Effect of in vitro gastrointestinal digestion on the antibacterial activity of bioactive dairy formulas supplemented with lactoferrin against Cronobacter sakazakii.

Milk is a source of proteins with high nutritional value and relevant biological activities. Bioactive milk proteins, like lactoferrin, are important for newborn development and can also be used as ingredients in functional products to improve health. Lactoferrin is essential in infant's diet, since protects against infections and promotes immune system maturation. Bovine lactoferrin is used to supplement formula milk in order to strengthen baby's defences against some pathogenic bacteria. Thus, lactoferrin supplemented formula can be a barrier against emergent pathogens, such as Cronobacter sakazakii, which has caused great concern in the last few years. Milk proteins generate bioactive peptides in the digestion process, and it is known that industrial processing can modify their susceptibility to digestion. Treatments such as heating have been shown to denature whey proteins and make them more easily digestible. Therefore, the aim of this study was to analyze the effect of technological treatments and gastrointestinal digestion on the antibacterial activity against C. sakazakii of proteins present in dairy formulas supplemented with lactoferrin. Commercial bovine lactoferrin has been shown to have antibacterial activity against C. sakazakii, both in the native state and after static in vitro gastrointestinal digestion. In addition, the digests obtained from dairy formulas subjected to technological treatments, either homogenization or pasteurization, have higher antibacterial activity than non-treated formulas. The release of low molecular weight peptides during the in vitro gastric digestion is probably the cause that would explain the enhanced antibacterial activity of the digested dairy formulas.

Persistence of Anti-S1 IgG against SARS-CoV-2 Eight Months after the Booster Dose of Vaccine in Naive and Previously Infected Healthcare Workers.

Our aim was to evaluate the immune response of healthcare workers included in the RIPOVAC study, after receiving a booster dose (third dose), in terms of intensity and persistence of induced antibodies. In the second phase of the RIPOVAC study, between December 2021 and January 2022, eight months after the second dose, 389 voluntary, immunocompetent, non-pregnant healthcare workers received a booster dose of SARS-CoV-2 vaccine, and a serum sample was obtained. Two groups of patients were established: with and without previous SARS-CoV-2 infection. In order to quantify anti-S1 IgG (AU/mL) we used CMIA (Abbott). All of the health workers were anti-S IgG positive 8 months after receiving the booster dose of the vaccine, with a mean of 17,040 AU/mL. In 53 patients without previous infection, antibody levels increased by a mean of 10,762 AU/mL. This figure is seven times higher than the one produced after the second dose (1506 AU/mL). The booster dose produces a robust elevation of the antibody level, which persists at 8 months, with levels significantly higher than those reached after the second dose, which allow one to predict a persistence of more than one year. The study demonstrates the efficacy of the booster dose of anti-SARS-CoV-2 vaccines.

Assessment of humoral immune response to two mRNA SARS-CoV-2 vaccines (Moderna and Pfizer) in healthcare workers fully vaccinated with and without a history of previous infection.

AIMS: Presence of anti-S1 region of SARS-CoV-2 spike protein was analysed, at two and eight months, in 477 immunocompetent healthcare workers in Zaragoza, Spain, vaccinated with mRNA-1273 (Moderna) or BNT162b2 (Pfizer). METHODS AND RESULTS: Antibody analysis was performed with Alinity i System (Abbott). At 2 months, 100% of vaccinated had anti-S1 IgG (mean = 13,285 AU ml-1 ). This value was significantly higher with Moderna (18,192 AU ml-1 ) than with Pfizer (10,441 AU ml-1 ). The mean value of anti-S1 IgG after vaccination was significantly higher in patients with than without previous infection (18,539 vs. 7919 AU ml-1 ); in both groups was significantly higher with Moderna than with Pfizer (21,881 vs. 15,733 AU ml-1 and 11,949 vs. 6387 AU ml-1 ), respectively. At 8 months, 100% of patients were IgG positive, with higher levels with Moderna than with Pfizer. Nevertheless, in ensemble of cases, a mean decrease of antibody levels of 11,025 AU ml-1 was observed. CONCLUSION: At 2 and 8 months after vaccination, IgG response persists with both vaccines but with important decrease which suggests the need for revaccination. SIGNIFICANCE AND IMPACT OF STUDY: The study contributes to know the immune status after vaccination with two of more used anti-SARS-CoV-2 vaccines. This knowledge is important for establishing the best vaccination strategy.

