Uncovering the neural control of laryngeal activity and subglottic pressure in anaesthetized rats: insights from mesencephalic regions.

To assess the possible interactions between the dorsolateral periaqueductal gray matter (dlPAG) and the different domains of the nucleus ambiguus (nA), we have examined the pattern of double-staining c-Fos/FoxP2 protein immunoreactivity (c-Fos-ir/FoxP2-ir) and tyrosine hydroxylase (TH) throughout the rostrocaudal extent of nA in spontaneously breathing anaesthetised male Sprague-Dawley rats during dlPAG electrical stimulation. Activation of the dlPAG elicited a selective increase in c-Fos-ir with an ipsilateral predominance in the somatas of the loose (p < 0.05) and compact formation (p < 0.01) within the nA and confirmed the expression of FoxP2 bilaterally in all the domains within the nA. A second group of experiments was made to examine the importance of the dlPAG in modulating the laryngeal response evoked after electrical or chemical (glutamate) dlPAG stimulations. Both electrical and chemical stimulations evoked a significant decrease in laryngeal resistance (subglottal pressure) (p < 0.001) accompanied with an increase in respiratory rate together with a pressor and tachycardic response. The results of our study contribute to new data on the role of the mesencephalic neuronal circuits in the control mechanisms of subglottic pressure and laryngeal activity.

Scaphanocephalus spp. (Trematoda: Opisthorchiidae) in intermediate and definitive hosts of the Yucatán Peninsula, Mexico, with a re-description of Scaphanocephalus expansus.

Scaphanocephalus is a small trematode genus belonging to the family Opistorchiidae. The genus currently contains only three species associated with marine fish as intermediate hosts and fish-eating birds as definitive hosts. Here, specimens of Scaphanocephalus were collected from the Osprey, Pandion haliaetus, and the White mullet, Mugil curema in the Yucatán Peninsula, Mexico. We report for the first-time DNA sequences of adult specimens of Scaphanocephalus, particularly S. expansus, as well as a sequence of a different species sampled as metacercaria. Morphological comparisons of Scaphanocephalus expansus confirmed the identity of the adult specimens, with minor morphological variations; Scanning electron photomicrographs were included, and the species was re-described. Phylogenetic analysis based on 28S rDNA sequences showed that Scaphanocephalus is monophyletic within Opisthorchiidae and consists of three independent lineages. Sequences of adults are identical to those of S. expansus. Instead, the sequence of the metacercaria sampled from the mesentery of Mugil curema nested with specimens reported as Scaphanocephalus sp. from a labrid fish in the Mediterranean Sea, herein named it as Scaphanocephalus sp. 2.

Optical Binding-Driven Micropatterning and Photosculpting with Silver Nanorods.

Controlling the nano- and micropatterning of metal structures is an important requirement for various technological applications in photonics and biosensing. This work presents a method for controllably creating silver micropatterns by laser-induced photosculpting. Photosculpting is driven by plasmonic interactions between pulsed laser radiation and silver nanorods (AgNRs) in aqueous suspension; this process leads to optical binding forces transporting the AgNRs in the surroundings, while electronic thermalization results in photooxidation, melting, and ripening of the AgNRs into well-defined 3D structures. This work call these structures Airy castles due to their structural similarity with a diffraction-limited Airy disk. The photosculpted Airy castles contain emissive Ag nanoclusters, allowing for the visualization and examination of the aggregation process using luminescence microscopy. This work comprehensively examines the factors that define the photosculpting process, namely, the concentration and shape of the AgNRs, as well as the energy, power, and repetition rate of the laser. Finally, this work investigates the potential applications by measuring the metal-enhanced luminescence of a europium-based luminophore using Airy castles.

Phylogenetic analyses based on molecular and morphological data reveal a new species of Strigea Abildgaard, 1790 (Digenea: Strigeidae) and taxonomic changes in strigeids infecting Neotropical birds of prey.

