Clinical features, severity, and immunological changes during venom immunotherapy in children and adults.

Background: Hymenoptera venom allergy (HVA) is among the most common causes of severe allergic reactions worldwide. Objective: To investigate clinical features and factors that affect the severity of HVA and to determine the alterations in immunologic biomarkers after venom immunotherapy (VIT). Methods: Seventy-six adults and 36 children were prospectively investigated. We analyzed specific immunoglobulin E (sIgE) and sIgG4 levels of venom extracts and components (rApi m1, rApi m10, rVes v1, rVes v5, rPol d5) before and after the first year of VIT. Results: Although cardiovascular symptoms were more common in adults (p < 0.001), the skin was the most affected organ in children (p = 0.009). Serum basal tryptase (sBT) levels were higher in the adults than the children (p < 0.001). The absence of urticaria (odds ratio [OR] 4.208 [95% confidence interval {CI}, 1.395-12.688]; p = 0.011) and sBT ≥ 5.2 ng/mL (OR 11.941 [95% CI, 5.220-39.733]; p < 0.001) were found as the risk factors for grade IV reactions. During VIT, changes in sIgE levels were variable. In the Apis VIT group, we observed remarkable increases in sIgG4 levels in Apis extract and rApi m1 but not in Api m10. Vespula extract, rVes v1, and rVes v5 sIgG4 levels were significantly increased in Vespula VIT group, we also detected significant increases in the Polistes extract and rPol d5 sIgG4 levels, which were not observed in the Apis VIT group. In the patients who received both Apis and Vespula VIT, increases in sIgG4 levels were observed for both venoms. Conclusion: Adults and children can have different clinical patterns. After 1 year, VIT induced a strong IgG4 response. Although Apis immunotherapy (IT) induced Apis sIgG4, excluding Api m10, Vespula IT induced both Vespula and Polistes sIgG4.

Dysbiosis in pregnant mice induced by transfer of human vaginal microbiota followed by reversal of pathological changes in the uterus and placenta via progesterone treatment.

OBJECTIVE: The vaginal microbiota dysbiosis induces inflammation in the uterus that triggers tissue damage and is associated with preterm birth. Progesterone is used to prevent labor in pregnant women at risk of preterm birth. However, the mechanism of action of progesterone still needs to be clarified. We aimed to show the immunomodulatory effect of progesterone on the inflammation of uterine tissue triggered by dysbiotic vaginal microbiota in a pregnant mouse model. METHODS: Healthy (n = 6) and dysbiotic (n = 7) vaginal microbiota samples isolated from pregnant women were transferred to control (n = 10) and dysbiotic (n = 14) pregnant mouse groups. The dysbiotic microbiota transferred group was treated with 1 mg progesterone (n = 7). Flow cytometry and immunohistochemistry analyses were used to evaluate inflammatory processes. Vaginal microbiota samples were analyzed by 16 S rRNA sequencing. RESULTS: Vaginal exposure to dysbiotic microbiota resulted in macrophage accumulation in the uterus and cellular damage in the placenta. Even though TNF and IL-6 elevations were not significant after dysbiotic microbiota transplantation, progesterone treatment decreased TNF and IL-6 expressions from 49.085 to 31.274% (p = 0.0313) and 29.279-21.216% (p = 0.0167), respectively. Besides, the macrophage density in the uterus was reduced, and less cellular damage in the placenta was observed. CONCLUSION: Analyzing the vaginal microbiota before or during pregnancy may support the decision for initiation of progesterone therapy. Our results also guide the development of new strategies for preventing preterm birth.

JAK-2 V617F Mutation in Endothelial Cells of Patients with Atherosclerotic Carotid Disease.

