Is adjustment disorder genetically correlated with depression, anxiety, or risk-tolerant personality trait?
Adjustment disorder has three main subtypes: adjustment disorder with depressed mood, adjustment disorder with anxiety, and adjustment disorder with disturbance of conduct. The disorder is moderately heritable and has lifetime comorbidities with major depressive disorder (MDD), anxiety disorders, or risk-tolerant personality. However, it remains unclear whether the degrees of genetic correlations between adjustment disorder and other psychiatric disorders and intermediate phenotypes are similar or different to those between MDD, anxiety disorders or risk-tolerant personality and these other psychiatric disorders and intermediate phenotypes. To compare patterns of genetic correlations, we utilized large-scale genome-wide association study summary statistics for adjustment disorder-related disorders and personality trait, eleven other psychiatric disorders and fifteen intermediate phenotypes. Adjustment disorder had highly positive genetic correlations with MDD, anxiety disorders, and risk-tolerant personality. Among other psychiatric disorders, adjustment disorder, MDD, anxiety disorders and risk-tolerant personality were positively correlated with risks for schizophrenia (SCZ), bipolar disorder (BD), SCZ + BD, attention-deficit/hyperactivity disorder, and cross disorders. In contrast, adjustment disorder was not significantly correlated with risks for obsessive-compulsive disorder, Tourette syndrome, or posttraumatic stress disorder despite significant genetic correlations of MDD or anxiety disorders with these disorders. Among intermediate phenotypes, adjustment disorder, MDD, anxiety disorders, and risk-tolerant personality commonly had a younger age at first sexual intercourse, first birth, and menopause, lower cognitive ability, and higher rate of smoking initiation. Adjustment disorder was not genetically correlated with extraversion, although the related disorder and personality were correlated with extraversion. Only adjustment disorder was correlated with a higher smoking quantity. These findings suggest that adjustment disorder could share a genetic etiology with MDD, anxiety disorders and risk-tolerant personality trait, as well as have a disorder-specific genetic etiology.


Properties of neurons in cat's dorsal lateral geniculate nucleus: a comparison between medial interlaminar and laminated parts of the nucleus.
We studied the receptive field properties of 460 cells in the cat's dorsal lateral geniculate nucleus (LGNd), 108 cells were located in the medial interlaminar nucleus (MIN) and 352 in the laminated part of the LGNd. In both the MIN and laminated parts of the LGNd, relay cells belonging to all three functional classes (W, X and Y) have been identified. Of cells in the laminated LGNd, about 32.5% were Y cells, about 54.5% were X cells and about 8.5% were W cells. By contrast, in the MIN, about 84% were Y cells, only about 4.5% being X cells and about 7.5%, W cells. In the laminated LGNd, Y cells represented 25% of cells with receptive fields near the area centralis (0-3 degrees eccentricity group) and about 42% in the group of cells with the most peripherally located receptive fields (20-40 degrees eccentricity group). A similar but much weaker trend was observed in the MIN. In the laminated LGNd but not in the MIN the receptive field center sizes increased with increasing eccentricity of receptive field position. At any eccentricity, receptive field centers of MIN Y cells tended to be larger than those of Y cells in the laminated LGNd. Response latency ranges to orthodromic and antidromic stimulation were the same for cells located in the laminated LGNd and those in the MIN. However, the mean response latency to stimulation of the optic chiasm was significantly shorter for Y cells in MIN than for Y cells in the laminated LGNd. Our results suggest that the most numerous cells observed histologically in the MIN, class 1 cells of Guillery ('66) are morphological equivalents of Y cells.


Single-room usage patterns and allocation decision-making in an Australian public hospital: a sequential exploratory study.
The aims are to (1) measure occupancy rates of single and shared rooms; (2) compare single room usage patterns and (3) explore the practice, rationale and decision-making processes associated with single rooms; across one Australian public health service. There is a tendency in Australia and internationally to increase the proportion of single patient rooms in hospitals. To date there have been no Australian studies that investigate the use of single rooms in clinical practice. This study used a sequential exploratory design with data collected in 2014. A descriptive survey was used to measure the use of single rooms across a two-week time frame. Semi-structured interviews were undertaken with occupancy decision-makers to explore the practices, rationale decision-making process associated with single-room allocation. Total bed occupancy did not fall below 99·4% during the period of data collection. Infection control was the primary reason for patients to be allocated to a single room, however, the patterns varied according to ward type and single-room availability. For occupancy decision-makers, decisions about patient allocation was a complex and challenging process, influenced and complicated by numerous factors including occupancy rates, the infection status of the patient/s, funding and patient/family preference. Bed moves were common resulting from frequent re-evaluation of need. Apart from infection control mandates, there was little tangible evidence to guide decision-making about single-room allocation. Further work is necessary to assist nurses in their decision-making. There is a trend towards increasing the proportion of single rooms in new hospital builds. Coupled with the competing clinical demands for single room care, this study highlights the complexity of nursing decision-making about patient allocation to single rooms, an issue urgently requiring further attention.


Extracorporeal shock wave lithotripsy produces a lower stone-free rate in patients with stones and renal cysts.
Renal cysts have a space-occupying effect and therefore can distort the pelvicalyceal anatomy. This distortion often produces abnormalities in normal urinary drainage. In the same way, it may effect the ability of the kidneys to become stone free after extracorporeal shock wave lithotripsy (ESWL). The purpose of the current study is to evaluate the effect of renal cysts on the outcome of ESWL. We studied 15 patients who had renal stones and coexistent renal cysts. Four patients had polycystic disease, five patients had multiple cysts and six patients has solitary ones. All cysts produced a distortion to the calyceal system of the kidneys, a fact confirmed by intravenous urography (IVU) and computed tomography (CT). All patients underwent ESWL and their stone-free status was evaluated 1 month later by ultrasound and plain kidney ureter bladder (KUB) X-ray. We had a total 60% (9/15) stone-free patients in our study group and a stone fragmentation rate of 100%. Patients with more cysts had lower stone-free rates. Patients with polycystic kidneys had a 25% (1/4) stone-free rate, while patients with multiple cysts and solitary cysts had, 60% (3/5) and 83.3% (5/6), respectively. These results are lower than the rates reported in patients without renal cysts. We believe that renal cysts may interfere with the passage of stone fragments, due to the impediment of drainage and urinary stasis from the stretching and distortion of the calyceal system by the renal cysts.


Fully uncemented glenoid component in total shoulder arthroplasty.
Loosening of the glenoid component remains the most common problem in total shoulder arthroplasty. It has been described that the round-backed, all-polyethylene components with cemented peg fixation perform better biomechanically and clinically than flat-backed, metal-backed, or keeled components. However, side effects of cementing have been described. We hypothesized that cementing of a specific type of all-polyethylene glenoid component with 3 peripheral pegs and 1 central anchor peg is not necessary to obtain good clinical and radiologic results. Thirty-four shoulders (34 patients), with a mean follow-up of 28.3 months, were evaluated clinically with the Constant-Murley score and the SF-12 Health Survey score. The fixation of the glenoid component was evaluated with computed tomography scan. The Constant-Murley score increased from 40.2 points (range, 13-73 points) preoperatively to 72 points (range, 54-93 points) postoperatively. The SF-12 Physical Component Summary score was 45, and the SF-12 Mental Component Summary score was 50. No signs of loosening were seen around the pegs or glenoid in 30 shoulders. Signs of loosening were seen around the central anchor peg and the peripheral pegs in 4 shoulders. There was no statistical difference between the clinical outcome of patients with and without signs of loosening. The clinical and radiologic evaluation of an uncemented all-polyethylene glenoid is promising, with good clinical results and with no signs of loosening in 88% of the patients on computed tomography scans.


A seasonal pattern in the onset of polymyalgia rheumatica and giant cell arteritis? A systematic review and meta-analysis.
Studies on the seasonality of onset of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) have shown conflicting results. The aim of this systematic literature review and meta-analysis is to determine from aggregated data whether there is a seasonal distribution for these diseases. A literature search was performed using Pubmed Central and Embase scientific databases. The incidences per 6-month periods, season or month of onset, that were reported in the studies were summarised in tables considering the two diseases as separate conditions or together. The Incidence Rate Ratio (IRR) for the cold period versus the warm period was pooled across studies by random effects meta-analysis weighed by inverse variance. Funnel plots and Egger test were used to explore possible publication biases. A sensitivity analysis was performed to weigh articles with a disproportionate number of patients compared to the rest. In the scientific literature 22 suitable papers were found: 6 on PMR with 803 patients, 11 on GCA with 2,807 patients, and 5 studies considering both diseases with 19,613 patients. There was considerable heterogeneity amongst studies regarding their quality, the classification criteria used, and the definition of onset of symptoms. No seasonal aggregation was found for GCA and PMR. The pooled IRR estimate of the meta-analysis (1.13[0.89,1.36]) showed a non-significant, higher frequency of diseases onset in the warm season. Our meta-analysis did not confirm a seasonal onset for PMR and GCA.


Urea: An important piece of Water Soluble Organic Nitrogen (WSON) over the Eastern Mediterranean.
The role of atmospheric urea on the biogeochemical cycle of Water Soluble Organic Nitrogen (WSON) in the Eastern Mediterranean was assessed by collecting and analyzing wet and dry deposition samples and size segregated aerosols during a one year period (2006). In rain water volume weighted mean (VWM) concentration of urea was found equal to 5.5μM. In atmospheric particles the average concentration of urea in coarse and fine mode was 0.9±1.9nmol N m(-3) (median 0.0nmol N m(-3)) and 2.2±3.0nmol N m(-3) (median 1.1nmol N m(-3)), respectively. The percentage contribution of urea to WSON fraction was 0% and 20% in coarse and fine particles respectively. On an annual basis 0.81mmol m(-2) and 1.78mmol m(-2) of urea were deposited via wet and dry deposition, contributing to WSON by 10% and 11% respectively. Regression analysis of urea with the main ions and trace metals measured in parallel suggest that soil and anthropogenic activities significantly contribute to atmospheric urea. Comparison of dry deposition of urea using size segregated deposition velocities with urea collected on a glass bead collector suggested the existence of significant fraction of urea in the gas phase.


