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BACKGROUND: Patients hospitalized for COVID-19 are at high risk of thrombotic complications and organ failure, and often exhibit severe inflammation, which may contribute to hypercoagulability. OBJECTIVES: To determine whether patients hospitalized for COVID-19 experience differing frequencies of thrombotic and organ failure complications and derive variable benefits from therapeutic-dose heparin dependent on the extent of systemic inflammation and whether observed benefit from therapeutic-dose anticoagulation varies depending on the degree of systemic inflammation. METHODS: We analyzed data from 1346 patients hospitalized for COVID-19 enrolled in the ATTACC and ACTIV-4a platforms who were randomized to therapeutic-dose heparin or usual care for whom levels of C-reactive protein (CRP) were reported at baseline. RESULTS: Increased CRP was associated with worse patient outcomes, including a >98% posterior probability of increased organ support requirement, hospital length of stay, risk of 28-day mortality, and incidence of major thrombotic events or death (patients with CRP 40-100 mg/L or ≥100 mg/L compared to patients with CRP

BACKGROUND: Acute kidney injury (AKI) in patients with COVID-19 is partly mediated by thromboinflammation. In noncritically ill patients with COVID-19, therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support. OBJECTIVES: We investigated whether therapeutic-dose heparin reduces the incidence of AKI or death in noncritically ill patients hospitalized for COVID-19. METHODS: We report a prespecified secondary analysis of the ACTIV4a and ATTACC open-label, multiplatform randomized trial of therapeutic-dose heparin vs usual-care pharmacologic thromboprophylaxis on the incidence of severe AKI (≥2-fold increase in serum creatinine or initiation of kidney replacement therapy (KDIGO stage 2 or 3) or all-cause mortality in noncritically ill patients hospitalized for COVID-19. Bayesian statistical models were adjusted for age, sex, D-dimer, enrollment period, country, site, and platform. RESULTS: Among 1922 enrolled, 23 were excluded due to pre-existing end stage kidney disease and 205 were missing baseline or follow-up creatinine measurements. Severe AKI or death occurred in 4.4% participants assigned to therapeutic-dose heparin and 5.5% assigned to thromboprophylaxis (adjusted relative risk [aRR]: 0.72; 95% credible interval (CrI): 0.47, 1.10); the posterior probability of superiority for therapeutic-dose heparin (relative risk < 1.0) was 93.6%. Therapeutic-dose heparin was associated with a 97.7% probability of superiority to reduce the composite of stage 3 AKI or death (3.1% vs 4.6%; aRR: 0.64; 95% CrI: 0.40, 0.99) compared to thromboprophylaxis. CONCLUSION: Therapeutic-dose heparin was associated with a high probability of superiority to reduce the incidence of in-hospital severe AKI or death in patients hospitalized for COVID-19.

Posterior semicircular canal dehiscence (PSCD) has been demonstrated to result in a third mobile window mechanism (TMWM) in the inner ear similar to superior semicircular canal dehiscence (SSCD). Typical clinical and instrumental features of TMWM, including low-frequency conductive hearing loss (CHL), autophony, pulsatile tinnitus, sound/pressure-induced vertigo and enhanced vestibular-evoked myogenic potentials, have been widely described in cases with PSCD. Nevertheless, video-head impulse test (vHIT) results have been poorly investigated. Here, we present six patients with PSCD presenting with a clinical scenario consistent with a TMWM and an impaired vestibulo-ocular reflex (VOR) for the affected canal on vHIT. In two cases, an additional dehiscence between the facial nerve and the horizontal semicircular canal (HSC) was detected, leading to a concurrent VOR impairment for the HSC. While in SSCD, a VOR gain reduction could be ascribed to a spontaneous “auto-plugging” process due to a dural prolapse into the canal, the same pathomechanism is difficult to conceive in PSCD due to a different anatomical position, making a dural herniation less likely. Alternative putative pathomechanisms are discussed, including an endolymphatic flow dissipation during head impulses as already hypothesized in SSCD. The association of symptoms/signs consistent with TMWM and a reduced VOR gain for the posterior canal might address the diagnosis toward PSCD.

