The ventral tegmental area revisited: is there an electrophysiological marker for dopaminergic neurons?

The ventral tegmental area (VTA) and in particular VTA dopamine (DA) neurons are postulated to play a central role in reward, motivation and drug addiction. However, most evidence implicating VTA DA neurons in these functions is based on indirect electrophysiological characterization, rather than cytochemical identification. These physiological criteria were first established in the substantia nigra pars compacta (SNc), but their validity in the VTA is uncertain. In the current study we found that while 88 ± 2% of SNc neurons labelled by the neuronal marker NeuN were co-labelled for the catecholamine enzyme tyrosine hydroxylase (TH), a much smaller percentage (55 ± 2%) of VTA neurons co-expressed TH. In addition, using in vitro whole-cell recordings we found that widely accepted physiological criteria for VTA DA neurons, including the hyperpolarization-activated inwardly rectifying non-specific cation current ( I _h), spike duration, and inhibition by DA D2 receptor agonists, do not reliably predict the DA content of VTA neurons. We could not distinguish DA neurons from other VTA neurons by size, shape, input resistance, I _h size, or spontaneous firing rate. Although the absence of an I _h reliably predicted that a VTA neuron was non-dopaminergic, and I _h(−) neurons differ from I _h(+) neurons in firing rate, interspike interval (ISI) standard deviation, and ISI skew, no physiological property examined here is both sensitive and selective for DA neurons in the VTA. We conclude that reliable physiological criteria for VTA DA neuron identification have yet to be determined, and that the criteria currently being used are unreliable.     

The prognostic value of Ki67 immunostaining in non-Hodgkin's lymphoma

The monoclonal antibody Ki67 recognizes an antigen expressed in all phases of the cell cycle except Go. It has been used in 141 biopsies from 138 patients with non-Hodgkin's lymphoma to identify proliferating cells in histological sections. A Ki67 index (the number of Ki67 positive tumour cells divided by the sum of Ki67 positive and negative tumour cells) has been derived by counting 1000 cells in each case. A correction for the presence of non-tumour cells has been incorporated by counting non-tumour cells in serial sections stained with a panel of other antibodies. A very strong correlation between a low Ki67 index (less than 20 per cent) and low grade histology and a high Ki67 index (greater than 20 per cent) and high grade histology was found (Chi2 = 98.0). Ninety-one patients could be analysed for survival and those with low grade lymphoma (n = 38) who had a relatively high Ki67 index (greater than 5 per cent) had a worse survival than those with an index of less than 5 per cent (p less than 0.05). In contrast, there was a trend for those patients with high grade disease with a very high Ki67 index (greater than 80 per cent) to have a better survival than those with a lower index (less than 80 per cent). The patients with high grade disease who achieved complete remission or good partial remission and had a Ki67 index of less than 80 per cent were more likely to relapse than those with an index of greater than 80 per cent (p less than 0.04). These findings could not be explained by the effect of other prognostic factors such as age, stage, or serum albumin. While the use of Ki67 immunostaining has potential drawbacks, it appears to be a simple and reproducible method of determining a tumour proliferative index which provides relevant clinical data.     

Testing human sera for antibodies against avian influenza viruses: Horse RBC hemagglutination inhibition vs. microneutralization assays

BACKGROUND: The hemagglutination inhibition (HI) assay is a frequently used method to screen human sera for antibodies against influenza A viruses. Because HI has relatively poor sensitivity in detecting antibodies against avian influenza A strains, a more complicated microneutralization (MN) assay is often preferred. Recent research suggests that the sensitivity of the HI assay can be improved by switching from the traditionally used turkey, guinea pig, human, or chicken RBCs to horse RBCs. OBJECTIVE: To evaluate the performance of the horse RBC HI when screening for human antibodies against avian influenza types H3, H4, H5, H6, H7, H9, H11, and H12. STUDY DESIGN: We evaluated the reproducibility of horse RBC HI and its agreement with MN results using sera from people exposed or not exposed to wild and domestic birds. RESULTS: The horse RBC HI assay had high reliability (90%-100%) and good agreement with MN assay results (52%-100%). CONCLUSION: The horse RBC HI assay is reliable, less expensive, less complex, and faster than the MN assay. While MN will likely remain the gold standard serologic assay for avian viruses, the horse RBC HI assay may be very useful as a screening assay in large-scale epidemiologic studies.     

