Correlation between pouch function and sexual function in patients with IPAA.
Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the treatment of choice for ulcerative colitis refractory to medical treatment and familial adenomatous polyposis. The objective of this study was to study the impact of postoperative pouch function on sexual function. Sexual function after IPAA surgery has also been compared to sexual function in the average Norwegian population. All patients having undergone IPAA from 2000 to June 2013 were identified from the hospital medical record files and sent validated questionnaires regarding their sexual function. Pouch function was scored according to Oresland score through a phone interview. Patients operated on or before June 2012 were asked to answer the same questionnaires twice with an interval of one year to see how stable sexual function is over time. Sixty-eight out of 100 consecutive patients answered the questionnaire regarding both sexual function and pouch function (44 men, 24 women). There was no significant relationship between pouch and sexual function in men (p-value 0.158, corr. coefficient - 0.216). In women there was a significant relationship (p-value - 0.01, corr. coefficient 0.517). There was no significant shift in sexual function during the study period. We found no significant correlation between sexual function and pouch function in men. In women, we found a significant correlation between poor pouch function and impaired sexual function. As similar studies have found, sexual function remains good after IPAA surgery. This is an important information for patients and physicians, both to inform patients correctly prior to surgery, and in the postoperative follow-up.


Array-CGH fine mapping of minor and cryptic HR-CGH detected genomic imbalances in 80 out of 590 patients with abnormal development.
During a 6-year period, 590 patients suspected of having a minor or cryptic genomic imbalance as the cause of mental retardation with dysmorphic signs +/- malformations have been investigated with high-resolution comparative genomic hybridisation (HR-CGH) in our diagnostic laboratory. Thirty-six patients had a small chromosomal aberration detected by routine karyotyping, and 554 patients had a normal G-banded karyotype. In the latter group, a genomic imbalance was detected by HR-CGH in 40 patients (7.2%): 29 deletions, 3 duplications, 4 unbalanced translocations, and 4 occult trisomy mosaicisms. When microarray-based comparative genomic hybridisation (array-CGH) became available, all HR-CGH-positive samples were also investigated by 1 Mb resolution array-CGH for more precise mapping. From the 514 patients with normal HR-CGH findings, a subset of 20 patients with particularly high suspicion of having a chromosomal imbalance was selected for array-CGH. In four of them (20%), an imbalance was detected: three deletions and one duplication. Of note, 73 out of the 80 array-CGH mapped patients had a de novo chromosomal rearrangement (91%). Taken together, this work provides phenotype-genotype information on 80 patients with minor and cryptic chromosomal imbalances.


Cheating in the name of others: Offering prosocial justifications promotes unethical behavior in young children.
The current research examined whether young children engage in unethical behavior to a greater extent when they have a prosocial justification for doing so. Participants (3- and 5-year-olds, N = 240) played a guessing game in which they were tempted to cheat to win a prize after promising not to do so. In Study 1, children were randomly assigned to either an experimental prosocial condition in which they were told that the prize would be given to a child who was unable to play the game or a control condition in which they were told that they would get to keep the prize for themselves. The 5-year-olds, but not the 3-year-olds, were more likely to cheat in the prosocial condition than in the control condition. Studies 2a and 2b revealed that older children's tendency to engage in prosocial cheating was driven by their concern with signaling to others that they are prosocial. These findings suggest that the tendency to act unethically to benefit others emerges early in development and that this tendency may reflect children's interest in prosocial signaling.


Treatment with novel RSV Ig RI-002 controls viral replication and reduces pulmonary damage in immunocompromised Sigmodon hispidus.
Respiratory syncytial virus (RSV) is a significant cause of bronchiolitis and pneumonia in several high health risk populations, including infants, elderly and immunocompromised individuals. Mortality in hematopoietic stem cell transplant recipients with lower respiratory tract RSV infection can exceed 80%. It has been shown that RSV replication in immunosuppressed individuals is significantly prolonged, but the contribution of pulmonary damage, if any, to the pathogenesis of RSV disease in this susceptible population is not known. In this work, we tested RI-002, a novel standardized Ig formulation containing a high level of RSV-neutralizing Ab, for its ability to control RSV infection in immunocompromised cotton rats Sigmodon hispidus. Animals immunosuppressed by repeat cyclophosphamide injections were infected with RSV and treated with RI-002. Prolonged RSV replication, characteristic of immunosuppressed cotton rats, was inhibited by RI-002 administration. Ab treatment reduced detection of systemic dissemination of viral RNA. Importantly, pulmonary interstitial inflammation and epithelial hyperplasia that were significantly elevated in immunosuppressed animals were reduced by RI-002 administration. These results indicate the potential of RI-002 to improve outcome of RSV infection in immunocompromised subjects not only by controlling viral replication, but also by reducing damage to lung parenchyma and epithelial airway lining, but further studies are needed.


Bicontinuous microemulsions containing Melaleuca alternifolia essential oil as a therapeutic agent for cutaneous wound healing.
The Melaleuca alternifolia essential oil (MEO) has been widely used due to its healing and antimicrobial action. Its incorporation into drug delivery systems is a reality, and numerous studies have already been developed for this purpose. In this regard, the aim of this work was to develop, characterize, and evaluate the in vivo pharmacological activity of bicontinuous microemulsions (BME) containing MEO. Through diagram construction, a formulation consisting of Kolliphor® HS 15 (31.05%), Span® 80 (3.45%), isopropyl myristate (34.5%), and distilled water (31%) was selected and MEO was incorporated in the proportion of 3.45% (v/v). Morphological analysis characterization confirms that the system studied herein is a BME. The evaluated formulation showed physicochemical characteristics that allow its topical use. Rheologically, samples were characterized as pseudo-plastic non-Newtonian thixotropic fluids. The chromatographic method developed is in accordance with the current recommendations. The extraction method used assured a 100% recovery of the pharmacological marker (terpinen-4-ol). In vivo studies suggest that BME loaded with MEO may contribute to the healing process of skin wounds. In addition, it demonstrated antibacterial activity for Gram-positive and Gram-negative bacteria. Therefore, the BME system loaded with MEO is promising as a healing and antimicrobial agent for skin wounds.Graphical abstract.


Severity of narcolepsy among French of different ethnic origins (south of France and Martinique).
The aim of the study was to describe the clinical and polygraphical characteristics of narcoleptics, with and without cataplexy and to assess HLA predisposition across two different ethnic populations. Patients were 126 men and 58 women referred to the Montpellier Sleep Disorders Center (Mtp) and 12 men and 8 women referred to the Fort-de-France Sleep Disorders Center (FdF) (Martinique, a French West Indy island) with symptoms of narcolepsy. Narcoleptics were included if they had both excessive daytime sleepiness and clear-cut cataplexy (for the group with cataplexy), a mean sleep latency of less than 8 minutes and at least two sleep onset REM periods. N/A. Narcolepsy without clear-cut cataplexy was rare (12/172) in the Mtp population whereas it was as frequent as full-blown narcolepsy (10/10) in the FdF population. Comparison between narcoleptics with cataplexy from the Mtp and FdF populations revealed a younger age of onset, a trend towards more severe sleepiness and lower frequency of cataplexy in Martinicans. Comparison between narcoleptics without cataplexy from the Mtp and FdF population revealed a higher frequency of hypnagogic hallucinations and sleep paralysis and a trend towards more severe sleepiness in Martinicans. 4.2% of the Mtp and 15% of the FdF patients were negative for HLA DR2. However all of them were positive for HLA DQ1. Moreover, a tight association with HLA DRB1*1503 was observed in Martinicans in contrast with DRB1*1501 in the Mtp population. Association with HLA DQB1*0602 was observed in 99.4% of narcoleptics with cataplexy and in 89.5% of those without cataplexy. Narcolepsy is a heterogeneous clinical syndrome, the more so as ethnic origins are considered. A modulating effect of HLA and non-HLA genes on symptoms disease may explain these differences.


Effect of food intake on protein and energy metabolism in finishing beef steers.
The effects of progressive reduction in food intake from 1.6 X maintenance (1.6 M) to approximately maintenance (M') and then to zero (fasting) on energy expenditure and leucine kinetics were examined in Hereford x Friesian finishing beef steers. Estimates of whole body protein synthesis and protein oxidation were obtained from the specific radioactivity of free leucine in blood and of exhaled carbon dioxide during continuous infusions of [1-14C]leucine. Protein synthesis contributed a minimum of 0.19 to total heat production across all three intakes. The apparent efficiencies with which synthesized protein was retained were 0.28 between 1.6 M and M' and 1.04 between M' and fasting. The greater efficiency below M' reflected probable use of amino acids as energy sources during fasting, which would be spared as soon as feed was available. Nitrogen derived from protein oxidation made a minor contribution to urine N at both 1.6 M (0.45) and M' (0.36) but provided a significant proportion to the increment in urine N between intakes (0.68). Amino acid absorption, estimated indirectly as the sum of protein oxidation and protein retention, represented only 0.28 of N intake at M' and 0.38 at 1.6 M but the contribution to the increment in N intake between these two diet levels was greater (0.56). The estimated efficiency of utilization of absorbed amino acids between M' and 1.6 M was 0.45.


Descemet's stripping endothelial keratoplasty under failed penetrating keratoplasty: visual rehabilitation and graft survival rate.
To evaluate graft survival, risk factors for failure, complications, and visual rehabilitation in patients who underwent Descemet's stripping endothelial keratoplasty (DSEK) under a failed penetrating keratoplasty (PK). Retrospective interventional case series. Sixty eyes (60 patients) treated at Price Vision Group, Indianapolis, Indiana. Graft diameters ranged from 8 to 9 mm and were ∼1 mm larger than the previous PK. The Descemet's membrane was not stripped in the majority (54, 84%). The graft was inserted using forceps or a Busin funnel glide (Moria, Anthony, France). The probability of graft survival was calculated by Kaplan-Meier survival analysis. Graft survival, best-corrected visual acuity (BCVA), and complications. The mean recipient age was 68 years (range, 17-95 years). Forty eyes had 1 previous failed PK, 14 eyes had 2 previous failed PKs, and 6 eyes had 3 previous failed PKs. Thirty-one eyes (52%) had preexisting glaucoma, and 16 eyes (27%) had prior glaucoma surgery (trabeculectomy in 4, shunt procedure in 12). Fifty-five grafts were performed for visual rehabilitation, and 5 grafts were performed for pain relief. Median follow-up was 2.3 years (range, 2 months to 6 years). Median preoperative BCVA was 1.23 logarithm of the minimum angle of resolution (logMAR) (range, 0.2-3, Snellen 20/340), and median postoperative visual improvement was 0.6 logMAR (6 lines), range -0.3 to +2.7. Four eyes had graft detachment (6.6%), 7 eyes (10.5%) had endothelial rejection, and 10 eyes (16.6%) had graft failure (primary failure in 2, secondary failure in 8). The overall secondary graft survival rates were 98%, 90%, 81%, and 74% at 1, 2, 3, and 4 years, respectively. Prior glaucoma shunt was the principal risk factor for graft failure. The graft survival rates were 100%, 96%, 96%, and 96% in eyes without a prior shunt versus 93%, 74%, 44%, and 22% with a prior shunt at 1, 2, 3, and 4 years, respectively (P=0.0005; relative risk = 20). Peripheral anterior synechiae (P=0.14), neovascularization (P=0.88), endothelial rejection (P=0.59), and number of prior PKs (P=0.13) were not independent risk factors for graft failure. Endothelial keratoplasty under a previous failed PK is a useful alternative to a repeat standard PK, particularly in eyes with an acceptable topography and refractive outcome before failure. Proprietary or commercial disclosure may be found after the references.


