Open Questions on the Origin of Eukaryotes.
Despite recent progress, the origin of the eukaryotic cell remains enigmatic. It is now known that the last eukaryotic common ancestor was complex and that endosymbiosis played a crucial role in eukaryogenesis at least via the acquisition of the alphaproteobacterial ancestor of mitochondria. However, the nature of the mitochondrial host is controversial, although the recent discovery of an archaeal lineage phylogenetically close to eukaryotes reinforces models proposing archaea-derived hosts. We argue that, in addition to improved phylogenomic analyses with more comprehensive taxon sampling to pinpoint the closest prokaryotic relatives of eukaryotes, determining plausible mechanisms and selective forces at the origin of key eukaryotic features, such as the nucleus or the bacterial-like eukaryotic membrane system, is essential to constrain existing models.


Freeze-tolerance of Trichinella muscle larvae in experimentally infected wild boars.
Freeze-tolerance of encapsulated Trichinella muscle larvae (ML) is mainly determined by Trichinella species, but is also influenced by host species, the age of the infection and the storage time and temperature of the infected meat. Moreover, the freeze-tolerance of the encapsulated species appears to be correlated to the development of thick capsule walls which increases with age. An extended infection period and the muscle composition in some hosts (e.g. herbivores) may provide freeze-avoiding matrices due to high carbohydrate contents. The present experiment compares freeze-tolerance of Trichinella spiralis and Trichinella britovi ML in wild boar meat 24 weeks post inoculation (wpi). Three groups of four wild boars were infected with 200, 2000 or 20,000 ML of T. britovi (ISS 1575), respectively. Additionally, three wild boars were inoculated with 20,000 ML of T. spiralis (ISS 004) and two animals served as negative controls. All wild boars were sacrificed 24 wpi. Muscle samples of 70 g were stored at -21°C for 19, 30 and 56 h, and for 1-8 weeks. Larvae were recovered by artificial digestion. Their mobilities were recorded using Saisam(®) image analysis software and their infectivities were evaluated using mouse bioassays. Samples frozen for 19, 30 and 56 h allowed recovery of mobile ML, but samples frozen for 1 or 2 weeks did not. Correspondingly, only T. spiralis and T. britovi larvae isolated from wild boar meat frozen for 19, 30 and 56 h established in mice. This study showed that freezing at -21°C for 1 week inactivated T. spiralis and T. britovi ML encapsulated in wild boar meat for 24 weeks.


Prevalence of High-risk Nonalcoholic Steatohepatitis (NASH) in the United States: Results From NHANES 2017-2018.
The population prevalence of high-risk non-alcoholic steatohepatitis (NASH), defined as nonalcoholic fatty liver disease activity score ≥4 and fibrosis stage ≥2, is unknown. The FibroScan-AST (FAST) score, calculated using liver stiffness measurement and controlled attenuation parameter values from FibroScan and aspartate aminotransferase levels, is a validated algorithm to identify individuals with high-risk NASH. We estimated the prevalence of high-risk NASH using the FAST score in the United States population. Data were derived from the National Health and Nutrition Examination Surveys 2017-2018, which included a total of 4218 adults with valid elastography measurements. FAST scores of ≥0.35 (sensitivity, 90%) and ≥0.67 (specificity, 90%) were used to identify adults with high-risk NASH in the general population. At 90% sensitivity for the FAST score, the prevalence of age-adjusted high-risk NASH was 5.8% and was higher among men (8.2% vs 3.6% in women) and in Hispanics (9.2% vs. 5.8% non-Hispanic (N.H.) Asians, 5.2% in N.H. whites, and 3.8% in N.H. blacks). The prevalence of high-risk NASH was 11.7% in those with metabolic syndrome and 22.5% in individuals with type 2 diabetes mellitus (T2DM). At 90% specificity for the FAST score, the prevalence of age-adjusted high-risk NASH was 1.2% and was higher among men (1.7% vs 0.8% in women) and in Hispanics (2.2% vs 1.0% in N.H. Asians, 0.9% in N.H. whites, and 0.4% in N.H. blacks). The prevalence of high-risk NASH was 3.4% in those with metabolic syndrome and 8.7% in adults with T2DM. We estimate at least 2 million adults have high-risk NASH in the United States. Moreover, the prevalence of high-risk NASH among individuals with T2DM is higher, ranging between 8.7% and 22.5%, supporting the case for coordinated case-finding and management.


Ultra-high resolution band-selective HSQC for nanomole-scale identification of chlorine-substituted 13 C in natural products drug discovery.
Ultra-high resolution band-selective HSQC (bsHSQC) has been employed for detection of 35 Cl-37 Cl isotope shifted 13 C NMR signals for assignment of regioisomerism in bromo-chloro natural products. Optimum pulse sequence and instrumental parameters for maximization of detection of the isotope shifts were explored. The chlorine isotope shifts (Δδ) were detected within crosspeaks and were shown to vary with hybridization of 13 C, substitution of 13 C, presence of β-chloro substituents, and their relative configuration. Deconvolution of Cl-substituted CH bsHSQC crosspeaks may provide other useful information, including a potentially MS-independent method for quantitating 37 Cl/35 C isotopic fractionation during the biosynthesis of halogenated natural products. Copyright © 2016 John Wiley & Sons, Ltd.


Potentiation of an anthrax DNA vaccine with electroporation.
DNA vaccines are a promising method of immunization against biothreats and emerging infections because they are relatively easy to design, manufacture, store and distribute. However, immunization with DNA vaccines using conventional delivery methods often fails to induce consistent, robust immune responses, especially in species larger than the mouse. Intramuscular (i.m.) delivery of a plasmid encoding anthrax toxin protective antigen (PA) using electroporation (EP), a potent DNA delivery method, rapidly induced anti-PA IgG and toxin neutralizing antibodies within 2 weeks following a single immunization in multiple experimental species. The delivery procedure is particularly dose efficient and thus favorable for achieving target levels of response following vaccine administration in humans. These results suggest that EP may be a valuable platform technology for the delivery of DNA vaccines against anthrax and other biothreat agents.


Exercise Training: The Holistic Approach in Cardiovascular Prevention.
Nowadays, there are robust clinical and pathophysiological evidence supporting the beneficial effects of physical activity on cardiovascular (CV) system. Thus, the physical activity is considered a key strategy for CV prevention. In fact, exercise training exerts favourable effects on all risk factors for CV diseases (i.e. essential hypertension, type 2 diabetes mellitus, hypercholesterolemia, obesity, metabolic syndrome, etc…). In addition, all training modalities such as the aerobic (continuous walking, jogging, cycling, etc.) or resistance exercise (weights), as well as the leisure-time physical activity (recreational walking, gardening, etc) prevent the development of the major CV risk factors, or delay the progression of target organ damage improving cardio-metabolic risk. Exercise training is also the core component of all cardiac rehabilitation programs that have demonstrated to improve the quality of life and to reduce morbidity in patients with CV diseases, mostly in patients with coronary artery diseases. Finally, it is still debated whether or not exercise training can influence the occurrence of atrial and ventricular arrhythmias. In this regard, there is some evidence that exercise training is protective predominantly for atrial arrhythmias, reducing the incidence of atrial fibrillation. In conclusion, the salutary effects evoked by physical acitvity are useful in primary and secondary CV prevention.


Using cell lysates to assess N-terminal acetyltransferase activity and impairment.
The vast majority of eukaryotic proteins are subjected to N-terminal (Nt) acetylation. This reaction is catalyzed by a group of N-terminal acetyltransferases (NATs), which co- or post-translationally transfer an acetyl group from Acetyl coenzyme A to the protein N-terminus. Nt-acetylation plays an important role in many cellular processes, but the functional consequences of this widespread protein modification are still undefined for most proteins. Several in vitro acetylation assays have been developed to study the catalytic activity and substrate specificity of NATs or other acetyltransferases. These assays are valuable tools that can be used to define substrate specificities of yet uncharacterized NAT candidates, assess catalytic impairment of pathogenic NAT variants, and determine the potency of chemical inhibitors. The enzyme input in acetylation assays is typically acetyltransferases that have been recombinantly expressed and purified or immunoprecipitated proteins. In this chapter, we highlight how cell lysates can also be used to assess NAT catalytic activity and impairment when used as input in a previously described isotope-based in vitro Nt-acetylation assay. This is a fast and highly sensitive method that utilizes isotope labeled 14C-Ac-CoA and scintillation to detect the formation of Nt-acetylated peptide products.


Epidemiology of SARS-CoV-2 during the first three waves in Scotland: a national record linkage study.
The early COVID-19 pandemic in Scotland-defined as the era before widespread access to vaccination and monoclonal antibody treatment-can be characterised into three distinct waves: March-July 2020, July 2020-April 2021 and May-August 2021. Each wave was met with various societal restrictions in an effort to reduce disease transmission and associated morbidity and mortality. Understanding the epidemiology of infections during these waves can provide valuable insights into future pandemic planning. Scottish RT-PCR testing data reported up until 8 August 2021, the day prior to most restrictions being lifted in Scotland, were included. Demographic characteristics including age, sex and social deprivation associated with transmission, morbidity and mortality were compared across waves. A case-control analysis for each wave was then modelled to further compare risk factors associated with death over time. Of the 349 904 reported cases, there were 18 099, 197 251 and 134 554 in waves 1, 2 and 3, respectively. Hospitalisations, intensive care unit admissions and deaths appeared highest in wave 2, though risk factors associated with COVID-19 death remained similar across the waves. Higher deprivation and certain comorbidities were associated with higher deaths in all waves. Despite the higher number of cases reported in waves 2 and 3, case fatality rates were lower: likely a combination of improved detection of infections in younger age groups, introduction of social measures and vaccination. Higher social deprivation and comorbidities resulted in higher deaths for all waves.


Applications of staffing, scheduling, and budgeting methodologies to hospital ancillary units.
A computer-aided methodology for integrating the budgeting, staffing, and labor productivity systems of Ancillary Services using Respiratory Therapy as an example is presented. The data needed, staffing computations and schedules, and productivity analysis are presented and discussed. A summary of the predicted savings and other benefits for the application hospital are presented with comparisons to present productivity systems.


Inverted papilloma of renal pelvis associated with contralateral ureteral malignancy and bladder recurrence.
We report a case of an inverted papilloma of the renal pelvis diagnosed at the same time as transitional cell carcinoma of the contralateral ureter. The diagnostic studies and surgical management are presented. Recurrence of an inverted papilloma in the bladder 1 year after treatment was confirmed histologically. Recurrence of this lesion and the association with urothelial malignancy suggest the need for close followup of patients with an inverted papilloma.


A biophysical miRNA-mRNA interaction model infers canonical and noncanonical targets.
We introduce a biophysical model of miRNA-target interaction and infer its parameters from Argonaute 2 cross-linking and immunoprecipitation data. We show that a substantial fraction of human miRNA target sites are noncanonical and that predicted target-site affinity correlates well with the extent of target destabilization. Our model provides a rigorous biophysical approach to miRNA target identification beyond ad hoc miRNA seed-based methods.


