The effect of the alliance on social recovery outcomes and usage in a moderated online social therapy for first-episode psychosis.

OBJECTIVES: We investigated the effect of the therapeutic alliance on both change in social recovery outcomes and usage of a moderated online social therapy platform for first-episode psychosis (FEP), Horyzons. DESIGN: Secondary analysis of a single group pilot trial. METHODS: Clients completed an alliance measure adapted for guided digital interventions at mid-treatment. A series of multi-level models evaluated change in outcomes by mid- and post-treatment assessments (relative to baseline) as a function of the overall alliance. Quasi-Poisson models evaluated the effect of the overall alliance on aggregated counts of platform usage. Exploratory analyses repeated these models in terms of the bond (human-human) or the task/goal (human-program) alliance. RESULTS: Stronger overall alliance at mid-treatment predicted lower loneliness at mid-treatment and lower social anxiety at mid- and post-treatment. It was also associated with higher completion of therapy activities and authoring of comments and reactions. A strong bond with an online therapist was associated with lower loneliness and higher perceived social support at mid-treatment, lower social anxiety at post-treatment as well as a higher number of reactions made on the social network. Stronger alliance with the platform's tasks and goals facilitated lower social anxiety at both follow-up assessments and was further associated with higher completion of therapy activities and reactions in the social network. CONCLUSIONS: The alliance may impact aspects of social recovery and usage in digital interventions for FEP. Specific aspects of the alliance (human-human and human-program relationships) should be considered in future research.

Comparative Passivation of Si(100) by H2 and D2 Atmospheres under Simultaneous Xe+ Bombardment: An X-ray Photoelectron Spectroscopy Analysis.

This study presents a comparison of H2 and D2 passivation on Si(100) under simultaneous Xe+ ion bombardment. The impact of Xe+ ions causes significant damage to the substrate surface, leading to an increase in H2 (D2) retention as Si-H (Si-D) bonds. The ion bombardment conditions are precisely controlled using a Kaufman ion gun. The atomic concentrations on the surface of the sample were investigated by quasi-in situ X-ray photoelectron spectroscopy. A simple methodology is employed to estimate the H (D) chemical concentration and the cover ratio of the sample, with regard to the oxygen concentration through residual water chemisorption present in the vacuum vessel. Differences in passivation are expected when using H2 or D2 atmospheres because their retained scission energies and physisorption properties differ. The results indicate an increase of the sticking coefficient for D2 and H2 under the ion bombardment. It is also found that the flux of H2 (D2) impinging on the surface contributes to play an important role in the whole process. Finally, a model is proposed to describe the phenomenon of the passivation of Si under Xe+ ion bombardment in the presence of H2 (D2).

The secretome from human-derived mesenchymal stem cells augments the activity of antitumor plant extracts in vitro.

Cancer is understood as a multifactorial disease that involve multiple cell types and phenotypes in the tumor microenvironment (TME). The components of the TME can interact directly or via soluble factors (cytokines, chemokines, growth factors, extracellular vesicles, etc.). Among the cells composing the TME, mesenchymal stem cells (MSCs) appear as a population with debated properties since it has been seen that they can both promote or attenuate tumor progression. For various authors, the main mechanism of interaction of MSCs is through their secretome, the set of molecules secreted into the extracellular milieu, recruiting, and influencing the behavior of other cells in inflammatory environments where they normally reside, such as wounds and tumors. Natural products have been studied as possible cancer treatments, appealing to synergisms between the molecules in their composition; thus, extracts obtained from Petiveria alliacea (Anamu-SC) and Caesalpinia spinosa (P2Et) have been produced and studied previously on different models, showing promising results. The effect of plant extracts on the MSC secretome has been poorly studied, especially in the context of the TME. Here, we studied the effect of Anamu-SC and P2Et extracts in the human adipose-derived MSC (hAMSC)-tumor cell interaction as a TME model. We also investigated the influence of the hAMSC secretome, in combination with these natural products, on tumor cell hallmarks such as viability, clonogenicity, and migration. In addition, hAMSC gene expression and protein synthesis were evaluated for some key factors in tumor progression in the presence of the extracts by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Multiplex, respectively. It was found that the presence of the hAMSC secretome did not affect the cytotoxic or clonogenicity-reducing activities of the natural extracts on cancer cells, and even this secretome can inhibit the migration of these tumor cells, in addition to the fact that the profile of molecules can be modified by natural products. Overall, our findings demonstrate that hAMSC secretome participation in TME interactions can favor the antitumor activities of natural products.

