The effect of bovine activin and follicle-stimulating hormone (FSH) suppressing protein/follistatin on FSH-induced differentiation of rat granulosa cells in vitro.
The time- and dose-dependent effects of bovine activin A and bovine follicle stimulating hormone (FSH) suppressing protein (FSP) or follistatin on basal and FSH-induced steroidogenesis and inhibin production were studied in granulosa cells from immature, diethylstilbestrol (DES)-treated rats. In the presence of rat FSH (20 ng/ml) which stimulates aromatase activity and the production of progesterone and inhibin, activin (0.3-100 ng/ml) augmented all three parameters, whereas FSP (0.3-100 ng/ml) enhanced progesterone production and attenuated the other two parameters. In the absence of FSH, the basal parameters were unaffected by treatment with either activin or FSP alone, except for a statistically significant increase in basal inhibin in the presence of activin alone (P less than 0.05, at doses of 30 and 100 ng/ml). Neither activin nor FSP influenced the timing of the maxima of FSH-induced activities over 5 days. These findings suggest that activin and FSP, both present in follicular fluid, may play an important role in the local regulation of granulosa cell differentiation.


Gradual strenuous running regimen predisposes to osteoarthritis due to cartilage cell death and altered levels of glycosaminoglycans.
To investigate the hypothesis that strenuous running is a predisposing factor for osteoarthritis. Wistar rats were divided into two groups: a control group (CG) and a trained group (TG). The TG underwent a strenuous treadmill running training regimen of controlled intensity, exhibiting progressively improvement of fitness over 12 weeks, running at least 55 km during this period and finally performing an ultra-endurance running exercise to exhaustion. After this period, rats from both groups were euthanized and their knees removed. The articular cartilage was dissected and submitted to histomorphometrical, histomorphological, and immunohistochemical analyses evaluating cell death pathway (caspase-3 and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL)) and inflammatory cytokines [interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α)]. In addition, the tissues were analyzed regarding the types and the content of glycosaminoglycans. The TG knee joints exhibited increase in the number of chondrocytes and chondrocyte clusters, as well as significantly increased levels of caspase-3, a protein involved in apoptosis, and of inflammatory cytokines IL-1α and TNF-α. In addition, histologically higher grades of osteoarthritis (Osteoarthritis Research Society International - OARSI grading), and significantly decreased levels of chondroitin sulfate and hyaluronic acid. Knee cartilage thickness and TUNEL did not significantly differ between the two groups. The articular cartilage of rats subjected to a strenuous running regimen of controlled intensity exhibited molecular and histological characteristics that are present in osteoarthritis.


Opposing roles and potential antagonistic mechanism between TGF-β and BMP pathways: Implications for cancer progression.
The transforming growth factor β (TGF-β) superfamily participates in tumour proliferation, apoptosis, differentiation, migration, invasion, immune evasion and extracellular matrix remodelling. Genetic deficiency in distinct components of TGF-β and BMP-induced signalling pathways or their excessive activation has been reported to regulate the development and progression of some cancers. As more in-depth studies about this superfamily have been conducted, more evidence suggests that the TGF-β and BMP pathways play an opposing role. The cross-talk of these 2 pathways has been widely studied in kidney disease and bone formation, and the opposing effects have also been observed in some cancers. However, the antagonistic mechanisms are still insufficiently investigated in cancer. In this review, we aim to display more evidences and possible mechanisms accounting for the antagonism between these 2 pathways, which might provide some clues for further study in cancer.


Synthesis of 1,2,3,4-tetrasubstituted naphthalenes through a cascade reaction triggered by silyl acetal activation.
1,2,3,4-Tetrasubstituted naphthalenes bearing four different substituents were synthesized in a regioselective manner through a fluoride-induced cascade reaction of lactol silyl ethers, which could be easily prepared from 4-alkynylisocoumarins and ketene silyl acetal.