Objective: It has been shown that clonal mutations occur in hematopoietic stem cells with advancing age and increase the risk of death due to atherosclerotic vascular diseases, just like in myeloproliferative neoplasms. It is known that endothelial cells (EC) and hematopoietic stem cells develop from a common stem cell called hemangioblast in early embryonic period. However, the presence of hemangioblast in the postnatal period is controversial. In this study, JAK2 gene variants was examined in patients with atherosclerotic carotid disease and without any hematological malignancy. Materials and Methods: Ten consecutive patients (8 men and 2 women) with symptomatic atherosclerotic carotid stenosis were included in this study. EC (CD31+CD45-) were separated from tissue samples taken by carotid endarterectomy. JAK2 variants was examined in EC, peripheral blood mononuclear cells and oral epithelial cells of the patients with next generation sequencing. Results: The median age of the patients was 74 (58-80) and the median BMI was 24,44 (18,42-30,85) kg/m2. Smoking history was present in 50%, hypertension in 80%, diabetes in 70%, and ischemic heart disease in 70% of the patients. JAK2V617F mutation was detected in peripheral blood mononuclear cells in three out of 10 patients, two of them also had JAK2V617F mutation in their EC. JAK2V617F mutation was not found in oral epithelial cells in any of the patients. Conclusion: In this study, for the first time in the literature, we showed that JAK2V617F mutation was found somatically in both peripheral blood cells and EC in patients with atherosclerosis. This finding may support that EC and hematopoietic cells originate from a common clone or that the somatic mutation can be transmitted to EC by other mechanisms. Examining the molecular and functional changes caused by JAK2V617F mutation in EC may help open a new avenue for treating atherosclerosis.

Live Donor Assessment Tool (LDAT): Reliability and Validity of the German Version in Living Kidney Donor Candidates.

BACKGROUND: The Live Donor Assessment Tool (LDAT) is a semi-structured psychosocial assessment tool for evaluating potential organ donors. It enables standardization of the psychosocial evaluation across institutions and allows the quantification of the evaluation result. OBJECTIVE: To evaluate the validity and reliability of the German version of the LDAT in living kidney donors. METHODS: We assessed the internal consistency and convergent validity (using known groups) of the German version of the LDAT in donor candidates who were evaluated at Hannover Medical School from May 2017 to December 2021. RESULTS: One hundred fifty-two donor candidates were evaluated. The mean age was 50.9 (standard deviation, 12.0), 99 were female (65.1%) and 53 (34.9%) were male candidates. LDAT scores ranged from 39 to 78 (possible maximum score = 82). The mean and median LDAT scores in the entire sample were 69 (standard deviation, 6.4) and 71 (95% confidence interval, 68; 70), respectively. The LDAT items demonstrated good internal consistency (α = 0.737). LDAT scores were significantly lower in high and moderate risk donors compared to a low/no risk group as determined by clinical evaluation. We found a significant positive association of the LDAT total score with age and a negative correlation with levels of depression and anxiety. The best cutoff score in our sample was 66.5 with an area under the curve of 93%. CONCLUSIONS: The German version of the LDAT was found to be a reliable and valid tool, which seems suitable to support psychosocial donor evaluation.

B Cell Subtypes in Individuals Received mRNA or Inactivated Vaccine Boosters After Fully Vaccinated with CoronaVac: A Longitudinal Study.

In this study, we aimed to investigate the changes in the B cell subpopulations after homologous or heterologous COVID-19 boosters. Blood samples were collected after baseline (3-5 months after two doses of CoronaVac), 1 and 3 months after BNT162b2 (n=28 and n=6), and CoronaVac (n=7 and n=4) boosters. Peripheral blood mononuclear cells (PBMCs) were isolated and stained with B cell markers, the ratios of naïve (CD19+CD20+CD27-), memory (CD19+CD20+CD27+), memory B cells expressing IgG (CD19+CD20+CD27+IgG+), and effector memory B cells (CD19+CD20+CD27+CD38+) were identified with flow cytometry. Significantly higher expression of memory B cells was observed in one month with BNT162b2 (12.16% one month, 5.98% three months) and CoronaVac (14.18% one month, 9.00% three months) boosters. IgG expressing memory B cell expression was significantly higher with BNT162b2 than with CoronaVac booster in one month (22.70% and 13.95%, respectively). The ratio of effector B cells in the first month after CoronaVac booster (25.44%) was significantly higher than the BNT162b2 booster (9.90%, p =0.0263).

