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Gene editing of human pluripotent stem cells is a promising approach for developing targeted gene therapies for metabolic diseases. Here, we present a protocol for generating a CRISPR-Cas12a gene knockout of protein tyrosine phosphatases in human embryonic stem cells. We describe steps for differentiating the edited clones into pancreatic islet-like spheroids rich in ß-like cells. We then detail procedures for implanting these spheroids under the murine kidney capsule for in vivo maturation.

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Two perturbations were investigated in acidogenic co-fermentation of waste activated sludge (WAS) and food waste in continuous mesophilic fermenters: increasing the organic loading rate (OLR) and changing the WAS. A control reactor maintained an OLR of 11 gVS/(L·d), while a test reactor had a prolonged OLR change to 18 gVS/(L·d). For each OLR, two WAS were studied. The change in OLR led to differentiated fermentation product profile without compromising the fermentation yields (∼300 mgCOD/gVS). At 11 gVS/(L·d), the product profile was dominated by acetic, butyric, and propionic acids while at 18 gVS/(L·d) it shifted to acetic acid, ethanol, and caproic acid. Reverting the OLR also reverted the fermentation profile. The biomass immigration with the WAS changed the fermentation microbial structure and introduced acetic acid-consuming methanogens, which growth was only delayed by the OLR increase. Microbial monitoring and post-fermentation tests can be used for early detection of acetic acid-consuming events.

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This work aims to improve the continuous co-fermentation of waste activated sludge (WAS) and food waste (FW) by investigating the long-term impact of temperature on fermentation performance and the underpinning microbial community. Acidogenic co-fermentation of WAS and FW (70:30 % VS-basis) to produce volatile fatty acids (VFA) was studied in continuous fermenters at different temperatures (25, 35, 45, 55 °C) at an organic loading rate of 11 gVS/(L·d) and a hydraulic retention time of 3.5 days. Two batches of WAS (A and B) were collected from the same wastewater treatment plant at different periods to understand the impact of the WAS microbioota on the fermenters' microbial communities. Solubilisation yield was higher at 45 °C (575 ± 68 mgCOD/gVS) followed by 55 °C (508 ± 45 mgCOD/gVS). Fermentation yield was higher at 55 °C (425 ± 28 mgCOD/gVS) followed by 35 °C (327 ± 17 mgCOD/gVS). Temperature also had a noticeable impact on the VFA profile. At 55 °C, acetic (40 %) and butyric (40 %) acid dominated, while acetic (37 %), butyric acid (31 %), and propionic acid (17 %) dominated at 35 °C. At 45 °C, an accumulation of caproic acid was detected which did not occur at other temperatures. Each temperature had a distinct microbial community, where the WAS microbiota played an important role. The biomass mass-balance showed the highest growth of microorganisms (51 %) at 35 °C and WAS_B, where a consumption of acetic acid was observed. Therefore, at 35 °C, there is a higher risk of acetic acid consumption probably due to the proliferation of methanogens imported from WAS.

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An altered gut microbiota is associated with type 1 diabetes (T1D), affecting the production of short-chain fatty acids (SCFA) and glucose homeostasis. We previously demonstrated that enhancing serum acetate and butyrate using a dietary supplement (HAMSAB) improved glycemia in non-obese diabetic (NOD) mice and patients with established T1D. The effects of SCFA on immune-infiltrated islet cells remain to be clarified. Here, we performed single-cell RNA sequencing on islet cells from NOD mice fed an HAMSAB or control diet. HAMSAB induced a regulatory gene expression profile in pancreas-infiltrated immune cells. Moreover, HAMSAB maintained the expression of ß-cell functional genes and decreased cellular stress. HAMSAB-fed mice showed preserved pancreatic endocrine cell identity, evaluated by decreased numbers of poly-hormonal cells. Finally, SCFA increased insulin levels in human ß-like cells and improved transplantation outcome in NOD/SCID mice. Our findings support the use of metabolite-based diet as attractive approach to improve glucose control in T1D.