Members of the genus Strigea Abildgaard, 1790 are endoparasites of birds distributed worldwide. Adults of an undescribed species of the genus Strigea were collected from the intestines of two hawk species (Rupornis magnirostris and Accipiter coperii). Other species identified as Parastrigea macrobursa that were described in Argentina were also recovered from two hawk species (Buteogallus urubitinga and Buteogallus anthracinus) in three localities along the coasts of Mexico. Specimens of the two species were sequenced for three molecular markers, the internal transcribed spacers locus (ITS1-5.8S rDNA- ITS2) and the domains D1-D3 from the large subunit from nuclear ribosomal DNA and the cytochrome c oxidase subunit 1 from mitochondrial DNA. The newly sequenced specimens were aligned with other strigeids sequences downloaded from GenBank. Maximum likelihood and Bayesian analyses inferred with each molecular marker revealed that our specimens of Strigea sp. formed an independent lineage, which is recognized herein as a new species, Strigea magnirostris n. sp., representing the first species in Mexico and the 16th in the Neotropical region. Morphologically, the new species is distinguished from other congeneric species from the Americas by having an oral sucker with several papillae around it, well-developed pseudosuckers (118-248 µm), a tegument covered with tiny spines, a larger cone genital (193-361 × 296-637) and a larger copulatory bursa (247-531 × 468-784). Our phylogenetic analyses revealed that P. macrobursa is not closely related to other members of the genus Parastrigea and is nested within Strigea, suggesting that P. macrobursa should be transferred to Strigea to form Strigea macrobursa n. comb., expanding its distribution range from Mexico to Argentina. Finally, the analyses also revealed that the taxonomy and systematics of Strigea should be re-evaluated, combining morphological and molecular characteristics.

Molecular and morphological characterization of Andracantha gravida (Alegret, 1941) (Acanthocephala: Polymorphidae) in piscivorous birds from the Gulf of Mexico.

Adult specimens of Andracantha gravida (Alegret, 1941) were recorded from the intestines of the double-crested cormorant Nannopterum auritus (Lesson) (type host) and brown pelican Pelecanus occidentalis L. in two localities from Mexico: Celestún, Yucatan (south-eastern) and Punta Piedra, Tamaulipas (north-eastern). The specimens of A. gravida are morphologically characterized by having a pipe-shaped body without swellings, the absence of small trunk spines between the two fields of spines on the foretrunk and a cylindrical proboscis with 14-16 rows of 10-12 hooks per row. Newly generated partial sequences of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene were generated from adult isolates of A. gravida from Mexico and compared with one sequence of A. gravida and with sequences of other polymorphid acanthocephalans available in GenBank. Phylogenetic analyses based on maximum likelihood and Bayesian inference methods of the cox1 dataset placed all the species of Andracantha in a single clade, with weak support. The analyses of the cox1 dataset placed Andracantha sigma Presswell, García-Varela & Smales, , as sister to the clade formed by A. gravida, Andracantha phalacrocoracis (Yamaguti, 1939), Andracantha leucocarboi Presswell, García-Varela & Smales, and an unidentified species of Andracantha from Japan. The newly generated cox1 sequences of A. gravida from piscivorous birds of Mexico formed a strongly supported clade with the published sequence of A. gravida from the double-crested cormorant from the south-eastern coast of Mexico. The intraspecific genetic divergence among isolates identified as A. gravida ranged from 0.0% to 2.2%. A cox1 haplotype network inferred with 14 sequences revealed the presence of nine haplotypes, two of which were shared between the populations of piscivorous birds from the north-eastern and south-eastern coasts of Mexico and seven of which were unique. The fixation index between the populations from north-eastern and south-eastern Mexico was low (0.06949), which suggests genetic flow. This can be explained by the migration patterns of the brown pelican and the double-crested cormorant along the coasts of the Gulf of Mexico.

Impact of the glutamatergic neurotransmission within the A5 region on the cardiorespiratory response evoked from the midbrain dlPAG.

Stimulation of the dorsolateral periaqueductal grey matter (dlPAG) in rats evokes an active defensive behaviour together with a cardiorespiratory response characterised by tachypnoea, tachycardia and hypertension. The dlPAG neurons involved in these responses are excitatory, presumably glutamatergic, due to the presence of vesicular glutamate transporter VGLUT2 within their axon terminals. Previously, our group described a functional interaction between dlPAG and the pontine A5 region. Accordingly, in the present work, in order to characterize the role of glutamate within this interaction, experiments were carried out in spontaneously breathing anaesthetized rats (sodium pentobarbitone 60 mg/kg i.p., suplemented with 20 mg/kg i.p.). The cardiorespiratory response evoked by electrical stimulation of the dlPAG (1 ms pulses, 20-50 µA, given at 100 Hz, during 5 s) was analysed before and after the microinjection, within the A5 region, of either kynurenic acid (non-specific glutamate receptor antagonist; 5-10 nmol), DAP-5 (NMDA antagonist; 1 pmol), CNQX (non-NMDA antagonist; 1 pmol) or MCPG (metabotropic antagonist; 0,1 nmol). Kynurenic acid decreased the intensity of both the tachypnoea (p < 0,001) and tachycardia (p < 0,001) induced by dl-PAG stimulation. Blockade of no-NMDA receptors reduced the increase of respiratory frequency, heart rate and pressor response to dl-PAG stimulation (p < 0,01, p < 0,001, p < 0,05 respectively). Blockade of either NMDA or metabotropic receptors reduced the dlPAG-evoked tachycardia and pressor response (p < 0,01; p < 0,05 respectively). These results suggest a neuromodulatory role for A5 region via glutamate neurotransmission of the dlPAG-evoked cardiorespiratory response, confirming the role of the ventrolateral pons in the neuronal circuits involved in respiratory and heart rate control.