Systematic review of early warning signs of relapse and behavioural antecedents of symptom worsening in people living with schizophrenia spectrum disorders.

BACKGROUND: Identification of the early warning signs (EWS) of relapse is key to relapse prevention in schizophrenia spectrum disorders, however, limitations to their precision have been reported. Substantial methodological innovations have recently been applied to the prediction of psychotic relapse and to individual psychotic symptoms. However, there has been no systematic review that has integrated findings across these two related outcomes and no systematic review of EWS of relapse for a decade. METHOD: We conducted a systematic review of EWS of psychotic relapse and the behavioural antecedents of worsening psychotic symptoms. Traditional EWS and ecological momentary assessment/intervention studies were included. We completed meta-analyses of the pooled sensitivity and specificity of EWS in predicting relapse, and for the prediction of relapse from individual symptoms. RESULTS: Seventy two studies were identified including 6903 participants. Sleep, mood, and suspiciousness, emerged as predictors of worsening symptoms. Pooled sensitivity and specificity of EWS in predicting psychotic relapse was 71% and 64% (AUC value = 0.72). There was a large pooled-effect size for the model predicting relapse from individual symptom which did not reach statistical significance (d = 0.81, 95%CIs = -0.01, 1.63). CONCLUSIONS: Important methodological advancements in the prediction of psychotic relapse in schizophrenia spectrum disorders are evident with improvements in the precision of prediction. Further efforts are required to translate these advances into effective clinical innovations.

The importance of cell uptake in photothermal treatments mediated by biomimetic magnetic nanoparticles.

Biomimetic magnetic nanoparticles (BMNPs) mediated by MamC have proven to be photothermal agents able to allow an optimized cytotoxicity against tumoral cells when used simultaneously as drug nanotransporters and as hyperthermia agents. However, it remains unclear whether BMNPs need to be internalized by the cells and/or if there is a threshold for internal Fe concentration for the photothermal therapy to be effective. In this study, three different situations for photothermal treatments have been simulated to disentangle the effect of BMNPs cell uptake on cell viability after photothermal treatments. Human hepatoblastoma (HepG2) cell line was treated with suspensions of BMNPs, and protocols were developed to have only intracellular BMNPs, only extracellular BMNPs or both, followed by photothermal exposure of the treated cell cultures. Our data demonstrate that: (1) Although the heating efficiency of the photothermal agent is not altered by its location (intra/extracellular), the intracellular location of BMNPs is crucial to ensure the cytotoxic effect of photothermal treatments, especially at low Fe concentration. In fact, the concentration of BMNPs needed to reach the same cytotoxic effect following upon laser irradiation of 0.2 W/cm2 is three times larger if BMNPs are located extracellularly compared to that needed if BMNPs are located intracellularly; (2) For a given location of the BMNPs, cell death increases with BMNPs (or Fe) concentration. When BMNPs are located intracellularly, there is a threshold for Fe concentration (∼ 0.5 mM at laser power intensities of 0.1 W/cm2) needed to affect cell viability following upon cell exposure to photothermia. (3) Bulk temperature rise is not the only factor accounting for cell death. Actually, temperature increases inside the cells cause more damage to cell structures and trigger cell death more efficiently than an increase in the temperature outside the cell.

Environmental and health implications of Pb-bearing particles in settled urban dust from an arid city affected by Pb-Zn factory emissions.

