Therapeutic Impasse Research Articles

Phenotypic and molecular characterization of vancomycin resistant Enterococci from wild birds: First detection of a plasmid-borne vanC1 in Enterococcus faecalis.

Vancomycin-resistant enterococci (VRE) are a public health concern as they lead to therapeutic impasses and play a pivotal role in the dissemination of vancomycin resistance genes. As recent evidence suggests that wildlife can play a role in the dissemination of bacterial resistomes, this study explored the potential role of Algerian wild birds as a reservoir of VRE. A total of 222 cloacal and fecal samples were collected from various wild bird species and screened for VRE using a selective medium. Of the 47 isolated strains, 22 were identified as Enterococcus casseliflavus with the vanC2/C3 gene, 24 as Enterococcus gallinarum (19 carrying vanC1 and five carrying vanC2/C3), and one strain as Enterococcus faecalis with the vanC1 gene. Twenty-four (24) strains were multidrug-resistant with 61.7% resistant to rifampicin while no resistance to teicoplanin, linezolid and gentamicin was found. Additionally, 53.20% of the strains exhibited at least one virulence factor. To our knowledge, this study represents the first documentation of the vanC1 gene in E. faecalis isolated from wild birds. Furthermore, this gene was found to be carried by a conjugative plasmid, highlighting its ability to spread among bacterial populations and lead to the emergence of novel resistance phenotypes.

Epidemiology of Infections Caused by ESBL-Producing Enterobacteriaceae and Antibiotic Resistance Profile of Strains Isolated at Meknes-Based Moulay Ismail Military Hospital: A Retrospective Study from January 2018 to December 2020

Introduction: Infections caused by ESBL-producing Enterobacteriaceae (ESBL-PE) pose a major public health challenge. In addition to their widespread presence and growing resistance to several categories of antibiotics, the medical management of these bacteria becomes intricate, potentially resulting in a therapeutic impasse. Our study's goal is to examine the regional epidemiological characteristics of ESBL-PE infections and present a current assessment of their antibiotic resistance. Methods: The retrospective investigation undertaken at the bacteriology laboratory of the Meknes-based Moulay Ismail Military Hospital, covering a period of three years (January 2018 to March 2021), specifically examines the isolates of ESBL-PE. Results: Among the 2596 strains of Enterobacteriaceae described, 16.4% were found to produce ESBL, with E. coli being accountable for 63.6% of these strains. 85.1% of these ESBL-PE were isolated from urine samples. Surgical services were the largest source of these ESBL-PE (54.3%), followed by the emergency department (22%), medical services (14.5%), and intensive care unit (9.2%). The antibiotic resistance of these ESBL-PE has been studied and found to be high for gentamicin (63%), tobramycin (66%), cotrimoxazole (85%), and ciprofloxacin (91%). Only 7% exhibited good sensitivity to amikacin, 4% to imipenem, and 5% to fosfomycin. Conclusion: The advent of ESBL-PE in our institution is a big challenge. To limit the use of carbapenems and prevent the spread of strains causing carbapenemases, other kinds of antibiotics can be utilized. The partnership between clinicians and the bacteriology laboratory is vital for efficiently preventing and monitoring the spread of these multidrug-resistant bacteria.

Can you be a peer if you don’t share the same health or social conditions? A qualitative study on peer integration in a primary care setting