Fibrous hamartoma of infancy. Radiologic-pathologic study of 21 cases: 8 with predominant pseudoangiomatous pattern.

Fibrous hamartoma of infancy (FHI) is a very rare benign soft tissue lesion that principally affects the axilla, trunk, and upper extremities of children younger than 2 years. It is usually cured by local excision. Histologically, these lesions have a triphasic morphology in an organoid pattern: mature adipose tissue, fibroblastic/myofibroblastic trabeculae, and small round cell nests in a myxoid matrix. However, morphologic variants have recently been described. Focal areas with a pseudoangiomatous pattern have been found in some FHI, but few cases with predominant pseudoangiomatous areas have been previously described in the medical literature. We report 21 new cases of FHI, 8 of them with a predominant pseudoangiomatous pattern. Our cases with a predominant pseudoangiomatous pattern did not present specific radiological findings.

A multicomponent reaction platform towards multimodal near-infrared BODIPY dyes for STED and fluorescence lifetime imaging.

We report a platform combining multicomponent reaction synthesis and automated cell-based screening to develop biocompatible NIR-BODIPY fluorophores. From a library of over 60 fluorophores, we optimised compound NIRBD-62c as a multimodal probe with suitable properties for STED super-resolution and fluorescence lifetime imaging. Furthermore, we employed NIRBD-62c for imaging trafficking inside cells and to examine how pharmacological inhibitors can alter the vesicular traffic between intracellular compartments and the plasma membrane.

Calcifying aponeurotic fibroma: Radiologic-pathologic analysis of ten cases and review of the literature.

Calcifying aponeurotic fibroma (CAF) is a very rare benign entity that principally affects the volar fascia, tendons, and aponeuroses of the hands and feet with a peak incidence of between 5 and 15 years, although there have been cases found for a wide age range and at various anatomical sites. We present ten CAF cases; consisting of eight children and two adults. CAF occurred in the extremities in nine of the cases and in the chest wall in one case. CAF ultrasound and radiological findings are nonspecific but may help orientate diagnosis. Magnetic resonance imaging should be performed when there are doubtful cases, when occurring in nontypical sites, and when there are cases of nontypical clinical presentation. Histologically, all cases showed two components, a fibromatosis-like component and a nodular component. Chondroid areas were present in five cases. Calcifications were observed in nine cases. ERG immunostaining showed the same patterns in all the cases; diffuse positivity in pericalcified areas, and patchy positivity in areas away from calcifications. CAF has distinctive histopathological features which should aid in the differential diagnoses with other entities.

Factores relacionados con la cesación de tabaco en un programa de atención integral del tabaquismo en Bogotá / Factors related to smoking cessation in a comprehensive tobacco care program in Bogotá