Percutaneous pedicle screw placements: accuracy and rates of cranial facet joint violation using conventional fluoroscopy compared with intraoperative three-dimensional computed tomography computer navigation.
The goal of this study was to compare the accuracy and cranial facet joint violation rates between percutaneous pedicle screw placements using conventional fluoroscopy and intraoperative 3-D CT (O-arm) computer navigation. We reviewed 194 pedicle screw of 28 consecutive patients who underwent minimally invasive lumbar or thoracic spinal stabilization. The accuracy of screw placement was evaluated according to two criteria published by Neo et al. and Upendra et al. Facet joint violation was evaluated according to the classification described by Babu et al. Upon Neo grading, CFT group had 19.4 % (14/72) pedicle breach rate and CT-IGN group had a 5.7 % (7/122) pedicle breach rate (p < 0.005). The same sets of screws were also assessed using the outcome-based classification established by Upendra. There were no screw caused neurovascular injuries (type 3 = 0) in both groups. The results showed that 87.5 % (63/72) screws had acceptable placements (type I) and 12.5 % (9/72) had unacceptable placements (type II) in CFT group. In contrast, 94.3 % (115/122) screw had acceptable placements (type I) and only 5.7 % (7/122) had unacceptable placements (type II) in CT-IGN group. Additionally, CFT group had a significantly higher facet joint violation rate of 30.5 % (11/36) than CT-IGN group that had a 3.8 % (3/79) violation rate (p < 0.005). This study indicated the use of intraoperative CT imaging (O-arm) navigation in PPS placement have very beneficial implications for MIS.


Endogenous regeneration of damaged retinal pigment epithelium following low dose sodium iodate administration: an insight into the role of glial cells in retinal repair.
The retinal pigment epithelium (RPE) has been reported to demonstrate feasible self-regenerative potential under specific conditions. However, the precise underlying mechanisms involved in this process are still elusive. Here, we performed a sequential morphological, molecular, and functional analysis of retinal injury and subsequent tissue regeneration after intravenous administration of a low dose of sodium iodate (15 mg/kg) in mice over long-term observation, up to 3 months post-injury. To assess the kinetics of the injury/recovery process, the electroretinography (ERG) responses were correlated with ongoing alterations in retinal structure and the global gene expression profile of injured retinas using genome-wide RNA microarray technology, western blotting and immunohistochemical analyses. We observed considerable improvement in the rod cell-mediated ERG response, which was accompanied by the regeneration of RPE within the injury site by the 3rd month post-injury. Our results confirm that the repairing mechanisms within injured retinas involve a significant glial cell reaction marked by glial cell proliferation, migration from their original location toward the injury site, followed by a significant overproduction of NTs such as BDNF, GDNF and NT-3. The global gene expression analysis revealed that initially up-regulated genes associated with cell death, apoptosis, acute response to stress pathways underwent considerable down-regulation in the late post-injury period. Accordingly, the genes implicated in nervous tissue remodeling and neuron development, the regulation of synaptic transmission and the establishment of localization were substantially induced by the 3rd month. Collectively, our observations support the view that Müller glial cells might well play an active role not only in retinal cell reorganization following injury but potentially also in RPE regeneration, which appears to be the key event in retinal reparative process. Furthermore, we provided novel compelling evidence of the crucial role of neurotrophins in the pathophysiology of retinal repair and identified the signaling pathways that are activated during this process.


C-reactive protein-to-lymphocyte ratio is a reliable marker in patients with COVID-19 infection: the CLEAR COVID study.
COVID-19 infection is characterized with elevation of inflammatory markers in bloodstream. A novel inflammatory marker, C-reactive protein (CRP)-to-lymphocyte ratio (CLR), is suggested to be associated with inflammation. We aimed to compare the CLR values of the deceased COVID-19 patients to the CLR of survived subjects. The patients with COVID-19 whom presented to outpatient or inpatient clinics of AbantIzzet Baysal University Hospital were enrolled to the present retrospective study. Subjects were grouped as either deceased or survived. CLR values of the groups were compared. Study cohort was consisted of 568 subjects in deceased and 4753 patients in survived group. Median CLR of the deceased and survived groups were 90 (0.2-1679)% and 11 (0.2-1062)%, respectively (p < 0.001). The sensitivity (75%) and specificity (70%) of CLR (> 23.4% level) in detecting mortality were higher than those of CRP and ferritin (AUC 0.80, p < 0.001, 95% CI 0.78-0.82). We suggest that elevated CLR levels in COVID-19 patients on admission should alert physicians for poor outcome.


Genome instability model of metastatic neuroblastoma tumorigenesis by a dictionary learning algorithm.
Metastatic neuroblastoma (NB) occurs in pediatric patients as stage 4S or stage 4 and it is characterized by heterogeneous clinical behavior associated with diverse genotypes. Tumors of stage 4 contain several structural copy number aberrations (CNAs) rarely found in stage 4S. To date, the NB tumorigenesis is not still elucidated, although it is evident that genomic instability plays a critical role in the genesis of the tumor. Here we propose a mathematical approach to decipher genomic data and we provide a new model of NB metastatic tumorigenesis. We elucidate NB tumorigenesis using Enhanced Fused Lasso Latent Feature Model (E-FLLat) modeling the array comparative chromosome hybridization (aCGH) data of 190 metastatic NBs (63 stage 4S and 127 stage 4). This model for aCGH segmentation, based on the minimization of functional dictionary learning (DL), combines several penalties tailored to the specificities of aCGH data. In DL, the original signal is approximated by a linear weighted combination of atoms: the elements of the learned dictionary. The hierarchical structures for stage 4S shows at the first level of the oncogenetic tree several whole chromosome gains except to the unbalanced gains of 17q, 2p and 2q. Conversely, the high CNA complexity found in stage 4 tumors, requires two different trees. Both stage 4 oncogenetic trees are marked diverged, up to five sublevels and the 17q gain is the most common event at the first level (2/3 nodes). Moreover the 11q deletion, one of the major unfavorable marker of disease progression, occurs before 3p loss indicating that critical chromosome aberrations appear at early stages of tumorigenesis. Finally, we also observed a significant (p = 0.025) association between patient age and chromosome loss in stage 4 cases. These results led us to propose a genome instability progressive model in which NB cells initiate with a DNA synthesis uncoupled from cell division, that leads to stage 4S tumors, primarily characterized by numerical aberrations, or stage 4 tumors with high levels of genome instability resulting in complex chromosome rearrangements associated with high tumor aggressiveness and rapid disease progression.


A combined oral contraceptive containing 30 mcg ethinyl estradiol and 3.0 mg drospirenone does not impair endothelium-dependent vasodilation.
Ethinyl estradiol (EE) increases endothelium-dependent vasodilation in young women, but certain progestins paired with EE in combination oral contraceptive pills (OCPs) have been shown to antagonize the vasodilatory effects of EE. Therefore, the purpose of this study was to investigate how endothelial function, serum biomarkers and resting blood pressures change across an OCP cycle in women using a monophasic OCP formulation containing the progestin drospirenone. Twelve women were studied during two hormone phases of their OCP cycle: once at the end of 3 weeks of active pills (30 mcg EE and 3.0 mg drospirenone) and once at the end of a week of placebo pills (no exogenous hormones) Endothelium-dependent vasodilation was greater during the active phase compared to the placebo phase (p<.001). In contrast, there was no difference in endothelium-independent dilation between hormone phases. These data suggest that the combination of 30 mcg EE and 3.0 mg drospirenone used in the active phase of this OCP increases endothelium-dependent vasodilation compared to a placebo phase.


Melanotic neuroectodermal tumor of infancy (pigmented melanoameloblastoma).
The paper describes a large pigmented maxillary tumor in a 46-day-old infant. The histological examination showed the tumor to be a melanotic neuroectodermal tumor of infancy (MNTI). No raised urinary levels of vanilmandelic acid could be shown. The tumor was surgically removed and during a 5 1/2-year follow-up period there was no clinical evidence of recurrence. The origin, behavior and treatment of these rare tumors are discussed.


Ultrasound-guided versus 'blind' intraparotid injections of botulinum toxin-A for the treatment of sialorrhoea in patients with Parkinson's disease.
To investigate the efficacy and safety of intraparotid botulinum toxin-A (BTX-A) injections into parotid gland using ultrasound-guided versus nonguided techniques for the treatment of sialorrhoea in patients with Parkinson's disease (PD). 15 patients with PD and sialorrhoea were included and divided into two groups. Group A patients (n=8) were injected with BTX-A using ultrasound guidance. Group B patients (n=7) were injected with BTX-A without ultrasound guidance. Saliva secretion was assessed quantitatively at baseline and at weeks 1, 4, and 12. Patients and/or caregivers also assessed the saliva secretion using visual analog scale (VAS). All patients except one reported subjective improvement in sialorrhoea at the first week. Group A patients showed significantly higher rate of saliva reduction at the first week, whereas in Group B the reduction was not statistically significant from baseline at the first week (P>0.05). Comparisons of quantitative saliva assessments at each follow-up visit also showed that ultrasound-guided injections were superior to blind injections for saliva reduction. VAS scores showed an improvement in the mean rate of saliva secretion in each group at first week (P<0.05). Two patients suffered from dry mouth in mild severity lasting 1 month. Intraparotid BTX-A injections using ultrasound guidance may be an effective, easy, and safe treatment for parkinsonian sialorrhoea.


