Exploring asymmetry induced entropy in tetraalkylammonium-urea DES systems: what can be learned from inelastic neutron scattering?

In this work, inelastic neutron scattering (INS) spectroscopy is used to investigate the impact of entropic factors on the behaviour of deep eutectic solvents (DES). Periodic density functional theory calculations (DFT) provide a reliable assignment of the vibrational modes of pure compounds. This assignment guides the analysis of INS spectra of binary mixtures - with particular attention to methyl torsional modes. Deviations from ideality in the mixtures of tetraalkylammonium salts with urea are readily determined through a simplified thermodynamic approach. This study reports and discusses the relationship between the cation's asymmetry, the INS spectra of the eutectic mixture and its deviation from ideality. Contrary to the majority of systems studied so far, the deep eutectic system comprised of [N2,2,2,1]Cl and urea appears to owe its deviation from ideality to entropic rather than enthalpic factors.

Vacinar ou arriscar? A mensagem da Organização Mundial de Saúde para promover a vacinação contra a covid-19 / Vaccinate or taking chances? The World Health Organization's message to promote vaccination against COVID-19

Resumo Centrando-se no impacto que a comunicação de risco emitida pelas organizações de saúde pública tem na mudança dos comportamentos da sociedade, esta investigação pretende analisar as mensagens-chave que a Organização Mundial de Saúde (OMS) definiu para promover o programa de vacinação contra a covid-19. Para cumprir este objetivo, enveredou-se por uma metodologia de estudo qualitativa, que privilegiou o uso da análise do conteúdo publicado nas páginas de Facebook e de Instagram da OMS, no período de 1 de abril a 31 de agosto de 2021. No total, foram analisadas 62 publicações. Os resultados mostraram que a OMS utilizou quatro eixo de comunicação para promover a importância da vacinação na sociedade: garantir a credibilidade e a transparência da informação transmitida; certificar a segurança e a eficácia da vacina; apelar ao sentido de responsabilidade coletiva; e associar a vacina à solução para pôr fim à pandemia. As conclusões do estudo mostram que, embora a equidade no acesso à vacina ainda seja uma realidade em construção, os quase 70% da população mundial vacinada sugerem que as mensagens enviadas pela OMS no contexto de comunicação de risco podem ter contribuído para a construção de uma imagem positiva do programa de vacinação.

Abstract Focusing on the impact that risk communication issued by public health organizations brings to changing societal behaviors, this research aimed to analyze the key messages that the World Health Organization (WHO) has defined to promote the COVID-19 vaccination program. In order to achieve this goal, a qualitative study methodology was used to analyze the content published on the WHO's Facebook and Instagram pages from April 1 to August 31, 2021. In total, 62 publications were analyzed. The results showed that the WHO used four key communication messages to promote the importance of vaccination in society: ensuring the credibility and transparency of the information transmitted; certifying the safety and efficacy of the vaccine; appealing to a sense of collective responsibility; and associating the vaccine with the solution to end the pandemic were the chosen communication axes. The conclusions of this study show that, although fair access to the vaccine is still a reality in the making, the fact that almost 70% of the world's population has been vaccinated suggests that the messages sent by the WHO in the context of risk communication may have contributed to building a positive image of the vaccination program.

A Rare First Presentation of Hodgkin's Lymphoma: Symptomatic Pericardial Effusion.

Symptomatic pericardial effusion occurring as the initial manifestation of Hodgkin's lymphoma is exceedingly uncommon, and there are limited documented instances in the available literature. Pericardial effusion can present various differential diagnoses, and among these, malignancy is an important yet less frequently encountered cause. A heightened level of suspicion is crucial for establishing an accurate diagnosis, particularly when the patient's clinical course deviates from the anticipated trajectory. Through this case, we aim to emphasize the significance of considering lymphoproliferative diseases as a pertinent possibility in the differential diagnosis of pericardial effusion. Additionally, we underscore the importance of promptly reaching a diagnosis, as it can help prevent severe complications and enhance the patient's prognosis.

