Attachment Disorganization: The Reunion of Attachment Theory and Psychoanalysis.

The author investigates the psychoanalytic implications of recent attachment research on the disorganized attachment category in infants and the unresolved for trauma and loss adult attachment classification with which it has been associated. The author first reviews empirical findings on attachment disorganization and then explores the ways in which they are consistent with and illuminated by psychoanalytic concepts. The focus is on linkages between disorganized attachment and Freud's theory of strain trauma and traumatic anxiety, Klein's theory of projective identification and the interplay between paranoidschizoid and depressive anxieties in development, and Blatt's theory of psychological development as resulting from the interplay of anaclitic and introjective developmental lines. In so doing, this article contributes to the reunion between attachment theory and psychoanalysis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Octave Illusion Revisited Again.

The octave illusion (D. Deutsch, 1974) occurs when 2 tones separated by an octave are alternated repeatedly, such that when the right ear receives the high tone, the left ear receives the low tone, and vice versa. Most subjects in the original study reported hearing a single tone that alternated from ear to ear, whose pitch also alternated from octave to octave, and D. Deutsch (1975a) proposed an explanation in terms of separate what and where auditory pathways. C. D. Chambers, J. B. Mattingley, and S. A. Moss (2002) argued that the perceived pitch difference generally corresponds more to a semitone and proposed an alternative explanation in terms of diplacusis. This article argues that Chambers et al. used problematic procedures and reports a new experiment on the octave illusion. The findings confirm that an octave difference is generally perceived, and they agree with the model of Deutsch (1975a) but are at variance with the diplacusis hypothesis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

New Perspectives on the Sustainable Employment of Chestnut Shells as Active Ingredient against Oral Mucositis: A First Screening

Oral mucositis (OM), a common side effect of oncological treatment, is an oral mucosal disorder characterized by painful ulcerations and increased risk of infection. The use of natural antioxidants to suppress the redox imbalance responsible for the OM condition has emerged as an interesting approach to prevent/treat OM. This study aims to explore the chestnut (Castana sativa) shells as potential active ingredient against OM. Therefore, chestnut shells were extracted at different temperatures (110–180 °C) by Subcritical Water Extraction (SWE), aiming to recover antioxidants. The extracts were also evaluated against microorganisms present in the oral cavity as well as on human oral cell lines (TR146 and HSC3). The highest phenolic content was obtained with the extraction temperature of 110 °C, exhibiting the best antioxidant/antiradical activities and scavenging efficiencies against HOCl (IC₅₀ = 4.47 μg/mL) and ROO^• (0.73 μmol TE/mg DW). High concentrations of phenolic acids (e.g., gallic and protocatechuic acids) and flavanoids (catechin, epicatechin and rutin) characterized the phenolic profile. The antimicrobial activity against several oral microorganisms present in the oral cavity during OM, such as Streptococcus, Staphylococcus, Enterococcus, and Escherichia, was demonstrated. Finally, the effects on HSC3 and TR146 cell lines revealed that the extract prepared at 110 °C had the lowest IC₅₀ (1325.03 and 468.15 µg/mL, respectively). This study highlights the potential effects of chestnut shells on OM.     

Patient-Derived Multiple Myeloma 3D Models for Personalized Medicine—Are We There Yet?

Despite the wide variety of existing therapies, multiple myeloma (MM) remains a disease with dismal prognosis. Choosing the right treatment for each patient remains one of the major challenges. A new approach being explored is the use of ex vivo models for personalized medicine. Two-dimensional culture or animal models often fail to predict clinical outcomes. Three-dimensional ex vivo models using patients’ bone marrow (BM) cells may better reproduce the complexity and heterogeneity of the BM microenvironment. Here, we review the strengths and limitations of currently existing patient-derived ex vivo three-dimensional MM models. We analyze their biochemical and biophysical properties, molecular and cellular characteristics, as well as their potential for drug testing and identification of disease biomarkers. Furthermore, we discuss the remaining challenges and give some insight on how to achieve a more biomimetic and accurate MM BM model. Overall, there is still a need for standardized culture methods and refined readout techniques. Including both myeloma and other cells of the BM microenvironment in a simple and reproducible three-dimensional scaffold is the key to faithfully mapping and examining the relationship between these players in MM. This will allow a patient-personalized profile, providing a powerful tool for clinical and research applications.     

