Altered long-range functional connectivity in PTSD: Role of the infraslow oscillations of cortical activity amplitude envelopes.

OBJECTIVE: Coupling between the amplitude envelopes (AEs) of regional cortical activity reflects mechanisms that coordinate the excitability of large-scale cortical networks. We used resting-state MEG recordings to investigate the association between alterations in the coupling of cortical AEs and symptoms of post-traumatic stress disorder (PTSD). METHODS: Participants (n = 96) were service members with combat exposure and various levels of post-traumatic stress severity (PTSS). We assessed the correlation between PTSS and (1) coupling of broadband cortical AEs of beta band activity, (2) coupling of the low- (<0.5 Hz) and high-frequency (>0.5 Hz) components of the AEs, and (3) their time-varying patterns. RESULTS: PTSS was associated with widespread hypoconnectivity assessed from the broadband AE fluctuations, which correlated with subscores for the negative thoughts and feelings/emotional numbing (NTF/EN) and hyperarousal clusters of symptoms. Higher NTF/EN scores were also associated with smaller increases in resting-state functional connectivity (rsFC) with time during the recordings. The distinct patterns of rsFC in PTSD were primarily due to differences in the coupling of low-frequency (infraslow) fluctuations of the AEs of beta band activity. CONCLUSIONS: Our findings implicate the mechanisms underlying the regulation/coupling of infraslow oscillations in the alterations of rsFC assessed from broadband AEs and in PTSD symptomatology. SIGNIFICANCE: Altered coordination of infraslow amplitude fluctuations across large-scale cortical networks can contribute to network dysfunction and may provide a target for treatment in PTSD.

Biopolymers Produced by Lactic Acid Bacteria: Characterization and Food Application.

Plants, animals, bacteria, and food waste are subjects of intensive research, as they are biological sources for the production of biopolymers. The topic links to global challenges related to the extended life cycle of products, and circular economy objectives. A severe and well-known threat to the environment, the non-biodegradability of plastics obliges different stakeholders to find legislative and technical solutions for producing valuable polymers which are biodegradable and also exhibit better characteristics for packaging products. Microorganisms are recognized nowadays as exciting sources for the production of biopolymers with applications in the food industry, package production, and several other fields. Ubiquitous organisms, lactic acid bacteria (LAB) are well studied for the production of exopolysaccharides (EPS), but much less as producers of polylactic acid (PLA) and polyhydroxyalkanoates (PHAs). Based on their good biodegradability feature, as well as the possibility to be obtained from cheap biomass, PLA and PHAs polymers currently receive increased attention from both research and industry. The present review aims to provide an overview of LAB strains' characteristics that render them candidates for the biosynthesis of EPS, PLA, and PHAs, respectively. Further, the biopolymers' features are described in correlation with their application in different food industry fields and for food packaging. Having in view that the production costs of the polymers constitute their major drawback, alternative solutions of biosynthesis in economic terms are discussed.

Formation of Alginate/Chitosan Interpenetrated Networks Revealed by EPR Spectroscopy.

This study analyzes the physico-chemical properties of interpenetrated polymer networks (IPNs) and semi-IPN resulting from cross-linking chitosan with glutaraldehyde and alginate with Ca2+ cations, as a function of the order in which the cross-linking agents are added to the polymer mixture. Three physico-chemical methods were used to assess the differences between systems: rheology, IR spectroscopy, and electron paramagnetic resonance (EPR) spectroscopy. While rheology and IR spectroscopy are commonly used to characterize gel materials, EPR spectroscopy is rarely used, but has the advantage of providing local information about the dynamics of a system. The rheological parameters, which describe the global behavior of the samples, show that semi-IPN systems have a weaker gel behavior and the order of introducing the cross-linker in the polymer systems plays a role. The IR spectra of samples resulting by adding only Ca2+ or Ca2+ as the first cross-linker are similar to that of the alginate gel, while the spectra of samples in which glutaraldehyde is firstly added resemble the chitosan gel spectrum. Using spin-labeled alginate and spin-labeled chitosan, we monitored the changes occurring in the dynamic of the spin labels due to the formation of IPN and semi-IPN. The results show that the order of adding the cross-linking agents influences the dynamic of the IPN network, and that the formation of the alginate network determines the characteristics of the entire IPN system. The EPR data were correlated with the rheological parameters and IR spectra of the analyzed samples.

