Enhanced nonlinearities in hybrid structure based on nanoporous membrane and a metallohelicate with promising application in nanophotonics and NLO.

The main purposes of this work are designing new hybrid structures based on alumina nanoporous membranes with specific metallosupramolecular structure as well as studies of their usefulness in nonlinear optics (NLO). The NLO studies of the hybrid material is performed on the basis of two methods: the first by the Maker fringe technique, where the second harmonic generation (SHG) signal is recorded by rotating the sample; and the second by SHG imaging microscopy, where the SHG signal is collected point by point on the sample surface. The enhanced SHG signals were obtained without the use of the corona poling method needed during the experiment on thin films in our previous works and clearly shows the efficiency of hybrid materials based on nanoporous membranes as promising materials in devices developed based on NLO.

Intravenous Nicotinamide Riboside Administration Has a Cardioprotective Effect in Chronic Doxorubicin-Induced Cardiomyopathy.

Doxorubicin, which is widely used to treat a broad spectrum of malignancies, has pronounced dose-dependent side effects leading to chronic heart failure development. Nicotinamide riboside (NR) is one of the promising candidates for leveling the cardiotoxic effect. In the present work, we performed a comparative study of the cardioprotective and therapeutic actions of various intravenous NR administration modes in chronic doxorubicin-induced cardiomyopathy in Wistar rats. The study used 60 mature male SPF Wistar rats. The animals were randomized into four groups (a control group and three experimental groups) which determined the doxorubicin (intraperitoneally) and NR (intravenous) doses as well as the specific modes of NR administration (combined, preventive). We demonstrated the protective effect of NR on the cardiovascular system both with combined and preventive intravenous drug administration, which was reflected in a fibrous tissue formation decrease, reduced fractional-shortening decrease, and better antioxidant system performance. At the same time, it is important to note that the preventive administration of NR had a more significant protective effect on the animal organism as a whole. This was confirmed by better physical activity parameters and vascular bed conditions. Thus, the data obtained during the study can be used for further investigation into chronic doxorubicin-induced cardiomyopathy prevention and treatment approaches.

Dumbbell-Shaped, Graft and Bottlebrush Polymers with All-Siloxane Nature: Synthetic Methodology, Thermal, and Rheological Behavior.

A methodology for synthesizing a wide range of dumbbell-shaped, graft and bottlebrush polymers with all-siloxane nature (without carbosilane linkers) is suggested. These macroarchitectures are synthesized from SiOH-containing compounds-silanol (Et3 SiOH) and siloxanol dendrons of the first and second generations, with various peripheral substituents (Me or Et)-and from linear siloxanes comprising terminal and internal SiH groups by the Piers-Rubinsztajn reaction. Products and key building blocks are obtained in yields up to 95%. These polymers are heat and frost-resistant siloxanes. As it turns out, the product physical properties are determined not only by the macromolecular structure, the linear chain length, the size and frequency of branched pendant, but also by the type of peripheral substituents-Me or Et-in the pendant. Thus, the viscosity of the graft polymers with branched pendant groups comprising peripheral Me-groups is more than ≈3-5 fold lower than that of analogous polymers with peripheral Et-groups.

Aerobic Co-/ N-Hydroxysuccinimide-Catalyzed Oxidation of p-Tolylsiloxanes to p-Carboxyphenylsiloxanes: Synthesis of Functionalized Siloxanes as Promising Building Blocks for Siloxane-Based Materials.

