In vivo monitoring of circadian timing in freely moving mice.
In mammals, the principal circadian pacemaker driving daily physiology and behavioral rhythms is located in the suprachiasmatic nucleus (SCN) in the anterior hypothalamus. The neural output of SCN is essential for the circadian regulation of behavioral activity. Although remarkable progress has been made in revealing the molecular basis of circadian rhythm generation within the SCN, the output pathways by which the SCN exert control over circadian rhythms are not well understood. Most SCN efferents target the subparaventricular zone (SPZ), which resides just dorsal to the SCN. This output pathway has been proposed as a major component involved in the outflow for circadian regulation. We have examined the downstream pathway of the central clock by means of multiunit neural activity (MUA) in freely moving mice. SCN neural activity is tightly coupled to environmental photic input and anticorrelated with MUA rhythm in the SPZ. In Clock mutant mice exhibiting attenuated circadian locomotor rhythmicity, MUA rhythmicity in the SCN and SPZ is similarly blunted. These results suggest that the SPZ plays a functional role in relaying circadian and photic signals to centers involved in generating behavioral activity.


Combined thrombophilic risk factors and essential thrombocythemia in patient with recurrent venous thromboembolic episodes-thirty-three-year follow-up.
We present the case of a 64 year-old female patient, with a clearly positive family history of venous thromboembolism (VTE), multiple VTE episodes (massive pulmonary embolism, ovarian venous plexus thrombosis, deep venous thrombosis with submassive pulmonary embolism and second deep venous thrombosis) and myocardial infarction. Laboratory tests revealed the resistance to the activated protein C, elevated FVIII and PAI-1. The patient was found to be a heterozygous carrier of FV Leiden, MTHFR C677T and PAI-1 4G/5G mutations. She was diagnosed with essential thrombocythemia at the age of 60. The thirty-three-year follow-up of our patient and detection of recurrent thrombotic episodes in the light of multiple coagulation defects with proved acquired risk factors, contributes to the risk stratification in the group of patients with very high risk. In case of our patient, we stress inadequacy of widely-accepted standard prevention measures. In our opinion, patients with very high risk require additional mechanic and specific medicament methods of VTE prevention.


Enhancing effect of thoracotomy and/or laparotomy on the development of the lung metastases in rats after intravenous inoculation of tumor cells.
To evaluate the effect of operative stress on the tumor growth, thoracotomy and/or laparotomy were performed 48 hours after the inoculation of Sato lung cancer cells in Donryu rats. The survival time, the number of metastatic foci on the surface of the lung and the per cent-area of metastatic foci in the frontal section through the pulmonary hilus were observed. Thoracotomy and laparothoracotomy reduced significantly the survival time as compared with the control but no significant difference was found between the two test groups subjected to operative stress. The number of percent-area of metastatic foci found were inversely related to the length of the survival time.


P systems with deadlock.
Rewriting P systems with parallel application of evolution rules, as defined in Besozzi et al. [Parallel rewriting P systems with deadlock. In: Hagiya, M., Ohuchi, A. (Eds.), Pre-Proceedings of DNA8 Conference, Hokkaido University, Japan, June 2002a, pp. 171-183], are considered here. Different kinds of parallelism methods are defined for string rewriting. The notion of deadlock is then introduced to describe situations where rules with mixed target indications are simultaneously applied to a common string. The generative power of parallel P systems with deadlock is analyzed, with respect to Lindenmayer systems, and some relations among different types of parallel P systems with or without deadlock, allowing to rewrite all occurrences of a single symbol, or all the symbols applying either any of the rules or only those belonging to a specific set (table) of rules are studied. Some open problems are also formulated.


Routine administration of intravenous calcium during exchange blood transfusion for treatment of severe neonatal hyperbilirubinaemia: a systematic review of quantitative evidence protocol.
The objective of this review is to assess the effectiveness of intravenous calcium given during exchange blood transfusion (EBT) in neonates.More specifically, the objectives of the review are to determine whether: Neonatal hyperbilirubinaemia is an abnormally high level of bilirubin in the circulating blood, resulting in clinically visible icterus or jaundice. A serum bilirubin level above 5 mg per dL (86 μmol per L) is a frequently encountered problem worldwide and is a common reason for neonates to present to the emergency department.Unconjugated bilirubin is toxic to infants' brains when the concentration exceeds a certain level. An unconjugated serum bilirubin concentration at toxicity level is described as 'severe hyperbilirubinaemia'. The concentrations that define toxic level vary, depending on the gestational age of the neonates and fetal maturity.Severe hyperbilirubinaemia can cause encephalopathy if not promptly treated, with significant complications such as athetoid cerebral palsy, sensorineural hearing loss, paralysis of upward gaze, dental enamel dysplasia and death.Recent reports indicate that these conditions, though rare, are still occurring despite the availability of efficient methods for treatment of hyperbilirubinaemia and its prevention.These complications can be prevented if the level of bilirubin is reduced rapidly with exchange blood transfusion.Exchange blood transfusion (EBT) is the most rapid and effective method for lowering serum bilirubin concentrations, but it is rarely needed when intensive phototherapy is effective.In the presence of hemolytic disease, severe anaemia, or a rapid rise in the total serum bilirubin level (greater than 1 mg per dL per hour in less than six hours), EBT is the recommended treatment. EBT also removes partially hemolyzed and antibody-coated erythrocytes and which is then replaced with uncoated donor red blood cells. If intensive phototherapy fails to lower the bilirubin level, then EBT is always considered as the next line of treatment in any newborn with non-hemolytic jaundice.Complications of EBT can include hypocalcaemia, seizures and even death within 24 hours. The potential seriousness of these complications makes clinicians consider intensive phototherapy before EBT.However, the option of intensive phototherapy may not be feasible and could be quite ineffective in resource limited settings where the required facilities and electrical power supply are inadequate. Under these circumstances neonates with severe hyperbilirubinaemia will most likely be treated with EBT.Exchange transfusion of blood collected with acid-citrate-dextrose (ACD) containing bags may produce hypocalcaemia.To decrease the morbidity from chelation of divalent cations by citrate, routine administration of calcium gluconate during EBT was advocated,but tetany, convulsion and death may still occur when ACD blood is used.However, there are controversies about the effectiveness of intravenous calcium in reducing these calcium-related morbidities. A preliminary search for systematic reviews in MEDLINE, the Cochrane Library, Campbell Library and the Joanna Briggs Database of Systematic Reviews and Implementation Reports failed to identify any existing publications on this topic. As a result, this review will examine current quantitative evidence regarding the effectiveness of routine administration of intravenous calcium during EBT in the treatment of severe hyperbilirubinaemia, with specific aim to describe incidences of hypocalcaemia, seizures and deaths after such a transfusion.


Identification of Glypican3 as a novel GLUT4-binding protein.
Insulin stimulates glucose uptake in fat and muscle primarily by stimulating the translocation of vesicles containing facilitative glucose transporters, GLUT4, from intracellular compartments to the plasma membrane. Although cell surface externalization of GLUT4 is critical for glucose transport, the mechanism regulating cell surface GLUT4 remains unknown. Using a yeast two-hybrid screening system, we have screened GLUT4-binding proteins, and identified a novel glycosyl phosphatidyl inositol (GPI)-linked proteoglycan, Glypican3 (GPC3). We confirmed their interaction using immunoprecipitation and a GST pull-down assay. We also revealed that GPC3 and GLUT4 to co-localized at the plasma membrane, using immunofluorescent microscopy. Furthermore, we observed that glucose uptake in GPC3-overexpressing adipocytes was increased by 30% as compared to control cells. These findings suggest that GPC3 may play roles in glucose transport through GLUT4.


Molecular mechanisms contributing to long-lasting synaptic plasticity at the temporoammonic-CA1 synapse.
The hippocampus and the nearby medial temporal lobe structures are required for the formation, consolidation, and retrieval of episodic memories. Sensory information enters the hippocampus via two inputs from entorhinal cortex (EC): One input (perforant path) makes synapses on the dendrites of dentate granule cells as the first set of synapses in the trisynaptic circuit, the other (temporoammonic; TA) makes synapses on the distal dendrites of CA1 neurons. Here we demonstrate that TA-CA1 synapses undergo both early- and late-phase long-term potentiation (LTP) in rat hippocampal slices. LTP at TA-CA1 synapses requires both NMDA receptor and voltage-gated Ca2+ channel activity. Furthermore, TA-CA1 LTP is insensitive to the blockade of fast inhibitory transmission (GABAA-mediated) and, interestingly, is dependent on GABAB-dependent slow inhibitory transmission. These findings indicate that the TA-CA1 synapses may rely on a refined modulation of inhibition to exhibit LTP.


Clinical differences of hand and rotary instrumentations during biomechanical preparation in primary teeth-A systematic review and meta-analysis.
The hand and rotary instruments are used for cleaning and shaping of root canals during biomechanical preparation in primary teeth. To determine clinical differences of hand versus rotary root canal instrumentation in primary teeth. Comprehensive searches were made in four electronic databases [MEDLINE (via PubMed), EMBASE, Google Scholar, and The Cochrane Central Register of Controlled Trials] till March 2020, and prospective studies that met the inclusion criteria were included. The primary outcome was instrumentation time, whereas the secondary outcomes were quality of obturation, obturation time, and clinical and radiographic success. From 604 screened studies, eleven studies qualified for meta-analysis. The random-effect model and generic inverse variance approach were used for meta-analysis. There was significant decrease in instrumentation time [MD-5.00 minutes (95% CI: 3.05-6.94), P < .00001, moderate evidence quality] and obturation time [MD-0.43 minutes (95% CI: 0.15-0.71), P = .003, low evidence quality] with rotary instrumentation. Optimal quality of obturation was achieved in significantly more number of teeth [risk ratio (RR) = 0.71(95% CI: 0.53-0.95),P = .02, moderate to high evidence quality] with rotary instrumentation. Similar clinical and radiographic success was observed in hand and rotary instrumentation techniques. Significant reduction in instrumentation time of five minutes was observed using rotary instrumentation with moderate quality evidence.