Focal parenchymal lung lesions showing a potential of false-positive and false-negative interpretations on integrated PET/CT.
We describe a number of benign focal lung lesions with increased 18F-FDG uptake that simulate lung cancer and malignant lesions that lead to false-negatives due to little 18F-FDG uptake on integrated PET/CT images. The integration of clinical history, morphologic findings of lung parenchymal lesions on the CT component, and metabolic activities on the PET component of integrated PET/CT can help reduce false interpretation of the study. A lung biopsy may be needed for lesions showing increased 18F-FDG uptake on PET for tissue confirmation irrespective of their morphology on CT.


Homo-oligomerization is essential for Toll/interleukin-1 receptor domain-containing adaptor molecule-1-mediated NF-kappaB and interferon regulatory factor-3 activation.
Toll-IL-1 receptor (TIR) domain-containing adaptor molecule-1 (TICAM-1, also named TIR domain-containing adaptor-inducing interferon (IFN)-beta or TRIF)) is a signaling adaptor of Toll-like receptor (TLR) 3/4 that activates the transcription factors, interferon regulatory factor-3 (IRF-3) and NF-kappaB leading to inducing IFN-beta production. The mechanisms by which TICAM-1 is activated by TLR3/4 to serve as a signaling platform are unknown. In this study, we show that homo-oligomerization of TICAM-1 is critical for TICAM-1-mediated activation of NF-kappaB and IRF-3. Both TIR and C-terminal domain of TICAM-1 mediated TICAM-1 oligomerization. Pro(434) located in the TIR domain and the C-terminal region, with the exception of the RIP homotypic-interacting motif, were determinants of TICAM-1 oligomerization. Mutation of TIR domain (P434H) or deletion of C-terminal domain greatly reduced TICAM-1-mediated NF-kappaB and IFN-beta promoter activation. TICAM-1 oligomerization at either the TIR domain or the C-terminal region resulted in recruitment of tumor necrosis factor receptor-associated factor 3, a downstream signaling molecule essential for TICAM-1-mediated IRF-3 activation, but not recruitment of the IRF-3 kinase complex, NF-kappaB-activating kinase-associated protein 1 and TANK-binding kinase 1. In addition, RIP homotypic-interacting motif mutant, which possesses two oligomerization motifs but not the RIP1 binding motif, also failed to recruit NF-kappaB-activating kinase-associated protein 1 and TANK-binding kinase 1. Thus, full activation and formation of TICAM-1 signalosomes requires oligomerization induced at two different sites and RIP1 binding.


Regio- and Diastereoselective Spirocyclopropanation of Benzofuran-Derived Azadienes through 1,4-Addition-Induced Dearomatization Reaction under Mild Conditions.
A Cs2CO3-mediated [2 + 1] cycloaddition of benzofuran-derived azadienes (BDAs) with bromomalonate by using a dearomatization strategy has been developed. Through this process, BDAs serve as a potential 2-atom synthon in the construction of a range of functionalized spirocyclopropane derivatives, such as spirobenzofuran-2-cyclopropanes and spiroindane-2-cyclopropanes.


Relationship between removal of circumflex iliac nodes distal to the external iliac nodes and postoperative lower-extremity lymphedema in uterine cervical cancer.
This study aimed to determine if there is a causal relationship between removal of the circumflex iliac nodes distal to the external iliac nodes (CINDEIN) and postoperative lower-extremity lymphedema (POLEL) after systematic lymphadenectomy in patients with cervical cancer. A retrospective chart review was performed for all living cervical cancer patients who underwent lymphadenectomy and were managed at Hokkaido Cancer Center between 1993 and 2013. The type of lymphadenectomy gradually shifted from lymphadenectomy with removal of CINDEIN to without CINDEIN dissection during this period. The study period was divided into two phases: from 1993-2007 (first phase) and from 2008-2013 (second phase). We identified patients with POLEL. Logistic regression analysis was used to select the risk factors for POLEL. Implementation of CINDEIN-dissection lymphadenectomy (94.0% vs. 20.6%, p<0.0001) and adjuvant radiotherapy (26.1% vs. 4.5%, p<0.0001) was significantly higher in the first phase than in the second phase. Of 398 patients evaluated, POLEL was noted in medical records of 80 (20.1%) patients with a median follow-up period of 78.0months. The occurrence rate of POLEL was significantly higher in the first phase than in the second phase (32.2% vs. 8.0%, p<0.0001), despite no change in the number of dissected lymph nodes between the two phases. Multivariate analysis showed that adjuvant radiation therapy (odds ratio=2.6, 95% confidence interval=1.4-4.8) and removal of CINDEIN (odds ratio=4.6, 95% confidence interval=2.4-9.0) were independent risk factors for POLEL. Elimination of CINDEIN dissection is helpful for reducing the incidence of POLEL.


Short-term and long-term outcomes in living donors for liver transplantation: Cohort study.
Although perioperative outcomes following donor hepatectomy (DH) have been reported, little is known about the long-term outcomes in living donors of liver transplantation. The aim of this study was to investigate the short-term and long-term outcomes following DH. A total of 408 living donors who underwent DH between 1996 and 2019 were analyzed in this retrospective study, focusing on short-term outcomes with respect to the operation period (era) and the graft type, as well as long-term outcomes. The overall incidence of postoperative complications was 40.4%. These included minor (30.4%), major (10.0%), and biliary (14.0%) complications. Short-term outcomes after DH slightly improved over time, and outcomes did not differ significantly between the graft types. With regards to long-term outcomes, the incidence of surgery-related complications such as keloids, incisional hernias, and mechanical bowel obstructions was 6.6% over a median follow-up of 7.2 years. In addition, some donors developed comorbidities such as lifestyle diseases and cancers during the follow-up period. Our study confirmed an improvement of perioperative outcomes in living donors. There was no significant association between the graft type and postoperative outcomes. Donors could develop various morbidities during long-term follow-up. Therefore, a careful perioperative management and long-term follow-up should be provided to living donors.


Robust identification of multiple-input single-output system response for efficient pickup noise removal from tokamak diagnostics.
Electromagnetic pickup noise in the tokamak environment imposes an imminent challenge for measuring weak diagnostic photocurrents in the nA range. The diagnostic signal can be contaminated by an unknown mixture of crosstalk signals from coils powered by currents in the kA range. To address this issue, an algorithm for robust identification of linear multi-input single-output (MISO) systems has been developed. The MISO model describes the dynamic relationship between measured signals from power sources and observed signals in the diagnostic and allows for a precise subtraction of the noise component. The proposed method was tested on experimental diagnostic data from the DIII-D tokamak, and it has reduced noise by up to 20 dB in the 1-20 kHz range.


Infant botulism: case report and clinical update.
Infant botulism occurs in infants between 1 week and 11 months of age and results from the in vivo production of neurotoxin by Clostridium botulinum. The clinical spectrum ranges from asymptomatic carriers, through various degrees of paralysis, to sudden death. The classic clinical presentation is an afebrile child with constipation and generalized weakness manifested by poor head control, poor suck, and weak cry. Symptoms can progress to include cranial nerve palsies, respiratory arrest, and adynamic ileus. Treatment is supportive in an intensive care setting. Antibiotics and antitoxin are not indicated. The morbidity and mortality is less than 3% in hospitalized patients and complete recovery can be expected. The environmental and dietary factors associated with infection are discussed.


Ice-active proteins and cryoprotectants from the New Zealand alpine cockroach, Celatoblatta quinquemaculata.
Celatoblatta quinquemaculata is moderately freezing tolerant. We have investigated low and high molecular weight compounds that may be associated with its survival. Glycerol and trehalose were identified as potential cryoprotectants, with trehalose at the higher concentration. Trehalose was at its highest concentration in late autumn, during the periods sampled. Water contents declined with time and were significantly lower in late autumn than in late summer. No thermal hysteresis activity was detected in haemolymph or in extracts of the head, muscles and the fat body. Extracts of the Malpighian tubules showed an hexagonal crystal growth form, as did those of the gut tissue and gut contents. The gut tissue had high levels of thermal hysteresis (approximately 2 degrees C) and the gut contents somewhat lower levels (approximately 0.6 degrees C). Recrystallization inhibition activity mirrored that of thermal hysteresis, with activity absent in the haemolymph or fat body cells but present in the gut tissues and contents. Activity was reduced by heating and was associated with a molecule >14kDa in size. These findings suggest an antifreeze protein is involved. In fed animals, ice nucleation is likely to start in the gut. Gut cells have a much greater resistance to freezing than do fat body or Malpighian tubule cells. The antifreeze protein may enable this tissue to survive freezing stress by inhibiting recrystallization.


Assessment of risk scores to predict mortality of COVID-19 patients admitted to the intensive care unit.
To assess the ABC2-SPH score in predicting COVID-19 in-hospital mortality, during intensive care unit (ICU) admission, and to compare its performance with other scores (SOFA, SAPS-3, NEWS2, 4C Mortality Score, SOARS, CURB-65, modified CHA2DS2-VASc, and a novel severity score). Consecutive patients (≥ 18 years) with laboratory-confirmed COVID-19 admitted to ICUs of 25 hospitals, located in 17 Brazilian cities, from October 2020 to March 2022, were included. Overall performance of the scores was evaluated using the Brier score. ABC2-SPH was used as the reference score, and comparisons between ABC2-SPH and the other scores were performed by using the Bonferroni method of correction. The primary outcome was in-hospital mortality. ABC2-SPH had an area under the curve of 0.716 (95% CI 0.693-0.738), significantly higher than CURB-65, SOFA, NEWS2, SOARS, and modified CHA2DS2-VASc scores. There was no statistically significant difference between ABC2-SPH and SAPS-3, 4C Mortality Score, and the novel severity score. ABC2-SPH was superior to other risk scores, but it still did not demonstrate an excellent predictive ability for mortality in critically ill COVID-19 patients. Our results indicate the need to develop a new score, for this subset of patients.


Spinal cord blood flow measured by 14C-iodoantipyrine autoradiography during and after graded spinal cord compression in rats.
The relations between degree of thoracic spinal cord compression causing myelographic block, reversible paraparesis, and extinction of the sensory evoked potential on one hand, and spinal cord blood flow on the other, were investigated. This was done in rats using the blocking weight-technique and 14C-iodoantipyrine autoradiography. A load of 9 g caused myelographic block. Five minutes of compression with that load caused a reduction of spinal cord blood flow to about 25%, but 5 and 60 minutes after the compression spinal cord blood flow was restored to 60% of the pretrauma value. A load of 35 g for 5 minutes caused transient paraparesis. Recovery to about 30% was observed 5 and 60 minutes thereafter. During compression at a load of 55 g, which caused almost total extinction of sensory evoked potential and irreversible paraplegia, spinal cord blood flow under the load ceased. The results indicate that myelographic block occurs at a load which does not cause irreversible paraparesis and that a load which permits sensory evoked potential to be elicited results in potentially salvageable damage.


