A versatile inhibitor of digestive enzymes in Aedes aegypti larvae selected from a pacifastin (TiPI) phage display library.
In Brazil, the major vector of arboviruses is Aedes aegypti, which can transmit several alpha and flaviviruses. In this work, a pacifastin protease inhibitor library was constructed and used to select mutants for Ae. aegypti larvae digestive enzymes. The library contained a total of 3.25 × 105 cfu with random mutations in the reactive site (P2-P2'). The most successfully selected mutant, TiPI6, a versatile inhibitor, was able to inhibit all three Ae. aegypti larvae proteolytic activities, trypsin-like, chymotrypsin-like and elastase-like activities, with IC50 values of 0.212 nM, 0.107 nM and 0.109 nM, respectively. In conclusion, the TiPI mutated phage display library was shown to be a useful tool for the selection of an inhibitor of proteolytic activities combined in a mix. TiPI6 is capable of controlling all three digestive enzyme activities present in the larval midgut extract. To our knowledge, this is the first time that one inhibitor containing a Gln at the P1 position showed inhibitory activity against trypsin, chymotrypsin, and elastase-like activities. TiPI6 can be a candidate for further larvicidal studies.


Expression of CD4 is correlated with an unfavorable prognosis in wild-type NPM1, FLT3-ITD-negative cytogenetically normal adult acute myeloid leukemia.
In the cytogenetically normal population of AML (CN-AML), FLT3-ITD-positive and wild-type NPM1 is correlated with a worse outcome, and FLT3-ITD-negative with NPM1-mut is correlated with a better outcome. This leaves a large subpopulation of CN-AML patients without NPM1 or FLT3-ITD mutations with heterogeneous outcomes with overall survivals (OS) ranging from several weeks to years. Therefore, new prognostic markers are needed to better risk stratify this subset of patients. The retrospective study included 60 de novo adult AML patients diagnosed at our institution with normal karyotype, no FLT3-ITD or NPM1 mutations, and who did not receive allogeneic hematopoietic stem cell transplantations. We investigated the prognostic significance of immunophenotypic markers and clinical laboratory features in this double-negative population. Older age (>60) and CD4 expression (14%) were significantly correlated with shorter event-free survival (EFS) (P < 0.001, P = 0.016, respectively). Expression of CD56 (12%), as well as lack of CD34 expression (19% of the cases), was also associated with a worse EFS (P = 0.048, P = 0.028, respectively). On multivariable analysis, CD4 expression and old age (>60) were identified as independent predictors for worse EFS (P = 0.016; P = 0.001, respectively) and OS (P = 0.048; P = 0.028, respectively). Our results indicate that CD4 expression and older age are adverse prognostic factors in wild-type NPM1, FLT3-ITD-negative CN-AML.


Monensin has no effect on growth and metabolism of Megasphaera elsdenii.
A rumen strain of Megasphaera elsdenii was grown on glucose and lactate in monensin-free and monensin-supplemented medium (10 mg/L). Monensin had no effect on growth rate, growth yields, metabolic pattern and composition of cells. Growth yields of dry matter and protein were higher in cultures supplied with glucose than in cultures supplied with lactate. The bacterium compensated the lower gain of energy from fermentation of lactate by rapid utilization of this substrate. Cells grown on glucose contained more saccharide and less protein than lactate-grown cells.


Reproductive phenologies of phyllostomid bat populations and ensembles from lowland Amazonia.
Natural selection should favor individuals that synchronize energy-demanding aspects of reproductive activity with periods of high resource abundance and predictability, leading to seasonal patterns of reproduction at the population level. Nonetheless, few studies-especially those on bats in the Neotropics-have used rigorous quantitative criteria to distinguish among phenological patterns for different populations from the same habitat or for the same species in different habitats. To explore such issues, we quantified annual patterns of reproduction in male and in female bats from lowland Amazonia (environs of Iquitos, Peru), and did so at the level of populations and ensembles. Five species exhibited unimodal patterns including Artibeus obscurus, A. planirostris, Carollia benkeithi, Phyllostomus hastatus, and Rhinophylla pumilio. Two species (A. lituratus and Glossophaga soricina) evinced bimodal patterns with reproductive peaks separated by patterns of inactivity, whereas four species (C. brevicauda, C. perspicillata, Sturnira lilium, and S. tildae) evinced a bimodal pattern in which peaks in activity occur in tandem, with the first peak generally markedly higher than the second peak. Frugivore, gleaning animalivore, and nectarivore ensembles exhibited bimodal, unimodal, and bimodal reproductive phenologies, respectively. Nonetheless, interannual variation in phenology (i.e., the monthly timing of peaks within a season rather than the number of peaks per year) characterized four (A. obscurus, C. brevicauda, C. perspicillata, and S. lilium) of the eight species and each of the three ensembles (frugivores, gleaning animalivores, and nectarivores) with adequate sampling. Regardless of interspecific variation in strategies, the phenology of reproduction enhances the likelihood that parturition and recruitment of young into the population occurs during the wet season, the period of likely highest resource abundance. Based on a comparison of our results with those from other well-studied bat populations, four species did not exhibit geographic variation in reproductive phenologies (A. obscurus, G. soricina, C. brevicauda, and R. pumilio), whereas three species evinced such geographic variation (A. lituratus, A. planirostris, and C. perspicillata). Climate change will likely alter the seasons and extents of propitious times for reproductive activities, as well as the reliability of proximate cues for initiating reproduction, compromising current reproductive strategies and leading to altered phenological patterns of reproduction or reproductive success, possibly resulting in local extinction of some species.


Cytogenetic changes in fish exposed to water of the river Rhine.
The induction of chromosome aberrations in fishes, exposed to Rhinewater, was investigated. The mudminnow, Umbra pygmaea, was chosen for this study, because of its ideal karyotype of 22 large chromosomes. Gill cells were used for chromosome studies. Fish, kept in Rhinewater for 11 days had chromosome breaks in approximately 30% of the metaphases studied. Control fish, exposed to a very good quality of untreated groundwater had breaks in about 8% of the metaphases. Several Rhinewater extracts were tested for their mutagenic potential in the Salmonella-microsome test. The fraction of aromatic compounds was found to be positive. This may indicate that one or more of the compounds present in this fraction were also responsible for the cytogenetic changes found in the fish.


Capacitance of bilayers in the presence of lipophilic ions.
The capacitance of glycerolmonooleate and egg phosphatidylcholine bilayer membranes in the presence of NaCl solutions containing tetraphenylborate, tetraphenylarsonium or dipicrylamine ions has been measured using alternating current techniques over a wide range of frequencies (1-200 kHz). The concentrations of ions corresponded to the lower limits of conductance saturation. Similar determinations were also made with solutions containing no lipophilic ions. The experimental method used in this work requires correction of admittance measurements for the solution resistance in series with the membrane, as well as careful area determinations. In all cases membrane capacitance levels off at sufficiently high frequencies to values which are independent of frequency. The high-frequency capacitance, which is regarded as the 'geometrical capacitance' due to dielectric polarization, is practically unaffected by the presence of lipophilic ions. The results support the assumption made in other studies, such as in charge pulse investigations, that the adsorption of lipophilic ions at concentrations up to the saturation range does not have an important effect on the dielectric properties of bilayers.


Hospital survival upon discharge of ill-neonates transported by ground or air ambulance to a tertiary center.
To evaluate the differences in hospital survival between modes of transport to a tertiary center in Colombia for critically ill neonates. Observational study of seriously ill neonates transported via air or ground, who required medical care at a center providing highly complex services. Data on sociodemographic, clinical, the Transport Risk Index of Physiologic Stability (TRIPS), and mode of transport were collected. Patients were described, followed by a bivariate analysis with condition (live or dead) at time of discharge as the dependent variable. A multiple Poisson regression with robust variance model was used to adjust associations. A total of 176 neonates were transported by ambulance (10.22% by air) over six months. The transport distances were longer by air (median: 237.5km) than by ground (median: 11.3km). Mortality was higher among neonates transported by air (33.33%) than by ground (7.79%). No differences in survival were found between the two groups when adjusted by the multiple model. An interaction between mode of transport and distance was observed. Live hospital discharge was found to be associated with clinical severity upon admittance, birth weight, hemorrhaging during the third trimester, and serum potassium levels when admitted. Mode of transport was not associated with the outcome. In Colombia, access to medical services through air transport is a good option for neonates in critical condition. Further studies would determine the optimum distance (time of transportation) to obtain good clinical outcomes according type of ambulance.


Effect of ventral tegmental 6-hydroxydopamine lesions on the locomotor stimulant action of nicotine in rats.
Convergent evidence suggests that the locomotor stimulant effect of nicotine is mediated by nicotinic receptors located on mesolimbic dopaminergic neurons. However, 6-hydroxydopamine lesions of the ventral tegmental area, resulting in substantial depletion of nucleus accumbens dopamine, were recently reported to have no effect on nicotine-induced locomotion. The present study sought to re-examine this issue. Rats received bilateral infusions of 6-hydroxydopamine or vehicle into the ventral tegmental area. Starting 3 weeks later, locomotor activity was tested after subcutaneous injection of saline, nicotine (0.4 mg/kg base), amphetamine (0.5 mg/kg) or scopolamine (0.5 mg/kg). In lesioned animals, the locomotor stimulant effects of nicotine and amphetamine were greatly reduced, whereas saline and scopolamine-induced activity was scarcely affected. Dopamine denervation was assessed by autoradiography, using [125I]RTI-55 to label plasmalemmal dopamine transporters. Labelling was reduced in nucleus accumbens core and shell and in the ventral tegmental area (by 87, 81 and 70%, respectively), and in nigrostriatal areas (52-77%). The locomotor stimulant effects of nicotine and amphetamine were correlated with residual [125I]RTI-55 labelling in mesolimbic and nigrostriatal regions (r=0.6-0.8). The present results provide further evidence that the locomotor stimulant effect of nicotine is dependent on the integrity of ascending dopamine neurons.


Endoscopic local injection of hypertonic saline-epinephrine solution to arrest hemorrhage from the upper gastrointestinal tract.
For the purpose of arresting hemorrhage from the upper gastrointestinal tract we developed a method of endoscopic local injection of hypertonic saline-epinephrine solution, consisting of 3.6% or 7.1% sodium chloride with 0.005% epinephrine, which was locally injected around the base of the bleeding vessel under endoscopy. During the period between October 1978 and September 1983, a total of 158 patients underwent treatment for hemostasis by this method. The major causes of bleeding in our study consisted of gastric ulcers (114) and duodenal ulcers (15). The overall effective rate of hemostasis was 98.1%. By applying this method, the rate of emergency operation for patients with bleeding from the upper gastrointestinal tract was significantly reduced from 21.7% (15/69) to 0.8% (1/128).