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Obesity-related complications such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) are well-established risk factors for the development of hepatocellular carcinoma (HCC). This review provides insights into the molecular mechanisms that underlie the role of steatosis, hyperinsulinemia and hepatic inflammation in HCC development and progression. We focus on recent findings linking intracellular pathways and transcription factors that can trigger the reprogramming of hepatic cells. In addition, we highlight the role of enzymes in dysregulated metabolic activity and consequent dysfunctional signalling. Finally, we discuss the potential uses and challenges of novel therapeutic strategies to prevent and treat NAFLD/T2D-associated HCC.

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OBJECTIVES: Type 1 diabetes (T1D) is caused by progressive immune-mediated loss of insulin-producing ß-cells. Inflammation is detrimental to ß-cell function and survival, moreover, both apoptosis and necrosis have been implicated as mechanisms of ß-cell loss in T1D. The receptor interacting serine/threonine protein kinase 1 (RIPK1) promotes inflammation by serving as a scaffold for NF-κB and MAPK activation, or by acting as a kinase that triggers apoptosis or necroptosis. It is unclear whether RIPK1 kinase activity is involved in T1D pathology. In the present study, we investigated if absence of RIPK1 activation would affect the susceptibility to immune-mediated diabetes or diet induced obesity (DIO). METHODS: The RIPK1 knockin mouse line carrying a mutation mimicking serine 25 phosphorylation (Ripk1S25D/S25D), which abrogates RIPK1 kinase activity, was utilized to assess the in vivo role of RIPK1 in immune-mediated diabetes or diet induced obesity (DIO). In vitro, ß-cell death and RIPK1 kinase activity was analysed in conditions known to induce RIPK1-dependent apoptosis/necroptosis. RESULTS: We demonstrate that Ripk1S25D/S25D mice presented normal glucose metabolism and ß-cell function. Furthermore, immune-mediated diabetes and DIO were not different between Ripk1S25D/S25D and Ripk1+/+ mice. Despite strong activation of RIPK1 kinase and other necroptosis effectors (RIPK3 and MLKL) by TNF+BV6+zVAD, no cell death was observed in mouse islets nor human ß-cells. CONCLUSION: Our results contrast recent literature showing that most cell types undergo necroptosis following RIPK1 kinase activation. This peculiarity may reflect an adaptation to the inability of ß-cells to proliferate and self-renewal.

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To maximize the opportunities of seagrass as a nature-based solution requires restoration to occur on a large scale. New methods and knowledge are required that can solve ecological bottlenecks, improving its reliability and effectiveness. Although there is increasing interest in the use of seeds for seagrass restoration there exists a limited understanding of how best to plant them with the most knowledge on germination and seedling emergence coming from laboratory studies. Here we present the results of a novel field study on the emergence success of seeds of the seagrass Zostera marina when subjected to varied planting treatments. Seeds were planted into hessian bags according to a factorial design of three treatments (sediment type, detritus addition, and nutrient addition). By adding nutrients to natural sediment, the present study provides some evidence of seagrass shoot emergence and maximum shoot length doubling. The present study provides evidence that even in heavily nutrient-rich environments, seagrass sediments may require additional nutrients to improve seedling emergence and growth. It also highlights the highly variable nature of planting seagrass seeds in shallow coastal environments. Critically this study provides increasing levels of evidence that small subtleties in the method can have large consequences for seagrass restoration and that for restoration to scale to levels that are relevant for nature-based solutions there remain many unknowns that require consideration.