Single image super-resolution for whole slide image using convolutional neural networks and self-supervised color normalization.
High-quality whole slide scanners used for animal and human pathology scanning are expensive and can produce massive datasets, which limits the access to and adoption of this technique. As a potential solution to these challenges, we present a deep learning-based approach making use of single image super-resolution (SISR) to reconstruct high-resolution histology images from low-resolution inputs. Such low-resolution images can easily be shared, require less storage, and can be acquired quickly using widely available low-cost slide scanners. The network consists of multi-scale fully convolutional networks capable of capturing hierarchical features. Conditional generative adversarial loss is incorporated to penalize blurriness in the output images. The network is trained using a progressive strategy where the scaling factor is sampled from a normal distribution with an increasing mean. The results are evaluated with quantitative metrics and are used in a clinical histopathology diagnosis procedure which shows that the SISR framework can be used to reconstruct high-resolution images with clinical level quality. We further propose a self-supervised color normalization method that can remove staining variation artifacts. Quantitative evaluations show that the SISR framework can generalize well on unseen data collected from other patient tissue cohorts by incorporating the color normalization method.


The N2-guanine adduct but not the C8-guanine or N6-adenine adducts formed by 4-nitroquinoline 1-oxide blocks the 3'-5' exonuclease action of T4 DNA polymerase.
When O-acetyl-4-(hydroxyamino)quinoline 1-oxide (Ac-4HAQO) reacts with double-stranded DNA at 37 degrees C the major products, N2-guanine, C8-guanine, and N6-adenine adducts, are formed in the proportions of 5:3:2, respectively. When the reaction is carried out with single-stranded DNA at 0 degree C, the products are found in the ratio 1:7:2. Unique 174-bp DNA fragments were modified in these ways and used as substrates for the 3'-5' exonuclease activity of T4 DNA polymerase. The results obtained showed that the exonuclease is blocked by the N2-guanine adduct but not the other two adducts. Interpretation of the cleavage patterns suggested that the enzyme stopped 2 nucleotides before the N2-guanine adduct. The N2-guanine adduct lies in the minor groove of the DNA double helix, while the other two adducts are found in the major groove. Apparently, only the former hinders progression of the enzyme.


Correction: Assessing the exchange coupling in binuclear lanthanide(iii) complexes and the slow relaxation of the magnetization in the antiferromagnetically coupled Dy2 derivative.
[This corrects the article DOI: 10.1039/C5SC01029B.].


Interactions between alpha-latrotoxin and trivalent cations in rat striatal synaptosomal preparations.
The interactions between alpha-latrotoxin (alpha-LTx), a neurosecretagogue purified from the venom of the black widow spider, and the trivalent cations Al3+, Y3+, La3+, Gd3+, and Yb3+ were investigated in rat striatal synaptosomal preparations. All trivalent cations tested were inhibitors of alpha-LTx-induced [3H]dopamine [( 3H]DA) release (order of potency: Yb3+ greater than Gd3+ approximately Y3+ greater than La3+ greater than Al3+). Only with Al3+ could inhibition of [3H]DA release be attributed to a block of 125I-alpha-LTx specific binding to synaptosomal preparations. The inhibitory effect of trivalent ions was reversible provided synaptosomes were washed with buffer containing EDTA. Trivalent ions also inhibited alpha-LTx-induced [3H]DA release at times when alpha-LTx-stimulated release was already evident. alpha-LTx-induced synaptosomal membrane depolarization was blocked by La3+, but not affected by Gd3+, Y3+, and Yb3+. alpha-LTx-stimulated uptake of 45Ca2+ was inhibited by all trivalent cations tested. These results demonstrate that there exist at least three means by which trivalent cations can inhibit alpha-LTx action in rat striatal synaptosomal preparations: (1) inhibition of alpha-LTx binding (Al3+); (2) inhibition of alpha-LTx-induced depolarization (La3+); and (3) inhibition of alpha-LTx-induced 45Ca2+ uptake (Gd3+, Y3+, Yb3+, La3+).