The influence of leadership practices and empowerment on Canadian nurse manager outcomes.
To examine the influence of senior nurse leadership practices on middle and first-line nurse managers' experiences of empowerment and organizational support and ultimately on their perceptions of patient care quality and turnover intentions. Empowering leadership has played an important role in staff nurse retention but there is limited research to explain the mechanisms by which leadership influences nurse managers' turnover intentions. This study was a secondary analysis of data collected using non-experimental, predictive mailed survey design. Data from 231 middle and 788 first-line Canadian acute care managers was used to test the hypothesized model using path analysis in each group. The results showed an adequate fit of the hypothesized model in both groups but with an added path between leadership practices and support in the middle line group. Transformational leadership practices of senior nurses empower middle- and first-line nurse managers, leading to increased perceptions of organizational support, quality care and decreased intent to leave. Empowered nurse managers at all levels who feel supported by their organizations are more likely to stay in their roles, remain committed to achieving quality patient care and act as influential role models for potential future leaders.


Operational tolerance is not always permanent: A 10-year prospective study in pediatric liver transplantation recipients.
Immunosuppression withdrawal can be safely performed in select liver transplantation recipients, but the long-term outcomes and sustainability of tolerance have not been well studied. We completed a 10-year prospective, observational study of 18 pediatric liver transplantation recipients with operational tolerance to (1) assess the sustainability of tolerance over time, (2) compare the clinical characteristics of patients who maintained versus lost tolerance, (3) characterize liver histopathology findings in surveillance liver biopsies; and (4) describe immunologic markers in patients with tolerance. Comparator patients from two clinical phenotype groups termed "stable" and "nontolerant" patients were used as controls. Of the 18 patients with operational tolerance, the majority of patients were males (n = 14, 78%) who were transplanted for cholestatic liver disease (n = 12, 67%). Median age at transplantation was 1.9 (range, 0.6-8) years. Median time after transplantation that immunosuppression had been discontinued was 13.1 (range, 2.9-22.1) years. As many as 11 (61%) maintained tolerance for a median of 10.4 (range, 1.9-22.1) years, whereas 7 (39%) lost tolerance after a median of 3.2 (range, 1.5-18.6) years. Populations of T regulatory cells (%CD4+ CD25hi CD127lo ) were significantly higher in patients with tolerance (p = 0.02). Our results emphasize that spontaneous operational tolerance is a dynamic and nonpermanent state. It is therefore essential for patients who are clinically stable off immunosuppression to undergo regular follow-up and laboratory monitoring, as well as surveillance biopsies to rule out subclinical rejection.


[Diagnosis and treatment of adjusment disorder in primary care].
Adjustment disorder (AD) corresponds to the combination of affective, cognitive and behavioral symptoms that appear after a stressful event. It is a frequent reason for consultation in primary care and is one of the most common diagnoses in suicide attempts attended in the emergency department. Its essential feature is that the symptoms must appear in direct relation to an event perceived as stressful, so it tends to be transitory if the event ceases or the patient adapts. The mainstay of treatment are psychosocial interventions, aimed at modifying the event or its consequences, supporting adaptation and optimizing resources to cope with the event. However, prescription of psychotropic drugs is favored in practice, when its use should be limited to symptomatic relief. This highlights the need to properly identify and treat it. This article presents the strategies for diagnosis and treatment of AD in primary care.


Kupffer cell-hepatocyte interactions and the changes in 1-14C-arachidonate incorporation in response to endotoxin in vitro.
The present experiments were undertaken to elucidate the effect of either the hepatocyte (HC) or hepatocyte supernatant on prelabeled endotoxin (LPS)-stimulated Kupffer cell (KC) arachidonic acid utilization. HC, KC, or their coculture were incubated for 18 hours with labeled 1-14C- arachidonic acid followed by a 24 hour incubation with 10 micrograms/ml LPS. LPS had no effect on the percent distribution of labeled arachidonate into the HC phospholipid or neutral lipid. KC showed a decreased percent neutral lipid labeled arachidonic acid distribution with generally no effect on the phospholipid. However, KC:HC cocultures or the addition of HC supernatant to KC exposed to LPS dramatically reversed the labeled arachidonate distribution into the KC with an increased incorporation into neutral lipid. Labeled PGE2 and PGD2 were increased in the KC following incubation with HC supernatant while only labeled PGE2 levels were elevated in the cocultures. The changes in the distribution of cell's labeled arachidonate required the addition of LPS. These results suggest that the HC can promote changes in the lipid fraction during sepsis by elaborating a substance that can modulate labeled arachidonate distribution in the KC lipids as well as stimulate prostaglandin production.


Selective anti-tubercular purines: synthesis and chemotherapeutic properties of 6-aryl- and 6-heteroaryl-9-benzylpurines.
6-Aryl- and 6-heteroaryl-9-benzylpurines have been synthesized employing palladium-catalyzed coupling reactions in the step forming the C-C or C-N bond between the aryl- or heteroaryl and the purine. The compounds were screened for activity against Mycobacterium tuberculosis as well as representative Gram+ and Gram- bacteria, and for cytotoxic effects on mammalian cells. Several potent antimycobacterials were identified. These compounds probably act by a novel and selective mechanism; they exhibit low toxicity toward other bacteria as well as mammalian cells.


Benign osteoblastoma: quantitative histological distinction from osteoid osteoma.
The author performed on 10 cases of benign osteoblastoma and osteoid osteoma a comparative quantitative histological analysis using an optical line-mesh grid for sampling. Tissue components under the line crossing were counted five hundred times in every case making a total of five thousand counts for each group. It was demonstrated that 1. in osteoblastoma the amount of stroma is roughly by 10 per cent elevated and the amount of osteoid about 10 per cent less in comparison with osteoid osteoma. 2. As far as the osteoblast lining, capillaries and giant cells are concerned, there is no basic numerical difference between the two lesions. Experiences gained by qualitative histological comparison are also described. His results are favouring the concept of benign osteoblastoma as an entity with true tumour nature.


Relationship between COVID-19 and weather: Case study in a tropical country.
This study aimed to evaluate the relationship between weather factors (temperature, humidity, solar radiation, wind speed, and rainfall) and COVID-19 infection in the State of Rio de Janeiro, Brazil. Solar radiation showed a strong (-0.609, p < 0.01) negative correlation with the incidence of novel coronavirus (SARS-CoV-2). Temperature (maximum and average) and wind speed showed negative correlation (p < 0.01). Therefore, in this studied tropical state, high solar radiation can be indicated as the main climatic factor that suppress the spread of COVID-19. High temperatures, and wind speed also are potential factors. Therefore, the findings of this study show the ability to improve the organizational system of strategies to combat the pandemic in the State of Rio de Janeiro, Brazil, and other tropical countries around the word.


[Treatment of complicated urethroceles in women by resection of the protruding dome].
Vaginal marsupialization appear the safest treatment of complicated urethroceles.


Synthesis and in vitro cytotoxicity of lipophilic platinum(II) complexes.
A number of lipophilic platinum(II) complexes of the general structures cis-[Pt(LA)2Cl2] and [Pt(LD)Cl2] were synthesised. Long chain amines (LA) and diamines (LD), prepared from lipidic amino acids, were used as ligands. The in vitro cytotoxicity of the complexes was evaluated against four cell lines (P388, NSCLC-N6, E39, M96). cis-Dichloro-bis(2-aminohexadecanol)platinum(II) was the most active against P388, NSCLC-N6 and E39 (IC50: 11 micrograms/ml, 25 micrograms/ml, 31 micrograms/ml), while dichloro(1,3-heptadecanediamine)platinum(II) presented the highest activity against M96 (IC50: 13 micrograms/ml).


Enteroscopic treatment of early postoperative small bowel obstruction.
Early postoperative small bowel obstruction (EPSBO) occurs in 1% of patients undergoing laparotomy and has a mortality rate exceeding 17%. Nasogastric (NG) decompression is successful in avoiding reoperation in 73% of patients. Repeat laparotomy has been recommended when obstruction does not resolve after 14 days of NG decompression. We report four patients with EPSBO treated successfully with push enteroscopy after failed NG decompression. Four patients who failed NG decompression underwent push enteroscopy instead of repeat laparotomy. EPSBO was diagnosed if obstruction lasting more than 14 days developed after initial resolution of postoperative ileus, high NG output persisted postoperatively for 21 days in the absence of sepsis, or radiographic signs of obstruction persisted. Small bowel series or computed tomography were utilized when radiographic assessment was necessary. The Olympus SIF 100 push enteroscope was introduced with an overtube using topical anesthesia and intravenous sedation. After maximal insertion, the enteroscope was withdrawn without evacuation of insufflated air. NG tubes were placed after enteroscopy and patients were followed clinically. Flatus, defecation, and tolerance of a general diet defined resolution of EPSBO. EPSBO resolved 24 to 36 h following enteroscopy, and all patients were discharged on general diets 48 h after return of bowel function. Readmission has not been necessary during 18- to 30-month follow-up. Our experience suggests that push enteroscopy is successful in treating EPSBO and should be considered prior to reoperation. Push enteroscopy may eliminate the hazards of repeat laparotomy and reduce the morbidity, treatment cost, and lengthy hospital stays associated with this uncommon surgical complication.


Degradation of polydispersed poly(L-lactic acid) to modulate lactic acid release.
Polydispersed poly(L-lactic acid) (PLLA) membranes comprised of blends of monodispersed PLLA of weight average molecular weight of 82,500 and 7600 were fabricated to investigate the effect of polydispersity on degradation characteristics. The PLLA blends exhibited large spherulites of high molecular weight chains embedded in a low molecular weight matrix. During degradation in phosphate buffer at pH 7.4 and 37 degrees C for 28 d, the release rate of lactic acid increased as the percentage of the low molecular weight component in the blend was increased. For low molecular weight compositions larger than 50%, voids were created in the degrading blends due to the degradation of low molecular weight chains and the concurrent dissolution of lactic acid, and also the release of undegraded particles of high molecular weight. These studies demonstrate the feasibility of modulating lactic acid release during in vivo degradation of PLLA implants by adjusting the polymer polydispersity.


Continuous erector spinae plane block for analgesia of sternum closure using a latissimus dorsi muscle flap for mediastinitis after coronary artery bypass grafting: a case report.
Erector spinae plane block (ESPB) is useful for providing analgesia after thoracic surgery. Previous reports show that ESPB is safely performed in patients receiving antithrombotic drugs. We effectively performed continuous ESPB in a patient receiving aspirin after coronary artery bypass grafting. A 62-year-old man with mediastinitis was scheduled for sternum closure using a latissimus dorsi muscle flap. He had gone coronary artery bypass grafting and was taking aspirin. After induction of general anesthesia and tracheal intubation, a catheter was inserted for ESPB from the T6 level under ultrasound monitoring and infusion of ropivacaine was started. Tracheal tube was removed in the operating room, cold sense was absent between T2-8, and analgesia was between T3-T8 after uneventful surgery. There were no complications associated with ESPB postoperatively. Continuous ESPB was a safe and useful analgesic method in a case undergoing sternum closure using a latissimus dorsi muscle flap.


