Bromodeoxyuridine and the detection of neurogenesis

Bromodeoxyuridine (BrdU) is widely used for labeling dividing cells to determine their fate. In particular, the analysis of neurogenesis in the adult mammalian brain has made significant progress through the use of this technique. However; when using BrdU for labeling, there are several issues to consider in order to minimalize possible cytotoxicity or false-positive labeling. This current review summarizes methodological and technical aspects of BrdU administration and detection, compares alternative methods and gives recommendations on how to avoid labeling artifacts.     

T-wave oversensing by an implantable cardioverter defibrillator after successful ablation of idiopathic ventricular fibrillation

Focal ablation of trigger premature ventricular complexes (PVCs) from the Purkinje system helped to suppress idiopathic ventricular fibrillation (VF) in an athlete who had suffered from frequent appropriate shock therapies. However, only a few days after successful ablation T-wave oversensing occurred during exercise and resulted in repetitive distressing defibrillator shocks. Despite lack of any changes on the surface ECG, the endocardially recorded electrogram revealed an unfavorable ratio of R-to-T-wave amplitude predisposing to double counting with accelerated heart rates. This case illustrates that T-wave oversensing may complicate the clinical course after successful ablation of malignant Purkinje ectopy.     

B-chronic lymphocytic leukemia cells and other B cells can produce granzyme B and gain cytotoxic potential after interleukin-21-based activation

B cells currently are not viewed as being capable of producing granzyme B or being cytotoxic. We found that B-chronic lymphocytic leukemia (B-CLL) cells treated with interleukin-21 (IL-21) produce low levels of granzyme B. The addition of either CpG oligodeoxynucleotide (ODN) or anti-B-cell-receptor antibody (anti-BCR) to IL-21 results in enhanced production of functional granzyme B by B-CLL cells. B-CLL cells treated with IL-21 and CpG ODN undergo apoptosis and are able to induce apoptosis of untreated bystander B-CLL cells. This effect can be inhibited by anti-granzyme B antibody. Benign human B cells, Epstein-Barr virus (EBV)-transformed lymphoblasts, and many standard lymphoma cell lines produce high levels of granzyme B in response to IL-21 and anti-BCR. Our results suggest that the ability to induce production of functional granzyme B by B cells could open new approaches to the therapy of B-CLL and other B-cell malignancies. Our findings also have significant implications for our understanding of the role of B cells for immune regulation and for a variety of immune phenomena, including cancer immunity, autoimmunity, and infectious immunity.     

Developing antenatal classes for women with HIV infection

As numbers of new HIV infections rise, innovative means of healthcare delivery for this patient group are being sought. This article describes the running of antenatal classes for pregnant women with HIV infection in a south-east London hospital, which aim to reduce mother-to-child HIV transmission. Led by a community-based clinical nurse specialist, the initiative adopts a multidisciplinary team approach.     

Neurolisteriosis mimicking herpes simplex encephalitis in an immunocompromized patient

Brain MRI was performed in an immunocompromized febrile and lethargic patient, revealing an asymmetric bilateral temporal lobe involvement, strongly suggestive of herpetic encephalitis. Nevertheless, PCR in CSF for Listeria monocytogens was positive. This case implies that Listeria might be considered in patients with clinical and imaging suspicion of herpetic encephalitis.     

Maternal serum concentrations of BDNF and depression in the perinatal period

There is accumulating evidence that a deficiency in brain-derived neurotrophic factor (BDNF) plays a critical role in the pathophysiology of depression. This is in line with the postulate that low BDNF levels in serum are associated with depression. However, the regulation of maternal BDNF serum levels in the perinatal period, and its relationship to maternal depression is unknown. In this study, serum BDNF concentrations were measured in 40 pregnant (follow-up: 30th and 37th week of gestation, 1 week and 8 weeks after childbirth) and 40 non-pregnant women (20-40 years old). The Edinburgh Postnatal Depression Scale (EPDS) was assessed in all subjects at all time points. Maternal serum levels of BDNF were markedly decreased, both before and after childbirth (median: <30% of non-pregnant controls). BDNF correlated with decreased Serotonin (5-HT) levels in serum (r>0.6 and p<0.001 at all time points). In contrast, there was no association with altered estrogen, progesterone, dehydroepiandrosterone or cortisol concentrations in serum. There were significantly higher cortisol levels in cases of maternal depression (EPDS scores>9 points) than in cases without depression. There was a trend to a decrease of BDNF and 5-HT levels in cases of maternal depression (as compared to cases without depression), but this was not significant. In conclusion, we demonstrate that women display markedly decreased BDNF serum levels before and after childbirth. This phenomenon might reflect an increased risk for the development of mood disorders in the perinatal period. However, the individual serum concentration of BDNF alone did not predict maternal depression in our study.     

Bictegravir/emtricitabine/tenofovir alafenamide in older individuals with HIV: Results of a 96-week,phase 3b,open-label,switch trial in virologically suppressed people ≥65 years of age

Objectives

Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is an effective treatment for HIV-1 infection; however, clinical trial data in older people living with HIV (PLWH) are lacking. The primary 24-week and secondary 48-week analyses of study GS-US-380-4449 (NCT03405935), which assessed the efficacy and safety of switching to B/F/TAF in older PLWH, have been published. Here we report the results of the final 96-week analyses from the study.

Methods

In this 96-week, phase 3b, open-label, single-arm trial, virologically suppressed PLWH aged ≥65 years switched from elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or a tenofovir disoproxil fumarate-based regimen to B/F/TAF. Viral suppression, resistance, immune response, safety, tolerability and adherence were evaluated through week 96.

Results

Of 90 participants screened, 86 were enrolled and switched to B/F/TAF. No participants had HIV-1 RNA ≥50 copies/ml (by FDA Snapshot algorithm) at weeks 72 or 96; virologic suppression rates were 94.2% (81/86; 95% CI 87.0–98.1) and 74.4% (64/86; 95% CI 63.9–83.2), respectively. No treatment-emergent resistance was observed, and CD4 counts remained stable. There were no study drug-related serious adverse events. Three participants experienced drug-related treatment-emergent adverse events that led to premature drug discontinuation. There were no clinically relevant changes from baseline to week 96 in fasting lipid parameters, and the median change in body weight at week 96 was 0.0 kg (IQR −2.3, 2.0). Median self-reported adherence was 100% (IQR 100–100%).

Conclusions

Switching to B/F/TAF is an effective long-term option for virologically suppressed adults ≥65 years of age, with favourable safety and tolerability profiles in this population.