Comparison of root apex's position between unilateral and bilateral palatally impacted canines: A pilot study.
The purpose was to determine whether the location of the root apices of unilateral palatally impacted canines differs from that of bilateral palatally impacted canines using cone-beam computed tomography. The subjects were divided into 3 groups: a bilateral palatally impacted canine group (BPG; n = 28), a unilateral palatally impacted canine group (UPG; n = 28), and a control group (CG; n = 28) that included contralateral normally erupted canines in the UPG. After selecting the root apex in the onDemand3D program, 3-dimensional coordinates were extracted. These 3-dimensional coordinates were converted using the MATLAB program to 2-dimensional coordinates via projection on the palatal plane. Procrustes analysis was used to superimpose these 2-dimensional coordinates. The x- and y-coordinates of the root apices were used to measure the distance between the origin and root apex. The distance between the root apex of the canine and the origin was 17.43 ± 1.78 mm in BPG, 17.96 ± 1.87 mm in UPG, and 13.96 ± 0.95 mm in CG. There was no statistically significant difference between UPG and BPG. However, there was a statistically significant difference between the CG and impacted groups (UPG and BPG). The same results were found for the x- and y-coordinates. The location of the root apices of unilateral palatally impacted canines is similar to that of bilateral palatally impacted. The location of root apices of palatally impacted canines differs from that of normally erupted canines.


Serpiginous Choroiditis Complicated with Choroidal Neovascular Membrane Detected using Optical Coherence Tomography Angiography: A Case Series and Literature Review
Serpiginous choroiditis (SC) is a rare, chronic, recurrent, progressive disease of unknown origin. The inflammatory process of SC can disrupt Bruch's membrane, allowing occasional choroidal vascular growth, leading to significant visual loss even in the healed stages of the disease. Optical coherence tomography angiography (OCTA) can help in the detection of choroidal neovascular membrane (CNV), leading to a definitive diagnosis and thereby guide the initiation of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment. We report herein two cases of SC complicated with a CNV detected with OCTA and treated with a series of anti-VEGF injections.


Determining the relationship between over-care burden and coping styles, and resilience in mothers of children with autism spectrum disorder.
Stress and over-care burden are problems for mothers of children with Autism Spectrum Disorder (ASD). Therefore, it seems necessary to evaluation of coping with stress according to the burden of care for these mothers. This study aimed to determine the relationship between care burden with coping styles and resilience of mothers of children with ASD. The present study is a descriptive-analytical study performed on mothers of children with ASD in Kermanshah, Iran. Participants in the study were selected by convenience sampling. A Demographic questionnaire, Caregiver Burden Inventory (CBI), Connor-Davidson Resilience Scale (CD-RISC), and Coping strategies questionnaire (CSQ) were used for collecting data. Then it was analyzed through an independent t-test, ANOVA, and Pearson correlation test. The mean total score of the burden of care was 95.5 ± 9.1, resilience was 52.7 ± 8.7, and coping styles were 92.4 ± 8.4. Mothers of children with autism experience a severe burden of care and moderate levels of resiliency. There was also a significant negative correlation between the burden of care and resilience) p < 0.001, r = -0.536), but no significant correlation was found between burden of care and coping style) p = 0.937, r = -0.010). According to the results of this study, it is necessary to pay more attention to the factors affecting resiliency. Also, considering the significant relationship between burden of care and resiliency, teaching strategies to increase resiliency can be used in the educational program for mothers with autistic children.


Approaches to crystal structure landscape exploration.
Three approaches to the exploration of the crystal structure landscape are outlined. These are crystal structure prediction, non-ambient crystallography and charge density analysis.


Patient Centered Medical Home: What May Be on the Horizon for Urologists.
Medicine has used acronyms for hundreds of years to describe clinical conditions. In urology the acronyms BPH (benign prostatic hyperplasia), ED (erectile dysfunction), IC (interstitial cystitis) and AUR (acute urinary retention) are examples with which we are all familiar. Today we use acronyms to describe the organizational and structural aspects of medicine. The 2 most recent medical acronyms are PPACA (Patient Protection and Affordable Care Act) and ACO (accountable care organization). Now a new acronym, PCMH (patient centered medical home), is looming on the horizon. This article defines patient centered medical home, discusses its purpose and finally attempts to predict its impact on clinical urological practices. At this time no menu is yet available for specialty groups, including urologists, to engage their participation in patient centered medical homes.


Reduced interhemispheric transmission in schizophrenia patients: evidence from event-related potentials.
Interhemispheric transfer was investigated in 14 schizophrenia patients and 15 age- and sex-matched healthy controls in a lateralized lexical decision task. Words and pseudowords were tachistoscopically presented either to the left or to the right visual hemifield. Event-related potentials were determined from a 65-channel electroencephalogram. Information transfer between hemispheres was assessed by the interhemispheric transmission time (IHTT), the N1-latency difference between ipsilateral and contralateral hemisphere.Controls, but not schizophrenia patients showed significantly faster IHTT from the right to the left hemisphere for words, while IHTT from the left to the right hemisphere did not differ between groups and stimuli. These findings are interpreted in terms of a deficit in schizophrenia to transfer verbal information from the right to the left hemisphere via the corpus callosum.


Changes in cerebral autoregulation and vasoreactivity after surgical aortic valve replacement: a prospective study.
What is the central question of this study? How are dynamic cerebral autoregulation and brain vasoreactivity influenced by severe aortic stenosis and its surgical treatment? What are the main findings and their importance? Dynamic cerebral autoregulation is preserved in the long term in patients with severe aortic stenosis and does not change after surgical aortic valve replacement. However, carbon dioxide vasoreactivity is impaired in these patients. Surgical aortic valve replacement (SAVR) alters the natural course of severe aortic stenosis (AS). In this study, we aimed to determine the effects of the disease on dynamic cerebral autoregulation and vasoreactivity (VR) and to assess their changes after SAVR. We recruited 23 patients diagnosed with severe AS eligible for SAVR and 15 healthy matched controls. AS patients had lower mean VR to CO2 (P = 0.005) than controls, but dynamic cerebral autoregulation was preserved. Cerebral haemodynamics showed no significant change after SAVR. Patients with smaller baseline aortic valve areas presented with smaller low frequency phase changes after surgery (P = 0.016). Severe AS does not seem to impact dynamic cerebral autoregulation but does reduce VR to CO2 . SAVR does not alter cerebral autoregulation nor vasoreactivity.


[Markers of hepatitis B virus infection in infants born of mothers who are HBs-antigen carriers with anti-HBe present and the problems of passive immunoprophylaxis].
In December, 1983 to December, 1985, blood sera of 14,603 pregnant women were tested for the detection of HBsAg carriers among them. A low level (1.1%) of HBsAg carrier state was demonstrated. HBeAg was detected in 5.2% of women-carriers of HBsAg, anti-HBe in 68.8%. The follow-up observations involved 59 babies born to the mothers HBsAg-carriers. The babies were divided into an experimental and a control group. The experimental group consisted of 22 babies who were given specific anti-HBs immunoglobulin, 37 babies of the control group did not receive this preparation. In the experimental group, 3 babies were found to be infected, all of them at the age of 9-12 months. In the control group the infection was detected in 9 babies, among them in 5 the markers of hepatitis B virus were detected at the age of 1-2 months. Based on these data, the efficacy of using anti-HBs immunoglobulin for prevention of neonatal hepatitis B is discussed.


Bone mineral density and serum 25-hydroxyvitamin D in subtypes of idiopathic benign paroxysmal positional vertigo.
Although the etiology of benign paroxysmal positional vertigo (BPPV) is idiopathic in most cases, the association of osteoporosis or vitamin D deficiency with BPPV has attracted much interest recently. While it is generally accepted that osteoporosis or vitamin D deficiency is related to the occurrence and/or recurrence of BPPV, the difference in serum vitamin D level and bone mineral density (BMD) among different subtypes of BPPV has not been investigated. We aimed to compare T-score of BMD score and serum 25-hydroxyvitamin D level among idiopathic BPPV patients with a different subtype. This study included 117 consecutive patients with idiopathic BPPV (26 men and 91 women; mean age, 55 ± 11 years; age range, 25 to 78 years) who underwent blood sampling for serum 25-hydroxyvitamin D level measurement and bone mineral densitometry of the anterior-posterior lumbar spine and femur between April 2018 and February 2019. Among 117 patients, 49 were diagnosed with posterior semicircular canal (PSCC) BPPV, 24 were diagnosed with lateral semicircular canal (LSCC) canalolithiasis, and 44 were diagnosed with LSCC cupulolithiasis. The mean T-score of BMD was -1.5 ± 0.9 in PSCC BPPV, -1.5 ± 1.3 in LSCC canalolithiasis, and -1.5 ± 1.1 in LSCC cupulolithiasis, which was not significantly different (p = 0.998, One-way ANOVA test). The mean level of 25-hydroxyvitamin D was 22.5 ± 10.6 ng/ml in PSCC BPPV, 26.8 ± 16.0 ng/ml in LSCC canalolithiasis, and 25.4 ± 9.6 ng/ml in LSCC cupulolithiasis, which was not significantly different (p = 0.262, One-way ANOVA test). The proportion of osteoporosis/osteopenia or vitamin D deficiency/insufficiency did not show significant difference among idiopathic BPPV patients with different subtypes, and findings of this study indicate that either serum level of vitamin D or T-score of BMD is not a distinguishable characteristic among different subtypes of BPPV.


Trends in Fast-Food and Sugar-Sweetened Beverage Consumption and Their Association with Social Environmental Status in South Korea.
As South Korea has enjoyed rapid economic development, Koreans' diet, particularly consumption of fast food (FF) and sugar-sweetened beverages (SSBs), has changed. To examine time trends in FF and SSB consumption and their associations with social environmental status (SEnS) in South Korea. Korean National Health and Nutrition Examination Surveys (KNHANES) were a series of population-based cross-sectional surveys. Data from the KNHANES conducted in 1998, 2001, 2005, and 2007-2009 for 49,826 Koreans aged ≥1 year were used. Consumption of FF and SSBs were assessed by a 24-hour recall. We defined two FF categories (Western-style and Korean-style) and one SSB category. Sex, age, household income, and residence regions were investigated. The primary sampling units, strata, and sampling weights were taken into account using SAS survey-related procedures. Logistic regression models were used to test associations between SEnS and FF consumption. Over an 11-year period, the proportion of participants' who consumed Western FF and SSBs on the surveyed day doubled (P<0.05). Per capita energy contribution from Western FF also increased in adults, men, and low-income groups. SSB consumption doubled (per capita: 32 to 82 kcal/day, only consumers: 123 to 166 kcal/day), but consumption of Korean-style FF decreased (P<0.05). Compared with the low-income rural resident group, the high-income urban resident group was much more likely to consume Western FF (OR=26.7[3.7, 193.4]) and SSBs (odds ratio [OR]=3.1 [2.4, 4.1]) in 1998. However, in recent years, the patterns changed; the high-income urban resident group was more likely to consume Korean-style FF (OR=2.0[1.3, 2.9]) and SSBs (OR=1.7[1.3, 2.1]). In South Korea, people who reported consuming Western FF and SSBs on the surveyed day almost doubled during 1998-2009, whereas those who consumed Korean FF decreased. SEnS was related to FF and SSB consumption.


