Calcium activation of cortical neurons by continuous electrical stimulation: Frequency dependence,temporal fidelity,and activation density

Electrical stimulation of the brain has become a mainstay of fundamental neuroscience research and an increasingly prevalent clinical therapy. Despite decades of use in basic neuroscience research and the growing prevalence of neuromodulation therapies, gaps in knowledge regarding activation or inactivation of neural elements over time have limited its ability to adequately interpret evoked downstream responses or fine-tune stimulation parameters to focus on desired responses. In this work, in vivo two-photon microscopy was used to image neuronal calcium activity in layer 2/3 neurons of somatosensory cortex (S1) in male C57BL/6J-Tg(Thy1-GCaMP6s)GP4.3Dkim/J mice during 30 s of continuous electrical stimulation at varying frequencies. We show frequency–dependent differences in spatial and temporal somatic responses during continuous stimulation. Our results elucidate conflicting results from prior studies reporting either dense spherical activation of somas biased toward those near the electrode, or sparse activation of somas at a distance via axons near the electrode. These findings indicate that the neural element specific temporal response local to the stimulating electrode changes as a function of applied charge density and frequency. These temporal responses need to be considered to properly interpret downstream circuit responses or determining mechanisms of action in basic science experiments or clinical therapeutic applications.     

Embryonic death in goats caused by the ingestion of Mimosa tenuiflora

To determine the teratogenic effect of Mimosa tenuiflora, the green fresh plant was administered ad libitum to 12 goats (Group 1) from day 1 to day 30 of gestation. Upon ultrasonographic examination, on day 30, not one of these goats was pregnant, demonstrating that M. tenuiflora causes embryonic death. Six goats (Group 2) ingested M. tenuiflora from day 30 to day 60 of pregnancy. Four goats delivered seven healthy kids and two were not pregnant based on ultrasonographic examination on day 45 suggesting late embryonic death. Three other groups of six goats each received the plant on days 60–90 (Group 3), 90–120 (Group 4), and 120–150 (Group 5) of gestation and a control group (Group 6) all delivered normal kids, except one goat in Group 4 that aborted and one adult goat from Group 5 that was found dead. It is concluded that M. tenuiflora causes embryonic death. The failure to induce malformations might have resulted from a high dose of an unknown active principle of the plant causing fetal death.     

Determination of biogenic amines and endotoxin in squid, musky octopus, Norway lobster, and mussel stored at room temperature

Little research has been published on the indicators of spoilage in Mediterranean molluscan shellfish and crustaceans. Thus is why we studied changes in the concentrations of endotoxin and four biogenic amines (histamine, putrescine, tyramine and cadaverine) in European common squid (Loligo subulata, Lamarck, 1798), musky octopus (Eledone moschata, Lamarck, 1798), Norway lobster (Nephrops norvegicus, Linnaeus, 1758), and mussel (Mytilus galloprovincialis, Lamarck, 1819) from the Adriatic Sea stored at room temperature for 24 h. Endotoxin load in fresh squid, Norway lobster, and mussel (<1 EU mg-1) indicated good microbiological quality of raw samples. Biogenic amine index (as the sum of histamine, putrescine, tyramine, and cadaverine) correlated well with endotoxin load in squid (r=0.978, p<0.001) and musky octopus (r=0.874, p<0.01). A good correlation was also found between endotoxin and putrescine in Norway lobster (r=0.777, p<0.05). The highest endotoxin load was found in decomposed mussels and was associated with histamine alone. In conclusion, increase in biogenic amine levels is species-specific. Endotoxin analysis could be used for rapid assessment of microbiological quality of cephalopods and shellfish.     

Chronic neural recordings using silicon microelectrode arrays electrochemically deposited with a poly(3,4-ethylenedioxythiophene) (PEDOT) film

Conductive polymer coatings can be used to modify traditional electrode recording sites with the intent of improving the long-term performance of cortical microelectrodes. Conductive polymers can drastically decrease recording site impedance, which in turn is hypothesized to reduce thermal noise and signal loss through shunt pathways. Moreover, conductive polymers can be seeded with agents aimed at promoting neural growth toward the recording sites or minimizing the inherent immune response. The end goal of these efforts is to generate an ideal long-term interface between the recording electrode and surrounding tissue. The goal of this study was to refine a method to electrochemically deposit surfactant-templated ordered poly(3,4-ethylenedioxythiophene) (PEDOT) films on the recording sites of standard 'Michigan' probes and to evaluate the efficacy of these modified sites in recording chronic neural activity. PEDOT-coated site performance was compared to control sites over a six-week evaluation period in terms of impedance spectroscopy, signal-to-noise ratio, number of viable unit potentials recorded and local field potential recordings. PEDOT sites were found to outperform control sites with respect to signal-to-noise ratio and number of viable unit potentials. The benefit of reduced initial impedance, however, was mitigated by the impedance contribution of typical silicon electrode encapsulation. Coating sites with PEDOT also reduced the amount of low-frequency drift evident in local field potential recordings. These findings indicate that electrode sites electrochemically deposited with PEDOT films are suitable for recording neural activity in vivo for extended periods. This study also provided a unique opportunity to monitor how neural recording characteristics develop over the six weeks following implantation.     

Navigating Latinas with breast screen abnormalities to diagnosis

BACKGROUND.