Response of stretch receptors to static inflations and deflations in an isolated tracheal segment.
It has been proposed on the basis of differing responses to static lung inflations that there are two types of pulmonary stretch receptor which are organized in series or in parallel with airway smooth muscle. However, in prior studies, in which we examined the responses of a few receptors in a number of animals, we were unable to confirm this finding. In the present study we sought to definitively address this question by examining the response of a reasonable sample of receptors (greater than or equal to 5) from a single airway with a controlled mechanical environment. We examined the firing patterns of slowly adapting receptors in a tracheal segment, isolated in vivo, during inflations and deflations to different static levels of pressure between -20 and +30 cm H2O. The relationship between afferent firing and intra-tracheal pressure under static conditions was determined. We did not observe any evidence to support the existence of two distinct subtypes of receptors. During these studies we also looked for abrupt changes in the variability of afferent firing during the period of adaptation after the end of an inflation or deflation. Such changes have been described for other receptors with branched endings capable of generating spike potentials. These changes occur when the region generating the spike train seen in the parent fiber switches from one branch to another (pace-maker switching) and reflect the difference in the intrinsic variability of each branch. In the majority of fibers studied we saw no evidence of such switching and thus of the presence of multiple encoders in the receptor structure.


Minimally invasive esophagectomy with cervical esophagogastric anastomosis.
Thoracoscopic dissection of the esophagus and laparoscopic dissection of the stomach with cervical esophagogastric anastomosis is a safe method for resection of esophageal and gastroesophageal junction malignancy. The setting was at University Tertiary Care Center. Subjects are patients with esophageal or gastroesophageal junction malignancy undergoing minimally invasive esophagectomy with cervical esophagogastric anastomosis. Technique of a 6-cm side-to-side stapled cervical esophagogastric anastomosis is described. The technique of minimally invasive esophagectomy with side-to-side stapled cervical esophagogastric anastomosis is described. Thoracoscopic dissection of the esophagus, laparoscopic dissection of the stomach, and a side-to-side stapled cervical esophagogastric anastomosis is safe, oncologically appropriate, and provides excellent functional results.


Challenges and strategies in communication with people with dementia and their informal caregivers in community pharmacies - a narrative approach.
People with dementia and their informal caregivers get in touch with the healthcare system predominantly via contacts with primary care providers. Among these, community pharmacists have been denominated as the health professionals most accessible to the public. Communication with and counselling people with dementia and their informal caregivers present particular challenges to pharmacists. This study aims to research the challenges faced and strategies used by community pharmacists who deal with people living with dementia and their informal caregivers. Within the context of two workshops with 74 participants, 15 small groups were formed, each of which generated and discussed a small story. Fourteen of those narratives were reported, tape recorded and transcribed. In these 14 narratives, community pharmacists reflected on their experiences with people with dementia or their informal caregivers. The narratives were systematically analysed and interpreted. Among the main challenges reported by the workshop participants are the difficulty of identifying a person with dementia; the question of what appropriate communication is; the only partially successful networking with doctors, nursing personnel and support institutions; unsuccessful counselling; and the tension between the economic situation and the care for people with dementia and their informal caregivers. In general, strategies for dealing with people with dementia are characterised by uncertainty whereas communication with informal caregivers is well rehearsed and effective. Community pharmacies require possibilities to retreat for counselling as well as the possibility for pharmacists to take time for people with dementia and their informal caregivers in everyday pharmacy life. Reflective spaces for narrations about difficult situations provide relief for staff in community pharmacies.


Simultaneous production of aromatics-rich bio-oil and carbon nanomaterials from catalytic co-pyrolysis of biomass/plastic wastes and in-line catalytic upgrading of pyrolysis gas.
An integrated process that includes catalytic co-pyrolysis of biomass/plastic wastes and in-line catalytic upgrading of pyrolysis gas were conducted to simultaneously produce aromatics-rich bio-oil and carbon nanotubes (CNTs). The influences of feedstocks blending ratio on the characteristics of bio-oil and CNTs were established. The reaction mechanism of carbon deposition during the system was also probed. The results showed that co-feeding plastic to biomass siginificantly enhanced the selectivity of monoaromatics (benzene, toluene, and xylene) from 5.6% for pure biomass to the maximum yield of 44.4% for 75.0% plastic ratio, and decreased naphthalene and its derivates from 85.9 to 41.7% correspondingly. The most synergistic effect on BTX selectivity occurred at 25% of plastic ratio. The multi-walled CNTs were successfully synethsized on Ni catalyst by utilizing prolysis gas as feedstocks. For pure biomass, the least CNTs yield with ultrafine diameters of 3.9-8.5 nm was generated via disproportionation reaction of CO which was derived from decarboxylation and decarbonylation of oxygenates on the ZSM-5 acid sites. With the rise of plastic ratio, sufficient hydrocarbons were produced for CNTs growth, endowing CNTs with long and straight tube walls, along with uniform diameters (~16 nm). The CNTs yield increased as high as 139 mg/g-cata. In addition, the decreased CO2 inhibited dry reforming with C1-C4 hydrocarbons and deposited carbon, avoiding excessive etching of CNTs. Thereby, high-purity CNTs with less defects were fabricated when plastic ratio was beyond 50% in the feedstock. The strategy is expected to improve the sustainability and economic viability of biomass pyrolysis.


Outcomes and Clinical Characteristics of Intracranial Hemorrhage in Patients with Hematologic Malignancies: A Systematic Literature Review.
Many clinical and demographic factors can influence survival of patients with hematologic malignancies who have intracranial hemorrhages (ICHs). Understanding the influence of these factors on patient survival can guide treatment decisions and may inform prognostic discussions. We conducted a systematic literature review to determine survival of patients with intracranial hemorrhages and concomitant hematologic malignancy. A systematic literature review was conducted and followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. PubMed/MEDLINE, Web of Science, Ovid, SCOPUS, and Embase databases were queried with the following terms: ("intracranial hemorrhages" OR "brain hemorrhage" OR "cerebral hemorrhage" OR "subdural hematoma" OR "epidural hematoma" OR "intraparenchymal hemorrhage") AND ("Hematologic Neoplasms" OR "Myeloproliferative Disorders" OR "Myelofibrosis" OR "Essential thrombocythemia" OR "Leukemia"). Abstracts and articles were screened according to inclusion and exclusion criteria that were determined a priori. Literature review yielded 975 abstracts from which a total of 68 full-text articles were reviewed. Twelve articles capturing 634 unique patients were included in the final qualitative analysis. Median overall survival for all patients ranged from 20 days to 1.5 months while median overall survival for the subset of patients having ICH within 10 days of diagnosis of hematologic malignancy was 5 days. Intraparenchymal hemorrhages, multiple foci of hemorrhage, transfusion-resistant low platelet counts, leukocytosis, low Glasgow Coma Scale scores at presentation, and ICH early in treatment course were associated with worse outcomes. Survival for patients with hematologic malignancies and concomitant ICHs remains poor. Early detection, recognition of poor prognostic factors, and correction of hematologic abnormalities essential to prevention and treatment of ICHs in this patient population.


Identification of cell binding sites in the laminin alpha 1 chain carboxyl-terminal globular domain by systematic screening of synthetic peptides.
The laminin alpha 1 chain carboxyl-terminal globular domain has been identified as a site of multiple biological activities. Using a systematic screening for cell binding sites with 113 overlapping synthetic peptide beads that covered this domain, we found 19 potential active sequences. Corresponding synthetic peptides were evaluated for direct cell attachment, spreading, and inhibition of cell spreading to a laminin-1 substrate using several cell lines. Five peptides (AG-10, AG-22, AG-32, AG-56, and AG-73) showed cell attachment activities with cell-type specificities. Cell spreading on AG-10 was inhibited by beta 1 and alpha 6 integrin antibodies and on AG-32 was inhibited by beta 1, alpha 2, and alpha 6 integrin antibodies. In contrast, cell adhesion and spreading on peptide AG-73 were not inhibited by these antibodies. The minimum active sequences of AG-10, AG-32, and AG-73 were determined to be SIYITRF, IAFQRN, and LQVQLSIR, respectively. These sequences are highly conserved among the different species and different laminin alpha chains, suggesting that they play a critical role for biological function and for interaction with cell surface receptors.


A systematic review and meta-analysis of suicidality in psychotic disorders: Stratified analyses by psychotic subtypes, clinical setting and geographical region.
We studied the prevalence of suicide attempts and cumulative incidence of completed suicide in schizophrenia (SZ), schizoaffective disorder (SZAF), delusional disorder (DD) and first-episode psychosis (FEP). A systematic review was performed using Scopus and PubMed databases (1990- July 2020). A random effects meta-analysis was conducted. Stratified analyses were conducted by diagnosis, clinical setting and geographical region. The prevalence of attempted suicide was 20.3% for SZ, 46.8% for SZAF, 11.1% for DD and 12.5% for FEP. Suicide attempts rates were higher for outpatient samples than for inpatient samples in SZ, SZAF and DD (but not FEP) studies. Analyses by geographical region in SZ showed greater prevalence of suicide attempts in North America and Northern Europe. The cumulative incidence of completed suicide was 2.0% for SZ, 2.4% for SZAF; 2.2% for DD and 1.9% for FEP. In schizophrenia and FEP studies, Northern European studies reported higher rates of completed suicide when compared to Western European countries. In conclusion, suicidal behaviour rates in psychoses differ by diagnoses, clinical setting and geographical region.


Unloader bracing in osteoarthritis of the knee - Is there a direct effect on the damaged cartilage?
Unloading knee braces represent a conservative treatment option for non-pharmalogical management of unicompartmental osteoarthritis of the knee. Though there is consensus on the clinical effectiveness of unloading, the effect mechanism of bracing remains part of a debate. Our study was designed to assess the effect of unloader bracing on damaged cartilage via MRI cartilage mappings. Fourteen patients (7 female, 7 male, mean age 43.1 ± 9.4 years) with unicompartmental cartilage wear in knees with varus or valgus malalignment were enrolled. Clinical scores, radiographs and MR-graphic properties (T2/T2* mapping, T1 Delayed Gadolinium Enhanced MRI of the cartilage (dGEMRIC) mapping, high-resolution PDw sequences) of knee cartilage were recorded before and three months after brace use. Bracing the knees for a mean of 14.4 ± 2.0 weeks (range 11 to 18 weeks) resulted in significant pain reduction (VAS changed from 5.9 ± 2.0 to 2.0 ± 1.3, p < 0.001) and improvement in knee function (KOOS increased from 42.1 ± 22.7 to 64.8 ± 18.7, p < 0.001). In the affected cartilage regions T2 relaxation times significantly decreased from 56.1 ± 11.4 ms to 46.5 ± 11.2 ms (p < 0.05). No changes in T1-dGEMRIC and T2* relaxation times, thickness or the extent of the damaged cartilage area could be detected. Our results suggest, that unloader bracing improves the biochemical properties of the damaged cartilage by increasing collagen and proteoglycan concentration as well as decreasing the cartilage edema.