Knowledge, attitudes and practices of young adults towards HIV prevention: an analysis of baseline data from a community-based HIV prevention intervention study in two high HIV burden districts, South Africa.
With an HIV incidence of 1.00 skewed against women (1.51), adolescents in South Africa are at high HIV risk. This paper assesses young adults' (18-24 years) knowledge, attitudes and practices regarding HIV prevention in Nkangala and OR Tambo districts. A cross-sectional household survey was conducted in two districts in 2017/8. Participants completed computer-assisted self-interviews on HIV knowledge, attitudes, behaviour practices, use of social media and condom use at last sex (proxy for high-risk sex). HIV knowledge was assessed using the South African-adapted UNAIDS scale. Descriptive analyses were conducted and logistic regression models were built to assess factors associated with being knowledgeable of HIV and condom use at last sex. One thousand nine hundred fifty-five participants were interviewed (90% response rate). Less than half (44.7%) had correct knowledge of HIV prevention and 73% used a condom at last sex. Social media use predicted high HIV knowledge as higher odds were observed among participants using the print media (aOR1.87; 1.34-2.60), WhatsApp (aOR1.55; 1.26-1.90), radio/television (aOR2.75; 1.15-6.55) although social networking sites' use protected against knowledge acquisition (aOR0.53; 0.34-0.82). Females (aOR0.75; 0.58-0.97) and participants reporting sexual risk were less likely to have HIV knowledge as negative associations were found for having multiple sexual partners in the last 3 months (aOR0.63;0.48-0.82) and ever having sex (aOR0.37;0.23-0.61). Participants who abused drugs (aOR1.40; 1.05-1.88) and had attitudes accepting people living with HIV (aOR2.05; 1.14-3.69) had higher odds of having HIV knowledge. Females (aOR0.70; 0.54-0.91), students (aOR0.52; 0.40-0.66) and participants who abused drugs (aOR0.58; 0.43-0.77) were less likely to report condom use at last sex. There is a correlation between media use and HIV knowledge, non-condom use and HIV knowledge, and high-risk sexual behaviours and less HIV knowledge. An aggressive community media campaign utilising locally available, preferred and accessible media platforms among young adults is required for behaviour change.


Alteration of delta 9-tetrahydrocannabinol-induced teratogenicity by stimulation and inhibition of its metabolism.
Treatment of pregnant mice with delta 9-tetrahydrocannabinol (THC) significantly increased the incidence of in utero deaths. SKF-525A pretreatment increased the incidence of THC-induced in utero deaths. THC also significantly reduced the body weight of surviving fetuses. Phenobarbital treatment antagonized THC-induced reduction of fetal body weight, but did not reduce resorption rate. Administration of THC, 50 or 200 mg/kg, did not induce fetal anomalies. However, both SKF-525A and phenobarbital treatment potentiated THC-induced cleft palates. SKF-525A treatment plus THC produced 36% cleft palates. Phenobarbital treatment plus THC produced 77% cleft palates. Pretreatments altered the level of tetrahydrocannabinol plus metabolites found in plasma, placenta, fetus and amnionic fluid. In general, SKF-525A increased levels and phenobarbital decreased levels. Two chemically reactive metabolites of THC are proposed, 9,10-epoxyhexahydrocannabinol and an 11-oxo derivative. SKF-525A pretreatment increased the concentration of both of these metabolites. Phenobarbital treatment increased the levels of the proposed 9,10-epoxyhexahydrocannabinol. Possible covalent binding of THC was observed. An active metabolite theory may apply to the teratogenic properties of THC.


Cosmetic blepharoplasty.
Cosmetic blepharoplasty provides a satisfying solution to correct undesirable changes and provides substantial rejuvenation to the patient. The ability to perform procedures under local anesthesia combined with a relatively short recovery time makes blepharoplasty surgery highly satisfying for the patient. Detailed knowledge of the orbital anatomy, meticulous planning, and surgical technique are the keys to achieving the ideal outcome and meeting patient expectations.


Busin Guide vs Forceps for the Insertion of the Donor Lenticule in Descemet Stripping Automated Endothelial Keratoplasty.
To compare two insertion methods in Descemet stripping automated endothelial keratoplasty (DSAEK): Busin guide-assisted vs Forceps-assisted insertion of the corneal lenticule graft. Prospective, consecutive, comparative, nonrandomized study. setting: Cornea clinic at the Toronto Western Hospital. study population: Sixty-three eyes of 63 consecutive patients were included. All patients underwent DSAEK for Fuchs endothelial dystrophy, pseudophakic bullous keratopathy, aphakic bullous keratopathy, failed graft, or iridocorneo endothelial syndrome. Twenty-six consecutive donor discs were inserted with the Busin guide and 37 consecutive eyes underwent forceps assisted insertion of the donor. main outcome measures: Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest refraction, corneal endothelial cell loss, and postoperative complications. Busin guide-assisted DSAEK group had significantly worse UCVA and lower donor endothelial cell counts preoperatively. No significant differences were noted in the intraoperative or postoperative complications. Six months following surgery, BCVA was not significantly different between groups: 20/37 in the Busin guide-assisted DASEK group vs 20/42 in the Forceps-assisted group (P = .39). Mean spherical equivalent was -0.02 diopters (D) and 0.82 D (P = .06), and mean refractive cylinder was 2.2 D and 1.31 D (P = .0006), respectively. Endothelial cell loss was significantly lower in the Busin guide-assisted DASEK group: 25% loss vs 34.3% loss in the Forceps-assisted DSAEK group. (P = .04). Although visual outcomes were not different between the groups studied, Busin guide-assisted DSAEK resulted in lower percentage of endothelial cell loss compared with forceps insertion, six months following surgery.


Environmental factors influencing the quantitative distribution of microcystin and common potentially toxigenic cyanobacteria in U.S. lakes and reservoirs.
Many species of cyanobacteria are capable of producing toxins and causing nuisance blooms, however response to environmental conditions is likely taxon-specific. Environmental factors influencing cyanobacterial composition and toxin production in lakes have been examined in many studies; yet are often confined to individual water bodies, or to a small number of systems within the same region. Here, data from the 2012 USEPA National Lakes Assessment are used to examine relationships between biovolume of common potentially-toxigenic cyanobacteria (Aphanizomenon spp., Cylindrospermopsis spp., Dolichospermum spp., Microcystis spp. and Planktothrix spp.) and environmental variables across the entire conterminous United States, and results are compared across nine distinct ecoregions. Total phosphorus and water clarity were identified as the most influential environmental factors correlated with phytoplankton community composition. The Northern, Southern and Temperate Plains ecoregions displayed the highest biovolumes of potentially toxigenic taxa on average, as well as highest mean concentrations of microcystin. In those three ecoregions, samples with microcystin concentrations greater than 1 ppb were primarily dominated by Planktothrix spp. while in all other ecoregions Dolichospermum spp. was the dominant genus. Canonical Correlation Analysis revealed a strong association between high microcystin concentrations and high nutrient concentrations (total nitrogen and total phosphorus), and between high microcystin concentrations and low percentage of watershed forest cover. Results from this study indicate that the likely occurrence of potentially toxigenic taxa in lakes and reservoirs is predictable on a biogeographical basis, depending on morphological and water quality characteristics. Data from this study may be useful to regional managers attempting to prevent or mitigate nuisance cyanobacterial blooms.


Signaling pathways in cancer metabolism: mechanisms and therapeutic targets.
A wide spectrum of metabolites (mainly, the three major nutrients and their derivatives) can be sensed by specific sensors, then trigger a series of signal transduction pathways and affect the expression levels of genes in epigenetics, which is called metabolite sensing. Life body regulates metabolism, immunity, and inflammation by metabolite sensing, coordinating the pathophysiology of the host to achieve balance with the external environment. Metabolic reprogramming in cancers cause different phenotypic characteristics of cancer cell from normal cell, including cell proliferation, migration, invasion, angiogenesis, etc. Metabolic disorders in cancer cells further create a microenvironment including many kinds of oncometabolites that are conducive to the growth of cancer, thus forming a vicious circle. At the same time, exogenous metabolites can also affect the biological behavior of tumors. Here, we discuss the metabolite sensing mechanisms of the three major nutrients and their derivatives, as well as their abnormalities in the development of various cancers, and discuss the potential therapeutic targets based on metabolite-sensing signaling pathways to prevent the progression of cancer.


Directional recordings of somatosensory evoked potentials from the sensory thalamus in chronic poststroke pain patients.
The aim of this feasibility study was to investigate the properties of median nerve somatosensory evoked potential (SEPs) recorded from segmented Deep Brain Stimulation (DBS) leads in the sensory thalamus (VP) and how they relate to clinical and anatomical findings. We analyzed four patients with central post-stroke pain and DBS electrodes placed in the VP. Median nerve SEPs were recorded with referential and bipolar montages. Electrode positions were correlated with thalamus anatomy and tractography-based medial lemniscus. Early postoperative clinical paresthesia mapping was performed by an independent pain nurse. Finally, we performed frequency and time-frequency analyses of the signals. We observed differences of SEP amplitudes recorded along different directions in the VP. SEP amplitudes did not clearly correlate to both atlas-based anatomical position and fiber-tracking results of the medial lemniscus. However, the contacts of highest SEP amplitude correlated with the contacts of lowest effect-threshold to induce paraesthesia. SEP recordings from directional DBS leads offer additional information about the neurophysiological (re)organization of the sensory thalamus. Directional recordings of thalamic SEPs bear the potential to assist clinical decision-making in DBS for pain.


A case of de novo translocation 16;21: trisomy 16q phenotype and origin of the aberration.
A male newborn with severe congenital abnormalities is described with a de-novo translocation 16;21 resulting in trisomy 16q. Clinical features were consistent with trisomy 16q cases reported in the literature. Molecular analysis indicate a formation mechanism of the rearrangement restricted to postzygotic mitosis. Therefore, a low recurrence risk for the parents could be delineated.


Epidemiology of Pneumocystis colonization in families.
Whether Pneumocystis colonization is transmitted in families with human immunodeficiency virus (HIV)-infected members is unknown. Using nested polymerase chain reaction of oropharyngeal or nasopharyngeal samples, we detected colonization in 11.4% of HIV-infected adults and in 3.3% of their children, but there was no evidence of clustering.