Psychiatric Aspects of Acute Porphyria: a Comprehensive Review.

PURPOSE OF REVIEW: The aim of this paper is to review psychiatric manifestations, comorbidities, and psychopharmacological management in individuals with acute porphyria (AP). RECENT FINDINGS: Recent literature begins to clarify associations between AP, schizophrenia, bipolar disorder, and other psychopathology. Broad psychiatric symptoms have been associated to acute porphyria (AP) and correspond to a spectrum of heterogeneous manifestations such as anxiety, affective alterations, behavioral changes, personality, and psychotic symptoms. These symptoms may be difficult to identify as being related to porphyria since symptoms may arise at any time during the disease process. In addition, these patients may present psychiatric conditions secondary to the disease, such as adjustment disorder and substance use disorders. Timely diagnosis and appropriate treatment of psychiatric manifestations positively impact the course of the disease.

The Addiction-Related Protein ANKK1 is Differentially Expressed During the Cell Cycle in Neural Precursors.

TaqIA is a polymorphism associated with addictions and dopamine-related traits. It is located in the ankyrin repeat and kinase domain containing 1 gene (ANKK1) nearby the gene for the dopamine D2 receptor (D2R). Since ANKK1 function is unknown, TaqIA-associated traits have been explained only by differences in D2R. Here we report ANKK1 studies in mouse and human brain using quantitative real-time PCR, Western blot, immunohistochemistry, and flow cytometry. ANKK1 mRNA and protein isoforms vary along neurodevelopment in the human and mouse brain. In mouse adult brain ANKK1 is located in astrocytes, nuclei of postmitotic neurons and neural precursors from neurogenic niches. In both embryos and adults, nuclei of neural precursors show significant variation of ANKK1 intensity. We demonstrate a correlation between ANKK1 and the cell cycle. Cell synchronization experiments showed a significant increment of ANKK1-kinase in mitotic cells while ANKK1-kinase overexpression affects G1 and M phase that were found to be modulated by ANKK1 alleles and apomorphine treatment. Furthermore, during embryonic neurogenesis ANKK1 was expressed in slow-dividing neuroblasts and rapidly dividing precursors which are mitotic cells. These results suggest a role of ANKK1 during the cell cycle in neural precursors thus providing biological support to brain structure involvement in the TaqIA-associated phenotypes.

Incidence of and risk factors for femoral fractures in the gap between hip and knee implants.

PURPOSE: The purpose of this study was to analyse the incidence of interprosthetic femoral fractures and describe risk factors for them. METHODS: Between 2009 and 2015, we selected patients who were carrying two implants (hip and knee) in the same femur. We collected demographic and clinical data and performed a radiological evaluation to analyse the gap between implants-the femoral canal area and total femoral area-in the axial plane. We defined interprosthetic fracture as that corresponding to a Vancouver type C fracture and types 1 and 2 according to the Su classification. RESULTS: We studied 68 patients who had total knee arthroplasty (TKA), and 44 patients who had total hip arthroplasty (THA); 24 patients an intramedullary nail. We found six interprosthetic fractures (8.8 %), all in patients with a non-cemented THA. There was a tendency towards statistical difference (p = 0.08). Patients with an additional implant at the proximal femur were statistically less likely to have an interprosthetic fracture (p = 0.04). In radiological results, we found more interprosthetic fractures in patients who had an increased femoral canal area in the axial plane just distal to the tip of the hip implant. CONCLUSIONS: Identifying risk factors for this specific type of fracture may facilitate their prevention. Better implant stability and the presence of a gap between stems in a lower canal zone appear to hinder the occurrence of interprosthetic fractures.

