Millifluidic magnetophoresis-based chip for age-specific fractionation: evaluating the impact of age on metabolomics and gene expression in yeast.

A novel millifluidic process introduces age-based fractionation of S. pastorianus var. carlsbergensis yeast culture through magnetophoresis. Saccharomyces yeast is a model organism for aging research used in various industries. Traditional age-based cell separation methods were labor-intensive, but techniques like magnetic labeling have eased the process by being non-invasive and scalable. Our approach introduces an age-specific fractionation using a 3D-printed millfluidic chip in a two-step process, ensuring efficient cell deflection in the magnetic field and counteracting magnetic induced convection. Among various channel designs, the pinch-shaped channel proved most effective for age differentiation based on magnetically labeled bud scar numbers. Metabolomic analyses revealed changes in certain amino acids and increased NAD+ levels, suggesting metabolic shifts in aging cells. Gene expression studies further underlined these age-related metabolic changes. This innovative platform offers a high-throughput, non-invasive method for age-specific yeast cell fractionation, with potential applications in industries ranging from food and beverages to pharmaceuticals.

Early detection and integrated care for adolescents and young adults with psychotic disorders: the ACCESS III study.

OBJECTIVE: The objective of the study was to investigate whether a combined intervention composed of early detection plus integrated care (EDIC) enhances outcomes in patients with early psychosis compared to standard care (SC). METHODS: ACCESS III is a prospective non-randomized historical control design 1-year study examining the efficacy of EDIC (n = 120) vs. SC (n = 105) in patients aged 12-29 years. Primary outcome was the rate of ≥6 months combined symptomatic and functional remission. Additional outcomes comprised the reduction of DUP and course of psychopathology, functioning, quality of life, and satisfaction with care. RESULTS: In observed cases, 48.9% in the EDIC and 15.2% in the SC group reached the primary endpoint. Remission was predicted by EDIC (OR = 6.8, CI: 3.15-14.53, P < 0.001); younger age predicted non-remission (OR = 1.1, CI: 1.01-1.19, P = 0.038). Linear regressions indicated a reduction of DUP in EDIC (P < 0.001), but not in SC (P = 0.41). MMRMs showed significantly larger improvements in PANSS positive (P < 0.001) and GAF (P < 0.01) scores in EDIC vs. SC, and in EDIC over time in CGI-Severity (P < 0.001) and numerically in Q-LES-Q-18 (P = 0.052). CONCLUSIONS: EDIC lead to significantly higher proportions of patients achieving combined remission. Moderating variables included a reduction of DUP and EDIC, offering psychotherapeutic interventions.

Clonal variegation and dynamic competition of leukemia-initiating cells in infant acute lymphoblastic leukemia with MLL rearrangement.

Distinct from other forms of acute lymphoblastic leukemia (ALL), infant ALL with mixed lineage leukemia (MLL) gene rearrangement, the most common leukemia occurring within the first year of life, might arise without the need for cooperating genetic lesions. Through Ig/TCR rearrangement analysis of MLL-AF4+ infant ALL at diagnosis and xenograft leukemias from mice transplanted with the same diagnostic samples, we established that MLL-AF4+ infant ALL is composed of a branching subclonal architecture already at diagnosis, frequently driven by an Ig/TCR-rearranged founder clone. Some MLL-AF4+ clones appear to be largely quiescent at diagnosis but can reactivate and dominate when serially transplanted into immunodeficient mice, whereas other dominant clones at diagnosis can become more quiescent, suggesting a dynamic competition between actively proliferating and quiescent subclones. Investigation of paired diagnostic and relapse samples suggested that relapses often occur from subclones already present but more quiescent at diagnosis. Copy-number alterations identified at relapse might contribute to the activation and expansion of previously quiescent subclones. Finally, each of the identified subclones is able to contribute to the diverse phenotypic pool of MLL-AF4+ leukemia-propagating cells. Unraveling of the subclonal architecture and dynamics in MLL+ infant ALL may provide possible explanations for the therapy resistance and frequent relapses observed in this group of poor prognosis ALL.

Mutual influence of posttraumatic stress disorder symptoms and chronic pain among injured accident survivors: a longitudinal study.

The relationship between acute stress disorder (ASD), posttraumatic stress disorder symptoms (PTSD), and chronic pain was investigated in a longitudinal study of injured accident victims (N = 323, 64.7% men). Assessments took place 5 days (T1), 6 (T2) months, and 12 (T3) months postaccident. Relations between pain and posttraumatic stress symptoms were tested by structural equation modeling. Subjects diagnosed with full or subsyndromal PTSD at T2 and at T3 (14 and 19%) reported significantly higher pain intensity. Cross-lagged panel analysis yielded a mutual maintenance of pain intensity and ASD or PTSD symptoms across T2. Across the second half year, PTSD symptoms impacted significantly on pain but not vice versa. Clinicians need to pay careful attention to PTSD symptoms in accident survivors suffering from chronic pain.