Reduction of manganese porphyrins by flavoenzymes and submitochondrial particles: a catalytic cycle for the reduction of peroxynitrite.
The reduction of manganese(III) meso-tetrakis((N-ethyl)pyridinium-2-yl)porphyrin (MnTE-2-PyP) to manganese(II) was catalyzed by flavoenzymes such as xanthine oxidase and glucose oxidase, and by Complex I and Complex II of the mitochondrial electron transport chain. The reduced manganese porphyrin has been previously shown to react rapidly with superoxide and carbonate radical anion. Herein, we describe the reaction of a reduced manganese porphyrin with peroxynitrite that proceeds as a two-electron process, has a rate constant greater than 7 x 10(6) M(-1) s(-1) (at pH 7.25 and 37 degrees C), and produces nitrite and the Mn(IV)Porphyrin. The Mn(II)/Mn(IV) redox cycle was used to divert peroxynitrite from the inactivation of succinate dehydrogenase. In a typical experiment, 5 microM MnTE-2-PyP in the presence of excess succinate was able to protect the succinate dehydrogenase and succinate oxidase activities of submitochondrial particles challenged with a cumulative dose of 140 microM peroxynitrite infused in the course of 2 h. Other MnPorphyrins that are reduced more slowly do not provide as much protection underscoring the rate limiting character of the reduction step. The data presented here serve to rationalize the pharmacological action of MnPorphyrins as peroxynitrite reduction catalysts in vivo and opens avenues for the development of MnPorphyrins to protect mitochondria from oxidative damage.


[Management of aflibercept in routine clinical practice].
Aflibercept is a new anti-vegf drug that, unlike ranibizumab and bevacizumab blocks both vegf-A and placental growth factor. Moreover, it binds with much greater strength and affinity to human VEGF-A165 than other endogenous vegf receptors, conferring it with a more extended effect and allowing a lower frequency of intravitreal injections. This facilitates the adoption of fixed treatment regimens other than monthly or individual regimens such as "treat and extend". Aflibercept is indicated for the treatment of neovascular (exudative) age-related macular degeneration (ARMD), visual alteration due to macular edema secondary to central retinal vein occlusion (CRVO) and visual alteration due to diabetic macular edema (DME). The present article reviews the management of aflibercept in routine clinical practice, based on the specifications of its new core data sheet, which includes all the therapeutic indications in which its use has been approved and evaluating the distinct alternatives and treatment regimens after the initial loading doses.


[Use of ultrasound tomography in the control of endoscopic retrograde bile duct drainage].
The sonography of three patients with a transpapillar catheter within the bile duct shows typically findings as the picture of catheter as a tubular structure with high level reflectivity, reduction of bile duct calibers and air in the bile ducts. The diminuation of the bile duct calibers is an argument for normal transpapillary bile flow and occurs before the change of laboratory parameters. In case of jaundice the differentiation between metastatic tumours of the liver and occlusion of the catheter is possible on the basis of ultrasound. After the diminuation of calibers of the bile ducts a metastatic tumours of liver are better to be seen.


Using the TI.VA algorithm to titrate the depth of general anaesthesia: a first-in-humans study.
The dose of anaesthetic and opioid drugs must be continuously adjusted after the induction of general anaesthesia to maintain an adequate depth of anaesthesia. The TI.VA algorithm is a multiple-input/multiple-output algorithm designed to optimise the balance between anaesthetic and opioid concentrations during general anaesthesia. It applies vector analysis to a two-dimensional matrix to quantify any inadequacy of the depth of anaesthesia at any given moment and determine any drug dose adjustments required to achieve an adequate depth of anaesthesia. This study aimed to capture preliminary data on the performance and safety of the TI.VA algorithm during total i.v. anaesthesia in patients. This prospective study enrolled nine patients with breast cancer scheduled to undergo surgery. General anaesthesia was induced under manual control using propofol and remifentanil. Anaesthesia was guided using the TI.VA algorithm from skin incision until surgical resection was completed. The quality of anaesthesia was assessed through an analysis of performance errors. A bispectral index global score (GSBIS) <50 was considered an acceptable target for algorithm performance. All nine procedures were completed without any adverse events and none of the patients recalled any intraoperative event. Overall, we analysed 3417 monitoring points corresponding to 285 min of surgery. All patients presented a GSBIS below the cut-off value of 50. The TI.VA algorithm provides adequate control of clinical anaesthesia. A more sophisticated prototype needs to be developed before the trial is expanded to include larger patient populations. NCT05199883.


Comparing enhancement and washout patterns of hepatic lesions between sonazoid-enhanced ultrasound and contrast-enhanced computed tomography.
To compare sonazoid-enhanced ultrasound (SEUS) and contrast-enhanced computed tomography (CECT) enhancement and washout patterns in hepatic lesions. Enhancement and washout patterns on SEUS were compared with those on CECT for 61 lesions. There were 36 hepatocellular carcinomas, three intrahepatic cholangiocarcinomas, three metastatic lesions, eight focal nodular hyperplasias, two angiomyolipomas, and nine undetermined benign lesions. Diagnosis was based on histopathology, or CECT and tumor markers, or findings on 2-year follow-up. All 61 lesions (100%) showed arterial enhancement on both SEUS and CECT. The "washout/no washout" agreement between SEUS and CECT for the 61 lesions was 93.4% (κ coefficient: 0.816). Of the 42 malignant lesions, 38 lesions (90.5%) showed washout on both SEUS and CECT. The remaining four malignant lesions, of which three lesions contained fibrosis (two intrahepatic cholangiocarcinomas and one scirrhous hepatocellular carcinoma), showed washout on SEUS but not on CECT. For the 19 benign lesions, agreement between SEUS and CECT was 100% (κ coefficient: 1), with seven lesions showing washout with both methods and 12 lesions showing no washout with both methods. The overall concordance rate between SEUS and CECT was good, but some differences were seen in the washout patterns of malignant lesions.


Crystal-associated arthropathies.
Crystal-associated arthritis constitutes one of the best-understood inflammatory processes involving joints in humans. It affects mainly middle-aged or elderly individuals and is often seen in association with signs of degenerative joint disease. Articular manifestations of crystalline deposition disease not uncommonly are also the first presentation of reversible metabolic or endocrine disorders. This is an important field for clinicians because the diagnosis can be rapidly and precisely made by synovial fluid analysis. Furthermore, the acute manifestations can be controlled effectively with the administration of colchicine, nonsteroidal anti-inflammatory agents or intra-articular corticosteroid injections. The chronic manifestations of gouty arthritis are also successfully managed with long-term hypouricemic therapy.


Clinical measures of islet function: usefulness to characterize defects in diabetes.
In healthy individuals, the ability of the pancreatic islets to sense and respond appropriately to changes in plasma glucose levels maintains plasma glucose levels within a narrow range despite broad fluctuations in nutrient intake and variable "demand" for insulin imposed by changes in insulin sensitivity. This ability of the pancreatic islets is lost in type 2 diabetes (T2DM). For studies on the pathophysiology of T2DM, methods for analyzing islet function are therefore required. Many methods of varying degrees of complexity have been developed and used to measure pancreatic beta-cell function in humans and to characterize the defects existing in patients with T2DM or precursors thereof (impaired fasting glucose [IFG] and impaired glucose tolerance [IGT]). Significant, although perhaps less progress has been made toward development of methods to characterize alpha-cell function. This work presents an overview of clinical measures of islet function, from simple static measures such as HOMA-beta to the more complex dynamic measures such as those utilizing stepped hyperglycemic clamps and acute administration of arginine to obtain more detailed information regarding the interaction of glucose and non-glucose secretagogues. We emphazise the need for accurate measures of alpha-cell function, and we discuss the strengths and limitations of the various methods, highlighting the many aspects of both alpha- and beta-cell function that become impaired during development of T2DM.


[Stenting or coronary artery bypass surgery for triple vessel disease?].
This review was undertaken to objectively analyse the cumulated medical literature on techniques of myocardial revascularization (angioplasty, bare metal stenting, drug eluting stenting, coronary artery surgery) in multivessel coronary artery disease. Randomized trials, meta analyses and registries comparing these treatment modalities show a short and long term advantage of surgery over percutaneous techniques for angina recurrence and need for repeat revascularization, although mortality and myocardial infarction rate do not seem statistically different. Diabetes mellitus, chronic renal failure and female gender represent high risk subgroups. Data on drug eluting stents are to date limited to the short term; however, it does not seem that drug eluting stents have resolved the need for repeat revascularization. Stenting addresses focal lesion whereas future revascularization occurs on other coronary sites by progression of coronary disease. Cardiologists should objectively inform the consenting coronary multivessel disease patient on the risk of repeat revascularization inherent to percutaneous techniques and on the weight of actual data favouring surgery in multivessel disease.


Proteomic profiling of human urinary proteome using nano-high performance liquid chromatography/electrospray ionization tandem mass spectrometry.
Urine, a blood filtrate produced by the urinary system, is an ideal bio-sample and a rich source of biomarkers for diagnostic information. Many components in urine are useful in clinical diagnosis, and urinary proteins can be strong indication for many diseases such as proteinuria, kidney, bladder and urinary tract diseases. To enhance our understanding of urinary proteome, the urine proteins were prepared by different sample cleanup preparation methods and identified by nano-high performance liquid chromatography electrospray ionization tandem mass spectrometry followed by peptide fragmentation pattern. The experimental results demonstrated that a total of 2283 peptides, corresponding to 311 unique proteins, were identified from human urine samples, in which 104 proteins with higher confidence levels. The present study was designed to establish optimal techniques to create a proteomic map of normal urinary proteins. Also, a discussion of novel approaches to urine protein cleanup and constituents is given.