Effect of BTN162b2 and CoronaVac boosters on humoral and cellular immunity of individuals previously fully vaccinated with CoronaVac against SARS-CoV-2: A longitudinal study.

BACKGROUND: It is essential to know about immune response levels after booster doses of the two different types of vaccines, mRNA, and the inactivated, currently used against COVID-19. For this purpose, we aimed to determine the effects of BNT162b2 (BNT) and CoronaVac (CV) boosters on the humoral and cellular immunity of individuals who had two doses of CV vaccination. METHODS: The study was conducted in three centers (Koc University Hospital, Istanbul University Cerrahpasa Hospital, and Istanbul University, Istanbul Medical School Hospital) in Istanbul, Turkey. Individuals who had been previously immunized with two doses of CV and no history of COVID-19 were included. The baseline blood samples were collected 3-5 months after the second dose of CV. Follow-up blood samples were taken 1 and 3 months after administration of third doses of CV, or one dose of BNT boosters. Neutralizing antibody titers were measured by plaque reduction assay. The CD4+ T cell, CD8+ T cell, effector CD4+CD38+CD69+ T cell, and effector CD8+CD38+CD69+ T cell ratios were determined by flow cytometry. The intracellular IFN-γ and IL-2 responses were measured by ELISpot assay. RESULTS: We found a 3.38-fold increase in neutralizing antibody geometric mean titers (NA GMT, 78.69) 1 month after BNT booster and maintained at the third month (NA GMT, 80). Nevertheless, in the CV booster group, significantly lower NA GMT than BNT after 1 month and 3 months were observed (21.44 and 28.44, respectively) (p < .001). In the ELISpot assay, IL-2 levels after BNT were higher than baseline and CV booster (p < .001) while IFN-γ levels were significantly higher than baseline (p < .001). The CD8+CD38+CD69+ and CD4+CD38+CD69+ T cells were stimulated predominantly in the third month of the BNT boosters. CONCLUSION: The neutralizing antibody levels after 3 months of the BNT booster were higher than the antibody levels after CV in fully vaccinated individuals. On the contrary, ratio of the effector T cells increased along with greater IFN-γ activation after BNT booster. By considering the waning immunity, we suggest a new booster dose with BNT for the countries that already had two doses of primary CV regimens.

Virulence Determinants of Colistin-Resistant K. pneumoniae High-Risk Clones.

We proposed the hypothesis that high-risk clones of colistin-resistant K. pneumoniae (ColR-Kp) possesses a high number of virulence factors and has enhanced survival capacity against the neutrophil activity. We studied virulence genes of ColR-Kp isolates and neutrophil response in 142 patients with invasive ColR-Kp infections. The ST101 and ST395 ColR-Kp infections had higher 30-day mortality (58%, p = 0.005 and 75%, p = 0.003). The presence of yersiniabactin biosynthesis gene (ybtS) and ferric uptake operon associated gene (kfu) were significantly higher in ST101 (99%, p ≤ 0.001) and ST395 (94%, p < 0.012). Being in ICU (OR: 7.9; CI: 1.43-55.98; p = 0.024), kfu (OR:27.0; CI: 5.67-179.65; p < 0.001) and ST101 (OR: 17.2; CI: 2.45-350.40; p = 0.01) were found to be predictors of 30-day mortality. Even the neutrophil uptake of kfu+-ybtS+ ColR-Kp was significantly higher than kfu--ybtS- ColR-Kp (phagocytosis rate: 78% vs. 65%, p < 0.001), and the kfu+-ybtS+ ColR-Kp survived more than kfu--ybtS- ColR-Kp (median survival index: 7.90 vs. 4.22; p = 0.001). The kfu+-ybtS+ ColR-Kp stimulated excessive NET formation. Iron uptake systems in high-risk clones of colistin-resistant K. pneumoniae enhance the success of survival against the neutrophil phagocytic defense and stimulate excessive NET formation. The drugs targeted to iron uptake systems would be a promising approach for the treatment of colistin-resistant high-risk clones of K. pneumoniae infections.

Immune profiling after minimally invasive lobectomy.

