Intermittierendes Fasten – Was gibt es Neues aus der Wissenschaft?

Die Diabetologie - Übergewicht und Adipositas erhöhen die Risiken für Stoffwechselstörungen und können zu einem Typ-2-Diabetes führen. Deshalb stellen die Behandlung...     

Choline-releasing glycerophosphodiesterase EDI3 drives tumor cell migration and metastasis

Metastasis from primary tumors remains a major problem for tumor therapy. In the search for markers of metastasis and more effective therapies, the tumor metabolome is relevant because of its importance to the malignant phenotype and metastatic capacity of tumor cells. Altered choline metabolism is a hallmark of cancer. More specifically, a decreased glycerophosphocholine (GPC) to phosphocholine (PC) ratio was reported in breast, ovarian, and prostate cancers. Improved strategies to exploit this altered choline metabolism are therefore required. However, the critical enzyme cleaving GPC to produce choline, the initial step in the pathway controlling the GPC/PC ratio, remained unknown. In the present work, we have identified the enzyme, here named EDI3 (endometrial differential 3). Purified recombinant EDI3 protein cleaves GPC to form glycerol-3-phosphate and choline. Silencing EDI3 in MCF-7 cells decreased this enzymatic activity, increased the intracellular GPC/PC ratio, and decreased downstream lipid metabolites. Downregulating EDI3 activity inhibited cell migration via disruption of the PKCα signaling pathway, with stable overexpression of EDI3 showing the opposite effect. EDI3 was originally identified in our screening study comparing mRNA levels in metastasizing and nonmetastasizing endometrial carcinomas. Both Kaplan-Meier and multivariate analyses revealed a negative association between high EDI3 expression and relapse-free survival time in both endometrial (P < 0.001) and ovarian (P = 0.029) cancers. Overall, we have identified EDI3, a key enzyme controlling GPC and choline metabolism. Because inhibition of EDI3 activity corrects the GPC/PC ratio and decreases the migration capacity of tumor cells, it represents a possible target for therapeutic intervention.     

Systematic review and meta-analysis of preterm birth and later systolic blood pressure

Lower birth weight because of fetal growth restriction is associated with higher blood pressure later in life, but the extent to which preterm birth (<37 completed weeks' gestation) or very low birth weight (<1500 g) predicts higher blood pressure is less clear. We performed a systematic review of 27 observational studies that compared the resting or ambulatory systolic blood pressure or diagnosis of hypertension among children, adolescents, and adults born preterm or very low birth weight with those born at term. We performed a meta-analysis with the subset of 10 studies that reported the resting systolic blood pressure difference in millimeters of mercury with 95% CIs or SEs. We assessed methodologic quality with a modified Newcastle-Ottawa Scale. The 10 studies were composed of 1342 preterm or very low birth weight and 1738 term participants from 8 countries. The mean gestational age at birth of the preterm participants was 30.2 weeks (range: 28.8-34.1 weeks), birth weight was 1280 g (range: 1098-1958 g), and age at systolic blood pressure measurement was 17.8 years (range: 6.3-22.4 years). Former preterm or very low birth weight infants had higher systolic blood pressure than term infants (pooled estimate: 2.5 mm Hg [95% CI: 1.7-3.3 mm Hg]). For the 5 highest quality studies, the systolic blood pressure difference was slightly greater, at 3.8 mm Hg (95% CI: 2.6-5.0 mm Hg). We conclude that infants who are born preterm or very low birth weight have modestly higher systolic blood pressure later in life and may be at increased risk for developing hypertension and its sequelae.     

Electrical stimulation site influences the spatial distribution of motor units recruited in tibialis anterior

Objective

To compare the spatial distribution of motor units recruited in tibialis anterior (TA) when electrical stimulation is applied over the TA muscle belly versus the common peroneal nerve trunk.

Methods

Electromyography (EMG) was recorded from the surface and from fine wires in superficial and deep regions of TA. Separate M-wave recruitment curves were constructed for muscle belly and nerve trunk stimulation.

