Precise positioning of gamma ray interactions in multiplexed pixelated scintillators using artificial neural networks.

INTRODUCTION: The positioning of γ ray interactions in positron emission tomography (PET) detectors is commonly made through the evaluation of the Anger logic flood histograms. Machine learning techniques, leveraging features extracted from signal waveform, have demonstrated successful applications in addressing various challenges in PET instrumentation. AIM: This paper evaluates the use of artificial neural networks (NN) for γ ray interaction positioning in pixelated scintillators coupled to a multiplexed array of silicon photomultipliers (SiPM). METHODS: An array of 16 Cerium doped Lutetium-based (LYSO) crystal pixels (cross-section 2x2 mm2) coupled to 16 SiPM (S13360-1350) were used for the experimental setup. Data from each of the 16 LYSO pixels was recorded, a total of 160 000 events. The detectors were irradiated by 511 keV annihilation γ rays from a Sodium-22 (22Na) source. Another LYSO crystal was used for electronic collimation. Features extracted from the signal waveform were used to train the model. Two models were tested: i) single multiple-class neural network (mcNN), with 16 possible outputs followed by a softmax and ii) 16 binary classification neural networks (bNN), each one specialized in identifying events occurred in each position. RESULTS: Both NN models showed a mean positioning accuracy above 85% on the evaluation dataset, although the mcNN is faster to train. DISCUSSION: The method's accuracy is affected by the introduction of misclassified events that interacted in the neighbour's crystals and were misclassified during the dataset acquisition. Electronic collimation reduces this effect, however results could be improved using a more complex acquisition setup, such as a light-sharing configuration. CONCLUSIONS: The methods comparison showed that mcNN and bNN can surpass the Anger logic, showing the feasibility of using these models in positioning procedures of future multiplexed detector systems in a linear configuration.

Keep Calm: Does parental preoperative anxiety affect post-tonsillectomy pain scores in children?

PURPOSE: To understand if high parental anxiety leads to increased post-tonsillectomy pain in children. METHODS: Prospective study including parents of children aged 3-10 years old submitted to tonsillectomy with or without adenoidectomy. To evaluate anxiety, parents were asked to fill the State-Trait Anxiety Inventory form-Y, with postoperative pain being evaluated with the Wong-Baker FACES pain scale at postoperative days 1, 3 and 7. Parents were also asked to register the number of days during which children took analgesic and the number of analgesic intakes needed. RESULTS: 41 parents were enrolled, of which 95.1% (n = 39) were female with a mean age of 35.64 years (SD 5.751), with 41 children also being enrolled, of which 85.4% of children (n = 35) underwent tonsillectomy and adenoidectomy. 43.9% (n = 18) of parents presented State anxiety scores above the cut-off level and 53.7% (n = 22) above the Trait anxiety scores above the cut-off. Children of parents with high State anxiety presented statistically higher pain scores in both the third (p = 0.035) and the seventh postoperative days (p = 0.006), with significantly longer use of analgesic medication (p = 0.043) being found, as well as a statistically higher number of analgesic intakes (p = 0.045) (Table 4). CONCLUSION: The present study establishes an association between preoperative parental anxiety, postoperative pain scores and the need for longer analgesic use in children undergoing tonsillectomy. This reinforces the importance of reducing parental anxiety and opens the door for further strategies to better post-tonsillectomy outcomes.

Lingual Frenotomy in Pediatric Ankyloglossia: A Diode Laser Approach in Two Case Reports.

Ankyloglossia can be related to a number of complications, such as breastfeeding difficulties or alterations in craniofacial development. Treatment can involve surgery to correct the altered lingual frenulum and can be performed by various techniques. The purpose of this paper is to present two case reports of ankyloglossia in pediatric patients of different ages, the diagnostic criteria, and the treatment decision rationale, which led to a lingual frenotomy performed with a diode laser.

National cross-sectional cluster survey of tuberculosis prevalence in Timor-Leste: a study protocol.