BackgroundPeer support has been extensively studied in specific areas of community-based primary care such as mental health, substance use, HIV, homelessness, and Indigenous health. These programs are often built on the assumption that peers must share similar social identities or lived experiences of disease to be effective. However, it remains unclear how peers can be integrated in general primary care setting that serves people with a diversity of health conditions and social backgrounds.MethodsA participatory qualitative study was conducted between 2020 and 2022 to explore the feasibility, acceptability, and perceived effects of the integration of a peer support worker in a primary care setting in Montreal, Canada. A thematic analysis was performed based on semi-structured interviews (n = 18) with patients, relatives, clinicians, and a peer support worker.FindingsFindings show that peers connect with patients through sharing their own hardships and how they overcame them, rather than sharing similar health or social conditions. Peers provide social support and coaching beyond the care trajectory and link identified needs with available resources in the community, bridging the gap between health and social care. Primary care clinicians benefit from peer support work, as it helps overcome therapeutic impasses and facilitates communication of patient needs. However, integrating a peer into a primary care team can be challenging due to clinicians’ understanding of the nature and limits of peer support work, financial compensation, and the absence of a formal status within healthcare system.ConclusionOur results show that to establish a relationship of trust, a peer does not need to share similar health or social conditions. Instead, they leverage their experiential knowledge, strengths, and abilities to create meaningful relationships and reliable connections that bridge the gap between health and social care. This, in turn, instills patients with hope for a better life, empowers them to take an active role in their own care, and helps them achieve life goals beyond healthcare. Finally, integrating peers in primary care contributes in overcoming obstacles to prevention and care, reduce distrust of institutions, prioritize needs, and help patients navigate the complexities of healthcare services.

Prevalence and Antibiotic Resistance Profile of Extended-Spectrum Beta-Lactamase-Producing Uropathogenic Enterobacteriaceae Isolated at the Bacteriology-Virology Laboratory of Chnu De Fann, Dakar

Introduction: Urinary tract infections caused by Enterobacteriaceae producing extended- spectrum β-lactamases represent a growing infectious risk, and in many cases may even lead to therapeutic impasses due to their multi-resistance to antibiotics. The aim of this study was to determine the antibiotic susceptibility profile of extended-spectrum betalactamase-secreting uropathogenic enterobacteriaceae isolated at the CHNU de Fann, Dakar .Material and Methods: This was a retrospective study lasting six months (from January 1 to June 30, 2018) concerning all uropathogenic E-BLSE strains isolated at the Bacteriology-Virology laboratory of the CHNU de Fann (Dakar). Results: This study revealed a high prevalence of E-BLSE isolation (41.8%), particularly in outpatients (65.67%). The most represented age group was between 60 and 80 years, with a percentage of 48.11%. E. coli was the most isolated germ (51.49%), followed by Klebsiella pneumoniae (26.87%). A study of the susceptibility profile of EBLSE to other antibiotic molecules revealed high levels of resistance, reaching 100% for sulfamethoxazole trimethoprim and fosfomycin, and 91.3% for fluoroquinolones. For aminoglycosides, high co-resistance was observed with gentamicin (85.7%), while it was low with amikacin (3.84%). Our results also showed 100% sensitivity to imipenem. Conclusion: The emergence of extended-spectrum ß-lactamase-producing urinary tract infections is a major public health problem. Faced with this alarming and worrying situation, and in order to limit the emergence of healthcare-associated infections, it has become imperative to improve hospital hygiene.

Targeted Photodynamic Therapy using a Vectorized Photosensitizer coupled to Folic Acid Analog induces Ovarian Tumor Cell Death and inhibits IL-6-mediated Inflammation

Ovarian cancer (OC) is one of the most lethal cancers among women. Frequent recurrence in the peritoneum due to the presence of microscopic tumor residues justifies the development of new therapies. Indeed, our main objective is to develop a targeted photodynamic therapy (PDT) treatment of peritoneal carcinomatosis from OC to improve the life expectancy of cancer patients. Herein, we propose a targeted-PDT using a vectorized photosensitizer (PS) coupled with a newly folic acid analog (FAA), named PSFAA, in order to target folate receptor alpha (FRα) overexpressed on peritoneal metastasis.This PSFAA was the result of the coupling of pyropheophorbide-a (Pyro-a), as the PS, to a newly synthesized FAA via a polyethylene glycol (PEG) spacer. The selectivity and the PDT efficacy of PSFAA was evaluated on two human OC cell lines overexpressing FRα compared to fibrosarcoma cells underexpressing FRα.Final PSFAA, including the synthesis of a newly FAA and its conjugation to Pyro-a, was obtained after 10 synthesis steps, with an overall yield of 19%. Photophysical properties of PSFAA in EtOH were performed and showed similarity with those of free Pyro-a, such as the fluorescence and singlet oxygen quantum yields (Φf = 0.39 and ΦΔ = 0.53 for free Pyro-a, and Φf = 0.26 and ΦΔ = 0.41 for PSFAA). Any toxicity of PSFAA was noticed. After light illumination, a dose-dependent effect on PS concentration and light dose was shown. Furthermore, a PDT efficacy of PSFAA on OC cell secretome was detected inducing a decrease of a pro-inflammatory cytokine secretion (IL-6).This new PSFAA has shown promising biological properties highlighting the selectivity of the therapy opening new perspectives in the treatment of a cancer in a therapeutic impasse.