Metal-rich particles originating from non-ferrous metallurgical activities are the primary source of atmospheric metals in urban environments. These particles vary in size, morphology, and elemental compositions and they undergo weathering processes that alter their composition and affect their toxicity. This study focuses on lead (Pb)-rich particles in settled urban dust within an arid and dusty city, Torreón in North Mexico, affected by Met-Mex Peñoles complex, one of the world's largest Ag-Cd-Pb-Zn smelting and refining facilities in operating since 1901. Torreón is characterized by arid conditions, temperature fluctuations, and low humidity. Dry atmospheric particles were collected in 2015 and 2017 from Torreón's urban area within a 3 km radius of the Met-Mex Peñoles complex. We used various analytical techniques, including scanning electron microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS), and X-ray powder diffraction (XRD) to determine the size, morphology, elemental composition and mineralogy of Pb-bearing particles. Our analysis revealed a range of Pb-bearing particle sizes and morphologies with varying Pb (0.3 to 51-87.2%) and other element contents, such as As (0.04 to 1-3.4%), Cd (0.4 to 3.3-5.1%), Cu (0.51-14.1%), Hg (ND-0.6%), and Zn (1.7 to 79-90.3%). XRD analysis confirmed the presence of Pb and Zn sulfides, Pb carbonates, Pb sulfate, and Pb oxides in urban dust, both as individual particles and agglomerates. Primary Pb minerals were linked to fugitive feed concentrates and smelter flue gas at Met-Mex Peñoles, while secondary Pb minerals, like Pb carbonates, Pb sulfate, and Pb oxides, resulted from direct emissions and weathering processes. Compared to galena, secondary Pb minerals exhibit higher chemical availability in the environment, posing greater risks to the environment and human health. As the particles analyzed are presumed to be resuspended rather than freshly emitted by Met-Mex, the presence of secondary Pb minerals in settled urban dust is predominantly linked to weathering processes. The physical and chemical transformations in Pb-rich particles contribute to increased Pb bioavailability and toxicity in urban dust, with substantial implications for environmental and human health. These findings highlight the potential consequences of weathered Pb-rich particle in urban areas, particularly in the arid and dusty city of Torreón.

ctDNA quantification improves estimation of outcomes in patients with high-grade osteosarcoma: a translational study from the OS2006 trial.

BACKGROUND: Osteosarcoma stratification relies on clinical parameters and histological response. We developed a new personalized stratification using less invasive circulating tumor DNA (ctDNA) quantification. PATIENTS AND METHODS: Plasma from patients homogeneously treated in the prospective protocol OS2006, at diagnosis, before surgery and end of treatment, were sequenced using low-passage whole-genome sequencing (lpWGS) for copy number alteration detection. We developed a prediction tool including ctDNA quantification and known clinical parameters to estimate patients' individual risk of event. RESULTS: ctDNA quantification at diagnosis (diagCPA) was evaluated for 183 patients of the protocol OS2006. diagCPA as a continuous variable was a major prognostic factor, independent of other clinical parameters, including metastatic status [diagCPA hazard ratio (HR) = 3.5, P = 0.002 and 3.51, P = 0.012, for progression-free survival (PFS) and overall survival (OS)]. At the time of surgery and until the end of treatment, diagCPA was also a major prognostic factor independent of histological response (diagCPA HR = 9.2, P < 0.001 and 11.6, P < 0.001, for PFS and OS). Therefore, the addition of diagCPA to metastatic status at diagnosis or poor histological response after surgery improved the prognostic stratification of patients with osteosarcoma. We developed the prediction tool PRONOS to generate individual risk estimations, showing great performance ctDNA quantification at the time of surgery and the end of treatment still required improvement to overcome the low sensitivity of lpWGS and to enable the follow-up of disease progression. CONCLUSIONS: The addition of ctDNA quantification to known risk factors improves the estimation of prognosis calculated by our prediction tool PRONOS. To confirm its value, an external validation in the Sarcoma 13 trial is underway.

[Regulación de la expresión de IL-33 e IL-17 por la modulación farmacológica de HIF-1 en un modelo murino de inflamación alérgica pulmonar].