Balance between maternal antiviral response and placental transfer of protection in gestational SARS-CoV-2 infection.

The intricate interplay between maternal immune response to SARS-CoV-2 and the transfer of protective factors to the fetus remains unclear. By analyzing mother-neonate dyads from second and third trimester SARS-CoV-2 infections, our study shows that neutralizing antibodies (NAbs) are infrequently detected in cord blood. We uncovered that this is due to impaired IgG-NAb placental transfer in symptomatic infection and to the predominance of maternal SARS-CoV-2 NAbs of the IgA and IgM isotypes, which are prevented from crossing the placenta. Crucially, the balance between maternal antiviral response and transplacental transfer of IgG-NAbs appears to hinge on IL-6 and IL-10 produced in response to SARS-CoV-2 infection. In addition, asymptomatic maternal infection was associated with expansion of anti-SARS-CoV-2 IgM and NK cell frequency. Our findings identify a protective role for IgA/IgM-NAbs in gestational SARS-CoV-2 infection and open the possibility that the maternal immune response to SARS-CoV-2 infection might benefit the neonate in 2 ways, first by skewing maternal immune response toward immediate viral clearance, and second by endowing the neonate with protective mechanisms to curtail horizontal viral transmission in the critical postnatal period, via the priming of IgA/IgM-NAbs to be transferred by the breast milk and via NK cell expansion in the neonate.

Myxozoan survey of thicklip grey mullet Chelon labrosus reinforces successful radiation of Myxobolus in mugiliform hosts.

A myxozoan survey was performed on specimens of thicklip grey mullet Chelon labrosus (Risso) captured from the Douro River estuary, northern Portugal. Eleven new species, all belonging to the genus Myxobolus Bütschli, 1882 (M. abdominalis n. sp., M. aestuarium n. sp., M. caudalis n. sp., M. chelonari n. sp., M. cucurbitiformis n. sp., M. douroensis n. sp., M. intestinicola n. sp., M. invictus n. sp., M. labicola n. sp., M. peritonaei n. sp., and M. pinnula n. sp.) are described based on microscopic and molecular data, confirming the known high radiation of these myxozoans in mullets. Additionally, Myxobolus pupkoi Gupta et al., 2022 is reported for the first time from C. labrosus, bringing forth a novel case of morphological plasticity between geographic isolates. We consider that molecular-based comparisons are imperative for the description of mugiliform-infecting Myxobolus, with distance estimation further matching two of the novel Myxobolus spp. with sphaeractinomyxon types previously reported from another Portuguese estuary. This finding supports sphaeractinomyxon as specific life cycle counterparts of Myxobolus that infect mullets. Phylogenetic analyses of 18S rDNA retrieved a monophyletic clade of mugiliform-infecting myxobolids comprising well-supported lineages of species parasitizing mullets from the genera Chelon, Mugil, Crenimugil, and Planiliza. The existence of more than one Chelon- and Planiliza-infecting lineage reveals that myxobolids parasitized members of these genera multiple times during their evolution. Lastly, the elevated number of unmatched sphaeractinomyxon sequences included in the Chelon-infecting lineages clearly shows that Myxobolus diversity hosted by this genus remains underrated.