Physiological and biochemical responses of Microcystis aeruginosa to phosphine (PH3) under elevated CO2.
Phosphine (PH3) is an important factor driving the outbreak of cyanobacterial blooms that produce toxic microcystin threating human health. To clarify the physiological and biochemical responses of cyanobacteria to PH3 under elevated CO2 concentration, Microcystis aeruginosa was used in the coupling treatment of 1000 ppmv CO2 and PH3 at different concentrations respectively. The chlorophyll a (Chl-a), carotenoid, net photosynthetic rate and total protein of M. aeruginosa exhibited evidently increasing tendency under the coupling treatment of 1000 ppmv CO2 and PH3 at different concentrations (7.51 × 10-3, 2.48 × 10-2, 7.51 × 10-2 mg/L). The coupling treatments resulted in the higher concentrations of Chl-a and carotenoid of M. aeruginosa, compared to those in the control and the treatment with CO2 alone, and their enhancement increased with the increase in PH3 concentrations. The total antioxidant capacity (T-AOC) in the coupling treatment with CO2 and PH3 of 2.48 × 10-2 mg/L and 7.51 × 10-3 mg/L showed increasing tendency, compared to the treatment with PH3 alone. Additionally, the coupling treatment with 1000 ppmv CO2 and PH3 also altered the pH and DO level in the culture medium. In this regard, the coupling treatment with CO2 and PH3 at an appropriate concentration can enhance the resistance of M. aeruginosa to PH3 toxicity and is beneficial to the reproduction of M. aeruginosa, presumably resulting in potential for the outbreak of cyanobacteria bloom. Given the concern about global warming and the increase in atmospheric CO2 level, our research laid a foundation for the scientific understanding of the correlation between PH3 and cyanobacteria blooms.


Case series of congenital heterotopic neuroglial tissue in the parapharyngeal space.
Cases of congenital heterotopic tissue presenting in the head and neck are frequent in the pediatric otolaryngology literature. Heterotopic glioneuronal tissue is rare and fewer than 20 cases of heterotopic glioneuronal tissue in the parapharyngeal space have been reported. We present two cases of infant children who were seen at the Children's Hospital of Pittsburgh in 2013 with glioneuronal heterotopic masses in the parapharyngeal space.


[Annular detachment of the chorioretina of vascular origin (author's transl)].
This paper relates the case of a 54-year-old woman with spontaneous annular detachment of the chorioretina in the right eye. Through examination and evolution confirm that it is an "uveal effusion", most probably in relation with choroïdal circulatory troubles and an affection of the pigment epithelium.


Effect of sacubitril/valsartan on investigator-reported ventricular arrhythmias in PARADIGM-HF.
Sudden death is a leading cause of mortality in heart failure with reduced ejection fraction (HFrEF). In PARADIGM-HF, sacubitril/valsartan reduced the incidence of sudden death. The purpose of this post hoc study was to analyse the effect of sacubitril/valsartan, compared to enalapril, on the incidence of ventricular arrhythmias. Adverse event reports related to ventricular arrhythmias were examined in PARADIGM-HF. The effect of randomized treatment on two arrhythmia outcomes was analysed: ventricular arrhythmias and the composite of a ventricular arrhythmia, implantable cardioverter defibrillator (ICD) shock or resuscitated cardiac arrest. The risk of death related to a ventricular arrhythmia was examined in time-updated models. The interaction between heart failure aetiology, or baseline ICD/cardiac resynchronization therapy-defibrillator (CRT-D) use, and the effect of sacubitril/valsartan was analysed. Of the 8399 participants, 333 (4.0%) reported a ventricular arrhythmia and 372 (4.4%) the composite arrhythmia outcome. Ventricular arrhythmias were associated with higher mortality. Compared with enalapril, sacubitril/valsartan reduced the risk of a ventricular arrhythmia (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.62-0.95; p = 0.015) and the composite arrhythmia outcome (HR 0.79, 95% CI 0.65-0.97; p = 0.025). The treatment effect was maintained after adjustment and accounting for the competing risk of death. Baseline ICD/CRT-D use did not modify the effect of sacubitril/valsartan, but aetiology did: HR in patients with an ischaemic aetiology 0.93 (95% CI 0.71-1.21) versus 0.53 (95% CI 0.37-0.78) in those without an ischaemic aetiology (p for interaction = 0.020). Sacubitril/valsartan reduced the incidence of investigator-reported ventricular arrhythmias in patients with HFrEF. This effect may have been greater in patients with a non-ischaemic aetiology.


Lizard herbivory in a sand dune environment: the diet of Angolosaurus skoogi.
Early observations of the feeding habits of Angolosaurus skoogi (Andersson), a 50-120 g lizard inhabiting the almost vegetationless dunes of the northern Namib Desert, indicated that this species was herbivorous. Less than two percent of living lizard species are predominantly herbivorous and these species tend to have a high body mass (>100 g). We therefore analysed fecal pellets of A. skoogi to obtain dietary details of this relatively rare lizard. Eighteen food taxa were identified: 81 percent by mass was composed of vegetable matter, of which 56 percent was an endemic, perennial cucurbit Acanthosicyos horrida. Both spatial and temporal variation in dietary composition were apparent. Ready access to water in the form of A. horrida is postulated to have allowed Angolosaurus to occupy this extreme habitat and to forage on components of the windblown detritus, a food source that would probably not be usable in other circumstances.


Genome-wide survey of putative serine/threonine protein kinases in cyanobacteria.
Serine/threonine kinases (STKs) have been found in an increasing number of prokaryotes, showing important roles in signal transduction that supplement the well known role of two-component system. Cyanobacteria are photoautotrophic prokaryotes able to grow in a wide range of ecological environments, and their signal transduction systems are important in adaptation to the environment. Sequence information from several cyanobacterial genomes offers a unique opportunity to conduct a comprehensive comparative analysis of this kinase family. In this study, we extracted information regarding Ser/Thr kinases from 21 species of sequenced cyanobacteria and investigated their diversity, conservation, domain structure, and evolution. 286 putative STK homologues were identified. STKs are absent in four Prochlorococcus strains and one marine Synechococcus strain and abundant in filamentous nitrogen-fixing cyanobacteria. Motifs and invariant amino acids typical in eukaryotic STKs were conserved well in these proteins, and six more cyanobacteria- or bacteria-specific conserved residues were found. These STK proteins were classified into three major families according to their domain structures. Fourteen types and a total of 131 additional domains were identified, some of which are reported to participate in the recognition of signals or substrates. Cyanobacterial STKs show rather complicated phylogenetic relationships that correspond poorly with phylogenies based on 16S rRNA and those based on additional domains. The number of STK genes in different cyanobacteria is the result of the genome size, ecophysiology, and physiological properties of the organism. Similar conserved motifs and amino acids indicate that cyanobacterial STKs make use of a similar catalytic mechanism as eukaryotic STKs. Gene gain-and-loss is significant during STK evolution, along with domain shuffling and insertion. This study has established an overall framework of sequence-structure-function interactions for the STK gene family, which may facilitate further studies of the role of STKs in various organisms.


[First-line treatment for non-neurogenic overactive bladder].
The aim was to synthesize current knowledge on overactive bladder (OAB) first-line treatments. A systematic literature review based on PubMed, Embase and Google Scholar was conducted in June 2020. Behavioral treatments are based on bladder training and timed voiding using a bladder diary. Lifestyle modifications should be suggested. They include reduction of fluid intake, consumption of caffeine, sodas, weight loss, avoidance of acidic fruit juices and of spicy and acidic salty diet, alkalization of urine by diet and possibly, vitamin D supplementation. Pelvic floor muscle training is mainly based on manual techniques, electrostimulation and/or biofeedback. It has been shown to be effective in treating OAB. In menopausal women, local hormone therapy improves all OAB symptoms. Oral drugs include anticholinergics and beta-3-agonists. Their efficacy is quite similar and superior to placebo. In case of failure of monotherapy, they may be combined. Apart from some lifestyle modifications, the efficacy of first-line treatments for OAB has been demonstrated by prospective controlled studies. They may be prescribed individually or in combination.


Heterogeneous Cu9S5/C nanocomposite fibers with adjustable electromagnetic parameters for efficient electromagnetic absorption.
One-dimensional carbon-based materials have emerged as promising electromagnetic wave absorption agents due to their outstanding conductivity, high stability, low weight, and easy availability. Properly optimizing their electromagnetic parameters is expected to further enhance the electromagnetic wave attenuation capacity. In this work, efficient Cu9S5/C nanocomposite fibers are prepared by a combined approach of electrospinning and subsequent carbonization-sulfurization processes. The Cu9S5 nanoparticles with size of ca. 100-200 nm were homogeneously embedded in fibrous carbon matrix with diameter of 300 nm. For electromagnetic wave absorption, the optimized composited nanofibers (Cu9S5/C-3) exhibited an extremely superb reflection loss of -65.4 dB (9.5 GHz, 2.7 mm) at a lower mass fraction (20 wt%). And the effective absorption bandwidth could be up to 4.1 GHz (8.0-12.1 GHz) with a matching thickness of 2.9 mm, covering the whole X-band. Electromagnetic wave attenuation mechanism investigation revealed that the performance enhancement originated from the synergy of various loss pathways, including interfacial polarization, dipole polarization, and conductive loss. The unique hierarchical structure from particle embedding, one-dimensional fiber, to three-dimensional network further amplified the performance advantages of each component. This work is anticipated to provide a feasible strategy to synthesize sulfide/carbon binary composite fibers for efficient electromagnetic wave absorption.


Manipulating the proximal triad His-Asn-Arg in human myeloperoxidase.
In mammalian peroxidases the proximal histidine is in close interaction with a fully conserved asparagine which in turn is hydrogen bonded with an arginine that stabilizes the propionate substituent of pyrrol ring D in bent conformation. In order to probe the role of this rigid proximal architecture for structural integrity and catalysis of human myeloperoxidase (MPO), the variants Asn421Asp, Arg333Ala and Arg333Lys have been recombinantly expressed in HEK cell lines. The standard reduction potential of the Fe(III)/Fe(II) couple of Asn421Asp was still wild-type-like (-50mV at pH 7.0) but the spectral properties of the ferric and ferrous forms as well as of higher oxidation states showed significant differences. Additionally, rates of ligand binding and oxidation of both one- and two-electron donors were diminished. The effect of exchange of Arg333 was even more dramatic. We did not succeed in production of mutant proteins that could bind heme at the active site. The importance of this His-Asn-Arg triad in linking the heme iron with the propionate at pyrrol ring D for heme insertion and binding as well as in maintenance of the architecture of the substrate binding site(s) at the entrance to the heme cavity is discussed.


