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The regioselective nitration of 9,9′-spirobifluorene under mild conditions is reported for the first time by operating under Menke’s and Crivello’s conditions. The optimized protocol allows obtaining 2-nitro and 2,2′-dinitro-9,9′-spirobifluorene in yields of 79 and 95% and, for the first time, 2,2′,7-trinitro-9,9′-spirobifluorene with 66% yield. Besides, the role of dinitrate salt in Crivello’s protocol has been now clarified, which opens novel scenarios in the preparation of functional materials.

Modern “omics” sciences, including metabolomics and microbiomics, are currently being applied to inflammatory autoimmune diseases, such as rheumatoid arthritis (RA), to investigate the interplay between microbiota, metabolic function, and the immune system. In recent decades, robust evidence has suggested that disruption of the normal composition of the microbiome, known as dysbiosis, in the gut and mouth of RA patients contributes to immune dysregulation and alterations in the metabolic pathways, shaping the pathogenesis of the disease and playing a central role in the risk and progression of RA. Metabolic pathways can be influenced by various agents such as the surrounding environment, lifestyle, and exposure to microbiota imbalance. In turn, the body’s metabolic homeostasis influences the immune response, making metabolomics helpful not only to understand pathogenesis pathways, but also to improve early disease detection and therapeutic chances. Combined gut microbiome and metabolome studies set out to unravel the interactions between these two entities, providing insights to discover new treatment targets and potential biomarkers to prevent joint damage. The purpose of this review is to summarize the main recent findings that suggest promising new research directions for the pathogenesis of RA.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common heritable multifocal cystic disease encountered in clinical practice, and it is usually diagnosed in patients with family history by the evidence of markedly enlarged kidneys with multiple bilateral cysts at ultrasound (U.S.), computed tomography (CT) scan, or magnetic resonance imaging (MRI). In most cases, genetic testing is not required. Though ADPKD diagnosis is often straightforward, misdiagnosis is possible. Here we present a case of ADPKD misdiagnosis, followed by a review of the most important kidney heritable multifocal cystic diseases. Our case report demonstrates that ADPKD can be erroneously diagnosed when other kidney heritable multifocal cystic diseases occur without their distinguishing manifestations and when there is no genetic characterization among the relatives. A proper diagnosis of heritable diseases is crucial, as it allows an appropriate management of family members who carry disease allele, apart from patient management. Therefore, we suggest a careful differential diagnosis with possible molecular genetic analysis in presentations with familial cystic kidneys and suspicious clinical and radiological features.

Background: Breast cancer is the most common malignancy in women, with high morbidity and mortality. Molecular alterations in breast cancer involve the expression or upregulation of various molecular targets that can be used for diagnostic nuclear medicine imaging and radiopharmaceutical treatment. Theragnostics is based on the binding of radionuclides to molecular targets. These radionuclides can induce a cytotoxic effect on the specific tumor cell (target) or its vicinity, thus allowing a personalized approach to patients with effective treatment and comparably small side effects. Aim: This review aims to describe the most promising molecular targets currently under investigation for theragnostics and precision oncology in breast cancer. Methods: A comprehensive literature search of studies on theragnostics in breast cancer was performed in the PubMed, PMC, Scopus, Google Scholar, Embase, Web of Science, and Cochrane library databases, between 2010 and 2022, using the following terms: breast neoplasm*, breast, breast cancer*, theragnostic*, theranostic*, radioligand therap*, RLT, MET, FLT, FMISO, FES, estradiol, trastuzumab, PD-L1, PSMA, FAPI, FACBC, fluciclovine, FAZA, GRPR, DOTATOC, DOTATATE, CXC4, endoglin, gastrin, mucin1, and syndecan1. Results: Fifty-three studies were included in the systematic review and summarized in six clinical sections: 1) human epidermal growth factor receptor 2 (HER2); 2) somatostatin receptors (SSTRS); 3) prostate-specific membrane antigen radiotracers (PSMA); 4) fibroblast activation protein-α targeted radiotracers; 5) gastrin-releasing peptide receptor-targeted radiotracers; 6) other radiotracers for theragnostics. Conclusion: The theragnostic approach will progressively allow better patient selection, and improve the prediction of response and toxicity, avoiding unnecessary and costly treatment.