Synthesis of organosilicon products with a "polar" functional group within organic substituents is one of the most fundamentally and practically important challenges in today's chemistry of silicones. In our study, we suggest a solution to this problem, viz., a high-efficiency preparative method based on aerobic Co-/ N-hydroxysuccinimide (NHSI) catalyzed oxidation of p-tolylsiloxanes to p-carboxyphenylsiloxanes. This approach is based on "green", commercially available, simple, and inexpensive reagents and employs mild reaction conditions: Co(OAc)2/NHSI catalytic system, O2 as the oxidant, process temperature from 40 to 60 °C, atmospheric pressure. This reaction is general and allows for synthesizing both mono- and di-, tri-, and poly( p-carboxyphenyl)siloxanes with p-carboxyphenyl groups at 1,1-, 1,3-, 1,5-, and 1,1,1-positions. All the products were obtained and isolated in gram amounts (up to 5 g) and in high yields (80-96%) and characterized by NMR, ESI-HRMS, GPC, IR, and X-ray data: p-carboxyphenylsiloxanes in crystalline state form HOF-like structures. Furthermore, it was shown that the suggested method is applicable for the oxidation of organic alkylarene derivatives (Ar-CH3, Ar-CH2-R) to the corresponding acids and ketones (Ar-C(O)OH and Ar-C(O)-R), as well as hydride silanes ([Si]-H) to silanols ([Si]-OH). The possibility of synthesizing monomeric (methyl) and polymeric (siloxane-containing PET analogue, Sila-PET) esters based on 1,3-bis( p-carboxyphenyl)disiloxane was studied. These processes occur with retention of the organosiloxane frame and allow to obtain the corresponding products in 90 and 99% yields.

Seizure susceptibility and infraslow modulatory activity in the intracranial electroencephalogram.

OBJECTIVE: Studies of infraslow amplitude modulations (<0.15 Hz) of band power time series suggest that these envelope correlations may form a basis for distant spatial coupling in the brain. In this study, we sought to determine how infraslow relationships are affected by antiepileptic drug (AED) taper, time of day, and seizure. METHODS: We studied intracranial electroencephalographic (icEEG) data collected from 13 medically refractory adult epilepsy patients who underwent monitoring at Yale-New Haven Hospital. We estimated the magnitude-squared coherence (MSC) at <0.15 Hz of traditional EEG frequency band power time series for all electrode contact pairs to quantify infraslow envelope correlations between them. We studied, first, hour-long background icEEG epochs before and after AED taper to understand the effect of taper. Second, we analyzed the entire record for each patient to study the effect of time of day. Finally, for each patient, we reviewed the clinical record to find all seizures that were at least 6 hours removed from other seizures and analyzed infraslow envelope MSC before and after them. RESULTS: Infraslow envelope MSC increased slightly, but significantly, after AED taper, and increased on average during the night and decreased during the day. It was also increased significantly in all frequency bands up to 3 hours preseizure and 1 hour postseizure as compared to background icEEG (61 seizures studied). These changes occurred for both daytime and nighttime seizures (28 daytime, 33 nighttime). Interestingly, there was significant spatial variability to these changes, with the seizure onset area peaking at 3 hours preseizure, then showing progressive desynchronization from 3 hours preseizure to 1 hour postseizure. SIGNIFICANCE: Infraslow envelope analysis may be used to understand long-term changes over the course of icEEG monitoring, provide unique insight into interictal electrophysiological changes related to ictogenesis, and contribute to the development of novel seizure forecasting algorithms.

The spatial and signal characteristics of physiologic high frequency oscillations.

OBJECTIVES: To study the incidence, spatial distribution, and signal characteristics of high frequency oscillations (HFOs) outside the epileptic network. METHODS: We included patients who underwent invasive evaluations at Yale Comprehensive Epilepsy Center from 2012 to 2013, had all major lobes sampled, and had localizable seizure onsets. Segments of non-rapid eye movement (NREM) sleep prior to the first seizure were analyzed. We implemented a semiautomated process to analyze oscillations with peak frequencies >80 Hz (ripples 80-250 Hz; fast ripples 250-500 Hz). A contact location was considered epileptic if it exhibited epileptiform discharges during the intracranial evaluation or was involved ictally within 5 s of seizure onset; otherwise it was considered nonepileptic. RESULTS: We analyzed recordings from 1,209 electrode contacts in seven patients. The nonepileptic contacts constituted 79.1% of the total number of contacts. Ripples constituted 99% of total detections. Eighty-two percent of all HFOs were seen in 45.2% of the nonepileptic contacts (82.1%, 47%, 34.6%, and 34% of the occipital, parietal, frontal, and temporal nonepileptic contacts, respectively). The following sublobes exhibited physiologic HFOs in all patients: Perirolandic, basal temporal, and occipital subregions. The ripples from nonepileptic sites had longer duration, higher amplitude, and lower peak frequency than ripples from epileptic sites. A high HFO rate (>1/min) was seen in 110 nonepileptic contacts, of which 68.2% were occipital. Fast ripples were less common, seen in nonepileptic parietooccipital regions only in two patients and in the epileptic mesial temporal structures. CONCLUSIONS: There is consistent occurrence of physiologic HFOs over vast areas of the neocortex outside the epileptic network. HFOs from nonepileptic regions were seen in the occipital lobes and in the perirolandic region in all patients. Although duration of ripples and peak frequency of HFOs are the most effective measures in distinguishing pathologic from physiologic events, there was significant overlap between the two groups.

