Is long-term follow-up solely by imaging tests safe in non-operated pancreatic neuroendocrine tumors?

INTRODUCTION: the diagnosis of asymptomatic sporadic nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) has increased significantly due to the widespread use of high-resolution imaging tests, which is why the most appropriate management at the time of diagnosis is the subject of debate, as is how to follow-up patients. AIMS: the objective of this study was to analyze the frequency of imaging and endoscopic studies performed during long-term follow-up. METHODS: a retrospective review was performed of a database collected between January 2008 and December 2020 of patients with an incidental diagnosis of small NF-PNETs; follow-up was closed in March 2023. The imaging tests performed at the time of diagnosis and long-term follow-up were recorded. Growing less than 1 mm per year has not been considered as a worrisome feature. Follow-up was performed through imaging tests, considering endoscopic cytology for lesions with a faster grow rate. RESULTS: fifty-eight patients were included; the median age was 69 years. The initial mean size of the lesions studied was 12.79 mm (5-27). Follow-up was carried out only with computed tomography (CT) or magnetic resonance imaging (MRI). The initial size did not influence the behavior of the lesion in a statistically significant manner. Twenty-eight tumors (45 %) increased in size, with a growth equal to or less than 4 mm in 24 cases. The mean follow-up time was 82.41 months (12-164). No patient developed metastasis or died from PNET progression. CONCLUSIONS: the follow-up of neuroendocrine tumors of small size can be performed safely with only imaging tests.

"Hemosuccus pancreaticus:" an uncommon form of presentation of pancreatic intraductal papillary mucinous neoplasm.

"Hemosuccus pancreaticus" (HP), "wirsungorrhagia" or "pseudohemobilia" is a rare cause of upper gastrointestinal bleeding consisting of blood loss along the duct of Wirsung with exteriorization through the ampulla of Vater. Due to its rarity, the literature on HP is limited to retrospective studies, case reports, and case series.

Enhanced cytotoxicity of highly water-soluble gold nanoparticle-cyclopeptide conjugates in cancer cells.

Conjugation of cytostatic drugs to nanomaterials seeks to improve their low bioavailability and selectivity to overcome the important associated side effects. In this work, we aimed to synthesize water-soluble gold nanoparticles as transporters for synthetic cyclic peptides with a potential anticancer activity but with a limited bioavailability. The highly water-soluble nanoparticles (2.5 nm diameter gold core) are coated with a mixture of polyethylene glycol linkers, one bearing a terminal hydroxyl group for increasing dispersibility in water, and the second bearing a carboxylic acid group for peptide conjugation through amide bond formation. Peptide-functionalized particles have a 9.7 ± 1.8 nm hydrodynamic diameter and are highly water-soluble and stable in solution for at least one year. The morphology of the gold cores as well as their organic coating was studied using Transmission Electron Microscopy, showing that the attachment of a limited number of peptides per nanoparticle leads to a uneven organic coating of two different thicknesses, one of 2.0 ± 0.6 nm formed by polyethylene glycol linkers, and a second of 3.6 ± 0.5 nm which includes the peptide. GNP significantly enhance the internalization of the cyclic peptide BPC734 in cells as compared to peptide in solution, with improved uptake in cancerous HT29 cells. Cytotoxicity studies show that peptide BPC734 in solution is toxic in the micromolar range, whereas peptide-functionalized particles are toxic at nanomolar peptide concentrations and with a significantly higher toxicity for cancerous cells. All these results, besides the stability and expected passive tumor targeting, make these particles a promising option for improving the bioavailability, efficacy, and selectivity in cancer therapy.

Quality of care provided to outpatients with hepatic cirrhosis in a teaching hospital.