INTRODUCTION: Timor-Leste has one of the world's highest estimated tuberculosis (TB) incidences, yet the data which informs this estimate is limited and the true burden of TB disease is not known. TB prevalence surveys offer the best means of determining robust estimates of disease burden. This study aims to provide an estimate of the prevalence of bacteriologically confirmed pulmonary TB in Timor-Leste and provide additional insights into diagnostic coverage and health-seeking behaviour of persons with symptoms suggestive of TB. METHODS AND ANALYSIS: A national population-based cross-sectional cluster survey will be conducted in which participants aged 15 years and older will be screened for pulmonary TB using an algorithm consisting of symptom screening and digital X-ray of the chest with computer-aided detection software for X-ray interpretation. Xpert Ultra and liquid culture methods will be used to confirm survey TB cases. Additional data will be collected from persons reporting symptoms suggestive of TB to assess health-seeking behaviour and access to TB diagnosis and care. The survey aims to screen a target sample population of 20 068 people, living within 50 clusters, representing every municipality of Timor-Leste. Bacteriologically confirmed pulmonary TB prevalence will be estimated using WHO-recommended methods. ETHICS AND DISSEMINATION: Research ethics approval has been granted by the human research ethics committee of the Northern Territory, Australia, and the Instituto Nacional da Saúde, Timor-Leste. The results will be published in a peer-reviewed scientific journal and disseminated with relevant stakeholders. TRIAL REGISTRATION NUMBER: ACTRN12623000718640.

A metagenomic prospective cohort study on gut microbiome composition and clinical infection in small bowel transplantation.

Two-thirds of small-bowel transplantation (SBT) recipients develop bacteremia, with the majority of infections occurring within 3 months post-transplant. Sepsis-related mortality occurs in 31% of patients and is commonly caused by bacteria of gut origin, which are thought to translocate across the implanted organ. Serial post-transplant surveillance endoscopies provide an opportunity to study whether the composition of the ileal and colonic microbiota can predict the emergence as well as the pathogen of subsequent clinical infections in the SBT patient population. Five participants serially underwent aspiration of ileal and colonic bowel effluents at transplantation and during follow-up endoscopy either until death or for up to 3 months post-SBT. We performed whole-metagenome sequencing (WMS) of 40 bowel effluent samples and compared the results with clinical infection episodes. Microbiome composition was concordant between participants and timepoint-matched ileal and colonic samples. Four out of five (4/5) participants had clinically significant infections thought to be of gut origin. Bacterial translocation from the gut was observed in 3/5 patients with bacterial infectious etiologies. In all three cases, the pathogens had demonstrably colonized the gut between 1-10 days prior to invasive clinical infection. Recipients with better outcomes received donor grafts with higher alpha diversity. There was an increase in the number of antimicrobial resistance genes associated with longer hospital stay for all participants. This metagenomic study provides preliminary evidence to support the pathogen translocation hypothesis of gut-origin sepsis in the SBT cohort. Ileal and colonic microbiome compositions were concordant; therefore, fecal metagenomic analysis could be a useful surveillance tool for impeding infection with specific gut-residing pathogens.

Sharp increase in gonorrhoea notifications among young people, EU/EEA, July 2022 to June 2023.

Gonorrhoea cases increased steeply in women aged 20 to 24 years across 15 EU/EEA countries in July to December 2022 and January to June 2023 with, respectively, 73% and 89% more cases reported than expected, based on historical data from 2015 to 2019. Smaller increases among men due to heterosexual transmission were observed in nine EU/EEA countries. Interventions to raise awareness among young people about sexually transmitted infection risks are needed, emphasising the benefit of safe sexual practices and testing.

Red seaweed biorefinery: The influence of sequential extractions on the functional properties of extracted agars and porphyrans.

Red seaweeds are exploited for their hydrocolloids, but other fractions are usually overlooked. In a novel approach, this study aimed to evaluate cold-water (CWE), ethanolic (EE), and alkaline (SE) extractions, alone and in sequence, to simultaneously: i) decrease the hydrocolloid extraction waste (valorizing bioactive side-streams and/or increasing extraction yield); and ii) increase the hydrocolloids' texturizing properties. It is the first time these extractions' synergetic and/or antagonistic effects will be accessed. For Porphyra dioica, a combination of CWE and EE was optimal: a positive influence on the melting temperature (increasing 5 °C to 74 °C) and sulphate content (a 3-fold reduction to 5 %) was observed, compared to a direct porphyran extraction. The same was observed for Gracilaria vermiculophyla, recovering two additional bioactive fractions without impacting the hydrocolloid's extraction (agar with 220 g/cm2 gelling strength and 14 % yield was obtained). The sequential use of CWE, EE, and SE was the most beneficial in Gelidium corneum processing: it enhanced agar's texturizing capacity (reaching 1150 g/cm2, a 1.5-fold increase when compared to a direct extraction), without affecting its 22 % yield or over 88 % purity. Ultimately, these findings clarified the effects of cascading biorefinery approaches from red seaweeds and their pertinence.