Children at familial risk for obesity: an examination of dietary intake, physical activity and weight status.
A large cohort of children was divided into two groups based on their parents' weight status. The high risk group had one or two overweight parent(s) (n = 92, 4.4 +/- 0.5 years), while the low risk group had no parent overweight (n = 95, 4.5 +/- 0.5 years). Weight of the two groups was similar at the start of the study but the high risk group gained marginally more weight over a one year period (P = 0.05). Although total energy intake was similar, the high risk group was consuming a larger percentage of energy from fat (P = 0.0004) and a smaller percentage from carbohydrate (P = 0.0002). Observed physical activity as similar for most levels but marginally higher for the stationary level and marginally lower in total activity in the high risk group. These results suggest a pattern that may lead to increased weight gain in a high risk group as they grow older.


A study of carbon dioxide-dependent strains of Streptococcus milleri.
Forty-four strains of non-haemolytic streptococci, from a variety of sites, that required CO2 for aerobic growth were identified as Streptococcus milleri. Of these strains, 40 (90%) possessed the Lancefield group-F antigen, the remainder being non-groupable with antisera to the group antigens A, C, F and G.


Phosphoinositides in the mammalian endo-lysosomal network.
The endo-lysosomal system is an interconnected tubulo-vesicular network that acts as a sorting station to process and distribute internalised cargo. This network accepts cargoes from both the plasma membrane and the biosynthetic pathway, and directs these cargos either towards the lysosome for degradation, the peri-nuclear recycling endosome for return to the cell surface, or to the trans-Golgi network. These intracellular membranes are variously enriched in different phosphoinositides that help to shape compartmental identity. These lipids act to localise a number of phosphoinositide-binding proteins that function as sorting machineries to regulate endosomal cargo sorting. Herein we discuss regulation of these machineries by phosphoinositides and explore how phosphoinositide-switching contributes toward sorting decisions made at this platform.


Proteasome limits plasticity-related signaling to the nucleus in the hippocampus.
Proteolysis by the ubiquitin-proteasome pathway has pleiotropic effects on both induction and maintenance of long-term synaptic plasticity. In this study, we examined the effect of proteasome inhibition on signaling to the nucleus during late-phase long-term potentiation. When a subthreshold L-LTP induction protocol was used, proteasome inhibition led to a significant increase in phosphorylated CREB (pCREB) in the nucleus. Inhibitors of cAMP-dependent protein kinase/protein kinase A, extracellular signal-regulated kinase and cGMP-dependent protein kinase/protein kinase G all blocked the proteasome-inhibition-mediated increase in nuclear pCREB after subthreshold stimulation. These results lay the groundwork for understanding a novel role for the proteasome in limiting signaling to the nucleus in the absence of adequate synaptic stimulation.


Analyzing 395,793 samples shows significant association between rs999737 polymorphism and breast cancer.
Large-scale genome-wide association studies (GWAS) have been conducted and reported the association between rs999737 polymorphism at 14q24.1 (RAD51L1) and breast cancer risk. Following studies investigated rs999737 polymorphism in European and Asian populations. However, some of these studies reported weak and no significant association. Here, we reevaluated this association using large-scale samples from previous 11 studies (n=395,793; 162,261 cases and 233,532 controls) from the PubMed database. We evaluated the genetic heterogeneity among the selected studies. The pooled odds ratio (OR) is calculated by the fixed effect model. All statistical tests for heterogeneity and meta-analysis were computed using R package. We did not identify significant heterogeneity among the included studies using the allele model (P=0.1314 and I (2)=33.4 %). We observed significant association between rs999737 and breast cancer using the allele model (P=2.47E - 35, OR=0.92, 95 % confidence interval (CI) 0.91-0.93). Our analysis further supports previous findings that the rs999737 polymorphism contributes to breast cancer susceptibility. We believe that our finding will be very useful for future genetic studies in breast cancer.