Genetic variations of penicillin-binding protein 1A: insights into the current status of amoxicillin-based regimens for Helicobacter pylori eradication in Malaysia.

Introduction. Resistance towards amoxicillin in Helicobacter pylori causes significant therapeutic impasse in healthcare settings worldwide. In Malaysia, the standard H. pylori treatment regimen includes a 14-day course of high-dose proton-pump inhibitor (rabeprazole, 20 mg) with amoxicillin (1000 mg) dual therapy.Hypothesis/Gap Statement. The high eradication rate with amoxicillin-based treatment could be attributed to the primary resistance rates of amoxicillin being relatively low at 0%, however, a low rate of secondary resistance has been documented in Malaysia recently.Aim. This study aims to investigate the amino acid mutations and related genetic variants in PBP1A of H. pylori, correlating with amoxicillin resistance in the Malaysian population.Methodology. The full-length pbp1A gene was amplified via PCR from 50 genomic DNA extracted from gastric biopsy samples of H. pylori-positive treatment-naïve Malaysian patients. The sequences were then compared with reference H. pylori strain ATCC 26695 for mutation and variant detection. A phylogenetic analysis of 50 sequences along with 43 additional sequences from the NCBI database was performed. These additional sequences included both amoxicillin-resistant strains (n=20) and amoxicillin-sensitive strains (n=23).Results. There was a total of 21 variants of amino acids, with three of them located in or near the PBP-motif (SKN402-404). The percentages of these three variants are as follows: K403X, 2%; S405I, 2% and E406K, 16%. Based on the genetic markers identified, the resistance rate for amoxicillin in our sample remained at 0%. The phylogenetic examination suggested that H. pylori might exhibit unique conserved pbp1A sequences within the Malaysian context.Conclusions. Overall, the molecular analysis of PBP1A supported the therapeutic superiority of amoxicillin-based regimens. Therefore, it is crucial to continue monitoring the amoxicillin resistance background of H. pylori with a larger sample size to ensure the sustained effectiveness of amoxicillin-based treatments in Malaysia.

Antibioprophylaxie chirurgicale et medicale courte de l’enfant

Antibiotic prophylaxis aims to counteract bacterial proliferation in order to reduce the risk of infection in a patient. The emergence of multi-resistant bacteria, which can lead to therapeutic impasses, has prompted the international medical community to regularly propose programs to optimize the use of antibiotics. In collaboration with the SFAR (Société Française d'Anesthésie Réanimation), the GPIP has updated its recommendations for good practice in surgical antibiotic prophylaxis in children, and for short antibiotic prophylaxis in medicine. These recommendations provide a general framework based on the analysis of national and international data, and more often than not on expert opinion, and are intended to support the implementation of local antibiotic prophylaxis protocols specific to each team.