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The loss of functional pancreatic ß-cell mass is an important hallmark of both type 1 and type 2 diabetes. The RNA-binding protein NOVA1 is expressed in human and rodent pancreatic ß-cells. Previous in vitro studies indicated that NOVA1 is necessary for glucose-stimulated insulin secretion and its deficiency-enhanced cytokine-induced apoptosis. Moreover, Bim, a proapoptotic protein, is differentially spliced and potentiates apoptosis in NOVA1-deficient ß-cells in culture. We generated two novel mouse models by Cre-Lox technology lacking Nova1 (ßNova1-/-) or Bim (ßBim-/-) in ß-cells. To test the impact of Nova1 or Bim deletion on ß-cell function, mice were subjected to multiple low-dose streptozotocin (MLD-STZ)-induced diabetes or high-fat diet-induced insulin resistance. ß-cell-specific Nova1 or Bim deficiency failed to affect diabetes development in response to MLD-STZ-induced ß-cell dysfunction and death evidenced by unaltered blood glucose levels and pancreatic insulin content. In addition, body composition, glucose and insulin tolerance test, and pancreatic insulin content were indistinguishable between control and ßNova1-/- or ßBim-/- mice on a high fat diet. Thus, Nova1 or Bim deletion in ß-cells does not impact on glucose homeostasis or diabetes development in mice. Together, these data argue against an in vivo role for the Nova1-Bim axis in ß-cells.

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The aim of this work was to evaluate whether the angular elevation of a sound source could generate auditory cues which improve the auditory distance perception in a similar way to that previously reported by visual modality. For this purpose, we compared ADP curves obtained with sources located both at the listeners' ears and at ground level. Our hypothesis was that the participants can interpret the relation between elevation and distance of ground-level sources (which are linked geometrically) so we expected them to perceive their distances more accurately than those at ear level. However, the responses obtained with sources located at ground level were almost identical to those obtained at the height of the listeners' ears, showing that, under the conditions of our experiment, auditory elevation cues do not influence auditory distance perception.

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The impact of food waste (FW) composition on co-fermentation performance was studied to elucidate if adjusting FW composition can be used to drive the fermentation yield and profile, which is relevant for biorefinery applications. First, the impact of individual FW components (i.e., fruit, vegetables, pasta, rice, meat, fish, and cellulose) was assessed. Subsequently, the effect of mixing a protein-rich component and a carbohydrate-rich component was studied (i.e., fish/fruit and fish/cellulose, and meat/rice and meat/vegetable). All experiments were carried out in mesophilic batch assays using waste activated sludge (WAS) as main substrate, the same mixture ratio (70 % WAS +30 % FW on VS basis), and no pH control. Results showed that each FW component had a distinct effect on VFA yield and profile, with protein-rich components reaching the highest VFA yields; 502 and 442 mgCOD/gVS for WAS/Fish and WAS/Meat, respectively. A positive interaction on VFA yield was observed when mixing a protein-rich and a carbohydrate-rich component. This interaction was not proportional to the co-substrates proportion in the mixtures. On the other hand, the VFA profile was clearly driven by the components in the mixture, including both WAS and FW composition. Overall, these results indicate that predicting the VFA yield of WAS/FW co-fermentation is not just related to FW composition, but FW composition could be used to adjust the VFA profile to a certain extent.

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We report Anthropogenic Marine Debris (AMD) in Chagos Archipelago in the Indian Ocean, globally amongst the most isolated island groups. AMD on 14 island beaches in five atolls were surveyed in 2019 using two techniques: Marine Debris Tracker (MDT) along littoral vegetation and photoquadrats in open beach. Over 60 % of AMD in both beach zones was composed of plastics, especially bottles and fragments (mean = 44.9 %, 27.2 %, range = 16.5-73.2 %, 4.8-55.9 % respectively in vegetation; mean = 28.7 %, 31.5 %, range = 17.7-40.7 %, 11.6-60.0 % respectively in open beach). The density of plastic debris in littoral vegetation (MDT data: 1995 bottles, 3328 fragments per 100 m2) was 10-fold greater than in open beach (photoquadrat data: 184 bottles, 106 fragments per 100 m2). Significant latitudinal variation in vegetation AMD occurred (8-fold greater in southern atolls, p = 0.006). AMD varied within island zones: most debris observed on oceanside beaches (oceanside vs lagoon, W = 365, p < 0.001; ocean vs island tip, W = 107, p = 0.034). Standardisation of surveys using the open-source MDT App is recommended. Debris accumulation hotspots overlapped with sea turtle nesting habitat, guiding future beach clean-up prioritisation.