Hydrogenation versus hydrogenolysis during alkaline electrochemical valorization of 5-hydroxymethylfurfural over oxide-derived Cu-bimetallics.
The electrochemical conversion of 5-Hydroxymethylfurfural, especially its reduction, is an attractive green production pathway for carbonaceous e-chemicals. We demonstrate the reduction of 5-Hydroxymethylfurfural to 5-Methylfurfurylalcohol under strongly alkaline reaction environments over oxide-derived Cu bimetallic electrocatalysts. We investigate whether and how the surface catalysis of the MOx phases tune the catalytic selectivity of oxide-derived Cu with respect to the 2-electron hydrogenation to 2.5-Bishydroxymethylfuran and the (2 + 2)-electron hydrogenation/hydrogenolysis to 5-Methylfurfurylalcohol. We provide evidence for a kinetic competition between the evolution of H2 and the 2-electron hydrogenolysis of 2.5-Bishydroxymethylfuran to 5-Methylfurfurylalcohol and discuss its mechanistic implications. Finally, we demonstrate that the ability to conduct 5-Hydroxymethylfurfural reduction to 5-Methylfurfurylalcohol in alkaline conditions over oxide-derived Cu/MOx Cu foam electrodes enable an efficiently operating alkaline exchange membranes electrolyzer, in which the cathodic 5-Hydroxymethylfurfural valorization is coupled to either alkaline oxygen evolution anode or to oxidative 5-Hydroxymethylfurfural valorization.


Modified-dropless protocol (nil intraocular) for micro-incision vitrectomy surgery (MIVS): a retrospective pilot study.
Perioperative infection and inflammation prophylaxis after ocular surgery has evolved over the years along with improvements in surgical equipment and a growing interest in alternatives to the standard topical eye drops. The purpose of this study is to evaluate the outcomes of a novel, modified-dropless protocol for 23-gauge (23-G), 25-gauge (25-G) and 27-gauge (27-G) micro-incision vitrectomy surgery (MIVS) that omits any intraocular injections of antibiotics or steroids. This Institutional Review Board-approved, single-surgeon retrospective study reviewed MIVS post-surgical outcomes in patients who received a modified-dropless protocol from February 2020 to March 2021. A total of 158 charts were reviewed, of which 150 eyes met the eligibility criteria. After each case, patients were administered a 0.5 cc subconjunctival injection of a 1:1 Cefazolin (50 mg/cc):Dexamethasone (10 mg/cc) in the inferior fornix and 0.5 cc of posterior Sub-Tenon's Kenalog (STK). No intravitreal injections were administered, and no pre- or postoperative antibiotic or steroid eye drops were prescribed. For patients allergic to penicillin, separate subconjunctival injections of 0.25 cc each of Vancomycin (10 mg/cc) and Dexamethasone (10 mg/cc) were administered. The primary safety parameter was postoperative cases of endophthalmitis. Secondary endpoints consisted of Best-Corrected Distance Visual Acuity (BCVA), intraocular pressure (IOP), and postoperative complications (retinal detachments, inflammation, need for additional surgery) within three months of surgery. Statistical analysis was performed using chi-square (χ²) tests for categorical values, and a Student's t-test to compare continuous outcomes. The majority of surgeries (96%) were performed with the 27G MIVS platform. There were no cases of postoperative endophthalmitis. Mean logMAR BCVA improved from 0.71 (± 0.67) to 0.61 (± 0.60) post-operatively (p = 0.02). Excluding patients who had silicone oil tamponade, postoperative BCVA improved from 0.67 (± 0.66) to 0.54 (± 0.55) (p = 0.003). Mean IOP increased from 14.6 (± 3.8) to 15.3 (± 4.1) (p = 0.05). Ten patients required further medication therapy for an increase in IOP, one had inflammatory signs, and 14 required a second surgical intervention mostly due to recurrences of initial surgical indication. A modified-dropless postoperative protocol involving subconjunctival and posterior sub-Tenon's injections only may be a safe and convenient alternative to topical eye drops for patients undergoing MIVS, but additional and larger studies are needed.


Knowledge, Attitudes, and Practices Towards COVID-19 Among Ecuadorians During the Outbreak: An Online Cross-Sectional Survey.
Preventing the transmission of SARS-CoV-2 (causative agent for COVID-19) requires implementing contact and respiratory precautions. Modifying human behavior is challenging and requires understanding knowledge, attitudes, and practices (KAPs) regarding health threats. This study explored KAPs among people in Ecuador. A cross-sectional, internet-based questionnaire was used to assess knowledge about COVID-19, attitudes toward ability to control COVID-19, self-reported practices related to COVID-19, and demographics. A total of 2399 individuals participated. Participants had moderate to high levels of knowledge. Participants expressed mixed attitudes about the eventual control of COVID-19 in Ecuador. Participants reported high levels of adoption of preventive practices. Binomial regression analysis suggests unemployed individuals, househusbands/housewives, or manual laborers, as well as those with an elementary school education, have lower levels of knowledge. Women, people over 50 years of age, and those with higher levels of schooling were the most optimistic. Men, individuals 18-29, single, and unemployed people took the riskiest behaviors. Generally, knowledge was not associated with optimism or with practices. Our findings indicate knowledge about COVID-19 is insufficient to prompt behavioral change among Ecuadorians. Since current COVID-19 control campaigns seek to educate the public, these efforts' impacts are likely to be limited. Given attitudes determine people's actions, further investigation into the factors underlying the lack of confidence in the ability of the world, and of Ecuador, to overcome COVID-19, is warranted. Edu-communicational campaigns should be accompanied by efforts to provide economically disadvantaged populations resources to facilitate adherence to recommendations to prevent the spread of the virus.


More evidence for low-dose aspirin in preventing pre-eclampsia.
Overview of: Henderson JT, Vesco KK, Senger CA, et al Aspirin use to prevent preeclampsia and related morbidity and mortality: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 2021;326:1192-1206.


Stiffness evaluation of contacting surfaces by bulk and interface waves.
This paper describes ultrasonic measurements of normal and tangential stiffnesses of the contacting interface between polished aluminum blocks subjected to nominal contact pressures up to about 3.8 MPa. These stiffnesses were evaluated by ultrasonic spectroscopy methods for the bulk (longitudinal and transverse) wave reflection coefficients and the anti-symmetric mode interface wave velocity. The measurements revealed the interfacial stiffnesses as functions of the frequency as well as the applied contact pressure. The ratio of the tangential and normal stiffnesses is discussed in the light of foregoing theoretical and experimental findings. Furthermore, possible explanations for the frequency dependence of the measured stiffnesses are reviewed, invoking the spatial inhomogeneity of the interfacial stiffness as well as its lossy nature.


Glutathione Transferase as a Potential Marker for Gut Epithelial Injury versus the Protective Role of Breast Milk sIgA in Infants with Rota Virus Gastroenteritis.
Secretory immunoglobulin A (SIgA) plays an important protective role in the recognition and clearance of enteric pathogens. This study was designed to assess if mucosal integrity "measured by secretory IgA (SIgA)" is a protective factor from more epithelial alteration "measured by glutathione transferase" in infants with Rota gastroenteritis and its relation to infants' feeding pattern. This study was conducted on 79 infants aged 6 months and less from those diagnosed as having gastroenteritis and admitted to Gastroenteritis Department in Abo El Rish Pediatric Hospital, Cairo University. Plasma glutathione s-transferases and Stool SIgA were measured using ELISA technique. Rota virus detection was done by Reverse transcriptase PCR. SIgA was found to be significantly positive in exclusive breast fed infants, Glutathione transferase was significantly more frequently positive in Rota positive cases than Rota negative cases by Reverse transcriptase PCR. A significant negative correlation between Glutathione transferase and Secretory IgA was found, (p < 0.05). Breast feeding should be encouraged and highly recommended in the first two years of life as it provides Secretory IgA to breast fed infants who in turn protect them against epithelial damage caused by Rota viral gastroenteritis.


Painting unknown worlds.
This paper sets out to discover more about the name 'Tarrant' whose ophthalmic paintings have regularly featured in ophthalmic textbooks over the past 50 years. Through a series of telephone calls, I have spoken to Tarrant about his life and work while I research the origins of ophthalmic illustrations charting the story behind this art movement. The paper also explores the eventual decline of retinal painting and the emergence of photography, concluding that due to the continuing advance of technology the ophthalmic photographer may eventually succumb to the same fate as the artist.


Comparison of pretreatment strategies of sugarcane baggase: experimental design for citric acid production.
Solid state fermentation was carried out to compare efficiency of acid, alkaline and urea pretreatment of sugarcane bagasse for production of citric acid using Aspergillus niger ATCC 9142. Plackett-Burman statistical design was used to evaluate significance of variables. Pretreatment of bagasse by urea was known as the most influential treatment to increase citric acid production (137.6g/kg of dry sugarcane bagasse and citric acid yield of 96% based on sugar consumed). Finally, up scaling was achieved to a 20L solid state fermentor in which humidity was constant in gas phase and urea-treated sugarcane bagasse. The produced acid concentration and yield in fermentor was 82.38g/kg of dry substrate and 26.45g/kgday, respectively.


The effect of recombinant human insulin-like growth factor-I on chronic puromycin aminonucleoside nephropathy in rats.
We recently demonstrated that recombinant hGH exacerbates renal functional and structural injury in chronic puromycin aminonucleoside (PAN) nephropathy, an experimental model of glomerular disease. Therefore, we examined whether recombinant human (rh) IGF-I is a safer alternative for the treatment of growth failure in rats with chronic PAN nephropathy. The glomerulopathy was induced by seven serial injections of PAN over 12 wk. Experimental animals (n = 6) received rhIGF-I, 400 micrograms/d, whereas control rats (n = 6) received the vehicle. rhIGF-I improved weight gain by 14% (p < 0.05), without altering hematocrit or blood pressure in rats with renal disease. Urinary protein excretion was unaltered by rhIGF-I treatment in rats with chronic PAN nephropathy. After 12 wk, the inulin clearance was higher in rhIGF-I-treated rats, 0.48 +/- 0.08 versus 0.24 +/- 0.06 mL/min/100 g of body weight in untreated PAN nephropathy animals, p < 0.05. The improvement in GFR was not associated with enhanced glomerular hypertrophy or increased segmental glomerulosclerosis, tubulointerstitial injury, or renal cortical malondialdehyde content. In rats with PAN nephropathy, administration of rhIGF-I increased IGF-I and GH receptor gene expression, without altering the steady state level of IGF-I receptor mRNA. In normal rats with intact kidneys, rhIGF-I administration (n = 4) did not alter weight gain, blood pressure, proteinuria, GFR, glomerular planar area, renal cortical malondialdehyde content, or glomerular or tubulointerstitial damage, compared with untreated animals (n = 4). rhIGF-I treatment reduced the steady state renal IGF-I mRNA level but did not modify gene expression of the IGF-I or GH receptors. We conclude that: 1) administration of rhIGF-I improves growth and GFR in rats with chronic PAN nephropathy and 2) unlike rhGH, long-term use of rhIGF-I does not worsen renal functional and structural injury in this disease model.