Abstract The decarbonization of the power generation and transport sector encourage the analysis of connection of distributed energy resources (DER), such as electric vehicles (EVs), to the electrical system, as well as the evaluation of their impact on smart cities. A better understanding of the negative impacts on the power systems will lead to propose mitigation measures and eventually revolutionize the way distributed generation works. This paper aims at modelling and evaluating the impact of EVs on a real distribution network. The energy system chosen operates at 60 Hz, 34.5 kV (medium voltage) and 0.208 kV (low voltage) and it is simulated using PSCAD/EMTDC. To reproduce realistic user consumption profiles, dynamic load profiles based on EV owners behaviour have been simulated. The vehicle‐to‐grid (V2G) technology is modelled to mitigate the impacts of high penetration of EVs by supporting the network from undervoltage. The results show the importance of active management in modern power systems, especially considering the increase in DER penetration expected for the coming years. This work shows the benefits of implementing V2G technology while highlighting the challenges involved in a real case.

Aims: Maternally inherited diabetes and deafness (MIDD) is a complex disorder characterized by multiorgan clinical manifestations, including diabetes, hearing loss, and ophthalmic complications. This pilot study aimed to elucidate the intricate interplay between nuclear and mitochondrial genetics, epigenetic modifications, and their potential implications in the pathogenesis of MIDD. Main methods: A comprehensive genomic approach was employed to analyze a Sicilian family affected by clinically characterized MIDD, negative to the only known causative m.3243 A > G variant, integrating whole-exome sequencing and whole-genome bisulfite sequencing of both nuclear and mitochondrial analyses. Key findings: Rare and deleterious variants were identified across multiple nuclear genes involved in retinal homeostasis, mitochondrial function, and epigenetic regulation, while complementary mitochondrial DNA analysis revealed a rich tapestry of genetic diversity across genes encoding components of the electron transport chain and ATP synthesis machinery. Epigenetic analyses uncovered significant differentially methylated regions across the genome and within the mitochondrial genome, suggesting a nuanced landscape of epigenetic modulation. Significance: The integration of genetic and epigenetic data highlighted the potential crosstalk between nuclear and mitochondrial regulation, with specific mtDNA variants influencing methylation patterns and potentially impacting the expression and regulation of mitochondrial genes. This pilot study provides valuable insights into the complex molecular mechanisms underlying MIDD, emphasizing the interplay between nucleus and mitochondrion, tracing the way for future research into targeted therapeutic interventions and personalized approaches for disease management.

The treatment of patients with rheumatoid arthritis (RA) has dramatically changed in the past 30 years. Currently, numerous conventional, biologic, and targeted synthetic DMARDs have been licensed and used following recommendations provided by international and national scientific societies. However, the availability of biosimilars and the increasing necessity of savings impacted on the local/national prescription of these drugs. The information provided by data sheet of every single drug is a decisive factor on the choice of a certain treatment merged with the patient’s profile. Thus, our purpose was to construct a rational algorithm for the treatment strategy in RA according to costs and the product leaflet of the biologic and targeted-synthetic DMARDs currently licensed in Italy. We used the most recent available recommendations and then we performed a review of the literature considering all the factors that are known to influence drug safety/effectiveness. All these factors were considered in the context of the data sheets of currently available originators and biosimilars.

Introduction Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) increases the risk of pulmonary embolism (PE). AECOPD and PE have similar symptoms which results in a high proportion of patients with AECOPD undergoing imaging to rule out PE. Finding predictors and explanatory factors of PE in AECOPD, such as purulence status, could help reduce the need for imaging. This systematic review with meta-analysis aims to evaluate if there is an association between purulence status in AECOPD and PE diagnosis.Methods and analysis MEDLINE, EMBASE and CENTRAL will be searched from database inception to April 2024. Randomised trials, cohort studies and cross-sectional studies on the prevalence of PE in patients with AECOPD will be included if the prevalence of PE based on the AECOPD purulence status is available. There will be no restriction on language. The primary outcome will be PE at the initial assessment and secondary outcomes will be all venous thromboembolism (deep venous thrombosis (DVT) and PE) and DVT, respectively, diagnosed at the initial assessment. Relative risks with their 95% CI will be calculated by using a Mantel-Haenszel random-effect model to compare the association between the risk of PE and the AECOPD purulence status (purulent vs non-purulent/unknown). Subgroup analyses will be performed based on the type of study, systematic search of PE versus no systematic search of PE and localisation of PE. Risk of bias will be evaluated by the ROBINS-E tool, publication bias will be evaluated with the funnel plot. The manuscript will be drafted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement.Ethics and dissemination This study does not require ethics approval. This work will be submitted for presentation at an international conference and for publication in a peer-reviewed journal.PROSPERO registration number CRD42023459429.

