Bridging personality dimensions and eating symptoms: A transdiagnostic network approach.

OBJECTIVE: Eating disorders (ED) have recently been studied from a network approach, conceptualising them as a complex system of interconnected variables, while highlighting the role of non-ED symptoms and personality dimensions. This study aims to explore the connections between personality and ED symptoms, identify central nodes, and compare the EDs network to a healthy control network. METHODS: We employed network analysis to examine the personality-ED symptom connections in 329 individuals with an ED diagnosis and 192 healthy controls. We estimated a regularised partial correlation network and the indices of centrality and bridge centrality to identify the most influential nodes for each group. Network differences between groups were also examined. RESULTS: Low Self-Directedness and high Harm avoidance emerged as central bridge nodes, displaying the strongest relationship with ED symptoms. Both networks differed in their global connectivity and structure, although no differences were found in bridge centrality and centrality indices. CONCLUSIONS: These findings shed light on the role of personality dimensions, such as Self-Directedness and Harm Avoidance in the maintenance of ED psychopathology, supporting the transdiagnostic conceptualisation of ED. This study advances a deeper understanding of the complex interplay between personality dimensions and ED symptoms, offering potential directions for clinical interventions.

Mediators between sexual abuse and eating disorder severity: A comparative case-control study in treatment-naïve patients.

OBJECTIVE: Sexual abuse is associated with eating disorders (EDs) severity. However, the psychological mediators of this association have received scant attention in the literature. METHOD: The present study aimed to evaluate the mediating role of psychological maladjustment, alexithymia, and self-esteem in the relationship between sexual abuse and EDs severity in a sample of 134 treatment-naïve patients with an EDs and 129 paired healthy controls. RESULTS: In the EDs group, EDs severity among participants who had been sexually abused was mediated by greater psychological maladjustment and alexithymia (indirect effects: ß = 12.55, 95% CI [6.11-19.87] p < 0.001; ß = 3.22, 95% CI [0.235-7.97] p < 0.05, respectively). By contrast, these variables had no significant mediating effect on EDs severity in the control group. DISCUSSION: These findings support the hypothesis of a disorder-related relationship between sexual abuse and alexithymia and psychological maladjustment, which, in turn, influences EDs severity. Alexithymia and psychological maladjustment appear to be promising therapeutic targets for patients with EDs who have a history of sexual abuse.

Staphylococcus aureus Breast Implant Infection Isolates Display Recalcitrance To Antibiotic Pocket Irrigants.

Breast implant-associated infections (BIAIs) are the primary complication following placement of breast prostheses in breast cancer reconstruction. Given the prevalence of breast cancer, reconstructive failure due to infection results in significant patient distress and health care expenditures. Thus, effective BIAI prevention strategies are urgently needed. This study tests the efficacy of one infection prevention strategy: the use of a triple antibiotic pocket irrigant (TAPI) against Staphylococcus aureus, the most common cause of BIAIs. TAPI, which consists of 50,000 U bacitracin, 1 g cefazolin, and 80 mg gentamicin diluted in 500 mL of saline, is used to irrigate the breast implant pocket during surgery. We used in vitro and in vivo assays to test the efficacy of each antibiotic in TAPI, as well as TAPI at the concentration used during surgery. We found that planktonically grown S. aureus BIAI isolates displayed susceptibility to gentamicin, cefazolin, and TAPI. However, TAPI treatment enhanced biofilm formation of BIAI strains. Furthermore, we compared TAPI treatment of a S. aureus reference strain (JE2) to a BIAI isolate (117) in a mouse BIAI model. TAPI significantly reduced infection of JE2 at 1 and 7 days postinfection (dpi). In contrast, BIAI strain 117 displayed high bacterial burdens in tissues and implants, which persisted to 14 dpi despite TAPI treatment. Lastly, we demonstrated that TAPI was effective against Pseudomonas aeruginosa reference (PAO1) and BIAI strains in vitro and in vivo. Together, these data suggest that S. aureus BIAI strains employ unique mechanisms to resist antibiotic prophylaxis treatment and promote chronic infection. IMPORTANCE The incidence of breast implant associated infections (BIAIs) following reconstructive surgery postmastectomy remains high, despite the use of prophylactic antibiotic strategies. Thus, surgeons have begun using additional antibiotic-based prevention strategies, including triple antibiotic pocket irrigants (TAPIs). However, these strategies fail to reduce BIAI rates for these patients. To understand why these therapies fail, we assessed the antimicrobial resistance patterns of Staphylococcus aureus strains, the most common cause of BIAI, to the antibiotics in TAPI (bacitracin, cefazolin, and gentamicin). We found that while clinically relevant BIAI isolates were more susceptible to the individual antibiotics compared to a reference strain, TAPI was effective at killing all the strains in vitro. However, in a mouse model, the BIAI isolates displayed recalcitrance to TAPI, which contrasted with the reference strain, which was susceptible. These data suggest that strains causing BIAI may encode specific recalcitrance mechanisms not present within reference strains.