Objective: To evaluate the effect of pharmacological modulation of HIF-1 on the expression of IL-33 and IL-17 in a murine model of allergic pulmonary inflam- mation (API) with different degrees of severity. Methods: 5 mice/group received ovalbumin (OVA) 1(mild), 2(moderate) or 3(severe) challenges via i.t. prior to allergen sensitization, in addition to the HIF-1 induction or inhibition groups, received EDHB (OVA+EDHB) i.p. or 2ME (OVA+2ME) i.t. respectively. Control groups received saline solution (SS) in the same way. HE (inflammatory infiltrate), PAS (mucus production) and immunohistochemical staining for HIF-1a, IL-33, IL-17 were performed, quantitatively analyzing by digital pathology. Results: We obtained different degrees of severity with a greater number of challenges, increasing the expression of HIF-1, correlating with the expression of IL-33/IL-17. Increasing or decreasing, respectively by pharmacological modulation. Conclusions: The above suggests that the high expression of HIF-1 favors the production of IL-33 and IL-17 contributing to the damage in lung tissue and the severity of the disease and these can be regulated through the modulation of HIF- 1.

Objetivo: Evaluar el efecto de la modulación farmacológica de HIF-1 en la expresión de IL-33 e IL-17 en un modelo murino de inflamación alérgica pulmonar (IAP) con diferentes grados de severidad. Métodos: 5 ratones/grupo recibieron ovoalbúmina (OVA) 1(leve), 2(moderada) o 3(severa) retos vía i.t. previa sensibilización como alergeno, además los grupos de inducción o inhibición de HIF-1a, recibieron EDHB (OVA+EDHB) i.p. o 2ME (OVA+2ME) i.t. respectivamente. Los grupos controles recibieron solución salina (SS) de igual forma. Se realizaron tinciones de HE (infiltrado inflamatorio), PAS (producción de moco) e inmunohistoquímicas de HIF-1a, IL-33, IL-17, analizando cuantitativamente por patología digital. Resultados: Obtuvimos diferentes grados de severidad a mayor número de retos, incrementando la expresión de HIF-1, correlacionando con la expresión de IL- 33/IL-17. Aumentando o disminuyendo, respectivamente por la modulación farmacológica. Conclusiones: Lo anterior sugiere que la alta expresión de HIF-1 favorece la producción de IL-33 e IL-17 contribuyendo al daño en el tejido pulmonar y la severi- dad de la enfermedad y estas pueden ser reguladas a través de la modulación de HIF-1.

Effects of endocrine disorders on maxillary and mandibular growth in Colombian children and adolescents: a cross-sectional study.

OBJECTIVE: To establish the influence of overweight/obesity, medicated hypothyroidism, and medicated non-syndromic hypogrowth on maxillary and mandibular growth. MATERIALS AND METHODS: The relation between 10 craniofacial anthropometric measurements and hypothyroidism (n = 216), overweight/obesity (n = 108), and non-syndromic hypogrowth (n = 250) were evaluated in patients aged 1-19 years and a control group of healthy patients (n = 587). A subgroup analysis was performed at the peak growth in all groups. RESULTS: Patients with overweight/obesity and hypothyroidism showed increased craniofacial growth, while hypogrowth patients showed differences in zygomatic width and nasal base growth. Females with hypothyroidism and non-syndromic hypogrowth showed decreased head circumference at peak growth. Several anthropometric measurements were increased in patients with overweight/obesity, including head circumference. When all age groups were analyzed, overweight/obese and hypothyroidism patients showed increased zygomatic width while decreased hypogrowth. Overall, most craniofacial anthropometric measurements in overweight/obese patients were increased. Finally, the peak growth in males with hypothyroidism and subjects with non-syndromic hypogrowth was delayed compared to the control group (p < 0.05). CONCLUSIONS: Children and adolescents with overweight/obesity and endocrine disorders showed alterations in craniofacial growth. Clinicians must be aware that the growth peak in these patients may be delayed when planning maxillary and mandibular orthopedic treatment.

[Translated article] Less superior adjacent syndrome and lower reoperation rate. Medium- and long-term results of cervical arthroplasty versus anterior cervical arthrodesis: Systematic review and meta-analysis of randomized clinical trials.