Effects of very early monocular and binocular enucleation on primary visual centers in the tammar wallaby (Macropus eugenii).
The role of retinal afferents and their binocular interactions in the development of mammalian primary visual centers has been studied in the marsupial wallaby. Monocular and binocular enucleation was performed prior to any retinal innervation of the visual centers. After monocular enucleation retinal projections were traced by horseradish peroxidase histochemistry and compared with those in normal animals and those during development. The topography of retinal projections to the superior colliculus and the dorsal lateral geniculate nucleus after monocular enucleation was determined by making retinal lesions and tracing the remaining projections with horseradish peroxidase. The position and nature of the filling defects in terminal label were compared with controls with similarly placed lesions. The superior colliculus and dorsal lateral geniculate nucleus ipsilateral to the remaining eye were shrunken. Projections to the ipsilateral superior colliculus, ipsilateral accessory optic nuclei, and ipsilateral suprachiasmatic nucleus, although enlarged, never approached the density contralaterally, as was also the case during normal development. The expanded projection in the ipsilateral superior colliculus came primarily from temporal and ventral retina. In the dorsal lateral geniculate nucleus, terminal bands and cellular laminae, although not identical to normal, did develop. During normal development overlap of afferents from the two eyes occurs in the binocular region. The decrease in volume of the nucleus ipsilateral to the remaining eye after monocular enucleation suggests that the monocular region disappears in the absence of appropriate input and the binocular region survives. Contralaterally there was no decrease in volume, compatible with this idea. The topography of retinal projections supports this interpretation. It was normal contralaterally while ipsilaterally it was appropriate for the normal binocular region. There was an expansion of the projection along the lines of projection in what would normally be binocular regions of the nucleus, where retinal afferents failed to segregate in the absence of binocular competition. After binocular enucleation the alpha and beta segments of the dorsal lateral geniculate nucleus were still recognizable but cell-sparse zones were absent, as was the characteristic orientation of primary dendrites of geniculocortical cells. There are rigid developmental constraints operating on the innervation of territory by retinal afferents from the two eyes, and many features of the mature pattern arise without binocular interactions during development.


Gonadal receptors. II. Effects of time and reaction volume upon the binding of human chorionic gonadotropin and human luteinizing hormone to particulate receptors.
The effect of reaction volume upon the binding of gonadotropins by particulate receptors was studied. Two experimental approaches were used: one involved increasing the reaction volume of the binding assay (i.e. diluting the hormone and receptor concentrations and will be referred to as buffer coincubation studies) and the other involved incubating the testicular homogenate in various buffer volumes prior to the binding assay (buffer preincubation stidies). The results showed that the number of hormone binding sites inferred from Scatchard analysis was inversely related to the reaction volume in the coincubation as well as in the preincubation studies. Time-dependent dissociation of receptors from the intact testis was demonstrated by perifusion studies and the loss of receptors from intact testis correlated with the appearance of soluble factors (Bhalla, V.K., Haskell, J., Grier, H. and Mahesh, V.B. (1976) J. Biol. Chem. 251, 4947--4957) in the eluate obtained. The results obtained along with those presented in the preceding manuscript (Chen, C.J.H., Lindeman, J.G., Trowbridge, C.G. and Bhalla, V.K. (1979) Biochim. Biophys. Acta 284, 407--435) question the validity of the rapid equilibrium model which assumes reversible hormone occupancy of a fixed number of receptor sites. An alternate binding model is proposed herein and its implications are discussed.


Outside the Classroom: An Evaluation of Equine Internships.
Equine internships provide real experiences for students but are lightly researched. This study explored student perceptions of equine internships. The hypothesis was, participants would report that equine internships were valuable and relate value with compensation, skill acquisition, networking, and job offers. An online survey examined respondents' perceived value of their internship. Of 228 respondents, 186 met the inclusion criteria. Data were examined using frequency counts, correlations, and chi-square measures of association. Breeding internships (29%) were most common, with western training and performance (18%) second highest. Fifty-three percent had an internship requirement for their undergraduate degree; this did not affect internship value. Internship value tended to be higher when housing (X2(4, N = 180) =9.2; P = .075) or compensation (X2(4, N = 180) =8.5; P = .057) were included and highest with both included X2(12, N = 180) = 25.5; P = .013). Most (90%) believed their internship added to their classroom experience; 71% felt academically prepared. Respondents gained equine-related skills (81%), soft skills (83%), customer relations (63%), business management (51%), and administrative skills (33%). Of respondents, 67% use skills gained during their internship in their current job, and 83% were able to network within the equine industry. Half of internships resulted in a job offer from that company or in their area of interest. Overall, 91% of the respondents felt their internship was valuable, and 87% would recommend their internship to others. Perceived internship value positively correlated with networking (R = 0.75; P < .0001), gaining equine skills (R = 0.49; P < .0001), and job offers (R = 0.24; P < .002). These results suggest that equine internships are positive experiences and valuable for students.


Corrigendum to Clinical outcomes of volume of disease on patients receiving enzalutamide vs. abiraterone acetate plus prednisone as first-line therapy for metastatic castration resistant prostate cancer.
[This corrects the article DOI: 10.1177/17588359231156147.].


Genetic control of somatic embryogenesis induction in Eucalyptus globulus Labill.
A reproducible protocol for somatic embryogenesis (SE) induction in Eucalyptus globulus from mature zygotic embryos is available since 2002. However, for the use of SE in tree breeding programs, the frequency of SE initiation needs to be improved and controlled, and this was investigated in 13 open-pollinated (OP) families over three consecutive years. A diallel mating design with five parent trees was used to study genetic control of SE induction. Results showed that SE induction varies across E. globulus families and over the years of seed production tested. Somatic embryogenesis was initiated on explants from 84% of the OP families tested in 2002 and 100% of the families tested in 2003 and 2004. The year 2003 gave best results for percentage of induction and total number of somatic embryos produced. Results concerning genetic control showed that SE induction is under the control of additive genetic effects, as 22.0% of variation in SE initiation was due to general combining ability (GCA) effect, whereas 6.4% was due to maternal effects. Neither specific combining ability (SCA) nor reciprocal effects were significant.


[Prevention of multiple pregnancy after IVF/ICSI by elective single embryo transfer--pilot study].
To reduce the number of multiple pregnancies after IVF/ICSI treatment by an elective single embryo transfer, without significant reduction of pregnancy rate (PR). A pilot study. Department of Obstetrics and Gynecology, University Hospital, Olomouc. The patients were devided into the three groups according to number and quality of transferred embryos: elective Single EmbryoTransfer (eSET, n = 14), Single EmbryoTransfer (SET, n = 21), and Double EmbryoTransfer--control group (DET, n = 85). After 3 days of cultivation the embryos were transferred. In all groups the following parameters were compared: age of the patient, number of oocytes obtained, fertilization rate, number of frozen embryos, pregnancy rate (PR), implantation rate (IR), abortions (AB) and the number of multiple pregnancy. In eSET group PR and (or IR) was 42.8%, in SET group PR and (or IR) was 19%. There were no monozygotic twins in these groups. In DET group PR was 40.7% and IR 25.9%. Nine of these 33 pregnancies were twins (27%). Because of small number of the patients detailed statistical analyses were not performed. An elective transfer of one "TOP" embryo can reduce the number of multiple pregnancies without significant decrease of pregnancy rate.


An improved HPLC-fluorescence stereoselective method for analysis of (+)-S- and (-)-R-sotalol enantiomers in plasma sample.
A simplified high performance chromatographic method (HPLC) was performed for sotalol enantiomers in plasma samples for purposes of investigation of the kinetic disposition of racemic sotalol in cardiac arrhythmic patients under multiple dose and multidrug therapy regimens. After addition of NaCl:Na2CO3 (4:1) and plasma protein precipitation by acetonitrile:methanol mixture (1:1) the supernatant was evaporated. The residue containing sotalol racemate was submitted to derivatization reaction with (-)-menthylcloroformate to R(-)- and S(+)-sotalol diastereoisomers. The diastereoisomers were resolved in HPLC, by a C18 column with fluorescent detection under lexcitation = 235 nm and lemission = 310 nm. The retention times for R- and S-sotalol were 20 and 22 minutes while that of internal standard S(-)-atenolol, was 17 minutes. The detection limit for each enantiomer was 12.5 ng/mL and intra-day/inter-day coefficients of variation were less than 10% for each enantiomer within a concentration range of 200 and 2000 ng/mL. The method was appropriate for the objective proposed.


[Pathogenic characteristics of Escherichia coli strains in cases of asymptomatic bacteriuria and symptomatic urinary tract infections].
The aim of this study was to examine if E. coli isolated from asymptomatic bacteriuria differed in pathogenic features from strains isolated from symptomatic infections of urinary tract. In this study 130 strains of E. coli isolated from women having asymptomatic bacteriuria and 112 strains isolated from patients with symptoms of urinary tract infection were examined. It was shown that E. coli isolated from patients with symptomatic urinary tract infection showed the more frequently ability to cause mannose-resistant haemagglutination of human erythrocytes, resistance to bactericidal activity of serum and haemolytic properties than those isolated from asymptomatic bacteriuria. These strains showed also the higher ability to adhere to Vero cells in tissue culture. Among E. coli strains isolated from persons with asymptomatic bacteriuria the pathogenic features were most frequently found in strains from healthy women and the most rarely in isolated from diabetic women.


X chromosome inactivaton and SV40 transformation of mammalian cells.
Five embryonic mouse cultures and one human fibroblast culture were transformed with SV40. The cultures were studied cytologically to see if the normal pattern of sex chromosome replication was maintained in SV40 transformed cells. Characteristic late replication patterns were observed for both the X and Y chromosomes, and there was no evidence for loss of the inactive X chromosome, even in cells with 4 or more X chromosomes. The human line was heterozygous at two X-linked loci and a clonal analysis showed that the expression of X-linked genes was not affected by SV40 transformation.


An upgraded CFA - FLC - MS/MS system for the semi-continuous detection of levoglucosan in ice cores.
A new Continuous Flow Analysis (CFA) system coupled with Fast Liquid Chromatography - tandem Mass Spectrometry (FLC-MS/MS) has been recently developed for determining organic markers in ice cores. In this work we present an upgrade of this innovative technique, optimized for the detection of levoglucosan in ice cores, a crucial tracer for reconstructing past fires. The upgrade involved a specific optimization of the chromatographic and mass spectrometric parameters, allowing for a higher sampling resolution (down to 1 cm) and the simultaneous collection of discrete samples, for off-line analysis of water stable isotopes and additional chemical markers. The robustness and repeatability of the method has been tested by the analysis of multiple sticks of ice cut from the same shallow alpine ice core, and running the system for several hours on different days. The results show similar and comparable trends between the ice sticks. With this upgraded system, a higher sensitivity and a lower limit of detection (LOD) was achieved compared to discrete analysis of alpine samples for levoglucosan measurements. The new LOD was as low as 66 ng L-1, a net improvement over the previous LOD of 600 ng L-1.