Seizure localization using three-dimensional surface projections of intracranial EEG power.

Intracranial EEG (icEEG) provides a critical road map for epilepsy surgery but it has become increasingly difficult to interpret as technology has allowed the number of icEEG channels to grow. Borrowing methods from neuroimaging, we aimed to simplify data analysis and increase consistency between reviewers by using 3D surface projections of intracranial EEG poweR (3D-SPIER). We analyzed 139 seizures from 48 intractable epilepsy patients (28 temporal and 20 extratemporal) who had icEEG recordings, epilepsy surgery, and at least one year of post-surgical follow-up. We coregistered and plotted icEEG ß frequency band signal power over time onto MRI-based surface renderings for each patient, to create color 3D-SPIER movies. Two independent reviewers interpreted the icEEG data using visual analysis vs. 3D-SPIER, blinded to any clinical information. Overall agreement rates between 3D-SPIER and icEEG visual analysis or surgery were about 90% for side of seizure onset, 80% for lobe, and just under 80% for sublobar localization. These agreement rates were improved when flexible thresholds or frequency ranges were allowed for 3D-SPIER, especially for sublobar localization. Interestingly, agreement was better for patients with good surgical outcome than for patients with poor outcome. Localization using 3D-SPIER was measurably faster and considered qualitatively easier to interpret than visual analysis. These findings suggest that 3D-SPIER could be an improved diagnostic method for presurgical seizure localization in patients with intractable epilepsy and may also be useful for mapping normal brain function.

Left subclavian artery pseudoaneurysm after blunt chest trauma with left upper extremity ischemia.

We describe a 74-year-old male with delayed onset of acute left upper extremity ischemia after blunt chest trauma with left clavicular fracture, resulting in left subclavian artery injury, including pseudoaneurysm formation, intramural hematoma, thrombosis, and distal embolization to the brachial artery. The patient presented with left upper extremity pain, forearm and hand numbness, and digital cyanosis. The patient was treated with a hybrid approach, consisting of transfemoral percutaneous deployment of a covered stent in the left subclavian artery and concomitant surgical thrombectomy of the left brachial artery, resulting in excellent recovery and resolution of symptoms.

Spatial distribution of intracranially recorded spikes in medial and lateral temporal epilepsies.

PURPOSE: Although seizures and interictal spikes are not always colocalized, there may be valuable localizing information in the spatial distribution of spikes. To test this hypothesis, we studied the spatial distribution of intracranially recorded interictal spikes in patients with medial temporal (MT) and lateral temporal (LT) neocortical seizure onset. METHODS: A total of 21 patients (MT n = 12, LT n = 9) who completed intracranial monitoring were selected for this study. Two 4-h intracranial electroencephalography (icEEG) epochs were analyzed, one during wake and one during sleep, both at least 6 h removed from seizures. Spikes detected automatically in medial temporal structures [hippocampal formation (H) and entorhinal cortex (EC)], and in five cortical areas (occipital, frontal, parietal, lateral temporal, and inferior temporal) were tabulated. RESULTS: Interictal spikes occurred broadly over medial temporal structures and cortical areas in MT and LT patients. The patients differed with a greater number of spikes in medial temporal structures in the MT group (p < 0.05 for H and p < 0.001 for EC) and a greater number of spikes in parietal (p < 0.01) and frontal (p < 0.001) areas in the LT group. There were sleep-related increases in spike rates in inferomedial temporal structures in both groups. The two groups could be separated with a classifier based on medial temporal and parietal and frontal spikes (p < 0.0001). DISCUSSION: MT and LT patients have different spatial distributions of interictal spikes and can be distinguished by the relative spike rates in medial temporal and extratemporal areas during sleep and wake.