Introducción. Los programas interdisciplinarios queincluyen tratamiento farmacológico y técnicas cognitivo-conductuales son efectivos en lograr la abstinenciatabáquica. Hay factores que condicionan el proceso de cesación. No hay estudios en Colombia de cesación tabáquica y los factores asociados. Pacientes y métodos.Pacientes consecutivos del programa de atención integral de cesación de tabaco de laFundación Neumológica Colombiana (EXFUMAIRE)de 2015-2019. Se definió cesación como la abstinencia al cigarrillo >12 meses. Diferencias entre grupos de cesación y no cesación con pruebas T, U de Mann-Whitney y χ2. Análisis multivariado para evaluar factores asociadosa la cesación.Resultados.Se incluyeron 170 sujetos de 55,8 ± 12,8años, el 50,6% mujeres. Hubo cesación en 113(66,5%). No hubo diferencias demográficas, historiade tabaquismo, comorbilidades o tratamiento farmacológico entre los grupos de cesación y no cesación. El 64,1% de los pacientes recibió terapia cognitivo-conductual y el 88,2% tratamiento farmacológico. La razón de no recibir terapia cognitivo-conductual fue la noaceptación del paciente, y la de no recibir tratamientofarmacológico la no disponibilidad del medicamento ono aceptación del paciente. El único factor asociado acesación en el análisis multivariado fue la motivaciónpor la escala Richmond (OR 0,81; p = 0,038).Conclusiones.La tasa de cesación de tabaquismo del66,5% fue alta. El único factor asociado con cesaciónfue la mayor motivación para cesar el tabaquismo. Lasbarreras para recibir el tratamiento farmacológico opsico-conductual son la no aceptación del paciente ola disponibilidad del medicamento. (AU)

Introduction. Interdisciplinary programs that include pharmacological treatment and cognitive behavioraltechniques are effective in achieving smoking abstinence. There are factors that condition the cessationprocess. There are no studies in Colombia on smokingcessation and the associated factors.Patients and methods.Consecutive patients of thecomprehensive smoking cessation care program of the Colombian Pneumological Foundation (EXFUMAIRE)from 2015-2019. Cessation was defined as abstinence from cigarettes >12 months. Differences between cessation and non-cessation groups with T-tests, Mann-Whitney U Test and χ2. Multivariate analysis to evaluatefactors associated with cessation.Results.A total of 170 subjects aged 55.8 ± 12.8years, 50.6% women were included. Cessation occurredin 113 (66.5%). There were no differences in the demographics, smoking history, comorbidities, or drug treatment between the cessation and non-cessation groups.A total of 64.1% of the patients received cognitivebehavioral therapy and 88.2% pharmacological treatment. The reason that cognitive behavioral therapy wasnot received was the non-acceptance of the patient and that of not receiving pharmacological treatment wasthe non-availability of the medication or non-acceptance of the patient. The only factor associated with smoking cessation in the multivariate analysis was the Richmond’ motivation scale (OR 0.81; p = 0.038).Conclusions.The smoking cessation rate of 66.5%was high. The only factor associated with cessation was the increased motivation to quit smoking. Barriers toreceive pharmacological or psycho-behavioral treatment are the non-acceptance of the patient or lack ofavailability of the medication. (AU)

Prevalence of pulmonary hypertension in COPD patients living at high altitude.

BACKGROUND: Pulmonary hypertension (PH) is associated with poor prognosis for patients with chronic obstructive pulmonary disease (COPD). Most of the knowledge about PH in COPD has been generated at sea level, with limited information associated with high altitude (HA). OBJECTIVES: To assess the prevalence and severity of PH in COPD patients living in a HA city (2,640 m). METHODS: Cross-sectional study in COPD patients with forced expiratory volume in the first second / forced vital capacity ratio (FEV1/FVC) post-bronchodilator <0,7. Transthoracic echocardiography (TTE), spirometry, carbon monoxide diffusing capacity, and arterial blood gasses tests were performed. Patients were classified according to the severity of airflow limitation. PH was defined by TTE as an estimated systolic pulmonary artery pressure (sPAP) > 36 mmHg or indirect PH signs; severe PH as sPAP > 60 mmHg; and disproportionate PH as an sPAP > 60 mmHg with non-severe airflow limitation (FEV1 > 50% predicted). RESULTS: We included 176 COPD patients. The overall estimated prevalence of PH was 56.3% and the likelihood of having PH increased according to airflow-limitation severity: mild (31.6%), moderate (54.9%), severe (59.6%) and very severe (77.8%) (p = 0.038). The PH was severe in 7.3% and disproportionate in 3.4% of patients. CONCLUSIONS: The estimated prevalence of PH in patients with COPD at HA is high, particularly in patients with mild to moderate airflow limitation, and greater than that described for COPD patients at low altitude. These results suggest a higher risk of developing PH for COPD patients living at HA compared to COPD patients with similar airflow limitation living at low altitude.