Background: Internuclear ophthalmoplegia (INO) is a disorder of eye movements caused by a lesion involving the medial longitudinal fasciculus (MLF) within the brainstem, and it is characterized by adduction impairment combined with contralateral dissociated abduction nystagmus. The frequency of acute ischemic stroke (AIS) presenting with INO as a predominant symptom is very low, and many patients suffering from this brainstem AIS are precluded from intravenous thrombolysis (IVT). Objective: To provide for the first time a magnetic resonance imaging (MRI) evidence of response to the IVT in brainstem wake-up stroke presenting with INO as an isolated symptom. Methods: Here, we described a rare case of pons AIS presenting with INO as a unique symptom of awakening. In order to differentiate an ischemic stroke from other stroke mimics, and to determine whether the patient was within the therapeutic window for IVT (wake-up stroke), brain MRI including DWI and FLAIR sequences was acquired. Results: A left paramedian pontine DWI/FLAIR mismatch was detected and the patient was considered eligible for IVT. After IVT, the patient made a full recovery with complete resolution of INO. Follow-up MRI at 1 month demonstrates the absence of ischemic lesions. Conclusion: Our case provides neuroradiological evidence of IVT efficacy in brainstem stroke, and it should prompt clinicians to rapidly perform MRI in wake-up onset INO and to just as quickly administer IVT, since INO is a functionally disabling deficit. Finally, this case demonstrates the value of MRI in diagnostic, prognostic, and therapeutic workup of posterior circulation wake-up stroke.

Purpose: To evaluate the agreement between pathological and radiological staging in oropharyngeal cancer by comparing the 7th and the 8th edition of the AJCC TNM system. Methods: This retrospective cohort study included 57 cases of oropharyngeal cancer with lymph node metastases staged with the 7th and 8th editions of the AJCC TNM system. Comparison between clinical and radiological features and differences in agreement rates were calculated between radiological and pathological staging for the primary tumor (T) and lymph nodes (N) in HPVpos and HPVneg cases. Results: Comparison of HPVpos and HPVneg revealed a significantly different distribution between early and advanced stages in the 8 th edition, with a relevant number of HPVpos patients redefined from advanced stages whit the 7 th ed. to early stages with 8 th ed. (p < 0.01); no significant differences were found when comparing all diagnostic methods for T and N. Conclusions: The 8th edition of the AJCC TNM seems to lead to better pretreatment staging. For both HPVpos and HPVneg, the agreement between pretreatment radiological and pathological staging.

Diabetes is a risk factor for greater severity of coronavirus disease 2019 (COVID-19). The stress hyperglycemia ratio (SHR) is an independent predictor of critical illness, and it is reported to have a stronger association than absolute hyperglycemia. The aim of this study was to assess the relationship of absolute hyperglycemia and SHR with the severity of COVID-19, since there are no studies investigating SHR in patients with COVID-19. We conducted a retrospective observational study on hospitalized patients with COVID-19 in the first months of the pandemic, regarding absolute hyperglycemia, SHR, and severity outcomes. Of the 374 patients, 28.1% had a previous diagnosis of type 2 diabetes. Absolute hyperglycemia (64.8% versus 22.7%; p < 0.01) and SHR [1.1 (IQR 0.9-1.3) versus 1.0 (IQR 0.9-1.2); p < 0.001] showed a statistically significant association with previous diabetes. Absolute hyperglycemia showed a significant association with clinical severity of COVID-19 (79.0% versus 62.7%; p < 0.001), need for oxygen therapy (74.8% versus 54.4%; p < 0.001), invasive mechanical ventilation (28.6% versus 11.6%; p < 0.001), and intensive care unit (30.3% versus 14.9%; p = 0.002), but not with mortality; by contrast, there was no statistically significant association between SHR and all these parameters. Our results are in agreement with the literature regarding the impact of absolute hyperglycemia on COVID-19 severity outcomes, while SHR was not a significant marker. We therefore suggest that SHR should not be evaluated in all patients admitted in the hospital for COVID-19, and we encourage the standard measures at admission of blood glucose and HbA1c levels. info:eu-repo/semantics/publishedVersion