Does parental stress improve after pediatric tonsillectomy?

OBJETIVE: Parental stress is defined as a subjective perception that parenting demands are higher than their resources and is reportedly higher in parents who have children with both chronic and acute illnesses. Ear-nose-throat (ENT) disorders, such as recurrent infections and obstruction sleep disorders, are one of the most prevalent comorbidities in pediatric age. Worldwide, tonsillectomy stands as the surgical treatment for these conditions, associated with a significant burden on both the children and their parents. The purpose of this study is to determine parental stress levels before and after tonsillectomy and to ascertain whether these levels improve after the children's surgery. METHODS: This is a prospective cohort study enrolling 48 parents accompanying their children aged 3-10 for outpatient tonsillectomy surgery in a tertiary portuguese hospital. Consent for participation in this study was obtained and parental stress was determined using the portuguese version of Parental Stress Scale (PSS). All parents completed PSS before surgery and at the 6-month follow-up evaluation. RESULTS: Of the 48 surveys obtained, 38 were mothers aged from 24 to 45 years. The median age of children was 3 (3-9) years and half were girls. Surgery was performed due to obstruction sleep disorders in about 71 % of children. The overall average stress level was 29,19 (standard deviation 7,5), with higher scores being associated with male children. At the 6-month reevaluation PSS was significantly lower (26,98), with a prominent reduction in the parental stress subscale in mothers comparing to fathers. CONCLUSIONS: These results highlight the importance of prompt diagnosis and treatment of children requiring tonsillectomy, as this condition may affect not only their physical health, but also parental relations, reflecting on their upbringing.

10 anos de experiência do programa de cirurgia robótica abdominal do Instituto Nacional de Câncer / Experience with 10 years of the abdominal robotic surgery program of Brazilian National Cancer Institute

Introdução: O primeiro sistema robótico utilizado em procedimentos cirúrgicos foi desenvolvido em 1994. Os primeiros pacientes do Sistema Único de Saúde do Brasil (SUS) foram beneficiados com essa tecnologia apenas a partir de 2012, após a instalação da plataforma robótica no Instituto Nacional de Câncer (INCA). Esse estudo avalia 10 anos de experiência do programa robótico na referida instituição. Método: Todos os procedimentos robóticos realizados pelo serviço de cirurgia abdominopélvica dessa instituição entre julho de 2012 a dezembro de 2022 foram analisados. Os dados foram coletados a partir do banco de dados do programa de robótica e por revisão de prontuários físicos e eletrônicos. Resultados: Foram realizados 280 procedimentos cirúrgicos robóticos. A maioria dos casos operados foi conduzida pelo grupo de cirurgia colorretal, correspondendo a 87,5% do total, sendo a ressecção anterior de reto a cirurgia mais realizada. Os demais casos foram operados pelo grupo hepatobiliar (4,6%), estômago (4,2%) e esôfago (3,6%). A taxa de conversão para cirurgia aberta foi de 10,3%. O período médio de internação foi inferior a 10 dias e 9,6% dos pacientes apresentaram reinternação dentro de 90 dias após a cirurgia. Do total, 43,5% dos pacientes foram submetidos a tratamento neoadjuvante com quimioterapia e/ou radioterapia. Durante o período analisado, 18,5% dos pacientes evoluíram com recidiva de doença, sendo a sobrevida global em 5 anos de aproximadamente 60%. Conclusão: Nos últimos 10 anos o uso da tecnologia robótica cresceu significativamente, promovendo melhora dos resultados clínicos. O programa de cirurgia robótica do INCA para tratamento do câncer foi o pioneiro no âmbito nacional dentro do SUS e possibilitou a divulgação e consolidação desta excelente ferramenta tecnológica no tratamento do câncer gastrointestinal. Os resultados apresentados revelam o êxito do programa, demonstrando taxa de complicações aceitável, tempo de internação reduzido e resultados oncológicos satisfatórios, disponibilizando aos pacientes do SUS tratamento cirúrgico atualizado e eficaz.