OBJECTIVES: Whether acute phase and immune responses are minimally affected following minimally invasive lung surgery needs further investigation. We performed a pilot study to evaluate the immune profile of patients who underwent video-assisted thoracoscopic surgery or robot-assisted thoracic surgery lobectomies for the treatment of suspicious or known stage I non-small-cell lung cancer. METHODS: Blood samples were taken preoperatively and 3 and 24 h postoperatively were analysed for C-reactive protein, glucose, cortisol, tumour necrosis factor alpha (TNF-α), interleukin 8 (IL-8) and interleukin 10 (IL-10) levels. TNF-α, IL-8 and IL-10 were also measured in lung tissues. T (CD4, CD8), B (CD19) and natural killer (CD56, CD16) cell counts and natural killer cell functions were analysed using a flow cytometry-based assay before and after surgery. RESULTS: Minimally invasive surgery (robot-assisted thoracic surgery + video-assisted thoracoscopic surgery) significantly decreased IL-10 (P = 0.016) levels after surgery. No significant differences were detected in TNF-α (P = 0.48) and IL-8 (P = 0.15) levels before and after surgery. C-reactive protein (P < 0.001), cortisol (P < 0.001) and glucose levels (P < 0.001) increased significantly after surgery. Lymphocyte, total T cell, CD3+CD4+ and CD3+CD8+ CD16+CD56+ cell counts were significantly lower on postoperative day 1. CONCLUSION: There seems to be a dynamic balance between pro- and anti-inflammatory cytokines and immune cells following minimally invasive lobectomy.

The impact of impending / onset of vision loss on depression, anxiety, and vision-related quality of life in Birdshot-Retinochoroiditis and Serpiginous Choroiditis.

To evaluate the impact of Birdshot-Retinochoroidopathy (BSRC) and Serpiginous Choroiditis (SC) on depression, anxiety, and vision-related quality of life. 72 individuals (BSRC: n = 28, SC: n = 8; healthy control group (HC): n = 36) completed the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and the Visual Function Questionnaire (VFQ-25). Multivariate linear regression models were used to analyze different subscales of the PHQ-9, the GAD-7 and the VFQ-25. The results showed that the mean of PHQ-9 was significantly higher while the mean of the VFQ-25 and its´ subscales were consistently lower in the disease group compared to HC. The mean of GAD-7 was not significantly lower in the disease group compared to HC. Stratification for different disease severity stages and duration of disease did not reveal any differences in sum scores of PHQ-9, GAD-7, and VFQ-25, whereas there were significant differences in some subscales of the VFQ-25. We conclude that BSRC and SC patients show higher levels of depression and a reduced visual quality of life due to imminent loss of vision. Because depression and quality of life are adversely affected by lack of social contacts and functioning, psychological treatment should enable patients to maintain their independence and ability to social interaction. Psychosomatic care should be taken in account for the treatment of BSRC and SC.

Factor Analyses and Validity of the Transplant Evaluation Rating Scale (TERS) in a Large Sample of Lung Transplant Candidates.

OBJECTIVE: It is well known that the occurrence of mental disorders is more common in lung transplant candidates compared to the general population. After transplantation mental disorders may negatively affect quality of life, adherence to immunosuppressive medication, as well as overall survival. Therefore, the identification of patients at risk is of utmost importance and in Germany pre-transplant psychosocial evaluation of the patients is required. To ensure high quality and comparability of these assessments, the use of psychometrically sound instruments is recommended. We applied the Transplant Evaluation Rating Scale (TERS), a broadly used expert interview. Two research groups have detected a two-factor structure of the TERS in different transplant samples; however, with slightly different results. The present study investigated which of the models would fit best in our sample of lung transplant patients. Additionally, we assessed convergent and predictive validity of the best fitting model to evaluate its clinical usefulness. METHODS: Between 2016 and 2019, 390 lung transplant candidates were evaluated and included in the study. The median age was 53 years and 54% were male. TERS interviews were conducted by trained medical doctors and psychologists. The participants completed questionnaires assessing quality of life and levels of depression and anxiety. Transplant- and disease-specific variables (lung disease, listing date, oxygen use) were taken from the patient charts. Confirmatory factor analysis was used to test the two proposed TERS-models in the present sample. RESULTS: The two-factor structure of the TERS reported by Hoodin and Kalbfleisch fit our sample best, showing good psychometric properties. The factor "emotional sensitivity" was highly correlated with quality of life and measures of psychosocial health while the factor "defiance" correlated with obstructive lung disease and older age but not with quality of life. The two factors showed differential predictive validity with regard to time until listing and pulmonary-specific quality of life 1 year after transplantation. CONCLUSIONS: The two factors showed good psychometric properties, and differential convergent and predictive validity. However, further studies concentrating on the predictive value of the TERS and its factors regarding somatic outcomes (mortality, graft functioning) are required.