Parents' mental health after the birth of an extremely preterm child: a comparison between bereaved and non-bereaved parents.

OBJECTIVE: To assess the impact of extremely preterm birth (24-26 weeks of gestation) on the mental health of parents two to six years after delivery, and to examine potential differences in post-traumatic growth between parents whose newborn infant died and those whose child survived. METHOD: A total of 54 parents who had lost their newborn and 38 parents whose preterm child survived were assessed by questionnaires with regard to depression and anxiety (HADS) and post-traumatic growth (PTGI). RESULTS: Neither group of parents had clinically relevant levels of depression and anxiety. Mothers showed higher levels of anxiety than fathers. Bereaved parents with no other, living child reported higher levels of depression than bereaved parents with one or more children. Mothers reported higher post-traumatic growth compared to fathers. In particular, bereaved mothers experienced the value and quality of their close social relationships more positively compared to the non-bereaved parents. CONCLUSION: In the long term, bereaved and non-bereaved parents cope reasonably well with an extremely preterm birth of a child. Post-traumatic growth appears to be positively related to bereavement, particularly in mothers.

[MRI staging of prostate cancer with the combined endorectal body phased-array coil and histologic correlation]. / Kernspintomographisches Staging des Prostatakarzinoms mittels kombinierter Endorektal-Body-Phased-Array-Spule und histopathologische Korrelation.

PURPOSE: Evaluation of the diagnostic value of the combined endorectal body-phased array technique regarding the staging of prostate cancers, especially in the differentiation between stages T2 and T3. MATERIALS AND METHODS: Forty-two patients with biopsy-proven or clinically suspected prostate cancer were examined on a 1.5 T scanner (Siemens, Symphony) prior to radical prostatectomy. T (2)-weighted TSE (axial, coronal) and T (2)-weighted FSE (axial) sequences were obtained with and without fat suppression. After application of 0.2 mmol/kg body-weight Gd-DTPA, T (1)-weighted GRE sequences were obtained using dynamic MRI. All images were prospectively interpreted by two observers. The MR images were correlated with the histopathological findings of wide-area sections of prostatectomy specimens. RESULTS: For the detection of extracapsular growth and seminal vesicle infiltration (T2 versus T3) the accuracy was between 94 % and 97 % (sensitivity 100 %, specificity between 87 % and 93 %, observer 1 and 2). In two cases with a histologically proven stadium pT2b, observer 1 had diagnosed stadium pT3a. The results of observer 2 were marginally better in only one case, which was histologically proven to be pT2b and overstaged as pT3a. MRI did not lead to under-staging of a single tumor with regard to the differentiation between T2 and T3. Overall, the staging of the tumor stages (T1 - T4) was correct in 25 of 33 cases (75 %). The dynamic MRI showed no improvement regarding sensitivity (100 %) and specificity (62 %) and achieved a staging accuracy of only 75 %. CONCLUSION: MRI performed with a combination of a pelvic phased-array coil (PPA) and integrated endorectal coil plays a significant role in the preoperative staging of prostate cancer. However, differentiation between capsular infiltration (T2) and penetration (T3) as well as evaluation of the seminal bladder (T3b) seem to be difficult.

Exposure to pulsed high-frequency electromagnetic field during waking affects human sleep EEG.

The aim of the study was to investigate whether the electromagnetic field (EMF) emitted by digital radiotelephone handsets affects brain physiology. Healthy, young male subjects were exposed for 30 min to EMF (900 MHz; spatial peak specific absorption rate 1 W/kg) during the waking period preceding sleep. Compared with the control condition with sham exposure, spectral power of the EEG in non-rapid eye movement sleep was increased. The maximum rise occurred in the 9.75-11.25 Hz and 12.5-13.25 Hz band during the initial part of sleep. These changes correspond to those obtained in a previous study where EMF was intermittently applied during sleep. Unilateral exposure induced no hemispheric asymmetry of EEG power. The present results demonstrate that exposure during waking modifies the EEG during subsequent sleep. Thus the changes of brain function induced by pulsed high-frequency EMF outlast the exposure period.

Subjective response to antipsychotic drugs.

Sixty-three newly admitted schizophrenic patients were given a test dose of thiothixene and their subjective response was recorded by a technician blind to clinical ratings. All patients were then treated wih thiothixene in an active milieu setting. Patients varied widely in their subjective responses. An initial dysphoric response was a powerful predictor of both immediate and eventual drug refusal. Before treatment, dysphoric responders tended to be less symptomatic and did significantly better on the Continuous Performance Test. Dysphoric responders experienced significantly more extrapyramidal symptoms following the test dose. Some dysphoric responders did have a good outcome when treated with very low doses. We recommend that patients with a history of dysphoric response be given a very low dose initially.