A hierarchical processing unit for multi-component behavior in the avian brain.
Multi-component behavior is a form of goal-directed behavior that depends on the ability to execute various responses in a precise temporal order. Even though this function is vital for any species, little is known about how non-mammalian species accomplish such behavior and what the underlying neural mechanisms are. We show that humans and a non-mammalian species (pigeons) perform equally well in multi-component behavior and provide a validated experimental approach useful for cross-species comparisons. Applying molecular imaging methods, we identified brain regions most important for the examined behavioral dynamics in pigeons. Especially activity in the nidopallium intermedium medialis pars laterale (NIML) was specific to multi-component behavior since only activity in NIML was predictive for behavioral efficiency. The data suggest that NIML is important for hierarchical processing during goal-directed behavior and shares functional characteristics with the human inferior frontal gyrus in multi-component behavior.


Alterations in tissue Mg++, Na+ and spinal cord edema following impact trauma in rats.
Alterations in water content and total tissue Na+ and Mg++ of rat spinal cord tissue were followed over time after a 100 g-cm impact injury to the T-9 spinal cord segment. Rats subjected to laminectomy but not trauma served as controls. In the injured segment there was a progressive increase in water content with increased Na+ and decreased Mg++ at 1 hour and 24 hours after trauma. At seven days, water and Na+ content remained elevated, whereas Mg++ levels had returned to preinjury baseline values. Because of its important role in many metabolic and physiological regulatory processes the early decline in Mg++ concentration after trauma may contribute to the development of secondary tissue damage after spinal cord injury.


Precise genome engineering in Pseudomonas using phage-encoded homologous recombination and the Cascade-Cas3 system.
A lack of generic and effective genetic manipulation methods for Pseudomonas has restricted fundamental research and utilization of this genus for biotechnology applications. Phage-encoded homologous recombination (PEHR) is an efficient tool for bacterial genome engineering. This PEHR system is based on a lambda Red-like operon (BAS) from Pseudomonas aeruginosa phage Ab31 and a Rac bacteriophage RecET-like operon (Rec-TEPsy) from P. syringae pv. syringae B728a and also contains exogenous elements, including the RecBCD inhibitor (Redγ or Pluγ) or single-stranded DNA-binding protein (SSB), that were added to enhance the PEHR recombineering efficiency. To solve the problem of false positives in Pseudomonas editing with the PEHR system, the processive enzyme Cas3 with a minimal Type I-C Cascade-based system was combined with PEHR. This protocol describes the utilization of a Pseudomonas-specific PEHR-Cas3 system that was designed to universally and proficiently modify the genomes of Pseudomonas species. The pipeline uses standardized cassettes combined with the concerted use of SacB counterselection and Cre site-specific recombinase for markerless or seamless genome modification, in association with vectors that possess the selectively replicating template R6K to minimize recombineering background. Compared with the traditional allelic exchange editing method, the PEHR-Cas3 system does not need to construct suicide plasmids carrying long homologous arms, thus simplifying the experimental procedure and shortening the traceless editing period. Compared with general editing systems based on phage recombinases, the PEHR-Cas3 system can effectively improve the screening efficiency of mutants using the cutting ability of Cas3 protein. The entire procedure requires ~12 days.


Macroporous monoliths with pH-induced switchable wettability for recyclable oil separation and recovery.
The effective separation and recovery of oils from water is important for the protections of ecosystems and the environment. Polymeric porous monoliths have been demonstrated as attractive absorbents for oil/water separation. However, the recyclability was mainly realized by squeezing, combustion, or centrifugation, which may restrict in elastic materials, destroy the adsorbates or need special apparatus. Thus it is desirable to developing monoliths with controllable oil absorption and desorption. A series of "smart" monoliths with pH-induced switchable wettability were fabricated by high internal phase emulsion (HIPE) polymerization and epoxide ring-opening for the incorporation of amine groups. The resultant monoliths and their wettabilities were examined using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), nitrogen adsorption/desorption and contact angle analysis, respectively. The oil separation efficiency and recyclability were evaluated. The monoliths with macroporous structure can undergo switchable wettability under reversible pH stimulation. As an absorbent, the monoliths not only separated and recovered organic solvents and oils (including crude oil) from aqueous mixtures through a reversible and recyclable absorption and desorption process upon alternating the pH between 7.0 and 1.0, but also continuously expulsed oils from water surfaces in a continuous manner with the aid of external driving pressures. Moreover, the monoliths also allowed the effective separation of surfactant-free and surfactant-stabilized oil-in-water emulsions with high separation efficiency.


The effects of dietary treatment with essential fatty acids on sciatic nerve conduction and activity of the Na+/K+ pump in streptozotocin-diabetic rats.
1. This study examined the effects of dietary essential fatty acid supplementation (5% (w/w) evening primrose oil) upon sciatic motor nerve conduction velocity and 86Rb+ pumping in sciatic nerve endoneurial preparations in rats with 4 to 5 weeks of streptozotocin-induced diabetes. 2. Control diabetic rats (dietary supplementation with 5% (w/w) hydrogenated coconut oil) exhibited a reduction in motor nerve conduction velocity (16%; P less than 0.05) compared to similarly-fed non-diabetic controls, but there was no significant alteration in ouabain-sensitive 86Rb+ pumping, a parameter reflecting activity of the Na+/K+ pump. 3. Treatment of diabetic rats with evening primrose oil prevented completely the development of the motor nerve conduction velocity deficit without affecting the severity of diabetes. Evening primrose oil treatment did not significantly affect motor nerve conduction velocity of non-diabetic animals. 4. Evening primrose oil treatment caused a significant reduction in activity of the Na+/K+ pump in sciatic nerves of diabetic animals (45%; P less than 0.05). 5. These results suggest that the acute conduction velocity defect arising in streptozotocin-diabetic rats, and the actions of evening primrose oil upon this, are independent of any effect on activity of the Na+/K+ pump. Other putative mechanisms are discussed.


Analgesic, anti-inflammatory and oxy-radical scavenger activity of imidazole and imidazole derivatives.
The author describes the recent work of his laboratory on imidazole. It increased the analgesic effects of morphine, and rivalled acetylsalicylic acid as an analgesic antipyretic agent. At 160 mg/kg, imidazole protected rats against indomethacin-induced gastric ulcers. It was equal to acetylsalicylic acid in reducing carrageenan inflammation, and was superior to it as anti-arthritic drug. Imidazole 2-hydroxybenzoate caused 36% inhibition of synovial fluid depolymerization.


Baseline characteristics of patients with acute ischemic stroke in a suburban area of Thailand.
Development in stroke care during the past two decades has greatly reduced mortality and dependence in many developed countries. However, we still lack information about baseline characteristics of patients with ischemic stroke in Thailand, especially in suburban areas. We sought to study characteristics of Thai patients with ischemic stroke, including carotid stenosis and aspirin nonresponders. In this preliminary study, we included all patients with acute/subacute ischemic stroke/transient ischemic attack from August 2006 to July 2007. Information about baseline characteristics, including medication, was collected. Carotid duplex studies were performed in all patients who were clinically stable. In all, 194 patients with ischemic stroke/transient ischemic attack were studied. Of patients, 62% came to the hospital within 24 hours after onset of symptoms, and 8% arrived within 3 hours. Stroke in the young was 13%. Of patients, 28% had already been on aspirin (aspirin nonresponder) before having a new ischemic stroke. Significant carotid stenosis was found in 17% (31 of 184) of the patients. Although fewer patients came to the hospital within 3 hours after stroke onset, other baseline characteristics of Thai patients with ischemic stroke do not much differ from those of other Asian countries.


Hyperacute measurement of brain-tissue oxygen, carbon dioxide, pH, and intracranial pressure before, during, and after cerebral angiography in patients with aneurysmatic subarachnoid hemorrhage in poor condition.
The objective of this study was to examine early changes of intracranial pressure (ICP) and brain oxygenation before, during, and after cerebral angiography in patients with poor-grade subarachnoid hemorrhage (SAH). Fourteen patients with poor-grade SAH without intracerebral hematoma were studied. A significant change in monitored variables (arterial gases, ICP, brain-tissue oxygen pressure [Ptio(2)], brain-tissue carbon dioxide pressure, and pH) was defined as a register deviation of more than 20% compared with the baseline. Critical Ptio(2) values (<15 mm Hg) or significant Ptio(2) decreases were considered to be impaired brain oxygenation. These data were correlated with the angiography findings and the presence of massive brain edema and hypodense areas in follow-up computed tomography (CT) scan controls. Neurotrend data were unavailable in 4 patients because of calibration failure. Impaired brain oxygenation during angiography was observed in 5 patients. Initial critical Ptio(2) values were found in 1 patient. Four patients developed a linear Ptio(2) and pH decrease after the angio-catheter canalized the examined vessels in the neck. Statistically significant correlation was found between brain pH and Ptio(2) changes in these patients (P < .001, Spearman rho). Arterial gases, ICP, and cerebral perfusion pressure did not show significant alterations at this time. Significant correlations existed between severe intracranial angiographic arterial caliber reduction and impaired Ptio(2) values (P < .01). Patients with impaired Ptio(2) values frequently showed lesions in CT scan controls (P < .05). This study documented several fluctuations in the brain oxygenation of patients with poor-grade SAH during angiography. Patients with severe intracranial angiographic arterial caliber reduction at this time have an increased risk for impaired brain oxygenation.


H3K27me3-modulated Hofbauer cell BMP2 signalling enhancement compensates for shallow trophoblast invasion in preeclampsia.
Preeclampsia (PE) is a common hypertensive pregnancy disorder associated with shallow trophoblast invasion. Although bone morphogenetic protein 2 (BMP2) has been shown to promote trophoblast invasion in vitro, its cellular origin and molecular regulation in placenta, as well as its potential role in PE, has yet to be established. Additionally, whether BMP2 and/or its downstream molecules could serve as potential diagnostic or therapeutic targets for PE has not been explored. Placentas and sera from PE and healthy pregnant women were subjected to multi-omics analyses, immunoblots, qPCR, and ELISA assays. Immortalized trophoblast cells, primary cultures of human trophoblasts, and first-trimester villous explants were used for in vitro experiments. Adenovirus expressing sFlt-1 (Ad Flt1)-induced PE rat model was used for in vivo studies. We find globally decreased H3K27me3 modifications and increased BMP2 signalling in preeclamptic placentas, which is negatively correlated with clinical manifestations. BMP2 is derived from Hofbauer cells and epigenetically regulated by H3K27me3 modification. BMP2 promotes trophoblast invasion and vascular mimicry by upregulating BMP6 via BMPR1A-SMAD2/3-SMAD4 signalling. BMP2 supplementation alleviates high blood pressure and fetal growth restriction phenotypes in Ad Flt1-induced rat PE model. Our findings demonstrate that epigenetically regulated Hofbauer cell-derived BMP2 signalling enhancement in late gestation could serve as a compensatory response for shallow trophoblast invasion in PE, suggesting opportunities for diagnostic marker and therapeutic target applications in PE clinical management. National Key Research and Development Program of China (2022YFC2702400), National Natural Science Foundation of China (82101784, 82171648, 31988101), and Natural Science Foundation of Shandong Province (ZR2020QH051, ZR2020MH039).