INTRODUCTION: a set of indicators to measure the quality of care of cirrhotic patients has been established and previously published studies report an adherence rate to clinical guide indications of 40-80 %. OBJECTIVE: to assess the adherence to quality indicators in a tertiary teaching hospital. METHODS: a retrospective observational study was performed of all cirrhotic outpatients seen during one semester in 2017. The charts were studied of 324 patients and quality indicators related to five domains were collected. An overall adherence to 14 quality indicators was recorded and analyzed based on the attending physician's experience. RESULTS: the results were excellent (more than 90 % adherence) for quality indicators related to prophylaxis of variceal bleeding and documentation of cirrhosis etiology, acceptable (60-90 % adherence) for hepatocellular carcinoma screening and disease severity assessment, and poor (less than 50 %) for vaccinations. Residents had significantly better results than experienced physicians in etiology, disease severity assessment and two indicators of prophylaxis of bleeding. Experienced physicians only presented a better adherence to hepatocellular carcinoma screening. CONCLUSIONS: despite excellent results for some quality indicators, most required improvement, especially vaccinations. The quality of care achieved by residents is equal to and even better than that of experienced physicians. Measuring quality of care is essential to analyze and improve the health care of cirrhotic outpatients and may be a useful tool for supervising specialists in training.

Design, synthesis, and biological evaluation of cyclic peptidotriazoles derived from BPC194 as novel agents for plant protection.

The search for novel antimicrobial agents to be used for plant protection has prompted us to design analogues incorporating non-natural amino acids. Herein, we designed and synthesized cyclic peptidotriazoles derived from the lead antimicrobial cyclic peptide c(Lys-Lys-Leu3 -Lys-Lys5 -Phe-Lys-Lys-Leu-Gln) (BPC194). In particular, Leu3 and Lys5 were replaced by a triazolyl alanine, a triazolyl norleucine or a triazolyl lysine. These peptides were screened for their antibacterial activity against Xanthomonas axonopodis pv. vesicatoria, Erwinia amylovora, and Pseudomonas syringae pv. syringae, for their hemolysis and for their phytotoxicity. Results showed that the type of triazolyl amino acid and the substituent present at the triazole influenced the antibacterial and hemolytic activities. Moreover, the position of this residue was also crucial for the hemolysis. The lead compounds BPC548 and BPC550 exhibited high antibacterial activity (MIC of 3.1 to 25 µM), low hemolysis (19 and 26% at 375 µM, respectively) and low phytotoxicity. Therefore, these analogues could be used as new leads for the development of effective agents to control pathogenic bacteria responsible for plant diseases of economic importance.

Links between parasitism, energy reserves and fecundity of European anchovy, Engraulis encrasicolus, in the northwestern Mediterranean Sea.

The European anchovy, Engraulis encrasicolus L. 1758, is one of the most sought-after target species in the northwestern Mediterranean Sea. However, this stock currently consists of small individuals, and landings are reported to have decreased considerably. The main purpose of this study was to assess, for the first time, the interrelationships between size, fecundity, energy reserves and parasitism in female anchovies, in order to analyse the potential implications for the health of northwestern Mediterranean anchovy stocks arising from the current shortage of large individuals. Results revealed that smaller individuals show lower fecundity, lower lipid content and a higher intensity of certain parasites. As it is known that smaller individuals now predominate in the population, the relationships found in this study indicate that the health of anchovies from the northwestern Mediterranean is currently impaired.

Synthetic Cyclolipopeptides Selective against Microbial, Plant and Animal Cell Targets by Incorporation of D-Amino Acids or Histidine.

Cyclolipopeptides derived from the antimicrobial peptide c(Lys-Lys-Leu-Lys-Lys-Phe-Lys-Lys-Leu-Gln) (BPC194) were prepared on solid-phase and screened against four plant pathogens. The incorporation at Lys5 of fatty acids of 4 to 9 carbon atoms led to active cyclolipopeptides. The influence on the antimicrobial activity of the Lys residue that is derivatized was also evaluated. In general, acylation of Lys1, Lys2 or Lys5 rendered the sequences with the highest activity. Incorporation of a D-amino acid maintained the antimicrobial activity while significantly reduced the hemolysis. Replacement of Phe with a His also yielded cyclolipopeptides with low hemolytic activity. Derivatives exhibiting low phytotoxicity in tobacco leaves were also found. Interestingly, sequences with or without significant activity against phytopathogenic bacteria and fungi, but with differential hemolysis and phytotoxicity were identified. Therefore, this study represents an approach to the development of bioactive peptides with selective activity against microbial, plant and animal cell targets. These selective cyclolipopeptides are candidates useful not only to combat plant pathogens but also to be applied in other fields.