Semi-Quantitative Assay to Measure Urease Activity by Urinary Catheter-Associated Uropathogens.

Catheter-associated urinary tract infections (CAUTIs) are one of the most common healthcare-associated infections in the US, accounting for over 1 million cases annually and totaling 450 million USD. CAUTIs have high morbidity and mortality rates and can be caused by a wide range of pathogens, making empiric treatment difficult. Furthermore, when urease-producing uropathogens cause symptomatic CAUTI or asymptomatic catheter colonization, the risk of catheter failure due to blockage increases. The enzyme urease promotes catheter blockage by hydrolyzing urea in urine into ammonia and carbon dioxide, which results in the formation of crystals that coat the catheter surface. If CAUTI is left untreated, the crystals can grow until they block the urinary catheter. Catheter blockage and subsequent failure reduces the quality of life for the chronically catheterized, as it requires frequent catheter exchanges and can promote more severe disease, including dissemination of the infection to the kidneys or bloodstream. Thus, understanding how urease contributes to catheter blockages and/or more severe disease among the broad range of urease-producing microbes may provide insights into better prevention or treatment strategies. However, clinical assays that detect urease production among clinical isolates are qualitative and prioritize the detection of urease from Proteus mirabilis, the most well-studied uropathogenic urease producer. While urease from other known urease producers, such as Morganella morganii, can also be detected with these methods, other uropathogens, including Staphylococcus aureus and Klebsiella pneumonia, are harder to detect. In this study, we developed a high throughput, semiquantitative assay capable of testing multiple uropathogens in a rapid and efficient way. We validated the assay using Jack Bean urease, the urease producing species: Proteus spp., M. morganii, K. pneumonia, and S. aureus strains, and the non-urease producer: Escherichia coli. This modified assay more rapidly detected urease-producing strains compared to the current clinical test, Christensen Urea Agar, and provided semiquantitative values that may be used to further investigate different aspects of urease regulation, production, or activity in these diverse species. Furthermore, this assay can be easily adapted to account for different environmental stimuli affecting urease production, including bacterial concentration, aeration, or addition of anti-urease compounds.

Low levels of proinflammatory cytokines in a transdiagnostic sample of young male and female early onset eating disorders without any previous treatment: A case control study.

Growing interest exists in the association of the immune system and its role in the development and maintenance of eating disorders (ED). Current evidence suggests that serum cytokine levels seem to be elevated in females with anorexia nervosa (AN). However, less is known in bulimia nervosa (BN) and other specified feeding and eating disorders (OSFED), specially in males. We aimed to perform a case-control study in a sample of forty eight young patients (38 females and 10 males) with early diagnosis of AN, BN or OSFED and without any previous treatment, compared with twenty nine healthy controls (19 females and 10 males) matched by age, sex and socioeconomic status. We evaluated eating-related psychopathology and depressive symptoms and measured serum concentration of proinflammatory cytokines IL-1ß, IL-6, and TNF-α and anti-inflammatory cytokine IL-10. Contrary to expectations, levels of IL-1ß and IL-6 were significantly lower in ED patients, compared with healthy controls. Comparing the different groups of females, we found elevated levels of IL-10 among ED patients therefore supporting the idea of an immunosuppressive status in the early stages. This could indicate that early onset patients without any previous treatment could remain in a reward-dependent state with a lower immune response.

A retrospective investigation of the prodromal stages of eating disorders and use of health services in young patients the year prior to the diagnosis.