Introduction: The first robotic system used in surgical procedures was developed in 1994. In 2012, the first robotic surgeries were performed in the Brazilian Public Health System (Sistema Único de Saúde - SUS), after the installation of the robotic platform at Brazilian National Cancer Institute (INCA). This study evaluates 10 years of experience with the robotic program at this Center. Method: All robotic procedures performed by the abdomino-pelvic surgery service of this center between july 2012 and december 2022 were reviewed. Data were collected from the database of the robotics program and review of physical and electronic medical records. Results: 280 robotic surgical procedures were performed. Most cases were conducted by the colorectal surgery group, corresponding to 87.5% of the cases, with anterior resection of the rectum being the most common procedure. The remaining cases were operated by the hepatobiliary group (4.6%), stomach group (4.2%) and esophagus group (3.6%). The conversion rate to open surgery was 10.3%. The average length of stay was less than 10 days and 9.6% of patients were readmitted within 90 days following surgery. Of all, 43.5% of the patients underwent neoadjuvant treatment with chemotherapy and/or radiotherapy. During the analyzed period, 18.5% of the patients had disease recurrence, with an overall 5-year survival of approximately 60%. Conclusion: In the last 10 years, the use of robotic technology has grown significantly, promoting improved clinical outcomes. INCA's robotic surgery program was a pioneer on the national scene within the SUS and enabled the dissemination and consolidation of this excellent technological tool in treatment of gastrointestinal cancer. The results presented reveal the success of the program, demonstrating an acceptable complication rate, reduced length of stay and satisfactory oncological results, providing SUS patients with updated and effective surgical treatment

Chiari Type 1 Malformation: An Unusual Cause of Tinnitus.

Chiari Malformations are a group of conditions defined in 1891 with 5 degrees being described. These malformations present with several symptoms such as cervical protrusion and are associated with hydrocephalus. Also, they can also present with different clinical signs and symptoms, such as deafness and tinnitus. We present a case of a 45-year-old man with unilateral tinnitus evaluated in otolaryngology office. No other symptoms on otolaryngological physical exam were detected in the audiogram performed it was described a significant unilateral sensorineural hearing loss. During the study of this patient, Magnetic Resonance Imaging was requested, showing a type I Chiari malformation. The patient was then observed by Ophthalmology, Neurology, and Neurosurgery. No other neurological symptoms of malformation Chiari syndrome or cranial nerve abnormalities were presented at the respective exam. The surgical management of these pathologies takes into account an adequate CSF and venous blood flow - that was seen in this patient, therefore, there was no surgical indication for decompression. The patient maintains its follow-up in the otolaryngology, neurology, and neurosurgery office, and tinnitus was minimized after prosthetic adaptation was recommended to optimize the quality of life, which was achieved.

Espondilodiscitis multifocal y meningoencefalitis por Staphylococcus aureus en un paciente inmunocomprometido / Multifocal spondylodiscitis and meningoencephalitis due to Staphylococcus aureus in an immunocompromised patient

Spondylodiscitis is a rare diagnosis, but its incidence has increased in recent years. It represents 3-5% of osteomyelitis, and the multifocal affliction is rare as it occurs in 4-8% of all spondylodiscitis. The occurrence of meningoencephalitis associated with spondylodiscitis is also a rare association. We present the case of a 54-year-old woman diagnosed with multifocal spondylodiscitis complicated with meningoencephalitis and intracanal and paravertebral abscess with identification in blood cultures of Staphylococcus aureus. Immunosuppression with infliximab was identified as a risk factor. The patient underwent targeted antibiotic therapy, opting for the conservative strategy due to the surgical risk. There was a positive evolution with imaging resolution of the intracanal abscess. This case is of particular importance due to its rarity of frequency and considering the etiological agent and the low frequency of this infection in patients under anti-TNF-alpha therapy. (AU)