[Incidence and causes of early end in awake surgery for language mapping not directly related to eloquence]. / Incidencia y causas de finalización anticipada de la cirugía con paciente despierto para mapeo del lenguaje, no relacionadas directamente con la elocuencia.

The incidence and causes that may lead to an early end (unfinished cortical/subcortical mapping) of awake surgery for language mapping are little known. A study was conducted on 41 patients with brain glioma located in the language area that had awake surgery under conscious sedation. Surgery was ended early in 6 patients. The causes were: tonic-clonic seizure (1), lack of cooperation due to fatigue/sleep (4), whether or not word articulation was involved, a decreased level of consciousness for ammonia encephalopathy that required endotracheal intubation (1). There are causes that could be expected and in some cases avoided. Tumour size, preoperative aphasia, valproate treatment, and type of anaesthesia used are variables to consider to avoid failure in awake surgery for language mapping. With these results, the following measures are proposed: l) If the tumour is large, perform surgery in two times to avoid fatigue, 2) if patient has a preoperative aphasia, do not use sedation during surgery to ensure that sleepiness does not cause worse word articulation, 3) if the patient is on valproate treatment, it is necessary to rule out the pre-operative symptoms that are not due to ammonia encephalopathy.

ßArrestin1 regulates the guanine nucleotide exchange factor RasGRF2 expression and the small GTPase Rac-mediated formation of membrane protrusion and cell motility.

ßArrestin proteins shuttle between the cytosol and nucleus and have been shown to regulate G protein-coupled receptor signaling, actin remodeling, and gene expression. Here, we tested the hypothesis that ßarrestin1 regulates actin remodeling and cell migration through the small GTPase Rac. Depletion of ßarrestin1 promotes Rac activation, leading to the formation of multipolar protrusions and increased cell circularity, and overexpression of a dominant negative form of Rac reverses these morphological changes. Small interfering RNA library screen identifies RasGRF2 as a target of ßarrestin1. RasGRF2 gene and protein expression levels are elevated following depletion of ßarrestin1, and the consequent activation of Rac results in dephosphorylation of cofilin that can promote actin polymerization and formation of multipolar protrusions, thereby retarding cell migration and invasion. Together, these results suggest that ßarrestin1 regulates rasgrf2 gene expression and Rac activation to affect membrane protrusion and cell migration and invasion.

Drug interactions with sunitinib.

PURPOSE: Sunitinib is a tyrosine kinase inhibitor indicated for the treatment of gastrointestinal stromal tumor, advanced renal cell carcinoma, and pancreatic neuroendocrine tumors. The aim of this article is to describe the pharmacological interactions between sunitinib and commonly prescribed drugs. METHOD: We reviewed available information on pharmacological interactions between sunitinib and concomitantly prescribed drugs. Drugs were grouped into different therapeutic groups according to the Anatomical Therapeutic Chemical (ATC) classification. RESULTS: Sunitinib interacts with CYP3A4 inducers or inhibitors and with P-glycoprotein and ABCG2 substrates. Pharmacodynamic interactions with drugs have also been found. CONCLUSION: Current information on drug interactions between sunitinib and other drugs is scarce and most of the times it is difficult to apply to clinical practice. Even so, this difficulty in managing drug interactions should not be a reason to ignore them as they can help to explain intolerances and treatment failures.

Analysis of the Functioning of Families of Children with Autism Spectrum Disorder: A Psychometric Study of the Family APGAR Scale.