Sense of Well-Being in Patients with Fibromyalgia: Aerobic Exercise Program in a Mature Forest-A Pilot Study.

Background and Objective. Most patients with fibromyalgia benefit from different forms of physical exercise. Studies show that exercise can help restore the body's neurochemical balance and that it triggers a positive emotional state. So, regular exercise can help reduce anxiety, stress, and depression. The aim of this study was to analyze the benefits of moderate aerobic exercise when walking in two types of forests, young and mature, and to assess anxiety, sleep, pain, and well-being in patients with fibromyalgia. Secondary objectives included assessing (i) whether there were differences in temperature, sound, and moisture, (ii) whether there was an improvement in emotional control, and (iii) whether there was an improvement in health (reduction in pain) and in physical and mental relaxation. Patients and Methods. A study involving walking through two types of forests (mature and young) was performed. A total of 30 patients were randomly assigned to two groups, mature and young forests. The participants were administered the following tests: the Spanish version of the Revised Fibromyalgia Impact Questionnaire (FIQR) at baseline and the end-point of the study, the State-Trait Anxiety Inventory (STAI) after each walk, and a series of questions regarding symptomatic evolution. Several physiological parameters were registered. Results. FIQR baseline and end-point scores indicated a significant decrease in the symptomatic subscale of the FIQ (SD = 21.7; z = -2.4; p = 0.041). The within-group analysis revealed that differences were significant with respect to days of intense pain, insomnia, and days of well-being only in the group assigned to the mature forest, not in the group assigned to the young forest. No differences were found with respect to anxiety. Conclusions. Although the main aim of this research was not achieved, as the results revealed no differences between the groups in the two forest types, authors could confirm that an aerobic exercise program consisting of walking through a mature forest can provide the subjective perception of having less days of pain and insomnia and more days of wellness, in patients with fibromyalgia.

Dependence scale for Alzheimer's disease: relationship with other clinical indicators and psychometric properties.

The objective of this cross-sectional and multicenter study was to evaluate the psychometric properties of the Spanish version of the Dependence Scale (DS) and to assess the relationship between dependence and clinical measures according to disease severity. Medical comorbidities, cognitive status and functional status, behavior, dependence, caregiver burden, and medical and social resources were assessed using standardized instruments. The sample consisted of 343 patients (32.1% mild, 36.7% moderate, and 31.2% severe), the mean age was 78.9 years (standard deviation=7.4), and 67.0% were women. Criterion and construct validity index of DS were appropriate. The DS standard error of measurement was ±1.23. The explained variance in DS ranged between 0.598 and 0.731, and the relative contribution of clinical measures depended on disease severity. Current findings confirm that the Spanish version of the DS has appropriate psychometric indices and suggest that clinical indicators have different contribution to dependence according to disease severity.

A convenient solid-phase strategy for the synthesis of antimicrobial cyclic lipopeptides.

A concise solid-phase synthesis of cyclic lipopeptides derived from the antimicrobial peptide c(Lys-Lys-Leu-Lys-Lys-Phe-Lys-Lys-Leu-Gln) (BPC194) was accomplished. Three different synthetic routes were explored. Best results were obtained using a protocol that includes as key steps: (i) synthesis of the cyclic peptidyl resin incorporating the Lys residue to be acylated protected at the N(ε)-amino group with an ivDde group, (ii) selective removal of the ivDde group, and (iii) acylation. These compounds were screened for their in vitro growth inhibition of bacterial and fungal phytopathogens and for their cytotoxic effects on eukaryotic cells. A sequence with high antimicrobial activity and low hemolysis was identified, constituting a good candidate for the design of new antimicrobial agents.