Title: Un inventaire des myxozoaires du mulet lippu Chelon labrosus confirme le rayonnement réussi de Myxobolus chez les hôtes mugiliformes. Abstract: Un inventaire des myxozoaires a été réalisé sur des spécimens de mulets lippus Chelon labrosus (Risso) capturés dans l'estuaire du fleuve Douro, au nord du Portugal. Onze nouvelles espèces, toutes appartenant au genre Myxobolus Bütschli, 1882 (M. abdominalis n. sp., M. aestuarium n. sp., M. caudalis n. sp., M. chelonari n. sp., M. cucurbitiformis n. sp., M. douroensis n. sp., M. intestinicola n. sp., M. invictus n. sp., M. labicola n. sp., M. peritonaei n. sp. et M. pinnula n. sp.) sont décrites sur la base de données microscopiques et moléculaires, confirmant le rayonnement connu de ces myxozoaires chez les mulets. De plus, Myxobolus pupkoi Gupta et al., 2022 est signalé pour la première fois chez C. labrosus, démontrant un nouveau cas de plasticité morphologique entre des isolats géographiques. Nous considérons que les comparaisons moléculaires sont impératives pour la description des Myxobolus infectant les mugiliformes, l'estimation de la distance correspondant en outre à deux des nouveaux Myxobolus spp. avec des types de sphaeractinomyxons précédemment signalés dans un autre estuaire portugais. Cette découverte soutient les sphaeractinomyxons en tant que contreparties spécifiques du cycle de vie de Myxobolus qui infectent les mulets. Les analyses phylogénétiques de l'ADNr 18S ont montré un clade monophylétique de Myxobolidae infectant les mugiliformes, comprenant des lignées robustes d'espèces parasitant les mulets des genres Chelon, Mugil, Crenimugil et Planiliza. L'existence de plusieurs lignées infectant Chelon et Planiliza révèle que les Myxobolidae ont parasité des membres de ces genres plusieurs fois au cours de leur évolution. Enfin, le nombre élevé de séquences de sphaeractinomyxons non appariées incluses dans les lignées infectant Chelon montre clairement que la diversité de Myxobolus hébergée par ce genre reste sous-estimée.

Central Venous Catheter-Associated Superior Vena Cava Syndrome.

Superior vena cava syndrome (SVCS) is caused by any obstruction to the superior vena cava (SVC); the most common causes are malignancy and extrinsic compression. The use of medical devices, such as central venous catheters, poses an important risk factor, as they cause changes in the blood flow and in the vessel wall. This report describes a case of a 70-year-old male with an implantable central venous port, due to previous neoplastic disease, as the cause of the SVCS. Authors advise that the placement of medical devices ought to be carefully accessed and constantly revised to be removed when no longer needed to prevent avoidable complications.

From PEF to PBF: What difference does the longer alkyl chain make a computational spectroscopy study of poly(butylene 2,5-furandicarboxylate).

This work explores the conformational preferences and the structure-property correlations of poly(butylene 2,5-furandicarboxylate) (PBF), a longer chain analogue of the most well-known biobased polyester from the furan family, poly(ethylene 2,5-furandicarboxylate) (PEF). A thorough computational spectroscopic study-including infrared, Raman and inelastic neutron scattering spectroscopy, combined with discrete and periodic density functional theory calculations-allowed the identification of dominant structural motifs in the amorphous and crystalline regions. Discrete calculations and vibrational spectroscopy of semi-crystalline and amorphous samples strongly support the predominance of gauche, trans, gauche conformations of the butylene glycol fragment in both the crystalline and amorphous domains. In what concerns the furandicarboxylate fragment, amorphous domains are dominated by syn,syn conformations, while in the crystalline domains the anti,anti forms prevail. A possible crystalline structure-built from these conformational preferences and including a network of C-H···O hydrogen bond contacts-was optimized using periodic density functional theory. This proposed crystal structure avoids the unrealistic structural features of the previously proposed X-ray structure, provides an excellent description of the inelastic neutron scattering spectrum of the semi-crystalline form, and allows the correlation between microscopic structure and macroscopic properties of the polymer.

Prognostic Role of Liver Biopsy in Patients With Severe Indeterminate Acute Hepatitis.

