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Most patients receiving atezolizumab-bevacizumab (AB) for hepatocellular carcinoma will eventually experience disease progression. Randomized clinical trials (RCTs) are undergoing to identify second-line treatments. Where RCTs are unavailable or patients are non-eligible, sorafenib is often prescribed based on approval and reimbursement policies. However, evidence supporting this approach is minimal. To assess the efficacy and safety of sorafenib in patients who permanently discontinued AB. The ARTE database prospectively collects patients treated with AB in a real-life setting. We analysed the outcome of patients who received sorafenib as second-line treatment. Amongst 213 patients, 130 (61.0 %) permanently discontinued AB. Of them, 54 received second- line treatments, and sorafenib was prescribed in 40 patients. The disease control rate (DCR) was 10.0 %. The median progression-free (PFS) and overall survival were 3.3 (95 % confidence interval [CI] 2.7-3.9) and 6.9 months (95 % CI 2.7-11.1), respectively. In patients progressing under AB, the efficacy of sorafenib on different outcomes is limited. [ABSTRACT FROM AUTHOR]

An increasing amount of evidence suggests that migraine is a response to cerebral energy deficiencies or oxidative stress levels that exceed antioxidant capacity. Current pharmacological options are inadequate in treating patients with chronic migraine, and a growing interest focuses on nutritional approaches as non-pharmacological treatments. The ketogenic diet, mimicking fasting that leads to an elevation of ketone bodies, is a therapeutic intervention targeting cerebral metabolism that has recently shown great promise in the prevention of migraines. Moreover, Mediterranean elements like vegetables, nuts, herbs, spices, and olive oil that are sources of anti-inflammatory elements (omega-3 fatty acids, polyphenols, vitamins, essential minerals, and probiotics) may create a positive brain environment by reducing imbalance in the gut microbiome. On the basis of these indications, a combined Mediterranean-ketogenic diet was administered to chronic migraine patients for 4 (T1) and 8 weeks (T2), and anthropometric estimations were collected at T1 and T2 while biochemical parameters at only T2. A significant reduction (p < 0.01) in migraine frequency and intensity was detected as early as 4 weeks of dietary intervention, which was associated with a reduced fat mass (p < 0.001) as well as Homa index (p < 0.05) and insulin levels (p < 0.01) after 8 weeks. Overall, Mediterranean-ketogenic diet may be considered an effective non-pharmacological intervention for migraine, with positive outcomes on body composition. [ABSTRACT FROM AUTHOR]

Feline infectious peritonitis (FIP) is an important cause of death in cats. Thoracic manifestations are less common than abdominal manifestations, and FIP-associated respiratory disease is poorly documented. This study aimed to investigate pathological findings in the respiratory tract of cats with FIP and the occurrence and distribution of feline coronavirus antigen in the respiratory tract using immunohistochemistry. A retrospective study was carried out on 112 cats with FIP, of which 66 had inflammatory histological lesions in the respiratory tract (58.9%) and were included in this study. Three major gross patterns were defined: marked fibrin deposition in the thoracic cavity with lung atelectasis; marked fibrin deposition in the thoracic cavity with lung pyogranulomas; and lung pyogranulomas without thoracic effusion. Histological analysis revealed primary lesions in the visceral pleura and lung parenchyma at a similar frequency, with multifocal to diffuse presentations. Marked lesions were commonly observed. Five major histological patterns were defined: pleuritis; pleuritis and vasculitis/perivascular injury in the lung parenchyma; pleuritis and pneumonia; perivascular injury in the parenchyma without pleuritis; and pneumonia without pleuritis. In the pleura and pulmonary parenchyma, FIP virus antigen was detected in perivascular and peribronchial macrophages and in macrophages within bronchial-associated lymphoid tissue and foci of necrosis and inflammation in the pleura and lung parenchyma. Co-infections with retroviruses were detected in 47 cats (71.2%), mainly with feline leukemia virus (62.2%). Although FIP is a systemic disease, some cats developed significant lesions in the thoracic cavity, including involvement of the upper respiratory tract and presenting respiratory signs, without other classic signs of FIP. This work advances our knowledge of FIP in the respiratory system, helping veterinarians to recognize the various presentations of this disease. [Display omitted] [ABSTRACT FROM AUTHOR]