Effects of working memory load on oscillatory power in human intracranial EEG.

Studies of working memory load effects on human EEG power have indicated divergent effects in different frequency bands. Although gamma power typically increases with load, the load dependency of the lower frequency theta and alpha bands is uncertain. We obtained intracranial electroencephalography measurements from 1453 electrode sites in 14 epilepsy patients performing a Sternberg task, in order to characterize the anatomical distribution of load-related changes across the frequency spectrum. Gamma power increases occurred throughout the brain, but were most common in the occipital lobe. In the theta and alpha bands, both increases and decreases were observed, but with different anatomical distributions. Increases in theta and alpha power were most prevalent in frontal midline cortex. Decreases were most commonly observed in occipital cortex, colocalized with increases in the gamma range, but were also detected in lateral frontal and parietal regions. Spatial overlap with group functional magnetic resonance imaging results was minimal except in the precentral gyrus. These findings suggest that power in any given frequency band is not a unitary phenomenon; rather, reactivity in the same frequency band varies in different brain regions, and may relate to the engagement or inhibition of a given area in a cognitive task.

Comorbidity of asthma and hypertension may be mediated by shared genetic dysregulation and drug side effects.

Asthma and hypertension are complex diseases coinciding more frequently than expected by chance. Unraveling the mechanisms of comorbidity of asthma and hypertension is necessary for choosing the most appropriate treatment plan for patients with this comorbidity. Since both diseases have a strong genetic component in this article we aimed to find and study genes simultaneously associated with asthma and hypertension. We identified 330 shared genes and found that they form six modules on the interaction network. A strong overlap between genes associated with asthma and hypertension was found on the level of eQTL regulated genes and between targets of drugs relevant for asthma and hypertension. This suggests that the phenomenon of comorbidity of asthma and hypertension may be explained by altered genetic regulation or result from drug side effects. In this work we also demonstrate that not only drug indications but also contraindications provide an important source of molecular evidence helpful to uncover disease mechanisms. These findings give a clue to the possible mechanisms of comorbidity and highlight the direction for future research.

Interictal spikes on intracranial recording: behavior, physiology, and implications.

PURPOSE: The physiological, pathological, and clinical meaning of interictal spikes (IISs) remains controversial. We systematically analyzed the frequency, occurrence, and distribution of IISs recorded from multiple intracranial electrodes in 34 refractory epileptic patients with respect to seizures and antiepileptic drug (AED) changes. METHODS: Continuous spike counts from all recorded contacts of all implanted electrodes, and also separately for the subset of contacts involved at seizure onset, were tabulated for every hour of every day of recording, and expressed as spikes per hour in six preselected, 24-h intervals (defined to exclude seizures): (1) on medications; (2) prepreseizure; (3) preseizure; (4) postseizure; (5) off meds; and (6) resumed meds. Mean spike rates were analyzed for differences between designated 24-h intervals. RESULTS: Spike rate in all recorded contacts consistently and significantly decreased after AED withdrawal, despite variability in initial spike rate, diurnal occurrence, seizure character/number/localization of onset, and type(s) of AED continued or withdrawn (p < 0.0001). A significant increase in spike rate was noted in the 24 h after seizures of medial temporal origin, in the medial temporal lobe contacts; neocortical onset seizures did not show any increase. CONCLUSIONS: These observations confirm and extend previous reports, suggesting a general effect of AED withdrawal, and a more specific effect of medial temporal lobe seizures, on IIS rate. AED mechanisms and efficacy might be demonstrated by quantifying IIS with changes in AEDs. Furthermore, variability in IIS rate after seizures distinguishes localization of seizure onset in medial temporal versus neocortical locations.

Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks.