Purpose This study aimed to evaluate the course of olfactory dysfunction [OD] due to upper respiratory tract infections [URTI] especially for COVID-19 [C19] in a multicentric design and to investigate possible predictors for the outcome. Methods In a multicentric study, patients (n = 147, of which 96 were women) with OD due to URTI, including C19 and non-C19 were evaluated at two visits with a standardized medical history and “Sniffin’ Sticks” extended psychophysical testing to examine the course and possible predictors for improvement of olfactory function. Results C19 patients showed better overall olfactory function (p p p = 0.20) except for a more pronounced improvement of odour threshold (p = 0.03) in C19. C19 patients with parosmia exhibited a higher probability of clinically relevant improvement of odour threshold, a better threshold in the second visit, and tended to have a better TDI-score at the second visit. Further possible predictors for an improving olfactory function were younger age, female gender, and had lower scores in olfactory tests at the first visit. Conclusions Patients with C19 and non-C19 URTI exhibit a similar improvement over 3–4 months except for the odour threshold, with a better TDI in both visits for C19. For C19 a better prognosis in terms of olfactory recovery was found for younger patients with parosmia and lower olfactory scores at the first visit. Still, for many patients with olfactory loss, an improvement that is experienced as complete may only occur over months and possibly years.

This paper argues that the current age is best understood as a theological age in that its normal approach to the world is one based on a high level of abstraction. Theology stands in contrast with piety, which derives much more from immediate experience and embodies common sense. The cultural and intellectual development of Europe and the West can be understood in terms of the interaction of two distinct modes of thinking and viewing the world, namely theology and piety, and the way in which theology has come to dominate Western culture to the detriment of piety. Hence, the dominance of Greek rationalism within the West has led to a one-sided culture that gives priority to rationalist modes of thought. There has been a continuing tradition of piety in the West, but its existence has tended to be somewhat fugitive as can be seen, for example, in Musil’s depiction of the ‘other condition’ and in J S Mill’s personal breakdown caused by an excess of theology. The implications of a theological approach for history are evident as historical developments are viewed through the rigid prisms of perspectives that either fragment the study of history into a series of disconnected narratives endowed with their unique telos or impose an all-encompassing narrative that erases differences as well as potentialities. In both cases, it is the theological mode of thought—which has dominated the West since the so-called birth of rationalism—that turns history into ideology. This paper contends that the current condition calls for a new history of philosophy that captures and responds to the crisis affecting the West’s self-understanding and sense of purpose.

PURPOSE Although representing the majority of newly diagnosed cancers, patients with breast cancer appear less vulnerable to COVID-19 mortality compared with other malignancies. In the absence of patients on active cancer therapy included in vaccination trials, a contemporary real-world evaluation of outcomes during the various pandemic phases, as well as of the impact of vaccination, is needed to better inform clinical practice. METHODS We compared COVID-19 morbidity and mortality among patients with breast cancer across prevaccination (February 27, 2020-November 30, 2020), Alpha-Delta (December 1, 2020-December 14, 2021), and Omicron (December 15, 2021-January 31, 2022) phases using OnCovid registry participants (ClinicalTrials.gov identifier: NCT04393974 ). Twenty-eight-day case fatality rate (CFR28) and COVID-19 severity were compared in unvaccinated versus double-dosed/boosted patients (vaccinated) with inverse probability of treatment weighting models adjusted for country of origin, age, number of comorbidities, tumor stage, and receipt of systemic anticancer therapy within 1 month of COVID-19 diagnosis. RESULTS By the data lock of February 4, 2022, the registry counted 613 eligible patients with breast cancer: 60.1% (n = 312) hormone receptor–positive, 25.2% (n = 131) human epidermal growth factor receptor 2–positive, and 14.6% (n = 76) triple-negative. The majority (61%; n = 374) had localized/locally advanced disease. Median age was 62 years (interquartile range, 51-74 years). A total of 193 patients (31.5%) presented ≥ 2 comorbidities and 69% (n = 330) were never smokers. In total, 392 (63.9%), 164 (26.8%), and 57 (9.3%) were diagnosed during the prevaccination, Alpha-Delta, and Omicron phases, respectively. Analysis of CFR28 demonstrates comparable estimates of mortality across the three pandemic phases (13.9%, 12.2%, 5.3%, respectively; P = .182). Nevertheless, a significant improvement in outcome measures of COVID-19 severity across the three pandemic time periods was observed. Importantly, when reported separately, unvaccinated patients from the Alpha-Delta and Omicron phases achieved comparable outcomes to those from the prevaccination phase. Of 566 patients eligible for the vaccination analysis, 72 (12.7%) were fully vaccinated and 494 (87.3%) were unvaccinated. We confirmed with inverse probability of treatment weighting multivariable analysis and following a clustered robust correction for participating center that vaccinated patients achieved improved CFR28 (odds ratio [OR], 0.19; 95% CI, 0.09 to 0.40), hospitalization (OR, 0.28; 95% CI, 0.11 to 0.69), COVID-19 complications (OR, 0.16; 95% CI, 0.06 to 0.45), and reduced requirement of COVID-19–specific therapy (OR, 0.24; 95% CI, 0.09 to 0.63) and oxygen therapy (OR, 0.24; 95% CI, 0.09 to 0.67) compared with unvaccinated controls. CONCLUSION Our findings highlight a consistent reduction of COVID-19 severity in patients with breast cancer during the Omicron outbreak in Europe. We also demonstrate that even in this population, a complete severe acute respiratory syndrome coronavirus 2 vaccination course is a strong determinant of improved morbidity and mortality from COVID-19.

