Amyloid-β alters ongoing neuronal activity and excitability in the frontal cortex

The effects of amyloid-β on the activity and excitability of individual neurons in the early and advanced stages of the pathological progression of Alzheimer's disease remain unknown. We used in vivo intracellular recordings to measure the ongoing and evoked activity of pyramidal neurons in the frontal cortex of APPswe/PS1dE9 transgenic mice and age-matched nontransgenic littermate controls. Evoked excitability was altered in both transgenic groups: neurons in young transgenic mice displayed hypoexcitability, whereas those in older transgenic mice displayed hyperexcitability, suggesting changes in intrinsic electrical properties of the neurons. However, the ongoing activity of neurons in both young and old transgenic groups showed signs of hyperexcitability in the depolarized state of the membrane potential. The membrane potential of neurons in old transgenic mice had an increased tendency to fail to transition to the depolarized state, and the depolarized states had shorter durations on average than did controls. This suggests a combination of both intrinsic electrical and synaptic dysfunctions as mechanisms for activity changes at later stages of the neuropathological progression.     

Uteroplacental circulation, preeclampsia, and maternal abdominal aortic stiffness in normal and compromised pregnancies

A study of 82 normal and 60 compromised pregnant women who were identified by uterine artery Doppler flow waveform systolic/diastolic ratio >95th percentile (increased peripheral resistance) was carried out to examine the elastic properties of the maternal abdominal aorta (AA). An aortic stiffness index (SI) was measured between 18 and 40 weeks at four-weekly intervals with a phase-locked loop ultrasound technique to estimate the aortic systolic and diastolic diameters and their correlation with blood pressure. In the normal group, the aortic systolic and diastolic diameters, as well as the SI, increased with the maternal age. In the compromised group, aortic diameter and blood pressure were normal, but the SI during the early second trimester was increased. Twenty-two women from the compromised group with an SI above the 95th percentile for their age had a significantly higher prevalence of preeclampsia in comparison with women with a normal SI (P<0.001). The aortic SI was significantly higher in severe than in mild preeclampsia. This study demonstrates that stiffness of the AA is increased in pregnant women with preeclampsia and that a progressive increase of the SI in serial studies is associated with severity of the disease. Aberrant hemodynamic adaptation in preeclampsia seems to include increased stiffness of the larger artery besides high resistance in small peripheral arteries.     

Glucose regulates cyclin D2 expression in quiescent and replicating pancreatic β-cells through glycolysis and calcium channels

Understanding the molecular triggers of pancreatic β-cell proliferation may facilitate the development of regenerative therapies for diabetes. Genetic studies have demonstrated an important role for cyclin D2 in β-cell proliferation and mass homeostasis, but its specific function in β-cell division and mechanism of regulation remain unclear. Here, we report that cyclin D2 is present at high levels in the nucleus of quiescent β-cells in vivo. The major regulator of cyclin D2 expression is glucose, acting via glycolysis and calcium channels in the β-cell to control cyclin D2 mRNA levels. Furthermore, cyclin D2 mRNA is down-regulated during S-G(2)-M phases of each β-cell division, via a mechanism that is also affected by glucose metabolism. Thus, glucose metabolism maintains high levels of nuclear cyclin D2 in quiescent β-cells and modulates the down-regulation of cyclin D2 in replicating β-cells. These data challenge the standard model for regulation of cyclin D2 during the cell division cycle and suggest cyclin D2 as a molecular link between glucose levels and β-cell replication.     

Humoral serological response to the BNT162b2 vaccine is abrogated in lymphoma patients within the first 12 months following treatment with anti-CD2O antibodies