The third window syndrome, often associated with the Tullio phenomenon, is currently most often observed in patients with a superior semicircular-canal dehiscence (SCD) but is not specific to this pathology. Clinical and vestibular tests suggestive of this pathology are not always concomitantly observed and have been recently complemented by the skull-vibration-induced nystagmus test, which constitutes a bone-conducted Tullio phenomenon (BCTP). The aim of this work was to collect from the literature the insights given by this bedside test performed with bone-conducted stimulations in SCD. The PRISMA guidelines were used, and 10 publications were included and analyzed. Skull vibration-induced nystagmus (SVIN), as observed in 55 to 100% of SCD patients, usually signals SCD with greater sensitivity than the air-conducted Tullio phenomenon (ACTP) or the Hennebert sign. The SVIN direction when the test is performed on the vertex location at 100 Hz is most often ipsilaterally beating in 82% of cases for the horizontal and torsional components and down-beating for the vertical component. Vertex stimulations are more efficient than mastoid stimulations at 100 Hz but are equivalent at higher frequencies. SVIN efficiency may depend on stimulus location, order, and duration. In SCD, SVIN frequency sensitivity is extended toward high frequencies, with around 400 Hz being optimal. SVIN direction may depend in 25% on stimulus frequency and in 50% on stimulus location. Mastoid stimulations show frequently diverging results following the side of stimulation. An after-nystagmus observed in 25% of cases can be interpreted in light of recent physiological data showing two modes of activation: (1) cycle-by-cycle phase-locked activation of action potentials in SCC afferents with irregular resting discharge; (2) cupula deflection by fluid streaming caused by the travelling waves of fluid displacement initiated by sound or vibration at the point of the dehiscence. The SVIN direction and intensity may result from these two mechanisms’ competition. This instability explains the SVIN variability following stimulus location and frequency observed in some patients but also discrepancies between investigators. SVIN is a recent useful insight among other bedside examination tests for the diagnosis of SCD in clinical practice.

In the management of symptomatic inoperable retroperitoneal sarcomas (RPS), palliative radiotherapy (RT) is a potential treatment option. However, the efficacy of low doses used in palliative RT is limited in these radioresistant tumors. Therefore, exploring dose escalation strategies targeting specific regions of the tumor may enhance the therapeutic effect of RT in relieving or preventing symptoms.In this case report, we present the case of an 87-year-old patient with rapidly growing undifferentiated liposarcoma in the retroperitoneum, where surgical and systemic therapies were ruled out due to age and comorbidities. RT was administered using volumetric modulated arc therapy, delivering 20 Gy in 4 fractions twice daily to the macroscopic tumor and 40 Gy in 4 fractions twice daily (simultaneous integrated boost) to the central part of the tumor (Gross Tumor Volume minus 2 cm). An 18F−FDG-PET-CT scan performed after RT demonstrated a complete metabolic response throughout the entire tumor mass. Although the patient eventually succumbed to metastatic spread to the bone, liver, and lung after 9 months, no local disease progression or pain/obstructive symptoms were observed.This case highlights the technical and clinical feasibility of delivering ablative doses of RT to the central region of the tumor and suggests the potential for achieving a complete metabolic response and durable tumor control.