Glycosylation-directed quality control of protein folding.
Membrane-bound and soluble proteins of the secretory pathway are commonly glycosylated in the endoplasmic reticulum. These adducts have many biological functions, including, notably, their contribution to the maturation of glycoproteins. N-linked glycans are of oligomeric structure, forming configurations that provide blueprints to precisely instruct the folding of protein substrates and the quality control systems that scrutinize it. O-linked mannoses are simpler in structure and were recently found to have distinct functions in protein quality control that do not require the complex structure of N-linked glycans. Together, recent studies reveal the breadth and sophistication of the roles of these glycan-directed modifications in protein biogenesis.


Pulling versus guiding: a modification of retrograde guided intubation.
We describe a modification of retrograde guided intubation. With the help of a gliding knot fixed around the side hole of the tracheal tube, we use the catheter to pull and guide the tracheal tube down the larynx and trachea. The technique offers several advantages: it is surprisingly fast, relatively atraumatic, easy to perform, and eliminates most causes of failure.


Normal ventilation/perfusion lung scan in patients with extensive chronic thromboembolism pulmonary hypertension: A case report.
Chronic thromboembolism pulmonary hypertension (CTEPH) is a common cause of severe pulmonary hypertension, resulting in significant morbidity and mortality. In patients with unexplained pulmonary hypertension, a ventilation-perfusion (VQ) scan should be considered the initial diagnostic test of choice. VQ scans are widely available with excellent sensitivity, specificity, and diagnostic accuracy. However, the occurrence of a normal VQ scan in the presence of CTEPH is believed to be rare. In fact, the rate of actual false negatives in VQ scans is unknown because pulmonary digital subtraction angiography and computed tomography pulmonary angiography are rarely performed in patients with a normal VQ scan. This study reports a patient with a high clinical likelihood of CTEPH due to a hypercoagulable state, recurrent deep vein thrombosis, and prior history of acute pulmonary embolism with negative VQ scans. He subsequently underwent pulmonary digital subtraction angiography, which revealed bilateral extensive emboli with partial recanalization of the organized thrombus. The patient underwent successful pulmonary endarterectomy, with marked improvement of his symptoms postoperatively.


An easy-to-use CRISPRi plasmid tool for inducible knockdown in E. coli.
CRISPR-interference (CRISPRi) is a powerful genetic tool with wide application in bacteria. In this work a single plasmid system is presented which expresses deactivated Cas9 and a short guide RNA sequence from separate inducible promoters, enabling up to 40-fold repression of target genes with minimal leaky repression in the uninduced state. The plasmid is designed for rapid spacer insertion with easy screening for correct clones, and a simple one-day protocol with >99.9% assembly efficiency is described. This plasmid is made available to the research community with a view to facilitating wider use of CRISPRi in bacterial systems.


Determination of Micro-Quantities of DNA Using DNAse and Fluorescence of Hoechst 33258 and Light-Scattering.
The DNA hydrolysis by deoxyribonuclease (DNAse I) in aqueous solution was studied, using fluorescence spectroscopy and high-sensitive light-scattering detection. Specific hydrolysis of high-polymer DNA or fragmented DNA by the enzyme led to a strong decrease in the fluorescence of the Hoechst dye. The hydrolysis of mitochondrial DNA was accompanied by a decrease in the fluorescence of the dye only in 1.6 times. Hydrolysis within minutes and even hours led to appearance of large polynucleotide fragments, but not to short oligonucleotides, that was confirmed using polarized fluorescence and highly sensitive measurement of light-scattering. At the moment of the time of formation of a complex between DNA and DNAse I, a strong light-scattering occurred, which then dropped sharply during hydrolysis of high-molecular DNA, and slowly decreased during hydrolysis of fragmented DNA. The proposed methods can be applied for selective detection of trace amounts of various types of DNA, as well as for studying their physic-chemical properties.


Effect of smoke generation sources and smoke curing duration on the levels of polycyclic aromatic hydrocarbon (PAH) in different suites of fish.
The research studied the impact of smoke generation sources on PAH contamination in four different smoke-cured fish (mackerel, sardine, tuna and Cigar minnows). The smoke sources used included acacia, sugarcane bagasse and mangrove. PAHs in the smoke-cured fish were analysed using Varian GC/MS (3800-GC) system. The mean total PAH concentrations in the smoked fish (n=108) ranged from 250.59-1376.09 μg/kg in tuna, cigar minnows, sardine and mackerel smoke-cured with sugarcane bagasse, mangrove and acacia for between 2 and 8h. The mean BaP levels for most fish cured with smoke from acacia and mangrove for between 2 and 8h were all above the European Commission set limit of 5.0 μg/kg. Positive correlations (at P=0.01, 2-tailed) were observed between PAH levels in smoked fish and lignin contents of wood type used for the smoke generation, the fat content and the smoke-curing duration. Risk assessment conducted using benzo[a]pyrene carcinogenic and mutagenic toxicity equivalency factors (TEF and MEF respectively) showed high risk associated with consuming fish smoke-cured with hard woods (acacia and mangroves). Sugarcane bagasse was found to be relatively the best and safest smoke-generating source for smoke-curing of fish among the three wood types when using the traditional kiln.


Medical management of benign prostatic hyperplasia: a canine model comparing the in vivo efficacy of alpha-1 adrenergic antagonists in the prostate.
Medical management of benign prostatic hyperplasia (BPH) is an alternative to surgical treatment of this disease. A major target for pharmacologic therapy is the alpha-1 adrenergic receptor, since activation of this receptor by endogenous catecholamines is thought to contribute to outlet obstruction. In the present study, we compared the potency of various alpha-1 adrenergic antagonists against epinephrine-induced contraction of the canine prostate. The drugs tested were dibenzyline, prazosin, terazosin and YM617. The rank order of potency, comparing inhibitory constants (Ki's), was found to be YM617 >> prazosin > terazosin > dibenzyline. This study is the first to compare all of these drugs directly in the prostate in vivo. The rank order of potency of the drugs is similar to the rank order of potency at other alpha-1 receptors. These results demonstrate that 1) our model is useful in confirming activity of drugs at the alpha-1 receptor and 2) the prostate alpha-1 receptor is similar to other alpha-1 receptors. Whether activity at the alpha-1 adrenergic receptor is a sufficient determinant of clinical efficacy of these drugs remains to be determined.


Effectiveness of the WHO-Authorized COVID-19 Vaccines: A Rapid Review of Global Reports till 30 June 2021.
Large clinical trials have proven the efficacy of the COVID-19 vaccine, and the number of studies about the effectiveness rapidly grew in the first half of the year after mass vaccination was administrated globally. This rapid review aims to provide evidence syntheses as a means to complement the current evidence on the vaccine effectiveness (VE) against various outcomes in real-world settings. Databases (PubMed, EMBASE, and MedRxiv) were searched up to 30 June 2021, (PROSPERO ID: 266866). A total of 39 studies were included, covering over 15 million participants from 11 nations. Among the general population being fully vaccinated, the VE against symptomatic SARS-CoV-2 infection was estimated at 89-97%, 92% (95% CI, 78-97%), and 94% (95% CI, 86-97%) for BNT162b2, ChAdOx1, and mRNA-1273, respectively. As for the protective effects against B.1.617.2-related symptomatic infection, the VE was 88% (95% CI, 85.3-90.1%) by BNT162b2 and 67.0% (95% CI, 61.3-71.8%) by ChAdOx1 after full vaccination. This review revealed a consistently high effectiveness of certain vaccines among the general population in real-world settings. However, scarce data on the major variants of SARS-CoV-2 and the shortness of the study time may limit the conclusions to the mRNA vaccines and ChAdOx1.


Inhibitory effect of osthole on alcohol-induced fatty liver in mice.
Alcohol is a major cause of fatty liver, the disease is a spectrum that is initiated with steatosis, and without therapy it is apt to develop inflammation, necrosis, fibrosis and finally cirrhosis. There are currently no ideal pharmacological reagents that can prevent or reverse this disease. Osthole is an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, a Chinese herbal medicine, which has been used in clinics for many years. It has many functions such as anti-inflammation, anti-osteoporosis and anti-tumor and so on, but there is no report about treatment of alcoholic fatty liver in mice. To examine the inhibitory effect of osthole on alcohol-induced fatty liver in mice and to investigate the potential mechanisms. A mouse model with alcoholic fatty liver was induced by orally feeding 52% erguotou wine by gavage when they were simultaneously treated with osthole 10, 20, 40 mg/kg for 4 weeks. Whereafter, the lipids in serum and hepatic tissue, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione hormone (GSH), tumor necrosis factor-alpha (TNF-alpha) in hepatic tissue, hepatic weight coefficient and its histological evaluation were measured. After treatment with osthole, the levels of serum total cholesterol (TC), triglyceride (TG), coefficient of hepatic weight, and the hepatic tissue contents of TC and TG were significantly decreased, the levels of MDA and TNF-alpha in liver were also decreased, while the GSH in liver was increased. Importantly, the histological evaluation of liver specimens demonstrated that osthole dramatically decreased lipid accumulation. Osthole could inhibit alcohol-induced fatty liver in mice, and the mechanism might be associated with its anti-oxidation and suppression of TNF-alpha production.


Morphometric immunohistochemical examination of the inflammatory tissue reaction after implantation of calcium phosphate-coated titanium plates in rats.
Calcium phosphate (CaP) preparations are established coatings for titanium-based medical implants used for bone reconstruction. However, biodegradation of the coating can result in microparticles that subsequently cause inflammatory reactions. The present study was therefore aimed at investigating the inflammatory response to two series of CaP-coated titanium plates: Ti-brushite (Ti-B) and Ti-hydroxyapatite (Ti-H) implants. Fifteen male LEW.1A rats received one plate of each series and a pellet (5 x 2 mm) of sol-gel derived silica/CaP (SCP implants) implanted into the back musculature. After 7, 14 and 28 days, five rats were killed and the implants were removed with the surrounding tissue. Quantitative immunohistochemistry was performed on frozen sections. Total monocytes/macrophages, tissue macrophages, T-cells, MHC-class-II-positive cells and proliferating cells were counted. For the Ti-B implants, the number of monocytes/macrophages remained constant while the other cell populations increased. In contrast, for the Ti-H implants the number of monocytes/macrophages decreased while the other cell populations remained constant. The SCP implants demonstrated degradation and scattering into smaller particles with an increase for all cell populations except the proliferating cells. Human mesenchymal stem cells demonstrated adherence and a flat morphology on Ti-B and Ti-H implants and no remarkable difference between both implants. Taken together, the in vivo data demonstrate that the short-term inflammatory response against a hydroxyapatite coating is lower in comparison to a brushite coating, and that the morphology of cells growing in vitro is similar on both layers.