Normalised family functioning is a predictor of individual well-being. The diagnosis of a family member with autism spectrum disorder (ASD) can alter the ordinary dynamics of family systems, having a variable impact on family functioning. This research employed a non-probability convenience sampling method to gather a sample of 327 families with and without children diagnosed with ASD. This study has dual objectives: to analyse the psychometric properties of the Spanish version of the Family APGAR Scale and to compare family functioning in families with and without a child with ASD. The results reveal several favourable psychometric properties in the application of the APGAR scale within families of children with ASD. The use of the Family APGAR Scale in the selected sample confirms that the functioning of families with children with ASD can be categorized as mildly dysfunctional, attributed to the inherent challenges in caring for and raising a child with ASD. The presence of ASD within family systems presents a challenge to typical family functioning, with significant differences observed between families with and without children with ASD. This underscores the necessity of implementing effective intervention programs based on empirical evidence to improve the quality of life for individuals with ASD and their families.

Safety and Performance of a New Burr Hole Covering Device: Results of the Multicenter COVER Registry.

BACKGROUND: Burr hole covering in brain surgical procedures can avoid complications and unaesthetic results. The aim of this registry was to assess the safety and performance of a new polymeric burr hole covering device (Cranial COVER, NEOS Surgery). METHODS: A multicenter, prospective, clinical registry design was used for the study. All the patients who fulfilled the inclusion criteria were included in the study and followed up for 6 months. Baseline clinical parameters, surgical variables (technical success of the implantation, surgeon satisfaction), postoperative variables (aesthetic and functional results, neuroimaging artifacts), and adverse events were evaluated. RESULTS: Forty-three Cranial COVER devices were implanted in 30 patients. Most of them were implanted in frontal locations (53.5%). After implantation, 97.7% of the devices completely covered the burr hole, and 100% perfectly adapted to the skull surface. All surgeons ranked their satisfaction with the implantation procedure as very high or high. No artifacts were detected in any of the neuroimaging studies performed and no adverse events related with the device or its implantation were reported during the follow-up. There were significantly more scalp depressions associated with uncovered than with Cranial COVER-covered burr holes (p = 0.040). Patient satisfaction with covered burr holes located in the frontal and parietal areas was 9.0 ± 1.4 over 10. CONCLUSION: Cranial COVER is a safe and reliable burr hole covering system that offers excellent cosmetic results and high satisfaction rates for both surgeons and patients. Cranial COVER is highly adaptable to the skull surface, and it was predominantly used in frontal locations due to their cosmetic importance.

Empathy among health science undergraduates toward the diagnosis of chronic pain: An experimental study.

OBJECTIVES: To analyse the empathetic response of future health professionals toward people diagnosed with chronic pain differentiated by the degree of visibility and credibility of symptoms. METHODS: A total of 203 undergraduates performed an experimental task using vignettes depicting different diagnoses of chronic pain and completed questionnaires measuring dispositional and situational empathy. A MANCOVA analysis was conducted. RESULTS: The main effects of chronic pain diagnoses did not significantly affect situational empathy (p = .587, η2 = 0.007, d = 0.229). The dispositional empathy variables perspective-taking and personal distress affected the situational empathy scores (p = .002, η2 = 0.072, d = 0.906, and p = .043, η2 = 0.032, d = 0.547, respectively). CONCLUSIONS: It would seem appropriate to foster intra-individual empathy factors among health science undergraduates such that they can more readily understand the process of individual adaptation to chronic pain and thus manage it more effectively. PRACTICE IMPLICATIONS: It would be useful for dispositional empathy to form part of the transversal competences of the training programmes of future health professionals from the beginning of their studies.

The thyroid hormone receptors as modulators of skin proliferation and inflammation.

We have analyzed the role of the thyroid hormone receptors (TRs) in epidermal homeostasis. Reduced keratinocyte proliferation is found in interfollicular epidermis of mice lacking the thyroid hormone binding isoforms TRα1 and TRß (KO mice). Similar results were obtained in hypothyroid animals, showing the important role of the liganded TRs in epidermal proliferation. In addition, KO and hypothyroid animals display decreased hyperplasia in response to 12-O-tetradecanolyphorbol-13-acetate. Both receptor isoforms play overlapping functional roles in the skin because mice lacking individually TRα1 or TRß also present a proliferative defect but not as marked as that found in double KO mice. Defective proliferation in KO mice is associated with reduction of cyclin D1 expression and up-regulation of the cyclin-dependent kinase inhibitors p19 and p27. Paradoxically, ERK and AKT activity and expression of downstream targets, such as AP-1 components, are increased in KO mice. Increased p65/NF-κB and STAT3 phosphorylation and, as a consequence, augmented expression of chemokines and proinflammatory cytokines is also found in these animals. These results show that thyroid hormones and their receptors are important mediators of skin proliferation and demonstrate that TRs act as endogenous inhibitors of skin inflammation, most likely due to interference with AP-1, NF-κB, and STAT3 activation.