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Marine mammals are under pressure from multiple threats, such as global climate change, bycatch, and vessel collisions. In this context, more frequent and spatially extensive surveys for abundance and distribution studies are necessary to inform conservation efforts. Marine mammal surveys have been performed visually from land, ships, and aircraft. These methods can be costly, logistically challenging in remote locations, dangerous to researchers, and disturbing to the animals. The growing use of imagery from satellite and unoccupied aerial systems (UAS) can help address some of these challenges, complementing crewed surveys and allowing for more frequent and evenly distributed surveys, especially for remote locations. However, manual counts in satellite and UAS imagery remain time and labor intensive, but the automation of image analyses offers promising solutions. Here, we reviewed the literature for automated methods applied to detect marine mammals in satellite and UAS imagery. The performance of studies is quantitatively compared with metrics that evaluate false positives and false negatives from automated detection against manual counts of animals, which allows for a better assessment of the impact of miscounts in conservation contexts. In general, methods that relied solely on statistical differences in the spectral responses of animals and their surroundings performed worse than studies that used convolutional neural networks (CNN). Despite mixed results, CNN showed promise, and its use and evaluation should continue. Overall, while automation can reduce time and labor, more research is needed to improve the accuracy of automated counts. With the current state of knowledge, it is best to use semi-automated approaches that involve user revision of the output. These approaches currently enable the best tradeoff between time effort and detection accuracy. Based on our analysis, we identified thermal infrared UAS imagery as a future research avenue for marine mammal detection and also recommend the further exploration of object-based image analysis (OBIA). Our analysis also showed that past studies have focused on the automated detection of baleen whales and pinnipeds and that there is a gap in studies looking at toothed whales, polar bears, sirenians, and mustelids.

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This study aimed to test the hypothesis that associates blindness with a reduced ability to judge the absolute distance from sound sources. Our working hypotheses were the following: (a) Within reach, a blind subject will be able to make up for the lack of vision using proprioceptive information to calibrate the acoustic distance perception cues. (b) As the source becomes unreachable, blind people will show greater biases since, out of reach, the proposed mechanism for calibration could not be used. To approach these topics, we carried out a series of auditory distance experiments in which we asked sighted and blind participants to report their distance estimates verbally or by reaching the sound source. Within-reach results showed that blind participants performed better than (reaching) or similar to (verbal report) the sighted. The verbal report results showed similar biases between both groups. However, blind participants had more compressive responses than the sighted. Furthermore, blind participants showed more biased responses in the far field than in the peripersonal space, while sighted participants showed similar biases regardless of distance. Our results strongly suggest that the blind can calibrate their distance estimations through the use of proprioceptive spatial information. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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The present work monitors structural changes in anionic membranes (DPPG; 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol)) caused by the native antimicrobial peptide (AMP) Hylin a1 (Hya1; IFGAILPLALGALKNLIK-NH2) and its synthetic analogue K0Hya1 (KIFGAILPLALGALKNLIK-NH2), with an extra positive residue of lysine at the N-terminus of the peptide chain. Anionic membranes were used to mimic anionic lipids in bacteria membranes. Differential scanning calorimetry (DSC) evinced that both peptides strongly disrupt the lipid bilayers. However, whereas the native peptide (+3) induces a space-average and/or time-average disruption on DPPG bilayers, the more charged, K0Hya1 (+4), appears to be strongly attached to the membrane, clearly giving rise to the coexistence of two different lipid regions, one depleted of peptide and another one peptide-disrupted. The membrane fluorescent probe Laurdan indicates that, in average, the peptides increase the bilayer packing of fluid DPPG (above the lipid gel-fluid transition temperature) and/or decrease its polarity. Spin labels, incorporated into DPPG membrane, confirm, and extend the results obtained with Laurdan, indicating that the peptides increase the lipid packing both in gel and fluid DPPG bilayers. Therefore, our results confirm that Laurdan is often unable to monitor structural modifications induced on gel membranes by exogenous molecules. Through the measurement of the leakage of entrapped carboxyfluorescein (CF), a fluorescent dye, in DPPG large unilamellar vesicles it was possible to show that both peptides induce pore formation in DPPG bilayers. Furthermore, CF experiments show that Hylin peptides are strongly bound to DPPG bilayers in the gel phase, not being able to migrate to other DPPG vesicles. Here we discuss the complementarity of different techniques in monitoring structural alterations caused on lipid bilayers by Hylin peptides, and how it could be used to help in the understanding of the action of other exogenous molecules on biological membranes.