Detection of tick-borne encephalitis virus RNA in ticks (Ixodes ricinus) by the polymerase chain reaction.
A polymerase chain reaction for the detection of tick-borne encephalitis virus (TBEV) RNA in ticks was developed. Two pairs of primers for nested PCR were selected from the 5'-NCR and the 5'-terminus of the C protein coding region, which are highly conserved among the TBEV isolates sequenced so far. The sensitivity of the nested PCR was tested by dilution experiments of a TBEV positive brain suspension. The specificity of the PCR products was confirmed by Southern blotting. In a pilot study, 60 homogenates of 7200 ticks (I. ricinus) were examined by PCR. Two homogenates were found positive. The PCR for TBEV RNA appears to be a valuable method to define endemic areas of TBE.


Trigemino-autonomic connections in the muskrat: the neural substrate for the diving response.
Stimulation of the anterior ethmoidal nerve of the muskrat produces a cardiorespiratory depression similar to the diving response. This includes an apnea, a parasympathetic bradycardia, and a selective increase in sympathetic vascular tone. However, the brainstem circuitry that links the afferent stimulus to the efferent autonomic responses is unknown. We used the anterograde transneuronal transport of the herpes simplex virus (HSV-1), strain 129, after its injection into the anterior ethmoidal nerve to determine the primary, secondary, and tertiary brainstem relays responsible for this cardiorespiratory response. In an effort to check the validity of this relatively untested tracer, we also injected the medullary dorsal horn with biotinylated dextran amine to determine the secondary trigemino-autonomic projections. Approximately 1 microl (6x10(6) PFU) of the HSV-1 virus was injected directly into the anterior ethmoidal nerve of muskrats. After 2-6 days, their trigeminal ganglions, spinal cords and brainstems were cut and immunohistologically processed for HSV-1. Initially (2 days), HSV-1 was observed only in the trigeminal ganglion. After approximately 3 days, HSV-1 was observed first in many brainstem areas optimally labeled between 4 and 4.5 days. In these cases, the ventrolateral superficial medullary dorsal horn, the ventral paratrigeminal nucleus and the interface between the interpolar and caudal subnuclei were labeled ipsilaterally. The nucleus tractus solitarius (NTS), especially its ventrolateral, dorsolateral, and commissural subnuclei were labeled as well as the caudal, intermediate and rostral ventrolateral medulla. Within the pons, the superior salivatory nucleus, the A5 area, the ventrolateral part of the parabrachial nucleus and the Kölliker-Fuse nucleus were labeled. Only after a survival of 4 days or more, the locus coeruleus, the nucleus raphe magnus, the nucleus paragigantocellularis, pars alpha, and the pontine raphe nucleus were labeled. Injections of biotinylated dextran amine were made into the medullary dorsal horn (MDH) in a location similar to that labeled after the viral injections. Fine fibers and terminals were labeled in the same brainstem areas labeled after injections of HSV-1 into the anterior ethmoidal nerve. This study outlines the potential brainstem circuit for the diving response, the most powerful autonomic reflex known. It also confirms the efficacy for using HSV-1, strain 129, as an anterograde transneuronal transport method.


In vitro mutagenesis of Xanthomonas campestris alpha-amylase gene by partially replacing deoxythymidine triphosphate with 5-bromo-2'-deoxyuridine-5'-triphosphate using a PCR technique.
Three mutants of the wild type alpha-amylase gene from Xanthomonas campestris pv. campestris 8004 were obtained using a PCR technique in which deoxythymidine triphosphate (dTTP) was partially replaced by 5-bromo-2'-deoxyuridine-5'-triphosphate (BrdUTP), at an optimal dTTP:BrdUTP ratio of 1000:1. Of thre three mutants that were obtained and which were sequenced, one mutant with 40 times higher activity than the wild type alpha-amylase gene product was obtained by using primary PCR products as a template for a second PCR reaction.


Specific antibodies contribute to the host protection against strains of Francisella tularensis subspecies holarctica.
T cells are crucial to the control and eradication of the facultative intracellular bacterium Francisella tularensis. A contributory role of humoral antibodies in the host defence remains to be assessed. We used B-cell-deficient mice to study the possible contribution of antibodies to the defence against the live vaccine strain (LVS) or a clinical isolate of F. tularensis, both belonging to the subspecies holarctica (type B). When B-cell-deficient (Igmu(-/-)) mice of the C57BL/10 background were administered immune serum one day before intradermal injection of LVS, they developed lower bacterial numbers in skin, liver, and spleen than did mice receiving normal serum, and survived a challenge inoculum that was lethal for mice given normal serum. Administration of immune serum to C57BL/10 mice afforded protection also against infection with the clinical isolate of F. tularensis subsp. holarctica. Five days after intradermal inoculation of bacteria of the isolate, animals receiving immune serum showed 4log10 lower bacterial counts in liver and spleen than mice administered normal serum. In mice primed by LVS infection, T-cell immunity and host protection were strong and only a marginal contribution of immune serum against a secondary intradermal infection was demonstrated. Together, these findings show that specific antibodies contribute to the host defence of mice against F. tularensis subsp. holarctica.


Effective connectivity modulations related to win and loss outcomes.
Previous studies have characterized the brain regions involved in encoding monetary reward and punishment outcomes. The question of how this information is integrated across brain regions has received less attention. Here, we investigated changes in effective connectivity related to the processing of positive and negative monetary outcomes using functional magnetic resonance imaging data from the Human Connectome Project. Specifically, subjects engaged in a card guessing game which could yield win, loss, or neutral outcomes. A general linear model was used to define a network of regions involved in win and loss outcome processing, including anterior insula, anterior cingulate cortex, and ventral striatum. Dynamic causal modelling (DCM) was implemented to study between-region couplings and outcome-related modulations thereof within this network. In addition, we explored the relation between effective connectivity patterns and choice behavior in the gambling task. Parametric empirical Bayesian modelling was conducted for group-level inferences of both DCM and the choice behavior. Behaviorally, both win and loss outcomes increased the probability of choice switches in subsequent gambles. In terms of connectivity, win outcomes were associated with increased extrinsic connectivity across the network, while loss outcomes featured a balance between increased and decreased extrinsic connectivity. Moreover, self-inhibitory connections tended to decrease for both win and loss outcomes. Interestingly, a substantial discrepancy was observed for occipital cortex connectivity, which was characterized by intrinsic disinhibition in loss but not in win trials. The observed differences in effective connectivity during the processing of positive and negative outcomes, despite similarities in average regional activity and choice behavior, highlight the value of exploring network dynamics in the context of incentive manipulations.


Port Placement Strategies for Robotic Pulmonary Lobectomy: A Narrative Review.
Despite the use of robotics becoming increasingly popular among thoracic surgeons worldwide, there remains debate over the best robotic approach for lung resections. In this paper, we delineated the main port placement strategies and discussed their advantages and disadvantages. A PubMed literature review was performed using key phrases such as "robotic lobectomy technique", "RATS lobectomy", and "port placement robotic lobectomy". After the final review, 22 articles were included as references, of which 10 described common robotic port mapping techniques. Several port strategies for robot-assisted pulmonary lobectomies have been proposed and described in the literature, each showing its own limitations and advantages. New robotic surgeons may choose their port strategy according to personal preference and previous surgical experience, especially regarding open or VATS resections. Robust data comparing different port placements in robotic surgery are lacking. Further research should be directed toward comparisons of clinical outcomes with different robotic approaches.


Functional beta1-integrins release the suppression of fibronectin matrix assembly by vitronectin.
beta1-null GD25 fibroblasts adherent to vitronectin fail to bind the N-terminal 70-kDa matrix assembly domain of fibronectin or to assemble fibronectin (Sakai, T., Zhang, Q., Fässler, R., and Mosher, D. F. (1998) J. Cell Biol. 141, 527-538). We have made four observations that extend this finding. First, the presence of vitronectin on a substrate that otherwise can support fibronectin assembly has a dominant-negative effect on assembly. Second, the dominant-negative effect is lost when active beta1A is expressed. Third, beta1A containing the extracellular D130A inactivating mutation has a dominant-negative effect on fibronectin assembly. Fourth, beta1-null cells adherent to vitronectin are flat and lack filopodia, whereas beta1-null cells adherent to fibronectin or beta1A-expressing cells adherent to either vitronectin or fibronectin are contracted and exhibit numerous filopodia. These results reveal, therefore, that GD25 cells adherent to vitronectin can only assume a shape suitable for assembly of fibronectin when there is a countervailing signal from functional beta1-integrins.


Prenatal Genetic Testing Options.
All patients should be offered prenatal screening and diagnosis. Testing options depend on many factors, including patient age, family history, and patient preference. Options are rapidly changing with emerging technology. Aneuploidy screening options include ultrasound, maternal analytes, and cell-free DNA. Prenatal chromosomal microarray is the recommended diagnostic test for patients with anomalies visualized on prenatal ultrasound. Prenatal whole exome sequencing is clinically available but is limited by challenges with counseling, interpretation, and turn-around time. Future technologies are emerging and may soon allow for translation of prenatal diagnosis to in utero therapy.


Surgical Excision with Rotational Flap Reconstruction for Basosquamous Cell Carcinoma in Xeroderma Pigmentosa: A Case Report.
Xeroderma pigmentosa (XP) is a rare autosomal recessive disorder which is characterized by a defect in nucleotide excision repair of DNA following exposure to UV radiation. This leads to hypersensitivity to sunlight causing pigmented skin lesions, photophobia and a 1000-fold increase in risk of developing cutaneous malignancies like basal cell carcinomas, squamous cell carcinomas and melanomas of head and neck. We present an interesting case of a 28 year old man with basosquamous cell carcinoma secondary to XP treated successfully with surgical excision and reconstruction with rotational flap technique.


Sonographic findings of pure ductal carcinoma in situ.
To investigate the characteristic sonographic (US) findings of pure ductal carcinoma in situ (DCIS) in a large series. We retrospectively reviewed the US findings of 126 cases of pure DCIS in 123 consecutive patients who underwent surgery for breast cancer in our hospital. We analyzed the US findings of the lesions according to mass or nonmass abnormality, shape, margin, orientation, echogenicity, echotexture, boundary echo, posterior acoustic features, presence of associated ductal dilatation, presence of intralesional cystic focus, and presence of microcalcifications on US. We compared the US characteristics of pure DCIS with and without mammographic microcalcifications. Seventy-eight cases of pure DCIS had microcalcifications and 48 had no microcalcifications on mammography (MG). Overall, 109 cases (86.5%) of pure DCIS were demonstrated on US. DCIS with microcalcifications on MG showed positive US findings in 79.5% of cases. The most common US finding was heterogeneous hyper- or isoechoic parenchyma with intralesional microcalcifications and without posterior acoustic features. DCIS without microcalcifications on MG showed positive US findings in 97.9% of cases. The most common US findings were masses with round or oval shape, microlobulated margin, parallel orientation, heterogeneous mild hypoechogenicity, and without boundary echo or posterior acoustic features. Ductal dilatations and intralesional cystic foci were present in 17.5% (22/126) and 23.8% (30/126) of pure DCIS, respectively. Overall, US could demonstrate 85.7% of pure DCIS cases, including 16 (12.7%) cases of clinically and mammographically occult pure DCIS. DCIS with and without microcalcifications on MG showed different US characteristics.