[Annual economic cost of informal care in Alzheimer's disease]. / Valor económico anual de la asistencia informal en la enfermedad de Alzheimer.

INTRODUCTION: The indirect cost associated with the care of patients with Alzheimer's disease is taken on primarily by the family. AIM: To describe the cost associated with time dedication, its annual evolution, associated characteristics and related caregiver burden. SUBJECTS AND METHODS: Non-institutionalized patients diagnosed with Alzheimer's disease who are managed on an out-patient basis in a diagnosis unit and their primary caregivers. Prospective and observational study conducted over 12 months. The patient's clinical features were assessed using the Cambrigde Cognitive Examination Revised for cognitive capacity, the Disability Assessment in Dementia for functional capacity and the Neuropsychiatric Inventory for non-cognitive disorders. Sociodemographic data were collected by means of the Cambridge Examination for Mental Disorders of the Elderly Revised. The caregiver's dedication, sociodemographic characteristics and burden (by means of the Zarit interview) were recorded. RESULTS: Sample comprised of 169 patients and 169 caregivers. The cost at baseline was 6364.8 euro/year, and was mainly associated with support in instrumental activities. At 12 months, an overall increase of 29% was observed (1846.8 euro/year). Cost increase was associated with physical (F = 25.2; df = 1; p < 0.001) and cognitive (F = 8.5; df = 1; p = 0.004) disability, patient age (F = 9.2; df = 1; p = 0.003) and with whether the caregiver was the only caregiver or not (F = 20.4; df = 1; p < 0.001). The cost of care explained 6.7% of the total variance of the burden perceived by caregivers. CONCLUSIONS: Care has a mean indirect cost of 6364.2 euro/year, with an annual increase of 29% that was associated with physical and cognitive disability, patient age and having one single caregiver.

Effect of morphological heterogeneity of somatic embryos of Melia azedarach on conversion into plants.

Embryogenic cultures were initiated from immature Melia azedarach (Meliaceae) zigotic embryos. Explants were induced on Murashige and Skoog (1962) medium with 4.54 microM thidiazuron or 0.45 microM dichlorophenoxyacetic acid. After 6 weeks of culture on induction medium, somatic embryos were categorized in four morphological classes based on the presence of single or fused embryos and if they remained united or not to the original explant; that were evaluated histologically. The somatic embryos of every category were transferred, in groups or individually, on a 1/4 MS medium. Bipolar embryos, the more typically normal ones, had well defined shoot and root apical meristems and produced single plants; subcultured individually their conversion was 28%, and subcultured in groups the conversion declined to 6.8%. Fused embryos subcultured in groups had only a 2.1% conversion and produced plants with fused stems. None conversion rate in the others classes was associated to poorly developed shoot and root meristematic areas or with their absence. The converted plants were acclimatized and transferred, in a mist, to soil, with an independent of the class 95% survival rate.

Effect of morphological heterogeneity of somatic embryos of Melia azedarach on conversion into plants

Embryogenic cultures were initiated from immature Melia azedarach (Meliaceae) zigotic embryos. Explants were induced on Murashige and Skoog (1962) medium with 4.54 microM thidiazuron or 0.45 microM dichlorophenoxyacetic acid. After 6 weeks of culture on induction medium, somatic embryos were categorized in four morphological classes based on the presence of single or fused embryos and if they remained united or not to the original explant; that were evaluated histologically. The somatic embryos of every category were transferred, in groups or individually, on a 1/4 MS medium. Bipolar embryos, the more typically normal ones, had well defined shoot and root apical meristems and produced single plants; subcultured individually their conversion was 28%, and subcultured in groups the conversion declined to 6.8%. Fused embryos subcultured in groups had only a 2.1% conversion and produced plants with fused stems. None conversion rate in the others classes was associated to poorly developed shoot and root meristematic areas or with their absence. The converted plants were acclimatized and transferred, in a mist, to soil, with an independent of the class 95% survival rate.