Analyses of inequalities related to prevention and cancer therapeutics/care show disparities between countries with different economic standing, and within countries with high Gross Domestic Product. The development of basic technological and biological research provides clinical and prevention opportunities that make their implementation into healthcare systems more complex, mainly due to the growth of Personalized/Precision Cancer Medicine (PCM). Initiatives like the USA‐Cancer Moonshot and the EU‐Mission on Cancer and Europe's Beating Cancer Plan are initiated to boost cancer prevention and therapeutics/care innovation and to mitigate present inequalities. The conference organized by the Pontifical Academy of Sciences in collaboration with the European Academy of Cancer Sciences discussed the inequality problem, dependent on the economic status of a country, the increasing demands for infrastructure supportive of innovative research and its implementation in healthcare and prevention programs. Establishing translational research defined as a coherent cancer research continuum is still a challenge. Research has to cover the entire continuum from basic to outcomes research for clinical and prevention modalities. Comprehensive Cancer Centres (CCCs) are of critical importance for integrating research innovations to preclinical and clinical research, as for ensuring state‐of‐the‐art patient care within healthcare systems. International collaborative networks between CCCs are necessary to reach the critical mass of infrastructures and patients for PCM research, and for introducing prevention modalities and new treatments effectively. Outcomes and health economics research are required to assess the cost‐effectiveness of new interventions, currently a missing element in the research portfolio. Data sharing and critical mass are essential for innovative research to develop PCM. Despite advances in cancer research, cancer incidence and prevalence is growing. Making cancer research infrastructures accessible for all patients, considering the increasing inequalities, requires science policy actions incentivizing research aimed at prevention and cancer therapeutics/care with an increased focus on patients' needs and cost‐effective healthcare. [ABSTRACT FROM AUTHOR]

Airway management is a critical component of the management of emergency department (ED) patients. The ED airway literature primarily focuses upon endotracheal intubation; relatively less is known about the ED use of extraglottic devices (EGDs). The goal of this study was to describe the frequency of use, success, and complications for EGDs among ED patients. The National Emergency Airway Registry (NEAR) is a prospective, multi-center, observational registry. It captures data on all ED patients at participating sites requiring airway management. Intubating clinicians entered all data into an online system as soon as practical after each encounter. We conducted a secondary analysis of these data for all ED encounters in which EGD placement occurred. We used descriptive statistics to characterize these encounters. Of 19,071 patients undergoing intubation attempts, 56 (0.3%) underwent EGD placement. Of 25 participating sites, 13 reported no cases undergoing EGD placement; the median number of EGDs placed per site was 2 (interquartile range 1–2.5, range 1–31). Twenty-nine (54%) patients had either hypotension or hypoxia prior to the start of airway management. Clinicians reported anticipation of a difficult airway in 55% and at least one difficult airway characteristic in 93% of these patients. Forty-one encounters entailed placement of a laryngeal mask airway (LMA®) Fastrach™, 33 of whom underwent subsequent successful intubation through the EGD and 7 of whom underwent intubation by alternative methods. An additional 10 encounters utilized a standard LMA® device. Providers placed 34 (61%) EGDs during the first intubation attempt. Seventeen EGD patients (30%) experienced peri-procedure adverse events, including 14 (25%) experiencing hypoxemia. None of these patients expired due to failed airways. EGD use was rare in this multi-center ED registry. EGD occurred predominantly in patients with difficult airway characteristics with favorable airway management outcomes. Clinicians should consider this emergency airway device for patients with a suspected difficult airway. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of the study is to assess body hydration in patients with posterior vitreous detachment (PVD) by bioelectrical impedance analysis (BIA). PVD, one of the most common eye diseases, is associated in both research and the collective image with reduced daily water intake, but this finding is not supported by strong evidence in the literature. PATIENTS AND METHODS: Based on Spectral Domain Optical Coherence Tomography (SD-OCT) evaluation, different PVD stages are identified: absent posterior vitreous detachment, partial posterior vitreous detachment (P-PVD), or complete posterior vitreous detachment (C-PVD). BIA is a simple, non-invasive bedside method used to assess body composition. Patients underwent BIA and completed a floaters symptoms. 30 patients were enrolled and divided into two groups according to the degree of vitreous detachment, in P-PVD (n=12) and C-PVD (n=18). Patients underwent BIA and completed a floaters symptoms questionnaire. BIA measured the Resistance (R), Reactance (Xc), Phase Angle (PhA), Total Body Water (TBW), Extracellular Water (ECW), Fat Mass (FM), Fat-Free Mass (FFM), and Body Cell Mass Index (BCMI). Finally, patients received a test to assess adherence to the Mediterranean diet (Mediterranean Diet Test Score, MDTS) with the addition of daily water intake. RESULTS: Relevant data were obtained from the BIA evaluation: the values of R and Xc were lower in the P-PVD group than C-PVD group (respectively 417.08±58.12 O vs. 476.94±51.29 O p=0.006 and 41.33±8.23 O vs. 50.61±7.98 O p=0.004). Instead, patients in the P-PVD group reported higher values of TBW and ECW than C-PVD group (respectively 44.13±7.57 L vs. 37.96±6.27 L p=0.021 and 21.03±4.06 L vs. 17.24±2.63 L p=0.004). CONCLUSIONS: In the present study, we reported a significant correlation between vitreous pathology and anthropometric and BIA measurements. [ABSTRACT FROM AUTHOR]