1-Butyl-3-methyl-imidazolium tri-bromido-(tri-phenyl-phosphane-κP)nickelate(II) butan-1-ol hemisolvate.
The solvated title salt, (C8H15N2)[NiBr3(P(C6H5)3)]·0.5C4H10O, was obtained in the form of single crystals directly from the reaction mixture. The mol-ecular structure consists of separated 1-butyl-3-methyl-imidazolium cations, tri-bromido-(tri-phenyl-phosphane)nickelate(II) anions and half a solvent mol-ecule of 1-butanol, all connected via multiple hydrogen contacts to form a three-dimensional network. The co-crystallized 1-butanol mol-ecule is disordered and adopts two orientations. The central C-C bonds of both orientations are located on an inversion centre (Wyckoff site 2b of space group P21/n). Thereby, each orientation has again two orientations with the OH group being located either on one or the other side of the C4 alkyl chain. The dried solvent-free compound exhibits a relatively low melting point (m.p. = 412 K).


PCaP2 regulates nuclear positioning in growing Arabidopsis thaliana root hairs by modulating filamentous actin organization.
PCaP2 plays a key role in maintaining the nucleus at a relatively fixed distance from the apex during root hair growth by modulating actin filaments. During root hair growth, the nucleus localizes at a relatively fixed distance from the apex. In Arabidopsis thaliana, the position of the nucleus is mainly dependent on the configuration of microfilaments (filamentous actin). However, the mechanisms underlying the regulation of actin dynamics and organization for nuclear positioning are largely unknown. In the present study, we demonstrated that plasma membrane-associated Ca(2+) binding protein 2 (PCaP2) influences the position of the nucleus during root hair growth. Abnormal expression of PCaP2 in pcap2 and PCaP2 over-expression plants led to the disorganization of actin filaments, rather than microtubules, in the apex and sub-apical regions of root hairs, which resulted in aberrant root hair growth patterns and misplaced nuclei. Analyses using a PCaP2 mutant protein revealed that actin-severing activity is essential for the function of PCaP2 in root hairs. We demonstrated that PCaP2 plays a key role in maintaining nuclear position in growing root hairs by modulating actin filaments.


Anomalous electronic structure and magnetoresistance in TaAs2.
The change in resistance of a material in a magnetic field reflects its electronic state. In metals with weakly- or non-interacting electrons, the resistance typically increases upon the application of a magnetic field. In contrast, negative magnetoresistance may appear under some circumstances, e.g., in metals with anisotropic Fermi surfaces or with spin-disorder scattering and semimetals with Dirac or Weyl electronic structures. Here we show that the non-magnetic semimetal TaAs2 possesses a very large negative magnetoresistance, with an unknown scattering mechanism. Density functional calculations find that TaAs2 is a new topological semimetal [ℤ2 invariant (0;111)] without Dirac dispersion, demonstrating that a negative magnetoresistance in non-magnetic semimetals cannot be attributed uniquely to the Adler-Bell-Jackiw chiral anomaly of bulk Dirac/Weyl fermions.


Mitochondrial membrane potential in living cells: evidence from studies with rhodamine 6 G as fluorescent probe.
Rhodamine 6 G as a cationic permeant fluorophore is demonstrated to be selectively accumulated by mitochondria of living pancreatic acinar cells from guinea pigs. The accumulation of the fluorescent dye was studied by means of the application of electron transport inhibitors in the respiratory chain, ionophores and some hydrogen donors. Besides, some unspecific staining processes were excluded. Using this technique, it becomes possible to estimate the energy state of living cells under various conditions of energy supply and demand.


Small molecule microarray: functional-group specific immobilization of small molecules.
Proteomic screening with small molecule microarrays can be a powerful tool in conjunction with various forward chemical genetics screening and high-throughput phenotype assays. Small molecule microarray screening can provide high quality information from the direct binding interaction between proteins of interest and a collection of small molecules in a high-throughput fashion. To realize this potential of small molecule microarray in the postgenomic era, the immobilization of small molecules on the surface of microscope glass slides has been a critical step, to apply small molecule library in protein screening assays and dissecting the protein network. In this chapter, we would like to focus on the protocol for the systematic immobilization of synthetic drug-like small molecules containing either specific functional handles or common functional groups.


Freeze-thaw assisted maleic acid pretreatment of eucalyptus to prepare cellulose nanocrystals and degraded lignin.
A green and effective method is proposed for the pretreatment of eucalyptus by freeze-thaw assisted maleic acid tactic, wherein the effects of freeze-thaw, maleic acid concentration, reaction time, and temperature on the fractionation were examined. Results showed that under optimal conditions (60% maleic acid, 120 °C, and 2 h), a remarkable removal of 74.5% lignin and 95.2% hemicellulose was achieved after freeze-thaw treatment. The resulting cellulose-rich solid residues were further processed with maleic acid to prepare cellulose nanocrystals, which displayed uniform sized rod-like structures and high crystallinity (62.51%). Moreover, maleic acid pretreatment resulted in lignin with low molecular weight (2110-2530) and excellent homogeneity (PDI ≤ 1.86), while maintaining a relatively intact structure. The lignin had high β-O-4 aryl ether bond contents (≥77.5%) and abundant phenolic hydroxyl contents (2.33-3.63 mmol/g). Overall, the process exhibits notable benefits in effectively separating lignocellulose for high valorization.


Marital status and health among the elderly.
Many studies have documented a longevity advantage for married persons relative to their unmarried counterparts in all age groups. However, these studies have failed to determine whether the advantage experienced by married elderly persons arises mostly from selection and causal processes which operated at younger ages. This paper employs data from the Longitudinal Study of Aging (1984-1990) to explore whether marital status continues to exert any influence on health and mortality at the older ages. In the presence of an extensive set of controls for health status at the baseline survey, a series of logistic models are used to determine: (1) the magnitude of marital status effects on disability and on mortality, among older males and older females; and (2) the extent to which the social environment and economic status of the elderly can account for the existing disability and mortality differences by marital status.


Reduced-toxicity allogeneic hematopoietic stem cell transplantation in congenital sideroblastic anemia.
The case of an infant girl with severe congenital sideroblastic anemia associated with a novel molecular defect in mitochondrial transporter SLC25A38 is presented. Her transfusion dependence was fully reversed following allogeneic hematopoietic stem cell transplantation using a modified reduced-intensity conditioning regimen, and she remains healthy 5 years posttransplant.


The effect of parenteral indomethacin on T-lymphocyte subpopulations and cytokine production in patients under major surgical operations.
Major surgical trauma has been considered as a cause of immunosuppression mainly through the production of prostaglandin E2 from activated monocytes/macrophages. In the present study we investigated the effect of parenteral indomethacin--a cyclo-oxygenase inhibitor--on T-lymphocyte subsets and cytokine production in patients under major operations. We studied 20 patients undergoing major surgical procedures, 10 of whom were randomly treated pre- and post-operatively with indomethacin (group 2) and 10 were not (group 2). We measured total T-cells, T-helper, T-suppressor, T-helper/T-suppressor (Th/Ts) cell ratio, NK-cells and interleukin (IL-1) and tumor necrosis factor production by endotoxin- or phytohemagglutinin-stimulated peripheral blood mononuclear cells, before operation and at days 1, 3 and 7 postoperatively. We detected a significant increase in Th/Ts cell ratio and an improvement in delayed type hypersensitivity response in the treated group at day 3. We believe that the above immunomodulating effect of in vivo cyclo-oxygenase inhibition may be beneficial in patients under major surgical procedures with a high susceptibility to postoperative infections.


Adenovirus-mediated intra-arterial delivery of cellular repressor of E1A-stimulated genes inhibits neointima formation in rabbits after balloon injury.
This study examined the effect on neointimal hyperplasia of adenovirus-mediated delivery of cellular repressor of E1A-stimulated genes (CREG) to the artery after balloon injury. Sixty rabbits were randomized into three groups and underwent balloon injury in the left common carotid arteries. The injured arterial segment was isolated by two inflated balloon catheters. Saline or recombinant adenovirus expressing CREG or green fluorescent protein was injected into the lumen of the isolated arterial segments and incubated for 30 minutes. The rabbits were euthanized for immunohistochemistry, Western blotting, and morphometric analysis at 3, 7, 14, and 28 days after balloon injury and in vivo gene transfer (5 rabbits for each time point). Common carotid artery angiography was performed before euthanasia. Immunohistochemistry and Western blot analysis demonstrated that CREG expression was significantly down-regulated in the acute phase of vascular injury and was gradually restored in the resolution phase. The changes of CREG expression were in parallel with those of the smooth muscle cell (SMC) differentiation markers SM alpha-actin and SM myosin heavy chain in the injured arteries. Adenovirus-mediated CREG transfer markedly increased CREG expression in the injured artery. Consequently, morphometric analysis revealed an approximate 50% reduction in the neointima and the intima/media ratio in CREG-transferred arteries compared with the saline and green fluorescent protein controls. Assay with 5-bromo-2-deoxyuridine showed that CREG transfer significantly inhibited SMC proliferation. In contrast, endothelialization of the injured artery was not affected by CREG transduction as assessed by CD31 immunostaining. These data suggest that forced expression of CREG in the artery wall after acute vascular injury inhibits SMC proliferation, induces cellular differentiation, and attenuates neointimal hyperplasia. CREG delivery may have therapeutic potential for the prevention of restenosis after vascular angioplasty.