The Relevance of Ferenczi in the Integrated Model of Brief Psychotherapy

This paper presents Sandor Ferenczi’s contributions to Short-Term Psychotherapy in general, specifically concretized in the Integrated ShortTerm Psychotherapy Model that has been developed at the SPPB (Portuguese Society of Brief Psichotherapy). Ferenczi’s proposal for the active participation of the therapist allows for a reformulation of the analytic framework, preventing the development of transfer neurosis and prioritizing the therapeutic relationship. The changes experienced and introduced by Ferenczi led to shifts in therapeutic work that remain relevant even today. We refer to the brevity of the therapeutic process, the focus on clients' needs, the interaction between patient and analyst, and the constant search for modifications to technique as ways to overcome therapeutic impasses and address patients' needs. The resonance of his clinical work is particularly evident in the therapeutic interventions, notably in the construction and development of the Therapeutic Alliance (TA). In summary, Ferenczi introduced a new level of therapeutic engagement within the inter-personal/inter-human sphere, relating to ethical issues and implications for the therapist’s personal requirements and training.

A revisited version of the disputatio for pharmacological training: An educational study

The disputatio is a pedagogical method existing since the Middle-Ages where students had to debate about a question asked by a "master", exercising their thinking and oratory skills. To move away from traditional vertical teaching methods, the disputatio has been revived by pharmacologists. Thus, for almost three successive years, several groups of young French pharmacologists and therapists confronted their ideas concerning a medical question at a therapeutic impasse. The aim here is to describe the initial feedback received from participants. An anonymous questionnaire was sent by email in May 2023 to the participants of the different disputationes of 2019, 2022 and 2023. Participants were asked about different aspects of their feelings before, during and after the disputatio, using the 5-point Likert scale. They were also asked to describe the event in 2 to 5 words. Finally, participants could leave their comments in a free-field and were asked to give an overall satisfaction score out of 10. Out of the 39 participants, 27 (69.2%) answered the questionnaire. Although 50% of respondents reported a feeling of anxiety before participating, most enjoyed the expert talks as well as working with people they did not know. Besides, over 66% reported having underestimated the skills they could share with colleagues from different backgrounds. Over 55% of respondents reported progress in methodology, and over 83% in pharmacology and/or therapeutics. Participants reported an overall satisfaction score of 8.6/10, and the main terms used to describe the event were "sharing", "enriching" and "meeting". The disputatio is an innovative training program whose pedagogical and human values were underlined by most of the participants. Beyond pharmacology and therapeutics, the principle of disputatio could be extended to other disciplines, spanning the centuries.

Differentiating authentic versus pseudo vulnerability in therapeutic practice.

The importance of empathy and attuned care as key ingredients in therapeutic healing has been widely recognized. However, empathy that is delivered in ways that are misaligned with the client's clinical presentation and emotional states or 'modes' can have the opposite effect, reinforcing unhelpful coping patterns, and hindering recovery. In this theoretical development paper, it is proposed that 'pseudo vulnerability' is an important yet overlooked source of therapeutic impasses, often resulting in unremitting clinical problems, and poor clinical outcomes. A range of commonly occurring pseudo vulnerable presentations are described, including Complaining Protector, Attention/Recognition Seeking, and Self-Pity/Victim, with the addition of a new mode Helpless Surrenderer. Guidance on differentiating pseudo vulnerable modes from each other and from the authentic Vulnerable Child mode are delineated via characteristic clinical presentations and typical therapist countertransference reactions. Methods for managing pseudo vulnerability to facilitate access to underlying authentic vulnerability are described.

Pitfalls and Opportunities of the Therapist’s Metacommunication: A Self-determination Perspective

Psychotherapy research identifies alliance ruptures and their resolutions as significant events in psychotherapy, influencing outcome. However, we know little about the process how such events influence outcomes, only assuming if clients stay in therapy that the rupture was resolved, and the outcome will be positive. The purpose of this paper is to problematize this assumption against the backdrop of self-determination theory, introducing motivation and relational positioning as relevant theoretical concepts for understanding rupture resolution and the effect on outcome. A therapeutic transcript demonstrating best practice for alliance rupture resolution in a brief integrative therapy is critically examined, calling the attention of both clinicians and researchers to the risk of prescribing and blindly following techniques during therapeutic impasses. Our analysis of metacommunication demonstrates how the therapist’s use of a certain technique for resolving threats to the therapeutic alliance can lead to the client’s external motivation and compliance, negatively influencing therapeutic outcome. Focusing on the therapist’s relational positioning we present two alternative courses of therapeutic action, ‘mindfulness in action’ and ‘embracing the patient’s ambivalence’, for supporting the client’s autonomous motivation for the therapy process.

