Prenatal exposure to inflammatory conditions increases Cx43 and Panx1 unopposed channel opening and activation of astrocytes in the offspring effect on neuronal survival

Several epidemiological studies indicate that children born from mothers exposed to infections during gestation, have an increased risk to develop neurological disorders, including schizophrenia, autism and cerebral palsy. Given that it is unknown if astrocytes and their crosstalk with neurons participate in the above mentioned brain pathologies, the aim of this work was to address if astroglial paracrine signaling mediated by Cx43 and Panx1 unopposed channels could be affected in the offspring of LPS‐exposed dams during pregnancy. Ethidium uptake experiments showed that prenatal LPS‐exposure increases the activity of astroglial Cx43 and Panx1 unopposed channels in the offspring. Induction of unopposed channel opening by prenatal LPS exposure depended on intracellular Ca²⁺ levels, cytokine production and activation of p38 MAP kinase/iNOS pathway. Biochemical assays and Fura‐2AM/DAF‐FM time‐lapse fluorescence images revealed that astrocytes from the offspring of LPS‐exposed dams displayed increased spontaneous Ca²⁺ dynamics and NO production, whereas iNOS levels and release of IL‐1β/TNF‐α were also increased. Interestingly, we found that prenatal LPS exposure enhanced the release of ATP through astroglial Cx43 and Panx1 unopposed channels in the offspring, resulting in an increased neuronal death mediated by the activation of neuronal P2X₇ receptors and Panx1 channels. Altogether, this evidence suggests that astroglial Cx43 and Panx1 unopposed channel opening induced by prenatal LPS exposure depended on the inflammatory activation profile and the activation pattern of astrocytes. The understanding of the mechanism underlying astrocyte‐neuron crosstalk could contribute to the development of new strategies to ameliorate the brain abnormalities induced in the offspring by prenatal inflammation. GLIA 2015;63:2058–2072     

Feature Extraction From Parametric Time–Frequency Representations for Heart Murmur Detection

The detection of murmurs from phonocardiographic recordings is an interesting problem that has been addressed before using a wide variety of techniques. In this context, this article explores the capabilities of an enhanced time–frequency representation (TFR) based on a time-varying autoregressive model. The parametric technique is used to compute the TFR of the signal, which serves as a complete characterization of the process. Parametric TFRs contain a large quantity of data, including redundant and irrelevant information. In order to extract the most relevant features from TFRs, two specific approaches for dimensionality reduction are presented: feature extraction by linear decomposition, and tiling partition of the t–f plane. In the first approach, the feature extraction was carried out by means of eigenplane-based PCA and PLS techniques. Likewise, a regular partition and a refined Quadtree partition of the t–f plane were tested for the tiled-TFR approach. As a result, the feature extraction methodology presented, which searches for the most relevant information immersed on the TFR, has demonstrated to be very effective. The features extracted were used to feed a simple k-nn classifier. The experiments were carried out using 45 phonocardiographic recordings (26 normal and 19 records with murmurs), segmented to extract 548 representative individual beats. The results using these methods point out that better accuracy and flexibility can be accomplished to represent non-stationary PCG signals, showing evidences of improvement with respect to other approaches found in the literature. The best accuracy obtained was 99.06 ± 0.06%, evidencing high performance and stability. Because of its effectiveness and simplicity of implementation, the proposed methodology can be used as a simple diagnostic tool for primary health-care purposes.     

Potassium supplementation lowers blood pressure and increases urinary kallikrein in essential hypertensives

In order to eludicate possible mechanism(s) involved in the blood pressure reduction induced by potassium (K) supplementation, we studied the changes of BP and of some of its regulatory systems, including levels of urinary kallikrein (UKal)--an index of renal kallikrein production. Twenty-four untreated essential hypertensives, with a basal BP of 147/96 +/- 13/7 mmHg and normal renal function, received in crossover, double-blind, randomised fashion, 64 mmol KCl or placebo during two periods of 4 weeks each. At the 4th week of potassium supplementation systolic, diastolic and mean BPs decreased by 6.3 +/- 2 (P less than 0.01), 3.0 +/- 2 and 4.1 +/- 2 (P less than 0.05) mmHg respectively for the supine position, and 5.0 +/- 2, 4.0 +/- 2 (P less than 0.05) and 4.0 +/- 1 (P less than 0.05) mmHg for the standing position. Urinary potassium (K) increased from 55 +/- 4 to 123 +/- 6 mmol/24 hours (P less than 0.001) and UKal from 692 +/- 69 to 1052 +/- 141 mU/24 hours (P less than 0.01). Serum K rose from 3.8 +/- 0.1 mEq/l to 4.1 +/- 0.1 mmol/l (P less than 0.001) and PRA from 0.77 +/- 0.12 to 0.99 +/- 0.14 ng/ml/h (P less than 0.05). Correlations were observed between UKal and urinary K (r = 0.44, P less than 0.0001); between differences in UKal and urinary K and in UKal and urinary Na (r = 0.50, P less than 0.0005 and r = 0.48, P less than 0.001 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnostic utility of the polymerase chain reaction for the diagnosis of Mycoplasma pneumoniae in elderly patients with community-acquired pneumonia

Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP) in children and young adults, but limited information about its prevalence in the elderly is available. The polymerase chain reaction (PCR) with primers targeting the cytadhesine P1 gene and the 16S rRNA gene was analyzed for detecting M. pneumoniae in throat washings of 84 patients, aged 60-96 years, with clinical diagnosis of CAP, from September 2002 through August 2004, in Santiago, Chile. PCR results were compared with serology performed by indirect immunofluorescence (IFI). Specimens from 11 of 84 patients (13.1%) were positive for M. pneumoniae by any test. The IFI test was positive in 8 (72.7%) patients and PCR in 7 (63.6%) cases. The acute phase sera allowed diagnosis of M. pneumoniae in 5 of 11 patients (45.4%), 4 of them showing an IgM response. PCR was negative in 4 patients with positive serology and 3 patients were positive only by PCR. The two PCR primers showed 100% correlation, and a similar sensitivity; no inhibitory specimens for PCR were detected. In conclusion, M. pneumoniae should be considered as a potential etiologic agent of CAP in the elderly. Its detection must be performed by a combination of PCR and serology.     

Differential effects of respiratory syncytial virus and adenovirus on mononuclear cell cytokine responses

Respiratory syncytial virus (RSV) and adenovirus (Advs) serotype 3 (Adv3) and 7h (Adv7h) are associated with mild to severe respiratory infection and are indistinguishable during the acute phases of the illnesses. However, outcome and long-term prognosis are different with both infections. RSV infection is associated with later development of asthma, and Adv, mainly Adv7h, with severe lung damage, bronchiectasis, and hyperlucent lung. We hypothesized that this difference could be partly due to different immune responses induced by these viruses. To test this hypothesis we quantified TCD4+, TCD8+, and BCD19+ expressing the interleukin-2 receptor-alpha chain (CD25) and interferon-gamma (IFN-gamma), interleukin (IL)-10, and IL-4 in the supernatant of peripheral blood mononuclear cells (PBMC) from school children infected in vitro with and without RSV, Adv7h, and Adv3 and after phytohemagglutinin (PHA) stimulation in the presence or absence of these viruses at a multiplicity of infection (MOI) of 1. PBMC from every child produced more IL-10 (p 相似文献   

Effect of high-frequency alternating current transcutaneous stimulation over muscle strength: a controlled pilot study

Background

High-frequency alternating currents of greater than 1 kHz applied on peripheral nerves has been used in animal studies to produce a motor nerve block. It has been evidenced that frequencies higher than 5 kHz are necessary to produce a complete peripheral nerve block in primates, whose nerve thickness is more similar to humans. The aim of the study was to determine the effect on muscle strength after the application of a high-frequency stimulation at 5 and 10 kHz compared to sham stimulation in healthy volunteers.

Findings

Transcutaneous stimulation at 5 kHz, 10 kHz and sham stimulation were applied to eleven healthy volunteers over the ulnar and median nerves for 20 min. Maximal handgrip strength was measured before, during, immediately after the intervention, and 10 min after the end of intervention. The 10 kHz stimulation showed a lower handgrip strength during the intervention (28.1 N, SEM 3.9) when compared to 5 kHz (31.1 N, SEM 3.6; p?<?0.001) and to sham stimulation (33.7 N, SEM 3.9; p?<?0.001). Furthermore, only stimulation at 10 kHz decreased handgrip strength when compared to baseline.

Conclusions

These findings suggest high-frequency stimulation has an inhibitory effect over muscle strength. Future studies are required in patients that are characterized by motor hyperactive such as spasticity or tremors.

Clinical trial registration

NCT, NCT03169049. Registered on 30 May 2017

     

Regulatory authorities and orthopaedic clinical trials on expanded mesenchymal stem cells

Skeletal injuries requiring bone augmentation techniques are increasing in the context of avoiding or treating difficult cases with bone defects, bone healing problems, and bone regeneration limitations. Musculoskeletal severe trauma, osteoporosis-related fractures, and conditions where bone defect, bone collapse or insufficient bone regeneration occur are prone to disability and serious complications. Bone cell therapy has emerged as a promising technique to augment and promote bone regeneration. Interest in the orthopaedic community is considerable, although many aspects related to the research of this technique in specific indications may be insufficiently recognised by many orthopaedic surgeons. Clinical trials are the ultimate research in real patients that may confirm or refute the value of this new therapy. However, before launching the required trials in bone cell therapy towards bone regeneration, preclinical data is needed with the cell product to be implanted in patients to ensure safety and efficacy. These preclinical studies support the end-points that need to be evaluated in clinical trials. Orthopaedic surgeons are the ultimate players that, through their research, would confirm in clinical trials the benefit of bone cell therapies. To further foster this research, the pathway to eventually obtain authorisation from the National Competent Authorities and Research Ethics Committees under the European regulation is reviewed, and the experience of the REBORNE European project offers information and important clues about the current Voluntary Harmonization Procedure and other opportunities that need to be considered by surgeons and researchers on the topic.