The use of catalytic surfaces has an enormous biotechnological potential. Surfaces provide a material to localize and concentrate enzymes or even bacterial cells to achieve biological reactions in a more efficient way. A promising approach to specifically direct bacterial attachment to a surface of choice is the induced expression of synthetic adhesins. In this way cells are re-programmed by the adhesin to bind a specific target. Synthetic adhesins are recombinant molecules obtained by the fusion of an autotransporter module to a single-chain nanobody. In this case, the nanobody part acts as the recognition module targeting cells to cognate antigens, functioning as a perfect glue. The protocol described in this chapter aims to explain all steps required to effectively gain the functionality of the system. Specifically, the protocol provides a way to quantify and visualize bacterial immobilization on the modified surface. The methodology is exemplified by Escherichia coli with the use of two well characterized systems: (i) intimin as surface display and a (ii) nanobody that targets fibrinogen as adhesin. [ABSTRACT FROM AUTHOR]

COVID-19 is a novel disease with a broad range of clinical patterns. Several patients show dysbiosis in the intestinal tract, with evidence of reduced beneficial bacteria, such as Bifidobacteria and Lactobacilli. It is well established that human gut microbiota dysbiosis is associated with several clinical conditions, including respiratory tract diseases due to the gut-lung axis. This narrative review discusses the role of nutrients in the relationship between the gut microbiota and the immune response in SARS-CoV-2 infection. In particular, we will focus on the benefits offered by vitamins and micronutrients on different aspects of COVID-19 disease while also discussing which diets seem to provide the most advantages. [ABSTRACT FROM AUTHOR]

European cancer research stakeholders met in October 2022 in Heidelberg, Germany, at the 5th Gago conference on European Cancer Policy, to discuss the current cancer research and cancer care policy landscape in Europe. Meeting participants highlighted gaps in the existing European programmes focusing on cancer research, including Europe's Beating Cancer Plan (EBCP), the Mission on Cancer (MoC), Understanding Cancer (UNCAN.eu), and the joint action CRANE, and put forward the next priorities, in the form of the Heidelberg Manifesto for cancer research. This meeting report presents all discussions that shed light on how infrastructures can be effectively shaped for translational, prevention, clinical and outcomes cancer research, with a focus on implementation and sustainability and while engaging patients and the public. In addition, we summarize recommendations on how to introduce frameworks for the digitalization of European cancer research. Finally, we discuss what structures, commitment, and resources are needed to establish a collaborative cancer research environment in Europe to achieve the scale required for innovation. [ABSTRACT FROM AUTHOR]