His-bundle pacing and atrioventricular nodal ablation for noncontrolled atrial arrhythmia: A technical challenge with major clinical benefits.

BACKGROUND: His-bundle pacing (HBP) is an appealing alternative to right ventricular pacing in patients referred for permanent ventricular pacing and atrioventricular nodal ablation (AVNA) because it preserves physiological ventricular activation. Only limited data regarding HBP combined with AVNA are available in the literature. OBJECTIVE: The purpose of this study was to provide further evidence on the feasibility and efficacy of this therapeutic approach in patients with uncontrolled atrial arrhythmia. METHODS: We prospectively included all patients who had undergone AVNA after HBP in 3 different hospitals between 2017 and 2022. RESULTS: AVNA following HBP lead implantation was performed in 75 patients. Complete atrioventricular (AV) block was obtained in 58 patients (77%), and significant modulation of AV nodal conduction (heart rate <60 bpm) was obtained in 12 patients (16%). AVNA failure was observed in 5 patients (7%). Recording of an atrial signal by the HBP lead was more frequently observed in patients with AVNA modulation/failure than in patients with complete AV block (11/17 vs 5/58; P <.001). No lead dislodgment occurred during the AVNA procedures. Acute His-bundle (HB) capture threshold increase >1 V occurred in 11 patients (15%), with return to baseline value on day 1 in 9 patients. New York Heart Association functional class and left ventricular ejection fraction significantly improved from baseline to last follow-up (3.0 ± 0.7 vs 1.6 ± 0.5; P <.001; and 47% ± 14% vs 60% ± 9%; P <.0001, respectively). CONCLUSION: AVNA combined with HBP for noncontrolled atrial arrhythmia was feasible and clinically efficient. Implanting the HB lead on the ventricular aspect of the tricuspid annulus avoiding atrial signal recording can facilitate AVNA.

Cognitive flexibility in post-traumatic stress disorder: Sustained interference associated with altered modulation of cortical oscillatory activity during task-switching.

Post-traumatic stress disorder (PTSD) is associated with deficits in cognitive flexibility, with evidence suggesting that these deficits may be a risk factor for the development of core PTSD symptoms. Understanding the neurophysiological substrate of this association could aid the development of effective therapies for PTSD. In this study, we investigated the relationship between post-traumatic stress severity (PTSS) in service members with combat exposure and the modulation of cortical oscillatory activity during a test of cognitive flexibility. Participants were assigned to three groups based on PTSS scores: low (well below a threshold consistent with a diagnosis of PTSD, n = 30), moderate (n = 32), and high (n = 29) symptom severity. Magnetoencephalography data were recorded while participants performed a cued rule-switching task in which two matching rules were repeated or switched across consecutive trials. Participants with high PTSS had longer reaction times for both switch and repeat trials, and showed evidence of sustained residual interference during repeat trials. During the cue-stimulus interval, participants with moderate and high PTSS showed higher relative theta power in switch trials over left dorsolateral prefrontal cortex (DLPFC). After test-stimulus onset, participants with high PTSS showed less suppression of beta band activity, which was present over multiple prefrontal, parietal, and temporal regions in switch trials, but it was confined to ventromedial prefrontal cortex in repeat trials. Higher theta band activity is a marker of effortful voluntary shifting of attention, while lower suppression of beta band activity reflects difficulties with inhibition of competing perceptual information and courses of action. These findings are consistent with a role for altered suppression of beta band activity, which can be due to less effective top-down bias signals exerted by DLPFC, in the etiology of cognitive flexibility deficits in PTSD.

AKAP9-Related Channelopathy: Novel Pathogenic Variant and Review of the Literature.