P11.11.A VOLUMETRIC AND SPATIAL ANALYSES OF TREATMENT-RELATED INJURY IN GLIOMA

Abstract BACKGROUND As diffuse glioma cannot yet be cured, benefits of therapeutic strategies should be carefully balanced against their burden. Postoperative ischemia is a relatively common adverse event of surgery, which can lead to serious neurological deficits. Radiation therapy (RT) can cause post-RT lesions, which may cause clinical symptoms and can create a therapeutic impasse since they mimic tumor progression. We aimed to explore the spatial and volumetric tumor and treatment characteristics in relation to development of treatment-related effects in glioma. Materials and METHODS We retrospectively included 144 WHO grade II-IV supratentorial glioma cases, which were resected from 2012 till 2014 and had early postoperative MRI with diffusion-weighted imaging (DWI). Tumors were delineated on preoperative contrast-enhanced T1 MRI for high grade gliomas and FLAIR for low grade gliomas. Postoperative ischemia was defined as new, confluent diffusion restriction on postoperative DWI. Post-RT injury was investigated in patients who received RT after first surgery and had at least 6 months of follow-up (FU), and was defined as new or increasing contrast-enhancement that subsequently stabilized or decreased during FU. After manual delineation and non-linear registration to MNI stereotaxic space, all lesions were investigated with regard to size and location of pre-operative tumor, resection cavity, residual tumor and extent of resection (EOR). Voxel-based analysis (VBA) was performed with family-wise error correction for multiple comparisons. RESULTS Postoperative ischemia occurred in 93 of 144 cases and was associated with a larger EOR (P=0.02). Ischemic volume was correlated with a larger preoperative tumor volume (P=0.009) and resection volume (P=0.001). Post-RT injury was found in 25 of 67 analyzed cases and was associated with a larger residual tumor volume (P=0.021) and a smaller EOR (P=0.005). VBA showed an association of the occurrence of post-RT lesions with a cluster of preoperative tumor voxels in the left temporal lobe and clusters of residual tumor voxels in the left temporal and right frontal region. No association in volume or location was found between postoperative ischemia and post-RT lesions. CONCLUSION Adverse events of glioma treatment may be influenced by tumor and treatment volumes. In our population, a larger EOR was associated with the occurrence of postoperative ischemia, and larger tumor and resection volumes were correlated with the volume of ischemia. Additionally, the occurrence of post-RT injury was associated with a larger residual tumor and a smaller EOR, as well as a left temporal preoperative tumor location and a right frontal or left temporal residual tumor location. A thorough examination of spatial and volumetric characteristics of the tumor, treatment and subsequent complications can help elucidate the etiology and guide treatment decisions.

Emergence of New Delhi Metallo-β-Lactamase (NDM) Genes Detected from Clinical Strains of Escherichia coli Isolated in Ouagadougou, Burkina Faso.

The emergence and spread of carbapenem resistance in Gram-negative bacilli such as Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa through the production of carbapenemases is a global phenomenon. It threatens patient care and leads to therapeutic impasses. This study aims to genotypically determine the prevalence of the most frequent carbapenemase genes among multidrug-resistant E. coli strains isolated from patients at a biomedical analysis laboratory. A total of fifty-three unduplicated E. coli strains isolated from patient samples with a multidrug-resistant (MDR) profile were subjected to polymerase chain reaction (PCR) testing for carbapenem resistance genes. This study allowed us to identify fifteen strains carrying resistance genes among the fifty-three E. coli strains. All fifteen strains produced the metallo-β-lactamase enzymes; this represents a rate of 28.30% of study strains. Among these strains, ten carried the NDM resistance gene, NDM and VIM genes were detected in three strains and VIM was identified in two strains of E. coli. However, carbapenemases A (KPC and IMI), D (OXA-48), and IMP were not detected in the strains studied. Thus, NDM and VIM are the main carbapenemases detected in the strains in our study.

