.11; p < 0.001); HR Loco-Regional Recurrence Free Survival (LRRFS) of 2.54 (95% CI: 1.47-4.40; p < 0.001); HR Overall Survival (OS) of 0.11 (95% CI: 0.01-0.77; p = 0.03). Conclusion: Performing the CTS could provide better CSS and LRRFS than SWMS regardless of the center performing the surgery, in advanced OTSSC

A Spitzer Transmission Spectrum for the Exoplanet GJ 436b, Evidence for Stellar Variability, and Constraints on Dayside Flux Variations

In this paper we describe a uniform analysis of eight transits and eleven secondary eclipses of the extrasolar planet GJ 436b obtained in the 3.6, 4.5, and 8.0 micron bands using the IRAC instrument on the Spitzer Space Telescope between UT 2007 June 29 and UT 2009 Feb 4. We find that the best-fit transit depths for visits in the same bandpass can vary by as much as 8% of the total (4.7 sigma significance) from one epoch to the next. Although we cannot entirely rule out residual detector effects or a time-varying, high-altitude cloud layer in the planet's atmosphere as the cause of these variations, we consider the occultation of active regions on the star in a subset of the transit observations to be the most likely explanation. We reconcile the presence of magnetically active regions with the lack of significant visible or infrared flux variations from the star by proposing that the star's spin axis is tilted with respect to our line of sight, and that the planet's orbit is therefore likely to be misaligned. These observations serve to illustrate the challenges associated with transmission spectroscopy of planets orbiting late-type stars; we expect that other systems, such as GJ 1214, may display comparably variable transit depths. Our measured 8 micron secondary eclipse depths are consistent with a constant value, and we place a 1 sigma upper limit of 17% on changes in the planet's dayside flux in this band. Averaging over the eleven visits gives us an improved estimate of 0.0452% +/- 0.0027% for the secondary eclipse depth. We combine timing information from our observations with previously published data to produce a refined orbital ephemeris, and determine that the best-fit transit and eclipse times are consistent with a constant orbital period. [ABRIDGED]Comment: 26 pages, 18 figures, 7 tables in emulateapj format. Accepted for publication in Ap

Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development

Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. Previous attempts to identify unique pathogenic mechanisms behind such differences were unsuccessful, and no studies have investigated the differentiation stage of tumor PCs in patients with AL and MM. We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). Based on bulk and single-cell RNA sequencing, we observed 13 TPs during transition of normal PCs throughout SLOs, PB, and BM. We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation–related TPs are upregulated in AL. Collectively, we provide a novel resource to understand normal PC development and the transcriptional reorganization of AL and other monoclonal gammopathies

Epidemiology of gastroenteropancreatic neuroendocrine neoplasms: a review and protocol presentation for bridging tumor registry data with the Italian association for neuroendocrine tumors (Itanet) national database

: Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care. STUDY REGISTRATION: This protocol was registered in clinicaltriasl.gov (NCT04282083)

Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group. Results SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

Multi-Organ Expression Profiling Uncovers a Gene Module in Coronary Artery Disease Involving Transendothelial Migration of Leukocytes and LIM Domain Binding 2: The Stockholm Atherosclerosis Gene Expression (STAGE) Study

Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n = 66/tissue) and atherosclerotic and unaffected arterial wall (n = 40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n = 15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n = 3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n = 49/48) and one visceral fat (n = 59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P = 0.008 and P = 0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n = 55/54) relating to carotid stenosis (P = 0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n = 16/17, P<10−27and−30). Genes in the transendothelial migration of leukocytes (TEML) pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module). In a second validation step, using three independent cohorts, the A-module was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004). The transcription co-factor LIM domain binding 2 (LDB2) was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, by cellular and lesion expression of LDB2, and by the expression of 13 TEML genes in Ldb2–deficient arterial wall. Thus, the A-module appears to be important for atherosclerosis development and, together with LDB2, merits further attention in CAD research

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time. Methods: The STAR Network \u201cDepot Study\u201d was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS &lt; 41 or BPRS 65 41). Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions\u2014conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently\u2014showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline. Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders