Resolve and dissolve-An ultrasound-guided investigation on the effects of hyaluronidase on different soft tissue fillers.

BACKGROUND: Nonsurgical cosmetic procedures, particularly the use of hyaluronic acid (HA)-based soft tissue fillers, are becoming increasingly popular. This trend has catalyzed the development of a plethora of HA-based products differing in product characteristics, thereby catering to an ever-widening spectrum of aesthetic applications. However, complications rise concomitant with the increasing number of procedures. Among the strategies to manage such adverse events is the enzymatic breakdown with hyaluronidase. OBJECTIVE: To analyze the response of different HA-based soft tissue filler materials to hyaluronidase injections. METHODS: A total of 11 different HA-based soft tissue fillers were evaluated using noninvasive ultrasound imaging to assess their behavior in response to hyaluronidase injections. The HA-based soft tissue fillers were categorized according to their product characteristics into a structuring, volumizing, and lip volumizing group. Standardized injections of 0.2 cc were performed in chicken breast to simulate human tissue. Ultrasound measurements of width, height, and calculated volume were performed immediately after filler injection, 1 h and 24 h following hyaluronidase injection. RESULTS: Regardless of the soft tissue filler analyzed, the most significant volume reduction occurred within the first h after applying hyaluronidase, with a 64.1% decrease from the initial volume. After 24 h, the total volume reduction reached 81.7%. No statistically significant differences were found when comparing the three groups at each follow-up time period, except for the height measurement after 1 h. While width was statistically significant in all groups between the investigated follow-up groups, the volume reduction was only statistically significant in the groups with the highest and second highest G' values (i.e., Group 1-structuring, Group 2-volumizing). CONCLUSION: The effectiveness of hyaluronidase in dissolving HA-based fillers is initially independent of product characteristics of HA-based fillers such as G-prime, with increased efficacy in fillers with higher G-prime values, as evidenced by significant volume reductions in such groups.

Generation of precision preclinical cancer models using regulated in vivo base editing.

Although single-nucleotide variants (SNVs) make up the majority of cancer-associated genetic changes and have been comprehensively catalogued, little is known about their impact on tumor initiation and progression. To enable the functional interrogation of cancer-associated SNVs, we developed a mouse system for temporal and regulatable in vivo base editing. The inducible base editing (iBE) mouse carries a single expression-optimized cytosine base editor transgene under the control of a tetracycline response element and enables robust, doxycycline-dependent expression across a broad range of tissues in vivo. Combined with plasmid-based or synthetic guide RNAs, iBE drives efficient engineering of individual or multiple SNVs in intestinal, lung and pancreatic organoids. Temporal regulation of base editor activity allows controlled sequential genome editing ex vivo and in vivo, and delivery of sgRNAs directly to target tissues facilitates generation of in situ preclinical cancer models.

Oncogenic context shapes the fitness landscape of tumor suppression.

Tumors acquire alterations in oncogenes and tumor suppressor genes in an adaptive walk through the fitness landscape of tumorigenesis. However, the interactions between oncogenes and tumor suppressor genes that shape this landscape remain poorly resolved and cannot be revealed by human cancer genomics alone. Here, we use a multiplexed, autochthonous mouse platform to model and quantify the initiation and growth of more than one hundred genotypes of lung tumors across four oncogenic contexts: KRAS G12D, KRAS G12C, BRAF V600E, and EGFR L858R. We show that the fitness landscape is rugged-the effect of tumor suppressor inactivation often switches between beneficial and deleterious depending on the oncogenic context-and shows no evidence of diminishing-returns epistasis within variants of the same oncogene. These findings argue against a simple linear signaling relationship amongst these three oncogenes and imply a critical role for off-axis signaling in determining the fitness effects of inactivating tumor suppressors.

Motivation toward Physical Activity and Healthy Habits of Adolescents: A Systematic Review.

Adolescence is a transformative period in which rapid physical, cognitive and psychosocial growth takes place. Laying the foundation for healthy behaviors is paramount during these formative years. The aim of this review is to determine which countries are leading in research on adolescents' motivation towards physical activity and healthy habits and their main findings. A systematic review was conducted following the PRISMA statement using the Web of Science and Scopus databases during the months of September to December 2022. The search terms used were: "Physical activity", "Motivation" and "Adolescents", in the following research areas: Education, Educational Research and Sport Sciences. A total of 5594 articles were identified, but only those that met the established criteria were included (32 articles). It is concluded that most of the research is led in Spain with 16 articles, followed by 3 in Chile, 2 in Portugal, 2 in Norway and the rest of the countries with 1. Likewise, most of the works include very similar aspects regarding the incidence of motivation towards the adherence to the practice of Physical Activity and healthy habits.

Adaptation and Validation of the Spanish Version of Kogan's Attitude toward Older People Scale (KAOP).

It is essential to understand the behavior and attitudes of nurses towards older people to improve clinical practice and quality of care in the gerontological sector. A clearer understanding of the attitudes that drive nurses toward the desire to work with older people would be a good starting point to encourage the development of positive and nurturing attitudes. A cross-sectional study with non-probabilistic sampling and a self-administered questionnaire was conducted among 381 nursing students of the Faculty of Nursing at the University of Castilla La-Mancha to evaluate the psychometric properties of the Spanish Version of the Kogan's Attitudes Towards Older People Scale (KAOP-S). Construct validity, internal consistency, and reliability were assessed. In total, 298 females and 83 males completed the questionnaires. Their mean age was 20.42 years. The results revealed a Cronbach's alpha coefficient of 0.75 for the scale, which is comparable with other published versions of the KAOP Scale. The results of the exploratory factor analysis established that the scale has a two-factor solution and an explained variance of 25% in the sample. The KAOP-S was found to be a reliable and valid tool with good content and construct validity for assessing nursing students' attitudes towards older people.

Development of a TaqMan qPCR assay for trypanosomatid multi-species detection and quantification in insects.

BACKGROUND: Trypanosomatid parasites are widely distributed in nature and can have a monoxenous or dixenous life-cycle. These parasites thrive in a wide number of insect orders, some of which have an important economic and environmental value, such as bees. The objective of this study was to develop a robust and sensitive real-time quantitative PCR (qPCR) assay for detecting trypanosomatid parasites in any type of parasitized insect sample. METHODS: A TaqMan qPCR assay based on a trypanosomatid-conserved region of the α-tubulin gene was standardized and evaluated. The limits of detection, sensitivity and versatility of the α-tubulin TaqMan assay were tested and validated using field samples of honeybee workers, wild bees, bumblebees and grasshoppers, as well as in the human infective trypanosomatid Leishmania major. RESULTS: The assay showed a detection limit of 1 parasite equivalent/µl and successfully detected trypanosomatids in 10 different hosts belonging to the insect orders Hymenoptera and Orthoptera. The methodology was also tested using honeybee samples from four apiaries (n = 224 worker honeybees) located in the Alpujarra region (Granada, Spain). Trypanosomatids were detected in 2.7% of the honeybees, with an intra-colony prevalence of 0% to 13%. Parasite loads in the four different classes of insects ranged from 40.6 up to 1.1 × 108 cell equivalents per host. CONCLUSIONS: These results show that the α-tubulin TaqMan qPCR assay described here is a versatile diagnostic tool for the accurate detection and quantification of trypanosomatids in a wide range of environmental settings.

The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants.

BACKGROUND: Fabry disease (FD) is an X-linked condition caused by variants in the GLA gene. Since females have two X chromosomes, they were historically thought to be carriers. Although increased knowledge has shown that females often develop the disease, data from Spain and other countries reported that females were undertreated. The aim of this study was to provide a wider and more recent description of the disease characteristics and associated management of females with a GLA variant in a Spanish cohort. RESULTS: Ninety-seven females from 12 hospitals were included in this retrospective study. Mean age was 50.1 ± 17.2 years. Median follow-up time from GLA variant identification was 36.1 months, and most (70.1%) were identified through family screening. Variants associated with classic/non-classic phenotypes were similarly distributed (40.2%/53.6%). Missense variants were the most prevalent (n = 84, 86.6%). In the overall group, 70.4% had major organ involvement (i.e., cardiac, renal, cerebrovascular, peripheral nervous system or gastrointestinal), and 47.3% also had typical Fabry signs (angiokeratoma, cornea verticillata or increased plasma lyso-Gb3). Cardiac involvement was the most prevalent (49.5%) and the main reason for treatment initiation. A total of 33 (34%) patients received disease-specific therapy, 55% of whom were diagnosed by family screening. Females carrying variants associated with a classic phenotype had higher frequencies of clinical manifestations (92.3%) and were predominant in the treated subgroup (69.7%). Despite this, there were 34 untreated females (56.7% of total untreated), with both phenotypes represented, who had major organ involvement, with 27 of cardiac, renal or cerebrovascular nature. Age or comorbidities in this subgroup were comparable to the treated subgroup (P = 0.8 and P = 0.8, respectively). CONCLUSIONS: Efforts have been made in recent years to diagnose and treat timely Fabry females in Spain. A high percentage of females with pathogenic variants, regardless of their associated phenotype, will likely develop disease. A proportion of females with severe disease in this cohort received specific treatment. Still a significant number of females, even with same profile as the treated ones, who may be eligible for treatment according to European recommendations, remained untreated. Reasons for this merit further investigation.

Sodium Homeostasis, a Balance Necessary for Life.

Body sodium (Na) levels must be maintained within a narrow range for the correct functioning of the organism (Na homeostasis). Na disorders include not only elevated levels of this solute (hypernatremia), as in diabetes insipidus, but also reduced levels (hyponatremia), as in cerebral salt wasting syndrome. The balance in body Na levels therefore requires a delicate equilibrium to be maintained between the ingestion and excretion of Na. Salt (NaCl) intake is processed by receptors in the tongue and digestive system, which transmit the information to the nucleus of the solitary tract via a neural pathway (chorda tympani/vagus nerves) and to circumventricular organs, including the subfornical organ and area postrema, via a humoral pathway (blood/cerebrospinal fluid). Circuits are formed that stimulate or inhibit homeostatic Na intake involving participation of the parabrachial nucleus, pre-locus coeruleus, medial tuberomammillary nuclei, median eminence, paraventricular and supraoptic nuclei, and other structures with reward properties such as the bed nucleus of the stria terminalis, central amygdala, and ventral tegmental area. Finally, the kidney uses neural signals (e.g., renal sympathetic nerves) and vascular (e.g., renal perfusion pressure) and humoral (e.g., renin-angiotensin-aldosterone system, cardiac natriuretic peptides, antidiuretic hormone, and oxytocin) factors to promote Na excretion or retention and thereby maintain extracellular fluid volume. All these intake and excretion processes are modulated by chemical messengers, many of which (e.g., aldosterone, angiotensin II, and oxytocin) have effects that are coordinated at peripheral and central level to ensure Na homeostasis.

Diagnosis of metastatic angiosarcoma of the aorta in colonic lesion biopsies.

Angiosarcomas are rare tumors that usually entail a poor prognosis because of extensive invasiveness and high rates of distant metastasis. Gastrointestinal tract involvement is uncommon but may cause digestive bleeding. A definitive diagnosis requires histological and immunohistochemical testing. Metastatic lesions to the gut usually have a typical morphology, which must be identified in order to avoid delay in the diagnosis and potential treatment of this malignant condition.

A consensus document on definition and diagnostic criteria for orthorexia nervosa.

PURPOSE: Since the term orthorexia nervosa (ON) was coined from the Greek (ὀρθός, right and ὄρεξις, appetite) in 1997 to describe an obsession with "correct" eating, it has been used worldwide without a consistent definition. Although multiple authors have proposed diagnostic criteria, and many theoretical papers have been published, no consensus definition of ON exists, empirical primary evidence is limited, and ON is not a standardized diagnosis. These gaps prevent research to identify risk and protective factors, pathophysiology, functional consequences, and evidence-based therapeutic treatments. The aims of the current study are to categorize the common observations and presentations of ON pathology among experts in the eating disorder field, propose tentative diagnostic criteria, and consider which DSM chapter and category would be most appropriate for ON should it be included. METHODS: 47 eating disorder researchers and multidisciplinary treatment specialists from 14 different countries across four continents completed a three-phase modified Delphi process, with 75% agreement determined as the threshold for a statement to be included in the final consensus document. In phase I, participants were asked via online survey to agree or disagree with 67 statements about ON in four categories: A-Definition, Clinical Aspects, Duration; B-Consequences; C-Onset; D-Exclusion Criteria, and comment on their rationale. Responses were used to modify the statements which were then provided to the same participants for phase II, a second round of feedback, again in online survey form. Responses to phase II were used to modify and improve the statements for phase III, in which statements that met the predetermined 75% of agreement threshold were provided for review and commentary by all participants. RESULTS: 27 statements met or exceeded the consensus threshold and were compiled into proposed diagnostic criteria for ON. CONCLUSIONS: This is the first time a standardized definition of ON has been developed from a worldwide, multidisciplinary cohort of experts. It represents a summary of observations, clinical expertise, and research findings from a wide base of knowledge. It may be used as a base for diagnosis, treatment protocols, and further research to answer the open questions that remain, particularly the functional consequences of ON and how it might be prevented or identified and intervened upon in its early stages. Although the participants encompass many countries and disciplines, further research will be needed to determine if these diagnostic criteria are applicable to the experience of ON in geographic areas not represented in the current expert panel. LEVEL OF EVIDENCE: Level V: opinions of expert committees.

Aetiological diagnosis of hyponatraemia in non-critical patients on total parenteral nutrition: A prospective multicentre study.

BACKGROUND: In patients receiving total parenteral nutrition (TPN), the frequency of hyponatraemia is high. However, the causes of hyponatraemia in TPN have not been elucidated, although diagnosis is required for appropriate therapy. The aim of this study is to describe the aetiology of hyponatraemia in non-critical hospitalised patients receiving TPN. METHODS: Prospective multicentre study in 19 Spanish hospitals. Non-critically hyponatraemic patients receiving TPN and presenting hyponatraemia over a 9-month period were studied. Data collected included sex, age, previous comorbidities, and serum sodium levels (SNa) before and following TPN initiation. Parameters for study of hyponatraemia were also included: clinical volaemia, the presence of pain, nausea, gastrointestinal losses, diuretic use, oedema, renal function, plasma and urine osmolality, urinary electrolytes, cortisolaemia, and thyroid stimulating hormone. RESULTS: 162 patients were included, 53.7% males, age 66.4 (SD13.8) years. Volume status was evaluated in 142 (88%): 21 (14.8%) were hypovolaemic, 96 (67.6%) euvolaemic and 25 (17.6%) hypervolaemic. In 111/142 patients the analytical assessment of hyponatraemia was completed. Hypovolaemic hyponatraemia was secondary to GI losses in 10/111 (9%), and to diuretics in 3/111 (2.7%). Euvolaemic hyponatraemia was due to Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) in 47/111 (42.4%), and to physiological stimuli of Arginine Vasopressin (AVP) secretion in 28/111 (25.2%). Hypervolaemic hyponatraemia was induced by heart failure in 19/111 (17.1%), cirrhosis of the liver in 4/111 (3.6%). CONCLUSIONS: SIADH was the most frequent cause of hyponatraemia in patients receiving TPN. The second most frequent cause was physiological stimuli of AVP secretion induced by pain/nausea.

Food Preferences in Undergraduate Nursing Students and Its Relationship with Food Addiction and Physical Activity.

The transition to college is a decisive stage for the acquisition of eating habits that continue into adulthood. The aim of this study is to assess the consumption of healthy elements of the Mediterranean diet in a group of university students and to evaluate whether the consumption pattern was related to sex, Body Mass Index (BMI), food addiction or the amount of physical activity performed. A total of 515 nursing students participated. The Mediterranean diet adherence questionnaire (PREDIMED), the food addiction scale (YFAS 2.0) and the International Physical Activity Questionnaire (IPAQ) were completed. For data analysis, multivariate analysis was performed with multiple linear regression and adjusted for sex, age, and BMI. The results showed that females consumed various types of meats (white/red, processed) in a healthier proportion (p < 0.05). Students that consumed more than one per day (unhealthy) of red/processed meats (mean difference (MD) = −0.49; 95% CI: −0.83; −0.15), soft drinks (MD = −0.82; 95% CI: 82−1.36; −0.27) and pastries (MD = −0.63; 95% CI: −0.97; −0.30) displayed higher food addiction scores. In addition, students who skipped breakfast also scored higher on food addiction (MD = 0.75; 95% CI: 0.31−1.19). Higher values of physical activity were observed in those who presented a healthy consumption of vegetables (MD = 140.86; 95% CI: 72.71−209.02), fruit (MD = 145.78; 95% CI: 69.35−222.21), legumes (MD = 136.46; 95% CI: 60.43−212.50) and nuts (MD = 74.36; 95% CI: 14.23−134.49). Students who consumed more red or processed meats, more pastries and more soft drinks had higher values of food addiction, while those who consumed more vegetables, fruits, legumes, and nuts had more minutes of physical activity per week. These findings invite us to insist on expanding knowledge regarding the health benefits of consuming a Mediterranean-type diet as a whole. The healthy consumption of fish, fruit and legumes should also be emphasized, especially among university students.

[Home and Ambulatory Artificial Nutrition (NADYA) Group report: home parenteral nutrition in Spain, 2019]. / Nutrición parenteral domiciliaria en España, 2019: informe del Grupo de Nutrición Artificial Domiciliaria y Ambulatoria NADYA.

INTRODUCTION: Aim: to communicate the home parenteral nutrition (HPN) data obtained from the HPN registry of the NADYA-SENPE group (www.nadya-senpe.com) for the year 2019. Material and methods: a descriptive analysis of the data collected from adult and pediatric patients with HPN in the NADYA-SENPE group registry from January 1 to December 31, 2019. Results: a total of 283 patients (51.9 % women), 31 children, and 252 adults from 47 Spanish hospitals were registered, which represents a prevalence rate of 6.01 patients per million inhabitants for year 2019. The most frequent diagnosis in adults was "palliative oncological" and "others" (21.0 %). In children, it was Hirschsprung's disease together with necrotizing enterocolitis, alterations in intestinal motility, and chronic intestinal pseudo-obstruction, with 4 cases each (12.9 %). The first reason for the indication was short-bowel syndrome in both children (51.6 %) and adults (37.3 %). The most used type of catheter was tunnelled both in children (75.9 %) and in adults (40.8 %). Sixty-eight episodes ended, all in adults, and the most frequent cause was death (54.4 %); 38.2 % were switched to oral. Conclusions: the number of collaborating centers and professionals in the NADYA registry is increasing. The main indications and reasons for HPN termination remain stable.

INTRODUCCIÓN: Objetivo: comunicar los datos de nutrición parenteral domiciliaria (NPD) obtenidos del registro del grupo NADYA-SENPE (www.nadya-senpe.com) del año 2019. Material y métodos: análisis descriptivo de los datos recogidos de pacientes adultos y pediátricos con NPD en el registro NADYA-SENPE desde el 1 de enero al 31 de diciembre de 2019. Resultados: se registraron 283 pacientes (51,9 %, mujeres), 31 niños y 252 adultos procedentes de 47 hospitales españoles, lo que representa una tasa de prevalencia de 6,01 pacientes/millón de habitantes/año 2019. El diagnóstico más frecuente en los adultos fue "oncológico paliativo" y "otros" (21,0 %). En los niños fue la enfermedad de Hirschsprung junto a la enterocolitis necrotizante, las alteraciones de la motilidad intestinal y la pseudoobstrucción intestinal crónica, con 4 casos cada uno (12,9 %). El primer motivo de indicación fue el síndrome del intestino corto tanto en los niños (51,6 %) como en los adultos (37,3 %). El tipo de catéter más utilizado fue el tunelizado tanto en los niños (75,9 %) como en los adultos (40,8 %). Finalizaron 68 episodios, todos en adultos: la causa más frecuente fue el fallecimiento (54,4 %). Pasaron a la vía oral el 38,2 %. Conclusiones: el número de centros y profesionales colaboradores con el registro NADYA va incrementándose. Se mantienen estables las principales indicaciones y los motivos de finalización de la NPD.

The Physical Education Class Perceived by Schoolchildren from 6 to 8 Years Old Expressed through Drawings.

Physical Education is one of the subjects that arouses the most interest in children. The aim of this study is to find out the opinion that primary school students have about the Physical Education class. Drawings from a sample of 62 students from an educational centre in the city of Jaén, aged between six and eight years old, were analysed. The results show that the larger size of the drawings corresponds to the aspects that are to be emphasised. This subject is carried out regularly in the sports pavilion of the centre, making frequent use of materials such as sticks, hoops or balls. Cheerful colours are used, reflecting their enthusiasm for the subject. The smiling facial expression represents the schoolchildren's interest in the subject. The most popular games or sports are basketball and pichi, both of them collective.

The Spanish Version of the Eating Habits Questionnaire (EHQ-ES) and Its Links to Symptoms and Concerns Characteristic of Eating Disorders among Young Adults.

The aim of the study was to investigate the psychometric properties (internal consistency, factor structure, and convergent validity) of the Spanish version of the Eating Habits Questionnaire (EHQ-ES) and its links to disordered eating in young adults. Two university student samples with a total of 487 participants (N1age = 21.75 ± 5.10; N2age = 21.17 ± 6.81) participated in the study. They filled out the Eating Habits Questionnaire and the Eating Attitudes Test. Our findings showed that the EHQ-ES demonstrated strong internal consistency, with a Cronbach's α = 0.903 and ω = 0.939. The EHQ-ES consists of 20 items to measure problems associated with healthy eating (α = 0.855, ω = 0.879), knowledge of healthy eating (α = 0.783, ω = 0.826) and feeling positively about healthy eating (α = 0.775, ω = 0.773). In addition, subscales of the EHQ correlated with subscales of the EAT-26, showing that Orthorexia Nervosa is associated with disordered eating in a sample of university students. The current study is the first to describe a Spanish version of the EHQ. This demonstrates that EHQ-ES is a reliable screening tool for Spanish-speaking young adults. Moreover, the EHQ-ES can be a useful instrument for assessing ON in research and clinical practice.

Aetiological diagnosis of hyponatraemia in non-critical patients on total parenteral nutrition: A prospective multicentre study.

BACKGROUND: In patients receiving total parenteral nutrition (TPN), the frequency of hyponatraemia is high. However, the causes of hyponatraemia in TPN have not been elucidated, although diagnosis is required for appropriate therapy. The aim of this study is to describe the aetiology of hyponatraemia in non-critical hospitalised patients receiving TPN. METHODS: Prospective multicentre study in 19 Spanish hospitals. Non-critically hyponatraemic patients receiving TPN and presenting hyponatraemia over a 9-month period were studied. Data collected included sex, age, previous comorbidities, and serum sodium levels (SNa) before and following TPN initiation. Parameters for study of hyponatraemia were also included: clinical volaemia, the presence of pain, nausea, gastrointestinal losses, diuretic use, oedema, renal function, plasma and urine osmolality, urinary electrolytes, cortisolaemia, and thyroid stimulating hormone. RESULTS: 162 patients were included, 53.7% males, age 66.4 (SD13.8) years. Volume status was evaluated in 142 (88%): 21 (14.8%) were hypovolaemic, 96 (67.6%) euvolaemic and 25 (17.6%) hypervolaemic. In 111/142 patients the analytical assessment of hyponatraemia was completed. Hypovolaemic hyponatraemia was secondary to GI losses in 10/111 (9%), and to diuretics in 3/111 (2.7%). Euvolaemic hyponatraemia was due to Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) in 47/111 (42.4%), and to physiological stimuli of Arginine Vasopressin (AVP) secretion in 28/111 (25.2%). Hypervolaemic hyponatraemia was induced by heart failure in 19/111 (17.1%), cirrhosis of the liver in 4/111 (3.6%). CONCLUSIONS: SIADH was the most frequent cause of hyponatraemia in patients receiving TPN. The second most frequent cause was physiological stimuli of AVP secretion induced by pain/nausea.

Revealing ARID1A Function in Gastric Cancer from the Bottom Up.

In this issue of Cancer Discovery, Lo and colleagues use CRISPR-based genome engineering in primary human gastric organoids to reveal the functional consequences of ARID1A loss in the early stages of gastric cancer. They show that ARID1A disruption is not tolerated in wild-type organoids, but in the context of TP53 loss, leads to WNT suppression, mucinous metaplasia, enhanced tumorigenicity, and selectively toxicity to BIRC5/Survivin inhibition.See related article by Lo et al., p. 1562.