BACKGROUND AND AIMS: Severe indeterminate acute hepatitis (sIAH) is a poorly understood rare disease with no specific therapy. This study aims to define the clinicopathological characteristics of sIAH and the role of liver biopsy in determining prognosis. METHODS: Patients with sIAH admitted to a single center between 2010 and 2019 were included. Histopathological patterns of liver biopsies were reviewed by 2 histopathologists, and key findings further were specified by multiplex immunofluorescence. Patients that died or underwent liver transplantation were analyzed as nonsurvivors. RESULTS: Of 294 patients with acute hepatitis, 43 with sIAH were included. Seventeen (39.5%) underwent liver transplantation and 7 (16.2%) died within 3 months. Multilobular necrosis was the predominant histopathological feature, being significantly more frequent in nonsurvivors (62.5% vs 21.1%; P = .016). Necrotic areas showed low HNF4α and Ki67 expression but high expression of CK19 and cell death markers identifying areas of severe tissue injury and inadequate regenerative response. Patients with multilobular necrosis had higher international normalized ratio, Model for End-Stage Liver Disease, and Model for End-Stage Liver Disease-Sodium scores compared with those without (P values for all markers <.05). Multivariate Cox analysis revealed that multilobular necrosis (hazard ratio, 3.675; 95% confidence interval, 1.322-10.211) and lower body mass index (hazard ratio, 0.916; 95% confidence interval, 0.848-0.991) independently predicted death or transplantation. CONCLUSIONS: The results of this study provide novel insights into the important role of liver biopsy in sIAH patients, suggesting that the presence of multilobular necrosis is an early indicator of poor prognosis.

Presence of multilobular necrosis on liver biopsy identifies corticosteroid responsiveness in acute indeterminate hepatitis.

BACKGROUND AND AIMS: Treatment of patients with severe indeterminate hepatitis (IAH) is an unmet need. Corticosteroids are often used in the management of these patients but criteria for the selection of patients for this intervention are arbitrary. The aims of this study were to analyse the clinical and pathological features of patients with IAH to define predictors of corticosteroid responsiveness. METHODS: This study included consecutive patients with acute indeterminate hepatitis admitted to a single hospital and underwent a liver biopsy. The clinical manifestation and histopathological features of steroid and non-steroid groups were compared and their relationship with corticosteroids response was evaluated. RESULTS: Forty-eight patients were included, 24 (50%) recovered and the other half underwent liver transplantation or died within 3-months. Of the 48 cases, 24 received corticosteroids (initial dose of 45 ± 12 mg prednisolone). Corticosteroids were initiated 2.7 ± 3.8 days after admission. Liver biopsy was performed 2-days (median, IQR 1-3) after admission. Fifteen (62.5%) patients receiving corticosteroids survived without transplantation compared with 9 (37.5%) that did not receive steroids (P = .149). In those with multilobular necrosis, 50% reduction in the death/transplantation rate was observed after steroid treatment (P = .018). In patients without multilobular necrosis and with or without perivenulitis, corticosteroids did not impact the outcome. Response to corticosteroids was independent of the MELD score. CONCLUSIONS: The presence of multilobular necrosis on liver biopsy helps identify a subgroup of IAH cases who may benefit from the administration of corticosteroids.

Identification of a Zika NS2B epitope as a biomarker for severe clinical phenotypes.

The identification of specific biomarkers for Zika infection and its clinical complications is fundamental to mitigate the infection spread, which has been associated with a broad range of neurological sequelae. We present the characterization of antibody responses in serum samples from individuals infected with Zika, presenting non-severe (classical) and severe (neurological disease) phenotypes, with high-density peptide arrays comprising the Zika NS1 and NS2B proteins. The data pinpoints one strongly IgG-targeted NS2B epitope in non-severe infections, which is absent in Zika patients, where infection progressed to the severe phenotype. This differential IgG profile between the studied groups was confirmed by multivariate data analysis. Molecular dynamics simulations and circular dichroism have shown that the peptide in solution presents itself in a sub-optimal conformation for antibody recognition, which led us to computationally engineer an artificial protein able to stabilize the NS2B epitope structure. The engineered protein was used to interrogate paired samples from mothers and their babies presenting Zika-associated microcephaly and confirmed the absence of NS2B IgG response in those samples. These findings suggest that the assessment of antibody responses to the herein identified NS2B epitope is a strong candidate biomarker for the diagnosis and prognosis of Zika-associated neurological disease.

Are Zika virus cross-reactive antibodies against aquaporin-4 associated to Neuromyelitis Optica Spectrum Disorder?