Disease-associated pathogenic variants in the A-Kinase Anchor Protein 9 (AKAP9) (MIM *604001) have been recently identified in patients with autosomal dominant long QT syndrome 11 (MIM #611820), lethal arrhythmia (ventricular fibrillation, polymorphic ventricular tachycardia), Brugada syndrome, and sudden unexpected death. However, AKAP9 sequence variations were rarely reported and AKAP9 was classified as a "disputed evidence" gene to support disease causation due to the insufficient genetic evidence and a limited number of reported AKAP9-mutated patients. Here, we describe a 47-year-old male carrying a novel frameshift AKAP9 pathogenic variant who presented recurrent syncopal attacks and sudden cardiac arrest that required a semi-automatic external defibrillator implant and an electric shock treatment of ventricular arrhythmia. This study provides insight into the mechanism underlying cardiac arrest and confirms that AKAP9 loss-of-function variants predispose to serious, life-threatening ventricular arrhythmias.

Evaluation of the Accessibility of Molecules in Hydrogels Using a Scale of Spin Probes.

In this work, we explored by means of electron paramagnetic resonance (EPR) spectroscopy the accessibility of a series of spin probes, covering a scale of molecular weights in the range of 200-60,000 Da, in a variety of hydrogels: covalent network, ionotropic, interpenetrating polymer network (IPN) and semi-IPN. The covalent gel network consists of polyethylene or polypropylene chains linked via isocyanate groups with cyclodextrin, and the ionotropic gel is generated by alginate in the presence of Ca2+ ions, whereas semi-IPN and IPN gel networks are generated in a solution of alginate and chitosan by adding crosslinking agents, Ca2+ for alginate and glutaraldehyde for chitosan. It was observed that the size of the diffusing species determines the ability of the gel to uptake them. Low molecular weight compounds can diffuse into the gel, but when the size of the probes increases, the gel cannot uptake them. Spin-labelled Pluronic F127 cannot be encapsulated by any covalent gel, whereas spin-labelled albumin can diffuse in alginate gels and in most of the IPN networks. The EPR spectra also evidenced the specific interactions of spin probes inside hydrogels. The results suggest that EPR spectroscopy can be an alternate method to evaluate the mesh size of gel systems and to provide information on local interactions inside gels.

Mapping of clinical research on artificial intelligence in the treatment of cancer and the challenges and opportunities underpinning its integration in the European Union health sector.

BACKGROUND: Although current efforts are made to diminish the incidence and burden of disease, cancer is still widely identified late at stage. This study aims to conduct a systematic review mapping the existent and emerging clinical research on artificial intelligence (AI) in the treatment of cancer and to underpin its integration challenges and opportunities in the European Union (EU) health sector. METHODS: A systematic literature review (SLR) evaluating global clinical trials (CTs; published between 2010 and 2020 or forthcoming) was concluded. Additionally, a horizon scanning (HS) exercise focusing on emerging trends (published between 2017 and 2020) was conducted. RESULTS: Forty-four CTs were identified and analyzed. Selected CTs were divided into three research areas: (i) potential of AI combined with imaging techniques, (ii) AI's applicability in robotic surgery interventions and (iii) AI's potential in clinical decision making. Twenty-one studies presented an interventional nature, nine papers were observational and 14 articles did not explicitly mention the type of study performed. The papers presented an increased heterogeneity in sample size, type of tumour, type of study and reporting of results. In addition, a shift in research is observed and only a small fraction of studies were completed in the EU. These findings could be further linked to the current socio-economic, political, scientific, technological and environmental state of the EU in regard to AI innovation. CONCLUSION: To overcome the challenges threatening the EU's integration of such technology in the healthcare field, new strategies taking into account the EU's socio-economic and political environment are deemed necessary.

Sirenomelia with associated systemic anomalies - an autopsy report in a full term neonate.

The mermaid syndrome, also known as sirenomelia, is considered an extremely rare congenital developmental disorder characterized by anomalies of the lower spine and lower limbs. Affected babies are born with partial or total leg fusion. Sirenomelia is thought to affect one in every 60,000 to 100,000 infants. We report a case of sirenomelia occurring in a 28-year-old multiparous woman, a heavy smoker with gestational diabetes. In the other 5 pregnancies, however, she gave birth to normal babies. The post mortem examination completed the diagnosis, revealing also multiple malformations of several systems: respiratory, gastro-intestinal, genito-urinary and cardiovascular. In our full term neonate case with grade VI sirenomelia, the presence of a single umbilical artery plus the abdominal aorta with an aberrant trajectory that ends in the umbilical cord differentiates this condition from caudal regression syndrome and also explains the under-development of pelvic organs (secondary to vascular steal phenomena).