Acidobacteria in freshwater ponds at Doñana National Park, Spain.

The Acidobacteria show a widespread distribution in natural ecosystems. In this study, we analyzed the presence of Acidobacteria in freshwater ponds at Doñana National Park (southwestern Spain). Nucleic acid sequence analysis, quantitative, real-time RT-PCR, and fluorescence in situ hybridization (FISH) were carried out. Acidobacteria in these aquatic environments were investigated using their 16S and 23S rDNA sequences and acidobacterial specific primer pairs through phylogenetic approaches. The presence of up to five subdivisions of Acidobacteria was detected during this study. The analyzed ponds exhibited distinctive patterns of acidobacterial clades. In order to detect their role in ecosystem functions, metabolically active Acidobacteria were detected based upon rRNA analyses. Quantitative, real-time RT-PCR showed a low percentage of metabolically active Acidobacteria at suboxic zones within the water column covered by surface Fe-rich films. Oxygen-saturated areas showed around 4% of total bacterial RNA belonging to Acidobacteria both in the water column and the sediment surface. The morphology of the most abundant Acidobacteria was revealed by FISH as cocci generally in pairs or chains. Enrichment cultures were also obtained and indicated a putative metabolism based on aerobic and heterotrophic characteristics likely taking advantage of the abundant organic matter present at the investigated sites. These results represent a significant contribution toward understanding the distribution and ecological role of the phylum Acidobacteria in natural ecosystems, specifically at Doñana National Park freshwater ponds.

Cerclage wire fixation of trochanteric osteotomies in complex hip revision: our experience and comparison with cable-plate fixation.

INTRODUCTION: Osteotomy of the greater trochanter is a commonly used procedure in complex revision hip arthroplasty in order to achieve a wide exposure to the femoral stem and acetabular components. There is no clinical evidence in favour of a specific fixation method. The aim of this study was to compare cable-plate with figure-of-eight cerclage wire fixation in patients requiring a trochanteric "slide" osteotomy. MATERIAL AND METHODS: In a retrospective study, 51 greater trochanteric "slide" osteotomies in complex acetabular revision arthroplasties were included. Patients were divided into 2 groups: 28 hips were fixed with 1 of 2 cable-plate systems (Dall-Miles staple, Stryker or Cable-Ready plate, Zimmer) and 23 with a figure-of-eight cerclage wire.Consolidation, osteolysis, migration of greater trochanter, bursitis of the trochanteric area, Trendelenburg gait and removal of osteosynthesis material were studied at 6 months follow-up. RESULTS: Both groups showed good union rates. The lysis rate was similar with 32% in the cable-plate group versus 29% in the cerclage wire group (p = 0.084). 43% of the hips with cable-plate and 22% of the cerclage wire had trochanteric migration (p = 0.297). Pain at the greater trochanter was less frequent in the cerclage wire group (9%) as compared to the cable-plate group (43%) (p = 0.007). Implant removal was more frequent in the cable-plate group (4 vs. 0 patients). Trendelenburg gait was found in 3 patients in the cerclage wire group as compared to 10 in the cable-plate group (p = 0.054). CONCLUSIONS: The cerclage wiring had superior clinical outcomes with similar radiographic results. The authors recommend the use of figure-of-eight cerclage wire when fixing a greater trochanteric "slide" osteotomy in complex revision hip arthroplasty.