Background and Objectives: This study aimed to compare the effects and safety of boldine combined with Phyllanthus niruri and Ononis spinosa plus tamsulosin vs. tamsulosin alone in medical expulsive therapy (MET) for distal ureteral calculi. Materials and Methods: This retrospective cohort study was conducted on 159 renal colic patients with distal ureteric stones (≤10 mm). Patients aged between 18 and 70 years or older with distal ureteral (below the sacroiliac joint) stones ≤10 mm (defined by the largest diameter in three planes) confirmed by urinary ultrasonography and/or native computed tomography (CT). Patients were divided into two groups: A and B. Patients in Group A received tamsulosin 0.4 mg plus boldine combined with Phyllanthus niruri and Ononis spinosa, while those in Group B received tamsulosin 0.4 mg. The rate of stone expulsion, duration of stone expulsion, the dose and the duration of nonsteroidal anti-inflammatory drugs (NSAIDs), analgesic use, and adverse effects of drugs were recorded. Results: No differences were reported in demographic profiles between the two groups. The stone expulsion rate in Group A (84.8%) was higher in comparison to Group B (52.5%); the mean time of stone expulsion was 16.33 ± 4.75 days in Group A and 19.33 ± 6.42 days in Group B. The mean requirement time of analgesia was significantly less in Group A, 2.42 ± 2.56, than in Group B, 6.25 ± 3.05. Drug-related adverse effects (headache, dizziness, nausea, vomiting, postural hypotension, backache, and running nose) were comparable between the two groups. Conclusions: Tamsulosin plus boldine combined with Phyllanthus niruri and Ononis spinosa as medical expulsion therapy is more effective for distal ureteric stones with less need for analgesics and a shorter stone expulsion time than tamsulosin alone.

Introduction Perceived workplace discrimination is a complex phenomenon involving unfair treatment in the workplace based on personal characteristics such as age, ethnicity, gender, or disability. The objective of this study is to explore the association of perceived workplace discrimination with health and occupational outcomes. Methods Following the PRISMA-ScR guidelines and the Joanna Briggs Institute methodology, a scoping review of articles published between 2000 and 2022 was conducted in databases such as Pubmed, Scopus, and PsyInfo. Inclusion criteria focused on studies exploring perceived workplace discrimination among workers, excluding those on patients, students, or the general population, and articles not written in English or Spanish. Results Of the 9,871 articles identified, 102 met the criteria and were analyzed. Research showed a progressive increase in the study of perceived workplace discrimination, with a majority of studies in North America and Europe and a predominance of cross-sectional designs. Most studies did not clearly define the concept of perceived workplace discrimination nor report the psychometric characteristics of the measurement instruments. A significant association was found between perceived discrimination and negative outcomes in workers' mental and physical health, as well as a negative impact on job satisfaction and an increase in absenteeism. Additionally, sociodemographic characteristics such as race/ethnicity, gender, and age influenced the perception of discrimination. Conclusions This review confirms that perceived workplace discrimination significantly impacts the health and job satisfaction of workers, with particular detriment in minorities and women. Despite an increase in research over the last two decades, there remains a lack of consistency in the definition and measurement of the phenomenon. Most studies have used cross-sectional designs, and there is a notable absence of research in the Latin American context.

IntroductionProstate-specific membrane antigen (PSMA) is a transmembrane protein expressed by normal prostatic tissue. Therefore, molecular imaging targeting PSMA (PSMA-PET) has gained particular interest and diffusion for PCa staging and restaging. Several factors may affect PSMA-PET results, and many tools have been proposed to improve patient selection. Furthermore, PSMA expression is not homogeneous among different tissues and within the prostate itself. The aims of this study were to evaluate immunohistochemistry (IHC) features of prostate biopsy samples and to assess their correlation with whole-mount specimens and PSMA-PET parameters.MethodsWe included consecutive high-risk PCa patients who underwent PSMA-PET for staging proposal at our institution from January 2022 to December 2022. The PET parameters selected were SUVmax, total volume (TV), and total lesion activity (TL). Each patient underwent multiparametric MRI (mpMRI) and fusion-targeted prostate biopsy prior to surgery. IHC analyses were performed on the index lesion cores. IHC visual score (VS) (1, 2, 3) and visual pattern (VP) (membranous, cytoplasmic, and combined) and the percentage of PSMA-negative tumor areas (PSMA%neg) within biopsy cores were evaluated.ResultsForty-three patients who underwent robotic radical prostatectomy after PSMA-PET were available for analyses. Concordance between VS and VP at biopsy and final pathology showed a Cohen’s kappa coefficient of 0.39 and 0.38, respectively. Patients with PSMA%neg 20% on biopsy cores in terms of SUVmax, PSMA-TL, and PSMA-TV (p = 0.5, p = 0.5, and p = 0.9 respectively).ConclusionsWe found a correlation between IHC VS and VP on targeted biopsy cores and SUVmax at PSMA-PET. However, the correlation between the IHC parameters of biopsy cores and final pathology was not as high as expected. Nevertheless, the presence of PSMA%neg

