Responses of human primary sensorimotor and supplementary motor areas to internally triggered unilateral and simultaneous bilateral one‐digit movements. A high‐resolution EEG study

We modelled the responses of human primary sensorimotor areas and supplementary motor area to simple, self-initiated unilateral and simultaneous bilateral middle finger movements using a novel high-resolution electroencephalography technology. The results support the view that these cortical motor areas are involved in parallel and present similar activity in the preparation, initiation, and execution of the contralateral and bilateral movements. Furthermore, the left primary sensorimotor area (dominant hemisphere) appears to be activated more than the right primary sensorimotor area during the preparation and performance of the ipsilateral movements.     

Rescue extracorporeal cardiopulmonary resuscitation in pediatric patients: a nine-year single-center experience in Zagreb,Croatia

AimTo investigate the risk factors and the outcomes of extracorporeal membrane oxygenation (ECMO) in pediatric patients treated at the University Hospital Center Zagreb, the largest center in Croatia providing pediatric ECMO.MethodsThis retrospective study enrolled all the pediatric patients who required E-CPR from 2011 to 2019. Demographic data, cardiac anatomy, ECMO indications, ECMO complications, and neurodevelopmental status at hospital discharge were analyzed.ResultsIn the investigated period, E-CPR was used in 16 children, and the overall survival rate was 37.5%. Six patients were in the neonatal age group, 5 in the infant group, and 5 in the “older” group. There was no significant difference between the sexes. Four patients had an out-of-hospital arrest and 12 had an in-hospital arrest. Twelve out of 16 patients experienced renal failure and needed hemodialysis, with 4 out of 6 patients in the survivor group and 8 out of 10 in the non-survivor group. Survivors and non-survivors did not differ in E-CPR duration time, lactate levels before ECMO, time for lactate normalization, and pH levels before and after the start of ECMO.ConclusionThe similarity of our results to those obtained by other studies indicates that the ECMO program in our hospital should be maintained and improved.

The use of extracorporeal cardiopulmonary resuscitation (E-CPR) is increasing (1). E-CPR is defined as an initiation of extracorporeal membrane oxygenation (ECMO) during active chest compressions. Its main goal is to provide immediate cardiovascular support to patients who do not react to CPR (2) and to lead to survival and a better neurological outcome (3). After administering CPR for more than 30 minutes, survival with conventional CPR measures ranges between 0%-5% (4,5).The most recent systematic review by the International Liaison Committee on Resuscitation from 2015 recommended that E-CPR should be considered for children with underlying cardiac conditions who have an in-hospital cardiac arrest when appropriate protocols, expertise, and equipment are available (6). According to the Extracorporeal Life Support Organization (ELSO) registry from 2017 (7), more than 60 000 people received extracorporeal life support (ECLS), between 2009 and 2015, with an overall survival rate of 61% (7). Pediatric ECMO experience in Slovenia shows that ECMO programs may be incorporated in smaller hospitals in the region (8-10). The ELSO database includes data on all reported pediatric ECMO runs, including those conducted with E-CPR, and in patients with congenital heart surgery and neonates with diaphragmatic hernia or meconium aspiration syndrome, etc. During the 6-year period, 3005 E-CPR runs were reported, with an overall survival to hospital discharge of 43% (7). A survival rate of 31% was reported by Ergűn et al (11) and in E-CPR patients with severe burn injury (12). The longer the CPR duration time, the lower was the survival to discharge rate. Matos et al reported an E-CPR survival-to-discharge rate of 33% after >35 min of chest compressions (13). Other studies reported that the overall survival rate of pediatric E-CPR cases was growing, with better neurological outcomes than among the patients in the CPR group only (14). Pilar et al found that in 73 pediatric cardiac patients requiring cardiopulmonary resuscitation for >30 min (15), the survival to hospital discharge was 43.8%, with 3/4 of the patients having normal neurological function or mild neurological disability (15). Based on ELSO registry, approximately 10% of all ECMO patients meet brain death criteria (7). One of the biggest single-center studies, involving 184 pediatric ECPR patients (16), showed a successful ECMO weaning in 63% of the patients and the overall survival rate to hospital discharge of 43%. In the same study, the risk factors linked to increased mortality were presupport pH<7.1, mechanical complications, and neurological complications (16). The E-CPR use can involve many complications, not necessarily linked to factors preceding cardiac arrest, such as low cardiac output syndrome or irreversible respiratory failure (17). Furthermore, common complications of ECMO treatment are fluid overload and acute kidney injury (18). Many studies showed renal replacement therapy (RRT) to be negatively associated with survival (15,16,18,19).This study assessed the risk factors and the outcomes of ECMO in the largest Croatian center providing pediatric E-CPR experience over nine years and compared the survivor and the non-survivor group.     