Zika virus (ZIKV) infection has been associated with the development of Neuromyelitis Optica Spectrum Disorder (NMOSD). ZIKV-induced antibodies that putatively cross-react to aquaporin-4 (AQP4) protein are suggested to cause inflammation of the optic nerve. A region of similarity between AQP4 and the ZIKV NS2B protein was identified. Our data showed that ZIKV-associated NMOSD patients develop anti-AQP4 antibodies, but not anti-ZIKV NS2B antibodies, revealing that cross-reacting antibodies are not the underlying cause of this phenotype. ZIKV infection in mice showed persistent viral replication in the eye tissue, suggesting that NMOSD symptoms are consequence of viral infection of the optic nerve cells.

Bellini duct carcinoma.

The modern era has brought an appreciation that renal cell carcinoma (RCC) includes diverse subtypes derived from the various parts of the nephron, each with its distinctive genetic basis and tumor biology. Carcinoma of the collecting ducts of Bellini (CDC) is a rare subtype of RCC, with a predictably poor prognosis. This rare subtype represents less than 1% of all kidney carcinomas. It derives from presumably numerous chromosomal losses. It is of chief importance to differentiate CDC from other types of renal cell cancer. Typically, it is characterized by a firm, centrally located tumor with infiltrative borders. Regarding the histopathologic characteristics, we can find complex, highly infiltrative cords with inflamed (desmoplastic) stroma, with high-grade nuclei and mitoses. Most reported cases of CDC had been high grade, advanced stage, and unresponsive to conventional therapies. This rare form of disease highlights the importance of multidisciplinary teams in the management of cancer patients.

Case Report: Primary Immunodeficiencies, Massive EBV+ T-Cell Lympoproliferation Leading to the Diagnosis of ICF2 Syndrome.

In immunocompromised patients, EBV may elicit B-cell transformation and proliferation. A 5-year-old microcephalic boy was admitted with fever and non-malignant polymorphic T-cell lymphoproliferative disease associated with EBV. A presumptive diagnosis of primary immunodeficiency with inability to control EBV was made and next-generation sequencing led to the identification of a novel ZBTB24 mutation (ICF2-syndrome). This case shows that susceptibility to EBV seems to be particular of ICF-2 as it has not been described in the other types of ICF. It is mandatory to raise the hypothesis of an underlying PID in case of severe EBV infection.

Primary Liver Lymphoma Presenting as Liver Nodules.

The liver is usually affected in advanced stages of lympho-proliferative diseases, but primary liver lymphomas (PLLs) are rare. The diagnosis is usually late, especially in patients without identifiable risk factors, with consequent worse prognosis. We report the case of a 59-year-old female with progressive worsening pain in the right hypochondrium and weight loss. She was previously healthy and had a family history of gastrointestinal and gynecologic neoplasms. During the initial investigation, three liver nodules suggestive of liver metastases were found. Nevertheless, no primary neoplasm was identified in a subsequent evaluation with imaging and endoscopic exams. Laboratory exams excluded hepatic infections, metabolic diseases, and acquired immunosuppression. Biopsy of the lesions revealed diffuse large B-cell lymphoma. Lymph node and medullar involvement were excluded, and the diagnosis of PLL was assumed. The patient started chemotherapy with R-CHOP. With this case, we intend to alert for this differential diagnosis of liver nodules, even in the absence of predisposing conditions for lymphoma. We point out the need to define universal diagnosis criteria for this pathology.

O fígado é geralmente afetado em estádios avançados de doenças linfoproliferativas, mas os linfomas primários do fígado são raros. O diagnóstico é habitualmente tardio, principalmente em doente sem fatores de risco identificados, e consequentemente com pior prognóstico. Apresentamos o caso de uma doente de 59 anos, com quadro álgico de intensidade crescente no hipocôndrio direito e perda ponderal. A doente era previamente saudável e tinha história familiar de neoplasia gastrointestinal e ginecológica. No estudo inicial, foram identificadas três imagens nodulares hepáticas sugestivas de metástases. No entanto, não se identificou tumor primário em exames de imagem nem endoscópicos. Foram também excluidas infeções hepáticas, doença metabólica e imunossupressão adquirida. A biópsia das lesões hepáticas revelou tratar-se de linfoma B difuso de grandes células. Foi excluido envolvimento ganglionar e medular pelo que se assumiu o diagnóstico de Linfoma Primário do Fígado. A doente iniciou quimioterapia com R-CHOP. Com este caso pretendemos alertar para a necessidade de equacionar este diagnóstico diferencial de nodulos hepáticos, mesmo na ausência de fatores de risco para linfoma. Também alertamos para a necessidade de se definirem critérios diagnósticos universais para esta patologia.