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Type 1 diabetes (T1D) results from autoimmune destruction of ß-cells in the pancreas. Protein tyrosine phosphatases (PTPs) are candidate genes for T1D and play a key role in autoimmune disease development and ß-cell dysfunction. Here, we assessed the global protein and individual PTP profiles in the pancreas from nonobese mice with early-onset diabetes (NOD) mice treated with an anti-CD3 monoclonal antibody and interleukin-1 receptor antagonist. The treatment reversed hyperglycemia, and we observed enhanced expression of PTPN2, a PTP family member and T1D candidate gene, and endoplasmic reticulum (ER) chaperones in the pancreatic islets. To address the functional role of PTPN2 in ß-cells, we generated PTPN2-deficient human stem cell-derived ß-like and EndoC-ßH1 cells. Mechanistically, we demonstrated that PTPN2 inactivation in ß-cells exacerbates type I and type II interferon signaling networks and the potential progression toward autoimmunity. Moreover, we established the capacity of PTPN2 to positively modulate the Ca2+-dependent unfolded protein response and ER stress outcome in ß-cells. Adenovirus-induced overexpression of PTPN2 partially protected from ER stress-induced ß-cell death. Our results postulate PTPN2 as a key protective factor in ß-cells during inflammation and ER stress in autoimmune diabetes.

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BACKGROUND: Short-chain fatty acids (SCFAs) produced by the gut microbiota have beneficial anti-inflammatory and gut homeostasis effects and prevent type 1 diabetes (T1D) in mice. Reduced SCFA production indicates a loss of beneficial bacteria, commonly associated with chronic autoimmune and inflammatory diseases, including T1D and type 2 diabetes. Here, we addressed whether a metabolite-based dietary supplement has an impact on humans with T1D. We conducted a single-arm pilot-and-feasibility trial with high-amylose maize-resistant starch modified with acetate and butyrate (HAMSAB) to assess safety, while monitoring changes in the gut microbiota in alignment with modulation of the immune system status. RESULTS: HAMSAB supplement was administered for 6 weeks with follow-up at 12 weeks in adults with long-standing T1D. Increased concentrations of SCFA acetate, propionate, and butyrate in stools and plasma were in concert with a shift in the composition and function of the gut microbiota. While glucose control and insulin requirements did not change, subjects with the highest SCFA concentrations exhibited the best glycemic control. Bifidobacterium longum, Bifidobacterium adolescentis, and vitamin B7 production correlated with lower HbA1c and basal insulin requirements. Circulating B and T cells developed a more regulatory phenotype post-intervention. CONCLUSION: Changes in gut microbiota composition, function, and immune profile following 6 weeks of HAMSAB supplementation were associated with increased SCFAs in stools and plasma. The persistence of these effects suggests that targeting dietary SCFAs may be a mechanism to alter immune profiles, promote immune tolerance, and improve glycemic control for the treatment of T1D. TRIAL REGISTRATION: ACTRN12618001391268. Registered 20 August 2018, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375792 Video Abstract.

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Fermentation (not anaerobic digestion) is an emerging biotechnology to transform waste into easily assimilable organic compounds such as volatile fatty acids, lactic acid and alcohols. Co-fermentation, the simultaneous fermentation of two or more waste, is an opportunity for wastewater treatment plants (WWTPs) to increase the yields of sludge mono-fermentation. Most publications have studied waste activated sludge co-fermentation with food waste or agri-industrial waste. Mixing ratio, pH and temperature are the most studied variables. The highest fermentation yields have been generally achieved in mixtures dominated by the most biodegradable substrate at circumneutral pH and mesophilic conditions. Nonetheless, most experiments have been performed in batch assays which results are driven by the capabilities of the starting microbial community and do not allow evaluating the microbial acclimation that occurs under continuous conditions. Temperature, pH, hydraulic retention time and organic load are variables that can be controlled to optimise the performance of continuous co-fermenters (i.e., favour waste hydrolysis and fermentation and limit the proliferation of methanogens). This review also discusses the integration of co-fermentation with other biotechnologies in WWTPs. Overall, this review presents a comprehensive and critical review of the achievements on co-fermentation research and lays the foundation for future research.