BACKGROUND: Hypertension and bronchial asthma are a major issue for people's health. As of 2014, approximately one billion adults, or ~ 22% of the world population, have had hypertension. As of 2011, 235-330 million people globally have been affected by asthma and approximately 250,000-345,000 people have died each year from the disease. The development of the effective treatment therapies against these diseases is complicated by their comorbidity features. This is often a major problem in diagnosis and their treatment. Hence, in this study the bioinformatical methodology for the analysis of the comorbidity of these two diseases have been developed. As such, the search for candidate genes related to the comorbid conditions of asthma and hypertension can help in elucidating the molecular mechanisms underlying the comorbid condition of these two diseases, and can also be useful for genotyping and identifying new drug targets. RESULTS: Using ANDSystem, the reconstruction and analysis of gene networks associated with asthma and hypertension was carried out. The gene network of asthma included 755 genes/proteins and 62,603 interactions, while the gene network of hypertension - 713 genes/proteins and 45,479 interactions. Two hundred and five genes/proteins and 9638 interactions were shared between asthma and hypertension. An approach for ranking genes implicated in the comorbid condition of two diseases was proposed. The approach is based on nine criteria for ranking genes by their importance, including standard methods of gene prioritization (Endeavor, ToppGene) as well as original criteria that take into account the characteristics of an associative gene network and the presence of known polymorphisms in the analysed genes. According to the proposed approach, the genes IL10, TLR4, and CAT had the highest priority in the development of comorbidity of these two diseases. Additionally, it was revealed that the list of top genes is enriched with apoptotic genes and genes involved in biological processes related to the functioning of central nervous system. CONCLUSIONS: The application of methods of reconstruction and analysis of gene networks is a productive tool for studying the molecular mechanisms of comorbid conditions. The method put forth to rank genes by their importance to the comorbid condition of asthma and hypertension was employed that resulted in prediction of 10 genes, playing the key role in the development of the comorbid condition. The results can be utilised to plan experiments for identification of novel candidate genes along with searching for novel pharmacological targets.

Molecular Relationships between Bronchial Asthma and Hypertension as Comorbid Diseases.

Comorbidity, a co-incidence of several disorders in an individual, is a common phenomenon. Their development is governed by multiple factors, including genetic variation. The current study was set up to look at associations between isolated and comorbid diseases of bronchial asthma and hypertension, on one hand, and single nucleotide polymorphisms associated with regulation of gene expression (eQTL), on the other hand. A total of 96 eQTL SNPs were genotyped in 587 Russian individuals. Bronchial asthma alone was found to be associated with rs1927914 (TLR4), rs1928298 (intergenic variant), and rs1980616 (SERPINA1); hypertension alone was found to be associated with rs11065987 (intergenic variant); rs2284033 (IL2RB), rs11191582 (NT5C2), and rs11669386 (CARD8); comorbidity between asthma and hypertension was found to be associated with rs1010461 (ANG/RNASE4), rs7038716, rs7026297 (LOC105376244), rs7025144 (intergenic variant), and rs2022318 (intergenic variant). The results suggest that genetic background of comorbidity of asthma and hypertension is different from genetic backgrounds of both diseases manifesting isolated.

A comparison of the power spectral density of scalp EEG and subjacent electrocorticograms.

OBJECTIVE: Our study investigated the effects of the intact skull on background EEG rhythms recorded simultaneously by subdural electrocorticography (ECoG) and scalp EEG. METHODS: We performed a retrospective analysis of twenty patients undergoing intracranial EEG monitoring. EEG and ECoG were recorded simultaneously from the central and occipital scalp and subjacent subdural electrodes removed (median 46 mm, interquartile 27-65) from the craniotomy. The power spectral density (PSD) of artifact-free EEG and ECoG segments and ratio of the scalp EEG to subjacent ECoG PSD was calculated. RESULTS: Overall both ECoG and scalp EEG power decreased by over three orders of magnitude from delta to gamma frequency band with an empirical inverse power relationship. The ratio of scalp EEG to ECoG PSD decreased across the delta and theta frequency bands, remained the same across the alpha, beta and low gamma bands, but increased at the higher frequency bands. CONCLUSIONS: EEG PSD mirrored changes in ECoG PSD across the frequency bands. As ECoG power continued to decrease above 42 Hz, extracranial voltage sources contributed to a greater fraction of scalp EEG power. SIGNIFICANCE: Monitoring the gamma frequency band using scalp EEG was limited by low power on ECoG and masking by extracranial voltage sources.

The relationship between seizures, interictal spikes and antiepileptic drugs.