Bellini duct carcinoma

The modern era has brought an appreciation that renal cell carcinoma (RCC) includes diverse subtypes derived from the various parts of the nephron, each with its distinctive genetic basis and tumor biology. Carcinoma of the collecting ducts of Bellini (CDC) is a rare subtype of RCC, with a predictably poor prognosis. This rare subtype represents less than 1% of all kidney carcinomas. It derives from presumably numerous chromosomal losses. It is of chief importance to differentiate CDC from other types of renal cell cancer. Typically, it is characterized by a firm, centrally located tumor with infiltrative borders. Regarding the histopathologic characteristics, we can find complex, highly infiltrative cords with inflamed (desmoplastic) stroma, with high-grade nuclei and mitoses. Most reported cases of CDC had been high grade, advanced stage, and unresponsive to conventional therapies. This rare form of disease highlights the importance of multidisciplinary teams in the management of cancer patients.

An uncommon intramedullary tumor: Primary medullary cone melanoma.

BACKGROUND: Melanoma is the third most common primary tumor to metastasize to the central nervous system (CNS). However, primary CNS melanoma is very rare, and primary intramedullary melanoma is even less frequently encountered, with only 27 cases published in the literature. There are no pathognomonic imaging characteristics, therefore, the diagnosis must be confirmed immunohistologically and the preferred treatment is the gross total resection. CASE DESCRIPTION: A 68-year-old male presented with low back pain of 2 months duration, and 1 week of urinary retention/anal sphincter incontinence. The neurologic examination revealed bilateral paraparesis (3/5 level) with bilateral Babinski signs, and a T10-T11 pin level. The lumbar CT-Scan showed a hyperdense intramedullary tumor arising from the conus medullaris. The patient underwent a D12-L2 laminectomy with myelotomy for gross-total tumor resection. Postoperatively, he regained motor function but the urinary incontinence remained unchanged. The diagnosis of a primary malignant melanoma was confirmed both histopathologically and immunohistochemically (e.g., staining revealed positive immunoreactivity for S100 protein and Melan A). CONCLUSIONS: Primary intramedullary spinal melanoma is very rare, and the diagnosis must be biopsy/operatively confirmed. Whether gross total resection is feasible depends on the extent of tumor infiltration of the cord/ adherence as well as the potential for clinical deterioration with overly aggressive removal.

Understanding the Structure and Dynamics of Nanocellulose-Based Composites with Neutral and ionic Poly(methacrylate) Derivatives using Inelastic Neutron Scattering and DFT Calculations.

Bacterial nanocellulose (BC)-based composites containing poly(2-hydroxyethyl methacrylate) (PHEMA), poly(methacroylcholine chloride) (PMACC) or poly(methacroylcholine hydroxide) (PMACH) were characterized by inelastic neutron scattering (INS) spectroscopy, combined with DFT (density functional theory) calculations of model systems. A reasonable match between calculated and experimental spectral lines and their intensities was used to support the vibrational assignment of the observed bands and to validate the possible structures. The differences between the spectra of the nanocomposites and the pure precursors indicate that interactions between the components are stronger for the ionic poly(methacrylate) derivatives than for the neutral counterpart. Displaced anions interact differently with cellulose chains, due to the different ability to compete with the O-H···O hydrogen bonds in cellulose. Hence, the INS is an adequate technique to delve deeper into the structure and dynamics of nanocellulose-based composites, confirming that they are true nanocomposite materials instead of simple mixtures of totally independent domains.