OBJECTIVE: To compare medium- and long-term postoperative surgical results, especially the adjacent syndrome rate, adverse event rate, and reoperation rate, of patients operated on with cervical arthroplasty or anterior cervical arthrodesis in published randomized clinical trials (RCTs), at one cervical level. METHODS: Systematic review and meta-analysis. Thirteen RCTs were selected. The clinical, radiological and surgical results were analyzed, taking the adjacent syndrome rate and the reoperation rate as the primary objective of the study. RESULTS: Two thousand nine hundred and sixty three patients were analyzed. The cervical arthroplasty group showed a lower rate of superior adjacent syndrome (P<0.001), lower reoperation rate (P<0.001), less radicular pain (P=0.002), and a better score of neck disability index (P=0.02) and SF-36 physical component (P=0.01). No significant differences were found in the lower adjacent syndrome rate, adverse event rate, neck pain scale, or SF-36 mental component. A range of motion of 7.91° was also found at final follow-up, and a heterotopic ossification rate of 9.67% in patients with cervical arthroplasty. CONCLUSION: In the medium and long-term follow-up, cervical arthroplasty showed a lower rate of superior adjacent syndrome and a lower rate of reoperation. No statistically significant differences were found in the rate of inferior adjacent syndrome or in the rate of adverse events.

Development and Evaluation of Zinc and Iron Nanoparticles Functionalized with Plant Growth-Promoting Rhizobacteria (PGPR) and Microalgae for Their Application as Bio-Nanofertilizers.

Micronutrient deficiencies are widespread and growing global concerns. Nanoscale nutrients present higher absorption rates and improved nutrient availability and nutrient use efficiency. Co-application of nanofertilizers (NFs) with biological agents or organic compounds increases NF biocompatibility, stability, and efficacy. This study aimed to develop and evaluate zinc and iron bio-nanofertilizers formulated with plant growth-promoting rhizobacteria (PGPR) and microalgae. Nanoparticles (NPs) were synthesized with the co-precipitation method and functionalized with Pseudomonas species and Spirulina platensis preparation. NPs were characterized and evaluated on seed germination, soil microbial growth, and early plant response under seedbed conditions. NPs corresponded to zinc oxide (ZnO; 77 nm) and maghemite (γ-Fe2O3; 68 nm). Functionalized nanoparticles showed larger sizes, around 145-233 nm. The seedling vigor index of tomato and maize was significantly increased (32.9-46.1%) by bacteria-functionalized ZnO- and γ-Fe2O3-NPs at 75 ppm. NFs at 250 and 75 ppm significantly increased bacterial growth. NFs also improved early plant growth by increasing plant height (14-44%), leaf diameter (22-47%), and fresh weight (46-119%) in broccoli and radish, which were mainly influenced by bacteria capped ZnO- and γ-Fe2O3-NPs at 250 ppm. Beneficial effects on plant growth can be attributed to the synergistic interaction of the biological components and the zinc and iron NPs in the bio-nanofertilizers.

New opto-electro-mechanical sensor for two-dimensions dosimetry based on radiochromic films.

This work presents the validation of a new Opto‒Electro-Mechanical (MOEM) system consisting of a matrix of photodetectors for two-dimensional dosimetry evaluation with radiochromic films. The proposed system is based on a 5 × 10 matrix of photodetectors controlled by both in-house electronic circuit and graphical user interface, which enables optical measurements directly. We present the first tests performed in an X-ray machine and 137Cs source with that array by using Gafchromic EBT3 films. We obtained similar results than with a standard method (e.g. flat-bed scanner). Results were compared with Monte Carlo simulations and very good agreement was found. Results show the feasibility of using this system for dose evaluations. To the best of our knowledge, this is the first MOEM sensor for radiotherapy. Further developments are ongoing to create an advanced 16 × 16 LDRs system covering 1.6 cm × 1.6 cm with a 1 mm of spatial resolution. We point to develop a portable dosimetry tool delivering dose maps in real time to improve the clinical application of radiochromic films.

Assessment of the PARP inhibitor talazoparib photosafety profile.