AIM: The aim of this study was to analyse the characteristics and the frequency of medical consultations in the year prior to the diagnosis and the intervention onset of the Eating Disorder, as well as the different prodromal symptoms. The final aim was to understand the origin of all referrals and their possible influence on the duration of untreated illness. METHODS: We selected 99 young patients (15-25 years) and 61 healthy controls. Their primary and specialized care medical records were both studied retrospectively. RESULTS: 87.6% of patients attended different consultations (primary care, specialized care and emergency department) the year prior compared to 67.2% of the controls (p = .002). The average number of consultations was 3.59 in the case group and 1.57 in the control group (p < .001). These consultations were related to prodromal symptoms in 57.4% compared to 16.4% for the controls (p < .001). They ranged from 29.8% of unspecific digestive symptoms, 22.8% of psychological symptoms, 19.3% of gynaecologic symptoms, 11.9% of weight variation, 8.8% of analytical changes, to 5.3% of malnutrition symptoms. Patients were mainly referred by Primary Care (42.7%). Overall, the mean of the Duration of Untreated Illness was of 7.45 months. CONCLUSIONS: The majority of reasons for consultation were related to symptoms that could be prodromal symptoms, but the patients were not diagnosed with an eating disorder. These findings highlight the importance of professionals understanding how to identify the warning signs of an eating disorder, so they can refer patients to a specialized unit to establish an early treatment.

Self-Masked Aldehyde Inhibitors: A Novel Strategy for Inhibiting Cysteine Proteases.

Cysteine proteases comprise an important class of drug targets, especially for infectious diseases such as Chagas disease (cruzain) and COVID-19 (3CL protease, cathepsin L). Peptide aldehydes have proven to be potent inhibitors for all of these proteases. However, the intrinsic, high electrophilicity of the aldehyde group is associated with safety concerns and metabolic instability, limiting the use of aldehyde inhibitors as drugs. We have developed a novel class of self-masked aldehyde inhibitors (SMAIs) for cruzain, the major cysteine protease of the causative agent of Chagas disease-Trypanosoma cruzi. These SMAIs exerted potent, reversible inhibition of cruzain (Ki* = 18-350 nM) while apparently protecting the free aldehyde in cell-based assays. We synthesized prodrugs of the SMAIs that could potentially improve their pharmacokinetic properties. We also elucidated the kinetic and chemical mechanism of SMAIs and applied this strategy to the design of anti-SARS-CoV-2 inhibitors.

Peptidomimetic Vinyl Heterocyclic Inhibitors of Cruzain Effect Antitrypanosomal Activity.

Cruzain, an essential cysteine protease of the parasitic protozoan, Trypanosoma cruzi, is an important drug target for Chagas disease. We describe here a new series of reversible but time-dependent inhibitors of cruzain, composed of a dipeptide scaffold appended to vinyl heterocycles meant to provide replacements for the irreversible reactive "warheads" of vinyl sulfone inactivators of cruzain. Peptidomimetic vinyl heterocyclic inhibitors (PVHIs) containing Cbz-Phe-Phe/homoPhe scaffolds with vinyl-2-pyrimidine, vinyl-2-pyridine, and vinyl-2-(N-methyl)-pyridine groups conferred reversible, time-dependent inhibition of cruzain (Ki* = 0.1-0.4 µM). These cruzain inhibitors exhibited moderate to excellent selectivity versus human cathepsins B, L, and S and showed no apparent toxicity to human cells but were effective in cell cultures of Trypanosoma brucei brucei (EC50 = 1-15 µM) and eliminated T. cruzi in infected murine cardiomyoblasts (EC50 = 5-8 µM). PVHIs represent a new class of cruzain inhibitors that could progress to viable candidate compounds to treat Chagas disease and human sleeping sickness.

Characteristics of patients in an eating disorder sample who dropped out: 2-year follow-up.

OBJECTIVE: This manuscript explores the characteristics of individuals diagnosed with an eating disorder who dropped out of treatment, compared with those who completed it. METHOD: The participants were 196 patients diagnosed with eating disorders (according to DSM-IV-TR criteria) who consecutively began treatment for the first time in an eating disorders unit. They were assessed at baseline with a set of questionnaires evaluating eating habits, temperament, and general psychopathology. During the follow-up period, patients who dropped out were re-assessed via a telephone interview. RESULTS: In the course of a 2-year follow-up, a total of 80 (40.8%) patients were labeled as dropouts, and 116 (59.2%) remaining subjects were considered completers. High TCI scores in the character dimensions of Disorderliness (NS4) (p < .01) and total Novelty Seeking (NST), along with low scores in Dependency (RD4), were significantly associated with dropout in the course of 2 years. Once the results were submitted to logistic regression analysis, dropout only remained associated with high scores in Disorderliness (NS4) and, inversely, with an initial Anorexia Nervosa (AN) diagnosis (p < .05). Reasons for dropout stated by the patients included logistic difficulties, subjective improvement of their condition, and lack of motivation. DISCUSSION: Clinicians should handle the first therapeutic intervention with particular care in order to enhance their understanding of clients and their ability to rapidly identify those who are at risk of dropping out of treatment. LEVEL OF EVIDENCE: Level III: Cohort Study.