Effect of initial antifungal therapy on mortality among patients with bloodstream infections with different Candida species and resistance to antifungal agents: A multicentre observational study by the Turkish Fungal Infections Study Group.

This study aimed to describe the effect of initial antifungal therapy on patient mortality and to detail the current distribution and resistance patterns of Candida spp. among patients with candidaemia. A prospective observational study was performed among consecutive patients with candidaemia from 10 Turkish medical centres between January 2015 and November 2018. The primary outcome was 10-day mortality. Species were identified using MALDI-TOF/MS. A total of 342 patients with candidaemia were included, of which 175 (51.2%) were male and 68 (19.9%) were aged <18 years. The most common species were Candida albicans (47.4%), Candida parapsilosis (26.6%), Candida tropicalis (9.6%) and Candida glabrata (7.6%). Among all Candida spp., the 10-day case fatality rate (CFR) was 32.2%. The CFR was highest in patients with C. albicans (57.3%) and lowest in patients with C. parapsilosis (21.8%). The resistance rate to fluconazole was 13% in C. parapsilosis, with no significant effect on mortality. No resistance to echinocandins was detected. In the multivariate analysis, being in the ICU [OR = 2.1 (95% CI 1.32-3.57); P = 0.002], renal failure [OR = 2.4 (1.41-3.97); P = 0.001], total parenteral nutrition [OR = 2 (1.22-3.47); P = 0.006], C. albicans infection [OR = 1.7 (1.06-2.82); P = 0.027] and echinocandin as primary agent [OR = 0.6 (0.36-0.99); P = 0.047] were significantly associated with mortality. Candidaemia is a deadly infection. Fluconazole resistance is emerging, although it was not significantly related to mortality. Using an echinocandin as the primary agent could be life-saving.

Psychometric Properties of the German Version of the Pulmonary-Specific Quality-of-Life Scale in Lung Transplant Patients.

The Pulmonary-Specific Quality-of-Life Scale (PQLS) is a validated self-report questionnaire assessing health-related quality of life (HRQoL) in patients with end-stage lung disease awaiting lung transplantation. The aim of our study was to evaluate the psychometric properties of the German version of the PQLS. One hundred and forty patients awaiting lung transplantation (55% men) with a median age of 53 years [Interquartile range (IQR) 13] answered the PQLS. A group of the participants (n = 43) was evaluated again 1 year later after transplantation. A confirmatory factor analysis (CFA) of the PQLS was conducted to test the three-factor structure of the PQLS. We examined the internal consistency of the scales using Cronbach's α. Convergent validity was explored through correlations with generic measures of HRQoL [Short-Form 8 Health Survey (SF-8), 10-item quality of life (QoL) scale], measures of depression (nine-item Patient Health Questionnaire-Depression Scale), anxiety (Generalized Anxiety Scale), and measures of lung disease severity (supplemental oxygen use, stairway steps). In the group of 43 patients assessed before and after transplantation, sensitivity to change was explored. The CFA confirmed the three-factor model with an acceptable fit. The PQLS total and the three subscale scores "task interference," "psychological," and "physical" showed acceptable internal consistency. The PQLS and its subscales showed a significant negative correlation with the 10-item QoL measure and the physical component score of the SF-8, whereas the mental component score of the SF-8 showed a significant negative correlation only with the PQLS subscale "psychological." Negative correlation was found due to the opposed alignment of the PQLS compared to the 10-item QoL and the SF-8. Symptoms of depression and anxiety were significantly and positively correlated with the subscale "psychological." Measures of lung disease severity also exhibited a significant positive correlation with the subscales "task interference" and "physical" but not "psychological." In patients 1 year after a successful transplantation, the PQLS scores were significantly reduced by 50%. The three-factor structure of the PQLS could be replicated using CFA. The results indicate good reliability, validity, and sensitivity to change of the German version of the PQLS.