Breast cancer is the leading cause of cancer‐related deaths in Latinas, chiefly because of later diagnosis. The time from screening to diagnosis is critical to optimizing cancer care, yet the efficacy of navigation in reducing it is insufficiently documented. Here, the authors evaluate a culturally sensitive patient navigation program to reduce the time to diagnosis and increase the proportions of women diagnosed within 30 days and 60 days.

METHODS.

The authors analyzed 425 Latinas who had Breast Imaging Reporting and Data System (BI‐RADS) radiologic abnormalities categorized as BI‐RADS‐3, BI‐RADS‐4, or BI‐RADS‐5 from July 2008 to January 2011. There were 217 women in the navigated group and 208 women in the control group. Women were navigated by locally trained navigators or were not navigated (data for this group were abstracted from charts). The Kaplan‐Meier method, Cox proportional hazards regression, and logistic regression were used to determine differences between groups.

RESULTS.

The time to diagnosis was shorter in the navigated group (mean, 32.5 days vs 44.6 days in the control group; hazard ratio, 1.32; P = .007). Stratified analysis revealed that navigation significantly shortened the time to diagnosis among women who had BI‐RADS‐3 radiologic abnormalities (mean, 21.3 days vs 63.0 days; hazard ratio, 2.42; P < .001) but not among those who had BI‐RADS‐4 or BI‐RADS‐5 radiologic abnormalities (mean, 37.6 days vs 36.9 days; hazard ratio, 0.98; P = .989). Timely diagnosis occurred more frequently among navigated Latinas (within 30 days: 67.3% vs 57.7%; P = .045; within 60 days: 86.2% vs 78.4%; P = .023). This was driven by the BI‐RADS‐3 strata (within 30 days: 83.6% vs 50%; P < .001; within 60 days: 94.5% vs 67.2%; P < .001). A lack of missed appointments was associated with timely diagnosis.

CONCLUSIONS.

Patient‐centered navigation to assist Latina women with abnormal screening mammograms appeared to reduced the time to diagnosis and increase rates of timely diagnosis overall. However, in stratified analyses, only navigated Latinas with an initial BI‐RADS‐3 screen benefited, probably because of a reduction in missed diagnostic appointments. Cancer 2013. © 2012 American Cancer Society.     

Bacterial vaginosis (BV) and the risk of incident gonococcal or chlamydial genital infection in a predominantly black population

OBJECTIVE: The objective of this study was to assess in prospective data whether bacterial vaginosis (BV) is associated with gonococcal/chlamydial cervicitis. STUDY: A total of 1179 women at high risk for sexually transmitted infections was followed for a median of 3 years. Every 6 to 12 months, vaginal swabs were obtained for Gram stain, culture of microflora, and Neisseria gonorrhoeae and Chlamydia trachomatis. A Gram stain score of 7 to 10 based on the Nugent criteria categorized BV. RESULTS: Baseline BV was associated with concurrent gonococcal/chlamydial infection (adjusted odds ratio, 2.83; 95% confidence interval [CI], 1.81-4.42). However, the association between BV and subsequent, incident gonococcal/chlamydial genital infection was not significant (adjusted relative risk [RR], 1.52; 95% CI, 0.74-3.13). Dense growth of pigmented, anaerobic Gram-negative rods (adjusted RR, 1.93; 95% CI, 0.97-3.83) appeared to elevate the risk for newly acquired gonococcal/chlamydial genital infection. CONCLUSIONS: BV was common among a predominantly black group of women with concurrent gonococcal/chlamydial infection but did not elevate the risk for incident infection.     

The role of anisometropia in the development of accommodative esotropia.

PURPOSE: To determine whether anisometropia increases the risk for the development of accommodative esotropia with hypermetropia. METHODS: Records of all new patients with a refractive error of +2.00 D or more (mean spherical equivalent of both eyes) over a 42-month period were reviewed. Three hundred forty-five patients were thus analyzed to determine the effect of anisometropia (>or=1 D) on the relative risk of developing accommodative esotropia and of developing unsatisfactory control with spectacles once esotropia was present. RESULTS: Anisometropia (>or=1 D) increased the relative risk of developing accommodative esotropia to 1.68 (P < .05). Anisometropia (>or=1 D) increased the relative risk for esotropia to 7.8 (P < .05) in patients with a mean spherical equivalent less than +3.00 D and increased it to 1.49 (P < .05) in patients with a mean spherical equivalent of +3.00 D or more (P = .016). In patients with esotropia and anisometropia (>or=1 D), the relative risk for a deviation that was unsatisfactorily controlled with spectacles was 1.72 (P < .05) compared with patients with esotropia but without anisometropia. Unsatisfactorily controlled esotropia was present in 33% of patients with anisometropia versus 0% of patients without anisometropia, with a mean hypermetropic spherical equivalent of less than +3.00 D (P = .003); however, anisometropia did not significantly increase the relative risk of unsatisfactory control of esotropia with spectacles in patients with a hypermetropic spherical equivalent of +3.00 D or more. Although amblyopia and anisometropia were closely associated, anisometropia increased the relative risk for esotropia to 2.14 (P < .05), even in the absence of amblyopia. CONCLUSIONS: Anisometropia (>or=1 D) is a significant risk factor for the development of accommodative esotropia, especially in patients with lower overall hypermetropia (>+3.00 D). Anisometropia also increases the risk that an accommodative esotropia will not be satisfactorily aligned with spectacles.