On the Search for Singularity in Supervision.

A central role of supervision is to help the supervisee develop the self-as-therapist by internalizing analytic theoretical convictions and clinical practices and creating an individualistic professional identity. Supervisors can help this process by viewing some of the supervisees' narrated therapeutic impasses as manifestations of creative rebellion. This creative rebellion helps them exercise their freedom of choice and become who they are as therapists. The creative rebellion metaphor can sometimes explain disruptions to the therapeutic process without threatening the cohesion of the supervisee's professional self and the integrity of the supervisory process.

Acacia senegal Budmunchiamines as a Potential Adjuvant for Rejuvenating Phenicol Activities towards Escherichia coli-Resistant Strains.

The continuous emergence of bacterial resistance alters the activities of different antibiotic families and requires appropriate strategies to solve therapeutic impasses. Medicinal plants are an attractive source for researching alternative and original therapeutic molecules. In this study, the fractionation of natural extracts from A. senegal and the determination of antibacterial activities are associated with molecular networking and tandem mass spectrometry (MS/MS) data used to characterize active molecule(s). The activities of the combinations, which included various fractions plus an antibiotic, were investigated using the "chessboard" test. Bio-guided fractionation allowed the authors to obtain individually active or synergistic fractions with chloramphenicol activity. An LC-MS/MS analysis of the fraction of interest and molecular array reorganization showed that most identified compounds are Budmunchiamines (macrocyclic alkaloids). This study describes an interesting source of bioactive secondary metabolites structurally related to Budmunchiamines that are able to rejuvenate a significant chloramphenicol activity in strains that produce an AcrB efflux pump. They will pave the way for researching new active molecules for restoring the activity of antibiotics that are substrates of efflux pumps in enterobacterial-resistant strains.

What to Do with the New Antibiotics?

Multidrug-resistant Gram-negative bacteria-related infections have become a real public health problem and have exposed the risk of a therapeutic impasse. In recent years, many new antibiotics have been introduced to enrich the therapeutic armamentarium. Among these new molecules, some are mainly of interest for the treatment of the multidrug-resistant infections associated with Pseudomonas aeruginosa (ceftolozane/tazobactam and imipenem/relebactam); others are for carbapenem-resistant infections associated with Enterobacterales (ceftazidime/avibactam, meropenem/vaborbactam); and finally, there are others that are effective on the majority of multidrug-resistant Gram-negative bacilli (cefiderocol). Most international guidelines recommend these new antibiotics in the treatment of microbiologically documented infections. However, given the significant morbidity and mortality of these infections, particularly in the case of inadequate therapy, it is important to consider the place of these antibiotics in probabilistic treatment. Knowledge of the risk factors for multidrug-resistant Gram-negative bacilli (local ecology, prior colonization, failure of prior antibiotic therapy, and source of infection) seems necessary in order to optimize antibiotic prescriptions. In this review, we will assess these different antibiotics according to the epidemiological data.

Population Dynamics, Plasma Cytokines and Platelet Centrifugation: Technical and Sociodemographic Aspects of 'Ovarian Rejuvenation'.

While advanced reproductive technologies have attained remarkable increases in sophistication, success, and availability since the 1980s, clinicians always meet a therapeutic impasse when the ovarian reserve reaches exhaustion. Irrespective of fertility aspirations, the decline in and eventual collapse of ovarian estrogen output means that menopause arrives with tremendous physiologic changes and reduced overall productivity. Because more women are gaining in longevity or delaying the age at pregnancy, the number of affected patients has never been larger. As concerns regarding standard hormone replacement therapy and the limitations of IVF are confronted, a workable path to enable primordial germ cell recruitment and de novo oocyte development would be welcome. Proof-of-concept case reports and clinical studies on autologous activated platelet-rich plasma (PRP) or its condensed cytokine derivatives suggest a way to facilitate these goals. However, ovarian PRP faces vexing challenges that place 'ovarian rejuvenation' under caution as it enters this therapeutic space. Here, we review key features of experimental human ovarian stem cell isolation/handling and reaffirm the need to harmonize laboratory protocols. Recognizing the regenerative science borrowed from other disciplines, specimen centrifugation, platelet processing, and condensed plasma cytokine enrichment are highlighted here. As the refinement of this rejuvenation approach would promise to reprogram adult ovarian physiology, the disruption of established treatment paradigms for infertility, menopause, and perhaps overall women's health seems likely. Emerging roles in reproductive biology and clinical practice are thus placed in a broader social and demographic context.