Resorcinarene Induced Assembly of Carotene and Lutein into Hierarchical Superstructures.
The manipulation of carotenoid-based hierarchical superstructures affords attractive properties that facilitate application in biology and photosynthesis. Here, tubular suprastructures formed from water-soluble amide-modified resorcinarene and β-carotene were reported, whereas microsheets were formed when β-carotene was replaced with lutein. These structures were characterized using various measurements, indicating the differences of binding sites between resorcinarene and β-carotene/lutein. Subsequently, the assembly mechanism was described by calculating the formation energy of the assemblies.


Trimethoprim-Sulfamethoxazole-associated early neutropenia in Mexican adults living with HIV: A cohort study.
Trimethoprim/sulfamethoxazole (TMP/SMX) is the antimicrobial of first choice in the treatment and prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients, particularly in people living with human immunodeficiency virus (HIV). TMP/SMX use entails different adverse effects, and its association with early neutropenia is minimally documented. This study aimed to identify the risk of early neutropenia associated with TMP/SMX use in adults living with HIV in Mexico. A prospective cohort study was conducted in TMP/SMX-naïve adults living with HIV admitted to a third-level hospital between August 2019 and March 2020. Socio-demographic, clinical, and laboratory data were collected. According to patients' diagnostic, if they required treatment or prophylaxis against PCP, medical staff decided to prescribe TMP/SMX, as it is the first-line treatment. The risk of TMP/SMX induced early neutropenia, as well as associated factors were analyzed through a bivariate model and a multivariate Poisson regression model. The strength of association was measured by incidence rate ratio (IRR) with 95% confidence interval. 57 patients were enrolled in the study, of whom 40 patients were in the TMP/SMX treatment-group for treatment or prophylaxis of PCP (204.8 person-years of observation, median 26.5 days) and 17 patients were in the non-treatment group because they did not need the drug for treatment or prophylaxis of PCP (87.0 person-years of observation, median 21 days). The incidence rate of early neutropenia in the TMP/SMX-treatment group versus non-treatment group was 7.81 and 1.15 cases per 100 person-years, respectively. After adjusting for stage 3 of HIV infection and neutrophil count <1,500 cells/mm3 at hospital admission, the current use of TMP/SMX was not associated with an increase in the incidence rate ratio of early neutropenia (adjusted IRR: 3.46; 95% CI: 0.25-47.55; p = 0.352). The current use of TMP/SMX in Mexican adults living with HIV was not associated with an increase in the incidence rate ratio of early neutropenia.


Quality-of-life evaluation during platinum-based neoadjuvant chemotherapies for urothelial carcinoma.
Although quality of life (QOL) is one of the most important considerations in patients treated with anticancer therapies, desirable regimens for neoadjuvant chemotherapy including QOL in locally advanced urothelial carcinoma remain unclear. The present study evaluated the influence of neoadjuvant platinum-based chemotherapy on QOL in patients with locally advanced urothelial carcinoma. Between June 2013 and March 2016, 83 urothelial carcinoma patients who received two courses of neoadjuvant chemotherapy were enrolled in this prospective observational study. Neoadjuvant regimens included gemcitabine + cisplatin (GCis) or gemcitabine + carboplatin (GCb) therapies. As a primary endpoint, we assessed QOL changes in each group before and after chemotherapy using the Quality of Life questionnaire on days 1, 3, and 15 of each cycle. Secondary endpoints included toxicity, safety, weight loss, renal function decline, and tumor responses. QOL analyses were performed in 39 patients receiving GCis and in 44 patients receiving GCb. Appetite loss, role functioning, nausea/vomiting, physical, and fatigue deteriorated >10% from baseline in the GCis group but not in the GCb group. Constipation worsened, whereas scores for pain and emotional items improved in both groups. Objective response rates were 38.5 and 43.2% in the GCis and GCb groups, respectively. Both GCis and GCb regimens were feasible in terms of QOL. The GCb regimen may be associated with a better QOL status especially in regard to gastrointestinal symptoms.


Current Status and Factors Associated with Clean Operating Rooms: A Survey of Hospitals in China.
Indoor air quality is controlled in the clean operating room (OR) to reduce the risk of surgical-site infections (SSIs). The aim of this study is to assess the usage and management of clean ORs in China and to identify factors associated with the risk of SSIs. An online survey was distributed to hospitals in China from August 5 to September 5, 2018 via the WeChat account of the Shanghai International Forum for Infection Control and Prevention. The questionnaire consisted of two parts: basic information (hospital type, level, and number of beds) and usage and management (number of ORs, usage time, maintenance mode, test frequency, compliance with current standards, and comfort of healthcare workers). The significance of factors associated with the cleanliness and maintenance of clean ORs was assessed by univariate and multivariate logistic regression analyses. Among 1,308 responding hospitals, 25.7% failed to comply with current standards. "Maintenance mode" had a significant effect on compliance with current standards for clean ORs (p < 0.0001) and "professional" maintenance was superior to "outsource or no" maintenance (odds ratio = 0.511, 95% confidence interval = 0.367-0.711). There was a significant difference in the comfort of healthcare workers in clean ORs that complied with current standards vs. those that did not (39.92% [388/972] vs. 64.28% [216/336], respectively, p < 0.0001). Humidity was the chief complaint among healthcare workers. Maintenance of clean ORs was significantly associated with the compliance of current standards. Noncompliance with current standards was associated with greater risks of SSIs. Maintenance of ORs for prevention of SSIs should consider the costs and benefits.


Dietary pattern as a predictor of change in BMI z-score among girls.
To describe child and adolescent dietary patterns and to determine associations between childhood dietary pattern and longitudinal change in body mass index (BMI) z-score among girls. Healthy girls (n = 101) aged 8-12 years at baseline and 11-19 years at follow-up participated in a longitudinal study of growth and development. Participants kept 7-day dietary records at two points in time. We incorporated time of day, frequency, and amount of energy consumed (defined as percentage of total energy consumed per dietary event) when characterizing dietary patterns. Girls ate an average of 4-5 times per day and consumed most energy in the afternoon and in the evening/night, rather than in the morning. After controlling for baseline BMI, the mean percentage of daily energy consumed in the evening/night was positively associated with change in BMI z-score (P = 0.039). Eating between 4.0 and 5.9 times per day overall and no more than 1.9 times in the evening/night daily were negatively associated with change in BMI z-score (P = 0.002 and 0.047, respectively), after controlling for baseline BMI z-score. Recommendations to decrease the percentage of energy coming from the evening/night meal and the number of dietary events to no more than six times per day and two times in the evening/night should be evaluated in future longitudinal investigations.


Predicting post-hepatectomy liver failure by combined volumetric, functional MR image and laboratory analysis.
To assess the efficacy of functional MR image with volumetric, liver function test and indocyanine green clearance (ICG) in identifying the patients who are at risk of post-hepatectomy liver failure (PHLF). We retrospectively included 115 patients undergoing gadoxetic acid-enhanced MR imaging before hepatectomy at one medical centre from January 2013 to December 2015. Contrast enhancement ratio (CER) between transitional and hepatobiliary phases (3 and 30 minutes post-contrast) was calculated. Total liver volume (TLV) and spleen volume (Sp) were measured. Post-operatively, the histological Ishak fibrosis score was collected. Potential risk factors for liver failure were analysed, and the performance was examined by receiver operating characteristic curve. Post-hepatectomy liver failure (PHLF) occurred in 16 patients (13.9%). TLV/SLV, ADC value, CERHBP/TP and total liver contrast enhancement ratio (tCER) were associated with PHLF (P < .05). Between PHLF and non-PHLF groups, remnant liver volume (RLV), RLV/SLV, Sp/RLV, remnant liver contrast enhancement ratio (rCER) and Ishak fibrosis score showed statistical difference. rCER showed superiority in diagnostic performance (AUC = 0.78) with the optimal cut-off value of 1.23. Gadoxetic acid-enhanced MR imaging with volumetric is a reliable method for evaluating functional liver volume and determining the risk of PHLF.


Retention correlation and orthogonality between reversed phase countercurrent chromatography and liquid chromatography based on solvent strength.
Correlation of elution performance between reversed phase countercurrent chromatography and liquid chromatography was investigated using five selected natural components. Theoretical guidance for orthogonality of two-dimensional countercurrent chromatography and liquid chromatography was proposed. The difference in retention behavior between countercurrent chromatography and liquid chromatography was studied when the mobile phase was composed of methanol and water by measuring the partition behavior of five selected compounds in two typical biphasic solvent systems composed of n-hexane-ethyl acetate-methanol-water and chloroform-methanol-water. An orthogonal diagram between countercurrent chromatography and liquid chromatography was obtained by normalized treatment of the measured partition coefficients and capacity factors. The experimental results showed that each biphasic solvent system used for countercurrent chromatography had a high orthogonality with liquid chromatography when a specific volume ratio was used.


Forkhead box proteins as the critical regulators of cisplatin response in tumor cells.
Cisplatin (CDDP) is one of the most common chemotherapy drugs used in a wide range of cancer patients; however, there is a high rate of CDDP resistance among cancer patients. Considering the side effects of cisplatin in normal tissues, it is necessary to predict the CDDP response in cancer patients. Therefore, identifying the molecular mechanisms involved in CDDP resistance can help to introduce the prognostic markers. Several molecular mechanisms such as apoptosis inhibition, drug efflux, drug detoxification, and increased DNA repair are involved in CDDP resistance. Regarding the key role of transcription factors in regulation of many cellular processes related to drug resistance, in the present review, we discussed the role of Forkhead box (FOX) protein family in CDDP response. It has been reported that FOX proteins mainly promote CDDP resistance through the regulation of DNA repair, autophagy, epithelial-mesenchymal transition (EMT), and signaling pathways. Therefore, FOX proteins can be introduced as the prognostic markers to predict CDDP response in cancer patients. In addition, considering that oncogenic role of FOX proteins, the CDDP treatment along with FOX inhibition can be used as a therapeutic strategy in cancer patients.


Nuclear roadblocks for mRNA export.
The THO complex and Sub2 RNA helicase have been shown to function in both transcription and mRNA processing. Rougemaille et al. (2008) now uncover evidence that THO/Sub2 coordinates mRNA processing and nuclear export.