Pleural line thickness reference values for preterm and term newborns.
In lung ultrasound (LUS), the pleural line is an artifact whose thickness depends on the underlying lung pathology. To date there are no published studies on normal values of pleural line thickness (PLT) in newborns. The aim of our study is to describe normal PLT values in term newborn (TN) and preterm newborn (PTN). We recruited eupneic TN and PTN, under 34 weeks of gestation, on their first 24 hours of life. Newborns presenting any respiratory distress since birth were excluded. LUS was performed in four areas: upper anterior, lower anterior, lateral and posterior. At each location, we measured PLT and values where compared. Intraobserver and interobserver agreement were assessed using the intraclass correlation coefficient (ICC), and the kappa coefficient. We included 23 TN with a median birth weight of 3365 g (interquartile range [IQR] 3100-3575 g) and a median gestational age of 39 weeks (IQR, 38-40 weeks). In the PTN group, 23 patients were included with a median birth weight of 1350 g (IQR, 1150-1590 g) and a median gestational age of 31 weeks (IQR, 30-32 weeks). Median PLT values were less than 1 mm, and there were no significant differences between groups at any locations, with the exception of the left lower anterior field (0.79 mm [IQR, 0.72-0.89 mm] vs 0.68 mm [IQR, 0.62-0.72 mm]). Intraobserver agreement was high: consistency ICC 0.77 (95% confidence interval [CI], 0.32-0.92) and absolute ICC 0.78 (95% CI, 0.34-0.93). Interobserver agreement was high for the definition of thin pleural line as less than 1 mm. TN and asymptomatic PTN have similar PLT values. Overall, PLT in healthy newborns should be less than 1 mm.


Evaluation of changes in root canal length and accuracy of the electronic apex locator during different stages of endodontic treatment and retreatment.
This study evaluated changes in the root canal length (RCL) and the accuracy of the electronic apex locator (EAL) during the different stages of endodontic treatment and retreatment. Fifty-six mesial root canals of mandibular molars were selected. The actual root canal length (AL) of the canals was obtained by inserting a size 15 hand file up to the apical foramen, under magnification. The electronic lengths were obtained at the "APEX" mark of Root ZX II, using an alginate model. Both measurements were performed at three different stages of the initial root canal treatment-unflared, flared, and concluded-and at two stages of retreatment, after achieving patency and repreparation. Data were statistically analyzed and the significance level established was 5%. All stages produced a significant reduction in the AL (p < 0.05). The greatest variation was observed between the unflared-flared stages (0.2 mm) and between concluded-patency stages (0.09 mm), with no difference between them (p > 0.05). The accuracy of Root ZX II was negatively affected after achieving patency, presenting statistically significant difference compared to the other stages (p < 0.05). A significant reduction in the RCL was observed along the different stages of endodontic treatment and retreatment. The EAL was accurate to measure the root canals in most stages, except after achieving patency for endodontic retreatment. Determining and monitoring the RCL is an essential step towards a favorable prognosis, since it reduced along the different stages evaluated. Root ZX II was not accurate for endodontic retreatment.


Pharmaceutical application of biomedical polymers. XXIX. Preliminary study on film dosage form prepared from chitosan for oral drug delivery.
The potential of chitosan films containing diazepam as an oral drug delivery was investigated in rabbits. The results indicated that a film composed of a 1:0.5 drug-chitosan mixture might be an effective dosage form that is equivalent to the commercial tablet dosage forms. The ability of chitosan to form films may permit its use in the formulation of film dosage forms, as an alternative to pharmaceutical tablets.


Human fertility: sociodemographic aspects.
This study analyzes the sociodemographic factors at the root of the reduction in fertility in developed countries and the way in which these are correlated to the increase in levels of infertility. The postponement of marriage and of bearing the first child, the transition still underway toward nontraditional family forms and unfavorable economic and institutional factors explain a considerable part of the increase in levels of infertility.


Cisplatin and vindesine combination chemotherapy in advanced malignant melanoma: an EORTC phase II study.
Sixty-one evaluable patients with measurable advanced malignant melanoma received 4-week courses of a combination of cisplatin 100 mg/m2 as a 24-hr i.v. infusion on day 1 and vindesine 3 mg/m2 as an i.v. bolus on days 1, 8, 15 for two courses and every other week thereafter. Two patients achieved complete response for 46 and 81+ weeks respectively, eleven patients achieved partial response for a median of 17 weeks (range 8-26) and three patients had no change for 24 weeks or more. The overall response rate of 21% did not seem to be affected by prior chemotherapy or site of indicator lesions, soft tissue vs visceral. Myelosuppression, consisting essentially of leucopenia, required dose schedule modifications in 41% of the first two courses and 12% of the remaining courses, but never produced major complications. Non-hematologic toxic effects were prominent, especially nausea and vomiting, which were universal. Alopecia was seen in 71% of the patients, neuromuscular manifestations in 39%, diarrhea in 30%, renal impairment in 25%, mucositis in 12%, ototoxicity in 7% and phlebitis in 3%. These results do not suggest striking additive or synergistic antitumor activity of cisplatin and vindesine in advanced malignant melanoma, at least with the method of drug administration selected for this trial.


Trimerization of β-cyclodextrin through the click reaction.
Triprop-2-ynyl benzene-1,3,5-tricarboxylate (A) is synthesized by the reaction of 1,3,5-benzenetricarbonyl trichloride with propargyl alcohol and (A) is clicked with mono-6-deoxy-6-azido-β-cyclodextrin (N3-β-CD) in the presence of copper(I) bromide catalyst. N3-β-CD has been prepared from β-cyclodextrin (β-CD) on treatment with toluenesulfonyl chloride (TsCl) and then with sodium azide (NaN3) in two consecutive steps. Further trimer of β-CD is characterized by (1)H NMR and FTIR studies. Solubility of β-cyclodextrin (β-CD) in water can be increased by increasing the number of alcoholic OH functionalities and hydrophobic cavities in a molecule by the trimerization of β-CD.


Cytotoxicity Evaluation of Bioresorbable Fixation Screws on Human Gingival Fibroblasts and Mouse Osteoblasts by Real-Time Cell Analysis.
To evaluate the effects of bioresorbable fixation screws (BFSs) on human gingival fibroblast (HGF) and mouse osteoblast (MC3T3-E1) cell viability. The KLS Martin SonicPins Rx, Synthes RapidSorb Cortex Screws, and Inion CPS Bioabsorbable Fixation System each were incubated in Dulbecco's Modified Eagle Medium for 72 hours according to ISO 10993-5 standards. A real-time cell analyzer was used to evaluate cell survival. After seeding 200-μL cell suspensions in the wells of an E-plate View 96, HGF and MC3T3-E1 cells were treated with the bioactive components released by the bioresorbable materials and monitored every 15 minutes for 96 hours. Statistical significance was determined using 1-way analysis of variance and Tukey-Kramer tests. There were significant differences in the HGF responses to the untreated control conditions and the Synthes (P < .01), Inion (P < .05), and KLS Martin (P < .05) treatments over 48 hours. The Synthes (P < .01) and Inion (P < .01) treatments produced lower HGF cell index values than the untreated control at 72 hours, whereas the KLS Martin treatment did not. When left to elute for 96 hours, there were no significant differences in values among the control and study groups for HGFs (P > .05). All tested BFSs decreased cell survival rates of M3T3C1 cells for 48 hours (P < .01), 72 hours (P < .001), and 96 hours (P < .001). Differences in the sensitivities of the 2 tested cell lines to the different BFSs might be the result of the different materials used to manufacture the screws. These results provide fundamental knowledge and new insights for the future design and development of new biocompatible BFSs for oral and maxillofacial surgery.


Selective detection of minor prototropic tautomers in low-symmetry tetraazaporphyrin derivatives by the combined use of electronic absorption, MCD, and CI calculations.
A series of low-symmetry metal-free tetraazaporphyrin (TAP) derivatives, i.e. monobenzo-substituted (1H2), adjacently dibenzo-substituted (2AdH2), oppositely dibenzo-substituted (2OpH2), and tribenzo-substituted (3H2) TAP derivatives, has been investigated by the combined use of electronic absorption, MCD, and CI calculations, proving the existence of two prototropic tautomers in 1H2 and 3H2.


Overexpression of microRNA gga-miR-21 in chicken fibroblasts suppresses replication of infectious bursal disease virus through inhibiting VP1 translation.
Previously we have identified a series of cellular miRNA molecules up- or down-regulated in infectious bursal disease virus (IBDV) infected chicken embryo fibroblasts and Bursa of Fabricius with gene microarray analysis. Here we studied in detail a relatively well studied miRNA, gga-miR-21, for better understanding miRNAs involvement in IBDV-host interactions. Chicken pri-gga-miRNA-21 and a control miRNA Caenorhabditis elegans pri-cel-lin-4 gene were cloned into a lentiviral vector, respectively. The resulting recombinant lentiviruses were used to infect chicken fibroblast cell line DF-1, and two stable cell lines, DF-miR-21 (overexpressing gga-miR-21) and DF-lin-4 (overexpressing cel-lin-4), were selected. Replication of IBDV in DF-miR-21, DF-lin-4 and DF-1 cells were compared and molecular mechanism of IBDV replication alteration was explored using bioinformatics, reporter gene system, qRT-PCR and Western blot analysis. IBDV replication was markedly lower in DF-miR-21 than in DF-lin-4 or DF-1 cells. A gga-miR-21 target sequence was identified within IBDV VP1 gene (1713-1734bp). Fusion of a 520nt long partial IBDV VP1 gene containing the target with a luciferase gene resulted in significantly lower transient luciferase activity in DF-miR-21 cells as compared to that in DF-lin-4 or DF-1 cell. Following IBDV infection of the cell lines, VP1 protein level in DF-miR-21 cells was dramatically lower than that in DF-lin-4 or DF-1 cells but VP1 mRNA level was not different. The finding indicated that gga-miR-21 could suppress IBDV replication through down regulating IBDV VP1 expression at translational level.