Distinguishing Barrett gastric foveolar dysplasia from reactive cardiac mucosa in gastroesophageal reflux disease.
Morphologic dysplasia remains the criterion standard of cancer risk in Barrett esophagus but poses many challenges including distinction from reactive inflammatory change. Gastric foveolar dysplasia, a newly described subtype comprising 15% to 20% of Barrett dysplasia, overlaps with reactive cardiac mucosa in gastroesophageal reflux disease (GERD). Despite the clinical importance of accurate distinction, the issue has not been studied. Review of 3698 biopsies from 461 Barrett patients yielded 160 biopsies with Barrett gastric foveolar dysplasia (74 low grade and 86 high grade). These were compared with inflamed cardia from 80 patients with GERD. Immunohistochemistry was performed for Lgl2, MUC2, MUC5AC, and MUC6. Comparing GERD with Barrett gastric foveolar dysplasia, surface nuclear stratification (85% versus 0%, P < .00001), upper mucosa-limited atypia (80% versus 0%, P < .0001), villiform architecture (52% versus 4%; P < .0001), full-thickness mucosal atypia (0% versus 100%, P < .00001), and crowded glandular architecture (0% versus 75%, P < .00001) all proved useful. Cytologic features were less helpful. Comparing low-grade gastric dysplasia alone, because its distinction from reactive cardia may be even more challenging, the listed features all remained significant. Loss or aberrant Lgl2 expression was much more typical of dysplasia (12% versus 99%; P = .0001). MUC proteins did not distinguish the groups. Surface nuclear stratification, "top-heavy" atypia, and noncrowded, villiform architecture were highly characteristic of reactive cardiac atypia in GERD, in comparison with the monolayered nuclei in crowded glands occupying the full mucosal thickness in Barrett gastric foveolar dysplasia. Loss or aberrant Lgl2 staining was useful in identifying Barrett gastric foveolar dysplasia.


Association study of the three functional polymorphisms (TAS2R46G>A, OR4C16G>A, and OR4X1A>T) with recurrent pregnancy loss.
This study was purposed to investigate whether genetic polymorphisms in the function of stop-gain are associated with a fetal or placental development play roles and a development of idiopathic recurrent pregnancy loss (RPL) in Korean females. Three stop-gain polymorphisms were selected using next-generation sequencing screening, which allows for the rigorous examination and discovery of previously uncharacterized stop-gain genes and stop-gain expression profiles. Accordingly, we investigated the association of stop-gain polymorphisms in Korean women with RPL. Three functional polymorphisms in the TAS2R46G>A (rs2708381), OR4C16G>A (rs1459101), and OR4X1A>T (rs10838851) genes were genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism assays and real-time PCR analysis. We determined that the OR4C16G>A polymorphism was associated with idiopathic RPL in Korean women (Adjusted odds ratio [AOR] 1.782; 95% confidence interval [CI] 1.004-3.163; P = 0.048, and AOR 1.766; 95% CI 1.020-3.059; P = 0.042). In addition, the prevalence of RPL was increased in women with the OR4C16GA + AA genotype and blood coagulation measures of prothrombin time (PT) > 10.4 s (AOR 8.292; 95% CI 2.744-25.054). We suggest that the OR4C16G>A polymorphism might serve as a clinically useful biomarker for the development, prevention, and prognosis of RPL.


Cholesterol interaction with the related steroidogenic acute regulatory lipid-transfer (START) domains of StAR (STARD1) and MLN64 (STARD3).
The steroidogenic acute regulatory (StAR)-related lipid transfer (START) domains are found in a wide range of proteins involved in intracellular trafficking of cholesterol and other lipids. Among the START proteins are the StAR protein itself (STARD1) and the closely related MLN64 protein (STARD3), which both function in cholesterol movement. We compared the cholesterol-binding properties of these two START domain proteins. Cholesterol stabilized STARD3-START against trypsin-catalyzed degradation, whereas cholesterol had no protective effect on STARD1-START. [(3)H]Azocholestanol predominantly labeled a 6.2 kDa fragment of STARD1-START comprising amino acids 83-140, which contains residues proposed to interact with cholesterol in a hydrophobic cavity. Photoaffinity labeling studies suggest that cholesterol preferentially interacts with one side wall of this cavity. In contrast, [(3)H]azocholestanol was distributed more or less equally among the polypeptides of STARD3-START. Overall, our results provide evidence for differential cholesterol binding of the two most closely related START domain proteins STARD1 and STARD3.


[The diagnostic value of perforin and granzyme B genes mRNA expression in acute rejection after hamster to rat orthotopic liver transplantation].
To explore the mRNA expression of perforin and granzyme B genes activated by cytotoxic T lymphocytes (CTL) for monitoring early acute rejection after liver transplantation. The mRNA expression of perforin and granzyme B genes in grafts after gold hamster to rat liver transplantation was examined by reverse transcriptase polymerase chain reaction. Histological findings were studied comparatively, and isogenic rat liver transplantation was the control. The mRNA expression of perforin and granzyme B genes began to be up-regulated on the day 3 after transplantation, when no histologic evidence of rejection was found. Levels of expression significantly increased after day 4 and persisted through the whole course of rejection. In contrast, the control group showed no expression of mRNA for perforin and granzyme B. The determination of mRNA expression of perforin and granzyme B genes are useful to early diagnosis of acute rejection of liver transplantation.


Glucose versus glucose-fat mixture in the course of total parenteral nutrition: effects on substrate utilisation and energy metabolism in malnourished children.
Energy substrate utilisation was evaluated over 21 days in two groups of malnourished children on total parenteral nutrition (TPN). Non-protein energy was infused as glucose (Group A; n = 7) or as a glucose/fat (1:1 v/v) mixture (Group B; n = 10). Results indicated that: 1) net glucose oxidation was related to glucose intake; 2) glucose storage was elevated in group A; 3) net fat synthesis occurred earlier in group B together with constant net fat oxidation which was inversely related to glucose intake (r = -0.89, p < 0.001); 4) lipogenesis from glucose occurred only when glucose intake exceeded 19.3g/kg/d; 5) energy expenditure increased by 36% (group A) and 18% (group B) during renutrition; 6) 73% and 82% of the energy administered in excess of energy required was stored in group A and B respectively. Hence, glucose/fat infusion appears to be more energy-efficient than glucose-alone in TPN of malnourished children.


[Determination and clinical application of the lecithin/sphingomyelin ratio in amniotic fluid by high performance liquid chromatography].
The lecithin/sphingomyelin (L/S) ratios in standard solution and amniotic fluid of 64 pregnant women were measured by high performance liquid chromatography (HPLC). The procedure is highly accurate, and the correlation coefficient between the HPLC value and standard solution was 0.984. The regression line was: Y = 0.8X + 0.17 (Y: standard solution X: HPLC values). In 64 pregnant women, 41 cases were delivered within 72 hrs of the amniotic fluid collection. The prediction of respiratory distress syndrome (RDS) was performed with variables of the L/S ratio less than 4.20. 8 of 9 babies (88.9% of sensitivity) who developed RDS and 3 of 3 (100% of sensitivity) other types of respiratory failure due to hydrothorax were predicted by this method. In conclusion, this method is simple, rapid and sensitive for the prediction of respiratory distress syndrome and other respiratory failure.


Antibacterial effect and wound healing ability of silver nanoparticles incorporation into chitosan-based nanofibrous membranes.
Silver nanoparticles (AgNPs) are widely explored to enhance the antibacterial property of medical devices such as wound dressings. However, no consensus has been reached on the efficacy and safety of AgNP incorporation. This study aimed (1) to elucidate the effect of proteins and inorganic ions on the antibacterial properties, (2) to confirm the antibacterial efficacy in vivo, and (3) to evaluate the wound healing ability of AgNPs incorporation into chitosan-based membranes. Three membranes with different amount of AgNPs were prepared. The antibacterial properties and silver release profile were evaluated after interacting with phosphate buffered saline or with serum in vitro. The antibacterial efficacy and the wound healing ability were explored in vivo. The results indicated that the biological environment had strong influences on the silver release: the inorganic ions resulted in a slow release whereas the proteins formed a barrier to block the silver release. Consequently, high amount of AgNPs incorporation was necessary to achieve in vivo antibacterial effects. Moreover, the addition of AgNPs did not alter the wound healing rate and tissue response. We can conclude that the AgNP incorporation can enhance antibacterial efficacy of biomaterials without altering the wound healing ability of the chitosan-based membranes.


Neural responses in cat visual cortex reflect state changes in correlated activity.
Cortical state is characterized by ongoing rhythmic neural activity. Changes in rhythmic activity and thus in cortical state are shown to occur spontaneously in the anesthetized cat. We were interested in whether these state changes have an affect on the cortical processing of sensory stimuli. This was investigated by recording spontaneous and stimulus-evoked local field potentials and multi-unit neuronal activity (MUA) from trans-cortical electrode arrays in the visual cortex of the anesthetized cat. Changes in cortical state were identified by calculating the cross-correlation strength and cross-coherency, between MUA channels at different layers and on separate electrode arrays. Spontaneous changes in rhythmic activity were associated with changes in the strength of stimulus-evoked multiple unit responses of cortical neurons. The highest multi-unit responses were found in periods when low-frequency rhythms of the electroencephalogram increase in magnitude and high-frequency rhythms decrease. Such changes in evoked responses were maximal at layer IV, the input layer of the visual cortex. Our findings suggest that stimulus response magnitude depends on rhythmic state and reflects changes in functional connectivity within the visual cortex.


The interaction of micro/nano plastics and the environment: Effects of ecological corona on the toxicity to aquatic organisms.
Concerns about the micro/nano plastics (MNPs) exposure risks have risen in recent years. The ecological corona (EC), which is generated by the interaction between MNPs and environmental substances, has a significant impact on their environmental fate and ecological risks. As the largest sink of MNPs, the aquatic environment is of great significance for understanding the environmental behaviour of MNPs. Transmission Electron Microscope (TME), Fourier Transform Infra-Red (FTIR), Scanning Electron Microscope (SEM), Dynamic Light Scattering (DLS) and other analytical methods have been used as effective methods to analyse the formation process of EC and detect the existing EC directly or indirectly on the surface of MNPs. The physicochemical properties of MNPs, complex aquatic environments and ageing time have been identified as the key factors affecting EC formation in aquatic environments. Moreover, the EC absorbed on MNPs significantly changed their environmental behaviour and toxicity to aquatic organisms. This review gives a full understanding of the EC formation progress on the surface of MNPs and different analytical methods for EC have been summarised which can further assist the ecological risk assessment of MNPs in the aquatic environment.