Use of Virtual Reality for Hybrid Closure of Multiple Ventricular Septal Defects.
A 28-month-old girl with multiple ventricular septal defects previously underwent surgical and transcatheter attempts at repair. Three-dimensional models were created from cardiac magnetic resonance-derived images. Viewing the models in virtual reality allowed the team to precisely locate the defects and decide on a hybrid transcatheter and surgical approach to ensure successful repair. (Level of Difficulty: Advanced.).


Mucoadhesive pickering nanoemulsions via dynamic covalent chemistry.
Submicron oil droplets stabilized using aldehyde-functionalized nanoparticles should adhere to the primary amine groups present at the surface of sheep nasal mucosal tissue via Schiff base chemistry. Well-defined sterically-stabilized diblock copolymer nanoparticles of 20 nm diameter were prepared in the form of concentrated aqueous dispersions via reversible addition-fragmentation chain transfer (RAFT) aqueous emulsion polymerization of 2,2,2-trifluoroethyl methacrylate (TFEMA) using a water-soluble methacrylic precursor bearing cis-diol groups. Some of these hydroxyl-functional nanoparticles were then selectively oxidized using an aqueous solution of sodium periodate to form a second batch of nanoparticles bearing pendent aldehyde groups within the steric stabilizer chains. Subjecting either hydroxyl- or aldehyde-functional nanoparticles to high-shear homogenization with a model oil (squalane) produced oil-in-water Pickering macroemulsions of 20-30 µm diameter. High-pressure microfluidization of such macroemulsions led to formation of the corresponding Pickering nanoemulsions with a mean droplet diameter of around 200 nm. Quartz crystal microbalance (QCM) experiments were used to examine adsorption of both nanoparticles and oil droplets onto a model planar substrate bearing primary amine groups, while a fluorescence microscopy-based mucoadhesion assay was developed to assess adsorption of the oil droplets onto sheep nasal mucosal tissue. Squalane droplets coated with aldehyde-functional nanoparticles adhered significantly more strongly to sheep nasal mucosal tissue than those coated with the corresponding hydroxyl-functional nanoparticles. This difference was attributed to the formation of surface imine bonds via Schiff base chemistry and was also observed for the two types of nanoparticles alone in QCM studies. Preliminary biocompatibility studies using planaria indicated only mild toxicity for these new mucoadhesive Pickering nanoemulsions, suggesting potential applications for the localized delivery of hydrophobic drugs.


A report of a desmoplastic ganglioglioma in a 12-year-old girl with review of the literature.
Desmoplastic infantile ganglioglioma is a supratentorial tumor that typically occurs in infants below the age of 24 months. Rare tumors with the same radiological and histological characteristics have been described in older subjects. We report a case of desmoplastic ganglioglioma in a 12-year-old girl with a 13 years follow-up. The patient presented with an inaugural generalized seizure. CT scan demonstrated a large superficial parieto-occipital mass, attached to the dura with solid and cystic components. Surgical resection was macroscopically complete. No adjuvant treatment was given. Thirteen years after surgery, the patient is symptom free. Histological examination revealed a pleomorphic tumor involving the meningeal space and the cortex. Meningeal portion was made of neoplastic astrocytes enmeshed in a dense network of connective tissue. The cortical component showed abnormal neurons, tumoral astrocytes and small foci of poorly differentiated cells with rare mitoses. Our observation and the seven others found in the literature indicate that desmoplastic gangliogliomas can occur in children and even in young adults. Despite some worrisome radiological and histological features, these tumors should not be misdiagnosed as malignant glioma. Like infantile cases, non-infantile desmoplastic gangliogliomas seem to have a favorable prognosis without additional therapy, if a total surgical resection can be performed.


Probabilistic models of species discovery and biodiversity comparisons.
Inferring large-scale processes that drive biodiversity hinges on understanding the phylogenetic and spatial pattern of species richness. However, clades and geographic regions are accumulating newly described species at an uneven rate, potentially affecting the stability of currently observed diversity patterns. Here, we present a probabilistic model of species discovery to assess the uncertainty in diversity levels among clades and regions. We use a Bayesian time series regression to estimate the long-term trend in the rate of species description for marine bivalves and find a distinct spatial bias in the accumulation of new species. Despite these biases, probabilistic estimates of future species richness show considerable stability in the currently observed rank order of regional diversity. However, absolute differences in richness are still likely to change, potentially modifying the correlation between species numbers and geographic, environmental, and biological factors thought to promote biodiversity. Applied to scallops and related clades, we find that accumulating knowledge of deep-sea species will likely shift the relative richness of these three families, emphasizing the need to consider the incomplete nature of bivalve taxonomy in quantitative studies of its diversity. Along with estimating expected changes to observed patterns of diversity, the model described in this paper pinpoints geographic areas and clades most urgently requiring additional systematic study-an important practice for building more complete and accurate models of biodiversity dynamics that can inform ecological and evolutionary theory and improve conservation practice.


Patient non-specific algorithm for seizures detection in scalp EEG.
Epilepsy is a brain disorder that affects about 1% of the population in the world. Seizure detection is an important component in both the diagnosis of epilepsy and seizure control. In this work a patient non-specific strategy for seizure detection based on Stationary Wavelet Transform of EEG signals is developed. A new set of features is proposed based on an average process. The seizure detection consisted in finding the EEG segments with seizures and their onset and offset points. The proposed offline method was tested in scalp EEG records of 24-48h of duration of 18 epileptic patients. The method reached mean values of specificity of 99.9%, sensitivity of 87.5% and a false positive rate per hour of 0.9.


The Characteristics and Level of Evidence of Clinical Studies Published in 5 Leading Orthodontic Journals.
The objective of this study was to assess the characteristics and level of evidence (LOE) of clinical studies recently published in leading orthodontic journals and to explore the association between the LOE and potentially related factors. The official online archives of 5 leading orthodontic journals were hand-searched to identify clinical research articles published during the period 2015-2017. The LOE of all included studies was assessed using a modified LOE classification system developed based on the Oxford LOE and Grading of Recommendations Assessment, Development and Evaluation (GRADE). Univariable and multivariable logistic regression analyses were performed to identify the association between the LOE of each article (high LOE vs. low LOE) and 7 factors. A total of 637 studies were included and assessed. Of these, 8 (1.3%) were of level 1, 160 (25.1%) level 2, 326 (51.2%) level 3, and 143 (22.4%) level 4. According to multivariable logistic regression analyses, journal of publication (P < .001), funding status (P = .003), and the geographic origin of the first author (P = .006) were significantly associated with the LOE. The number of studies with high LOE in leading orthodontic journals was limited. There is still need for further improvement in the overall LOE of clinical studies in orthodontics.


Correction: Zhang et al. Biodegradable Starch/Chitosan Foam via Microwave Assisted Preparation: Morphology and Performance Properties. Polymers 2020, 12, 2612.
Jeffrey M [...].


Influence of Three Contrasting Detrital Carbon Sources on Planktonic Bacterial Metabolism in a Mesotrophic Lake.
Abstract Lakes receive organic carbon from a diversity of sources which vary in their contribution to planktonic microbial food webs. We conducted a mesocosm study to test the effects of three different detrital carbon sources (algae, aquatic macrophytes, terrestrial leaves) on several measures of microbial metabolism in a small meso-eutrophic lake (DOC approximately 5 mg/L). Small DOC additions (DeltaC < 1 mg/L) affected bacterial numbers, growth, and pathways of carbon acquisition. Macrophyte and leaf detritus significantly increased TDP and color, but bacterial densities initially (+12 h) were unaffected. After 168 h, densities in systems amended with terrestrial detritus were 60% less than in controls, while production rates in mesocosms with macrophyte detritus were 4-fold greater. Detritus treatments resulted in greater per-cell production rates either through stable cell numbers and greater growth rates (macrophyte-C) or lower densities with stable production rates (terrestrial-C). After only 12 h, rates of leucine aminopeptidase (LAPase) activity were 2.5x greater in macrophyte-C systems than in controls, but LAPase and beta-N-acetylglucosamindase activities in systems amended with terrestrial-C were only 50% of rates in controls. After 168 h, beta-xylosidase rates were significantly greater in communities with terrestrial and phytoplankton detritus. Microbial utilization of >20% of 102 carbon sources tested were affected by at least one detritus addition. Macrophyte-C had positive (6% of substrates) and negative (14%) effects on substrate use; terrestrial detritus had mainly positive effects. An ordination based on carbon-use profiles (+12 h) revealed a cluster of macrophyte-amended communities with greater use of psicose, lactulose, and succinamic acid; controls and algal-detritus systems were more effective in metabolizing two common sugars and cellobiose. After 168 h, communities receiving terrestrial detritus were most tightly clustered, exhibiting greater use of raffinose, pyroglutamic acid, and sebacic acid. Results suggest that pelagic bacterial communities respond to changes in organic carbon source rapidly and by different routes, including shifts in per-cell production rates and variations in degradation of a variety of compounds comprising the DOC pool.


Microbial insights towards understanding the role of hydrochar in enhancing phenol degradation in anaerobic digestion.
Anaerobic digestion (AD) of wastewater is the most promising bioprocess for organic conversion, however, phenol is toxic and resistant to anaerobic degradation. The current study compared the effect of hydrochar and granular activated carbon (GAC) on AD of phenol at four concentrations (100 mg/L, 250 mg/L, 500 mg/L and 1000 mg/L). Results demonstrated that hydrochar significantly improved the methane production rate and reduced the lag phase at all concentrations of phenol. The methane production rate was improved by about 50% at both 100 mg/L and 250 mg/L phenol, while it was raised by >160% at 500 mg/L and 1000 mg/L phenol by hydrochar. The GAC only increased the methane production rate at 500 mg/L and 1000 mg/L due to high adsorption capacity. Further, the adsorption of phenol by hydrochar had no apparent impact on the methane production rate, even though certain amounts of phenol were adsorbed. At 500 mg/L, the amount of methane produced significantly increased, so 16S rRNA transcripts sequencing and metabolomic analysis were conducted. 16S rRNA transcripts sequencing analysis indicated that hydrochar resulted in the enrichment of syntrophic bacteria (e.g., Syntrophorhabdus & Syntrophobacter) and Methanosaeta, which might be related with direct interspecies electron transfer. Further, it was noticed that the growth of Methanobacterium was repressed at 500 mg/L phenol, while hydrochar promoted its growth. Phenol was degraded into L-tyrosine and then followed the benzoate degradation pathway for methane production as revealed by metabolomic analysis. In addition, metabolomic analysis also revealed that hydrochar promoted the degradation of all metabolites and enhanced the phenol degradation into methane.