Talazoparib (TLZ) is a poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor employed for the treatment of breast cancer. This drug displays an absorption band in the UVA region, and therefore investigation of the possible phototoxic side-effects associated to its administration results of enormous relevance. In this context, we describe here a photochemical and photobiological study to ascertain the photosafety profile of TLZ. Concerning transient species, the singlet and triplet excited states of TLZ were detected by fluorescence (λmax em = 440 nm) and laser flash photolysis experiments (λmax abs = 400 nm), respectively. Remarkably, TLZ irradiation with UVA light in aqueous solution resulted in formation of a stable photooxidated product, TLZ-P, whose absorption band is extended until the visible region. From in vitro experiments, phototoxicity was revealed for the parent drug by neutral red uptake (NRU) assays, with a PIF value of ca 7; besides, TLZ induced formation of reactive oxygen species (ROS) and produced significant damage to both proteins and DNA. By contrast, the singlet and triplet excited states of TLZ-P were not detected, and no photodamage was observed in the NRU experiments. Overall, the results indicate that TLZ induces phototoxicity, whereas its photoproduct exhibits photosafety.

Identification of the ATPase alpha subunit of Trypanosoma cruzi as a potential biomarker for the diagnosis of Chagas disease.

BACKGROUND: Chagas disease (CD) is considered by the World Health Organisation (WHO) a neglected disease endemic to the Americas, but it has spread throughout the world due to migrations. The disease is almost 100% curable if detected in time. Still, the lack of rapid diagnostic tests with sufficient sensitivity and specificity leads to a chronic phase with a mortality of about 50,000 people worldwide per year. METHODS: Using the total proteins extracted from serum samples of patients confirmed with chronic phase CD; we performed the Bio-SELEX strategy. The best aptamers were selected using next-generation sequencing (NGS) based on their most abundant sequences (reads and rpm). Then, selected aptamers were used to isolate potential biomarkers directly from serum samples of patients with chronic phase CD using pull-down and mass spectrometry experiments. RESULTS: CH1 aptamer was the aptamer selected after the NGS results analysis. The pull-down and mass spectrometry experiments identified the presence of the ATPase alpha subunit of T. cruzi circulating in serum samples of patients with chronic phase CD. CONCLUSIONS: We report the ATPase alpha subunit of T. cruzi as a potential biomarker for chronic phase CD and CH1 aptamer as a potential tool for diagnosing CD.

Paciente con lesión medular cervical y vértigo posicional paroxístico benigno tratado con maniobras de reposición de partículas / Patient with cervical spinal cord injury and benign paroxysmal positional vertigo treated with particle repositioning maneuvers

El vértigo posicional paroxístico benigno (VPPB) se caracteriza por episodios cortos y bruscos de vértigo cuando la cabeza se mueve en posiciones específicas. El tratamiento son las terapias de reposición de partículas. En general el VPPB es subdiagnosticado, no reportado y por lo tanto no es tratado de forma adecuada. Presentamos el caso de un paciente con lesión medular y VPPB. Paciente de 72 años que sufre una fractura de C5 y como resultado una lesión medular C5 AIS C que necesitó la fijación quirúrgica. En la unidad de lesionados medulares se documentó VPPB del conducto semicircular lateral izquierdo y se trató mediante el uso de terapias de reposición específicas; el paciente mejoró progresivamente y pudo concluir el tratamiento rehabilitador. Las unidades de lesión medular con acceso a unidades de rehabilitación vestibular pueden realizar el diagnóstico y tratamiento específico del VPPB, minimizando los riesgos para el paciente.(AU)

Benign paroxysmal positional vertigo (BPPV) is characterized by short, sudden episodes of vertigo when the head moves in specific positions. The treatment is particle repositioning maneuvers. BPPV usually is underdiagnosed, unreported and therefore not adequately treated. We present the case of a patient with spinal cord injury and BPPV. A 72-year-old patient who suffered a C5 fracture with spinal cord injury C5 AIS C that required surgical fixation. In the spinal cord injury unit BPPV of the left lateral semicircular canal was documented and treated using specific repositioning maneuvers, the patient progressively improved and was able to complete the rehabilitation treatment. The spinal cord injury unit with access to vestibular rehabilitation units can carry out the diagnosis and specific treatment of BPPV, minimizing the risks for the patient.(AU)