Nuclear transit of the intracellular domain of the interferon receptor subunit IFNaR2 requires Stat2 and Irf9.
Regulated intramembrane proteolysis (RIP) is the primary signaling mechanism for some receptors, such as Notch and the amyloid precursor protein. In addition, some receptor type tyrosine kinases, such as HER4, are able to signal via both kinase activation and regulated receptor proteolysis. Previously, we showed that the IFNaR2 subunit of the type I interferon receptor can be cleaved in a two step process that resembles RIP and that the IFNaR2 intracellular domain (IFNaR2-ICD) can mediate gene transcription in a Stat2 dependent manner. Here, we demonstrate that IFNaR2-ICD, Stat2 and Irf9 form a ternary complex. Furthermore, Stat2 and Irf9 are required for the nuclear transit of a GFP-linked IFNaR2-ICD construct (GFP-ICD). Additional experiments monitoring the nuclear localization of GFP-ICD demonstrate that Stat2 serves an adaptor role, mediating the interaction between the IFNaR2-ICD and Irf9, while the bipartite nuclear localization signal within Irf9 is the primary determinant driving nuclear transit of the ICD containing complex. Overall, the data suggest that liberation of the IFNaR2-ICD by regulated proteolysis could trigger a novel mechanism for moving the transcription factor Stat2 to the nucleus.


Flavor development in peach fruit treated with 1-methylcyclopropene during shelf storage.
The objective of this study was to investigate flavor development, and subsequent consumer acceptance, in peach fruit treated with 1-methylcyclopropene (1-MCP) during the room-temperature storage. Gas chromatography coupled to mass spectrometry (GC-MS) and proton nuclear magnetic resonance (1H NMR) showed that 12 compounds were significantly affected by 1-MCP. Of these, linalyl acetate and sucrose contribute positively to consumer acceptance, while benzaldehyde and histidine have negative effects. 1-MCP treatment inhibits the emission of aroma during the early storage of peach fruit but not during later storage period, and extends the time required for peaches to reach maximum consumer acceptance from 2 to 4 days. This shift may be due to increased levels of positive flavor compounds (linalyl acetate and sucrose) and decreased levels of negative flavor compounds (benzaldehyde and histidine) later in the storage period.


Dipeptidyl peptidase-8 induces sorafenib resistance via binding with c-Rel to mediate NF-κB signaling in hepatocellular carcinoma.
Sorafenib is the important first-standard drug for patients with advanced hepatocellular carcinoma (HCC). A major obstacle to successful treatment is sorafenib resistance. However, the mechanism of sorafenib resistance is unclear. The present study aimed to determine the involvement of dipeptidyl peptidase-8 (DPP8) in sorafenib resistance. DPP8 expression was detected using quantitative real-time PCR (qPCR) and western blot analysis. The effect of DPP8 on sorafenib resistance was examined using terminal deoxynulceotidyl transferase nick-end-labeling (TUNEL), colony formation, flow cytometry, luciferase reporter, immunofluorescence, and immunoprecipitation (IP) assays. We found that DPP8 mRNA and protein levels were dramatically upregulated in HCC. Gene set enrichment analysis (GSEA) illustrated that DPP8 might be involved in apoptosis regulation. Downregulation of DPP8 substantially promoted the sensitivity of HCC cells to sorafenib. Further analysis showed that DPP8 might regulate nuclear factor kappa B (NF-κB) signaling, which was confirmed using a luciferase reporter assay. Downregulation of DPP8 decreased the expression levels of downstream genes of the NF-κB pathway. IP showed that DPP8 can interact with NF-κB subunit c-Rel, an important protein of NF-κB signaling. Finally, a drug combination of sorafenib and Val-boroPro induced higher mortality of HCC cells than sorafenib alone in DPP8-upregulated cells. Our findings indicated that using the inhibitor Val-boroPro might be a promising method to enhance sorafenib sensitivity in advanced HCC.


Naltrexone attenuates the subjective effects of amphetamine in patients with amphetamine dependence.
Amphetamine abuse and dependence is a global health concern with a collateral increase in medical and social problems. Although some of the neurobiological mechanisms underlying amphetamine dependence and its devastating effects in humans are known, the development of rational and evidence-based treatment is lagging. There is evidence from preclinical studies suggesting that the endogenous opioid system plays a role in mediating some of the behavioral and neurochemical effects of amphetamine in a variety of controlled settings. In the present study we assessed the effects of naltrexone, an opioid antagonist (50 mg) on the subjective physiological and biochemical response to dexamphetamine (30 mg) in 20 amphetamine-dependent patients. Patients received naltrexone/amphetamine followed by placebo/amphetamine, 1 week apart in a randomized double-blind placebo-controlled design. The primary objective of the study was to evaluate the effect of pretreatment with naltrexone on the subjective response to amphetamine, using a Visual Analog Scale. The secondary objective was to investigate the effects of naltrexone on physiological and biochemical responses to amphetamine, as measured by changes in blood pressure, heart rate, skin conductance, and cortisol. Naltrexone significantly attenuated the subjective effects produced by dexamphetamine in dependent patients (p<0.001). Pretreatment with naltrexone also significantly blocked the craving for dexamphetamine (p<0.001). There was no difference between the groups on the physiological measures. The results suggest that the subjective effects of amphetamine could be modulated via the endogenous opioid system. The potential of naltrexone as an adjunct pharmaceutical for amphetamine dependence is promising.


Evaluation of lannate 20, a carbamate pesticide in the germ cells of male mice.
Lannate 20, a carbamate pesticide, was evaluated for its effects on the germ cells of Swiss albino male mice, by the sperm morphology assay and meiotic chromosome preparations. The three sublethal concentrations of 20, 40, and 60 mg/kg body wt administered by the oral intubation method produced significant results (P less than 0.01) with both the above protocols in the said test system under study, thus indicating that lannate 20 is mutagenic in mice.


Ocular hypotony in myotonic dystrophy.
Ocular hypotony is a common, unexplained feature of myotonic dystrophy. Some investigators have ascribed the decrease in intraocular pressure to unusually high outflow facility. The present study demonstrates that increased outflow facility in myotonics is often artifactitious. When corrected for ocular rigidity, outflow facility is frequently normal. The present study presents indirect evidence that ocular hypotony in myotonics results from reduced aqueous production or increased uveoscleral outflow.


Review of the evidence for an association between infant feeding and childhood cancer.
To assess the association between infant feeding and childhood cancer, a qualitative review of 9 published case-control studies was undertaken. The results of this synthesis suggest that children who are never breast-fed or are breast-fed short-term have a higher risk than those breast-fed for > or = 6 months of developing Hodgkin's disease (HD), but not non-Hodgkin's lymphoma or acute lymphoblastic leukemia. HD has features of a complex cellular immune disorder and of chronic infection. Human milk contains an extensive array of anti-microbial activity and appears to stimulate early development of the infant immune system. Artificially fed infants negotiate exposure to infectious agents without the benefits of this immunologic armament and do not do as well as breast-fed infants in resisting infection. Thus, human milk may make the breast-fed infant better able to negotiate future carcinogenic insults by modulating the interaction between infectious agents and the developing infant immune system or by directly affecting the long-term development of the infant immune system. Further research should attempt to confirm the association between infant feeding and HD in large, population-based, case-control studies. Improved measurement of infant feeding must be addressed if future studies are to advance our understanding of this association. In addition, studies of specific measures of immunity, particularly of cellular immune responses, should be conducted in populations of breast-fed and non-breast-fed young children.


High resolution imaging of the intracranial vessel wall at 3 and 7 T using 3D fast spin echo MRI.
High resolution MRI of the intracranial vessel wall provides important insights in the assessment of intracranial vascular disease. This study aims to refine high resolution 3D MRI techniques for intracranial vessel wall imaging at both 3 and 7 T using customized flip angle train design, and to explore their comparative abilities. 11 patients with intracranial artery disease (four atherosclerotic plaques, six aneurysms and one reversible cerebral vasoconstriction syndrome) were imaged at 3 and 7 T with a 3D T 1-weighted fast-spin-echo sequence (SPACE) both pre and post Gd contrast injection. Wall to lumen contrast ratio (CRwall-lumen), contrast enhancement ratio (ER) and the sharpness of the vessel wall were quantified. Two experienced radiologists evaluated the image quality on a 0-5 scale. Both 3 and 7 T achieved good image quality with high resolution (nominal 0.5 mm isotropic) and whole brain coverage. The CRwall-lumen and the ER measurements were comparable (p > 0.05). The 7 T images were significantly sharper (sharpness: 2.69 ± 0.50 vs. 1.88 ± 0.53 mm(-1), p < 0.001) with higher image quality (reader 1 score: 3.5 ± 1.1 vs. 2.4 ± 1.1, p = 0.002) compared to 3 T. 3D T 1-weighted SPACE can be used for intracranial vessel wall evaluation at both 3 and 7 T. 7 T provides significantly better image quality and improves the confidence of diagnosis.


Changes in Enterohepatic Circulation after Duodenal-Jejunal Bypass and Reabsorption of Bile Acids in the Bilio-Pancreatic Limb.
Duodenal-jejunal bypass (DJB) shows great effects on weight loss and diabetes improvement. Previously, we reported that the bilio-pancreatic (BP) limb plays an important role in glycemic improvement and in serum bile acid (BA) level increase as reported by Miyachi et al. (Surgery 159(5):1360-71, 2016). This study aimed to investigate the mechanism of BA elevation after DJB and the relationship between these effects and BP-limb length. Otsuka Long-Evans Tokushima Fatty rats with diabetes were randomly assigned into four groups: one sham group and three DJB groups. Three DJB groups were defined according to the BP-limb length: 0 cm, 15 cm, and 30 cm. The lengths of the alimentary limb and common channel were set equally in each DJB groups. Body weight, glucose tolerance, and BA levels in the liver, bile juice, portal vein, and intestinal contents were assessed postoperatively. Changes in enterohepatic circulation of BAs were assessed using labeled BA. BA elevation after DJB was higher with longer BP-limb. In the 30-cm group, the serum total BA level and BA levels in the portal vein, liver, and bile juice were greater than those in other groups. The enterohepatic circulation was shortened in the 15-cm and 30-cm groups. Shortening of the "enterohepatic circulation" by early reabsorption of BAs in the BP-limb, not by the early influx of bile juice into the ileum, was the main cause of BA elevation after DJB. Thus, glycemic improvement and elevation of BA concentration after DJB depend on the BP-limb length.