Psychiatric aspects of high-risk pregnancy.
The intensity and ramifications of emotional reactions to high-risk pregnancy make liaison work in this field interesting, challenging, and rewarding. The potential benefits include not only improved obstetric patient care, but also risk reduction in the mother-child relationship that follows.


Reliability and measurement error of tests used for the assessment of throwing performance in overhead athletes: A systematic review.
Throwing Performance (TP) is important in throwing sports. Several tests have been designed to assess TP, and the reliability of these tests was examined in various studies. The aim of this systematic review was to critically appraise and synthesize the studies that examined the reliability of TP tests. A systematic search was conducted on PubMed, Scopus, CINAHL and SPORTDiscus to identify studies related to TP and reliability. The quality of the included studies was examined through the Quality Appraisal of Reliability Studies (QAREL) tool. Reliability was assessed using the intraclass correlation coefficient (ICC), while responsiveness was assessed using the minimal detectable change (MDC). Sensitivity analysis was conducted to identify whether low-quality studies may have biased the recommendations of this review. Seventeen studies were found eligible. The results showed a moderate level of evidence to suggest that TP tests have good reliability (ICC≥0.76). This recommendation was also applied separately when TP tests were used to measure throwing velocity, distance covered, endurance and throwing accuracy. Also, summated MDC scores were reported to assist coaches in decision-making when using TP tests to detect real performance changes. However, sensitivity analysis showed that there is a significant number of low-quality studies. This review revealed that the tests used for throwing performance assessment are reliable; however, due to a significant number of low-quality studies, these results should be used cautiously. Important recommendations of this review may be used in future studies to design high-quality studies.


Phenotype and biological characteristics of endometrial mesenchymal stem/stromal cells: A comparison between intrauterine adhesion patients and healthy women.
Intrauterine adhesion (IUA) is a uterine disorder with partial or total obstruction of the uterine cavity and/or the cervical canal primarily caused by intrauterine operations and infections. It is the most common cause of uterine infertility and recurrent abortion. However, the reasons for endometrium repair disorders in patients with IUA are still unclear. While increasing evidence demonstrates that endometrial mesenchymal stem/stromal cells (EMSCs) contribute to the regeneration and repair of endometrium, the roles of EMSCs in the pathogenesis of IUA have not been reported. We investigated the differences of phenotype and biological characteristics between EMSCs from women with IUA and healthy women. Firstly, the fibrosis of endometrium were measured by immunohistochemistry and Masson staining. Second, we used immunofluorescence to detect the location of EMSCs in endometrial tissue, and the proportion of CD146+ CD140b+ in the two groups was compared by flow cytometry. Then, plate colony formation experiment, CCK-8 assay, flow cytometry, would-healing assay, and transwell invasion experiment were used to compare the cloning ability, proliferation, cell cycle, migration and invasion capabilities respectively. Finally, we compared the potential angiogenesis and immunosuppression capabilities. Our results showed that there were fewer CD146+ CD140b+ cells in patients with IUA, and the clone-forming, migration, invasion, angiogenic and immunosuppressive abilities of the EMSCs of patients with IUA were significantly decreased compared with those of healthy women. There are some differences between the EMSCs of IUA patients and healthy women, which may be related to the occurrence of IUA and dysfunction of endometrium.


Comparison of Anterior Capsule Polishing on the Rate of Neodymium: YAG Laser Capsulotomy After Two Multifocal Intraocular Lens Implantation.
To compare the impact of anterior capsule polishing (ACP) during cataract surgery on the rate of neodymium: YAG (Nd: YAG) laser capsulotomy in pseudophakic eyes with two multifocal intraocular lenses (MIOLs). Data were collected on patients who underwent cataract surgery and implanted segmental refractive MIOLs (SBL-3, Lenstec) or diffracted MIOLs (AT LISA tri 839MP, Carl Zeiss Meditec). The participants were divided into ACP and non-ACP groups based on whether the anterior capsule was polished. The primary outcome measure was whether Nd: YAG capsulotomy was performed during the 3 years follow-up. We used Kaplan-Meier survival curves to determine the time from IOL implantation to Nd: YAG laser capsulotomy. ACP and non-ACP groups comprised 70 and 60 eyes, respectively. One year postoperatively, 7.14% of ACP group eyes and 8.33% of non-ACP group required Nd: YAG laser capsulotomy (P > 0.99). After 2 years, it was 24.29 and 18.33%, respectively (P = 0.52), while after 3 years, it reached 30.0 and 28.33% (P = 0.85). No distinct difference existed in the probability of using Nd: YAG laser in both groups evaluated using Kaplan-Meier survival curves (P = 0.81). Patients with diffractive MIOLs (AT LISA tri 839MP) implantation were more likely to require Nd: YAG laser capsulotomy (P < 0.01). Polishing the anterior capsule had no remarkable effect on reducing the rate of Nd: YAG laser capsulotomy following phacoemulsification in MIOLs. Patients with diffractive MIOLs implantation had a high probability of requiring Nd: YAG laser capsulotomy.


Surveillance of tick-borne encephalitis in emerging risk areas in southern Sweden: a retrospective case finding study.
Tick-borne encephalitis (TBE) is an emerging infection causing CNS infection of various severity. Good knowledge of the incidence in the population and defined risk areas is important in risk communication and vaccination recommendations. The aim of this study was to investigate potential underreporting by retrospectively diagnose TBE among patients with viral CNS infections of unknown etiology in a region with emerging risk areas for TBE, and define variables associated with performed TBE serology at the time of infection. Epidemiological data and microbiological diagnostics of cases with viral CNS infection of unknown etiology treated at departments of infectious diseases and pediatrics in Skåne County during 2000-2012 were investigated. Analyses to evaluate variables associated with performed TBE serology at the time of infection were performed. Retrospective TBE serology was performed on stored blood samples when available. TBE serology was already performed at the time of CNS infection in 193 out of 761 cases. Department, type of clinical manifestation, time period of illness, and whether Borrelia serology had been performed were independent variables associated with having had TBE serology performed or not at the time of illness. Only one of 137 cases, where samples could be retrospectively analyzed for TBE, turned out positive. This study shows a low frequency of TBE sampling among patients with meningoencephalitis in a region with emerging risk for TBE. A higher awareness of TBE as differential diagnosis could contribute to earlier detection of new risk areas and adequate preventive advice to the public.


Subclinical intestinal duplication in a cat.
An abdominal mass was identified upon palpation of the abdomen in a normal, asymptomatic, 1-year-old female domestic shorthair cat presented for elective ovariohysterectomy. Radiographic and ultrasound examinations demonstrated a well-circumscribed caudal abdominal mass. Ultrasound guided needle aspiration cytology was consistent with an accumulation of squamous epithelial cells. The mass was associated with the jejunum and was excised via resection anastomosis of the intestinal segment after ovariohysterectomy. Histologic examination provided the diagnosis of an intestinal duplication lined with epithelium typical of that in the esophagus. The cat recovered without complications.


Detection of the prodrug-activating enzyme carboxypeptidase G2 activity with chemical exchange saturation transfer magnetic resonance.
The purpose of this study is to evaluate if the differential exchange rates with bulk water between amine and amide protons can be exploited using chemical exchange saturation transfer magnetic resonance (CEST-MR) to monitor the release of glutamate induced by carboxypeptidase G2 (CPG2), an enzyme utilized in cancer gene therapy. Z spectra of solutions of the CPG2 substrate, 3,5-difluorobenzoyl-L-glutamate (amide), and glutamate (amine) were acquired at 11.7 T, 37 °C, across different pH (5-8). The ability of CEST-MR to monitor CPG2-mediated release of glutamate was assessed in extracts of CPG2-expressing cancer cells and purified solution of CPG2. The addition of CPG2 to a solution containing 3,5-difluorobenzoyl-L-glutamate led to a marked and progressively increasing CEST effect (+3 ppm), concomitant with the time-dependent release of glutamate induced by CPG2. CEST-MR allows the detection of CPG2 activity in vitro and supports the translation of CEST-MRI to assess CPG2-based gene therapy in vivo.


Population pharmacokinetics of prophylactic cefoxitin in patients undergoing colorectal surgery.
To elucidate whether a dose of 2 g cefoxitin as a prophylactic agent in patients undergoing elective colorectal surgery is able to maintain free drug concentrations above the minimum inhibitory concentration of the microorganisms involved in surgical site infection. This was a prospective study involving 56 patients electively undergoing rectal or colon surgery. All plasma concentration-time data were analyzed simultaneously using the population approach to estimate population pharmacokinetic parameters and study the influence of the subjects' demographic characteristics, disease status, surgical procedure, and clinical laboratory values on the pharmacokinetic properties of cefoxitin. A one-compartment open model was chosen to describe plasma concentrations of cefoxitin. Since cefoxitin is eliminated almost entirely via the kidney, creatinine clearance was identified as a covariate of cefoxitin clearance. The relationship between total cefoxitin clearance (CL) and creatinine clearance (CL(CR)) was best described using a nonlinear model [CL = 11.5 × (CL(CR)/77)(0.52)]. The population apparent volume of distribution was 12 L. Computer simulations carried out to determine the probability to maintain free plasma concentrations above 8 mg/L (the concentration threshold for susceptible bacteria) 2 h after drug administration revealed that this probability decreased from 84% in patients with a CL(CR) of 40 mL/min to 28% in patients with a CL(CR) of 100 mL/min. To ensure cefoxitin target concentrations during surgery, we recommend that cefoxitin be administered every 1.5 h in patients with a CL(CR) ≥ 60 mL/min and every hour if the CL(CR) is ≥ 100 mL/min. Administration by continuous infusion preceded by a bolus injection should also be considered.


Experience with a noninvasive evaluation for cerebral vascular disease.
This report describes a newly developed noninvasive method for extracranial cerebrovascular evaluation. Two hundred consecutive cases were studied at the Massachusetts General Hospital and matched with clinical and angiographic findings. There were three false negative and five false positive results. Two ulcerated plaques without stenosis were not detected. Management routes for different groups of patients with central nervous system symptoms are outlined. We emphasize the usefulness of monitoring postoperative ophthalmic artery pressure to aid in the early detection of carotid occlusion in patients developing neurologic symptoms following carotid endarterectomy.