Change pattern of somatosensory-evoked potentials after occlusion of segmental vessels: possible indicator for spinal cord ischemia.
Paraplegia was reported after occlusion of the segmental vessels during anterior spinal surgery. The aim of this study was to investigate the effect of occlusion of the segmental vessels on the somatosensory-evoked potential (SEP) monitoring and analyze its potential risk for cord ischemia. Thirty-one patients with thoracic scoliosis underwent anterior spinal surgery. T5-T11 segmental vessels on the convexity were occluded with microvascular clamps at the point 2 cm from the intravertebra foramen. The SEPs were recorded 5 min before occlusion and 2, 7, 12 and 17 min after occlusion. The SEPs were analyzed with two indices i.e. P40 latency and P40 amplitude. All SEP waveforms recorded during the test were regular and recognizable. Compared to 5 min before occlusion, the P40 latencies at 2 min and 7 min after occlusion significantly increased 3.39% and 2.76% on an average, the P40 amplitudes at 2 min after occlusion significantly declined 26% (peak to peak) or 22% (peak to baseline) on an average (P<0.05). But the changes of SEPs were temporary. The SEPs began to restore at 12 min after occlusion and returned to the pre-occlusion level at 17 min after occlusion. No neurologic complications occurred in all patients after surgery. These results suggest that SEP is a possible indicator for ischemia of the spinal cord which is a dynamic course and cannot be considered an "all-or-none" phenomenon. Without the factors such as developmental deformities of the spinal cord, vascular variation and potential cord ischemia, occlusion of the segmental vessels would be safe during the anterior spinal surgery.


A comparison of the efficacy of donepezil in Parkinson's disease with dementia and dementia with Lewy bodies.
Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) overlap in phenomenology and neurochemical deficits. We hypothesised they would not differ in their response to the cholinesterase inhibitor donepezil. We recruited 70 subjects, 30 DLB and 40 PDD, in an open label study to compare the efficacy of donepezil in these two patient groups. They were assessed at baseline, 4, 12 and 20 weeks. The main outcome measures were the Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI) and motor sub-section of the Unified Parkinson's Disease Rating Scale (UPDRS III). PDD patients were younger than DLB and had more severe parkinsonism at baseline. The groups were similar on all other variables of interest. By 20 weeks the mean MMSE score increased by 3.9 points in the DLB group and by 3.2 points in PDD. The mean NPI score reduced by 14.6 points for DLB and 12.0 points for PDD. These treatment effects were all significant compared to baseline (p < 0.001) but there were no significant between-group treatment differences (MMSE p = 0.56, NPI p = 0.39). UPDRS III motor scores did not change significantly from baseline values in either group. Although adverse effects were common (69%) they were usually mild and 64 patients (91%) completed the study. The four patients who did withdraw with adverse effects all had a PDD diagnosis. Donepezil produced similar improvements in cognition and behaviour in DLB and PDD. This supports the hypothesis that the two disorders are closely related clinically and neurobiologically. Larger scale, placebo controlled clinical trials are needed to provide an evidence base to guide the clinical use of cholinesterase inhibitors in Lewy body disease.


Patterns of contraceptive use among Thai women aged ≥40 and at risk of pregnancy.
The aims of the study were to identify the patterns of contraceptive use among Thai women aged ≥40 years and the reasons for not using contraception. This cross-sectional study included sexually active women aged 40-49 years in Khon Kaen, Thailand. Information on contraceptive practice and reasons for not using contraception was collected through a self-reported questionnaire. The unmet need for a modern method of contraception and the unmet need for any method of contraception were calculated based on the percentage of participants who were not using contraception but who wanted to postpone or prevent pregnancy. Of 400 women, 75.5% were currently using some form of contraception, with female sterilisation being the most used (35%). The main reasons for not using contraception included perceived low risk of pregnancy, health concerns, infrequent sexual intercourse and wish to become pregnant. The unmet need for a modern method of contraception was 23.3% (95% confidence interval [CI] 0.20%, 0.29%). Having children was a significant protective factor (adjusted odds ratio [OR] 0.18; 95% CI 0.08, 0.37; p = 0.000). The unmet need for any method of contraception was 12% (95% CI 0.09%, 0.16%). Previous abortion was a significant risk factor for not using any contraception (adjusted OR 2.23; 95% CI 1.12, 4.44; p = 0.022). Although the use of contraception was common, some participants displayed a lack of knowledge and/or did not practise family planning. Our findings address the importance of improving knowledge about the risks of pregnancy and the need for effective contraception in this population.


Radiomics and deep learning methods for the prediction of 2-year overall survival in LUNG1 dataset.
In this study, we tested and compared radiomics and deep learning-based approaches on the public LUNG1 dataset, for the prediction of 2-year overall survival (OS) in non-small cell lung cancer patients. Radiomic features were extracted from the gross tumor volume using Pyradiomics, while deep features were extracted from bi-dimensional tumor slices by convolutional autoencoder. Both radiomic and deep features were fed to 24 different pipelines formed by the combination of four feature selection/reduction methods and six classifiers. Direct classification through convolutional neural networks (CNNs) was also performed. Each approach was investigated with and without the inclusion of clinical parameters. The maximum area under the receiver operating characteristic on the test set improved from 0.59, obtained for the baseline clinical model, to 0.67 ± 0.03, 0.63 ± 0.03 and 0.67 ± 0.02 for models based on radiomic features, deep features, and their combination, and to 0.64 ± 0.04 for direct CNN classification. Despite the high number of pipelines and approaches tested, results were comparable and in line with previous works, hence confirming that it is challenging to extract further imaging-based information from the LUNG1 dataset for the prediction of 2-year OS.


Effects of irradiation on grafted skin.
The reaction of grafted skin to irradiation was studied in the rat and the optimum time for irradiation postoperatively was determined. There was a close correlation between the radiosensitivity and the vascularity of the graft and its recipient bed. Grafts showed different reactions depending on the time of irradiation after grafting. Those in the early hypovascular stage showed reactions similar to those of normal control skin. Severe reactions were observed in the hypervascular stage. Grafts in the late hypovascular stage showed more moderate reactions.


Mouse gonadal differentiation in vitro in the presence of fetal calf serum.
Other workers have shown that fetal calf serum (F.C.S.) inhibits the differentiation of the rat testis, and disrupts established testicular cords, in vitro. To investigate the possibility of a serum effect in the mouse, indifferent urogenital complexes and differentiated gonads were removed from sexed fetuses and cultured for 7 days in medium with or without the addition of fetal calf serum. Cultures were assessed by light and electron microscopy. Testicular and ovarian differentiation occurred in the presence of fetal calf serum. Serum did not prevent basal lamina development in testicular cords of explants cultured to the equivalent of day-17 control testes.


Sleep quality, depression state, and health status of older adults after silver yoga exercises: cluster randomized trial.
Sleep disturbances, depression, and low perception of health status are commonly seen in elderly population; however, clinicians tend to underestimate or overlook the presence of these symptoms and assume them to be a part of normal aging. Non-pharmacological methods that promote a mind-body interaction should be tested to enhance the mental health of older adults. To test the effects of 6 months of silver yoga exercises in promoting the mental health of older adults in senior activity centers, especially their sleep quality, depression, and self-perception of health status. Cluster randomized trial. Eight senior activity centers, southern Taiwan. A sample of 139 participants was recruited, and 128 of them completed the study. (1) community-dwelling older adults ages 60 and over, (2) no previous training in yoga, (3) able to walk without assistance, (4) cognitively alert based on the Short Portable Mental Status Questionnaire (SPMSQ) score of eight or higher, and (5) independent or mildly dependent in self-care based on a Barthel Index (BI) score of 91 or higher. The mean age of the participants was 69.20 +/- 6.23 years, and the average number of chronic illness was 0.83 +/- 0.90. The average BI score of the participants was 99.92 +/- 0.62, and the mean SPMSQ score was 9.90 +/- 0.30. Participants were randomly assigned into either the experimental (n=62) or the control (n=66) group based on attendance at selected senior activity centers. A 70-min silver yoga exercise program was implemented three times per week for 6 months as the intervention for the participants in the experimental group. Most of the mental health indicators of the participants in the experimental group had significantly improved after the silver yoga interventions, and many of the indicators improved after 3 months of intervention and were maintained throughout the 6 months study. The mental health indicators of the participants in the experimental group were all better than the participants in the control group (all p<.05). After 6 months of silver yoga exercises, the sleep quality, depression, and health status of older adults were all improved.


Simultaneous determination of capecitabine and its metabolites by HPLC and mass spectrometry for preclinical and clinical studies.
A reverse-phase high-performance liquid chromatography method with electrospray ionization and detection by mass spectrometry is described for the simultaneous determination of capecitabine, its intermediate metabolites (DFCR, DFUR) and the active metabolite 5-fluorouracil in mouse plasma, liver and human xenograft tumours. The method was also cross-validated in human plasma and human tumour for clinical application. The method has greater sensitivity than previously published methods with an equivalent accuracy and precision. It uses less biological material (plasma, tissue) and should therefore be applicable to biopsies in patients treated with capecitabine.


Effect of the beta-3 adrenergic receptor Trp64Arg and uncoupling protein 1-3826 A>G genotypes on lipid and apolipoprotein levels in overweight/obese and non-obese Chinese subjects.
The beta-3 adrenergic receptor (β3-AR) Trp64Arg and uncoupling protein 1 (UCP1) -3826 A>G polymorphisms have been reported to be associated with obesity and/or lipid metabolism in some populations. This study examined the possible association of the β3-AR and UCP1 polymorphisms with overweight/obesity or lipid variation in a Southwest Chinese population. A total of 418 Han Chinese (249 overweight/obese and 169 healthy control subjects) in the Chengdu area were studied using PCR-RFLP analysis. Total serum cholesterol (TC) and triglycerides (TGs) were measured using an enzymatic method. High density lipoprotein cholesterol (HDL-C) was determined after sodium phosphotungstate/magnesium chloride precipitation of low-density lipoproteins by polyvinyl sulfate. Serum apolipoproteins were quantified by radial immunodiffusion. The genotype and allele frequencies of the β3-AR Trp64Arg and UCP1 -3826 A>G polymorphisms in overweight/obese subjects exhibited no significant differences compared to the controls. However, subjects carrying the β3-AR TrpTrp genotype and UCP1 AG genotype had higher TG levels than those carrying the Arg allele and AA genotype, respectively (P<0.05), while controls carrying the β3-AR Arg allele had significantly higher TC and apo AII concentrations than those carrying the TrpTrp genotype (P<0.05). Additionally, subjects carrying the UCP1 AG genotype exhibited elevated apo C-II and apo C-III levels compared to those carrying the AA genotype (P<0.05). We were unable to find an association of the UCP1 and β3-AR polymorphisms with low HDL-cholesterolemia in the overweight/obese subjects. The present study provides evidence that the β3-AR Trp64Arg and UCP1 -3826 A>G polymorphisms are associated with TG levels in overweight/obese Chinese subjects and that the two polymorphisms are also associated with certain lipid and apolipoprotein variations, depending on BMI. However, these polymorphisms are not associated with overweight/obesity or low HDL-cholesterolemia in a Chinese population from the Chengdu area.