Baseline Dietary Restraint Predicts Negative Treatment Outcomes after 12 Months in Children and Adolescents with Obesity Participating in a Lifestyle Intervention.

OBJECTIVE: Current lifestyle interventions for children and adolescents with obesity often exclude patients with an eating pathology, leaving the impact of eating pathologies on treatment outcomes largely unconsidered. We investigated the predictive value of disordered eating symptoms on BMI z-score reduction in a sample of 111 German children and adolescents with overweight (90th percentile ≤ BMI < 97th percentile) and obesity (BMI > 97th percentile) aged 7-15 years in an outpatient lifestyle intervention program. METHODS: We defined a BMI z-score reduction of more than 5% after 12 months as a successful outcome. Disordered eating symptoms (i.e., dietary restraint, emotional eating, external eating, and binge eating) were assessed at baseline with the Eating Pattern Inventory (EPI-C) and the "bulimia" scale of the Eating Disorder Inventory (EDI-2). Covariates were: baseline z-BMI, age, gender, and maternal education level. RESULTS: Multiple regression analysis revealed that dietary restraint significantly predicted change in BMI z-scores between baseline and T1. Higher levels of dietary restraint were associated with a lower BMI z-score reduction between T0 and T1. To compare non-completers with completers on the 4 eating behavior scales, we used MANCOVA. At baseline, children who subsequently dropped out of the program prematurely showed significantly higher dietary restraint scores than children who completed the intervention, irrespectively of their gender, age, and BMI z-score at baseline and their mother's education level. DISCUSSION: Our results provide further evidence that the analysis of treatment processes in lifestyle intervention programs for children and adolescents with overweight and obesity should take into account a broader multidimensional approach including eating and dietary habits.

Effect of Interferon alfa-2a Treatment on Adaptive and Innate Immune Systems in Patients With Behçet Disease Uveitis.

Purpose: To investigate the effect of interferon alfa-2a on T regulatory (Treg) cells, T helper 17 (Th17) cells, and expression of Toll-like receptors (TLRs) in Behçet disease (BD) patients with uveitis. Methods: Twenty-seven patients who received interferon alfa-2a for active BD uveitis despite conventional immunomodulatory therapies and healthy controls were enrolled. Peripheral blood Treg and Th17 cell frequencies were determined by flow cytometry as gated cells for CD3+CD4+Foxp3+ and CD3+CD4+IL17A+, respectively. Th17 RAR-related orphan receptor (ROR)γt mRNA expression was verified by real-time PCR (RT-PCR). Treg and Th17 cell cytokines were detected by ELISA in the supernatant of short-term cell cultures. RT-PCR was used to assess expression of TLR-2, TLR-3, TLR-4, TLR-8, and TLR-9 using cDNA prepared from CD4+ T cells and monocytes. Results: Treg and Th17 cell frequencies and Th17 RORγt expression were significantly elevated, and IL-10 concentration in Treg cell supernatants was significantly lower in BD patients than in controls. Th17 IL-17, IL-6, IL-21, IL-22, IL-23, IFN-γ, and TNF-α concentrations were significantly higher and all TLR expressions were significantly elevated in patients. Interferon alfa-2a led to a significant reversal in Treg and Th17 cell frequencies, Th17 RORγt expression, Treg and Th17 cell cytokine production, and TLR expression by CD4+ T cells and monocytes. Conclusions: Despite a relative increase in Treg cells, impaired IL-10 production suggests that Treg dysfunction may play a role in induction of BD uveitis. Favorable effects of interferon alfa-2a may be associated with recovery of Treg cell function, suppression of Th17 cells, and reduced expression of TLRs on CD4+ T cells and monocytes.