La espondilodiscitis es un diagnóstico poco frecuente, pero su incidencia ha aumentado en los últimos años. Representa el 3-5% de las osteomielitis, y la afección multifocal es rara, ya que se da en el 4-8% de todas las espondilodiscitis. La aparición de meningoencefalitis asociada a espondilodiscitis también es una asociación poco frecuente. Presentamos el caso de una mujer de 54 años diagnosticada de espondilodiscitis multifocal complicada con meningoencefalitis y absceso intracanal y paravertebral con identificación en hemocultivos de Staphylococcus aureus. Se identificó como factor de riesgo la inmunosupresión con infliximab. La paciente fue sometida a antibioterapia dirigida, optándose por la estrategia conservadora debido al riesgo quirúrgico. Hubo una evolución positiva con resolución imagenológica del absceso intracanal. Este caso es de especial importancia por su escasa frecuencia y teniendo en cuenta el agente etiológico y la baja frecuencia de esta infección en pacientes bajo terapia anti-TNF-alfa. (AU)

Pernicious Anemia With Spuriously Normal B12 Levels.

We present a 29-year-old man admitted to our hospital with fatigue for two months of duration and recent palpitations, lightheadedness, blurred vision and nausea. Workup showed pancytopenia with severe macrocytic anemia, laboratory and blood smear features of hemolysis, low reticulocyte percentage and a negative direct Coombs test. B12 and folate levels were normal. As bone marrow aspirate was suggestive of megaloblastic anemia and upper endoscopy showed atrophic gastritis, we ordered homocysteine (elevated) and intrinsic factor (IF) antibodies (positive). The workup led to the diagnosis of pernicious anemia with spuriously normal B12 levels. Replacement therapy allowed a rapid recovery. We highlight that the presence of IF antibodies can interfere with the competitive binding assays commonly used to measure B12 levels.

Mental health and post-traumatic stress disorder in firefighters: an integrated analysis from an action research study.

Introduction: The presence of post-traumatic stress disorder (PTSD) symptomatology in firefighters is an ever-pressing issue that requires close attention for adequate interventions. The present study investigated PTSD and global psychopathology prevalence in a sample of highly risk-exposed Portuguese firefighters, collected after the widespread deadly wildfires in 2017 that ravaged the country. Following an action research approach, the aim of this study was to depict this sample and examine the impact of cumulative adverse experiences on their mental health, which is a phenomenon worth attention. Method: From an initial sample of 283 firefighters who manifested interest in participating, a total of 139 firefighters from the Coimbra District, of whom 130 unequivocally experienced a potentially traumatic/adverse event as a firefighter, completed BSI (to obtain indicators on psychopathology), QEPAT (an inventory of adverse events possibly experienced as a firefighter), and PCL-5 (a measure of PTSD symptomatology) through an online survey during the year 2018 by the Regional Medical Organization, as proposed and supervised by the local Centre for Prevention and Treatment of Psychological Trauma (CPTTP). Results: We found a global prevalence of 8.6% of possible PTSD and 14.4% of possible psychopathology (n = 139). When considering only firefighters who unequivocally reported a potentially traumatic/adverse event as a firefighter (n = 130), 9.2% present possible PTSD, and 13.8% present possible global psychopathology. This sample experienced a mean of 28 adverse events during firefighting work. Linear regressions (n = 118) demonstrated that the perceived severity of the most traumatic event reported and the experience of more adverse events were both related to an increase in PTSD symptomatology. Global psychopathology was associated with PCL-5 scores, with an emphasis on paranoid ideation, hostility, depression, anxiety, and phobic anxiety. Discussion: The severe wildfires of 2017 did not impact PTSD scores in this sample (collected the year after), suggesting that cumulative adverse events are more important than particular episodes. However, the number of reported events was related to PTSD scores. These results can be used to develop interventions that target all firefighters by addressing risk and protective factors. This action research study motivated specialized aid for firefighters involved in this study.

Does the media (also) keep the score? Media-based exposure to the Russian-Ukrainian war and mental health in Portugal.