Synthesis and photodynamic properties of adamantylethoxy Zn(II) phthalocyanine derivatives in different media and in human red blood cells.
Novel unsymmetrically substituted Zn(II) phthalocyanine bearing an adamantylethoxy group (AZnPc) was synthesized by the ring expansion reaction of boron(III) subphthalocyanine chloride with an appropriated phthalonitrile derivative (APc). Also, APc was used to obtain a new Zn(II) phthalocyanine bearing four adamantylethoxy groups (A(4)ZnPc) by cyclotetramerization reaction. The spectroscopic and photodynamic properties of these photosensitizers were compared with those of a Zn(II) phthalocyanine substituted by four methoxy groups (M(4)ZnPc) in different media. Similar results were obtained in N,N-dimethylformamide. However, a higher photodynamic activity was found for AZnPc in a biomimetic system formed by reverse micelles. This behavior was also observed in the presence of human red blood (HRB) cells, which were used as an in vitro cellular model. Thus, AZnPc was the most effective photosensitizer to produce HRB cells hemolysis. The photodynamic effect produced a decrease in the HRB cells osmotic stability leading to the release of hemoglobin. Studies of photodynamic action mechanism showed that photohemolysis of HRB cells was protected in the presence of azide ion, while the addition of mannitol produced a negligible effect on the cellular photodamage, indicating the intermediacy of O(2)((1)Δ(g)). Therefore, the presence of an adamantyl unit in the phthalocyanine macrocycle represents an interesting molecular architecture for potential phototherapeutic agents.


In-hospital mortality of hepatorenal syndrome in the United States: Nationwide inpatient sample.
Hepatorenal syndrome (HRS) is a life-threatening condition among patients with advanced liver disease. Data trends specific to hospital mortality and hospital admission resource utilization for HRS remain limited. To assess the temporal trend in mortality and identify the predictors for mortality among hospital admissions for HRS in the United States. We used the National Inpatient Sample database to identify an unweighted sample of 4938 hospital admissions for HRS from 2005 to 2014 (weighted sample of 23973 admissions). The primary outcomes were temporal trends in mortality as well as predictors for hospital mortality. We estimated odds ratios from multi-level mixed effect logistic regression to identify patient characteristics and treatments associated with hospital mortality. Overall hospital mortality was 32%. Hospital mortality decreased from 44% in 2005 to 24% in 2014 (P < 0.001), while there was an increase in the rate of liver transplantation (P = 0.02), renal replacement therapy (P < 0.001), length of hospital stay (P < 0.001), and hospitalization cost (P < 0.001). On multivariable analysis, older age, alcohol use, coagulopathy, neurological disorder, and need for mechanical ventilation predicted higher hospital mortality, whereas liver transplantation, transjugular intrahepatic portosystemic shunt, and abdominal paracentesis were associated with lower hospital mortality. Although there was an increase in resource utilizations, hospital mortality among patients admitted for HRS significantly improved. Several predictors for hospital mortality were identified.


α-Lipoic acid alleviates ferroptosis in the MPP+ -induced PC12 cells via activating the PI3K/Akt/Nrf2 pathway.
Parkinson's disease (PD) is a typical neurodegenerative disease. α-Lipoic acid (α-LA) can reduce the incidence of neuropathy. The present study explored the role and mechanism of α-LA in 1-methyl-4-phenylpyridinium (MPP+ )-induced cell model of PD. The PD model was induced via treating PC12 cells with MPP+ at different concentrations. MPP+ and α-LA effects on PC12 cells were assessed from cell viability and ferroptosis. Cell viability was detected using the cell counting kit-8 assay. Malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), iron, reactive xygen species (ROS), and glutathione (GSH) concentrations, and ferroptosis-related protein SLC7A11 and GPx4 expressions were used for ferroptosis evaluation. p-PI3K, p-Akt, and nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels were detected. The PI3K/Akt/Nrf2 pathway inhibitors were applied to verify the role of the PI3K/Akt/Nrf2 pathway in α-LA protection against MPP+ -induced decreased cell viability and ferroptosis. MPP+ -reduced cell viability and induced ferroptosis as presented by increased MDA, 4-HNE, iron, and ROS concentrations, and reduced levels of GSH and ferroptosis marker proteins (SLC7A11 and GPx4). α-LA attenuated MPP+ -induced cell viability decline and ferroptosis. The PI3K/Akt/Nrf2 pathway was activated after α-LA treatment. Inhibiting the PI3K/Akt/Nrf2 pathway weakened the protection of α-LA against MPP+ treatment. We highlighted that α-LA alleviated MPP+ -induced cell viability decrease and ferroptosis in PC12 cells via activating the PI3K/Akt/Nrf2 pathway.


Tumor-specific design of PEGylated gadolinium-based nanoscale particles: Facile synthesis, characterization, and improved magnetic resonance imaging of metastasis lung cancer.
Herein we report the synthesis and characterization of the antifouling Gadolinium oxide (Gd2O3) nanoparticles (NPs) modified with PEG with improved biocompatibility for MR imaging purposes. In this report, using the solvothermal decomposition of Gadolinium (III) in the presence of Na3cit, monitored by surface modification with PEG and L-Cys. The synthesized nanoparticles were confirmed by the TEM, DLS and UV-Visible spectroscopy. The morphological results show normal distance across of the flawless Gd2O3-PEG-Cys-NPs show 7.9 ± 0.4 nm, discretely, with a thin size exchange. This infers the surface adjustment does not obviously alteration the center size of the Gd2O3-NPs when contrasted with the perfect sodium citrate-balanced out Gd2O3-NPs. The Gd2O3-PEG-L-Cys-NPs are highly stable at room temperature, water dispersible and importantly less cytotoxic at high concentration of the NPs. The T1-weighted MR phantasm readings evidentially displayed that the formed PEG coated Gd2O3-PEG and Gd2O3-PEG-Cys-NPs with and without Cys may be performed as the promising T1-weighted MR imaging. The NPs displays no signs of toxicity against the human blood, which represents the biocompatibility for the human medicine applications. The Gd2O3-PEG-Cys-NPs shows relatively, high r1 acceptable cytocompatibility, target specific cancer cells and activate the dual mode MR imaging of lung metastasis cancer model in vitro. The development of versatile zwitterion functionalized Gd2O3 may be promising as an active nanoparticle probe for improved multi-model of MR imaging agents for various cancer diseases.


Multichannel modulation of depolarizing and repolarizing ion currents increases the positive rate-dependent action potential prolongation.
Prolongation of the action potential duration (APD) could prevent reentrant arrhythmias if prolongation occurs at the fast excitation rates of tachycardia with minimal prolongation at slow excitation rates (i.e., if prolongation is positive rate-dependent). APD prolongation by current anti-arrhythmic agents is either reverse (larger APD prolongation at slow rates than at fast rates) or neutral (similar APD prolongation at slow and fast rates), which may not result in an effective anti-arrhythmic action. In this report we show that, in computer models of the human ventricular action potential, the combined modulation of both depolarizing and repolarizing ion currents results in a stronger positive rate-dependent APD prolongation than modulation of repolarizing potassium currents. A robust positive rate-dependent APD prolongation correlates with an acceleration of phase 2 repolarization and a deceleration of phase 3 repolarization, which leads to a triangulation of the action potential. A positive rate-dependent APD prolongation decreases the repolarization reserve with respect to control, which can be managed by interventions that prolong APD at fast excitation rates and shorten APD at slow excitation rates. For both computer models of the action potential, ICaL and IK1 are the most important ion currents to achieve a positive rate-dependent APD prolongation. In conclusion, multichannel modulation of depolarizing and repolarizing ion currents, with ion channel activators and blockers, results in a robust APD prolongation at fast excitation rates, which should be anti-arrhythmic, while minimizing APD prolongation at slow heart rates, which should reduce pro-arrhythmic risks.


Clinical and genetic features in pyridoxine-dependent epilepsy: a Chinese cohort study.
To characterize the clinical and genetic characteristics of a large cohort of patients with pyridoxine-dependent epilepsy (PDE). We retrospectively collected clinical and genetic information of 33 (15 males, 18 females; mean [SD] age 4y 11mo [2y 5mo]; 1y 3mo-10y 4mo) patients with PDE from 31 unrelated families at a single centre. There were many types of seizures, with focal seizures in 32 cases. Dravet syndrome was suspected clinically in two patients. Electroencephalogram (EEG) was normal in seven patients at the initial stage and then in 17 patients during pyridoxine maintenance therapy. Genetic studies revealed 26 kinds of variants in ALDH7A1 and four in PLPBP with 18 variants unreported previously, and 48 ALDH7A1 variants were located in exon 11, 12, 14, and 17 or intron 9 and 11. In addition, three patients carried different exons deletion. Among these, seizures could be controlled for several years in one patient by levetiracetam monotherapy. Another patient remained seizure free for up to 7 months without therapy. All patients received oral pyridoxine treatment, with only one case (with exon 8-13 deletion) showing poor control. This study illustrates the range of clinical presentations and genetic causes in PDE, as well as responsiveness to antiepileptic drugs. A relationship between EEG and pyridoxine therapy could be seen in many cases. Seizure control was seen in all with pyridoxine monotherapy except for one patient. There is a parallel relationship between electroencephalogram and pyridoxine therapy in many patients. Patients with pyridoxine-dependent epilepsy may respond well to low-dose pyridoxine.


Effects of fibroblast growth factor 2 on osteoblastic proliferation and differentiation by regulating bone morphogenetic protein receptor expression.
Fibroblast growth factors (FGFs) are known to play a critical role in bone growth and development, affecting both osteogenesis and chondrogenesis. Fibroblast growth factor 2 (FGF-2) is produced intracellularly by osteoblasts and secreted into the surrounding matrix in bone.The dose-dependent effects of FGF-2 were tested to examine the relationship between FGF-2 and osteoblast proliferation and differentiation. Tests used included a cell viability test, an alkaline phosphatase activity test, and a Western blot analysis.Cultures growing in the presence of FGF-2 showed an increased value for 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay and a decreased value for alkaline phosphatase activity. Results of the Western blot analysis showed that the addition of FGF-2 seems to decrease osteocalcin and bone morphogenetic protein receptor IA.These data show that FGF-2 in the tested dosage within MC3T3-E1 cells seems to affect proliferation and differentiation. Results of the Western blot analysis may add some possible mechanisms, and it may be suggested that treatment of FGF-2 may have an influence on the expression of bone morphogenetic protein receptors in osteoprecursor cells. Further elucidation of the mechanisms related to this mechanism within the in vivo model may be necessary to ascertain greater detail.