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Introducción. La escala de estado funcional (FSS, por su sigla en inglés) fue desarrollada para medir la morbilidad adquirida en los pacientes pediátricos. Objetivo. Estimar la incidencia de morbilidad adquirida en la unidad de cuidados intensivos pediátrica (UCIP), la presencia de factores asociados y describir el estado funcional tras el alta hospitalaria. Población y métodos. Cohorte prospectiva. Todas las admisiones en UCIP entre agosto de 2016 y julio de 2017. Se utilizó FSS para medir la morbilidad adquirida durante la hospitalización y hasta 1 año después del alta. Se realizó un análisis univariado para investigar los factores asociados con morbilidad. Resultados. Se incluyeron 842 pacientes. La incidencia de morbilidad en UCIP fue del 3,56 % (30/842) y persistió en el 0,7 % de toda la cohorte al alta hospitalaria (6/842). Antes del año, 3 de los 6 pacientes mejoraron la condición funcional. El análisis univariado mostró asociación entre la morbilidad adquirida en UCIP y el puntaje PIM2 (odds ratio [OR, por su sigla en inglés]: 1,04; intervalo de confianza del 95 % [IC95 %]: 1,01-1,07; p = 0,007), la edad menor a 1 año (OR: 2,93; IC95 %: 1,36-6,15; p = 0,004), el uso de asistencia respiratoria mecánica (ARM) (OR: 7,83; IC95 %: 3,31-18,49; p = 0,0001) y de catéteres venosos centrales (CVC) (OR: 38,08; IC95 %: ,16-280,95; p = 0,0001), y hospitalizaciones prolongadas (OR: 9,65; IC95 %: 4,33-21,49; p = 0,0001). Conclusiones. La incidencia de morbilidad fue del 3,56 % y se asoció con la edad menor a 1 año, la gravedad de los pacientes al momento de la admisión, el uso de ARM y CVC, y las hospitalizaciones prolongadas

Introduction. The Functional Status Scale (FSS) was developed to measure acquired morbidity in pediatric patients. Objective. To estimate the incidence of acquired morbidity in the pediatric intensive care unit (PICU) and the presence of associated factors, and describe functional status after hospital discharge. Population and methods. Prospective cohort. All PICU admissions between August 2016 and July 2017. The FSS was used to measure acquired morbidity during hospitalization and up to 1 year after discharge. A univariate analysis was performed to investigate morbidity-associated factors. Results. A total of 842 patients were included. The incidence of morbidity at the PICU was 3.56 % (30/842) and persisted at 0.7 % for the entire cohort at hospital discharge (6/842). Within 1 year after discharge, the functional status of 3/6 patients improved. The univariate analysis showed an association between acquired morbidity at the PICU and the PIM2 score (odds ratio [OR]: 1.04; 95 % confidence interval [CI]: 1.01-1.07; p = 0.007), age younger than 1 year (OR: 2.93; 95 % CI: 1.36-6.15; p = 0.004), the use of assisted mechanical ventilation (AMV) (OR: 7.83; 95 % CI: 3.31-18.49; p = 0.0001) and central venous catheter (CVC) (OR: 38.08; 95 % CI: 5.16-280.95; p = 0.0001), and prolonged hospital stays (OR: 9.65; 95 % CI: 4.33-21.49; p = 0.0001). Conclusions. The incidence of morbidity was 3.56 % and was associated with an age younger than 1 year, patient severity at the time of admission, the use of AMV and CVC, and prolonged hospital stays