Niveles séricos de PAPP-A y beta-hCG en el primer trimestre del embarazo como predictores de resultados obstétricos desfavorables en el Hospital Universitario Nuestra Señora de Candelaria / Serum levels of PAPP-A and beta-hCG in the first trimester of pregnancy as predictors of unfavourable obstetric outcomes at Hospital Universitario Nuestra Señora de Candelaria

Muchos estudios han documentado la asociación entre valores bajos de PAPP-A y β-hCG en el suero materno durante el primer trimestre, así como efectos materno-fetales adversos.Para valorar dicha relación, en nuestro medio se llevó a cabo un análisis retrospectivo de casos y controles anidado en una cohorte de pacientes con embarazo único en quienes se realizó el cribado del primer trimestre entre 2017 y 2018. Se consideraron casos aquellas pacientes con niveles de MoM PAPP-A y/o β-hCG iguales o inferiores al percentil 5, y como controles a una muestra aleatorizada de pacientes con niveles séricos por encima de dicho percentil.El análisis de nuestros resultados demostró que en los grupos con niveles bajos de MoM PAPP-A y MoM β-hCG se observó un mayor riesgo de desarrollar crecimiento intrauterino restringido que en el grupo control (OR: 2,7 y 3,17, respectivamente). En el grupo MoM PAPP-A≤p5 también se obtuvo un riesgo 3,8 veces superior de estados hipertensivos del embarazo (IC: 1,94-7,83) y 7,9 veces mayor de muerte fetal anteparto (IC:1,09-217,4). Estas dos variables no resultaron estadísticamente significativas en el grupo MoM β-hCG ≤p5.Nuestros hallazgos confirmaron que los niveles bajos de PAPP-A y β-hCG en el suero de las gestantes se asoció con un riesgo elevado de desarrollar complicaciones obstétricas, por lo que podrían utilizarse para la detección precoz de las mismas y prevención de malos resultados obstétricos.

Many studies have documented the association between low PAPP-A and β-hCG values in maternal serum during the first trimester and adverse maternal-foetal effects.To assess this relationship a retrospective analysis of cases and controls was carried out, based on a cohort of patients with a single pregnancy who underwent first-trimester screening between 2017 and 2018. For the group of cases, patients with MoM levels PAPP-A and/or β-hCG equal to or below the 5th percentile were selected. The control group was obtained by making a randomized selection of all patients with MoM PAPP-A levels and/or β-hCG above that percentile.The analysis of our results showed that in groups with low levels of MoM PAPP-A and MoM β- hCG, we observed a higher risk of developing restricted intrauterine growth than in the control group (OR: 2.7 and 3.17, respectively). In the MoM PAPP-A ≤p5 group we also obtained a 3.8-foldhigher risk of global hypertensive states of pregnancy (CI: 1.94-7.83) and 7.9-fold higher risk of antepartum foetal death (CI: 1.09- 217.4). These two variables were not statistically significant in the MoM β-hCG ≤p5 group.Our findings confirmed that low levels of PAPP-A and β-hCG in the serum of pregnant women are associated with a high risk of developing obstetric complications, so they could be used for their early detection and the prevention of poor obstetric results.

[Multidisciplinary nutritional consensus on assessment and nutritional dietary treatment in patients with chronic kidney disease and SARS-CoV-2 infection]. / Consenso multidisciplinar sobre la valoración y el tratamiento nutricional y dietético en pacientes con enfermedad renal crónica e infección por SARS-CoV-2. Consenso de nutrición en enfermedad renal crónica e infección por SARS-CoV-2.

The presence of malnutrition in patients with chronic kidney disease (CKD) is high, it can be made worse by SARS-CoV-2 infection.The nutritional assessment should be adapted to minimize the infection, recommending monitoring: weight loss percentage, body mass index (BMI), loss of appetite, analytical parameters and functional capacity using the dynamometer. As well as the sarcopenia assessment using the SCARF scale, and the possibility of using the GLIM criteria in those patients who have been tested positive by MUST.It is important to adapt the nutritional recommendations in the caloric and protein intake, to the CKD stage and to the SARS-CoV-2 infection stage. In patients with hypercatabolism, to prioritize preserving the nutritional status (35 kcal/kg weight/day, proteins up to 1.5 g/kg/day). The rest of the nutrients will be adapted to CKD stage and the analytical values.In the post-infection stage, a complete nutritional assessment is recommended, including sarcopenia. The energy and protein requirements in this phase will be adapted to the nutritional status, with special attention to the loss of muscle mass.Dietary recommendations need to be tailored to side effects of SARS-CoV-2 infection: anorexia, dysphagia, dysgeusia, and diarrhea.Anorexia and hypercatabolism makes it difficult to meet the requirements through diet, therefore the use of oral nutritional supplements is recommended as well as the enteral or parenteral nutrition in severe phases.