Results

During muscle belly stimulation, significantly more current was required to generate M-waves that were 5% of the maximal M-wave (M_max; M_5%max), 50% M_max (M_50%max) and 95% M_max (M_95%max) at the deep versus the superficial recording site. In contrast, during nerve trunk stimulation, there were no differences in the current required to reach M_5%max, M_50%max or M_95%max between deep and superficial recording sites. Surface EMG reflected activity in both superficial and deep muscle regions.

Conclusions

Stimulation over the muscle belly recruited motor units from superficial to deep with increasing stimulation amplitude. Stimulation over the nerve trunk recruited superficial and deep motor units equally, regardless of stimulation amplitude.

Significance

These results support the idea that where electrical stimulation is applied markedly affects how contractions are produced and have implications for the interpretation of surface EMG data.     

Neisseria gonorrhoeae with high-level resistance to azithromycin: case report of the first isolate identified in the United States

We report on the first Neisseria gonorrhoeae isolate in the United States identified with high-level resistance to azithromycin. This report discusses the epidemiologic case investigation, the molecular studies of resistance-associated mutations and N. gonorrhoeae multiantigen sequence typing, and challenges posed by emerging gonococcal antimicrobial resistance.     

Blood pressure tracking in children and adolescents

Background

High blood pressure is a major risk factor for cardiovascular disease. Blood pressure tracking could help to identify individuals with potential hypertension. Therefore, we have asked whether or not tracking was of predictive value for the development of hypertension in early life.

Methods

Blood pressure was routinely measured in 13,261 children and adolescents in outpatient clinics as well as during hospitalization. In one analysis, 568 individuals with elevated and normotensive blood pressure values were evaluated after 2, 4, and 6 years of follow-up. In a second analysis, 2,157 individuals with normotensive blood pressure were examined in a paired t test.

Results

The follow-up analysis showed a significant tracking effect. However, the Pearson correlation coefficients of the systolic and diastolic blood pressure standard deviation scores (SDS) decreased over time. Upon the follow-up after 6 years, 35.6 % of the children and adolescents with elevated blood pressure values remained in the elevated range group. Of the children within the normotensive blood pressure range, 80.4 % remained normotensive after 6 years. Children with normotensive blood pressure showed a stronger tracking than those who had had one hypertensive blood pressure reading. Children with higher body mass index (BMI) at follow-up changed blood pressure SDS track from initially normal to higher blood pressure values.

Conclusions

Blood pressure tracking in children and adolescents is moderate. We conclude that the predictive power of a single hypertensive blood pressure measurement during a single visit is rather small, and thus repetitive measurements across several consecutive visits are necessary.     

Seroprevalence of anti-N-methyl-d-aspartate receptor antibodies in women with ovarian teratoma

Recently antibodies against neuronal receptors have been identified as cause of a new type of encephalitis. The anti-N-methyl-d-aspartate receptor (anti-NMDA-R) encephalitis is the prototype of these disorders. Patients have a high incidence of teratomata. Removal of teratoma is considered the essential treatment of anti-NMDA-R encephalitis. Here, we aimed to investigate whether neurologically asymptomatic individuals suffering from ovarian teratomata may have positive anti-NMDA-R antibodies to be detected by an established assay. Over a time period of 15 months, all patients suffering from ovarian teratomata without neurological symptoms were included in this prospective study. Twenty consecutive patients were pair matched to patients with other benign ovarian disease and healthy controls. Preoperatively, patients had a gynaecological examination, transvaginal ultrasound, neurological examination and determination of anti-NMDA-R antibodies. None of the patients or controls presented with neurological symptoms. All tumours could be removed completely by laparoscopy. Anti-NMDA-R antibodies were absent in the group of patients with teratomata as well as in patients with benign ovarian tumours and healthy controls. Testing for anti-NMDA-R antibodies revealed negative findings in well-characterised patients with ovarian teratomata lacking neurological symptoms. Our data support the current clinical practice that a systematic screening for anti-NMDA-R antibodies in teratoma patients is not indicated.