Localizing antibody-defined immunoreactivity in Porphyromonas gingivalis HtpG recognized by human serum utilizing selective protein expression.
Earlier studies suggested that specific immunoreactive domains of the prokaryotic homologue of Hsp90, HtpG, might contribute to the virulence of the periodontal pathogen, Porphyromonas gingivalis (Pg) [J. Periodontol. 70 (1999) 1185]. Since serum antibodies to this protein appeared to be associated with oral health, we developed a rapid epitope-mapping system that could be tailored to detect antibodies against specific immunoreactive regions of the Pg HtpG protein. This paper describes the use of Caulobacter crescentus (Cc) and the creation of a Cc RsaA fusion protein library that defined specific regions of the Pg HtpG protein. The fusion protein library was used to identify immunoreactive regions in the Pg HtpG dominant in patient and control sera. The development of methods to rapidly localize dominant immunoreactive regions in protein antigens may prove useful for the development of screening tests, vaccines and therapeutics in periodontal and other infectious diseases.


Isolated skip nodal metastasis is rare in T1 and T2 oral tongue squamous cell carcinoma.
Nodal metastasis from oral tongue squamous cell carcinoma follows a predictable pattern. Isolated level IV involvement, termed skip metastases, is described. This study attempts to identify the incidence of skip metastasis. Case series with chart review. Tertiary academic hospital. Fifty-two consecutive patients with T1 to T4 N0 stage who underwent excision of the primary tumor with neck dissection (levels I-IV). Retrospective study. The incidence of isolated level III or IV involvement pathologically and isolated nodal recurrence in levels III and IV was analyzed. Pathologically, isolated level III involvement occurred in 2 (3.8%) patients. Isolated level IV occurred in 1 (1.9%) patient. Mean follow-up was 24 months. Two patients had recurrence in the primary site; 1 had recurrence in neck level II. None had recurrence in level III or IV. Skip metastasis is rare in T1 and T2 oral tongue squamous cell carcinoma. Inclusion of level IV is not mandatory in selective neck dissection for clinically and radiologically negative neck disease in early tumors (T1 and T2).


Mitochondrial ischemia-reperfusion injury of the transplanted rat heart: improved protection by preservation versus cardioplegic solutions.
Cold ischemia time and preservation of organs are limited by I/R injury leading to primary nonfunction of the graft. In a rat heart transplant model, we compared cardioplegic St Thomas (ST) to histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin preservation solutions in terms of contractile function, and mitochondrial respiratory and enzymatic defects after prolonged cold ischemia and reperfusion. Contractile function was scored after transplantation and 24 h of reperfusion. Mitochondrial function was investigated by high-resolution respirometry of permeabilized myocardial fibers. Graft performance in terms of contractile function declined with the duration of cold storage. Recovery was significantly improved after 10 h of cold storage in HTK compared with ST (cardiac scores, 3.3+/-0.5 and 1.8+/-0.8, respectively). Tissue lactate dehydrogenase was better preserved in HTK than ST. Increase of tissue water content (edema) was less pronounced in HTK than ST (3.33+/-0.14 and 3.73+/-0.21 mg/mg dry weight, respectively). Similar cardiac scores (2.6+/-0.9 and 2.9+/-1.2, respectively) and mitochondrial respiratory parameters were obtained after preservation in HTK and University of Wisconsin. Decline in contractile function of individual grafts correlated well with loss of mitochondrial respiratory capacity, whereas citrate synthase activity remained largely preserved, indicating specific damage of respiratory complexes. Our data provide evidence for the superiority of preservation solutions versus a cardioplegic solution for prolonged cold storage of the heart. The correlation of graft performance and mitochondrial function indicates the potential of high-resolution respirometry for quantitative assessment of myocardial injury upon cold I/R, providing a basis for diagnostic approaches and evaluation of improved preservation solutions for heart transplantation.


Application of sulfur microparticles for solid-phase extraction of polycyclic aromatic hydrocarbons from sea water and wastewater samples.
The application of sulfur microparticles as efficient adsorbents for the solid-phase extraction (SPE) and determination of trace amounts of 10 polycyclic aromatic hydrocarbons (PAHs) was investigated in sea water and wastewater samples using high performance liquid chromatography coupled with an ultraviolet detector (HPLC-UV). Parameters influencing the preconcentration of PAHs such as the amount of sulfur, solution flow rate and volume, elution solvent, type and concentration of organic modifier, and salt effect were examined. The results showed that at a flow rate of 10 mL min(-1) for the sample solutions (100mL), the PAHs could be adsorbed on the sulfur microparticles and then eluted by 2.0 mL of acetonitrile. For HPLC-UV analysis of extracted PAHs, the calibration curves were linear in the range of 0.05-80.0 μg L(-1); the coefficients of determinations (r(2)) were between 0.9934 and 0.9995. The relative standard deviations (RSDs) for eight replicates at two concentration levels (0.5 and 4.0 μg L(-1)) of PAHs were lower than 7.3%, under optimized conditions. The limits of detection (LODs, S/N = 3) of the proposed method for the studied PAHs were 0.007-0.048 μg L(-1). The recoveries of spiked PAHs (0.5 and 4 μg L(-1)) in the wastewater and sea water samples ranged from 78% to 108%. The simplicity of experimental procedure, high extraction efficiency, short sample analysis, and using of low cost sorbent demonstrate the potential of this approach for routine trace PAH analysis in water and wastewater samples.


Using subjective cognitive decline to identify high global amyloid in community-based samples: A cross-cohort study.
We aimed to examine the contribution of subjective cognitive decline (SCD) to reduce the number of β-amyloid (Aβ) positron emission tomography scans required for recruiting Aβ+ clinically normal individuals in clinical trials. Three independent cohorts (890 clinically normal: 72 yrs ± 6.7; Female: 43.4%; SCD+: 24%; apolipoprotein E [APOE] ε4+: 28.5%; Aβ+: 32%) were used. SCD was dichotomized from one question. Using logistic regression, we classified Aβ+ using the SCD dichotomy, APOEε4, sex, and age. SCD increased odds of Aβ+ by 1.58 relative to non-SCD. Female APOEε4 carriers with SCD exhibited higher odds of Aβ+ (OR = 3.34), whereas male carriers with SCD showed a weaker, opposing effect (OR = 0.37). SCD endorsement reduces the number of Aβ positron emission tomography scans to recruit Aβ+ individuals by 13% and by 9% if APOEε4 status is known. SCD helps to classify those with high Aβ, even beyond the substantial effect of APOE genotype. Collecting SCD is a feasible method for targeting recruitment for those likely on the AD trajectory.


A Novel Assessment of Metabolic Pathways in Peritoneal Metastases from Low-Grade Appendiceal Mucinous Neoplasms.
There is a paucity of targeted therapies for patients with pseudomyxoma peritonei (PMP) secondary to low-grade appendiceal mucinous neoplasms (LAMNs). Dysregulated metabolism has emerged as a hallmark of cancer, and the relationship of metabolomics and cancer is an area of active scientific exploration. We sought to characterize phenotypic differences found in peritoneal metastases (PM) derived from LAMN versus adenocarcinoma. Tumors were washed with phosphate-buffered saline (PBS), microdissected, then dissociated in ice-cold methanol dried and reconstituted in pyridine. Samples were derivatized in tert-butyldimethylsilyl (TBDMS) and subjected to gas chromatography-coupled mass spectrometry. Metabolites were assessed based on a standard library. RNA sequencing was performed, with pathway and network analyses on differentially expressed genes. Eight peritoneal tumor samples were obtained and analyzed: LAMNs (4), and moderate to poorly differentiated adenocarcinoma (colon [1], appendix [3]). Decreases in pyroglutamate, fumarate, and cysteine in PM from LAMNs were found compared with adenocarcinoma. Analyses showed the differential gene expression was dominated by the prevalence of metabolic pathways, particularly lipid metabolism. The gene retinol saturase (RETSAT), downregulated by LAMN, was involved in the multiple metabolic pathways that involve lipids. Using network mapping, we found IL1B signaling to be a potential top-level modulation candidate. Distinct metabolic signatures may exist for PM from LAMN versus adenocarcinoma. A multitude of genes are differentially regulated, many of which are involved in metabolic pathways. Additional research is needed to identify the significance and applicability of targeting metabolic pathways in the potential development of novel therapeutics for these challenging tumors.


18F-FDG PET/CT-Based Radiomics Nomogram for Prediction of Bone Marrow Involvement in Pediatric Neuroblastoma: A Two-Center Study.
To assess the predictive ability of an 18F-FDG PET/CT-based radiomics nomogram for bone marrow involvement in pediatric neuroblastoma. A total of 241 neuroblastoma patients who underwent 18F-FDG PET/CT at two medical centers were retrospectively evaluated. Data from center A (n = 200) were randomized into a training cohort (n = 140) and an internal validation cohort (n = 60), while data from center B (n = 41) constituted the external validation cohort. For each patient, two regions of interest were defined using the tumor and axial skeleton. The clinical factors and radiomics features were derived to construct the clinical and radiomics models. The radiomics nomogram was built by combining clinical factors and radiomics features. The area under the receiver operating characteristic curves (AUCs) were used to assess the performance of the models. Radiomics models created from tumor and axial skeleton achieved AUCs of 0.773 and 0.900, and the clinical model had an AUC of 0.858 in the training cohort. By incorporating clinical risk factors and axial skeleton-based radiomics features, the AUC of the radiomics nomogram in the training cohort, internal validation cohort, and external validation cohort was 0.932, 0.887, and 0.733, respectively. The axial skeleton-based radiomics model performed better than the tumor-based radiomics model in predicting bone marrow involvement. Moreover, the radiomics nomogram showed that combining axial skeleton-based radiomics features with clinical risk factors improved their performance.


Statistical optimization of process parameters for exopolysaccharide production by Aureobasidium pullulans using sweet potato based medium.
Statistical experimental designs were applied to optimize the fermentation medium for exopolysaccharide (EPS) production. Plackett-Burman design was applied to identify the significance of seven medium variables, in which sweet potato and yeast extract were found to be the significant variables for EPS production. Central composite design was applied to evaluate the optimum condition of the selected variables. Maximum EPS production of 9.3 g/L was obtained with the predicted optimal level of sweet potato 10 %, yeast extract 0.75 %, 5.5 pH, and time 100 h. The determined (R 2) value was 0.97, indicating a good fitted model for EPS production. Results of this study showed that sweet potato can be utilized as a low-cost effective substrate for pullulan production in submerged fermentation.