Roles of Calcium Signaling in Gene Expression and Photosynthetic Acclimatization of Solanum lycopersicum Micro-Tom (MT) after Mechanical Damage

A momentary increase in cytoplasmic Ca²⁺ generates an oscillation responsible for the activation of proteins, such as calmodulin and kinases, which interact with reactive oxygen species (ROS) for the transmission of a stress signal. This study investigated the influence of variations in calcium concentrations on plant defense signaling and photosynthetic acclimatization after mechanical damage. Solanum lycopersicum Micro-Tom was grown with 0, 2 and 4 mM Ca²⁺, with and without mechanical damage. The expression of stress genes was evaluated, along with levels of antioxidant enzymes, hydrogen peroxide, lipid peroxidation, histochemistry, photosynthesis and dry mass of organs. The ROS production generated by mechanical damage was further enhanced by calcium-free conditions due to the inactivation of the oxygen evolution complex, contributing to an increase in reactive species. The results indicated that ROS affected mechanical damage signaling because calcium-free plants exhibited high levels of H₂O₂ and enhanced expression of kinase and RBOH1 genes, necessary conditions for an efficient response to stress. We conclude that the plants without calcium supply recognized mechanical damage but did not survive. The highest expression of the RBOH1 gene and the accumulation of H₂O₂ in these plants signaled cell death. Plants grown in the presence of calcium showed higher expression of SlCaM2 and control of H₂O₂ concentration, thus overcoming the stress caused by mechanical damage, with photosynthetic acclimatization and without damage to dry mass production.     

Therapeutic Efficacy and Outcomes of Remdesivir versus Remdesivir with Tocilizumab in Severe SARS-CoV-2 Infection

The infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) generated many challenges to find an effective drug combination for hospitalized patients with severe forms of coronavirus disease 2019 (COVID-19) pneumonia. We conducted a retrospective cohort study, including 182 patients with severe COVID-19 pneumonia hospitalized between March and October 2021 in a Pneumology Hospital from Cluj-Napoca, Romania. Among patients treated with standard of care, 100 patients received remdesivir (R group) and 82 patients received the combination of remdesivir plus tocilizumab (RT group). We compared the clinical outcomes, the inflammatory markers, superinfections, oxygen requirement, intensive care unit (ICU) admission and mortality rate before drug administration and 7 days after in R group and RT group. Borg score and oxygen support showed an improvement in the R group (p < 0.005). Neutrophiles, C-reactive protein (CRP) and serum ferritin levels decreased significantly in RT group but with a higher rate of superinfection in this group. ICU admission and death did not differ significantly between groups. The combination of remdesivir plus tocilizumab led to a significantly improvement in the inflammatory markers and a decrease in the oxygen requirement. Although the superinfection rate was higher in RT group than in R group, no significant difference was found in the ICU admission and mortality rate between the groups.     

Prediction of Drug Synergism between Peptides and Antineoplastic Drugs Paclitaxel, 5-Fluorouracil,and Doxorubicin Using In Silico Approaches

Chemotherapy is the main treatment for most early-stage cancers; nevertheless, its efficacy is usually limited by drug resistance, toxicity, and tumor heterogeneity. Cell-penetrating peptides (CPPs) are small peptide sequences that can be used to increase the delivery rate of chemotherapeutic drugs to the tumor site, therefore contributing to overcoming these problems and enhancing the efficacy of chemotherapy. The drug combination is another promising strategy to overcome the aforementioned problems since the combined drugs can synergize through interconnected biological processes and target different pathways simultaneously. Here, we hypothesized that different peptides (P1–P4) could be used to enhance the delivery of chemotherapeutic agents into three different cancer cells (HT-29, MCF-7, and PC-3). In silico studies were performed to simulate the pharmacokinetic (PK) parameters of each peptide and antineoplastic agent to help predict synergistic interactions in vitro. These simulations predicted peptides P2–P4 to have higher bioavailability and lower T_max, as well as the chemotherapeutic agent 5-fluorouracil (5-FU) to have enhanced permeability properties over other antineoplastic agents, with P3 having prominent accumulation in the colon. In vitro studies were then performed to evaluate the combination of each peptide with the chemotherapeutic agents as well as to assess the nature of drug interactions through the quantification of the Combination Index (CI). Our findings in MCF-7 and PC-3 cancer cells demonstrated that the combination of these peptides with paclitaxel (PTX) and doxorubicin (DOXO), respectively, is not advantageous over a single treatment with the chemotherapeutic agent. In the case of HT-29 colorectal cancer cells, the combination of P2–P4 with 5-FU resulted in synergistic cytotoxic effects, as predicted by the in silico simulations. Taken together, these findings demonstrate that these CPP6-conjugates can be used as adjuvant agents to increase the delivery of 5-FU into HT-29 colorectal cancer cells. Moreover, these results support the use of in silico approaches for the prediction of the interaction between drugs in combination therapy for cancer.