Mycobacterium tuberculosis subverts the differentiation of human monocytes into dendritic cells

Intracellular pathogens have developed strategies for evading elimination by the defenses of the host immune system. Here we describe an escape mechanism utilized by Mycobacterium tuberculosis that involves the interference with the generation of fully competent DC from monocytes. We show that monocytes infected with live M. tuberculosis differentiated into mature, CD83+ and CCR7+ DC (Mt-MoDC), but were characterized by a selective failure in the expression of the family of CD1 molecules. These cells also showed levels of MHC class II and CD80 (B7.1) that were reduced in comparison with LPS-matured DC. In addition, Mt-MoDC produced TNF-alpha and IL-10, but were unable to secrete IL-12. The generation of Mt-MoDC required the infection of monocytes with live M. tuberculosis, since infection with heat-killed bacteria partially abrogated the effects on monocyte differentiation. Interestingly, Mt-MoDC revealed an impaired antigen-presentation function as assessed by the reduced capability to induce proliferation of cord blood T lymphocytes. Further, naive T lymphocytes expanded by Mt-MoDC were unable to secrete cytokines, in particular IL-4 and IFN-gamma, suggesting that they could be ineffective in helping the macrophage-mediated killing of intracellular mycobacteria. Our results suggest that the interference with monocyte differentiation into fully competent DC is an evasion mechanism of M. tuberculosis that could contribute to its intracellular persistence by avoiding immune recognition.     

Observations on the arterial baroreflex in neurally mediated vasodepressor syncope

The arterial baroreflex was studied in subjects who had recently had an episode of vasodepressor syncope. This was determined using 2–3 mcg/kg intravenous boluses of phenylephrine and assessing the bradycardic response. The values were measured in ms/mmHg and expressed as the angular coefficient of the regression line between the increase in R—R interval on the electrocardiograph and the systolic arterial pressure. In subjects examined immediately after the vasodepressor syncope episode the bradycardic response was much more marked than in controls (p < 0.01) and in the subjects themselves 6 months after the episode, provided that they were symptom-free (p < 0.01). It is concluded that in vasodepressor syncope there is a phase in which the baroreflex is highly sensitive and that this is due not to a lowering of the stimulation threshold but to a gain in the efferent arc, which explains a vagotonic response.     

Optodynamic energy-conversion efficiency during an Er:YAG-laser-pulse delivery into a liquid through different fiber-tip geometries

When an erbium-laser pulse is directed into water through a small-diameter fiber tip (FT), the absorption of the laser energy superheats the water and its boiling induces a vapor bubble. We present the influence of different FT geometries and pulse parameters on the vapor-bubble dynamics. In our investigation, we use a free-running erbium: yttrium aluminum garnet (Er:YAG) (λ=2.94 μm) laser that was designed for laser dentistry. Its pulse is directed into the water through FTs with a flat and conical geometry. Our results show that in the case of the conical FT, a spherical bubble is induced, while a channel-like bubble develops for the flat FT. The ratio between the mechanical energy of the liquid medium and the pulse energy, which we call the optodynamic energy-conversion efficiency, is examined using shadow photography. The results indicate that this efficiency is significantly larger when a conical FT is used and it increases with increasing pulse energy and decreasing pulse duration. The spherical bubbles are compared with the Rayleigh model in order to present the influence of the pulse duration on the dynamics of the bubble's expansion.     

Effect of different combination of maternal and postnatal diet on adipose tissue morphology in male rat offspring

Purpose: Adipose tissue expansion can occur through several different ways and, under certain conditions, can be connected with chronic inflammation. TNF-α is one of the important cytokines involved in this process. Prolonged inflammation in obesity can lead to obesity-related insulin resistance and tissue dysfunction. The aim of our study was to investigate how different combination of maternal and postnatal diet affects offspring adipose tissue morphology and adipose tissue TNF-α expression.

Methods: Ten female Sprague Dawley rats, 9 weeks old, were randomly divided into two groups and fed either standard laboratory chow or food rich in saturated fatty acids during 6 weeks and then mated with the same male rat. After birth and lactation male rat offspring from both groups were divided into four subgroups depending on the diet they were fed until 22 weeks old. Samples of white adipose tissue were taken from the subcutaneous, epididymal, and perirenal fat pad. On tissue sections, histomorphometric analysis was conducted using CellProfiler program v 2.1.1, and immunohistochemical staining for TNF-α was performed.