Effects of high-intensity inspiratory muscle warm-up on inspiratory muscle strength and accessory inspiratory muscle activity.
This study aimed to determine the effects of work-matched moderate-intensity and high-intensity inspiratory muscle warm-up (IMW) on inspiratory muscle strength and accessory inspiratory muscle activity. Eleven healthy men performed three IMWs at different intensities, namely, placebo, moderate-intensity, and high-intensity, set, respectively, at 15 %, 40 %, and 80 % of maximal inspiratory mouth pressure (MIP). MIP was measured before and after IMW. Electromyography (EMG) was recorded for the sternocleidomastoid muscle (SCM) and intercostal muscles (IC) during IMW. MIP increased significantly in the moderate-intensity condition (104.2 ± 5.1 %, p < 0.05) and high-intensity condition (106.5 ± 6.2 %, p < 0.01) after IMW. The EMG amplitudes of the SCM and IC during IMW were significantly higher in the order of high-intensity, moderate-intensity, and placebo conditions. There was a significant correlation between changes in MIP and EMG amplitude of the SCM (r = 0.60, p < 0.01) and IC (r = 0.47, p < 0.01) during IMW. These findings suggest that high-intensity IMW increases neuromuscular activity in the accessory inspiratory muscles, which may improve inspiratory muscle strength.


Chronic UVB exposure enhances in vitro percutaneous penetration of 5-aminulevulinic acid in hairless mouse skin.
(Pre)cancerous skin lesions accumulate more protoporphyrin IX (PpIX) upon topical application of 5-aminolevulinic acid (ALA) than the surrounding normal skin. This might be the result of a higher percutaneous penetration of ALA into (pre)cancerous skin. ALA penetration through (1) healthy skin with intact stratum corneum, (2) healthy skin with reduced stratum corneum (i.e. tape stripped skin) and (3) diseased skin with dysplastic and thickened epidermis (chronically UVB-exposed skin) was determined in an in vitro model with hairless mouse skin. More ALA had penetrated through chronically UVB-exposed skin than through normal non-exposed skin after 8 hours ALA application. The amount of ALA penetrated through chronically UVB-exposed skin was smaller than through tape stripped skin. The stratum corneum barrier function is less effective in chronically UVB-exposed skin than in normal non-exposed skin, but more effective than in tape stripped skin. A higher penetration rate of ALA into (pre)cancerous lesions may be (partly) responsible for the greater accumulation of PpIX in such lesions.


Contractile properties of the human triceps surae with some observations on the effects of temperature and exercise.
The contractile properties of the triceps of five healthy male subjects (mean age 22 years) during electrically stimulated and voluntary isometric muscle contractions were investigated and some observations made on the effects of muscle heating and cooling and dynamic exercise. The times to peak twitch tension (TPT) and half relaxation time (1/2RT) were 111 +/- 20 ms and 83 +/- 13 ms respectively. Heating and prior exercise decreased, and cooling severely prolonged, TPT and 1/2RT. Exercise and heating had no effect on supramaximal twitch tension (Pt0) but cooling the muscle to a temperature of 24.3 degrees C reduced it by 52%. The effects of repetitive stimuli on Pt0 were dependent on frequency; at 0.2 Hz potentiation was observed but at 2 Hz, Pt0 was depressed under control conditions. Heating had no effect on these responses but cooling reversed the 2 Hz and abolished 0.2 Hz response. Post-tetanic potentiation of the twitch was observed under all conditions of measurement. At submaximal stimulation voltages, heating and exercise enhanced twitch and tetanic tensions, but at supramaximal voltages heating reduced tetanic tension (P0) at 10 Hz (by 115 N), though not at 20 Hz. Exercise decreased P0 at both frequencies of stimulation. Cooling significantly reduced the maximal voluntary contraction and P0 at 20 Hz. At submaximal voltages, heating enhanced and cooling severely depressed tetanic tensions at high frequency (100 Hz) stimulation. A 2-min fatigue test was unaffected by heating but cooling reduced force generation at the onset of, and the decline of force during, the test. It was concluded that studies of the contractile properties of human muscle in vivo should be based on supramaximal stimulation, and that temperature and prior exercise should be carefully standardised in order to obtain reliable and meaningful results.


Immunomodulatory effect of a proprietary polyherbal formulation on healthy participants: A single- blind, randomized, placebo- controlled, exploratory clinical study.
Clinical study for immunity. The present study aimed to assess the effect of proprietary polyherbal formulation (PPHF), labelled as Kofol immunity tablets (KIT) on innate and adaptive immune responses in healthy individuals, on the backdrop of COVID-19 pandemic. Single-blind, randomized, placebo-controlled, exploratory study in institutional setting. Post Ethics Committee permission, screened healthy individuals of either sex aged 18-35 years were randomized to PPHF/Placebo for 2 months. Major assessment variables included peak expiratory flow rate (PEFR), questionnaire-based immune status, perceived stress, and quality of life (QOL) with immune-specific cell counts (CD4+, CD8+), cytokines (interferon gamma [IFN-γ], tumor necrosis factor-alpha [TNF-α], interleukin 10 [IL-10]), and oxidative stress in red blood cells (RBCs) (malondialdehyde (MDA), glutathione peroxidase [GPx]), done at day 60. Mean ± standard deviation and paired/unpaired t-test for parametric data analysis while median (range) and Wilcoxon Rank sum test/Mann-Whitney test for nonparametric data analysis, were done. Categorical data was analyzed using Chi-square test. GraphPad InStat software, version 9 was used with p < 0.05, as the level of statistical significance. Of 52 recruited, 28 individuals completed the study. PPHF significantly increased PEFR, improved immune status along with QOL compared to baseline. It also decreased perceived stress from moderate and severe grade to mild. Serum IFN-γ levels remained almost constant post-PPHF treatment. PPHF significantly decreased MDA and increased GPx in RBCs. Significant decrease and increase in TNF-α and IL-10, respectively, were seen in PPHF group. The safety parameters post-PPHF treatment remained within normal reference ranges. PPHF is an efficacious and safe formulation with immunomodulatory potential.


The effects of dopamine on renin release in the isolated perfused rat kidney.
In the isolated and perfused kidney of the rat, the stimulant effect of dopamine on renin release is blocked by propranolol and not by haloperidol. This suggests that the release of renin induced by dopamine is due to the activation of beta-receptors.


Cis-acting induction of adenovirus transcription.
At early times after adenovirus infection, transcription from all early viral promoters requires the expression of a 289 amino acid phosphoprotein encoded in the pre-early transcription unit E1A. Mutations in E1A result in a marked delay in the induction of early viral transcription. To distinguish between possible models that could account for this delayed transcription, superinfection experiments were performed. Cells were first infected with one E1A mutant, incubated until viral transcription was detectable, and then superinfected with a second E1A mutant with distinguishable transcripts from early region 3 (E3). We found that the second virus to infect the cell recapitulated the delayed transcription induction of E3. Therefore, the delayed expression of early regions after infection with E1A mutants is the result of a time-dependent cis-acting modification of the template. Models which can account for these observations and for the function of E1A protein are discussed.


Estriol concentrations in urine and serum in patients with various intestinal diseases.
Pregnant women with ulcerative colitis shows frequently low estriol values in both serum and urine. 18 patients with ulcerative colitis, 4 patien;s with mb. Crohn, and 3 patients with a by-pass operation were examined. Low estriol concentrations were seen only in the patients with ulcerative colitis especially in patients, where an operation has been performed. In one patient with severe diarrhea the estriol concentration in serum was low until the intestinal function normalised and the estriol concentration went up exactly when the diarrhea stopped. However, no unequivocal connection between low estriol concentrations and diarrhea could be demonstrated.


Determination of sub-nanogram amounts of dihydroergotamine in plasma and urine using liquid chromatography and fluorimetric detection with off-line and on-line solid-phase drug enrichment.
A highly sensitive and selective high-performance liquid chromatographic method, involving sample pre-treatment, column switching and fluorimetric detection, is described for the determination of dihydroergotamine in plasma and urine samples. The pre-chromatographic sample treatment consists of extraction by means of an Extrelut column for plasma samples, and pre-separation with enrichment steps on a Sep-Pak column for urine samples. The samples are then injected onto a pre-separation column (Aquapore), and the fraction containing dihydroergotamine are automatically diverted onto an analytical column (ODS reversed phase). An acetonitrile-ammonium carbamate gradient is used as the mobile phase. High recovery of dihydroergotamine from both plasma (87%) and urine (100%) and a detection limit as low as 100 pg/ml were achieved, with a linear response up to 5 ng/ml. The assay demonstrated a high degree of selectivity with regard to the extensive metabolism of dihydroergotamine especially to the main metabolite 8'-hydroxydihydroergotamine. The assay was successfully applied for more than one year to the determination of plasma and urine concentrations of dihydroergotamine after parenteral administration.


Age-appropriate cognition and subtle dopamine-independent motor deficits in aged tau knockout mice.
The microtubule-associated protein tau is expressed throughout the nervous system, most highly in neurons but also in glial cells. Its functions in adult and aging mammals remain to be defined. Previous studies in mouse models found either protective or detrimental effects of genetic tau ablation. Though tau ablation prevented synaptic, network, and cognitive dysfunctions in several models of Alzheimer's disease and made mice more resistant to epileptic seizures, a recent study described a parkinsonian phenotype in aging Tau knockout mice. Here we tested cognition and motor functions in Tau(+/+), Tau(+/-), and Tau(-/-) mice at approximately 1 and 2 years of age. Tau ablation did not impair cognition and caused only minor motor deficits that were much more subtle than those associated with the aging process. Tau ablation caused a mild increase in body weight, which correlated with and might have contributed to some of the motor deficits. However, tau ablation did not cause significant dopaminergic impairments, and dopamine treatment did not improve the motor deficits, suggesting that they do not reflect extrapyramidal dysfunction.


Whole-exome sequencing identified mutational profile of a case with T-cell chronic lymphocytic leukemia.
We believe that our report and further case reports on T-cell chronic lymphocytic leukemia with genetic profile will contribute to the molecular classification of this rare but distinct disease.