The Russian-Ukrainian war (RUW) is responsible for extensive individual suffering and a socio-economic impact on the world and is reshaping global affairs. Many studies have focused on direct exposure to conflict and several public health policies have been devised. Nonetheless, indirect exposure through media has received minimal attention and there is limited evidence that mental health symptoms and disorders may arise as a result. We explored the role of voluntary or involuntary media-based exposure to the RUW on individuals' mental health including stress symptoms, coping strategies, daily functioning, and worries across demographic variables. In our sample, subjects with involuntary and higher amount of exposure seem to have higher stress symptoms. Also, those who had previous ruminations on war issues could be at risk of developing more post-traumatic stress symptoms. Therefore, media appears to be a conduit that spreads negative consequences of community trauma beyond directly affected communities.

Ulva rigida Valorization into Poly(3-hydroxybutyrate), Organic Acids and Functional Ingredients.

Halomonas elongata 1H9T is a moderate halophilic strain able to produce poly(3-hydroxybutyrate) (P(3HB)), a biodegradable plastic, and gluconic acid, a valuable organic acid with wide industrial applications. In this work, the green alga Ulva rigida was used as platform to produce cultivation substrates for microbial conversion as well as functional ingredients, targeting its full valorization. The liquor obtained by autohydrolysis presented the highest concentration of oligosaccharides and protein, being an interesting feedstock to produce functional ingredients. The acid and/or enzymatic hydrolysis liquors are adequate as substrates for microbial processes. Shake flask assays with H. elongata revealed that the N-rich liquor produced after acidic treatment was the best suited for cell growth while the N-poor liquor produced by the enzymatic treatment of acid-pretreated algae residues produced the highest P(3HB) titers of 4.4 g/L. These hydrolysates were used in fed-batch cultivations as carbon and protein sources for the co-production of gluconic acid and polymer achieving titers of 123.2 g/L and 7.2 g/L, respectively. Besides gluconic acid, the Krebs cycle intermediate 2-oxoglutaric acid, also called alpha-ketoglutaric acid (KGA), was produced. Therefore, the co-production of P(3HB) and acids may be of considerable interest as an algal biorefinery valorization strategy.

Different Methods for Assessing Tooth Colour-In Vitro Study.

Colour assessment using digital methods can yield varying results, and it is important for clinicians to recognize the potential variability intra and inter-device. This study aimed to compare the L*a*b* values of VITA Classical (VC) and VITA Toothguide 3D-MASTER (VM) guides using two methods, SpectroShade (SS) and eLAB. Thirty-four measurements per tab were performed by a single operator across three batches of each guide. Intraclass correlation coefficients (ICC) between batches were calculated. Values <0.5, 0.5-0.75, 0.75-0.9, and >0.90 were classified as poor, moderate, good, and excellent reliability, respectively. Results were reported as mean and standard deviation of the L*a*b* values and respective colour differences (ΔE00) for each tab and method. Statistical analyses were performed with an independent t-test, α = 0.05. ICC values between batches were excellent for all L*a*b*, except for a* component in eLAB. There were statistically significant differences between methods in most L*a*b* values. The intra-device mean ΔE00 was 0.5 ± 0.6 for VC, 0.5 ± 0.8 for VM in SS, 1.1 ± 0.8 for VC, 1.1 ± 0.9 for VM in eLAB. The mean ΔE00 inter-device was 4.9 ± 1.7 for VC, 5.0 ± 1.7 for VM. Both methods demonstrated good internal consistency, with high ICC values and low intra-device colour differences, but exhibited high variability between methods, higher for a* the component.

Panobinostat-loaded folate targeted liposomes as a promising drug delivery system for treatment of canine B-cell lymphoma.