Nanoparticle-functionalized dressings for the treatment of third-degree skin burns - histopathological and immunohistochemical study.

Skin burns are one of the most common injuries associated with increased morbidity and mortality, especially in the children and the elderlies. Severe burns, especially, result in a systemic immune and inflammatory response, which may reflect in multiple organ insufficiency, and a fast and effective local restorative process is essential for functionality recovering, as well as for interrupting the generalized systemic response. We have aimed here to assess the effect of different wound dressings in what it regards the morphology and clinical restoration after a skin burn. On a rat animal model, we have evaluated the macroscopic and histopathological features of controlled third degree skin burns in control animals versus treatments with local dressings of silver sulfadiazine (SDA) cream, simple gel (G), gel + silver nanoparticles (AgNPs) (G+NPS), gel + exosomes (G+EXO) and gel + AgNPs + exosomes (Gel+NPS+EXO), at 14 days and, respectively, 21 days after the lesion. Tissue fragments were harvested and processed for histopathology and immunohistochemistry. Immunofluorescence was utilized to evaluate the maturity of underlaying granulation tissue based on double stainings for smooth muscle actin (SMA) and cluster of differentiation 31 (CD31). Our study showed variability in what it regards the vessel density and immunoexpression of SMA between the treatments, and image analysis revealed that most SMA reduction and blood vessel density reduction in the maturing granulation tissue occurred for the G+NPS and G+NPS+EXO treatments. A complete re-epithelization was also observed for the G+NPS+EXO treatment. Overall, our results show that improved topic treatments promote faster re-epithelization and reparation of the dermis after skin burn lesions, providing thus an avenue for new treatments that aim both local recuperation and systemic infection prevention.

Cortisol and Oxytocin Could Predict Covert Aggression in Some Psychotic Patients.

Background: The covert or indirect type of aggression has a risk of converting in violent acts and, considering that, it is very important to identify it in order to apply effective preventive measures. In cases of psychotic patients, the risk of becoming violent is harder to predict, as even neuter stimuli may be perceived as threat and trigger aggression. Treating all the psychiatric patients as potential aggressive subjects is not the best preventive measure as only a few of them are aggressive and this measure may further enhance the stigma on mentally ill patients. There is a current need for better understanding of covert aggression and to find objective measures, such as biological markers, that could be indicative of potential violent behavior. In this work, we try to investigate the role of cortisol and oxytocin as potential biomarkers of aggression in patients with psychosis. Material and Methods: We analyzed the level of peripheral oxytocin (pg/mL) and cortisol level (ng/mL) in 28 psychotic patients (they were not on psychotropic treatment at the moment of admission and those with substance abuse or personality disorder were excluded from the study) and correlated it with the intensity of aggression reported by the patient (overt and covert type) using the Overt Covert Aggression Inventory and the level of observed aggression of the patient in the past 7 days (rated by the health care provider) using the Modified Overt Aggression Scale. Results: We found that psychotic patients with a higher level of covert aggression had a lower level of cortisol (61.05 ± 8.04 ng/mL vs. 216.33 ± 12.6.9 ng/mL, p ˂ 0.01) and a higher level of oxytocin (102.87 ± 39.26 vs. 70.01 ± 25.07, p = 0.01) when compared with patients with a lower level of covert aggression. Furthermore, we observed significant negative correlation between cortisol and covert aggression (r = -0.676, p < 0.001) and between oxytocin and covert type of aggression (r = 0.382, p = 0.04). Moreover, we found that a lower level of cortisol together with a higher level of oxytocin are significant predictors of a style of internalized manifestation of aggression, with the predictive model explaining 55% of the variant of the internalized manifestation of aggression (F (2.25) = 17.6, p < 0.001, ß = 0.35, R2 = 55.2). We did not find significant correlations between cortisol and overt aggression, and neither between oxytocin and overt aggression. Positive correlations were also found between the overt type of self-reported aggression and overt aggression reported by the rater (r = 0.459, p = 0.01). Conclusions: The importance of a predictive model in understanding covert aggression is imperative and the results of our study show that oxytocin and cortisol warrant to be further investigated in establishing a definitive predictive model for covert aggression.