Dynamic Excimer (DYNEX) Imaging of Lipid Droplets.

Unraveling cellular physiological processes via luminescent probes that target specific cellular microenvironments is quite challenging due to the uneven distribution of probes. Herein, we designed a new dynamic excimer (DYNEX) imaging method that involves the sensitive detection of nanosecond-scale dynamic molecular contacts of a fluorescent acridone derivative and reveals the cell microenvironment polarity. Using our method, we specifically tracked cell lipid droplets in fibroblast colon carcinoma cells. These organelles play a central role in metabolic pathways, acting as energy reservoirs in regulatory processes. DYNEX imaging provides the inner polarity of cell lipid droplets, which can be related to lipid contents and metabolic dysfunctions. This new methodology will inspire development of novel multidimensional fluorescent sensors that are able to provide target-specific and orthogonal information at the nanosecond scale.

Phylogenetic affinities of Forticulcitinae (Haploporidae) parasites of mullet from the Americas, with the description of three new species and notes on the genera and key species.

Members of Forticulcitinae Blasco-Costa, Balbuena, Kostadinova & Olson, 2009 include endoparasites of mullet fishes distributed worldwide. Adult specimens were collected from the intestines of white mullet (Mugil curema) and flathead grey mullet (Mugil cephalus) from five localities in the Gulf of Mexico and a single locality in Venezuela. Photogenophores were sequenced for two nuclear molecular markers, the large subunit (LSU) and second internal transcribed spacer (ITS2) of nuclear rDNA. The new sequences were aligned with other sequences downloaded from GenBank. The maximum likelihood and Bayesian inferences were deduced using the combined dataset (LSU + ITS2). The phylogenetic analyses revealed four new lineages belonging to Forticulcitinae. Three new species are described in the present study. Ekuarhuni mexicanus n. sp. can be differentiated from its congeneric species by presenting a longer hermaphroditic sac length (136-180 µm) and a wider testis (91-123 µm). Forticulcita macropharyngis n. sp. and Forticulcita venezuelensis n. sp. are the 8th and 9th species described in Forticulcita. Both species belong to the diminutive morphotype of Forticulcita. Forticulcita macropharyngis n. sp. can be morphologically distinguished from the other congeneric species by the presence of a massive and muscular pharynx (46-110 µm long, 74-106 µm wide). Forticulcita venezuelensis n. sp. is the second species of the studied genus recorded in South America and can be differentiated from congeneric species by possessing the largest testis (138-201 µm long, 83-100 µm wide). Finally, the fourth lineage corresponds to Overstreetoides Andrade-Gómez & García-Varela, 2021; however, few specimens of this lineage were collected, precluding any description of the species. In addition, a key is proposed for differentiating the genera and species of Forticulcitinae.

Synthesis, biological, and photophysical studies of molecular rotor-based fluorescent inhibitors of the trypanosome alternative oxidase.

We have recently reported on the development and trypanocidal activity of a class of inhibitors of Trypanosome Alternative Oxidase (TAO) that are targeted to the mitochondrial matrix by coupling to lipophilic cations via C14 linkers to enable optimal interaction with the enzyme's active site. This strategy resulted in a much-enhanced anti-parasite effect, which we ascribed to the greater accumulation of the compound at the location of the target protein, i.e. the mitochondrion, but to date this localization has not been formally established. We therefore synthesized a series of fluorescent analogues to visualize accumulation and distribution within the cell. The fluorophore chosen, julolidine, has the remarkable extra feature of being able to function as a viscosity sensor and might thus additionally act as a probe of the cellular glycerol that is expected to be produced when TAO is inhibited. Two series of fluorescent inhibitor conjugates incorporating a cationic julolidine-based viscosity sensor were synthesized and their photophysical and biological properties were studied. These probes display a red emission, with a high signal-to-noise ratio (SNR), using both single- and two-photon excitation. Upon incubation with T. brucei and mammalian cells, the fluorescent inhibitors 1a and 2a were taken up selectively in the mitochondria as shown by live-cell imaging. Efficient partition of 1a in functional isolated (rat liver) mitochondria was estimated to 66 ± 20% of the total. The compounds inhibited recombinant TAO enzyme in the submicromolar (1a, 2c, 2d) to low nanomolar range (2a) and were effective against WT and multidrug-resistant trypanosome strains (B48, AQP1-3 KO) in the submicromolar range. Good selectivity (SI > 29) over mammalian HEK cells was observed. However, no viscosity-related shift could be detected, presumably because the glycerol was produced cytosolically, and released through aquaglyceroporins, whereas the probe was located, virtually exclusively, in the trypanosome's mitochondrion.