Harnessing a P450 fatty acid decarboxylase from Macrococcus caseolyticus for microbial biosynthesis of odd chain terminal alkenes.
Alkenes are industrially important platform chemicals with broad applications. In this study, we report a direct microbial biosynthesis of terminal alkenes from fermentable sugars by harnessing a P450 fatty acid (FA) decarboxylase from Macrococcus caseolyticus (OleTMC). We first characterized OleTMC and demonstrated its in vitro H2O2-independent activities towards linear C10:0-C18:0 FAs, with higher activity for C16:0-C18:0 FAs. Next, we engineered a de novo alkene biosynthesis pathway, consisting of OleTMC and an engineered E. coli thioesterase (TesA) with compatible substrate specificities, and introduced this pathway into E. coli for terminal alkene biosynthesis from glucose. The recombinant E. coli EcNN101 produced a total of 17.78 ± 0.63 mg/L odd-chain terminal alkenes, comprising of 0.9% ± 0.5% C11 alkene, 12.7% ± 2.2% C13 alkene, 82.7% ± 1.7% C15 alkene, and 3.7% ± 0.8% C17 alkene, and a yield of 0.87 ± 0.03 (mg/g) on glucose. To improve alkene production, we identified and overcame the electron transfer limitation in OleTMC, by introducing a two-component redox system, consisting of a putidaredoxin reductase (CamA) and a putidaredoxin (CamB) from Pseudomonas putida, into EcNN101, and demonstrated the alkene production increased ~2.8 fold. Finally, to better understand the substrate specificities of OleTMC observed, we employed in silico protein modeling to illuminate the functional role of FA binding pocket.


A novel nucleosome assembly procedure (with a little help from pectin).
The acidic polysaccharide pectin (alpha-1,4-polygalacturonic acid) has been introduced as a nucleosome assembly facilitator as a substitute for polyglutamic acid. The pectin-assembled nucleosomes were indistinguishable from polyglutamic acid-assembled nucleosomes by thermal denaturation and DNAse I digestion. Pectin had two major advantages over polyglutamic acid-the yield of assembled cores was approximately 50% higher and the pectin could be easily removed after completion of the reassembly procedure by dialysis following pectinase cleavage.


The perioperative management of the arthroscopic patient.
This article has described the perioperative management of the arthroscopic patient. As emphasized, preoperative planning requires a precise diagnosis, patient education, and selective procedures. The operative management is sophisticated, exacting, and challenging, as discussed in other articles of this issue. Finally, the postoperative management is specifically directed toward pathology and procedure. Recovery times are variable, and complications are not insignificant and can lead to prolonged patient morbidity and financial loss. It is important to consider patient goals versus reality, patient willingness to opt for acceptable versus optimal results, and if the procedure is necessary versus justified versus contraindicated. If all of these factors are kept in mind by the surgeon and conveyed to the patient, arthroscopic surgery can be extremely rewarding to both.


Beriplex P/N reverses severe warfarin-induced overanticoagulation immediately and completely in patients presenting with major bleeding.
In an open non-randomized study, 10 patients with major bleeding and an Internationalized Normal Ratio (INR) greater than 14 were treated with 5 mg of intravenous vitamin K and 30 iu/kg of a single concentrate containing factors II, VII, IX and X (Beriplex P/N; Aventis Behring). The levels of these factors before and immediately after treatment were 4.7, 1.6, 8.5 and 1.1 iu/dl and 94, 30, 66 and 91 iu/dl respectively. The median INR before treatment was greater than 20 and, after treatment, 1.1. All patients had a satisfactory clinical response with immediate cessation of bleeding, and no thromboembolic complications occurred.


Sirtuin1: a promising serum protein marker for early detection of Alzheimer's disease.
Sirtuin (SIRT) pathway has a crucial role in Alzheimer's disease (AD). The present study evaluated the alterations in serum sirtuin1 (SIRT1) concentration in healthy individuals (young and old) and patients with AD and mild cognitive impairment (MCI). Blood samples were collected from 40 AD and 9 MCI patients as cases and 22 young healthy adults and 22 healthy elderly individuals as controls. Serum SIRT1 was estimated by Surface Plasmon Resonance (SPR), Western Blot and Enzyme Linked Immunosorbent Assay (ELISA). A significant (p<0.0001) decline in SIRT1 concentration was observed in patients with AD (2.27 ± 0.46 ng/µl) and MCI (3.64 ± 0.15 ng/µl) compared to healthy elderly individuals (4.82 ± 0.4 ng/µl). The serum SIRT1 concentration in healthy elderly was also significantly lower (p<0.0001) compared to young healthy controls (8.16 ± 0.87 ng/µl). This study, first of its kind, has demonstrated, decline in serum concentration of SIRT1 in healthy individuals as they age. In patients with AD and MCI the decline was even more pronounced, which provides an opportunity to develop this protein as a predictive marker of AD in early stages with suitable cut off values.


The prognostic value of [F]FDG-PET in nonrefractory partial epilepsy.
Regional abnormalities of cerebral glucose metabolism, as identified by 18-fluorodeoxyglucose positron emission tomography (FDG-PET) have prognostic value regarding the outcome of epilepsy surgery in patients with refractory partial epilepsy. The value of FDG-PET abnormalities in nonrefractory patients has not been investigated systematically. This study examines whether FDG-PET could be used for early identification of nonrefractory epilepsy in patients who will become pharmacoresistant later during the course of their disease. We investigated interictal abnormalities of cerebral glucose metabolism by using FDG-PET in 125 consecutive patients with nonrefractory cryptogenic partial epilepsy and normal cranial magnetic resonance imaging (MRI), and we compared relative changes in seizure frequency in 90 patients after > or =2 years of follow-up. Regional asymmetry of tracer distribution was seen in 43 of the 90 patients. Forty-one patients had regional glucose hypometabolism in the temporal and two patients in an extratemporal region. No difference between patients with and without a hypometabolic focus was found regarding seizure freedom after follow-up. This held true also for the subgroup of patients with epilepsy onset within 1 year before admission. Only patients with regional glucose metabolism showed an increase in seizure frequency. Multivariate analysis showed that only anticonvulsive treatment before index admission and the possibility of localizing the epileptogenic focus by using all available clinical and EEG data were independently associated with continuing seizures after a median follow-up period of 43 months. Regional hypometabolism in FDG-PET is not significantly associated with a lower likelihood of successful anticonvulsant drug therapy in patients with nonrefractory partial epilepsy. Careful analysis of all routinely available clinical and neurophysiologic data has a much better predictive power to identify patients with medically refractory epilepsy early in the course of the disease. However, if PET data are available, they could help in identifying patients with a less benign course.


Lifetime socioeconomic determinants of health trajectories among older adults.
Drawing on life course theory and research, we explored how socioeconomic circumstances during childhood and adulthood shape self-reported health trajectories among older Mexican adults. We used data from the Mexican Health and Aging Study panel survey (2001-2015) and used sequence analysis to estimate types of self-reported health trajectories in older adulthood. We then explored the association between those health trajectories and socioeconomic determinants at different life stages, including education, occupation, employment, economic status, parental education, and adverse living conditions and illnesses during childhood. Our contributions are threefold. First, we identified four types of health trajectories for men and eight for women, representing a more nuanced longitudinal health status profile than previously shown. Second, we found that childhood and adult socioeconomic circumstances influence self-reported health trajectories at older age. Third, our results suggest there is no simple monotonic relationship between life course circumstances and self-reported health trajectories.


Protecting maize from rootworm damage with the combined application of arbuscular mycorrhizal fungi, Pseudomonas bacteria and entomopathogenic nematodes.
Diabrotica virgifera virgifera LeConte, the western corn rootworm (WCR), is the most destructive pest of maize in North America, and has recently spread across central Europe. Its subterranean larval stages are hard to reach with pesticides and it has evolved resistance to conventional management practices. The application of beneficial soil organisms is being considered as a sustainable and environmental friendly alternative. In a previous study, the combined application in wheat fields of arbuscular mycorrhizal fungi, entomopathogenic Pseudomonas bacteria, and entomopathogenic nematodes was found to promote growth and protection against a natural pest infestation, without negative cross effects. Because of the insect-killing capacity of the bacteria and nematodes, we hypothesized that the application of these organisms would have similar or even greater beneficial effects in WCR-infested maize fields. During three consecutive years (2015-2017), we conducted trials in Missouri (USA) in which we applied the three organisms, alone or in combinations, in plots that were artificially infested with WCR and in non-infested control plots. For two of the three trials, we found that in plots treated with entomopathogenic nematodes and/or entomopathogenic Pseudomonas bacteria, roots were less damaged than the roots of plants in control plots. During one year, WCR survival was significantly lower in plots treated with Pseudomonas than in control plots, and the surviving larvae that were recovered from these plots were lighter. The bacterial and nematodes treatments also enhanced yield, assessed as total grain weight, in one of the trials. The effects of the treatments varied considerable among the three years, but they were always positive for the plants.


Harmine exerts anxiolytic effects by regulating neuroinflammation and neuronal plasticity in the basolateral amygdala.
Increasing evidence indicates that an altered immune system is closely linked to the pathophysiology of anxiety disorders, and inhibition of neuroinflammation may represent an effective therapeutic strategy to treat anxiety disorders. Harmine, a beta-carboline alkaloid in various medicinal plants, has been widely reported to display anti-inflammatory and potentially anxiolytic effects. However, the exact underlying mechanisms are not fully understood. Our recent study has demonstrated that dysregulation of neuroplasticity in the basolateral amygdala (BLA) contributes to the pathological processes of inflammation-related anxiety. In this study, using a mouse model of anxiety challenged with Escherichia coli lipopolysaccharide (LPS), we found that harmine alleviated LPS-induced anxiety-like behaviors in mice. Mechanistically, harmine significantly prevented LPS-induced neuroinflammation by suppressing the expression of pro-inflammatory cytokines including IL-1β and TNF-α. Meanwhile, ex vivo whole-cell slice electrophysiology combined with optogenetics showed that LPS-induced increase of medial prefrontal cortex (mPFC)-driven excitatory but not inhibitory synaptic transmission onto BLA projection neurons, thereby alleviating LPS-induced shift of excitatory/inhibitory balance towards excitation. In addition, harmine attenuated the increased intrinsic neuronal excitability of BLA PNs by reducing the medium after-hyperpolarization. In conclusion, our findings provide new evidence that harmine may exert its anxiolytic effect by downregulating LPS-induced neuroinflammation and restoring the changes in neuronal plasticity in BLA PNs.


Isolation of Aeromonas salmonicida in association with purple-pigmented bacteria in sediment from a Scottish loch.
Aeromonas salmonicida was recovered in close association with an unidentified purple-pigmented organism, which was isolated from sediment in a Scottish loch during November (1997) and February (1998). However, there has not been any evidence of A. salmonicida infections, specifically furunculosis, associated with the fish in this loch.