Cotton (Gossypium hirsutum L.) boll rotting bacteria vectored by the brown stink bug, Euschistus servus (Say) (Hemiptera: Pentatomidae).
To determine the capacity of the brown stink bug (BSB) (Euschistus servus) to transmit an infective Pantoea agglomerans strain Sc 1-R into cotton (Gossypium hirsutum) bolls. A laboratory colony of BSB was maintained on fresh green beans. Either sterile or Sc 1-R contaminated beans were offered to adult insects. Strain Sc 1-R holds rifampicin resistance (Rif(r) ). Insects were then caged with unopened greenhouse-grown bolls. After 2 days, BSB were surface sterilized, ground, and then plated on media with and without Rif. Two weeks later, seed with lint were ground and plated on media with and without Rif. Microbes were recovered on nonselective media from all BSBs and from seed/lint at concentrations reaching 10(9) CFU g(-1) tissue. Rif(r) bacteria were recovered strictly from insects exposed to Sc1-R and from diseased seed/lint of respective bolls. Euschistus servus was capable of transmitting strain Sc 1-R into bolls resulting in disease. Insects not exposed to the pathogen deposited bacteria yet the nonpathogenic microbes produced insignificant damage to the boll tissue. This is the first study to concretely show the capacity of the BSB to transmit an infective P. agglomerans strain resulting in boll disease.


Short-term plasticity at the calyx of Held.
Synapses show widely varying degrees of short-term facilitation and depression. Several mechanisms have been proposed to underlie short-term plasticity, but the contributions of presynaptic mechanisms have been particularly difficult to study because of the small size of synaptic boutons in the mammalian brain. Here we review the functional properties of the calyx of Held, a giant nerve terminal that has shed new light on the general mechanisms that control short-term plasticity. The calyx of Held has also provided fresh insights into the strategies used by synapses to extend their dynamic range of operation and preserve the timing of sensory stimuli.


Varicose veins arising from the pelvis due to ovarian vein incompetence.
Vulval varices and perivulval veins are common though often unrecognised, and pelvic pain is a common complaint, sometimes without an obvious cause, hence treatment is not always successful. An association between these two problems has long been established, and some cases of pelvic pain are clearly associated with venous pathology. Often, these patients present to the vein clinic with recurrent varicose veins, because the standard procedures have failed and the pelvic origin was not recognised. The understanding of the pathology has evolved and will be reviewed. To establish diagnosis, the communication from the atypical varicose veins in the legs to the ovarian veins must be shown and incompetence of one or both ovarian veins must be demonstrated. Treatment requires elimination of the retrograde flow in the ovarian veins. This can be by either surgical ligation and removal or obliteration with coils and sclerosant. Having removed the cause and relieved the pelvic symptoms, the leg veins can then be successfully treated.


Fractal Dynamics in the RR Interval of Craniopharyngioma and Adrenal Tumor in Adolescence.
Heart rate variability (HRV) is the physiological phenomenon of variation in the time interval between heartbeats. It is measured by the variation in the beat-to-beat interval and/or RR variability (where R is a point corresponding to the peak of the QRS complex of the ECG wave and RR is the interval between successive Rs) and other components extracted from these. HRV is a field of research interest in pathophysiology (in general) and cancer prognosis (more specifically). Adolescents with adrenal tumor or craniopharyngioma were investigated, herein. Αutonomic nervous system recordings were performed with Task Force® Monitor (gold standard of the Task Force of the European Society of Cardiology and the North American Society of Electrophysiology). The RR interval (RRI) time series calculations were performed with the MatLab® computational environment and included the estimation of fractal dimension and Lyapunov exponent. Fractal dimensions were calculated by estimating N and R, where N represents the number of "squares" needed for a fractal shape to be completed and their respective "square size" R. By definition, if the first derivative of d ln N/d ln R remains constant for a space of R, this is the fractal dimension of the shape, in the present case of the time series trajectory. We found that RRI manifested different fractal dynamics, thus, a complex pattern of progression in these two morbid entities, suggesting the need for further investigation in ANS contribution to tumor pathophysiology.


Individual- and Neighbourhood-Level Indicators of Subjective Well-Being in a Small and Poor Eastern Cape Township: The Effect of Health, Social Capital, Marital Status, and Income.
Our study used multilevel regression analysis to identify individual- and neighbourhood-level factors that determine individual-level subjective well-being in Rhini, a deprived suburb of Grahamstown in the Eastern Cape province of South Africa. The Townsend index and Gini coefficient were used to investigate whether contextual neighbourhood-level differences in socioeconomic status determined individual-level subjective well-being. Crime experience, health status, social capital, and demographic variables were assessed at the individual level. The indicators of subjective well-being were estimated with a two-level random-intercepts and fixed slopes model. Social capital, health and marital status (all p < .001), followed by income level (p < .01) and the Townsend score (p < .05) were significantly related to individual-level subjective well-being outcomes. Our findings showed that individual-level subjective well-being is influenced by neighbourhood-level socioeconomic status as measured by the Townsend deprivation score. Individuals reported higher levels of subjective well-being in less deprived neighbourhoods. Here we wish to highlight the role of context for subjective well-being, and to suggest that subjective well-being outcomes may also be defined in ecological terms. We hope the findings are useful for implementing programs and interventions designed to achieve greater subjective well-being for people living in deprived areas.


The market reaction to syndicated loan announcements before and during the COVID-19 pandemic and the role of corporate governance.
This study examines the wealth effects of syndicated loan announcements before and after the onset of the COVID-19 outbreak. Using a sample of 637 loan announcements by European borrowers, we find significantly higher wealth gains during the pandemic compared to the pre-pandemic period. The results suggest that the certification of multiple lenders loans conveys a positive signal for the borrowers' creditworthiness during the pandemic-driven economic meltdown. We further show that certain corporate governance mechanisms, such as board size, gender diversity, and CEO duality and compensation, are related differently to borrowers' excess returns before and after the COVID-19 pandemic. The results are robust to alternative model specifications that control for different estimation models and event windows. They also hold after addressing self-selection bias.


Multi-channel open tubular traps for headspace sampling, gas chromatographic fraction collection and olfactory assessment of milk volatiles.
A headspace sampling method is described for concentrating milk volatiles onto a multi-channel open tubular silicone rubber trap (MCT) for thermal desorption into a GC-FID. Sections of the chromatographic profile, single peaks or combinations of compounds are recaptured with secondary MCTs during a subsequent run. The recaptured aroma is released in a controlled manner by heating the MCT in a portable heating device. An aroma release window of several minutes allows up to six people the opportunity to sniff each aroma fraction more than once. Olfactory results suggest that a synergistic combination of 2-heptanone and 2-nonanone could be responsible for a pungent cheese, sour milk-like aroma. MCTs containing single components or fractions can be desorbed into a GC-MS for compound identification.


Pulmonary sequestration presenting as mitral valve insufficiency.
Although pulmonary sequestrations commonly present with infectious complications, problems relating to high blood flow through the lesion are rarely apparent. A 4-year-old girl was referred for cardiac catheterization and evaluation for mitral valve surgery. An echocardiogram had demonstrated left atrial and ventricular enlargement and significant mitral regurgitation with an enlarged valve annulus. Angiography results showed a very large aorta to left atrial shunt through an unsuspected intralobar sequestration. Lobectomy with removal of the sequestration resulted in significant improvement in cardiac chamber size and function over a 2.5-year follow-up period, thus obviating the need for cardiac surgery and removing a potential source of infection. Careful evaluation of chest imaging studies will lead to the correct diagnosis and treatment in patients with pulmonary sequestration who are thought initially to have primary cardiac disease.


Natural killer function in flow cytometry. II. Evaluation of NK lytic activity by means of target cell morphological changes detected by right angle light scatter.
Morphological changes that occur in K562 cells after natural killing produce profound changes in cellular light scattering properties. The possibility of gating out all the effector cells by thresholding on perpendicular light scatter and the subsequent identification of two distinct clusters of cells, which correspond to dead and viable targets, have permitted the measurement of natural killer activity in vitro. The changes in scattering properties after cell death are mainly determined by the variation of internal refractive index of the dying cell. A comparison of the scattering and propidium iodide staining procedures showed good correlation. The morphological detection and measurement of cellular death is therefore used to estimate NK lytic activity. This methodology permits the measurement of NK activity without staining the target and the measurement of perpendicular light scatter provides an alternative approach to the study of lytic processes in vitro.


Are dopamine-related genotypes risk factors for excessive gestational weight gain?
Excessive gestational weight gain is associated with postpartum weight retention and downstream child obesity. Dopamine plays a critical role in the regulation of energy intake and body weight. The purpose of this study was to examine the relationship between excessive gestational weight gain and dopamine pathway-related polymorphisms, namely the variable nucleotide tandem repeat in the 3'untranslated region (UTR) region of the SLC6A3 (DAT-1) dopamine transporter gene and the 30-base pair variable nucleotide tandem repeat polymorphism of the 5'UTR of the monoamine oxidase-A (MAO-A) gene. Ninety-three women of mean age 31.7 ± 4.2 years were recruited from the Ottawa and Kingston birth cohort and assessed at 12-20 weeks' gestation. Mean body mass index was 22.7 ± 2.5 kg/m(2). Excessive gestational weight gain was defined according to the 2009 Institute of Medicine guidelines based on body mass index. Genotype analyses were performed using polymerase chain reaction and agarose gel electrophoresis. There was no relationship between the prevalence or magnitude of excessive gestational weight gain among women with the 3' UTR single nucleotide polymorphism of the DAT-1 gene. However, 70% (19 of 27) of women carrying the MAO-A 4/4 (high activity) allele exceeded recommendations for gestational weight gain compared with 48% (32 of 60) of those with the pooled 3/3, 3/4, and 3/3.5 (low activity) alleles (P < 0.05). Similarly, those with the MAO-A 4/4 allele had significantly greater gestational weight gain than those with the 3/3, 3/4, or 3/3.5 pooled genotypes (19.3 ± 4.1 versus 17.0 ± 5.0 kg, P = 0.03). Carriers of the 4/4 variants of the MAO-A gene may be at increased risk for excessive gestational weight gain.