The effect of stimulation frequency on transcranial evoked potentials.
Transcranial magnetic stimulation-evoked electroencephalography potentials (TEPs) have been used to study motor cortical excitability in healthy subjects and several neurological conditions. However, optimal recording parameters for TEPs are still debated. Stimulation rates could affect TEP amplitude due to plasticity effects, thus confounding the assessment of cortical excitability. We tested whether short interpulse intervals (IPIs) affect TEP amplitude. We investigated possible changes in TEP amplitude and global mean field amplitude (GMFA) obtained with stimulation of the primary motor cortex at IPIs of 1.1-1.4 s in a group of healthy subjects. We found no differences in TEP amplitude or GMFA between the first, second and last third of trials. Short IPIs do not affect TEP size and can be used without the risk of confounding effects due to short-term plasticity.


How are substrates recognized by the ubiquitin-mediated proteolytic system?
A necessary step in the degradation of proteins by the ubiquitin system is recognition by the ubiquitin-protein ligases(s). Various structural features of the proteolytic substrate render it susceptible to conjugation with ubiquitin. The N-terminal residue plays a major role in this process, with distinct sites on the ligase(s) recognizing specific types of N-termini. Post-translational modification of some of these residues is required prior to their recognition. A free N terminus is not the only marker; proteins with either free or blocked N termini can be recognized via structural domains that are downstream and distinct from this residue.


[Preparation and Performance Evaluation of Polyacrylamide Hydrogel Coating on the Surface of Silicone Rubber Nasogastric Tube].
To prepare the hydrogel coating on the surfaces of nasogastric tubes and to evaluate its effect on the insertion of nasogastric tubes in a rabbit model. The polyacrylamide (PAAm) hydrogel coating was prepared by UV-induced free radical polymerization. The morphology of the PAAm coating and its interfacial bonding with the silicone rubber substrates of nasogastric tubes were observed with scanning electron microscope. The composition of the coating was analyzed by Fourier transform infrared (FTIR) spectrometer and X-ray photoelectron spectrometer (XPS). The water absorption power and stability of the coating were measured by the weighing method. Water contact angle meter was used to measure the wettability of the coating and tribometer was used to determine the friction coefficient of the silicone rubber substrates before and after the modification. The cytotoxicity of the coating on L929 murine fibroblast cell line was explored with CCK-8 assay after 24-h coculturing of the L929 cell line with silicone rubber substrates before and after modification. An animal model of nasogastric tube insertion in New Zealand rabbits was used to evaluate the effect of the lubrication coating by assessing the insertion time and nasal damage. In this study, PAAm hydrogel coating was prepared and constructed on the surface of silicone rubber nasogastric tubes. The coating, with a three-dimensional network structure, showed strong interfacial bonding with silicone rubber substrates. The appearance of amino and carbonyl groups indicated that the PAAm hydrogel coating was grafted on the surfaces of nasogastric tubes. Before the modification, the silicone rubber substrate essentially did not absorb much water, whereas, after the modification, the silicone rubber substrate showed significant improvement of as much as 2.9% in water absorption. After sonication for 90 min, the weight loss rate was only 0.15%. Compared with pristine nasogastric tubes, the water contact angle of the modified nasogastric tubes was reduced from 111.9°±2.2° to 58.9°±1.5° ( t=22.59, P<0.05). In addition, the friction coefficient of silicone rubber nasogastric tubes decreased by 69.3% from 0.378±0.05 to 0.116±0.004 ( t=42.80, P<0.05) after modification. Moreover, there was no significant difference in the cytocompatibility between L929 cells cocultured with pristine nasogastric tube and those cocultured with modified nasogastric tube. The animal experiment of nasogastric tube insertion showed that the insertion time of the modified nasogastric tubes was reduced from (41.6±7.8) s to (12.4±2.9) s ( t=8.509, P<0.05). Laryngoscopy revealed that the PAAm hydrogel coating significantly reduced the mucosal damage caused by the insertion of nasogastric tubes. In this study, PAAm hydrogel coating with strong interfacial bonding was prepared on the surface of silicone rubber nasogastric tubes. The coating has excellent hydrophilic lubrication property and cytocompatibility, effectively shortens the insertion time, and reduces the damage caused by nasogastric tube insertion.


Intracranial hemorrhage after carotid endarterectomy.
Among 1500 carotid endarterectomies performed between 1975 and 1984, 11 ipsilateral intracranial hemorrhages (IH) occurred between the first and tenth postoperative days for an incidence of 0.7%. The mortality rate among these patients was 36%. The only recognizable predisposing factor was relief of high-grade carotid stenosis (greater than 90%) whereas other factors such as age (58 to 81 years), preoperative hypertension (systolic blood pressure 120 to 160 mm Hg), preoperative head CT scans showing recent infarction (only one in five positive), and preoperative cerebral infarction (only 1 of 11 patients) did not play a role. All patients had normal coagulation studies. No patient required a shunt because all tolerated cross-clamping of the carotid artery. Postoperative systolic blood pressures were 200 to 240 mm Hg in 6 of 11 patients. The time of occurrence of IH extended from the immediate postoperative period to the tenth postoperative day (mean interval 3.3 days). Treatment consisted of craniotomy in five patients; four survived and one recovered completely. Of the six patients treated nonoperatively, three survived and two completely recovered. IH shares equal incidence with recurrent thrombosis, cross-clamping ischemia, and embolization as a cause of perioperative stroke. Although all except IH can be prevented by current practice, the means of preventing IH are not apparent; however, careful monitoring of blood pressure to prevent uncontrolled hypertension deserves consideration.


Single breath-hold extended free-breathing navigator-gated three-dimensional coronary MRA.
To acquire the center of k-space while extending three-dimensional free-breathing navigator-gated coronary magnetic resonance (MR) angiography by an initial single breath-hold. This approach was successfully applied in eight healthy adult subjects. Resulting images were compared with conventionally acquired free-breathing navigator-gated MR angiograms. The acquisition of k-space center during the single breath-hold resulted in a 26% increase (P < 0.05) of signal-to-noise ratio. Visible length of the right coronary artery, as well as contrast-to-noise ratio between the blood and the myocardial muscle, were identical. The breath-hold extension was shown to be a valuable technique that may be combined with first-pass contrast-enhanced MR imaging.


Lewy Body Disease Primate Model with α-Synuclein Propagation from the Olfactory Bulb.
Lewy body diseases (LBDs), which are pathologically defined as the presence of intraneuronal α-synuclein (α-Syn) inclusions called Lewy bodies, encompass Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies. Autopsy studies have shown that the olfactory bulb (OB) is one of the regions where Lewy pathology develops and initiates its spread in the brain. This study aims to clarify how Lewy pathology spreads from the OB and affects brain functions using nonhuman primates. We inoculated α-Syn preformed fibrils into the unilateral OBs of common marmosets (Callithrix jacchus) and performed pathological analyses, manganese-enhanced magnetic resonance imaging, and 18 F-fluoro-2-deoxy-d-glucose positron emission tomography up to 6 months postinoculation. Severe α-Syn pathology was observed within the olfactory pathway and limbic system, while mild α-Syn pathology was seen in a wide range of brain regions, including the substantia nigra pars compacta, locus coeruleus, and even dorsal motor nucleus of the vagus nerve. The brain imaging analyses showed reduction in volume of the OB and progressive glucose hypometabolism in widespread brain regions, including the occipital lobe, and extended beyond the pathologically affected regions. We generated a novel nonhuman primate LBD model with α-Syn propagation from the OB. This model suggests that α-Syn propagation from the OB is related to OB atrophy and cerebral glucose hypometabolism in LBDs. © 2022 International Parkinson and Movement Disorder Society.


Phase II evaluation of dibromodulcitol and actinomycin D, hydroxyurea, and cyclophosphamide in previously untreated patients with malignant melanoma.
In this Eastern Cooperative Oncology Group (ECOG) phase II study, dibromodulcitol (DBD) and a combination of actinomycin D, hydroxyurea, and cyclophosphamide (AHC) were compared with methyl-CCNU, the current ECOG standard, in patients who had received no prior chemotherapy for disseminated malignant melanoma. The response rates were 6% (3/50) for AHC, 9% (3/34) for DBD, and 14% (7/49) for methyl-CCNU. Median survival times were 4, 5, and 6 months, respectively. Neither regimen appears to offer any advantage over methyl-CCNU as front-line therapy for patients with disseminated melanoma.


A genotype and phenotype analysis of SMAD6 mutant patients with radioulnar synostosis.
SMAD6 variants have been reported in patients with radioulnar synostosis (RUS). This study aimed to investigate the genotypes and phenotypes for a large cohort of patients with RUS having mutant SMAD6. Genomic DNA samples were isolated from 251 RUS sporadic patients (with their parents) and 27 RUS pedigrees. Sanger sequencing was performed for the SMAD6 coding regions. For positive probands, co-segregation and parental-origin analysis of SMAD6 variants and phenotypic re-evaluation were performed for their family members. We identified 50 RUS probands with SMAD6 variants (13 co-segregated with RUS in pedigrees and 37 in RUS-sporadic patients). Based on the new and previous data, we identified SMAD6 mutated in 16/38 RUS pedigrees and 61/393 RUS sporadic patients, respectively. Overall, 93 SMAD6 mutant patients with RUS were identified, among which 29 patients had unilateral RUS, where the left side was more involved than the right side (left:right = 20:9). Female protective effects and non-full penetrance were observed, in which only 6.90% mothers (vs. ~50% fathers) of SMAD6 mutant RUS probands had RUS. Pleiotropy was observed as a re-evaluation of SMAD6 mutant families identified: (a) three families had axial skeletal malformations; (b) two families had polydactyly; and (c) eight families had other known malformations. SMAD6 was mutated in 42.11% RUS pedigrees and 15.52% RUS sporadic patients. The RUS patients with SMAD6 variants exhibit both non-full-penetrance, variable expressivity, pleiotropy, female protective effects, and the left side is more susceptible than the right side.


miR-148b reverses cisplatin-resistance in non-small cell cancer cells via negatively regulating DNA (cytosine-5)-methyltransferase 1(DNMT1) expression.
The emergence of drug resistance in cancer patients limits the success rate of clinical chemotherapy. MicroRNAs (miRNAs) may play a role in chemoresistance and may be involved in modulating of some drug resistance-related pathways in cancer cells. In this study, the involvement of microRNA-148b (miR-148b) and its roles in the development of chemoresistance in lung cancer are determined. This study was performed in two lung cancer cell lines (A549 and SPC-A1). The levels of miR-148b and DNMT1 mRNA expression were determined by using Quantitative Real-Time PCR. Proteins of DNMTs are represented by western blot assay. Cell viability was assessed by MTT assay. Cell apoptosis was evaluated using flow cytometry. The data showed a down-regulated of miR-148b expression and evaluated methyltransferases (DNMTs) expression in cisplatin-resisted human non-small cell lung cancer (NSCLC) cell line-A549/DDP and SPC-A1/DDP compared with their parental A549 and SPC-A1 cell line. In transfection experiments, miR-148b mimics reduced the DNMT1 expression, as well as enhanced the sensitivity of cells to cisplatin and cisplatin-induced apoptosis in A549/DDP or SPC-A1/DDP cells. While miR-148b inhibitor increased DNMT1 expression, as well as attenuated the sensitivity of cells to cisplatin in A549 and SPC-A1 cells. miR-148b was showed to exert negative effect on DNMT1 expression by targeting its 3'UTR in A549/DDP and A549 cells. Importantly, silenced DNMT1 increases cisplatin sensitivity of A549/DDP cells and over-expressed DNMT1 reverses pro-apoptosis effect of miR-148b mimic. miR-148b reverses cisplatin-resistance in non-small cell cancer cells via negatively regulating DNMT1 expression.