Results: Greater mean surface area of subcutaneous and epididymal adipocytes was found in groups of male rat offspring with altered diet. In perirenal adipose tissue, the highest number of adipocytes was measured in the group where both mother and offspring were fed a high-fat diet. Adipocyte staining intensity for TNF-α did not differ significantly between the groups.

Conclusions: Together with our previously published data, our results lead to the conclusion that alteration of postnatal diet can lead to TNF-α and adipocyte morphology changes.     

Relationship between international normalized ratio values,vitamin K-dependent clotting factor levels and in vivo prothrombin activation during the early and steady phases of oral anticoagulant treatment

BACKGROUND AND OBJECTIVES: In vitro studies have shown that the rate of prothrombin activation is linearly related to the concentration of factor II (FII) in the assay system, suggesting a key role of prothrombin levels in the expression of the antithrombotic activity of oral anticoagulant treatment (OAT). We investigated the in vivo relationship between prothrombin activation and vitamin K-dependent clotting factor levels during the early and steady phases of OAT in patients and in healthy volunteers. DESIGN AND METHODS: The changes in international normalizezd ratio (INR) and in the plasma levels of FVII, FX, FII, protein C (PC) and prothrombin fragment 1.2 (F1+2) induced by OAT were monitored over 9 days in 10 patients not on heparin starting warfarin after heart valve replacement (HVR) and in 9 healthy volunteers submitted to an 8-day course of warfarin treatment. FII and F1+2 plasma levels were also measured in 100 patients on stable oral anticoagulant treatment with INRs ranging from 1.2 to 6.84. RESULTS: Because HVR patients had subnormal FVII, FX and FII levels after surgery, INR values > 2.0 were attained already 24 hours after the first warfarin dose. In healthy volunteers, INR values greater than 2.0 were first observed after 72 hours. Nadir levels of FVII, PC, FX and FII were reached between 40 and 88 hours in HVR patients and between 72 and 192 hours in healthy volunteers. The FII apparent half-disappearance time (t/2) was 99 hours in HVR patients and 115 hours in healthy volunteers (p = ns). In HVR patients there was no normalization of initially elevated F1+2 levels until day 7 with an apparent t/2 of 132 hours. In healthy volunteers, a decrease to subnormal F1+2 levels was observed by day 8 of treatment (apparent t/2 = 107 hours). In both HVR patients and healthy volunteers, FII and PC levels were independent predictors of the changes in F1+2 levels (p = 0.0001). In patients on stable OAT, only FII levels were independent predictors of the variation in F1+2 levels (p = 0.0001). INTERPRETATION AND CONCLUSIONS: During the early phase of oral anticoagulant treatment in vivo prothrombin activation is a function of the balance between FII and PC levels and is not significantly prevented until nadir levels of FII are obtained. This provides an explanation for the requirement of overlapping heparin and oral anticoagulant treatment for at least 48 hours after the achievement of therapeutic INR values in patients with thromboembolic diseases. In addition, in vivo prothrombin activation is a function of FII levels rather than INR values also in patients on stable oral anticoagulant treatment.     

The Variants in the 3′ Untranslated Region of the Matrix Metalloproteinase 9 Gene as Modulators of Treatment Outcome in Children with Asthma

Purpose

The maintaining of asthma control is difficult due to high variability in response to therapy among patients. Since matrix metalloproteinase 9 (MMP9) is implicated in inflammation and remodeling of asthmatic airways, it could be associated with adequate response to asthma therapy. The aim of this study was to investigate whether variants in 3′ end of the MMP9 gene are associated with clinical phenotype and responsiveness to treatment in children with asthma.

Methods

The study included 127 asthmatic children from Slovenia. Variants in the 3′ end of the MMP9 gene were analyzed by direct DNA sequencing and the obtained results were correlated with clinical parameters.

Results

Two variants were detected, rs13925 and rs20544. For the variant rs20544, statistically significant difference in airway hyperresponsiveness (p?=?0.011) and asthma control (p?=?0.049) between genotypes was found. Patients with TT genotype had lower airway sensitivity, and after 12 months of treatment showed significant improvement in Asthma Control Test (ACT) scores compared to CC and CT genotype. For the variant rs13925, the association with lung function was observed. The carriers of A allele showed noticeable improvement of lung function after the first 6 months of treatment in comparison to the carriers of G allele (p?=?0.046).

Conclusion

The main finding of our study is the association of MMP9 genotypes rs20544 TT and rs13925 AA and AG with better asthma control, and indirectly better response to treatment. Based on these results, MMP9 deserves further research as a potential predictive biomarker for asthma.