Awareness, acceptability, and satisfaction of teledermatology consultation among social-media users in Nepal.
Teledermatology refers to the use of telecommunication in consulting one's skin problem to a dermatologist at distance. This study aims to identify the awareness, acceptability, preferred technical tools, willingness to use, comfortability, and satisfaction of teledermatology among social-media users in Nepal. It was an exploratory cross-sectional study performed on 360 social-media users, subjected to web-based interview based on pretested proforma containing questions to address: awareness of telemedicine, type and tools preferred for teledermatology, willingness to use, comfortability, and satisfaction of teledermatology services. Most of the participants (60.8%) were initially unaware of telemedicine. Despite this, the majority (81.9%) were willing to use the services after being aware, mostly during the follow-up (36.6%). Most of the participants (61.1%) preferred the hybrid model for teleconsultation, while mobile was the preferred technical tool (68.1%) mostly because of its compatibility (84.1%) and portability (56.3%). The majority of the participants felt that teledermatology consultation would be beneficial (77.2%) and they mostly preferred it directly from a dermatologist (85.6%). About two-thirds (64.2%) also believed that teledermatology consultation would eliminate the need for a face-to-face consultation. The majority would be comfortable (68.1%) if their skin lesions are photographed and sent to a dermatologist and would be satisfied (62.5%) with the consultations, through Wi-Fi and mobile data both (55.6%), and via Facebook (97.2%) and Viber (70.8%). Despite being unaware of telemedicine, the participants were willing to use teledermatology consultation and thought that they would be comfortable and satisfied with it.


Unexpected positive effects of myocardial infarction on couples.
This article describes a small-scale study of five couples that was conducted after the husbands had recovered from a heart attack. According to the findings, two of the couples reported that the recuperative period lent a clearly positive dimension to an otherwise threatening experience.


[Analysis of food and energy value of the menu of some municipal pre-school educational institutions of the Kaliningrad Region].
Evaluation of nutrition allows one to foresee the possibility of occurrence of various developmental disorders of children, including diseases associated with the metabolic syndrome. At an early age, not only eating habits are laid, but the foundation for future physical and mental health is created. Lack of attention to compliance with the physiological norms of nutrition can lead to significant economic losses upon the transition of this generation to the status of the economically active population. Aim - an analysis of children's diets in municipal pre-school educational institutions (kindergarten) in Kaliningrad. We investigated the nutrition of children aged 4-7 years based on a 10-day menu of three full-time kindergarten in Kaliningrad. The actual consumption of meals by the weight method of 9 groups of children (an average of 30 people) was also determined. The content of nutrients was assessed for compliance with the physiological requirements. By assessing the array of data on the nutritional value of the diet presented, the main marker indicators of diet compliance with physiological needs were determined, such as animal protein content, PUFA level, the ratio of mineral substances: sodium and potassium, calcium, magnesium and phosphorus. The protein content in the diet exceeded the physiological need by 10-14%, while the plant protein prevailed. There was a slight deficit of polyunsaturated fatty acids due to inadequate consumption of fish; carbohydrate intake was within normal limits. The sodium content in the rations significantly exceeded norm (on average, 1800 mg per day), due to the frequent inclusion of dishes with components with high salinity and hidden salt. Despite the inclusion of cottage cheese in the ration, the average calcium content was 18% lower than the recommended level. Vitamin A consumption was about 50% of the physiological norm. It was established, in general, that the studied menu were brought into compliance with the physiological norms. It is recommended to provide a variety of menus by introducing animal protein into the rations through the use of fermented dairy products and fish dishes. It is recommended to use local species of aquatic biological resources in order to reduce the price load in the formation of the menu. Suggestions for improving the menu allowing to significantly reduce sodium consumption by changing the formulations of some salads except for the use of salted and pickled vegetables are justified.


Quality of Life Among Breast and Colon Cancer Patients Before and After First-Cycle Chemotherapy.
This study aimed to compare the functioning, symptoms, and quality of life (QoL) of patients with breast or colon cancer before and after their first-cycle (FC) chemotherapy. One-group pretest/posttest design. The study utilized the standardized Arabic-translated Quality of Life Questionnaire Version 3 from the European Organization for Research and Treatment of Cancer in measuring the functioning, symptoms, and QoL of 120 Saudi patients diagnosed with breast or colon cancer. Dependent t test was used in analyzing the presence of significant differences in mean scores before and after chemotherapy with periods ranging from 14 days to 21 days following the treatment protocol. The findings revealed significant differences in the functioning, symptoms, and QoL among patients with breast or colon cancer before and after FC chemotherapy (p < .001). Baseline scores showed higher physical, role, emotional, cognitive, and social functioning; lesser symptoms; lower financial difficulties; and better overall global health status compared to post-FC chemotherapy. Assessing the QoL of patients with breast or colon cancer undergoing FC chemotherapy is essential to establish a holistic care plan in supporting and alleviating the unfavorable effects of chemotherapy and implement patient-centered interventions that aid in the enhancement of their overall QoL.


Analyses of Protein Turnover at the Cell Plate by Fluorescence Recovery After Photobleaching During Cytokinesis.
Membrane trafficking is central to cell plate construction during plant cytokinesis. Studies on cell plate formation can provide answers to basic biology questions including molecular mechanisms of membrane trafficking, tissue patterning, and cytoskeletal dynamics. Consequently, a detailed understanding of cytokinesis depends on the characterization of molecules that function in the formation, transport, targeting, and fusion of membrane vesicles and delivery of proteins to the developing and maturing plate. This chapter describes a pipeline based on fluorescence recovery after photobleaching (FRAP) to measure and analyze turnover of peripheral or transmembrane proteins on the cell plate. The approach described here can also be applied in other biological contexts.


Genome-wide analysis of the SMXL gene family in common bean and identification of karrikin-responsive PvSMXL2 as a negative regulator of PEG-induced drought stress.
Common bean (Phaseolus vulgaris L.) is a major legume crop worldwide, but its growth and development frequently face challenges due to abiotic stresses, particularly drought. Proper supplement of copper could mitigate the adverse effects of drought, but excessive accumulation of this metal in plants can be harmful. The suppressor of MAX2 1-like (SMXL) gene family, which plays important roles in various plant processes, including stress responses, remains poorly understood in common bean. In this study, we identified nine orthologues of SMXL genes in common bean, which are located on six chromosomes and classified into four subgroups. Basic molecular properties, including theoretical isoelectric point (PI), molecular weight (MW), grand average of hydropathicity (GVIO), gene structure, and conserved motifs were characterized, and numerous cis-elements in promoters were predicted. The expression patterns of PvSMXL genes were found to be distinct under 10% polyethylene glycol (PEG)-induced drought stress and 200 μM Cu treatments. Most PvSMXLs showed reduced expression in response to Cu treatment, whereas nearly half PvSMXLs exhibited inducible expression under drought stress. PvSMXL2, which exhibited a rapid response to karrikin 1 (KAR1), an active form of the plant growth regulators newly found in the smoke of burning plant material, was down-regulated by both PEG-induced drought and Cu stresses. Transient silencing of PvSMXL2 resulted in enhanced drought stress tolerance without conferring Cu tolerance. These findings provide valuable insights into the functions of SMXL genes in common bean under abiotic stress conditions.


The molecular basis of spinocerebellar ataxia type 48 caused by a de novo mutation in the ubiquitin ligase CHIP.
The spinocerebellar ataxias (SCAs) are a class of incurable diseases characterized by degeneration of the cerebellum that results in movement disorder. Recently, a new heritable form of SCA, spinocerebellar ataxia type 48 (SCA48), was attributed to dominant mutations in STIP1 homology and U box-containing 1 (STUB1); however, little is known about how these mutations cause SCA48. STUB1 encodes for the protein C terminus of Hsc70 interacting protein (CHIP), an E3 ubiquitin ligase. CHIP is known to regulate proteostasis by recruiting chaperones via a N-terminal tetratricopeptide repeat domain and recruiting E2 ubiquitin-conjugating enzymes via a C-terminal U-box domain. These interactions allow CHIP to mediate the ubiquitination of chaperone-bound, misfolded proteins to promote their degradation via the proteasome. Here we have identified a novel, de novo mutation in STUB1 in a patient with SCA48 encoding for an A52G point mutation in the tetratricopeptide repeat domain of CHIP. Utilizing an array of biophysical, biochemical, and cellular assays, we demonstrate that the CHIPA52G point mutant retains E3-ligase activity but has decreased affinity for chaperones. We further show that this mutant decreases cellular fitness in response to certain cellular stressors and induces neurodegeneration in a transgenic Caenorhabditis elegans model of SCA48. Together, our data identify the A52G mutant as a cause of SCA48 and provide molecular insight into how mutations in STUB1 cause SCA48.


Assessing the risk of oil spill impacts and potential biodiversity loss for coastal marine environment at the turn of the COVID-19 pandemic event.
The Tuscan Archipelago, with its great environmental and economic importance, is one of the highest oil spill density areas in the Western Mediterranean. In this study, an interdisciplinary approach, based on numerical applications and experimental methods, was implemented to quantify the risk of oil spill impact along the rocky shores of this archipelago in relation to the maritime activities. The risk, defined as a combination of the hazard and the damage, was quantified for the biennial 2019-2020 in order to account for the effects generated by the COVID-19 pandemic restrictions on the local maritime traffic. A high-resolution oceanographic and particle tracking model was applied to simulate the trajectories of possible oil spill events and to quantify the hazard of impacts on the coast of numerical particles, daily seeded in correspondence of those marine sectors that are characterised by relevant traffic of vessels. The damage, expressed as the product of exposure and vulnerability, was estimated following an extensive sampling approach aimed at quantifying the ecological status of the rocky shores in four selected islands of the Tuscan Archipelago. Results revealed and quantified the direct relationship between the temporary reduction of the maritime traffic due to the pandemic restrictions, and the probability of suffering damage from oil spill impact along the archipelago's rocky shores, which was highly context-dependent.


Peritoneal sarcomatosis: site of origin for the establishment of an in vitro and in vivo cell line model to study therapeutic resistance in dedifferentiated liposarcoma.
Approximately 50-70 % of patients with retroperitoneal or intraabdominal sarcoma develop a relapse after surgical therapy, including peritoneal sarcomatosis, an extremely rare site of metastatic disease which is associated with an extremely poor prognosis. Accordingly, the establishment of a permanent cell line derived from peritoneal sarcomatosis might provide a helpful tool to understand the biological behavior and to develop new therapeutic strategies. Thus, we established and characterized a liposarcoma cell line (Lipo-DUE1) from a peritoneal sarcomatosis that was permanently cultured without showing any morphological changes. Lipo-DUE1 cells exhibited a spindle-shaped morphology and positive staining for S100. Tumorigenicity was demonstrated in vitro by invasion and migration assays and in vivo by using a subcutaneous xenograft mouse model. In addition, aCGH analysis revealed concordant copy number variations on chromosome 12q in the primary tumor, peritoneal sarcomatosis, and Lipo-DUE1 cells that are commonly observed in liposarcoma. Chemotherapeutic sensitivity assays revealed a pronounced drug-resistant phenotype of Lipo-DUE1 cells to conventionally used chemotherapeutic agents. In conclusion, we describe for the first time the establishment and characterization of a liposarcoma cell line derived from a peritoneal sarcomatosis. Hence, in the future, the newly established cell line Lipo-DUE1 might serve as a useful in vitro and in vivo model to investigate the biological behavior of liposarcoma and to assess novel targeted therapies.