Low-density lipoprotein cholesterol and suicidal behaviour in a large sample of first-episode psychosis patients.

OBJECTIVES: Our aims were to confirm the relationship between lipid and lipoprotein concentrations and suicidal behaviour in first-episode psychosis (FEP) patients. METHODS: Suicidal behaviour was explored in a large FEP sample (N = 383). Baseline lipid profile was compared between those who attempted or completed suicide and those who not presented suicidal behaviour. RESULTS: Low-density lipoprotein cholesterol (LDL-c) (OR = 0.99, 95% CI= 0.98-1.00) and depressive symptoms (OR = 1.15, 95% CI = 1.06-1.24) were significantly related with suicidal behaviour. CONCLUSIONS: Lipid profile test may be considered in the assessment of suicide risk in psychosis and LDL-c an important biological marker.

Planning Abilities in Patients with Anorexia Nervosa Compared with Healthy Controls.

OBJECTIVE: Altered cognitive functioning could have an important role in the development and maintenance of Anorexia Nervosa (AN). The majority of previous research has focused on flexibility and global-detail processing. The aim of this study was to explore planning abilities in women with AN. METHOD: Women with AN (n = 32) were compared to healthy controls (n = 42) using two different types of neuropsychological tasks for the assessment of planning abilities: Tower of London (ToL), a classic measure of planning abilities, and Zoo Map test, a more ecologically valid planning measure. Measures of AN psychopathology, anxiety, depression, and obsessive compulsivity were also collected. RESULTS: The AN group did not differ from controls in the ToL (all p-values p > .05), although they performed significantly worse than controls in the main score of the Zoo Map (p = .02). A worse performance in the Zoo Map test More was associated with more eating disorders (rho = -.44, p = .018) and depressive (rho = -.42, p = .026) symptoms in the AN group. CONCLUSIONS: Our study suggests the presence of subtle planning difficulties in women with AN which might be better detected using tasks with increased ecological validity.

Changes in Body Composition in Anorexia Nervosa: Predictors of Recovery and Treatment Outcome.

The restoration of body composition (BC) parameters is considered to be one of the most important goals in the treatment of patients with anorexia nervosa (AN). However, little is known about differences between AN diagnostic subtypes [restricting (AN-R) and binge/purging (AN-BP)] and weekly changes in BC during refeeding treatment. Therefore, the main objectives of our study were twofold: 1) to assess the changes in BC throughout nutritional treatment in an AN sample and 2) to analyze predictors of BC changes during treatment, as well as predictors of treatment outcome. The whole sample comprised 261 participants [118 adult females with AN (70 AN-R vs. 48 AN-BP), and 143 healthy controls]. BC was measured weekly during 15 weeks of day-hospital treatment using bioelectrical impedance analysis (BIA). Assessment measures also included the Eating Disorders Inventory-2, as well as a number of other clinical indices. Overall, the results showed that AN-R and AN-BP patients statistically differed in all BC measures at admission. However, no significant time×group interaction was found for almost all BC parameters. Significant time×group interactions were only found for basal metabolic rate (p = .041) and body mass index (BMI) (p = .035). Multiple regression models showed that the best predictors of pre-post changes in BC parameters (namely fat-free mass, muscular mass, total body water and BMI) were the baseline values of BC parameters. Stepwise predictive logistic regressions showed that only BMI and age were significantly associated with outcome, but not with the percentage of body fat. In conclusion, these data suggest that although AN patients tended to restore all BC parameters during nutritional treatment, only AN-BP patients obtained the same fat mass values as healthy controls. Put succinctly, the best predictors of changes in BC were baseline BC values, which did not, however, seem to influence treatment outcome.