Parathyroid hormone and calcitonin secretion in uraemic infants.
In six infants aged between 4 and 8 months with chronic renal failure, we have studied blood levels of calcium (Ca), phosphorus (P), alkaline phosphatase, immunoreactive parathyroid hormone (PTH), and calcitonin (CT), as well as urinary excretion of Ca, P, hydroxyproline and cyclic AMP under basal conditions and during an infusion of 20 mg/kg of 10% Ca gluconate in normal saline over 4 h. Under basal conditions four infants had normal serum Ca and P values, alkaline phosphatase levels at the upper limit of normal, and very high PTH (range: 1450--2550 pg Eq/ml) and CT (range: 700--1900 pg/ml) levels. The urinary Ca excretion was low, whereas the urinary excretion of P, hydroxyproline and cyclic AMP was high. During Ca infusion, the total serum Ca and CT levels increased, PTH fell without however reaching the normal upper limit, and urinary P and cyclic AMP excretion decreased. In two infants with osteodystrophy and the highest levels of PTH (2900 and 3500 pg Eq/ml respectively) there was no suppression of PTH during Ca infusion.


The role of cardiovascular magnetic resonance in heart failure.
Cardiovascular Magnetic Resonance (CMR) is an accepted gold standard for non-invasive, accurate, and reproducible assessment of cardiac mass and function. The interest in its use for viability, myocardial perfusion and coronary artery imaging is also widespread and growing rapidly as the hardware and expertise becomes available in more centres, and the scans themselves become more cost effective. In patients with heart failure, accurate and reproducible serial assessment of remodelling is of prognostic importance and the lack of exposure to ionizing radiation is helpful. The concept of an integrated approach to heart failure and its complications using CMR is fast becoming a reality, and this will be tested widely in the coming few years, with the new generation of dedicated CMR scanners.


Cellular reactions to implantation of a microdialysis tube in the rat hippocampus.
Microdialysis tubes, used for measurements of extracellular neurotransmitter concentrations, were implanted in rat dorsal hippocampus to study the adjacent tissue reaction. The brain was examined 1-60 days after the implantation. Within the first 2 days, normal neuropil and only occasional hemorrhage surrounded the microdialysis tube. Three days following the implantation astrocytes close to the dialysis tube, hypertrophied. Hypertrophic astrocyte processes invaded the spongy fiber wall. There was no increase in the number of astrocytes. Fourteen days after the fiber insertion layers of reticulin-positive fibers separated astrocytes and the remaining neuropil from the fiber wall. Late tissue changes (1 and 2 months) consisted of collagen deposits and occasional granuloma formation. These results can be used to predict the optimal time for commencing microdialysis after the fiber implantation.


Fixed-dose combination therapy for Parkinson's disease with a spotlight on entacapone in the past 20 years: a reduced pill burden and a simplified dosing regime.
Parkinson's disease (PD) is a progressive, chronic neurodegenerative disorder. The main neuropathological cause of the disease is the death of dopaminergic neurons in the substantia nigra. Unfortunately, there is no curative treatment yet. The gold-standard of the treatment is levodopa (LD). During the course of the disease, motor complications develop, which postulates the addition of entacapone (ENT) to the dopaminergic medication. Previous studies have suggested that patients have a better quality of life when entacapone is added in a combination with LD. A systematic literature search was performed. Articles were identified through PubMed (MEDLINE), Web of Science, Ovid, and ClinicalTrials.gov databases. The following search terms were used: 'Levodopa' AND 'Carbidopa' OR 'Benserazide' AND 'Entacapone'. The search period was between 2000 and 2020. Twenty randomized and 10 non-randomized clinical trials (12,893 subjects) were included in the qualitative analysis. The systematic review was written in line with the PRISMA guideline. ENT administered in combination with LD resulted in a better quality of life compared to separate tablets. Therefore, in PD patients where impaired motor performance develops and the application of entacapone is necessary, it is suggested to be administered in a single tablet form.


Dopamine D1 and D4 receptor subtypes differentially modulate recurrent excitatory synapses in prefrontal cortical pyramidal neurons.
Although dopamine (DA) effects in the prefrontal cortex (PFC) have been studied extensively, the function of steady-state ambient levels of DA in the regulation of afferent excitatory transmission in PFC pyramidal neurons remains relatively unexplored. Using intracellular sharp-electrode and whole-cell recordings combined with intracellular labeling in brain slices, we found that D1/D5 receptor blockade did not alter synaptic responses in the PFC, but D1/D5 receptor activation consistently enhanced recurrent synaptic excitation in the majority of pyramidal neurons tested. In contrast, D4 receptor blockade resulted in an evoked complex multiple spike discharge pattern that contained both early and late (presumably multisynaptic) components of the evoked response that is contingent upon the preservation of axon collaterals of the neuron under study. Moreover, GABAergic interneurons were found to play a role in both responses; blockade of GABA(a)-mediated inhibition caused bath application of DA to convert monosynaptic excitatory postsynaptic potentials (EPSPs) to complex spike bursts riding on the late component of the EPSP. On the other hand, during the blockade of GABA(a)-mediated conductances, administration of a D4 receptor antagonist failed to facilitate evoked multiple spike discharge. Morphological analysis of axon collaterals of labeled neurons revealed that neurons in which the D4 receptor blockade induced the putative polysynaptic response had axon collaterals that were largely preserved. These data suggest that DA exerts a bidirectional modulation of PFC pyramidal neurons in brain slices provided that local network connections with interneurons are preserved, with D4 receptors under tonic stimulation by ambient low levels of DA, whereas D1/D5 receptors activated upon phasic DA input.


Uncrossed retino-geniculate and retino-tectal projections in the hereditary unilaterally microphthalmic rats.
The dorsal lateral geniculate nucleus (CGLd) of the hereditary unilaterally microphthalmic rats showed a diminution of volume and an increase of neuronal density on the contralateral side of the vestigial eye without the optic nerve (about 60 and 160% of the normal, respectively; P less than 0.001). No significant changes were observed in the ipsilateral CGLd. Uncrossed retino-CGLd and -tectal projections were studied using the anterograde axonal transport of HRP in adult rats with the congenital unilateral microphthalmia. Aberrant expansions of the uncrossed retinal projection widely covered CGLd and the superficial layers of the superior colliculus (SCS). The distribution pattern of expanded uncrossed retinal pathway in the mutant was essentially similar to that of neonatally one-eyed rats.


Clinical and immunological study of 7 patients with minocycline-induced autoimmune phenomena.
Prolonged treatment with minocycline for acne vulgaris has been associated with the development of arthralgia, arthritis, and other autoimmune phenomena. We characterized the clinical, laboratory, and immunological profiles of seven patients with this syndrome. Clinically the patients were studied with special emphasis on prior minocycline treatment, presenting symptoms, physical findings, course, and outcome. Laboratory tests included fluorescent antinuclear and antineutrophil cytoplasmic (ANCA) antibodies, as well as antibodies to myeloperoxidase, bactericidal permeability increasing protein, elastase, cathepsin G, lactoferrin, cardiolipin, and histone. All 7 patients presented with polyarthritis or arthralgia, morning stiffness, and fever after 6 to 36 months of minocycline treatment. The skin was involved in five patients (three with livedo reticularis and two with subcutaneous nodules). Two patients had chronic active hepatitis. Increased titers of perinuclear ANCA (p-ANCA) were detected in all seven patients; five patients had fluorescent antinuclear antibodies, two had antihistone autoantibodies and one had anticardiolipin antibodies. Antigenic characterization of p-ANCA disclosed antibodies to bactericidal permeability increasing protein in one patient, to elastase in three patients, and to cathepsin G in five patients. Symptoms resolved in five patients upon discontinuation of minocycline; the other two patients were treated with corticosteroids and also achieved remissions. Minocycline-induced autoimmune syndrome is characterized by reversible polyarthralgia or arthritis, morning stiffness, fever, frequent skin involvement, occasional chronic active hepatitis, and increased titers of p-ANCA with various minor p-ANCA-related antigens.


Untangling the Strands of Hairy Cell Leukemia: The Clinicopathological Spectrum over Eleven Years at a Tertiary Care Center.
Hairy Cell Leukemia (HCL) is an uncommon, indolent lymphoproliferative disorder of mature B lymphoid cells, accounting for 2% of all lymphoid tumors. The present study evaluated the clinical-hematological profile of HCL patients diagnosed at a single tertiary care center over a 11-year period. The retrospective observational study was done between October 2010 and September 2021. The relevant clinical and laboratory information were retrieved from hospital medical records and electronic databases. The statistical analysis was performed using version 23.0 of SPSS. 66 (5.9%) of 1125 cases of chronic lymphoproliferative disorder were HCL. Splenomegaly was found in 47 (71.2%), hepatomegaly in 26 (39.5%), and lymphadenopathy in 17 (25.7%) of the cases. The mean hemoglobin, total leukocytes count, and platelets count were 8.04 g/dl, 6.76 X 109/L, and 77 X 109/L, respectively. Pancytopenia was detected in 40 cases (60.61 %). Bone marrow biopsies were majorly hypercellular and showed predominantly diffuse infiltration by atypical lymphoid cells. In two patients, initially thought of having refractory/hypoplastic anemia, the bone marrow biopsy and flow cytometry revealed HCL involvement. 42 cases of HCL underwent flow cytometry. CD20, CD 11c, CD 25 and CD 103 were positive in all the cases. The aberrant expression of CD5, CD10, and CD23 was found in frequencies of 5.71 %, 31.42 %, and 19.35%, respectively. In 40 cases for which follow-up information was available, there was full remission in 26 patients (65%), and later three showed relapse (7.5%) of which one died, and persistent leukemic activity in five (10%). Eight patients (20%) died even before the initiation of treatment. One patient died within one month of therapy. No patient was examined for BRAF V600E mutation analysis. CD 10+ HCL was the most prevalent atypical immunophenotypic subgroup. Bone marrow biopsy and flow cytometry are crucial diagnostic tools to rule out hairy cell leukemia. However, BRAF V600E mutation analysis should be performed in cases with unusual presentation or resistance to treatment.


Modulation of the long-latency reflex to stretch by the supplementary motor area in humans.
Surface-recorded, electromyographic responses to 200-ms ramp stretches were studied in the wrist flexor muscles from both arms of a patient with clinical and radiographic evidence of infarction in the right supplementary motor area (SMA). They were compared with those from 8 age-matched control subjects. The latencies of the spinal component of the stretch reflex were slightly longer than normal in both arms of the patient (normal subjects: 28.5 +/- 2.6 ms; patient: 35 ms, right arm and 32 ms left arm). However, the amplitude and duration of the short-latency response were identical in both arms. The onset of the long-latency response to stretch was symmetrical in both the patient's arms and was slightly later than normal (normal subjects 55.5 +/- 4.0 ms, patient: 72 ms right arm and 70 ms left arm); however, its duration was considerably prolonged in the arm contralateral to the SMA lesion (normal subjects: 44.8 +/- 6.0 ms; patient: 48 ms right arm. 105 ms left arm). These results are consistent with the hypothesis that the long-latency stretch reflex is mediated via a transcortical loop.


Acute-on-chronic acalculous cholecystitis in a Black child. A case report and review of the literature.
A case of acute-on-chronic acalculous cholecystitis in a 7-year-old Black child is reported. The incidence causation, differential diagnosis and management of acalculous cholecystitis in childhood and the confusion caused by the terminology are briefly discussed.