O transtorno dismórfico corporal (TDC) é um transtorno psiquiátrico caracterizado pela preocupação excessiva e distorcida com a aparência física. Na especialidade da cirurgia plástica, é comum que pacientes busquem procedimentos estéticos para corrigir supostas imperfeições corporais decorrentes do TDC. O objetivo desta revisão sistemática é avaliar a prevalência do TDC em pacientes candidatos e/ou submetidos a procedimentos estéticos na especialidade da cirurgia plástica. Foram selecionados estudos que abordam a prevalência do TDC em pacientes submetidos a procedimentos estéticos, publicados entre 2010 e 2022. Os resultados indicam uma prevalência elevada de TDC em pacientes que buscam procedimentos estéticos na cirurgia plástica. A revisão também destaca a importância da avaliação psicológica pré-operatória e do tratamento adequado para pacientes com TDC ou outras condições mentais que possam interferir no resultado da cirurgia e na satisfação do paciente. Uma abordagem multidisciplinar envolvendo cirurgiões plásticos e profissionais de saúde mental é fundamental para garantir a segurança e a satisfação dos pacientes submetidos a procedimentos estéticos.

(1) Background: Biliary tract cancers (BTCs) are a heterogeneous group of neoplasms with dismal prognosis and the role of adjuvant chemoradiotherapy in high-risk resected patients is unclear. (2) Methods: We retrospectively analyzed the outcomes of BTC patients who received curative intent surgery with microscopically positive resection margins (R1) and adjuvant chemoradioradiotherapy (CCRT) or chemotherapy (CHT) from January 2001 to December 201. (3) Results: Out of 65 patients who underwent R1 resection, 26 received adjuvant CHT and 39 adjuvant CCRT. The median recurrence-free survival (RFS) in the CHT and CHRT groups was 13.2 and 26.8 months, respectively (p = 0.41). Median overall survival (OS) was higher in the CHRT group (41.9 months) as compared to the CHT group (32.2 months), but the difference was not statistically significant (HR 0.88; p = 0.7). A promising trend in favor of CHRT was observed in N0 patients. Finally, no statistically significant differences were observed between patients undergoing adjuvant CHRT after R1 resection and patients treated with chemotherapy alone after R0 surgery. (4) Conclusions: Our study did not show a significant survival benefit with adjuvant CHRT over CHT alone in BTC patients with positive resection margins, while a promising trend was observed.

A Sistemática Filogenética é reconhecida como um dos principais eixos para a compreensão crítica da biodiversidade. Esta ciência busca ordená-la de maneira lógica, objetivando a compreensão dos processos que são responsáveis por gerar os padrões que por ela são apresentados. Para tal, trata a evolução biológica, ou seja, o reconhecimento da descendência com modificação e de suas implicações para as relações de ancestralidade e descendência entre as diversas linhagens de seres vivos, como seu paradigma central. No entanto, no Brasil, ainda persistem problemas relacionados ao ensino inadequado e desatualizado da Teoria Evolutiva. Assim, neste trabalho serão apresentados os principais obstáculos epistemológicos relacionados ao aprendizado de evolução e como eles surgiram ao longo da história das ciências naturais. De forma a mostrar como se relacionam entre si e de que maneira contribuem para a manutenção do atual problema denominado impedimento taxonômico. Por fim, serão expostas as potencialidades do estímulo ao pensamento filogenético, isto é, evolutivo, para a compreensão crítica da biodiversidade. Assim, concordamos que o combate às lacunas atuais no conhecimento sobre a biodiversidade deve ser pensado em múltiplos níveis de atuação e investigação científica. Sendo um deles o ensino de Ciências e Biologia, destacamos o papel dos professores, com as potencialidades advindas do desenvolvimento de abordagens didáticas inovadoras junto a um planejamento curricular voltado ao combate dos vícios responsáveis por fomentarem a existência de tais lacunas.

