Time-lapse electrical recordings of single neurons from the mouse neocortex

The ability of the brain to adapt to environmental demands implies that neurons can change throughout life. The extent to which single neurons actually change remains largely unstudied, however. To evaluate how functional properties of single neurons change over time, we devised a way to perform in vivo time-lapse electrophysiological recordings from the exact same neuron. We monitored the contralateral and ipsilateral sensory-evoked spiking activity of individual L2/3 neurons from the somatosensory cortex of mice. At the end of the first recording session, we electroporated the neuron with a DNA plasmid to drive GFP expression. Then, 2 wk later, we visually guided a recording electrode in vivo to the GFP-expressing neuron for the second time. We found that contralateral and ipsilateral evoked responses (i.e., probability to respond, latency, and preference), and spontaneous activity of individual L2/3 pyramidal neurons are stable under control conditions, but that this stability could be rapidly disrupted. Contralateral whisker deprivation induced robust changes in sensory-evoked response profiles of single neurons. Our experiments provide a framework for studying the stability and plasticity of single neurons over long time scales using electrophysiology.     

Overcoming medication stigma in peer recovery: A new paradigm

Background: Treatment for opioid use disorder involving opioid-based pharmacotherapies is considered most effective when accompanied by psychosocial interventions. Peer-led support groups are widely available and have been described by many as fundamental to the recovery process. However, some individuals using medications face stigma in these settings, which can be contradictory and counterproductive to their recovery. Methods: This paper describes the development of the “Ability, Inspiration and Motivation” or “AIM” group, an alternative peer support group that aims to remove medication stigma from peer recovery. Qualitative interviews with staff, peers, and clients of a community-based buprenorphine treatment program were used to establish the core components of the curriculum to support client needs. Results: Staff, peers, and clients of the buprenorphine program indicated a need and desire to establish a peer recovery group that recognizes persons on medication as being in recovery and destigmatizes use of medication to treat opioid addiction. A respectful environment, holistic perspective on health, spirituality, sharing, and celebration were all established as necessary pillars of the AIM group curriculum. Conclusions: The community-based effort to establish and develop the AIM group demonstrates that combining the strengths of a peer support with evidence-based medication treatment is both possible and desirable. Shifting the culture of peer recovery groups to support the use of medications may have implications for improving treatment retention and should be considered as a potential strategy to reduce the burden of the opioid epidemic.     

1,4,5-Inositol trisphosphate-operated intracellular Ca(2+) stores and angiotensin-II/endothelin-1 signaling pathway are functional in human embryonic stem cell-derived cardiomyocytes

On the basis of previous findings suggesting that in human embryonic stem cell-derived cardiomyocytes (hESC-CM) the sarcoplasmic reticulum Ca(2+)-induced release of calcium machinery is either absent or immature, in the present study we tested the hypothesis that hESC-CM contain fully functional 1,4,5-inositol trisphosphate (1,4,5-IP(3))-operated intracellular Ca(2+) ([Ca(2+)](i)) stores that can be mobilized upon appropriate physiological stimuli. To test this hypothesis we investigated the effects of angiotensin-II (AT-II) and endothelin-1 (ET-1), which activate the 1,4,5-IP(3) pathway, on [Ca(2+)](i) transients and contractions in beating clusters of hESC-CM. Our major findings were that in paced hESC-CM both AT-II and ET-1 (10(-9) to 10(-7) M) increased the contraction amplitude and the maximal rates of contraction and relaxation. In addition, AT-II (10(-9) to 10(-7) M) increased the [Ca(2+)](i) transient amplitude. The involvement of 1,4,5-IP(3)-dependent intracellular Ca(2+) release in the inotropic effect of AT-II was supported by the findings that (a) hESC-CM express AT-II, ET-1, and 1,4,5-IP(3) receptors determined by immunofluorescence staining, and (b) the effects of AT-II were blocked by 2 microM 2-aminoethoxyphenyl borate (a 1,4,5-IP(3) receptor blocker) and U73122 (a phospholipase C blocker). In conclusion, these findings demonstrate for the first time that hESC-CM exhibit functional AT-II and ET-1 signaling pathways, as well as 1,4,5-IP(3)-operated releasable Ca(2+) stores.     

Application of amniotic membrane dressings in patients with skin damage

The application of amniotic membranes in patients diagnosed with skin damage is a valid treatment option. A care plan following the Virginia Henderson model and NANDA, NOC and NIC taxonomy was applied to 36 patients admitted to the Dr. Miguel Enríquez hospital with different cutaneous lesions. This membrane has already been used for years due to its healing properties. These are attributed to antimicrobial properties reducing infection risk and promoting epithelial activity. They can decrease the need for the use of antibiotics, expendable materials, and can be applied during long periods of healing. This decreases the cost of wide spectrum antibiotic treatments, as well as the time patients spend in hospital. We present the results of this application in cases with several types of skin lesions.     