Twenty years after the Berlin Declaration on Open Access to Knowledge in the Sciences and Humanities (2003), it is necessary to analyze its influence, identify problems, and postulate urgent actions to be taken. If the values expressed by the Berlin Declaration have helped to shape the scientific landscape of the new millennium, there is a need to evaluate its application in initiatives undertaken at the international level. The “roads” taken by the Open Access are here highlighted, with particular attention to the role of institutional repositories, the involvement of libraries, and the need to promote Open Science. In Italy, the National Plan for Open Science (PNSA) guides the implementation of Open Science by focusing on open access, data management, and collaborations between institutions. Numerous initiatives such as ICDI, Skills4EOSC, CoPER, and projects such as Data Steward@Unibo, show the growing commitment to Open Science. Critical issues remain, however, regarding research evaluation, as the debate on Transformative Agreements also reveals. New skills and awareness are opening up for libraries in this regard: for the benefit of scholars, researchers, and every citizen.

A 73-year-old woman arrived at the ER claiming to be experiencing low back pain. To investigate the source of her pain, she was admitted to the Internal Medicine department. After a heterogeneous abdominal mass in the right upper quadrant was discovered by abdominal point-of-care ultrasonography (POCUS), it was confirmed by an abdominal CT scan, which also identified a metastatic lytic bone lesion in the L4. This finding is consistent with a malignant tumor of the right adrenal gland. POCUS was repeated right after the occurrence of dyspnea, and a 40x6 mm floating thrombus in the inferior vena cava was detected. A conservative approach with anticoagulants was chosen, with improvement of the clinical conditions. The diagnosis of adrenal carcinoma was ultimately made possible by the mass biopsy. POCUS is a safe, low-cost method that provides prompt results at the patient's bedside. We support the implementation of POCUS in all clinical departments, as it provides significant contributions to the assessment of prognosis and diagnosis.

A identidade corporal e a expressão da sexualidade na cultura ocidental são marcadas por tabus, devendo ser restritas à intimidade das “quatro paredes”. Entretanto, a experiência da intimidade é construída socialmente e carrega consigo todas as marcas de um tempo histórico, no qual os corpos estão inscritos. As mulheres prostitutas que desafiam os prescritivos morais da sexualidade atrelados à reprodução e ao matrimônio e que monetizam a experiência sexual, sofrem penalidades sociais, como a exclusão. O objetivo deste trabalho é refletir, a partir do filme Uma linda mulher, o modo como a identidade corporal das mulheres profissionais do sexo é significado socialmente, com base na literatura brasileira. A metodologia eleita é a análise de filme, por meio das categorias temáticas: objetificação do corpo feminino, invisibilização social do corpo feminino e adestramento corporal. As vestimentas, a composição estética de uma profissional do sexo pertencente a um contexto de classe baixa, como retratado no filme pela personagem Vivian, são alvo de um estereótipo de vulgaridade e a reduz a um objeto sexual. Essas mulheres tornam-se mais vulneráveis aos diversos tipos de violência, abuso e exploração, que, além da desumanização dos corpos, promove a invisibilização e o descarte para aqueles que não alimentam o estereótipo da prostituição. Para pertencer à classe das mulheres “respeitáveis”, rendem-se ao adestramento corporal e cultural, tornando-se este o passaporte para a visibilidade social. Tal percurso ocorre no filme com a personagem Vivian, que passa por um adestramento do seu corpo, por meio da contenção de seus hábitos gestuais anteriores, a fim de performar socialmente o lugar de uma mulher moralmente respeitável, o que também pode ser entendido como violência, podendo ser considerada uma ilustração do cenário brasileiro.