Background: Tauopathies that include e.g. frontotemporal dementia and Alzheimer's disease, are neurodegenerative diseases characterized by accumulation of hyperphosphorylated Tau in the brain. Tau is a tempting drug target for tauopathies but no Tau‐targeting therapies are in clinical use. We have recently shown that small‐molecular inhibitors of prolyl oligopeptidase (PREP) can activate protein phosphatase 2A (PP2A) by regulating PREP‐PP2A interaction. PP2A is the main phosphatase regulating Tau, and therefore, we decided to test the efficacy of a reference PREP inhibitor, KYP‐2047, and novel PREP ligands on cellular and animal models of tauopathies. Method: The compounds, KYP‐2047 and HUP‐46, 55 and 59 (1, 5 and 10 μM), were first screened in the GFP‐2N4R‐Tau transfected HEK‐293 cells where the Tau aggregation was induced by small‐dose okadaic acid (OA; 10 nM), a PP2A inhibitor. The results were verified by using 2N4R‐Tau transfected HEK‐293 cells with 10 nM OA. After the treatment the cells were fractioned to RIPA soluble and SDS‐fractions, and total Tau and S262 phosphorylated Tau (pS262 Tau) levels were studied by Western blot (WB). Finally, KYP‐2047 and HUP‐46 were tested in PS19 Tau transgenic mouse. PS19 mice were treated with the ligands for 4 weeks (10 mg/kg/day, Alzet minipump i.p.) starting from 5.5 months old when the behavioral deficits were observed. After the treatment, the mice behavior was tested by Barnes Maze and locomotor activity assay, and total Tau, pS262 Tau and PP2A levels were studied. Result: In the GFP‐Tau aggregation assay, all compounds decreased the GFP signal as an indicative of Tau aggregation with 10 mM concentration but HUP‐46 was the most effective (Fig. 1). WB that showed that PREP ligands had the most significant effect on total Tau and pS262 Tau in the SDS‐fraction. In the PS19 mice, KYP‐2047 restored normal behavior in Barnes maze and locomotor activity assay. HUP‐46 had similar effect but did not reach significance (Fig. 2). However, both compounds reduced significantly total Tau and pS262 Tau levels in mouse hippocampus and cortex, and activated PP2A (Fig. 3). Conclusion: Small‐molecular PREP ligands, such as KYP‐2047 and HUP‐46 have disease‐modifying effects on cellular and animal models of tauopathies. [ABSTRACT FROM AUTHOR]

Copyright of Estudios Filosóficos is the property of Estudios Filosoficos and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Estudios Filosóficos is the property of Estudios Filosoficos and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

OBJECTIVE: This study examines the role of MTHFR gene polymorphism (rs1801133) in women with lipedema (LIPPY) body composition parameters compared to a control group (CTRL). SUBJECTS AND METHODS: We carried out a study on a sample of 45 LIPPY and 50 women as a CTRL. Body composition parameters were examined by Dual-energy X-ray Absorptiometry (DXA). A genetic test was performed for the MTHFR polymorphism (rs1801133, 677C>T) using a saliva sample for LIPPY and CTRL groups. Mann-Whitney tests evaluated statistically significant differences between four groups (carriers and non-carriers of the MTHFR polymorphism for LIPPY and CTRL groups) on anthropometric/body composition parameters to identify patterns. RESULTS: LIPPY showed significantly higher (p<0.05) anthropometric parameters (weight, BMI, waist, abdominal, hip circumferences) and lower waist/hip ratio (p<0.05) compared to the CTRL group. The association between the polymorphism alleles related to the rs1801133 MTHFR gene and the body composition values LIPPY carriers (+) showed an increase in fat tissue of legs and fat region of legs percentage, arm's fat mass (g), leg's fat mass (g), and leg's lean mass (g) (p<0.05) compared to CTRL (+). Lean/fat arms and lean/fat legs were lower (p<0.05) in LIPPY (+) than in CTRL (+). In the LIPPY (+), the risk of developing the lipedema disease was 2.85 times higher (OR=2.85; p<0.05; 95% confidence interval = 0.842-8.625) with respect to LIPPY (-) and CTRL. CONCLUSIONS: The presence or absence of MTHFR polymorphism offers predictive parameters that could better characterize women with lipedema based on the association between body composition and MTHFR presence. [ABSTRACT FROM AUTHOR]