Signaling survival: how axons rescue their glia.
The trophic theory of cell survival hypothesizes that cell number is regulated by survival signals generated by other cells. Work published in this issue of Developmental Cell confirms that neurons can provide trophic support for glia in Drosophila, and fills in important molecular details of this interaction.


Three-Dimensional Patient-Matched Template Guides Are Able to Increase Mean Diameter and Length and to Improve Accuracy of Cortical Bone Trajectory Screws: A 5-Year International Experience.
To analyze whether significant differences exist between free-hand three-dimensional (3D) planning-guided cortical bone trajectory (CBT) screw placement and 3D-printed template-guided CBT screw positioning in terms of accuracy, size of screws, and potential complications. In this retrospective study, data of adult patients in whom CBT screws were placed for lumbar degenerative pathologies were extracted from a prospectively collected database and analyzed. Patients in whom screws were placed using free-hand 3D planning-guided technique were compared with patients in whom screws were positioned using customized 3D-printed templates. Size of the screws, accuracy, clinical outcomes, and complications were analyzed. The study evaluated 251 patients (1004 screws). The free-hand 3D planning-guided group included 158 patients (632 screws), and the 3D-printed template-guided group included 93 patients (372 screws). The 3D-printed template-guided group involved screws of larger size from L3 to S1. Differences between the 2 groups in terms of accuracy parameters reached statistical significance (P ≤ 0.05). With the use of 3D patient-matched template guides, mean diameter and length of CBT screws could be safely increased due to improved accuracy of screw placement. Based on previous evidence regarding CBT biomechanical properties, these advantages could allow increased fixation strength over traditional convergent pedicle screw trajectories. Further biomechanics studies are needed.


The significance of stimulation in the leucocyte migration test as an indicator of cellular hypersensitivity--studies using Tamm-Horsfall glycoprotein as antigen.
To determine whether stimulation of leucocyte migration in the presence of an antigen is a reliable indicator of sensitization, the results of leucocyte migration using a kidney antigen (Tamm-Horsfall glycoprotein) were compared with those of lymphocyte transformation using the same antigen and with the lymphocyte cytotoxicity for cells known to synthesize this antigen. There was a close correlation between the results of all three tests and these findings strongly suggest that the stimulation of leucocyte migration as an immunological phenomenon was as valid as inhibition in demonstrating sensitization.


Allopurinol protects against manganese-induced oxidative stress in the striatum and in the brainstem of the rat.
Levels of uric acid, xanthine, hypoxanthine, ascorbic acid (AA), dehydroascorbic acid, glutathione (GSH), noradrenaline (NA), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and and 3-methoxytyramine were determined in the striatum and/or in the brainstem of 3-month-old male Wistar rats given manganese (MnCl2, 200 mg/kg/day for 7 days by gavage) alone or associated with allopurinol. Allopurinol alone (300 mg/kg/day for 4 days by gavage) decreased uric acid and increased xanthine levels both in the striatum and in the brainstem; moreover, allopurinol decreased the striatal DOPAC + HVA/DA ratio. Allopurinol antagonised the Mn-induced: (a) increase in the DOPAC + HVA/DA ratio; (b) increase in uric acid levels and AA oxidation; and (c) decrease in GSH and NA levels. We conclude that allopurinol may protect against Mn-induced oxidative stress by inhibiting both DA oxidative metabolism and xanthine oxidase-mediated formation of reactive oxygen species.


da Vinci's window facilitates drawings of total and partial occlusion in young children.
When two or more objects are present in a scene, children 5 and 6 years of age rarely draw the scene such that one object totally or partially occludes another object. Instead they draw complete objects. The present study separated two components of drawing: perspective taking and graphic skill. Perspective taking was examined by comparing a free viewing condition with a restricted viewing condition in which a model could only be viewed through four apertures. Graphic skill was examined by comparing drawings requiring total occlusion with drawings requiring partial occlusion under both viewing conditions. Experiment 1 showed that 90% of 5- and 6-year-olds drew total occlusions under restricted viewing conditions but only 32% did so in the free viewing condition. Experiment 2 showed that drawings of partial occlusion were unaffected by viewing condition among 5-year-olds, but that restricted viewing increased the number of partial occlusions that 6-year-olds drew. Thus, failures of young children to draw occlusions have less to do with graphic skill than was previously thought. Instead, it is suggested that young children have a more general difficulty selecting one perspective and maintaining it over time.


Ion channel degeneracy enables robust and tunable neuronal firing rates.
Firing rate is an important means of encoding information in the nervous system. To reliably encode a wide range of signals, neurons need to achieve a broad range of firing frequencies and to move smoothly between low and high firing rates. This can be achieved with specific ionic currents, such as A-type potassium currents, which can linearize the frequency-input current curve. By applying recently developed mathematical tools to a number of biophysical neuron models, we show how currents that are classically thought to permit low firing rates can paradoxically cause a jump to a high minimum firing rate when expressed at higher levels. Consequently, achieving and maintaining a low firing rate is surprisingly difficult and fragile in a biological context. This difficulty can be overcome via interactions between multiple currents, implying a need for ion channel degeneracy in the tuning of neuronal properties.


Practical synthesis of Taxol side chain.
Practical large scale synthesis of N-benzoyl-(2R,3S)-phenylisoserine methyl ester of the Taxol side chain has been attained from the coupling of chiral imine of N-[(S)-methylbenzyl]benzaldimine with (Z)-alpha-methoxy trimethylsilyl ketene acetal followed by the sequential reactions of lactamization, demethylation, methanolysis and N-benzoylation.


Quantitative myocardial perfusion single-photon emission computed tomographic imaging: quo vadis? (Where do we go from here?).
Quantitative myocardial perfusion single-photon emission computed tomography can be improved further by technical advancements that are imminent in the clinical setting. These improvements are directed toward two main goals: (1) increasing the accuracy that the myocardial count distribution from tomographic slices represents the true tracer concentration and (2) increasing the accuracy of extracting this myocardial count distribution for quantitative analysis. Once these advancements are fully validated and implemented clinically, the clinical value of these cardiac diagnostic tests will be enhanced by increased accuracy of detecting and characterizing myocardial hypoperfusion and coronary artery disease.


The effects of curcumin (diferuloylmethane) on body composition of patients with advanced pancreatic cancer.
Curcumin is a natural product that is often explored by patients with cancer. Weight loss due to fat and muscle depletion is a hallmark of pancreatic cancer and is associated with worse outcomes. Studies of curcumin's effects on muscularity show conflicting results in animal models. Retrospective matched 1:2 case-control study to evaluate the effects of curcumin on body composition (determined by computerized tomography) of 66 patients with advanced pancreatic cancer (22 treated,44 controls). Average age (SEM) was 63(1.8) years, 30/66(45%) women, median number of prior therapies was 2, median (IQR) time from advanced pancreatic cancer diagnosis to baseline image was 7(2-13.5) months (p>0.2, all variables). All patients lost weight (3.3% and 1.3%, treated vs. control, p=0.13). Treated patients lost more muscle (median [IQR] percent change -4.8[-9.1,-0.1] vs. -0.05%[-4.2, 2.6] in controls,p<0.001) and fat (median [IQR] percent change -6.8%[-15,-0.6] vs. -4.0%[-7.6, 1.3] in controls,p=0.04). Subcutaneous fat was more affected in the treated patients. Sarcopenic patients treated with curcumin(n=15) had survival of 169(115-223) days vs. 299(229-369) sarcopenic controls(p=0.024). No survival difference was found amongst non-sarcopenic patients. Patients with advanced pancreatic cancer treated with curcumin showed significantly greater loss of subcutaneous fat and muscle than matched untreated controls.


Three-tissue microphysiological system for studying inflammatory responses in gut-liver Axis.
The interaction between the gut and the liver, often known as the gut-liver axis, play crucial roles in modulating the body's responses to the xenobiotics as well as progression of diseases. Dysfunction of the axis can cause metabolic disorders as well as obesity, diabetes, and fatty liver disease. During the progression of such diseases, inflammatory responses involving the immune system also play an important part. In this study, we developed a three-tissue microphysiological system (MPS) that can accommodate three different cell types in separated compartments connected via fluidic channels in a microfluidic device. Using computational fluid dynamics, geometry of fluidic channels and flow conditions were optimized for seeding and culturing different cell types in the three-tissue MPS. Caco-2 (gut), RAW264.7 (immune), and HepG2 (liver) cells were seeded and cultured in the chip. Stimulation of the gut cells in the MPS with lipopolysaccharide (LPS) resulted in induction of inflammatory response and production of nitric oxide (NO) in all connected chambers. The anti-inflammatory effect of luteolin was demonstrated. Our study demonstrates that the three-tissue MPS can recapitulate the inflammatory responses involving the gut, liver and immune cells.


Evidence for cytochrome P450 3A expression and catalytic activity in rat blood lymphocytes.
Freshly isolated peripheral blood lymphocytes from control rats were found to catalyze the N-demethylation of erythromycin, known to be mediated by cytochrome P450 3A (CYP3A) isoenzymes in rat liver. Pretreatment of rats with dexamethasone (100 mg/kgx3 days, i.p.), a CYP3A inducer, resulted in 3-4-fold increase in the activity of erythromycin demethylase (EMD) in freshly isolated peripheral blood lymphocytes. This increase in the enzyme activity was found to be associated with an increase in the rate of the reaction and affinity of the substrate towards the enzyme. Significant inhibition of the EMD activity on in vitro addition of ketoconazole, a specific CYP3A inhibitor in liver and polyclonal antibody raised against rat liver CYP3A have suggested that EMD activity in blood lymphocytes is catalyzed primarily by CYP3A isoenzymes. Further, immunoblot analysis with polyclonal antibody raised against rat liver CYP3A revealed significant immunoreactivity, co-migrating with the liver isoenzyme, indicating constitutive expression of CYP3A in blood lymphocytes. Pretreatment with dexamethasone was found to significantly increase the expression of CYP3A protein in freshly isolated rat blood lymphocytes, as observed with liver. Likewise, significant CYP3A mRNA detected in control rat blood lymphocytes has further demonstrated constitutive expression of CYP3A isoenzymes in blood lymphocytes. Furthermore, several fold increase in CYP3A mRNA expression following pretreatment with dexamethasone showed similarities in the regulation of CYP3A isoenzymes in rat blood lymphocytes with the liver enzyme. The data suggest that the blood lymphocytes can be used to monitor tissue expression of CYP3A isoenzymes and validate the suitability of lymphocytes as surrogates of CYP status in less accessible target tissues.