Patients with lymphoma, especially those treated with anti-CD20 monoclonal antibodies, suffer high COVID-19-associated morbidity and mortality. The goal of this study was to assess the ability of lymphoma patients to generate a sufficient humoral response after two injections of BNT162b2 Pfizer vaccine and to identify factors influencing the response. Antibody titers were measured with the SARS-CoV-2 IgG II Quant (Abbott^©) assay in blood samples drawn from lymphoma patients 4±2 weeks after the second dose of vaccine. The cutoff for a positive response was set at 50 AU/mL. Positive serological responses were observed in 51% of the 162 patients enrolled in this cross-sectional study. In a multivariate analysis, an interval of <12 months between the last anti-CD20 monoclonal antibody dose and the second vaccine dose (odds ratio=31.3 [95% confidence interval: 8.4-116.9], P<0.001) and presence of active lymphoma (odds ratio=4.2 (95% confidence interval: 2.1-8.2), P=0.006) were identified as negative response predictors. The rate of seropositivity increased from 3% in patients vaccinated within 45 days after the last monoclonal antibody administration to 80% in patients vaccinated >1 year after this therapy. The latter percentage was equal to that of patients never exposed to monoclonal antibodies. In conclusion, lymphoma patients, especially those recently treated with anti- CD20 monoclonal antibodies, fail to develop sufficient humoral response to BNT162b2 vaccine. While a serological response is not the only predictor of immunity, its low level could make this population more vulnerable to COVID-19, which implies the need for a different vaccination schedule for such patients.     

Characteristic diameter pulse waveform patterns of the inferior vena cava in fetuses with abnormalities of cardiac structure

BACKGROUND: Changes in the vessel lumen diameter pulse waveform closely follow changes in the transmural pressure pulse waveform. AIM: To study diameter pulse waveform recorded noninvasively from the fetal inferior vena cava (IVC) in fetuses with cardiac abnormality. STUDY DESIGN: A paired ultrasonic phase-locked echo tracking system with a high sampling frequency (3000 Hz) was used to follow the movement of diametrically opposite points of the IVC. The lumen was measured as the interval between these points. SUBJECTS: We studied 80 normal fetuses (20 to 40 weeks) and 11 fetuses with cardiac abnormality. RESULTS: The four component waves of the IVC diameter pulse waveform (A, X, V, Y) were identified and measured in the fetal recording. In the normal group, the A and V values increased linearly with advancing gestation. There was an increase in the depth of X and Y descents. Each cardiac abnormality produced characteristic changes in the A, X, V and Y waves of the IVC diameter pulse waveform. The most impressive IVC diameter pulse waveform pattern in fetal cardiac abnormality was the depth of the X descent from the A crest to X trough. In the circumstance of pulmonary stenosis, the A wave was large and prominent (deeper X descent, high pulsatility waveform). In the presence of a dilated right ventricle, or an incompetent tricuspid valve, the X descent was shallow (low pulsatility waveform). CONCLUSION: The fetal IVC diameter pulse waveform can be simply recorded. The high pulsatility waveform may result from increased end-diastolic pressure with a consequent increased resistance to flow into the ventricle from the atrium. The low pulsatility waveform may indicate depressed myocardial function.     

Biofeedback, Brief Psychotherapy and Tension Headache

SYNOPSIS
The present study was performed to compare the effectiveness of broadly-based biofeedback and brief eclectic psychotherapy in alleviating tension headache. Twenty-four patients diagnosed as suffering from this disorder were randomly assigned to one of four conditions: biofeedback, brief psychotherapy, biofeedback plus brief psychotherapy and waiting-list control. Results indicated the equivalent effectiveness of the three active treatments in ameliorating various behavioral and psychophysiological aspects of tension headache. Contrary to expectation, broad-gauged biofeedback produced more psychological gains than brief eclectic psychotherapy, The behavioral and psychophysiological findings are discussed in terms of a shared symptom-removal focus, whereas the unexpected psychological findings are considered in light of headache patients' characteristic resistance to the psychological explanations of their illness afforded by psychotherapy.     

A new cryptic virus belonging to the family Partitiviridae was found in watermelon co-infected with Melon necrotic spot virus

A novel virus was detected in watermelon plants (Citrullus lanatus Thunb.) infected with Melon necrotic spot virus (MNSV) using SOLiD next-generation sequence analysis. In addition to the expected MSNV genome, two double-stranded RNA (dsRNA) segments of 1,312 and 1,118 bp were also identified and sequenced from the purified virus preparations. These two dsRNA segments encode two putative partitivirus-related proteins, an RNA-dependent RNA polymerase (RdRP) and a capsid protein, which were sequenced. Genomic-sequence analysis and analysis of phylogenetic relationships indicate that these two dsRNAs together make up the genome of a novel Partitivirus. This virus was found to be closely related to the Pepper cryptic virus 1 and Raphanus sativus cryptic virus. It is suggested that this novel virus putatively named Citrullus lanatus cryptic virus be considered as a new member of the family Partitiviridae.