Spatio-temporal nested patterns in macroinvertebrate assemblages across a pond network with a wide hydroperiod range.

Nestedness has been widely used to measure the structure of biological communities and occurs when species-poor sites contain subsets of species-rich ones. Here, we examine nested patterns across the macroinvertebrate assemblages of 91 ponds in Doñana National Park, Spain, and explore temporal variation of nestedness and species richness in 19 temporary ponds over 2 years with differing rainfall. Macroinvertebrate assemblages were significantly nested; both pond spatial arrangement and environmental variation being important in driving nested patterns. Despite the nested structure observed, a number of taxa and ponds deviate from this pattern (termed idiosyncratic), by occurring more frequently than expected in species-poor sites, or having assemblages dominated by species largely absent from species-rich sites. Aquatic adults of winged insects, capable of dispersal, were more highly nested than non-dispersing taxa and life-history stages. Idiosyncratic taxa were found in ponds spanning a wide range of hydroperiods, although nestedness was higher in more permanent waterbodies. Monthly sampling demonstrated a gradual increase of species richness and nestedness from pond filling to April-May, when the most temporary ponds started to dry. Although the degree of nestedness of individual pond assemblages varied from month to month, the overall degree of nestedness in the two study years was practically identical despite marked differences in hydroperiod. Our results suggest that differential colonization and environmental variation are key processes driving the nested structure of Doñana ponds, that macroinvertebrate assemblages change in a predictable manner each year in response to cycles of pond wetting and drying, and that connectivity and environmental variability maintain biodiversity in pond networks.

Reproducibility of shear wave velocity measurements by acoustic radiation force impulse imaging of the liver: a study in healthy volunteers.

OBJECTIVES: The purposes of this study were to investigate interobserver reproducibility using acoustic radiation force impulse imaging and to develop an acoustic radiation force impulse scoring system. METHODS: Fifty healthy volunteers with normal liver function test values were selected for the study. Shear wave velocity measurements, expressed in meters per second, were taken in a deep portion of liver segment 6. Two observers with different levels of experience performed the measurements independently and blindly. RESULTS: All of the measurements taken by the 2 observers were valid, even in volunteers with a body mass index of greater than 28 kg/m(2). The results point to very good interobserver reproducibility of shear wave velocity measurements, with an intraclass coefficient correlation of 0.86 (P < .001). CONCLUSIONS: The results of this study show that shear wave velocity measurements using the acoustic radiation force impulse technique and a standardized protocol are accurate and reproducible.

On the Use of Digital Subtraction Angiography in Stereoelectroencephalography Surgical Planning to Prevent Collisions with Vessels.

OBJECTIVE: Stereoelectroencephalography (SEEG) consists of the implantation of microelectrodes for the electrophysiological characterization of epileptogenic networks. To reduce a possible risk of intracranial bleeding by vessel rupture during the electrode implantation, the stereotactic trajectories must follow avascular corridors. The use of digital subtraction angiography (DSA) for vascular visualization during planning is controversial due to the additional risk related to this procedure. Here we evaluate the utility of this technique for planning when the neurosurgeon has it available together with gadolinium-enhanced T1-weighted magnetic resonance sequence (T1-Gd) and computed tomography angiography (CTA). METHODS: Twenty-two implantation plans for SEEG were initially done using T1-Gd imaging (251 trajectories). DSA was only used later during the revision process. In 6 patients CTA was available at this point as well. We quantified the position of the closest vessel to the trajectory in each of the imaging modalities. RESULTS: Two thirds of the trajectories that appeared vessel free in the T1-Gd or CTA presented vessels in their proximity, as shown by DSA. Those modifications only required small shifts of both the entry and target point, so the diagnostic aims were preserved. CONCLUSIONS: T1-Gd and CTA, despite being the most commonly used techniques for SEEG planning, frequently fail to reveal vessels that are dangerously close to the trajectories. Higher-resolution vascular imaging techniques, such as DSA, can provide the neurosurgeon with crucial information about vascular anatomy, resulting in safer plans.