Greater nasal nitric oxide output during inhalation: effects on air temperature and water content.
The nose conditions the temperature and humidity of nasal air, and the nasal mucosal vasculature supplies heat and water for these processes. We hypothesize that nitric oxide (NO) modulates these processes through vasoactive effects on nasal mucosal vasculature. We measured the temperature, humidity and NO concentrations of nasal air during inhalation and exhalation across the nose and calculated net heat, water and NO output before (controls, n=7) and after inhibition of NO synthase by topical l-NAME (N=5) in healthy humans. We found that calculated NO output across the nasal passages is approximately three-fold greater during inhalation (503+/-105 nL/min) compared with exhalation (162+/-56 nL/min). Moreover, topical administration of l-NAME decreased nasal air temperature and humidity conditioning and NO output, but these effects were limited to inhalation. We conclude that nasal NO output is greater during inhalation than exhalation in humans. Our findings also support a role of nasal NO in temperature and humidity conditioning of nasal air.


Cytokine regulation of female-macrophage resistance to Leishmania mexicana parasites. Role of IL-12p70.
In previous studies, carried out in humans, we showed that females are resistant to Leishmania mexicana infection. We also showed that 17β-estradiol (E2) induces killing of parasites inside of murine macrophages. In this work, we compared, for the first time, L mexicana survival inside of male (male BMDM) and female (female BMDM) bone marrow-derived macrophages (BMDM) treated in vitro with E2 or dihydrotestosterone (DHT). We also compared their levels of nitric oxide (NO), interleukin (IL)-6, IL-10, IL-12p70 and tumour necrosis factor (TNF-α). We found that female BMDM are a lot less susceptible to infection as compared with male BMDM. 17β-estradiol induced killing of most parasites inside of female BMDM. Dihydrotestosterone, on the other hand, induced some parasite killing inside of some infected male BMDM. Interleukin-6 levels were higher in female BMDM treated with either hormone. Neither TNF-α nor IL-10 levels showed significant differences compared with sham controls. Interestingly IL-12p70 was more abundantly produced by sham female BMDM as compared with sham male BMDM. Only female BMDM treated with E2 trigger a robust IL-12p70 production, but it was significantly reduced in male BMDM. This suggests IL-12p70 is an important factor in female-macrophage resistance to L mexicana parasites.


COVID-19 Vaccine Perspective Among University Lecturers and Students: A Qualitative Study of Pre Implementation of Vaccination.
The determinants of vaccine preferences and hesitancy varied by time and place. The aim of this study was to assess the perspective of a COVID-19 vaccine among university-based groups. This qualitative research involved lecturers and students, and a selection of online focused group discussion was conducted based on the following criteria, including representatives of the health and non-health faculties, with at least 8 attendees in lecturer groups, and 8 participants in student groups. This study is described in 8 themes covering various issues about COVID-19 vaccine, such as views on COVID-19 vaccine, fake news, vaccine implementation by government. The assessment of vaccine perspective shows that although awaited by some people, it also creates contradictions. This is due to the massive amount of information available regarding the vaccine descriptions. The role of the government as the main policy maker is to provide the right information and to make the right decisions about vaccines and vaccination implementation.


ACE2 inhibits proliferation of smooth muscle cell through AT1R and its downstream signaling pathway.
To investigate the effect of the angiotensin converting enzyme 2 (ACE2) on AT1R expression, ERK1/2 and STAT3 protein phosphorylation in rat vascular smooth muscle cells (VSMCs) was studied. VSMCs were transfected with a lentiviral vector including the ACE2 gene and with siRNA to regulate the level of ACE2 in VSMCs. The levels of mRNA and proteins of ACE2, AT1R, ERK1/2, p-ERK1/2, STAT3, and p-STAT3 in VSMCs were examined using real-time PCR and western blot. The proliferation of VSMCs was observed by CCK-8 assay and BrdU measurement. Upregulation of ACE2 inhibited the growth of cells elicited by angiotensin II (Ang II). ACE2 significantly suppressed the level of the AT1 receptor (AT1R) protein induced by Ang II and phosphorylated the ERK1/2 and STAT3 proteins in the downstream signaling pathway. The transcriptional and translational levels of ACE2 were significantly lower in the si-ACE2 group than in the control group. The level of AT1R mRNA and protein, both with the phosphorylation expression of ERK1/2 and STAT3 protein in the siACE2 group and the Ang II group, were significantly enhanced than those in the control group. ACE2 significantly inhibited the growth of VSMCs. ACE2 inhibited the proliferation of VSMCs by suppressing AT1R and the downstream ERK1/2 and STAT3 signaling axes. Also, Ang II enhanced the level of AT1R and phosphorylated ERK1/2 and STAT3 by inhibiting the level of the ACE2 mRNA and protein.


Ketoconazole therapy for hormonally refractive metastatic prostate cancer.
Twenty-two patients who had progressive metastatic prostatic carcinoma (Stage D2) despite androgen-deprivation therapy (bilateral orchiectomy, 10 cases; bilateral orchiectomy followed by diethylstilbestrol, 7 cases; diethylstilbestrol, 3 cases; combined megestrol acetate and low-dose estrogen, 2 cases) were treated with ketoconazole. Of 19 evaluable patients, 2 (11%) achieved a partial response (for 6 and 8 months) and 7 others (37%) achieved stabilization of disease (for periods of 3-8 months). Of 16 patients in whom pain was a prominent clinical feature, 13 (81%) noted improvement in pain for periods of one to eight months (median 3 months). We conclude that ketoconazole is a useful addition to our current armory for management of patients with metastatic prostatic cancer resistant to prior hormonal therapy.


Current status of the development of trans-platinum antitumor drugs.
The discovery in the 1990s of several trans-Pt complexes with in vitro and in vivo activity against tumor cells sensitive and/or resistant to cisplatin has forced the re-evaluation of the structure-activity relationships for platinum antitumor drugs. Because the determinant factors of cytotoxic activity of trans-platinum complexes do not follow the same patterns as those found for cisplatin and its analogues, the differences in cellular and biochemical pharmacology between trans-platinum antitumor complexes and cisplatin might be systematically exploited to design novel trans-platinum complexes with a clinical profile complementary to that of cisplatin and related analogues. Therefore, there may exist a novel molecular rationale for new platinum antitumor drugs development in the twenty-first century.


Multiplex array analysis of serum cytokines offers minimal predictive value for cognitive function in the subacute phase after stroke.
The effects of inflammation on post-stroke cognitive function are still unclear. This study investigated the correlation between the Th17-related cytokines in peripheral blood and post-stroke cognitive function after ischemic stroke in the subacute phase. A retrospective cohort study. Academic acute inpatient rehabilitation facility. One hundred and fourteen patients with first ischemic stroke were categorized as the poor cognitive recovery group (n = 58) or good cognitive recovery group (n = 56) based on their cognitive MRFS efficiency. All subjects received routine physical, occupational, and speech-language pathology therapy. Serum cytokines/chemokine (IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, IL-17E, IL-17F, IL-21, IL-22, IL-23, IL-27, IL-28A, IL-31, IL-33, GM-CSF, IFN-γ, MIP-3 α, TNF-α, and TNF-β) levels were measured in duplicate using Human Th17 magnetic bead panel and multiplex array analysis (Luminex-200 system). The primary functional outcome was a gain in functional independence measure (FIM) cognitive subscore at discharge. The secondary outcome measures were FIM total score at discharge, length of stay in the hospital, and discharge destination. Cognitive Montebello Rehabilitation Factor Score (MRFS) and cognitive MRFS efficiency were calculated. Demographic and clinical characteristics were obtained from the medical record. The good cognitive recovery group had an interesting trend of higher IL-13 than the poor cognitive recovery group (good cognitive recovery group 257.82 ± 268.76 vs. poor cognitive recovery group 191.67 ± 201.82, p = 0.049, unit: pg/ml). However, Pearson's correlation analysis showed no significant correlation between cytokine levels and gain of cognition, cognitive MRFS, or cognitive MRFS efficiency. Receiver operating characteristic (ROC) analysis of cytokines also suggested a low accuracy of prediction as a predictor for post-stroke cognitive recovery improvement. Our preliminary findings suggested that the level of serum cytokines had minimal predictive value for the recovery of cognitive function during the subacute inpatient rehabilitation after stroke.


Activation of the Na+-K+(NH4+)-2Cl(-)- cotransporter from rat submandibular glands in response to VIP.
A cellular suspension from rat submandibular glands was prepared with collagenase. The intracellular pH (pHi) was estimated with 2',7'-bis-(2-carboxy-ethyl)-5(6)-carboxyfluorescein (BCECF). After exposure to NH4Cl, the pHi transiently increased (diffusion of NH3) and then dropped (influx of NH4+). Isoproterenol increased 2.5-fold the rate of NH4+ influx; bumetanide, an inhibitor of the Na+-K+-2Cl(-)-cotransporter blocked the response to isoproterenol, confirming that the beta-adrenergic agonist stimulated the cotransporter. Forskolin (1 micromol/L) mimicked the response to isoproterenol. VIP (1 nmol/L(-1) micromol/L) also increased the activity of the cotransporter. Cyclic AMP rather than calcium was the mediator of this activation since 1) carbachol which increased the [Ca2+]i fivefold increased the uptake of NH4+ by only 50%; 2) only high concentrations of VIP significantly increased the [Ca2+]i; 3) incubation in the presence of EGTA had no effect on the response to VIP; 4) low concentrations (nmol/L) of the neuropeptide increased the intracellular level of cAMP; and 5) the stimulation of the cotransporter by VIP, forskolin, and isoproterenol was inhibited by H8, an inhibitor of cAMP-dependent protein kinase. It is concluded that the Na+-K+-2Cl(-)-cotransporter of rat submandibular glands is activated by isoproterenol, forskolin, and neuropeptides of the VIP family by a mechanism involving cAMP-dependent processes. The activation of the cotransporter by VIP could partly explain the potentiating effect of VIP on the response to sialagogues like substance P or muscarinic agonists.


Probabilistic risk assessment of heavy metals in urban farmland soils of a typical oasis city in northwest China.
Previous studies lacked quantitative evaluation studies of the probability of ecology and human health risks from soil heavy metals. This study assessed heavy metal risk level by collecting topsoil samples from a typical oasis city (Wuwei) in northwest China and then quantitatively evaluating the ecological risk from heavy metals by incorporating the uncertainty of health risk model parameters into the risk assessment. This study found that anthropogenic activities have influenced the accumulation of heavy metals in the study area and that the risk of contamination of soil heavy metals was characterized as light to moderate contamination and low ecological risk. On this basis, the species sensitivity distribution curves of heavy metals were constructed using species acute toxicity data, the predicted no effect concentrations of heavy metals were derived, and a probabilistic ecological risk evaluation was conducted. The results show that the current soil environmental quality standards in China are not effective in protecting species diversity. In addition, the probability of ecological risk for Cr, Ni and As in the study area was 63.3%, 23.8% and 7.1%, however, traditional pollution assessment methods underestimate the hazard of Cr. Monte Carlo simulations have shown that the probability of the carcinogenic risk of Cr (adults: 79.4%; children: 94.5%) and As (adults: 78.9%; children: 94.0%) is high, the probability of the total carcinogenic risk exceeding 1E-06 is 99.0%, the probability of the non-carcinogenic risk is low, and the slope factor and reference dose can significantly affect the evaluation of human health risks.