Post-traumatic stress disorder is associated with alterations in evoked cortical activation during visual recognition of scenes.

We recorded magnetoencephalography data during a visual recognition task in participants with combat exposure (n = 40, age: 41.2 ± 7.2 years) to investigate the relationship between the evoked brain activity, behavioral performance, and the severity of their post-traumatic stress symptoms assessed using the PTSD Check List for DSM V version (PCL-5). In an initial study session, participants were presented with a series of images of outdoor scenes and were instructed to study the images for an upcoming recognition test. In a subsequent session, the original images were shown intermixed with novel images while participants performed the recognition task. PCL-5 scores were negatively correlated with discrimination performance and with the recognition accuracy for original images. During the recognition session, higher PCL-5 scores were associated with reduced relative power of the evoked response to original images from 100 ms to 300 ms following the image onset over a distributed brain network including the bilateral inferior frontal gyri, left middle frontal gyrus, left supramarginal gyrus, right precuneus and the bilateral superior temporal gyri. These findings indicate that the lower recognition performance in participants with higher PTSD symptom severity is associated with altered cortical activity in brain regions that are known to play a role in the elaboration on visual cues that supports recollection.

Can permanent His bundle pacing be safely started by operators new to this technique? Data from a multicenter registry.

BACKGROUND: Right ventricular pacing (RVP) induces ventricular asynchrony in patients with normal QRS and increases the risk of heart failure and atrial fibrillation in long term. His bundle pacing (HBP) is a physiological alternative to RVP, and could overcome its drawbacks. Recent studies assessed the feasibility and safety of HBP in expert centers with a vast experience of this technique. These results may not apply to less experienced centers. We aim to evaluate the feasibility and safety of permanent HBP performed by physicians who are new to this technique. METHODS: We included all patients who underwent pacemaker implantation with attempt of HBP in three hospitals between September 2017 and January 2020. Indication for HBP was left to operators' discretion. All the operators were new for HBP. His bundle (HB) electrical parameters were recorded at implant, 3- and 12-month follow-up. RESULTS: HBP was successful in 141 of 170 patients (82.9%); selective HBP was obtained in 96 patients and nonselective HBP in 45. The mean procedure and fluoroscopy durations were 67.0 ± 28.8 min, and 7.3 ± 8.1 min (3.1 ± 4.1 Gy·cm2 ), respectively. The mean HB paced QRS duration was 106 ± 18 ms. The mean HB capture threshold was 1.29 ± 0.77 V and did not increase at 3- and 12-month follow-up. The ventricular lead revision was required in five patients. Our results showed a rapid technical learning allowing a high procedure success rate (89.8%) after 15 procedures. CONCLUSION: HBP performed by operators new to this technique appeared feasible and safe. This should encourage HBP to be performed in patients expected to experience high RVP burden.

Model Systems for Evidencing the Mediator Role of Riboflavin in the UVA Cross-Linking Treatment of Keratoconus.

Riboflavin under UVA radiation generates reactive oxygen species (ROS) that can induce various changes in biological systems. Under controlled conditions, these processes can be used in some treatments for ocular or dermal diseases. For instance, corneal cross-linking (CXL) treatment of keratoconus involves UVA irradiation combined with riboflavin aiming to induce the formation of new collagen fibrils in cornea. To reduce the damaging effect of ROS formed in the presence of riboflavin and UVA, the CXL treatment is performed with the addition of polysaccharides (dextran). Hyaluronic acid is a polysaccharide that can be found in the aqueous layer of the tear film. In many cases, keratoconus patients also present dry eye syndrome that can be reduced by the application of topical solutions containing hyaluronic acid. This study presents physico-chemical evidence on the effect of riboflavin on collagen fibril formation revealed by the following methods: differential scanning microcalorimetry, rheology, and STEM images. The collagen used was extracted from calf skin that contains type I collagen similar to that found in the eye. Spin trapping experiments on collagen/hyaluronic acid/riboflavin solutions evidenced the formation of ROS species by electron paramagnetic resonance measurements.