The association of serum leptin levels with food addiction is moderated by weight status in adolescent psychiatric inpatients.

Leptin is essential for the control of energy homeostasis and eating behaviour. We investigated potential associations between serum leptin levels and food addiction in adolescent psychiatric inpatients (n = 228). The most frequent psychiatric diagnoses were mood disorders, anxiety disorders, and substance use disorders. More than three quarters of the study group suffered from more than one psychiatric disorder. Food addiction was assessed with the Yale Food Addiction Scale. Leptin was determined in serum. Analyses were conducted for the whole body weight range and for distinct weight categories to evaluate a potential impact of known nonlinearity between leptin levels and satiety due to leptin resistance in obese. A weak negative association between food addiction and leptin in normal weight patients (ß = -0.11, p = .022) was detected. In contrast, food addiction was associated with a significantly higher serum leptin (ß = 0.16. p = .038) in overweight patients. Food addiction in normal weight patients might be associated with restrained eating, previously shown to involve reduced leptin levels. The small positive association of food addiction with higher serum leptin in overweight patients might reflect leptin resistance and overeating.

Impact of the ST101 clone on fatality among patients with colistin-resistant Klebsiella pneumoniae infection.

Objectives: We describe the molecular characteristics of colistin resistance and its impact on patient mortality. Methods: A prospective cohort study was performed in seven different Turkish hospitals. The genotype of each isolate was determined by MLST and repetitive extragenic palindromic PCR (rep-PCR). Alterations in mgrB were detected by sequencing. Upregulation of pmrCAB, phoQ and pmrK was quantified by RT-PCR. mcr-1 and the genes encoding OXA-48, NDM-1 and KPC were amplified by PCR. Results: A total of 115 patients diagnosed with colistin-resistant K. pneumoniae (ColR-Kp) infection were included. Patients were predominantly males (55%) with a median age of 63 (IQR 46-74) and the 30 day mortality rate was 61%. ST101 was the most common ST and accounted for 68 (59%) of the ColR-Kp. The 30 day mortality rate in patients with these isolates was 72%. In ST101, 94% (64/68) of the isolates had an altered mgrB gene, whereas the alteration occurred in 40% (19/47) of non-ST101 isolates. The OXA-48 and NDM-1 carbapenemases were found in 93 (81%) and 22 (19%) of the total 115 isolates, respectively. In multivariate analysis for the prediction of 30 day mortality, ST101 (OR 3.4, CI 1.46-8.15, P = 0.005) and ICU stay (OR 7.4, CI 2.23-29.61, P = 0.002) were found to be significantly associated covariates. Conclusions: Besides ICU stay, ST101 was found to be a significant independent predictor of patient mortality among those infected with ColR-Kp. A significant association was detected between ST101 and OXA-48. ST101 may become a global threat in the dissemination of colistin resistance and the increased morbidity and mortality of K. pneumoniae infection.

Eating-related Psychopathology and Food Addiction in Adolescent Psychiatric Inpatients.

OBJECTIVE: Our aims were to investigate the relationship between food addiction and mental disorders including eating disorders (ED), eating-related psychopathology and body mass index-standard deviation score in a sample of adolescent psychiatric inpatients. METHODS: Food addiction was assessed with the Yale Food Addiction Scale (YFAS). Eating-related psychopathology was measured with the Three-Factor Eating Questionnaire (TFEQ). Psychiatric diagnoses were assessed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The sample consisted of n = 242 adolescent psychiatric inpatients, of which n = 37 (15.3%) met criteria for an ED. Multiple regression analysis was used to examine the association between YFAS symptom count, TFEQ scales and ED controlling for age and gender. RESULTS: Food addiction frequency was 16.5%, and the mean YFAS symptom count was 2.39 (SD: 1.60). In patients with food addiction, TFEQ scale scores were significantly higher than patients without food addiction. Frequency of ED was 42.9% in patients with and 9.9% in patients without food addiction. The TFEQ subscales disinhibition and hunger as well as diagnosis of ED were associated with YFAS symptom count. DISCUSSION: Food addiction in adolescent psychiatric inpatients occurs with rates higher than those seen in community samples of children, adolescents and adults. Food addiction might be associated with eating styles related to susceptibility to hunger and feelings of loss of control. The implications of high-YFAS scores in restricting-type anorexia nervosa warrant further investigations to explore which and how the respective items are interpreted in this ED subgroup. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

[Is nutritional obesity a substance use disorder?] / Alimentär bedingte Adipositas: eine Suchtkrankheit?