Simultaneous measurements of clear air turbulence at the tropopause by high-power radar and instrumented aircraft.
Large amplitude Kelvin-Helmholtz billows observed by radar at a height of almost 11 km are shown to have been associated with clear air turbulence which produced a vertical aircraft acceleration of 0.65g.


Experimental lead encephalopathy in the suckling rat: concentration of lead in cellular fractions enriched in brain capillaries.
Five-day old rats subjected to short-term (2-day) lead exposure by gastric gavage of aqueous lead acetate at the highest non-lethal dosage (1mgPb/g body weight/day) developed a hemorrhagic encephalopathy. Capillaries and microvessels isolated from brains of these rats showed abnormal morphology consisting of an increased number of irregularly dispersed endothelial nuclei and swollen, vacuolated endothelial cells. Lead was concentrated in isolated brain capillary-microvessel fractions, as demonstrated by both atomic absorption and 210Pb tracer methods. When lead exposure was continued for 20 days (at the maximal dosage regime compatible with a 60% survival rate), the rats recovered from the initial encephalopathy and capillaries and microvessels isolated from brains of these rats appeared morphologically normal. This recovery occurred despite continued high levels of lead in the blood and in the isolated capillary-microvessel fractions, suggesting that, as capillary endothelial cells mature, they are able to adapt to the presence of large amounts of lead.


Water-soluble ions in dust particles depending on meteorological conditions in urban environment.
The particle size distribution of particulate matter (PM) and concentrations of water-soluble ions were observed in airborne aerosol in the City of Ostrava (the Czech Republic, Moravian-Silesian Region) during winter 2016. The Ostrava area ranks among the most polluted areas not only within the Czech Republic but also in Europe due to the high concentration of industry, especially metallurgy, in this area. The selected water-soluble ions: were studied in different grain size classes of particulate matter separated into 7 fractions (from 0.0175 to 9.93 μm) collected by an electrical low pressure impactor ELPI+. Assessment of the influence of meteorological parameters and various sources of contamination (transportation, industry, and residential burning) in heavily environmentally-burdened urban areas was attempted. This study proved that (K)+ is related to metallurgical processes and its role as an indicator of biomass combustion is negligible. The highest concentrations of all water-soluble ions were determined in particles below 0.952 μm that is generally related to combustion processes. At increased air temperature (in the interval from 0 °C to 10 °C), concentrations of both dust particles and the sum of water-soluble ions are decreasing.


Quantification of regurgitant lesions by MRI.
We examined 46 patients with angiographically documented regurgitant lesions (26 patients with mitral regurgitation, 20 patients with aortic regurgitation) using an 0.5 Tesla magnet. In each patient a multislice-multiphase spinecho sequence in sagittal-coronal double angulated plane was performed to assess left and right ventricular volumes, ejection fraction and regurgitant fraction. Additionally a blood flow sensitive gradient echo technique was done to visualize direction and extension of the regurgitant jet. MRI data were compared with quantitative and qualitative assessment of regurgitation by angiography and echocardiography. Using the gradient echo technique MRI could demonstrate the regurgitant jet in all patients. A linear correlation for volume parameters by MRI and angio was found with best correlation for the left ventricular stroke volume (r = 0.82, p less than 0.0001). Furthermore MRI regurgitant fraction correlated with angiographically determined regurgitant fraction in patients with aortic regurgitation (r = 0.91, p less than 0.0001) and mitral regurgitation (r = 0.67, p less than 0.001), respectively. Semiquantitative assessment of regurgitation by gradient echo technique showed an agreement with angiographic grading by Sellers in 70% of mitral and 75% of aortic regurgitation, respectively. The comparison of MRI and color Doppler sonography showed only moderate correlation of r = 0.72 (p less than 0.01).


Secretory proteins from adrenal medullary cells are carboxyl-methylated in vivo and released under their methylated form by acetylcholine.
The carboxyl methylation of secretory proteins in vivo was investigated in bovine adrenal medullary cells in culture. Chromogranin A, the major intragranular secretory protein in adrenal medullary cells, and other secretory proteins were found to be carboxyl-methylated within secretory vesicles. The in vivo labeling pattern using [methyl-3H]methionine and the in vitro labeling pattern using S-adenosyl-[methyl-14C]methionine of intravesicular secretory proteins were similar. The detection of methylated chromogranin A in mature secretory vesicles required 3-6 h, a time consistent with the synthesis and storage of secretory proteins in this tissue. Carboxyl-methylated chromogranin A was secreted from medullary cells by exocytosis via activation of nicotinic cholinergic receptor and recovered still under the methylated form in the incubation medium. Since protein-carboxyl-methylase is cytosolic, these results suggest that methylation of secretory proteins is a cotranslational phenomenon.


Production and physicochemical characterization of bacterial poly gamma- (glutamic acid) to investigate its performance on enhanced oil recovery.
Bacillus licheniformis LMG 7559, which is capable of producing extracellular poly gamma- (glutamic acid) (PGA), was provided for the biopolymer synthesis. Using a modified PGA medium for PGA production, the isolated biopolymer, undergone dialysis process mainly for desalination and removal of other impurities. The bacteria produced high molecular weight biopolymers with a weight average molecular weight (M̅n) of 1.6 × 105 g/mole identified by gel permeation chromatography (GPC). Furthermore, GPC analysis was utilized to determine the poly-dispersity of PGA as well as molecular weight variation by cultivation time. The heavy weight fraction of 1.85 × 105 g/mole with poly-dispersity index of 7.42 was distinguished. For the extracted and dialyzed biopolymer, thermal properties were studied using DSC/TGA by which a mass loss of 36 percent was observed. Eventually, the biopolymer solution was injected into the oil saturated heterogeneous porous medium to evaluate the recovery factor enhancement by PGA flooding. It was found that 31.45% of oil in place was recovered by biopolymer flooding, whereas only 16.6% of oil in place was obtained by water flooding.


Snail-inspired AFG/GelMA hydrogel accelerates diabetic wound healing via inflammatory cytokines suppression and macrophage polarization.
Diabetic foot ulcers (DFUs) are a severe and rapidly growing diabetic complication, but treating DFUs remains a challenge for the existing therapies are expensive and highly non-responsive. Recently, we discovered that a natural adhesive from snail mucus can promote skin wound healing. Herein, inspired by the finding, we developed a double-network hydrogel biomaterial that composed of snail glycosaminoglycan (AFG) and methacrylated gelatin (GelMA), in which AFG is the main bioactive component of snail mucus and GelMA provides a scaffold mimicking the proteins in snail mucus. The biomimetic hydrogel exhibited strong tissue adhesion, potent anti-inflammatory activity, and excellent biocompatibility. The biodegradable AFG/GelMA hydrogel markedly promoted chronic wound healing in both STZ-induced type 1 diabetic rat and db/db mouse models after a single treatment. Further mechanistic research showed that the hydrogel significantly attenuated inflammation by sequestrating pro-inflammatory cytokines, as well as downregulated their expression by inhibiting NF-ĸB signaling pathway, and it can also promote macrophage polarization to M2 phenotype. Taken together, the bioinspired hydrogel can effectively promote the transition of chronic wounds from inflammation to proliferation stage. These data suggest that the AFG/GelMA hydrogel is a promising therapeutic biomaterial for the treatment of chronic diabetic wounds.


Antibiotic use and resistance: Information sources and application by dentists in Jordan.
The availability of evidence-based information sources for dentists is essential to influence antibiotic prescribing practices and we need to understand how dentists interact with such sources and how this influences their practice. The present study aimed to evaluate dentists' preferred sources of information and their awareness of available information and initiatives on prudent antibiotic prescribing practices in Jordan. An online cross-sectional questionnaire was administered to dentists between July to September 2021. It was an adapted version of the European Centre for Disease Prevention and Control (ECDC) survey for antibiotic use and resistance. A total of 204 dentists responded to the survey. The main sources of information regarding avoiding unnecessary antibiotic prescribing were published guidelines (35.5%), the dental professional body (20.0%), colleagues or peers (18.6%), and scientific organizations (17.2%), with the influence of these sources on changing prescribers' views being 40.7%, 9.8%, 10.3%, and 14.2%, respectively. Of the surveyed dentists, 9.3%, 33.8%, and 56.9% were aware, unaware, and unsure of the presence of national action plans on antimicrobial resistance, respectively. Dentists reported their desire to receive more information about resistance to antibiotics (57.8%), medical conditions for which antibiotics are used (52.9%), how to use antibiotics (41.2%), prescribing of antibiotics (39.7%), and links between the health of humans, animals, and the environment (26.0%). The study provided insights into the information available to and used by dentists, which can inform effective antimicrobial stewardship strategies for improving antibiotic prescribing.


Early structural changes in cartilage and bone are required for the attachment and invasion of inflamed synovial tissue during destructive inflammatory arthritis.
To elucidate the mechanisms involved in cartilage damage in an experimental model of rheumatoid arthritis (RA) by specifically addressing the time course of extracellular matrix degradation and the contribution of cell-matrix interactions for initiation and perpetuation of this process. The human tumour necrosis factor (TNF) transgenic (hTNFtg) mouse model of RA was used to analyse the time course of pannus attachment to the cartilage and cartilage destruction, respectively, and crossed hTNFtg mice with interleukin (IL)-1(-/-) animals were used to investigate the role of IL-1 on these TNF-induced mechanisms in vivo. In addition, an in vitro attachment assay using synovial fibroblasts (SFs) from hTNFtg mice and freshly isolated articular cartilage was used to determine the role of proteoglycan loss in attachment of SFs and the role of the transmembrane heparan sulfate proteoglycan syndecan-4. In vivo analyses of hTNFtg mice showed that proteoglycan loss induced by IL-1 precedes and constitutes an important prerequisite for these processes as, in hTNFtg mice, IL-1 deficiency protected from the loss of cartilage proteoglycans and almost completely prevented the attachment and subsequent invasion of inflamed synovial tissue into cartilage. In vitro studies confirmed that loss of cartilage proteoglycans is required for attachment of SFs and that syndecan-4 is prominently involved in SF attachment and activation. The results of this study suggest that the loss of cartilage proteoglycans is an early event in the course of destructive arthritis that facilitates the attachment of the inflamed synovial membrane and also initiates matrix degradation and inflammation through cell-matrix interactions.