The Effect of Silver Nanoparticles on Antioxidant/Pro-Oxidant Balance in a Murine Model.

This study aimed to evaluate the subacute effect of two types of Ag-NPs(EG-AgNPs and PVP-EG-AgNPs) on antioxidant/pro-oxidant balance in rats. Seventy Wistar rats (35 males and 35 females) were divided in 7 groups and intraperitoneally exposed for 28 days to 0, 1, 2 and 4 mg/kg bw/day EG-Ag-NPs and 1, 2 and 4 mg/kg bw/day PVP- EG-Ag-NPs. After 28 days, the blood was collected, and the total antioxidant capacity (TAC), thiobarbituric reactive species (TBARS),protein carbonyl (PROTC) levels, reduced glutathione (GSH) levels and catalase (CAT) activity were determined. EG-Ag-NPs determined protective antioxidant effects in a dose-dependent manner. The exposure to the 4 mg/kg bw/day EG-Ag-NPs determines both in males and females a significant increase in TAC and CAT and a significant decrease in TBARS and PROTC only in females. The PVP-EG-AgNPs showed a different trend compared to EG-AgNPs. At 4 mg/kg bw/day the PVP-EG-AgNPs induce increased PROTC levels and decreased GSH (males and females) and TAC levels (males). The different mechanisms of EG-AgNPs and PVP-EG-AgNPs on antioxidant-/pro-oxidant balance can be explained by the influence of coating agent used for the preparation of the nanoparticles in the formation and composition of protein corona that influence their pathophysiology in the organism.

Altered modulation of beta band oscillations during memory encoding is predictive of lower subsequent recognition performance in post-traumatic stress disorder.

We studied the relationship between electrophysiological markers of memory encoding, subsequent recognition performance, and severity of PTSD symptoms in service members with combat exposure (n = 40, age: 41.2 ± 7.2 years) and various levels of PTSD symptom severity assessed using the PTSD Check List for DSM V version (PCL-5). Brain activity was recorded using magnetoencephalography during a serial presentation of 86 images of outdoor scenes that were studied by participants for an upcoming recognition test. In a second session, the original images were shown intermixed with an equal number of novel images while participants performed the recognition task. Participants recognized 76.0% ± 12.1% of the original images and correctly categorized as novel 89.9% ± 7.0% of the novel images. A negative correlation was present between PCL-5 scores and discrimination performance (Spearman rs = -0.38, p = 0.016). PCL-5 scores were also negatively correlated with the recognition accuracy for original images (rs = -0.37, p = 0.02). Increases in theta and gamma power and decreases in alpha and beta power were observed over distributed brain networks during memory encoding. Higher PCL-5 scores were associated with less suppression of beta band power in bilateral ventral and medial temporal regions and in the left orbitofrontal cortex. These regions also showed positive correlations between the magnitude of suppression of beta power during encoding and subsequent recognition accuracy. These findings indicate that the lower recognition performance in participants with greater PTSD symptom severity may be due in part to ineffective encoding reflected in altered modulation of beta band oscillatory activity.

The clinical-morphological profile of tuberculous pleurisies - our experience in relation to literature data.