Near-infrared fluorescence imaging for sentinel lymph node identification in colon cancer: a prospective single-center study and systematic review with meta-analysis.
Near-infrared (NIR) fluorescence imaging has the potential to overcome the current drawbacks of sentinel lymph node mapping (SLNM) in colon cancer. Our aim was to provide an overview of current SLNM performance and of factors influencing successful sentinel lymph node (SLN) identification using NIR fluorescence imaging in colon cancer. A systematic review and meta-analysis was conducted to identify currently used methods and results. Additionally, we performed a single-center study using indocyanine green (ICG) as SLNM dye in colon cancer patients scheduled for a laparoscopic colectomy. SLNs were analyzed with conventional hematoxylin-and-eosin staining and additionally with serial sectioning and immunohistochemistry (extended histopathological assessment). A true-positive procedure was defined as a tumor-positive SLN either by conventional hematoxylin-and-eosin staining or by extended histopathological assessment, independently of regional lymph node status. SLN procedures were determined to be true negatives if SLNs and regional lymph nodes revealed no metastases after conventional and advanced histopathology. SLN procedures yielding tumor-negative SLNs in combination with tumor-positive regional lymph nodes were classified as false negatives. Sensitivity, negative predictive value and detection rate were calculated. This systematic review and meta-analysis included 8 studies describing 227 SLN procedures. A pooled sensitivity of 0.63 (95% CI 0.51-0.74), negative predictive value 0.81 (95% CI 0.73-0.86) and detection rate of 0.94 (95% CI 0.85-0.97) were found. Upstaging as a result of extended histopathological assessment was 0.15 (95% CI 0.07-0.25). In our single-center study, we included 30 patients. Five false-negative SLNs were identified, resulting in a sensitivity of 44% and negative predictive value of 80%, with a detection rate of 89.7%. Eight patients had lymph node metastases, in three cases detected after extended pathological assessment, resulting in an upstaging of 13% (3 of 23 patients with negative nodes by conventional hematoxylin and eosin staining). Several anatomical and technical difficulties make SLNM with NIR fluorescence imaging in colon cancer particularly challenging when compared to other types of cancer. As a consequence, reports of SLNM accuracy vary widely. Future studies should try to standardize the SLNM procedure and focus on early-stage colon tumors, validation of tracer composition, injection mode and improvement of real-time optical guidance.


Comparison between angiotensin-converting enzyme inhibitor and angiotensin receptor blocker after percutaneous coronary intervention.
The inhibitors for renin-angiotensin-aldosterone system (RAAS) have different mechanisms of action in coronary artery disease (CAD). This study sought to compare the clinical outcomes between angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) therapy in patients with CAD undergoing contemporary percutaneous coronary intervention (PCI). Based on the National Health Insurance claims data in South Korea, patients aged 18 years or older who had undergone PCI between July 2011 and June 2015 were enrolled. The study participants were classified either as patients with acute myocardial infarction (AMI, n = 21,747) or angina (n = 28,708). And according to the post PCI discharge medications, patients were categorized into ACEI and ARB therapy groups. The primary endpoint was all-cause death, and the two groups were compared using a propensity-score matching analysis. The study population had a median follow-up of 2.2 years (interquartile range, 1.2-3.2). In the propensity-score matched AMI group (8341 pairs), the occurrence of all-cause death was significantly lower in the ACEI group than in the ARB group (hazard ratio [HR] of ACEI, 0.823; 95% confidence interval [CI]: 0.715-0.947; p = 0.006). In the propensity-score matched angina group (10,878 pairs), there was no difference in the incidence of the primary endpoint between the ACEI and ARB groups (HR of ACEI, 1.113; 95% CI: 0.986-1.257; p = 0.084). In this nationwide Korean cohort study, ACEI therapy in patients with AMI and concomitant PCI showed a significant reduction in all-cause mortality rates when compared to that with ARB therapy.


Ecotypic variation in root respiration rate among elevational populations ofAbies lasiocarpa andPicea engelmannii.
Small trees ofAbies lasiocarpa (Hook.) Nutt. andPicea engelmannii Parry were collected along two elevational transects in the central Rocky Mountains, and the effects of low temperature on their root respiration activity were measured after growth in cool and warm soil temperature treatments.Picea engelmannii roots respired significantly faster than those ofA. lasiocarpa, and trees of both species collected from high elevations respired significantly faster than those from lower elevations. The mean Q10 and mean activation energy of respiration were 2.0 and 47.2 kJ mol-1, respectively; they did not differ between transects, species, elevations of collection, or the soil temperature treatments. The results suggest ecotypic differentiation has occurred along these transects resulting in higher root respiration rates at higher elevations.


Advances in spiral fMRI: A high-resolution dataset.
We present data collected for the research article "Advances in Spiral fMRI: A High-resolution Study with Single-shot Acquisition" (Kasper et al. 2022). All data was acquired on a 7T ultra-high field MR system (Philips Achieva), equipped with a concurrent magnetic field monitoring setup based on 16 NMR probes. For task-based fMRI, a visual quarterfield stimulation paradigm was employed, alongside physiological monitoring via peripheral recordings. This data collection contains different datasets pertaining to different purposes: (1) Measured magnetic field dynamics (k0, spiral k-space trajectories, 2nd order spherical harmonics, concomitant fields) during ultra-high field fMRI sessions from six subjects, as well as concurrent temperature curves of the gradient coil, to explore MR system and subject-induced variability of field fluctuations and assess the impact of potential correction methods. (2) MR Raw Data, i.e., coil and concurrent encoding magnetic field (trajectory) data, of a single subject, as well as nominal spiral gradient waveforms, precomputed B0 and coil sensitivity maps, to enable testing of alternative image reconstruction approaches for spiral fMRI data. (3) Reconstructed image time series of the same subject alongside behavioral and physiological logfiles, to reproduce the fMRI preprocessing and analysis, as well as figures presented in the research article related to this article, using the published analysis code repository. All data is provided in standardized formats for the respective research area. In particular, ISMRMRD (HDF5) is used to store raw coil data and spiral trajectories, as well as measured field dynamics. Likewise, the NIfTI format is used for all imaging data (anatomical MRI and spiral fMRI, B0 and coil sensitivity maps).


The impact of technology systems and level of support in digital mental health interventions: a secondary meta-analysis.
The majority of people with a chronic disease (e.g., diabetes, hypertension, COPD) have more than one concurrent condition and are also at higher risk for developing comorbidities in mental health, including anxiety and depression. There is an urgent need for more relevant and accurate data on digital interventions in this area to prepare for an increase demand for mental health services. The aim of this study was to conduct a meta-analysis of the digital mental health interventions for people with comorbid physical and mental chronic diseases to compare the effect of technology systems and level of support. This secondary meta-analysis follows a rapid review of systematic reviews, a virtual workshop with knowledge users to identify research questions and a modified Delphi study to guide research methods: What types of digital health interventions (according to a recognized categorization) are the most effective for the management of concomitant mental health and chronic disease conditions in adults? We conducted a secondary analysis of the primary studies identified in the rapid review. Two reviewers independently screened the titles and abstracts and applied inclusion criteria: RCT design using a digital mental health intervention in a population of adults with another chronic condition, published after 2010 in French or English, and including an outcome measurement of anxiety or depression. Seven hundred eight primary studies were extracted from the systematic reviews and 84 primary studies met the inclusion criteria Digital mental health interventions were significantly more effective than in-person care for both anxiety and depression outcomes. Online messaging was the most effective technology to improve anxiety and depression scores; however, all technology types were effective. Interventions partially supported by healthcare professionals were more effective than self-administered. While our meta-analysis identifies digital intervention's characteristics are associated with better effectiveness, all technologies and levels of support could be used considering implementation context and population. The protocol for this review is registered in the National Collaborating Centre for Methods and Tools (NCCMT) COVID-19 Rapid Evidence Service (ID 75).


A Welfare Measure of "Offset Effects" in Health Insurance.
Changing health insurance coverage for one service may affect use of other insured services. When improving coverage for one service reduces use of another, the savings are referred to as "offset effects." For example, costs of better coverage for prescription drugs may be partly "offset" by reductions in hospital costs. Offset effects have welfare implications but it has not been clear how to value these impacts in design of health insurance. We show that plan-paid - rather than total -- spending is the right welfare measure of the offset effect, and go on to develop a "sufficient statistic" for evaluating the welfare effects of change in coverage in the presence of multiple goods. We derive a simple rule for when a coverage improvement increases welfare due to offset effects.


Pericardial heterografts: why do these valves fail?
Eighteen explanted pericardial heterografts were studied (16 standard Ionescu-Shiley, one Hancock, and one Mitroflow). Regurgitation was the reason given for explantation of all the Ionescu-Shiley valves. The other two valves were removed for technical reasons. All the Ionescu-Shiley valves had commissural tears and there was concomitant gross calcification in 10 of the 16 valves. In addition, an apparent increase in cusp area had caused "leaflet sagging". The explanted leaflets were thicker and stiffer than leaflets from an unimplanted valve. These features were confirmed directly with an animal model of subcutaneous implantation. Examination with an electron microscope revealed that these changes in mechanical properties seemed to be linked to fiber separation and infiltration by an amorphous proteinlike matrix. The durability of the glutaraldehyde-fixed pericardium depended on a number of factors. Early and midterm failure appeared to be stress induced. Predisposition to high mechanical stresses near the stent was exacerbated by the changes induced by the host environment. This problem was aggravated further in the Ionescu-Shiley valves by stress concentrations around the hole associated with the holding suture. In the long term, collagen disruption associated with leaflet flexure was followed by secondary calcification at the boundary between the intact and disrupted material.


Interaction of cationic phosphorus dendrimers (CPD) with charged and neutral lipid membranes.
Despite the rapid development of modern pharmaceutics, delivery of drugs to sites of action is not always effective. The research on new targeting delivery systems of pharmacologically active molecules is of great importance. Surface properties such as surface charge of drug delivery particles frequently define their pharmacokinetic profile; hence the efficiency of drugs can be increased by application of nanoparticles having appropriate surface properties. The aim of the present work was to study the interactions of cationic phosphorus-containing dendrimers (CPD) with model lipid membranes with no charge or bearing surface charge. The interactions of two generations of phosphorus dendrimers on the thermotropic behavior of model lipid membranes composed of DMPC (uncharged) or DMPC/DPPG (negatively charged) were studied using differential scanning calorimetry (DSC). The results of this study showed that CPDs can alter the thermotropic behaviour of the bilayer by reducing the cooperativity of phospholipids and this effect strongly depends on membrane surface charge. The information resulting from this study may be applied to the rational design of new drug carriers combining liposomal and dendrimeric technology.