Hypodermic needles are sometimes reused in animal research settings to preserve the viability of and to conserve limited quantities of injected material. However, the reuse of needles is strongly discouraged in human medicine to prevent inju- ries and the spread of infectious disease. No official guidelines prohibit needle reuse in veterinary medicine, although the practice may be discouraged. We hypothesized that reused needles would be significantly more blunt than unused needles and that reuse for additional injections would cause more animal stress. To test these ideas, we evaluated mice that were injected subcutaneously in the flank or mammary fat pad to generate cell line xenograft and mouse allograft models. Needles were reused up to 20 times, based on an IACUC-approved protocol. A subset of reused needles was digitally imaged to determine needle dullness based on the area of deformation from the secondary bevel angle; this parameter was not different between new needles and needles that had been reused 20 times. In addition, the number of times a needle was reused was not significantly related to audible mouse vocalization during injection. Finally, nest building scores for mice that were injected with a needle used 0 through 5 times were similar to those of mice injected with a needle had been used 16 through 20 times. Among the 37 reused needles that were tested, 4 were positive for bacterial growth; the only organisms cultured were Staphylococcus spp. Contrary to our hypothesis, reusing needles for subcutaneous injections did not increase animal stress based on analysis of vocalization or nest building.

A partire dal 2016 gli investimenti comunali sono in continua crescita e si prospetta nei prossimi anni una grande quantità di progetti infrastrutturali, finanziati dal PNRR, che le amministrazioni comunali dovranno gestire. Tuttavia, non tutti i Comuni partono dalla stessa dotazione di infrastrutture sul loro territorio, quindi per un adeguato riparto delle risorse occorre stimare il capitale fisso attualmente a disposizione degli enti locali. Utilizzando il metodo dell'inventario permanente e le spese per investimento dei comuni lombardi nel periodo 2000-2019, si è quindi ricostruito lo stock di capitale pubblico a livello comunale per la Lombardia. Attraverso un modello di regressione semplice, mostriamo come lo stock di infrastrutture sia fortemente determinato dalla popolazione e da alcune caratteristiche socio-economiche e territoriali dei comuni, quali il reddito pro capite, l'altitudine, i chilometri di strade comunali e la presenza di aree ad alta pericolosità idraulica o di frane. Infine, stimiamo lo stock di infrastrutture standard e mettiamo in evidenza come i comuni di piccolissime dimensioni (< 1.000 abitanti) e di grandi dimensioni (>20.000 abitanti) presentino un deficit di infrastrutture rispetto allo standard.

Following the practice-changing results observed in several hematological and solid tumors, immunotherapy with immune checkpoint inhibitors (ICIs) has been tested in cholangiocarcinoma (CCA) patients. However, ICI monotherapy has had disappointing results in CCA, and phase I–III clinical trials have assessed whether combinatorial strategies including immunotherapy plus other anticancer agents may have a synergistic activity. The TOPAZ-1 trial has recently highlighted improved survival in CCA patients receiving first-line durvalumab plus gemcitabine–cisplatin compared with gemcitabine plus cisplatin alone, and several guidelines consider adding durvalumab to the reference doublet as standard of care. This article provides an overview of durvalumab pharmacology, safety and efficacy in CCA, highlighting current and future research directions in this setting.

The structural elucidation of metabolite molecules is important in many branches of the life sciences. However, the isomeric and isobaric complexity of metabolites makes their identification extremely challenging, and analytical standards are often required to confirm the presence of a particular compound in a sample. We present here an approach to overcome these challenges using high-resolution ion mobility spectrometry in combination with cryogenic vibrational spectroscopy for the rapid separation and identification of metabolite isomers and isobars. Ion mobility can separate isomeric metabolites in tens of milliseconds, and cryogenic IR spectroscopy provides highly structured IR fingerprints for unambiguous molecular identification. Moreover, our approach allows one to identify metabolite isomers automatically by comparing their IR fingerprints with those previously recorded in a database, obviating the need for a recurrent introduction of analytical standards. We demonstrate the principle of this approach by constructing a database composed of IR fingerprints of eight isomeric/isobaric metabolites and use it for the identification of these isomers present in mixtures. Moreover, we show how our fast IR fingerprinting technology allows to probe the IR fingerprints of molecules within just a few seconds as they elute from an LC column. This approach has the potential to greatly improve metabolomics workflows in terms of accuracy, speed, and cost.