Today, food addiction has become an increasing area of research. Multiple studies aim to characterize individuals in terms of food addiction based on the assumption, that hyperpalatable foods rich of salt, sugar and fat may induce a cluster of behavioral changes that may resemble a substance use disorder, despite the fact that to date there is no evidence, that nutritional factors lead to an addictive eating-like behavior in humans. In this review article, we aim to introduce the basic experiments, that build the framework upon which food addiction is being investigated and to critically discuss the concept of food addiction.

Hair Cortisol Concentrations in Adolescent Girls with Anorexia Nervosa are Lower Compared to Healthy and Psychiatric Controls.

OBJECTIVE: In anorexia nervosa (AN) hypercortisolism has been described using urine, plasma and saliva samples as short-term markers for the hypothalamic-pituitary-adrenal (HPA)-axis. Here, for the first time, we analyse hair cortisol concentration (HCC) as a marker for long-term integrated cortisol secretion in female patients with AN compared to female healthy controls (HC) and female psychiatric controls (PC). METHODS: HCC was assessed in 22 female adolescent psychiatric inpatients with AN compared to 20 female HC and to 117 female PC of the same age range. For further analyses we examined the associations of age and body mass index (BMI) with HCC. RESULTS: Log HCC was lower in AN-patients compared to HC (p = 0.030). BMI-standard deviation scores (SDS) but not age correlated with log HCC (BMI-SDS: r = 0.19, bias corrected accelerated 95% confidence interval: [.04, .34], p = 0.015; age: r = 0.10, bias corrected accelerated 95% confidence interval: [-.07, .25], p = 0.213) when combining AN, HC and PC samples. DISCUSSION: We find lower HCC in AN, compared to HC and PC, respectively. Based on the relationship between HCC and BMI-SDS across AN, HC and PC, we argue that HCC might not capture endocrine alterations because of AN pathology-related processes but rather shows consistent relationships with BMI, which extent even to the very low range of BMI values, as present in AN patients. Alternatively, incorporation of cortisol into the hair follicle might have been compromised because of trophic hair follicle disturbances that had been reported in AN patients, previously. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Agmatine Reverses Sub-chronic Stress induced Nod-like Receptor Protein 3 (NLRP3) Activation and Cytokine Response in Rats.

The activation of Nod-like receptor protein 3 (NLRP3) has lately been implicated in stress and depression as an initiator mechanism required for the production of interleukin (IL)-1ß and IL-18. Agmatine, an endogenous polyamine widely distributed in mammalian brain, is a novel neurotransmitter/neuromodulator, with antistress, anxiolytic and antidepressant-like effects. In this study, we examined the effect of exogenously administered agmatine on NLRP3 inflammasome pathway/cytokine responses in rats exposed to restraint stress for 7 days. The rats were divided into three groups: stress, stress+agmatine (40 mg/kg; i.p.) and control groups. Agmatine significantly down-regulated the gene expressions of all stress-induced NLRP3 inflammasome components (NLRP3, NF-κB, PYCARD, caspase-1, IL-1ß and IL-18) in the hippocampus and prefrontal cortex (PFC) and reduced pro-inflammatory cytokine levels not only in both brain regions, but also in serum. Stress-reduced levels of IL-4 and IL-10, two major anti-inflammatory cytokines, were restored back to normal by agmatine treatment in the PFC. The findings of the present study suggest that stress-activated NLRP3 inflammasome and cytokine responses are reversed by an acute administration of agmatine. Whether antidepressant-like effect of agmatine can somehow, at least partially, be mediated by the inhibition of NLRP3 inflammasome cascade and relevant inflammatory responses requires further studies in animal models of depression.