This essay presents collaborative research related to the National Endowment for the Humanities-Arts and Humanities Research Council grant-funded project Connecting Threads, a website that brings together academics and curators across the United Kingdom and the United States who seek to contribute to wider decolonization work in the humanities and engage communities whose contributions to global cultures of textiles and fashion have historically been ignored. The Connecting Threads research team uses the Dutch Textile Trade Project's data and web applications to deepen understanding of the Madras kerchief, a large checked cotton square cloth that circulated in Afro-diasporic communities in the Caribbean during the eighteenth and nineteenth centuries. [ABSTRACT FROM AUTHOR]

Australia's pavilions at the Franco-British Exhibition (London, 1908) and the Exposition Internationale des Arts et Techniques dans la Vie Moderne (Paris, 1937) were among the first to represent the new nation to the world, yet both have eluded close examination. Through a comparative history of each pavilion and its displays, this article seeks to demonstrate the evolving strategies towards using the visual arts to help forge both a national identity and a distinctive cultural identity. [ABSTRACT FROM AUTHOR]

Background: To study the effect of greater occipital nerve (GON) block on migraine-associated photophobia levels. Photophobia is one of the most bothersome symptoms reported by migraine patients. Studies investigating the impact of migraine treatment on this symptom are scarce. Methods: This is an observational prospective case–control study. Patients with migraine and photophobia attending a Headache Clinic were recruited. Cases were defined as patients in whom GON block was performed, following usual clinical practice guidelines. All patients were evaluated with the Hospital Anxiety and Depression Scale, the Migraine Specific Quality of Life Questionnaire, the Utah Photophobia Symptom Impact Scale (UPSIS-12), and the Korean Photophobia Questionnaire (KUMC-8); both in the first visit (V1) and one week after (V2). Results: Forty-one patients were recruited, 28 (68.3%) cases and 13 (31.7%) controls. At V1, there were no significant differences in the median [p25-p75] score of UPSIS-12 in cases vs controls (32.0 [21.0–34.0] vs 30.5 [22.0–37.0], P = 0.497) or KUMC-8 (6.5 [5.5–7.0] vs 7.0 [6.0–8.0], P = 0.463). At V2, cases experimented a significant improvement in UPSIS-12 of −5.5 [−8.8 to −1.3] and in KUMC-8 of −0.5 [−2.0 to 0], whereas there were no significant changes in the control group. Migraine with aura patients presented higher UPSIS-12 score at V1 (33.5 [24.5–37.0] vs 26.0 [16.0–35.0]) and lesser improvement at V2 after GON block compared with migraine without aura patients (−4.0 [−6.0 to −1.0] vs −8.0 [−17.0 to −2.0]), although statistical significance was not achieved (P = 0.643 and P = 0.122, respectively). There was no significant variation in the remaining scales. Conclusions: Greater occipital nerve block improves migraine-associated photophobia, measured with UPSIS-12 and KUMC-8. Patients without aura may exhibit a greater improvement. Physicians could consider GON block for management of photophobia in migraine patients. [ABSTRACT FROM AUTHOR]

During chronic kidney disease (CKD), typical alterations in the gut microbiota are observed. The kidney no longer plays the role of the main excretory organ as this function is performed by the intestine. In CKD patients, an alteration of intestinal permeability and a degradation of the protective mucous layer are observed. These changes in the intestinal barrier allow the passage of bacterial material from the intestine to the bloodstream through the intestinal wall. This phenomenon contributes to the induction of the chronic inflammatory state, typical of CKD. In nephropathic patients, there is an increase in circulation of p-cresyl sulfate (p-CS), indoxyl sulphate (IS), indole- 3 acetic acid (IAA) and trimethylamine-N-oxide (TMAO), all gut-derived uremic toxins. The changes in gut microbiota composition are related to CKD stage and this phenomenon is exacerbated in hemodialysis (HD) adult and pediatric patients. Interestingly, it is observed a positive shift in gut microbiota composition after renal transplantation and at the same time a reduction of circulating gut-derived uremic toxins. Either gut dysbiosis or uremic toxins accumulation contribute to the CKD onset and progression. [ABSTRACT FROM AUTHOR]