El presente trabajo trata de una investigación orientada a analizar fuentes científicas y legales para determinar la trascendencia en el proceso histórico de gestión de las políticas públicas en educación intercultural y su correspondencia con los planteamientos de los pueblos indígenas. Se realiza una revisión bibliográfica para construir la descripción de los pueblos y nacionalidades indígenas en el Ecuador, de cara a abordar la importancia de la valoración de sus culturas y lenguas en el proceso del reconocimiento de la interculturalidad y la implementación de la Educación Intercultural Bilingüe (EIB). Se analiza la incorporación de la identidad plurinacional y pluricultural en la normativa ecuatoriana, para luego considerar el proceso de ejecución de políticas públicas en la EIB. Los resultados mostraron que, si bien existen avances en la institucionalización de la EIB en el país, la implementación de las políticas públicas, muchas veces se contraponen a las propuestas e intereses de los pueblos indígenas, provocándose una acción paralela y no correspondiente. Es necesario contribuir al fortalecimiento de la EIB con la participación de los pueblos y nacionalidades para que se incorporen las reivindicaciones de sus derechos a una educación en coherencia y correspondencia con la diversidad.

La Pancreatitis Aguda Recurrente (PAR) es una entidad frecuente de la que hay pocos datos publicados. El objetivo del estudio es hallar la tasa y factores de riesgo asociados a PAR en nuestro medio. Es un estudio retrospectivo, unicéntrico, de pacientes ingresados por Pancreatitis Aguda (PA) y seguidos posteriormente. Se dividen en 2 grupos de pacientes: 1.- pacientes con un solo episodio de PA (PAS) y 2.- pacientes con más de un ingreso por PA (PAR). Se comparan variables clínicas, demográficas y de resultado. Resultados: 561 pacientes fueron incluidos y seguidos durante una media de 67,63 meses. 18,9% tuvieron al menos otro ingreso por PA. La mayoría sufrieron un solo episodio de PAR (93%). La etiología más frecuente fue biliar (67%). En el análisis univariado, una menor edad (p 0,004), la ausencia de hipertensión arterial (p 0,013) y de SIRS (p 0,022) se asociaron con PAR. En el análisis multivariado solo una menor edad se relacionó con PAR (OR 1,015, 95%, IC 1,00-1,029). No encontramos diferencias en las variables resultados entre ambos grupos. La PAR cursó de forma más leve (9% de pancreatitis moderada/graves o graves versus 19%). Casi un 70% de los pacientes con PAR biliar no tenían realizada una colecistectomía tras el ingreso índice. En este subgrupo de PAR, la edad OR 0,964 (95% IC 0,946-0,983), la colecistectomía OR 0,075 (95% IC 0,189-0,030) y la colecistectomía más colangiografía retrógrada OR 0,190 (95% IC 0,219-0,055) se asociaban a ausencia de PAR. Conclusión: Nuestra tasa de PAR fue 18,9%, con una menor edad como factor de riesgo. La etiología biliar fue la más frecuente que podría haberse evitado de haber realizado colecistectomía o colecistectomía más colangiografía retrógrada tras el primer ingreso.