Impact of Green Gold Nanoparticle Coating on Internalization, Trafficking, and Efficiency for Photothermal Therapy of Skin Cancer.

Skin cancer is a global health issue and mainly composed of melanoma and nonmelanoma cancers. For the first clinical proof of concept on humans, we decided to study good prognosis skin cancers, i.e., carcinoma basal cell. In UE, the first-line treatment remains surgical resection, healing most of the tumors, but presents aesthetic disadvantages with a high reoccurrence rate on exposed areas. Moreover, the therapeutic indications could extend to melanoma and metastasis, which is a different medical strategy that could combine this treatment. Indeed, patients with late-stage melanoma are in a therapeutic impasse, despite recent targeted and immunological therapies. Photothermal therapy using gold nanoparticles is the subject of many investigations due to their strong potential to treat cancers by physical, thermal destruction. We developed gold nanoparticles synthesized by green chemistry (gGNPs), using endemic plant extract from Reunion Island, which have previously showed their efficiency at a preclinical stage. Here, we demonstrate that these gGNPs are less cytotoxic than gold nanoparticles synthesized by Turkevich's method. Furthermore, our work describes the optimization of gGNP coating and stabilization, also taking into consideration the gGNP path in cells (endocytosis, intracellular trafficking, and exocytosis), their specificity toward cancerous cells, their cytotoxicity, and their in vivo efficiency. Finally, based on the metabolic switch of cancerous cells overexpressing Glut transporters in skin cancers, we demonstrated that glucose-stabilized gGNP (gGNP@G) enables a quick internalization, fourfold higher in cancerous cells in contrast to healthy cells with no side cytotoxicity, which is particularly relevant to target and treat cancer.

Working with primitive mental states in couples

The author proposes the importance and relevance of working with primitive mental states in couples and that a failure to recognise and work with these states can lead to a therapeutic impasse. This article highlights how an understanding of such a mode of psychic experience has emerged largely from work with individual patients. Moreover, it suggests how couples presenting with such primitive mental states require the analyst to be available as an undifferentiated object. This provides a containment function that allows for psychic transformation and growth. Couples whose psychic function has been derailed to such a regression point are thus allowed to regain their usual level of functioning. This outcome in turn provides a platform for further growth which involves the capacity to work with symbolic processes. It is proposed that such understandings and ways of working with primitive mental states and their associated anxieties have a cross-cultural applicability.

Absorption Spectra Description for T-Cell Concentrations Determination and Simultaneous Measurements of Species during Co-Cultures

Advanced Therapy Medicinal Products are promising drugs for patients in therapeutic impasses. Their complex fabrication process implies regular quality controls to monitor cell concentration. Among the different methods available, optical techniques offer several advantages. Our study aims to measure cell concentration in real time in a potential closed-loop environment using white light spectroscopy and to test the possibility of simultaneously measuring concentrations of several species. By analyzing the shapes of the absorption spectra, this system allowed the quantification of T-cells with an accuracy of about 3% during 30 h of cultivation monitoring and 26 h of doubling time, coherent with what is expected for normal cell culture. Moreover, our system permitted concentration measurements for two species in reconstructed co-cultures of T-cells and Candida albicans yeasts. This method can now be applied to any single or co-culture, it allows real-time monitoring, and can be easily integrated into a closed system.