Low-frequency air–bone gap (ABG) associated with pulsatile tinnitus (PT) and normal impedance audiometry represents a common finding in patients with third window syndromes. Other inner disorders, including Meniere’s disease (MD), perilymphatic fistula and intralabyrinthine schwannoma, might sometimes result in a similar scenario. On the other hand, PT is frequently associated with dural arteriovenous fistula (DAVF), while conductive hearing loss (CHL) is extremely rare in this clinical setting. A 47-year-old patient was referred to our center with progressive left-sided PT alongside ipsilateral fullness and hearing loss. She also experienced headache and dizziness. Otoscopy and video-oculographic examination were unremarkable. Conversely, a detailed instrumental audio-vestibular assessment revealed low-frequency CHL with normal impedance audiometry, slight left-sided caloric weakness, slightly impaired vestibular-evoked myogenic potentials on the left and normal results on the video-head impulse test, consistent with an MD-like instrumental profile. Gadolinium-enhanced brain MRI revealed an early enhancement of the left transverse sinus, consistent with a left DAVF between the left occipital artery and the transverse sinus, which was then confirmed by angiography. A trans-arterial embolization with Onyx glue was performed, resulting in a complete recession of the symptoms. Post-operatively, the low-frequency ABG disappeared, supporting the possible role of venous intracranial hypertension and abnormal pressure of inner ear fluids in the onset of symptoms and offering new insights into the pathomechanism of inner ear CHL.

Surgical plugging of the superior semicircular canal (SSC) represents an effective procedure to treat disabling symptoms in superior canal dehiscence (SCD), despite resulting in an impaired vestibulo-ocular reflex (VOR) gain for the SSC. On the other hand, SSC hypofunction on video head impulse test (vHIT) represents a common finding in patients with SCD exhibiting sound/pressure-induced vertigo, a low-frequency air–bone gap (ABG), and enhanced vestibular-evoked myogenic potentials (VEMPs). “Spontaneous canal plugging” has been assumed as the underlying process. Nevertheless, missing/mitigated symptoms and/or near-normal instrumental findings would be expected. An endolymphatic flow dissipation has been recently proposed as an alternative pathomechanism for SSC VOR gain reduction in SCD. We aimed to shed light on this debate by comparing instrumental findings from 46 ears of 44 patients with SCD exhibiting SSC hypofunction with post-operative data from 10 ears of 10 patients with SCD who underwent surgical plugging. While no difference in SSC VOR gain values was found between the two groups (p = 0.199), operated ears developed a posterior canal hypofunction (p = 0.002). Moreover, both ABG values (p = 0.012) and cervical/ocular VEMP amplitudes (p < 0.001) were significantly higher and VEMP thresholds were significantly lower (p < 0.001) in ears with SCD compared to operated ears. According to our data, canal VOR gain reduction in SCD should be considered as an additional sign of a third window mechanism, likely due to an endolymphatic flow dissipation.

Abstract Background Kleefstra syndrome (KS) is a rare genetic condition affecting the euchromatic histone methyltransferase 1 (EHMT1) gene, typically presenting with developmental delay, generalized hypotonia, distinctive facial dysmorphisms, and neuropsychiatric anomalies. Methods We collected longitudinal magnetic resonance imaging (MRI) data of a child with KS and cerebrospinal fluid (CSF) dissection over 16 years and reviewed the literature focusing on articles reporting MRI findings in KS based on a PubMed search. Results An 18‐year‐old female with KS presented with developmental delay at age 18 months and seizures at age 10 years. At age 23 months, MRI showed ventriculomegaly. Follow‐up MRI nine years later showed CSF dissection from the right lateral ventricle, which progressed similarly in the contralateral side 3 years later and stabilized over time. To date, only 20 articles report MRI findings from 49 patients with KS. The brain imaging findings range from normal (about 25%) to various abnormalities, including ventriculomegaly, white matter signal abnormalities, and dysmorphic corpus callosum and brainstem structures. CSF dissection was not found in any cases with white matter or other abnormalities. Conclusions CSF dissection may be a rare neuroimaging finding of KS. Its etiology is unclear, but we speculate that epigenetic mutations could indirectly affect the development and integrity of ependymal cell lining along the ventricles. Alternatively, the long‐standing hydrocephalus may have caused the development of pseudodiverticula and subsequent CSF dissection.