High amounts of grains in the equine diet led to high starch intake, causing gut alterations. Aimed at reducing harmful effects, Macleaya cordata extract (MCE) is a phytogenic additive that stands out for its antibiotic and anti-inflammatory effects proven in different species. However, there is no useful information for horses. The objective of this study was to evaluate the effects of different levels of the inclusion of commercial MCE on body weight (BW), body condition score (BCS), total apparent digestibility (AD) of nutrients, faecal pH and fermentative products, on ponies fed a high-starch diet. Eight healthy gelding Mini Horse ponies were used. The study design was contemporary double Latin-square 4 × 4 in the experimental unit, with the animal inside each experimental period (n = 8 experimental units per group). The experiment was conducted over four 20-d periods. Basal diet attended 1.75% BW dry matter daily and starch intake was 2.2 g/kg BW/meal. The experimental groups were as follows: control – without food additive; S1–1 mg/kg BW MCE; S1.5–1.5 mg/kg BW MCE and S2–2 mg/kg BW MCE. The data were analysed by PROC MIXED of SAS (p < 0.05). Tendency was considered when 0.05 < p < 0.1. Our results showed higher ether extract (EE) AD for S2 group (63.75%) when compared with the control (54.55%) (p = 0.0377). Lactate was lower (p = 0.0391) in S1 (3.27 mmol/l) and S2 (3.24 mmol/l) groups, although pH was not different between groups. Iso-valerate was greater in S1 group (2.29 mmol/l; p = 0.0289), and a tendency of higher butyrate values was found for S1 and S2 groups (p = 0.0980). We concluded that MCE supplementation probably positively influences equine resident microbiota, improving EE AD and increasing iso-valerate concentration. It can also minimise harmful high-starch impact. We recommend further studies using MCE in horses for a better understanding of its local activity and possible benefits.

Despite the fact that gastric syphilis is considered rare, it is reported as a type of organic involvement that is present in a large proportion of secondary syphilis cases, even though gastritis presenting with symptoms is extremely rare. Clinical, radiological, and endoscopic findings are non-specific and frequently mimic the symptoms of gastric adenocarcinoma or lymphoma, making diagnosis difficult. Immunostaining is required for this diagnosis. We would like to emphasize the importance of being suspicious of GS when a gastric mass exhibits the histologic features of an inflammatory pseudotumor (IPT), as previously reported for nodal IPT caused by luetic infection. We described a 56-year-old man who presented to the oncology department with a 3-month history of anorexia, epigastric pain, nausea, vomiting, and weight loss, as well as an initial radiological and endoscopic suspicion of gastric adenocarcinoma, in which immune staining allowed us to diagnose GS. In addition, we conducted an updated scoping review of the scientific literature to show the clinical, laboratory, and therapeutic findings in GS patients over the last 65 years.

The alveolar epithelial glycocalyx is a dense anionic layer of glycosaminoglycans (GAGs) and proteoglycans that lines the apical surface of the alveolar epithelium. In contrast to the pulmonary endothelial glycocalyx, which has well-established roles in vascular homeostasis and septic organ dysfunction, the alveolar epithelial glycocalyx is less understood. Recent preclinical studies demonstrated that the epithelial glycocalyx is degraded in multiple murine models of acute respiratory distress syndrome (ARDS), particularly those that result from inhaled insults (so-called “direct” lung injury), leading to shedding of GAGs into the alveolar airspaces. Epithelial glycocalyx degradation also occurs in humans with respiratory failure, as quantified by analysis of airspace fluid obtained from ventilator heat moisture exchange (HME) filters. In patients with ARDS, GAG shedding correlates with the severity of hypoxemia and is predictive of the duration of respiratory failure. These effects may be mediated by surfactant dysfunction, as targeted degradation of the epithelial glycocalyx in mice was sufficient to cause increased alveolar surface tension, diffuse microatelectasis, and impaired lung compliance. In this review, we describe the structure of the alveolar epithelial glycocalyx and the mechanisms underlying its degradation during ARDS. We additionally review the current state of knowledge regarding the attributable effect of epithelial glycocalyx degradation in lung injury pathogenesis. Finally, we address glycocalyx degradation as a potential mediator of ARDS heterogeneity, and the subsequent value of point-of-care quantification of GAG shedding to potentially identify patients who are most likely to respond to pharmacological agents aimed at attenuating glycocalyx degradation.

Sudden cardiac death (SCD) pathophysiological point of view can be either mechanical or electrical. In case of mechanical SCD, the most frequent causes are pulmonary thromboembolism and cardiac tamponade due to intrapericardial rupture (aortic dissection, heart rupture). This distinction is important because cardiac arrest retains survival potential through cardiopulmonary resuscitation and defibrillators only if the rhythm is shockable. The heart diseases that can cause SCD vary according to the age of the individual. In young people, primary electrical diseases (‘ion channel diseases’) and cardiomyopathies (particularly hypertrophic and arrhythmogenic), both genetically determined and therefore potentially recurred in the proband’s family, as well as myocarditis and coronary anomalies prevail; in adult–elderly populations, coronary atherosclerosis with its complications and degenerative valve diseases (aortic stenosis and mitral valve prolapse) predominate. In this short text, the main structural heart diseases characterized by electrical instability at risk of SCD will be recalled, with a focus on coronary, myocardial, and valvular diseases.