[Adaptation and convergent validity of a telephone-based Mini-Mental State Examination]. / Adaptación y validez convergente de una versión telefónica del Mini-Mental State Examination.

BACKGROUND AND OBJECTIVE: To adapt to Spanish and to determine the convergent validity of a Telephone Mini-Mental State Examination (t-MMSE) in order to assess the cognitive functions in Alzheimer's disease (AD) patients. PATIENTS AND METHOD: Prospective and observational study of a clinical sample consisting of patients with dementia from a memory clinic. Consecutive sampling of participants was used and convergent validity of the t-MMSE and MMSE scores was determined using several statistics measures. Patients were randomly assigned depending on the administration of the in-person/telephone test (MMSE and t-MMSE) or telephone/in-person (t-MMSE and MMSE) test within a 1- to 7-day interval. The effect of the confusion variables (age, gender, years of education, dementia severity, presence or absence of hearing impairment and administration order) on the concordance between the in-person and telephone MMSE versions was analysed. RESULTS: After translating and retranslating the t-MMSE, of 141 participants, 77.47% subjects completed the protocol of the study. For the total score, the statistics for the convergent validity suggested a high consistency, independently of the order of test administration (intraclass correlation coefficient = 0.87, Spearman's rho = 0.77); for the all subscores, it suggested moderate and good correlations. The difference between subscores did not range more than 1 point in any case. Confusion variables did not affect the variability of the performance scores between t-MMSE and MMSE. CONCLUSIONS: The t-MMSE can be used as a good tool to estimate the MMSE score of patients with dementia.

Cryopreservation of somatic embryos of paradise tree (Melia azedarach L.).

In paradise tree (Melia azedarach L.), immature zygotic embryos sampled from immature fruits are the starting material for the production of somatic embryos. These somatic embryos are employed for freezing experiments. Immature fruits could be stored at 25 degrees C for up to 80 days without impairing the embryogenic potential of zygotic embryos, which represents a four-fold increase in immature fruit storage duration, compared with previous studies. Among the three cryopreservation techniques tested for freezing paradise tree somatic embryos, namely desiccation, encapsulation-dehydration and pregrowth-dehydration, only encapsulation-dehydration and pregrowth-dehydration led to successful results. The optimal protocol was the following: i) somatic embryos (encapsulated or not) pretreated in liquid Murashige & Skoog medium with daily increasing sucrose concentration (0.5 M/0.75 M/1.0 M); ii) dehydrated with silica gel to 21 - 26% moisture content (fresh weight basis), for encapsulation-dehydration, or to 19% moisture content, for pregrowth-dehydration; iii) frozen at 1 degree C/min from 20 degrees C to -30 degrees C with a programmable freezing apparatus; iv) rapid immersion in liquid nitrogen. The highest recovery achieved was 36% with encapsulation-dehydration and 30% with pregrowth-dehydration. Regrowth of frozen embryos was direct in most cases, as secondary embryogenesis originating from the root pole was observed on only around 10% of cryopreserved somatic embryos. Plants recovered from cryopreserved embryos presented the same phenotypic traits as non-frozen control plants.

Posibles factores incidentes en el tratamiento de la sensibilidad al ruido / Possible incident factors in the treatment of sensibility to noise

Sobre la base de la teoría de Eysenck, se plantea la hipótesis de que los sujetos distímicos serán accesibles al tratamiento de la sensibilidade al ruido y por medio de técnicas de relajación, en tanto que los sujetos histéricos no lo serán. A un grupo de sujetos voluntarios, sensibles al ruido, se le aplica el tratamiento en cuatro sesiones. La comparación de las curvas individuales de sensibilidad al ruido, pre y pos-tratamiento y el análisis del cruce de variables realizado, evidencia que, contrariamente a la hipóteses planteada, el factor de mayor incidencia en los resultados del tratamiento, es el grado de sensibilidad al ruido que presentan los sujetos experimentales