Sociocultural Practices Affecting the Care of Preterm Infants in the Ghanaian Community.
Although culture is an integral part of health, there is scarcity of evidence on the influence of culture on caregiving experiences of parents of preterm infants. The aim of this study was to explore the influence of sociocultural practices on caring for preterm infants in the Ghanaian community. Narrative inquiry was utilized to explore the influence of sociocultural practices on the care of preterm infants from 21 mothers, 9 fathers, and 12 household members. Data were collected through face-to-face semistructured interviews and observations at participants' homes. Analysis of data resulted in three threads/themes-respect for the elderly, use of herbal medicines, and communal living. Community and extended family members have great influence on the care of preterm infants. Traditional herbal medicines are considered effective in treating traditional illnesses among preterm infants. Understanding the influence of culture on the care of vulnerable preterm infants in the community is essential in developing interventions for infant survival.


Role of the host stroma in cancer and its therapeutic significance.
Current cancer research focuses mainly upon the cancer cells in malignant tumours and is providing a growing database about aberrations in their genetic composition. However, tumours also contain non-cancerous host tissue, referred to as the stroma, which plays an active and indispensable role in tumour growth and influences the virulence of the neoplasm towards the host. Many cell types inhabit the stroma, amidst apparently inert fibrous and viscous matrix material, composed of complex polysaccharides, proteins and other molecules. Actually, all of these elements are in constant turnover, causing unpredictable evolution in the properties of the community. This article provides pathologic observations and data on reciprocal interactions between these stromal and neoplastic components of tumours and how they change during the course of the disease. Malignant progression depends upon dauntingly intricate communications between different specialised lineages within the cellular society, which enable rapid adaptation to changing circumstances. Opportunistic misuse of such communication networks enables tumour cells to recruit and incorporate adjacent normal stroma into their midst, so that they may grow, infiltrate and parasitise the host. The absolute dependency of primary tumours and metastases on their diverse stromal components for survival and their insatiable need to continuously recruit more stroma to support expansion, renders them vulnerable to strategies capable of disrupting the cellular interactions involved. This dependency is of critical importance for cancer therapy research, and proposed methods for turning this parasitic behaviour of tumours against themselves are suggested below.


A Prospective, Randomized Trial Comparing Liposomal Bupivacaine vs Fascia Iliaca Compartment Block for Postoperative Pain Control in Total Hip Arthroplasty.
Increasing demand for total hip arthroplasty (THA) in a climate of increasing focus on clinical outcomes, patient satisfaction, and cost has created a need for better acute postoperative pain control for patients. An ideal pain control method would have few side effects, decreased opioid consumption, improved pain control, early ambulation, and decreased hospital length of stay (LOS). We performed a prospective randomized, controlled study involving 79 patients undergoing elective THA between June 2015 and February 2016. Forty patients received liposomal bupivacaine and 39 patients received a fascia iliaca compartment block (FICB). In addition, the medical records of 28 patients who underwent elective THA between May 2015 and December 2015 were retrospectively examined. The primary outcome was visual analog scale pain scores and the secondary outcomes were LOS and total opioid consumption. SPSS, version 22, was used to run 1-way analysis of variance with contrast and Mood's median test on the data. There were statistically significant decreases in pain intensity (P = .019) and LOS (P = .041) in both the liposomal bupivacaine group and the FICB group compared with those in the retrospective control group. In addition, only the FICB group showed statistically significant decreased total opioid consumption compared with that in the retrospective group (P = .028). Patients undergoing elective THA have decreased overall pain intensity and a shorter LOS with multimodal pain management regimen that includes either liposomal bupivacaine or FICB. Patients who received FICB required less overall total opioids than the control group.


[Experimental model of primary cultured metastatic melanoma by fine needle aspiration].
Establish an experimental model of metastatic melanoma primary culture cells from fine-needle aspiration biopsies (FNAB). Two metastatic melanoma primary culture cells from (FNAB) have been developed from patients who had been submitted to excision of metastatic lesions and they were identified by immunohistochemical analyses using S-100 and MB-45 melanoma markers. The culture diagnostic was confirmed by immunohistochemical. The technique of FNAB offers the advantage of providing a sequential analysis of the same tumor nodules throughout treatment, and is a minimally invasive procedure with almost no associated morbidity. The establishment of metastatic melanoma primary culture from FNAB samples showed a viable technique.


Distributed neural actions of anti-parkinsonian therapies as revealed by PET.
There is a limited understanding of how different anti-parkinsonian treatments act at the neuronal systems level. Using positron emission tomography we examined the effects of levodopa and deep brain stimulation of the subthalamic nucleus on patterns of regional cerebral blood flow in patients with Parkinson's disease during a homogenous cognitive-behavioural state rather than during an unspecified resting state. We found that when medicated precuneus, frontal, parietal, cerebellar and midbrain areas were relatively more activated than when stimulated, whereas when stimulated the precentral gyrus, caudate and thalamus were relatively more activated than when medicated. Areas that were activated by both treatments included the temporal gyri, anterior thalamus, and midbrain. Regions of prefrontal cortex showed relatively greater activation in the "off treatment" conditions of both the medicated and stimulated groups. Our findings suggest that the two treatment methods may lead to symptomatic relief via both common and different sites of action.


The density and protein content of calcium oxalate crystals precipitated from human urine: a tool to investigate ultrastructure and the fractional volume occupied by organic matrix.
One of the key debates in biomineralisation studies is the extent to which components of the organic matrix become occluded into the crystal lattice during growth. Here, the relationship between protein content and density of calcium oxalate crystals grown in human urine has been investigated in order to determine which fraction of crystal volume is non-mineral. The density of crystals varied from 1.84 to 2.08 g/cm3 while the protein content ranged from 0.1 to 2.1% (w/w). There was an inverse relationship between measured density and protein content which was qualitatively and quantitatively consistent with predictions based on reasonable densities for the mineral and non-mineral components. The coefficients of the fitted equation suggest that, at 2% protein (w/w), the volume of non-mineral would be 5.0% (v/v). The density values we observed are incompatible with fractional volumes of 20%. The results confirm that the occlusion of a small but possibly significant amount of protein into a crystal lattice is possible, but cast doubt on the hypothesis that protein acts as a major intracrystalline ultrastructural element. Moreover, the methodology developed for this study offers a simple and robust method for interrogating organic/inorganic associations in a range of biological and medical systems.


Geospatial multivariate analysis of COVID-19: a global perspective.
This manuscript presents a geospatial and temporal analysis of the COVID'19 along with its mortality rate worldwide and an empirical evaluation of social distance policies on economic activities. Stock Market Indices, Purchasing Manager Index (PMI), and Stringency Index values are evaluated with respect to rising COVID-19 cases based on the collected data from Jan 2020 to June 2021. The findings for the stock market index reveal the highest negative correlation coefficient value, i.e., -0.2, for the Shanghai index, representing a negative relation on stock markets, whereas the value of the correlation coefficient is minimum for Indian markets, i.e., 0.3, indicating the most impact by COVID-19 spread. Further, the results concerning PMI show that the highest value of the correlation coefficient is for the China i.e., -0.52, points to the sharpest pace of contraction. This reflects the lower value of the correlation indicating that the economy is on the way of growth, which can be seen from the PMI value of the various countries. The manuscript presents a novel geospatial model by empirically evaluating the correlation coefficient of COVID-19 with stock market index, PMI, and stringency index to understand the effect of COVID-19 on the global economy.


Upregulation of cyclin-dependent kinase inhibitors CDKN1B and CDKN1C in hepatocellular carcinoma-derived cells via goniothalamin-mediated protein stabilization and epigenetic modifications.
Cell cycle deregulation is common in human hepatocellular carcinoma (HCC). To ensure proper cell cycle controlling, cyclin/cyclin-dependent kinases (CDK) complexes are tightly regulated by CDK inhibitors (CKIs) in normal cells. However, insufficient cyclin-dependent kinase inhibitor 1B (CDKN1B, also known as p27Kip1) and CDKN1C (p57Kip2) proteins are characteristics of high-risk HCC. In two HCC-derived cell lines with distinct genetic backgrounds, we identified a small natural compound, goniothalamin (GTN), serving as an inducer of CKIs. In TP53-mutated (Y220C) and retinoblastoma 1 (RB1)-positive Huh-7 cells, GTN stabilized CDKN1B protein levels by targeting the degradation of its specific E3 ubiquitin ligase (S-phase kinase-associated protein 2). Alternatively, in TP53- and RB1-negative Hep-3B cells, GTN increased CDKN1C transcription and its subsequent translation by acting as a histone deacetylase inhibitor. In both cell lines, GTN induced G0/G1 cell cycle arrest, delayed S phase entry of cells and inhibited anchorage-independent cell growth which might be attributed to the upregulation of CKIs and downregulation of several positive cell cycle regulators, including CDC28 protein kinase regulator subunit 1B, cyclin E1 and D1, cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, E2F transcription factor 1 and/or transcription factor Dp-1. Therefore, GTN might represent a novel class of anticancer drug that induces CKIs through post-translational and epigenetic modifications.