The Effect of Nutritional Interventions on Long-Term Patient Survival in Advanced Chronic Kidney Disease.

Patients with end-stage kidney disease (ESKD) are at high risk of malnutrition and subsequent related mortality when starting dialysis. However, there have been few clinical studies on the effect of nutritional interventions on long-term patient survival. A 2-year longitudinal study was conducted from January 2012 to December 2016. A total of 186 patients with non-dialysis ESKD started the nutritional education program (NEP), and 169 completed it. A total of 128 patients participated in a NEP over 6 months (personalized diet, education and oral supplementation, if needed). The control group (n = 45) underwent no specific nutritional intervention. The hospitalization rate was significantly lower for the patients with NEP (13.7%) compared with the control patients (26.7%) (p = 0.004). The mortality odds ratio for the patients who did not receive NEP was 2.883 (95% CI 0.993-8.3365, p = 0.051). The multivariate analysis showed an independent association between mortality and age (OR, 1.103; 95% CI 1.041-1.169; p = 0.001) and between mortality and the female sex (OR, 3.332; 95% CI 1.054-10.535; p = 0.040) but not between mortality and those with NEP (p = 0.051). Individualized nutrition education has long-term positive effects on nutritional status, reduces hospital admissions and increases survival among patients with advanced CKD who are starting dialysis programs.

Chimeric Drug Design with a Noncharged Carrier for Mitochondrial Delivery.

Recently, it was proposed that the thiophene ring is capable of promoting mitochondrial accumulation when linked to fluorescent markers. As a noncharged group, thiophene presents several advantages from a synthetic point of view, making it easier to incorporate such a side moiety into different molecules. Herein, we confirm the general applicability of the thiophene group as a mitochondrial carrier for drugs and fluorescent markers based on a new concept of nonprotonable, noncharged transporter. We implemented this concept in a medicinal chemistry application by developing an antitumor, metabolic chimeric drug based on the pyruvate dehydrogenase kinase (PDHK) inhibitor dichloroacetate (DCA). The promising features of the thiophene moiety as a noncharged carrier for targeting mitochondria may represent a starting point for the design of new metabolism-targeting drugs.

Multidisciplinary nutritional consensus on assessment and nutritional dietary treatment in patients with chronic kidney disease and SARS-CoV-2 infection.

The presence of malnutrition in patients with Chronic Kidney Disease (CKD) is high, it can be made worse by SARS-CoV2 infection. The nutritional assessment should be adapted to minimize the infection, recommending monitoring: weight loss percentage, body mass index (BMI), loss of appetite, analytical parameters and functional capacity using the dynamometer. As well as the sarcopenia assessment using the SCARF scale, and the possibility of using the GLIM criteria in those patients who have been tested positive by MUST. It is important to adapt the nutritional recommendations in the caloric and protein intake, to the CKD stage and to the SARS-CoV2 infection stage. In patients with hypercatabolism, to prioritize preserving the nutritional status (35 kcal/kg weight/day, proteins up to 1.5 g/kg/day). The rest of the nutrients will be adapted to CKD stage and the analytical values. In the post-infection stage, a complete nutritional assessment is recommended, including sarcopenia. The energy and protein requirements in this phase will be adapted to the nutritional status, with special attention to the loss of muscle mass. Dietary recommendations need to be tailored to side effects of SARS-CoV-2 infection: anorexia, dysphagia, dysgeusia, and diarrhea. Anorexia and hypercatabolism makes it difficult to meet the requirements through diet, therefore the use of oral nutritional supplements is recommended as well as the enteral or parenteral nutrition in severe phases.

Clinical presentation, sonographic features and treatment options of segmental stiff skin syndrome.

Segmental stiff skin syndrome is a rare genetic connective tissue disease, which is often misdiagnosed. High-frequency ultrasonography can represent a useful clinical adjunct in the differential diagnosis of this condition, in conjunction with the clinical and histopathological findings. Treatment options are limited and evidence is scarce. We present the clinical, sonographic and histological features of five paediatric patients diagnosed at our institution and discuss their response to treatment.