Dissociation of conditioned locomotion and Fos induction in response to stimuli formerly paired with cocaine

A discrete stimulus (flashing light) was paired with cocaine (20 mg/kg) to induce conditioned locomotion. To identify brain regions activated during this response, Fos was measured with immunohistochemistry. Although paired subjects displayed robust conditioned locomotion, Fos was not increased in any limbic brain regions analyzed. In contrast, pairing of cocaine with generalized contextual cues (whole room) produced conditioned locomotion and Fos activation in the prelimbic portion of prefrontal cortex and the nucleus accumbens core. These results suggest that the pattern of neuronal activation during cocaine-conditioned activity differs depending on whether a discrete or contextual stimulus is used as a conditioned stimulus. The possibility that expectancy and frustrative nonreward contribute to Fos expression in rats conditioned to contextual cues is discussed.     

Introduction: The Quest for Birth Equity and Justice—Now is the Time

Maternal and Child Health Journal -     

Associations Between LGBTQ-Affirming School Climate and Intimate Partner Violence Victimization Among Adolescents

Prevention Science - Intimate partner violence (IPV) impacts sexual minority adolescents at rates equal to or greater than the rate it impacts heterosexual adolescents. We investigated whether...     

Editorial Commentary: There Is Value in Standardizing the Position of the Arm During Magnetic Resonance Imaging Arthrogram of the Shoulder When Evaluating for Suspected Instability (and It Doesn’t Have to Be Painful to the Patient!)

Evaluating and treating a shoulder with suspected instability remains a challenge for all. Most authors and surgeons would agree that clinical history and physical examination of the patient are the most important aspects of this evaluation. Over the past 15 years, however, radiographic imaging has become a much more prevalent (and essential) component. Magnetic resonance imaging arthrogram has become the gold standard to evaluate a patient for suspected instability and is currently considered the most appropriate advanced study by the American College of Radiologists to do so in both traumatic and atraumatic presentations.     

Patient Outcomes in the Years After a DXA-BMD Treatment Monitoring Test: Improved Medication Adherence in Some,But Too Little Too Late

The role of mid-treatment monitoring dual-energy X-ray absorptiometry–bone mineral density (DXA-BMD) for bisphosphonate-treated patients with osteoporosis remains unsettled. A common reason for such monitoring is to encourage ongoing medication adherence. We sought to determine if a DXA-BMD treatment monitoring test was associated with improved medication adherence and whether improved adherence after a DXA-BMD treatment monitoring test was associated with subsequent reduction in fracture rates. Using linked administrative databases within Manitoba, Canada, we performed a retrospective cohort study of women starting and continuing antiresorptive therapy in whom a mid-treatment DXA-BMD monitoring test was performed. From the provincial pharmacy database, we estimated medication adherence by calculating annual medication possession ratio (MPR) and determining the change in MPR with respect to change (stable/decrease) in the DXA-BMD monitoring test, in addition to fracture rates before and after the test. The cohort comprised 3418 women, 90.7% treated with oral bisphosphonate, with pharmacy data for the 3 years before and after the mid-treatment DXA-BMD. Median (interquartile range) MPR was 0.84 (0.49–0.99) in the year before DXA-BMD and 0.84 (0.48–0.99) in the year after DXA-BMD (p = 0.37). Among those whose DXA-BMD declined, MPR in the prior year was 0.54 (0.04–0.92) but improved to 0.70 (0.31–0.92) in the year after DXA-BMD (p < 0.001). Among those whose DXA-BMD monitoring test was stable/improved, the fracture rate before the monitoring DXA-BMD was 10.1 per 1000 person-years and in those whose DXA-BMD monitoring test showed a decrease, the rate was 23.7 per 1000 person-years (p < 0.001). Despite improved adherence in those with DXA-BMD decline, the post DXA-BMD fracture rate was 22.4 per 1000 person-years versus 12.9 per 1000 person-years in those who had stable DXA-BMD (p < 0.001). A mid-treatment DXA-BMD reassessment strategy may be useful to focus attention upon adherence, but for optimal fracture outcomes, treatment adherence should be specifically addressed at the commencement of therapy. © 2021 American Society for Bone and Mineral Research (ASBMR).