Montelukast plus cetirizine in the prophylactic treatment of seasonal allergic rhinitis: influence on clinical symptoms and nasal allergic inflammation.
The aim of our study was to investigate effects of 6-week pretreatment of seasonal allergic rhinitis (AR) with cetirizine, and montelukast, alone and in combination. Antihistamine/antileukotriene treatment is effective in AR. Antihistamines may prevent AR symptoms while prophylactic activity of antileukotrienes remains unclear. Sixty AR patients, aged 18-35 years, were randomized to receive placebo, montelukast only, cetirizine only, or montelukast plus cetirizine, 6 weeks prior and 6 weeks after the beginning of grass pollen season. Mean self-recorded in-season symptom scores and mean weekly all-symptom scores were analyzed. In 31 patients, nasal lavages were performed before treatment, and at the end of the study, i.e. 12 weeks after the treatment initiation. Eosinophil and basophil counts, eosinophil cationic protein (ECP), and mast cell tryptase (MCT) levels were evaluated in lavage samples. Combined montelukast/cetirizine pretreatment significantly reduced in-season symptom score for sneezing, eye itching, nasal itching, rhinorrhea, and congestion. Montelukast plus cetirizine were more effective than cetirizine alone in preventing eye itching, rhinorrhea, and nasal itching. Moreover, combined pretreatment with montelukast and cetirizine delayed appearance of AR symptoms. Eosinophil nasal lavage fluid counts were significantly increased during pollen season in placebo and montelukast-only groups. No differences were observed in basophil counts. The in-season ECP level was significantly increased in all groups except montelukast-plus-cetirizine group. In-season MCT levels were not increased. Combined antihistamine and antileukotriene treatment started 6 weeks before the pollen season is effective in preventing AR symptoms and reduces allergic inflammation in nasal mucosa during natural allergen exposure.


When a parent has a stroke: clinical course and prediction of mood, behavior problems, and health status of their young children.
The purpose of this research was to describe the clinical course of children's functioning (depression, behavioral problems, and health status) during the first year after parental stroke and to determine which patient-, spouse-, or child-related factors at the start of inpatient rehabilitation can predict children's functioning after parental stroke at 1-year poststroke. Interviews with 82 children (4 to 18 years of age) and their parents (n=55) shortly after admission to a rehabilitation center, 2 months after discharge from inpatient rehabilitation, and 1 year after stroke. Depression was assessed using the Children Depression Inventory, behavioral problems with the Child Behavior Check List, and health status with the Functional Status II. Potential predictors were gender and age (child), activities of daily living disability and communication ability (patient), and spouse's depression and perception of the marital relationship. At the start of the stroke patient's rehabilitation, 54% of the children had > or =1 subclinical or clinical problems, which improved to 29% 1 year after stroke. Children's functioning 1 year after stroke could best be predicted by their functioning at the start of rehabilitation. Spouse depression and perception of marital relationship were also significant predictors. A total of 28% to 58% of the variance in children's functioning could be explained. Children's functioning after parental stroke improved during the first year after stroke. Identifying children at risk for problems 1 year after stroke requires assessment of children's functioning and the healthy spouse's depressive symptoms and perception of the marital relationship at the start of rehabilitation. This demonstrates the need for a family-centered approach in stroke rehabilitation.


Identification of photoproducts of fungicide cyprodinil and elucidation of transformation mechanism in water using LC-IT-TOF-MS/MS technique.
This study aimed at investigating photodegradation of cyprodinil in aquatic solution under the simulated natural light or UV-visible irradiation (290-800 nm) using LC-MS/MS techniques. Effects of pH, nitrate ion, Fe (III), humic acid and TiO2 on photolysis kinetics of cyprodinil were explored. The photodegradation followed first-order reaction kinetics, and linear accelerating effects of Fe (III), nitrate ion and TiO2 with concentrations ranging from 0.1 to 5.0 mg L(-1) on photodegradation were remarkably observed. HA at low concentration ranges (<3.0 mg L(-1)) enhanced cyprodinil photodegradation while the photocatalytic rate was weakened with more addition of HA. The degradation rate in alkaline solutions was greater than in acidic solutions. Six main transformation products (TPs) were separated and identified based on mass spectra data and density functional theory (DFT) quantum calculations, and their kinetic evolutions were also investigated. Ultimately, a tentative transformation mechanism was proposed based the identified TPs and their kinetic evolutions. The results indicated that one α-H on pyridine ring of cyprodinil was hydroxylated to form TPs 1. TPs 1 underwent a series of photochemical reactions involving ring-opening, addition of one H2O molecule and demethylation on three-member ring to form TPs 2, which was further hydroxylated on benzene ring to form TPs 6. TPs 3-5 were three isomers from Hofmann-Martius rearrangement of cyprodinil. These findings were of utmost importance for elucidating environmental fate of cyprodinil in aquatic ecosystem and further environmental risk evaluation.


Integrating Foundational and Clinical Science Remotely by Combining Team-Based Learning and Simulation.
Integrating foundational and clinical science in medical and other professional healthcare degree programs has been well established as a means to enhance learning. However, implementation remains challenging, and a significant gap exists in guidance for non-professional degree programs to effectively accomplish both types of integration. Additionally, many modalities described in the literature are resource-intensive, scale poorly to larger groups, and are widely inaccessible. We present an online modality combining team-based learning and a simulation-based learning experience that fosters vertical and horizontal integration of physiology, pharmacology, and clinical science. The tools utilized include a vital sign simulator, video conferencing software, and a document-sharing platform. The activity demonstrated improved knowledge comparing pre- and posttests and evidence that the activity helped students integrate physiology, pharmacology, and clinical medicine. The novel structure is effective and accessible, uses open-source software and standard equipment available to most undergraduate and graduate faculty, and is adaptable to in-person, hybrid-remote, and fully remote delivery. The online version contains supplementary material available at 10.1007/s40670-023-01817-9.


Energy expenditure for cyclic retention of NH3/NH4+ during N2 fixation by Klebsiella pneumoniae.
The permeability coefficient for NH3 through bacterial membranes was determined to be around 2 X 10(-3) cm X s-1. This value was used to calculate the outward diffusion of NH3 from intracellular pools and the energy costs for reabsorption as NH4+. For an N2-fixing continuous culture of Klebsiella pneumoniae an energy expenditure of around 4 ATP per NH3 produced was calculated, thus increasing significantly the energy requirement for N2 fixation in vivo.


Histopathological and Biochemical Changes in the Gills of Anabas testudineus on Exposure to Polycyclic Aromatic Hydrocarbon Naphthalene.
Naphthalene, a polycyclic aromatic hydrocarbon, is generated by various distillation, petroleum, and coal-tar production units and is used worldwide as mothballs, soil fumigants, and toilet deodorants. Considering the susceptibility of aquatic animals to different types of stressors in several water bodies, this study was carried out to evaluate the impact of naphthalene on the architecture of gill tissue including response of various enzymes like cholinesterase (ChE) activity, lactate dehydrogenase (LDH) activity, and lipid peroxidation (LPX) level of the freshwater fish Anabas testudineus. Activities of antioxidants like catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH) were also evaluated. Constant loss of gill structure and secondary lamellar fusion was observed in fishes exposed to various concentrations of naphthalene. ChE, LDH, LPx, CAT, Gpx and GSH activities indicated significant variation (p < 0.05) between the control and experimental groups. ChE activity was lowered in experimental fishes; however, LDH activity, LPx levels, and CAT activity were elevated in response to various concentrations of naphthalene as compared to control group. Both GPx and GSH activities decreased in the gill tissue of the experimental fishes. Thus, a conclusion was drawn that naphthalene is a potent toxicant capable of inflicting tissue damage leading to physiological changes in the exposed fishes.


Rhoifolin from Plumula Nelumbinis exhibits anti-cancer effects in pancreatic cancer via AKT/JNK signaling pathways.
This study aimed to evaluate the anti-pancreatic cancer effects of flavonoids in Plumula Nelumbinis. High-performance liquid chromatography/quadrupole time-of-flight mass spectrometry showed that apiin, rhoifolin, and vitexin were three principal components in total flavonoids derived from Plumula Nelumbinis, with vitexin being the most abundant component. Cell viability assay revealed that apiin, rhoifolin, and vitexin could inhibit proliferation of PANC-1 and ASPC-1, with rhoifolin showing the maximum inhibitory effect. Rhoifolin inhibited cell proliferation and promoted apoptosis of pancreatic cancer cells, which was associated with up-regulated JNK and p-JNK as well as down-regulated p-AKT. Rhoifolin also inhibited cell migration and invasion, and increased the antioxidant capacity in PANC-1 and ASPC-1. Besides, AKT activator (SC79) or JNK inhibitor (SP600125) effectively reversed the anticancer effects of rhoifolin in pancreatic cancer. Quantitative proteomics analysis showed that rhoifolin altered proteomic profiles in pancreatic cancer cells. Western blot analysis showed that rhoifolin down-regulated transforming growth factor beta 2 (TGF-β2), the regulator of proteoglycan synthesis, with the concomitant down-regulation of phosphorylated SMAD family member 2 (SMAD2), the downstream effector of TGF-β2. In conclusion, rhoifolin regulates the AKT/JNK/caspase-3 and TGF-β2/SMAD2 signaling pathways, which may contribute to its anti-pancreatic cancer effects.


Intraoperative monitoring of lower cranial nerves in skull base surgery: technical report and review of 123 monitored cases.
The fundamental goal of skull base surgery is tumor removal with preservation of neurological function. Injury to the lower cranial nerves (LCN; CN 9-12) profoundly affects a patient's quality of life. Although intraoperative cranial nerve monitoring (IOM) is widely practiced for other cranial nerves, literature addressing the LCN is scant. We examined the utility of IOM of the LCN in a large patient series. One hundred twelve patients underwent 123 skull base operations with IOM between January 1994 to December 1999. The vagus nerve (n=37), spinal accessory nerve (n=118), and the hypoglossal nerve (n=83) were monitored intraoperatively. Electromyography (EMG) and compound muscle action potentials (CMAP) were recorded from the relevant muscles after electrical stimulation. This data was evaluated retrospectively. Patients who underwent IOM tended to have larger tumors with more intricate involvement of the lower cranial nerves. Worsening of preoperative lower cranial nerve function was seen in the monitored and unmonitored groups. With the use of IOM in the high risk group, LCN injury was reduced to a rate equivalent to that of the lower risk group (p>0.05). The immediate feedback obtained with IOM may prevent injury to the LCN due to surgical manipulation. It can also help identify the course of a nerve in patients with severely distorted anatomy. These factors may facilitate gross total tumor resection with cranial nerve preservation. The incidence of high false positive and negative CMAP and the variability in CMAP amplitude and threshold can vary depending on individual and technical factors.