AIM: The authors made a morphological evaluation of pleural tissue fragments from patients hospitalized in Thoracic Surgery Department of the Emergency County Hospital of Craiova, Romania, over a period of 26 years, diagnosed with tuberculous lesions in the Pathology Department of the same Hospital. PATIENTS, MATERIALS AND METHODS: The studied material consisted of pleural tissue samples taken by biopsy or surgical excision from 39 cases coming out of 841 patients investigated in the above-mentioned period of time and diagnosed from histological point of view with tuberculosis (TB). Granuloma cell population was assessed using immunohistochemical method. For diagnostic confirmation, Ziehl-Neelsen staining has been used as a rule but, in some cases, immunohistochemistry was also used. RESULTS: TB lesions predominated in men usually around or over 50 years old. The diagnostic was suspected in almost half of the cases. Right cavity was more affected and the extended fibrosis was present in a significant number of cases. The inflammatory conflict was of reactive type, with giant Langhans cells granulomas and acidophilic necrosis but sometimes with superinfection or significant fibrous sequelae. CONCLUSIONS: Pleural effusions of TB origin are a reality more and more present due to the recrudescence of pulmonary TB in the last decades. Their presence should be suspected if faced to a unilateral pleural effusion with free-flowing fluid occurred almost often to a man of any age from youth to elderly.

Post-traumatic stress disorder is associated with altered modulation of prefrontal alpha band oscillations during working memory.

OBJECTIVE: To investigate the relationship between the severity of PTSD symptoms, modulation of alpha band oscillations, and behavioral performance in a working memory task. METHODS: Magnetoencephalography data were recorded in 35 participants with combat exposure and various degrees of PTSD symptom severity while they performed a modified Sternberg working memory task: briefly presented sets of two or six letters had to be held in memory and participants indicated whether subsequent probe letters were present or absent from these sets. RESULTS: PTSD scores were positively correlated with the false positive rate in the high memory load condition. Higher rates of false recognition were associated with negative probes that were seen in recent previous trials (negative probe recency effect) or were physically similar with the list letters. The relative alpha band power in the left middle frontal gyrus was negatively correlated with both PTSD scores and false positive rates. CONCLUSIONS: Reduced task specific modulation of alpha band oscillations in left middle frontal cortex may reflect alterations in the functions of pattern separation and suppression of memory traces for irrelevant or no longer relevant information in PTSD. SIGNIFICANCE: The lower amplitude of prefrontal alpha band oscillations may represent an important physiological basis for core PTSD symptoms and can provide a target for interventions to augment response to treatment.

Toxicity and health impact of nanoparticles. Basic biology and clinical perspective.

Stroke has limited restorative treatment options. In search of new therapeutic strategies for the ischemic brain, cell-based therapies offered new hope, which has been, in the meanwhile, converted into a more realistic approach recognizing difficulties related to unfavorable environments causing low survival rates of transplanted neuronal precursors. Stem cell therapies are based on the transplantation of neuronal precursor cells (NPCs), adult stem cells propagated in cell culture or inducible pluripotent cells (iPSCs) obtained from patients and trans-differentiated into neural cells. Of these, autologous iPSCs have the advantage to be used in stroke patients because they do not raise ethical concerns and the risk of graft rejection is low. However, the use of stem cells for stroke therapy in humans has to take into account many factors including, dosage, route of administration, toxicity and side effects. For example, nanoparticles (NPs) may increase the efficacy of drugs and therapeutic cells delivery to the diseased brain. Medication dosages are generally determined by clinical trials done in relatively young, healthy people. However, in vivo and clinical data evaluating the toxic effects of NPs on neural cells are still scarce especially in the aged brain, which has a decreased homeostatic capacity and a reduced ability to cope with internal and environmental stress, as compared to the young brain. Previous studies in rodents indicate that aging along with neurodegenerative diseases may promote a proinflammatory state and leads to the development of gliosis in the aged brains. On the other hand, the nonspecific interaction between the shell of NPs and brain proteins leads to the adsorption of opsonins on their surface, forming the so-called "corona", thereby becoming ideal candidates to attract phagocytic microglia resulting in NPs engulfment and thus exacerbating neuronal death. Therefore, when designing NPs for clinical use, it should be considered that their systemic administration is associated with potential risks, especially in the aged subjects. Recently, NPs have been shown in recent years to play a crucial role in cell signaling processes involved in stroke recovery. Extracellular vesicles (EVs) are secreted by virtually all type of cells in the body and have been shown to reflect the physiological and metabolic status of the host cells. Thus, understanding the disease-specific contents of EVs would enable the discovery of novel predictive biomarkers.