OBJECTIVE: A considerable decrease in spike rate accompanies antiepileptic drug (AED) taper during intracranial EEG (icEEG) monitoring. Since spike rate during icEEG monitoring can be influenced by surgery to place intracranial electrodes, we studied spike rate during long-term scalp EEG monitoring to further test this observation. METHODS: We analyzed spike rate, seizure occurrence and AED taper in 130 consecutive patients over an average of 8.9days (range 5-17days). RESULTS: We observed a significant relationship between time to the first seizure, spike rate, AED taper and seizure occurrence (F (3,126)=19.77, p<0.0001). A high spike rate was related to a longer time to the first seizure. Further, in a subset of 79 patients who experienced seizures on or after day 4 of monitoring, spike rate decreased initially from an on- to off-AEDs epoch (from 505.0 to 382.3 spikes per hour, p<0.00001), and increased thereafter with the occurrence of seizures. CONCLUSIONS: There is an interplay between seizures, spikes and AEDs such that spike rate decreases with AED taper and increases after seizure occurrence. SIGNIFICANCE: The direct relationship between spike rate and AEDs and between spike rate and time to the first seizure suggests that spikes are a marker of inhibition rather than excitation.

Progressive change in sleep over multiple nights of intracranial EEG monitoring.

OBJECTIVE: We evaluated changes to sleep structure during continuous intracranial EEG (icEEG) monitoring of epilepsy patients undergoing localization of the seizure onset area. METHODS: We studied 28 adult epilepsy patients who underwent icEEG monitoring for a median of 12 nights. We used a metric calculated from relative delta power (RDP) to evaluate the emergence of sleep cycles for every night of monitoring. We further evaluated the effect of seizures and AEDs on trends in the RDP metric. RESULTS: We observed oscillations corresponding to sleep cycles in the RDP time-series. There was a significant increasing trend in our RDP sleep metric over the course of monitoring. Seizures and AEDs did not significantly affect this trend. CONCLUSIONS: The RDP metric increased during icEEG monitoring, independent of seizures and AEDs. This increase may be due to a number of factors and these factors appear to outweigh the effects of seizures and AEDs. SIGNIFICANCE: Our results indicate that sleep is not uniform during icEEG monitoring, rather there is a considerable increasing, multi-night change in sleep structure.

Regional and network relationship in the intracranial EEG second spectrum.

OBJECTIVE: We examined low-frequency amplitude modulations of band power time-series, i.e. the second spectrum, of the intracranial EEG (icEEG) for evidence of support for spatial relationships between different parts of the brain and within the default mode network (DMN). METHODS: We estimated magnitude-squared coherence (MSC) of the running power in the delta, theta, alpha, beta, and gamma frequency bands for one-hour background icEEG epochs recorded from 9 patients. We isolated two test areas within the DMN and one control area outside it. We tested if the relationship between DMN areas was stronger than the relationship between each of these areas and the control location, and between all intrahemispheric contact pairs with similar intercontact distance. RESULTS: We observed very low values of second spectrum relationship between different parts of the brain, except at very short distances. These relationships are strongest in the delta band and decrease with increasing frequency, with gamma band relationships being the weakest. Our DMN-specific analysis showed no enhanced connectivity in the second spectrum in DMN locations in any frequency band. CONCLUSIONS: Though we observed significantly nonzero relationships in lower frequency bands, second spectrum relationships are consistently very low across the entire brain in every frequency band. SIGNIFICANCE: This study suggests a lack of support for the DMN in the icEEG second spectrum.

Remote complications of spilled gallstones during laparoscopic cholecystectomy: causes, prevention, and management.

In the last 11 years (November 1989-December 2000), 5526 laparoscopic cholecystectomies were performed in a community residency training program. Two cases (0.04%) of remote complications secondary to spilled gallstones were identified. A 75-year-old woman presented with a sterile abscess in the abdominal wall containing gallstones 4 years and 4 months after an elective laparoscopic cholecystectomy. The second patient, a 43-year-old woman, presented with a subdiaphragmatic/subhepatic abscess containing gallstones. The abscess grew the same bacteria that were present 2 years and 3 months previously during a laparoscopic cholecystectomy for acute gangrenous cholecystitis. In both cases, pigmented gallstones were identified. Causes of gallstone spillage, means of prevention, and ways of managing this complication are discussed.