Prostate cancer is the most frequently diagnosed cancer in men in the United States. Among the different available treatment options, radiation therapy is recommended for localized or even advanced disease. Erectile dysfunction (ED) often occurs after radiation therapy due to neurological, vascular, and endocrine mechanisms resulting in arterial tone alteration, pudendal-nerve neuropraxia, and lastly fibrosis. Considering the influence of quality of life on patients’ treatment choice, radiation-therapy-induced ED prevention and treatment are major issues. In this narrative review, we briefly summarize and discuss the current state of the art on radiation-therapy-induced ED in PCa patients in terms of pathophysiology and available treatment options.

La necesidad de generar alimentos en forma continua para el consumo de la población requiere del desarrollo de nuevos productos alimenticios y de la mejor utilización de estos, las salchichas de atún de Ecuador son productos en el cual está incursionando la industria pesquera y son una gran oportunidad de consumo en el mercado argentino, puesto que, es un país donde acostumbran a consumir embutidos a la parrilla, siendo este un producto diferente al tradicional, así, existen empresas que se dedican a la elaboración y comercialización de este tipo de producto a base de carne de pescado, y que en este caso la materia prima es el atún que contiene dentro de sus propiedades el Omega 3 y una gran cantidad de vitaminas que ayudan al sistema inmunológico del ser humano. El presente artículo tiene como objetivo lograr que la empresa que expone sus productos, sea más competitiva para satisfacer las necesidades del mercado argentino contribuyendo como gran oportunidad de negocio a los productores ecuatorianos y una oportunidad de comercialización del producto en el mercado argentino, la metodología que se llevó a cabo en la investigación fue mixta, las técnicas de recolección de datos que se usaron fueron encuestas, entrevistas con ellos se obtuvieron resultados concisos para la elaboración del articulo para de esta manera poder determinar estrategias para la comercialización del producto en el mercado argentino. Con base en la investigación realizada, la factibilidad del mercado objetivo depende de los posibles distribuidores, niveles de consumo y tipos de consumidores existentes.

Background: Leber congenital amaurosis is the first form of inherited retinal dystrophy (IRD) treated with a gene therapy approach using voretigene neparvovec (VN). To date, 42 patients have been treated, 25 of whom, treated at Clinica Oculistica Vanvitelli (Naples), have shown – after 45 days of treatment – a significant increase in dim-light visual function, a widening of the visual field, and an increase in central visual acuity. Objective: A workshop has been organized to foster rapid access, investigate the current organizational scenario, and identify a value framework suitable for making gene therapy delivery efficient in terms of efficacy, safety, and sustainability. Methods: The workshop involved 14 experts in clinical genetics, ophthalmology, and vitreoretinal surgery. All experts were subjected to questions related to three topics: diagnostic-therapeutic pathway of IRD patients, essential requirements for gene therapy delivery centres, and standardized model for therapy delivery. All contributions were judged to be of equal value. Results: The panel identified: the steps of the diagnostic pathway to achieve early diagnosis; the essential criteria that delivery centres must possess in terms of experience, multidisciplinary team, and technical equipment; a standardized model for VN administration. A network of few centres was identified as the best organizational model for VN delivery since it would ensure the gaining of experience and clinical excellence. Conclusion: This paper provides a perspective that can be used as a starting point to standardize the diagnostic-therapeutic pathway of IRD patients and define the essential requirements that centres must meet for VN administration.

La investigación es un eje transversal en la educación en general. El proceso investigativo es la Génesis del conocimiento. La educación superior, por otro lado, depende de las habilidades de investigación de los docentes y estudiantes. El propósito de este estudio es describir la importancia de la investigación en el ámbito superior. La metodología empleada fue de investigación descriptiva, de tipo documental. Se debe concluir que la investigación tiene una gran importancia en el proceso de formación de profesionales, es decir, en la educación superior. La calidad y la actualización constante depende de las habilidades investigativas que desarrollen durante su proceso de formación. La investigación es el medio mediante el cual se encuentran soluciones a los problemas, se da respuesta a las interrogantes y además permite obtener información objetiva con el fin de crear y ofrecer estrategias; que inviten a mejorar las condiciones de adquirir nuevos conocimientos para promover el proceso de aprendizaje.