Weekly carfilzomib,lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: A phase 1b study

Twice-weekly carfilzomib (27 mg/m²) with lenalidomide-dexamethasone (KRd) is a standard-of-care in relapsed or refractory multiple myeloma (RRMM). This phase 1b study evaluated KRd with once-weekly carfilzomib in RRMM. Patients received carfilzomib (30-minute infusion; 56 or 70mg/m²) on days 1, 8, and 15; lenalidomide 25 mg on days 1-21; and dexamethasone 40 mg on days 1, 8, 15, and 22 (day 22 omitted for cycles 9+) of 28-day cycles. Primary objective was safety/tolerability; efficacy was a secondary objective. Fifty-six RRMM patients enrolled: 22 during dose evaluation (56-mg/m², n = 10; 70-mg/m², n = 12) and 34 during dose expansion (all initiated dosing at 70 mg/m²). After 2 fatal adverse events (AEs) during 70-mg/m² dose expansion, dosage reduction to 56 mg/m² was permitted. Results are presented for carfilzomib 56-mg/m² (n = 10) and 70-mg/m² groups (dose evaluation/expansion; n = 46). Median carfilzomib dose was 53.2 mg/m² (56-mg/m² group) and 62.4 mg/m² (70-mg/m² group). Grade ≥3 AE rates were 70.0% (56 mg/m²) and 69.6% (70 mg/m²). Overall response rates were 90.0% (56 mg/m²) and 89.1% (70 mg/m²); ≥very good partial response rates were 50.0% (56 mg/m²) and 73.9% (70 mg/m²). Once-weekly KRd was active with acceptable toxicity in RRMM, supporting further evaluation of this regimen.     

Interventricular Septum and Posterior Wall Thickness Are Associated With Higher Systolic Blood Pressure

Elevated blood pressure (BP) is a known factor that affects the structure of the left ventricle. The association between left ventricular hypertrophy (LVH) and BP in normotensive individuals is poorly understood. All individuals who underwent routine echocardiography and BP measurements as aircrew candidates for the Israeli Air Force in the years 2006 to 2012 were identified. Participants with normal values were included. Associations between echocardiographic characteristics and BP were studied. A total of 2386 participants were included. Mean systolic BP was 125.31±11.18 mm Hg and mean diastolic BP was 68.69±9.02 mm Hg. Interventricular septal (IVS) thickness was positively correlated with systolic BP (P<.001, correlation coefficient 0.121) and significantly inversely correlated with heart rate and hematocrit level (P<.001 for both). Men with evidence of IVS or posterior wall thickening on echocardiography, even within the normal range, may require a closer follow‐up of BP.     

Non-medical use of opioid analgesics in contemporary Brazil: Findings from the 2015 Brazilian National Household Survey on Substance Use

ABSTRACT

Prior studies on substance use in Brazil have not focused on opioid misuse, previously thought to be nearly non-existent. This paper presents new findings on heroin and non-medical use of opioid analgesics. Data come from the 2015 Brazilian Household Survey on Substance Use (BHSU-3), a nationally representative survey estimating epidemiological parameters related to substance use by residents across Brazil. BHSU-3 used stratified multi-stage probability sampling across multiple geographic domains of interest, resulting in 16,273 interviews with household residents. Lifetime heroin use among Brazilians was 0.3 (95% C.I:0.2–0.4). Lifetime, past-year, and past-month non-medical use of opioid analgesics were respectively 2.9 (95%C.I.:2.3–3.4), 1.4 (95%C.I.:1.1–1.7) and 0.6 (95%C.I.:0.4–0.8). Past-year prevalence of non-medical opioid analgesics use was lower among males [Prevalence Ratio (PR): 0.54 (95% C.I.:0.36–0.78)], those aged 12–24 [0.56 (95% C.I.:0.34–0.92)], persons with monthly family incomes between R$1,501–3,000 [0.59 (95% C.I.:0.38–0.92)] or greater than R$3,000 [0.64 (95% C.I.:0.42–0.98)], and persons who were unemployed [0.65 (95% C.I.:0.46–0.92)]. Non-medical use of opioids in Brazil may be more prevalent than previously recognised. Proper measurement and evaluation of opioid misuse across Brazil and other Latin American countries is critical to understand and prevent opioid-related harms.     

Oral levothyroxine therapy postbariatric surgery: Biopharmaceutical aspects and clinical effects

Background

Bariatric surgery can lead to changes in the oral absorption of many drugs. Levothyroxine is a narrow therapeutic drug for hypothyroidism, a common condition among patients with obesity.