Introduction: Cancer is a major public health problem with over 19 million cases reported in 2020. Similarly to humans, dogs are also largely affected by cancer, with non-Hodgkin's lymphoma (NHL) among the most common cancers in both species. Comparative medicine has the potential to accelerate the development of new therapeutic options in oncology by leveraging commonalities between diseases affecting both humans and animals. Within this context, in the present study, we investigated the potential of panobinostat (Pan)-loaded folate-targeted PEGylated liposomes (FA-PEG-Pan-Lip) for the treatment of canine B-cell lymphoma, while contributing to new perspectives in comparative oncology. Methods and results: Two formulations were developed, namely: PEG-Pan-Lip and FA-PEG-Pan-Lip. Firstly, folate receptor expression in the CLBL-1 canine B-cell lymphoma cell line was assessed. After confirming receptor expression, both Pan-loaded formulations (PEG-Pan-Lip, FA-PEG-Pan-Lip) demonstrated dose-dependent inhibitory effects on CLBL-1 cell proliferation. The FA-PEG-Pan-Lip formulation (IC50 = 10.9 ± 0.03 nM) showed higher cytotoxicity than the non-targeted PEG-Pan-Lip formulation (IC50 = 12.9 ± 0.03 nM) and the free panobinostat (Pan) compound (IC50 = 18.32±0.03 nM). Moreover, mechanistically, both Pan-containing formulations induced acetylation of H3 histone and apoptosis. Flow cytometry and immunofluorescence analysis of intracellular uptake of rhodamine-labeled liposome formulations in CLBL-1 cells confirmed cellular internalization of PEG-Lip and FA-PEG-Lip formulations and higher uptake profile for the latter. Biodistribution studies of both radiolabeled formulations in CD1 and SCID mice revealed a rapid clearance from the major organs and a 1.6-fold enhancement of tumor uptake at 24 h for 111In-FA-PEG-Pan-Lip (2.2 ± 0.1 %ID/g of tumor) compared to 111In-PEG-Pan-Lip formulation (1.2±0.2 %ID/g of tumor). Discussion: In summary, our results provide new data validating Pan-loaded folate liposomes as a promising targeted drug delivery system for the treatment of canine B-cell lymphoma and open innovative perspectives for comparative oncology.

TANGO2 Deficiency Disorder: Two Cases of Developmental Delay Preceding Metabolic Crisis.

BACKGROUND: TANGO2 deficiency disorder is a rare genetic disease caused by biallelic defects in TANGO2 gene. METHODS: We report the clinical phenotype of two children with TANGO2 deficiency disorder. RESULTS: Patient 1 is a female child presenting with developmental delay and microcephaly during the second year of life, who evolved with severe cognitive impairment, facial dysmorphisms, spastic paraparesis, and atonic seizures. At age 13 years, she was hospitalized due to an episode of rhabdomyolysis complicated with cardiac arrhythmia and hypothyroidism. Patient 2 is a female child with dysmorphic facial features, cleft palate, and developmental delay who was diagnosed with DiGeorge syndrome. At age three years, she presented with an acute episode of severe rhabdomyolysis in the context of human herpesvirus 6 infection. After the resolution of this acute episode, she maintained recurrent muscle weakness with axial hypotonia and progressive spasticity of the lower extremities. In both patients, diagnosis of TANGO2 deficiency disorder was only confirmed after an acute metabolic crisis. CONCLUSIONS: A high index of suspicion for TANGO2 deficiency disorder is needed in patients with developmental delay or other neurological symptoms and episodic rhabdomyolysis.

Microalgae to Bioenergy: Optimization of Aurantiochytrium sp. Saccharification.

Microalgae are a promising feedstock for bioethanol production, essentially due to their high growth rates and absence of lignin. Hydrolysis-where the monosaccharides are released for further fermentation-is considered a critical step, and its optimization is advised for each raw material. The present study focuses on the thermal acid hydrolysis (with sulfuric acid) of Aurantiochytrium sp. through a response surface methodology (RSM), studying the effect of acid concentration, hydrolysis time and biomass/acid ratio on both sugar concentration of the hydrolysate and biomass conversion yield. Preliminary studies allowed to establish the range of the variables to be optimized. The obtained models predicted a maximum sugar concentration (18.05 g/L; R2 = 0.990) after 90 min of hydrolysis, using 15% (w/v) biomass/acid ratio and sulfuric acid at 3.5% (v/v), whereas the maximum conversion yield (12.86 g/100 g; R2 = 0.876) was obtained using 9.3% (w/v) biomass/acid ratio, maintaining the other parameters. Model outputs indicate that the biomass/acid ratio and time are the most influential parameters on the sugar concentration and yield models, respectively. The study allowed to obtain a predictive model that is very well adjusted to the experimental data to find the best saccharification conditions for the Aurantiochytrium sp. microalgae.