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Introduction: The Functional Status Scale (FSS) was developed to measure acquired morbidity in pediatric patients. Objective: To estimate the incidence of acquired morbidity in the pediatric intensive care unit (PICU) and the presence of associated factors, and describe functional status after hospital discharge. Population and methods: Prospective cohort. All PICU admissions between August 2016 and July 2017. The FSS was used to measure acquired morbidity during hospitalization and up to 1 year after discharge. A univariate analysis was performed to investigate morbidity-associated factors. Results: A total of 842 patients were included. The incidence of morbidity at the PICU was 3.56 % (30/842) and persisted at 0.7 % for the entire cohort at hospital discharge (6/842). Within 1 year after discharge, the functional status of 3/6 patients improved. The univariate analysis showed an association between acquired morbidity at the PICU and the PIM2 score (odds ratio [OR]: 1.04; 95 % confidence interval [CI]: 1.01-1.07; p = 0.007), age younger than 1 year (OR: 2.93; 95 % CI: 1.36-6.15; p = 0.004), the use of assisted mechanical ventilation (AMV) (OR: 7.83; 95 % CI: 3.31-18.49; p = 0.0001) and central venous catheter (CVC) (OR: 38.08; 95 % CI: 5.16-280.95; p = 0.0001), and prolonged hospital stays (OR: 9.65; 95 % CI: 4.33-21.49; p = 0.0001). Conclusions: The incidence of morbidity was 3.56 % and was associated with an age younger than 1 year, patient severity at the time of admission, the use of AMV and CVC, and prolonged hospital stays.

Introducción. La escala de estado funcional (FSS, por su sigla en inglés) fue desarrollada para medir la morbilidad adquirida en los pacientes pediátricos. Objetivo. Estimar la incidencia de morbilidad adquirida en la unidad de cuidados intensivos pediátrica (UCIP), la presencia de factores asociados y describir el estado funcional tras el alta hospitalaria. Población y métodos. Cohorte prospectiva. Todas las admisiones en UCIP entre agosto de 2016 y julio de 2017. Se utilizó FSS para medir la morbilidad adquirida durante la hospitalización y hasta 1 año después del alta. Se realizó un análisis univariado para investigar los factores asociados con morbilidad. Resultados. Se incluyeron 842 pacientes. La incidencia de morbilidad en UCIP fue del 3,56 % (30/842) y persistió en el 0,7 % de toda la cohorte al alta hospitalaria (6/842). Antes del año, 3 de los 6 pacientes mejoraron la condición funcional. El análisis univariado mostró asociación entre la morbilidad adquirida en UCIP y el puntaje PIM2 (odds ratio [OR, por su sigla en inglés]: 1,04; intervalo de confianza del 95 % [IC95 %]: 1,01- 1,07; p = 0,007), la edad menor a 1 año (OR: 2,93; IC95 %: 1,36-6,15; p = 0,004), el uso de asistencia respiratoria mecánica (ARM) (OR: 7,83; IC95 %: 3,31-18,49; p = 0,0001) y de catéteres venosos centrales (CVC) (OR: 38,08; IC95 %: 5,16-280,95; p = 0,0001), y hospitalizaciones prolongadas (OR: 9,65; IC95 %: 4,33-21,49; p = 0,0001). Conclusiones. La incidencia de morbilidad fue del 3,56 % y se asoció con la edad menor a 1 año, la gravedad de los pacientes al momento de la admisión, el uso de ARM y CVC, y las hospitalizaciones prolongadas.

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Type 1 diabetes develops in childhood and adolescence, with peak incidence in the early teenage years. There is an urgent need for an accurate method to detect insulin-producing ß-cells in patients that is not affected by alterations in ß-cell function. As part of our research program to design specific probes to measure ß-cell mass, we recently developed a novel insulin-binding peptide probe (IBPP) for the detection of ß-cells in vivo. Here, we applied our innovative method to show specific labeling of this IBPP to human and mouse fixed ß-cells in pancreatic islets. Importantly, we showed staining of human and mouse islets in culture without any negative functional or cell viability impact. Moreover, the IBPP-stained mouse islets after tail vein injection in vivo, albeit with batch differences in staining efficiency. In conclusion, we provide evidence showing that the IBPP can be used for future accurate detection of ß-cell mass in a variety of preclinical models of diabetes.

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