Etiological influences on the stability of autistic traits from childhood to early adulthood: evidence from a twin study.
Autism spectrum disorders (ASD) are persistent and lifelong conditions. Despite this, almost all twin studies focus on childhood. This twin study investigated the stability of autistic traits from childhood to early adulthood and explored the degree to which any stability could be explained by genetic or environmental factors. Parents of over 2500 twin pairs completed questionnaires assessing autistic traits when twins were aged either 9 or 12 years and again when twins were aged 18. Bivariate twin analysis assessed the degree of phenotypic and etiological stability in autistic traits across this period. Genetic overlap in autistic traits across development was also tested in individuals displaying a broad ASD phenotype, defined as scoring within the highest 5% of the sample. Autistic traits displayed moderate phenotypic stability (r = .39). The heritability of autistic traits was 76-77% in childhood and 60-62% in adulthood. A moderate degree of genetic influences on childhood autistic traits were carried across into adulthood (genetic correlation = .49). The majority (85%) of the stability in autistic traits was attributable to genetic factors. Genetic influences on autistic traits were moderately stable from childhood to early adulthood at the extremes (genetic correlation = .64). Broad autistic traits display moderate phenotypic and etiological stability from childhood to early adulthood. Genetic factors accounted for almost all phenotypic stability, although there was some phenotypic and etiological instability in autistic traits. Thus, autistic traits in adulthood are influenced by a combination of enduring and unique genetic factors.


Protein Bioavailability in Animal Model.
All the nutrients in food are not absorbed by our system. The relative amount of nutrition from an administered dosage through which it enters the system of circulation and the rate at which the level of nutrition appears in the systemic circulation is called 'bioavailability'. Although plant foods have high nutrient contents our digestion system cannot absorb it fully. Hence, it becomes necessary to determine the bioavailability of the administered sample to check the overall effect on the living system. Animal food preparation, protein bioavailability in animal model, food efficiency, apparent digestibility, protein digestibility tests, etc., are mentioned in well explained methodologies.


Prospective Immunophenotyping of CD8+ T Cells and Associated Clinical Outcomes of Patients With Oligometastatic Prostate Cancer Treated With Metastasis-Directed SBRT.
This study examined the effects of metastasis-directed stereotactic body radiation therapy (mdSBRT) on CD8+ T-cell subpopulations and correlated post-mdSBRT immunophenotypic responses with clinical outcomes in patients with oligometastatic prostate cancer (OPCa). Peripheral blood mononuclear cells were prospectively isolated from 37 patients with OPCa (≤3 metastases) who were treated with mdSBRT. Immunophenotyping identified circulating CD8+ T-cell subpopulations, including tumor-reactive (TTR), effector memory, central memory (TCM), effector, and naïve T cells from samples collected before and after mdSBRT. Univariate Cox proportional hazards regression was used to assess whether changes in these T-cell subpopulations were potential risk factors for death and/or progression. The Kaplan-Meier method was used for survival. Cumulative incidence for progression and new distant metastasis weas estimated, considering death as a competing risk. Median follow-up was 39 months (interquartile range, 34-43). Overall survival at 3 years was 78.2%. Cumulative incidence for local progression and new distant metastasis at 3 years was 16.5% and 67.6%, respectively. Between baseline and day 14 after mdSBRT, an increase in the TCM cell subpopulation was associated with the risk of death (hazard ratio, 1.22 [95% confidence interval, 1.02-1.47]; P = .033), and an increase in the TTR cell subpopulation was protective against the risk of local progression (hazard ratio, 0.80 [95% confidence interval, 0.65-0.98]; P = .032). An increase in the TTR cell subpopulation was protective against the risk of disease progression, and an increase in the TCM cell subpopulation was associated with the risk of death in patients with OPCa treated with mdSBRT. Disease control may be further improved by better understanding the CD8+ T-cell subpopulations and by enhancing their antitumor effect.


Predictors and consequences of prescription drug misuse during middle school.
Non-medical prescription drug use (NMPDU) is a growing public health problem among adolescents. This is the first study to examine the correlates of early NMPDU initiation during middle school, and how early initiation is associated with four domains of functioning in high school (mental health, social, academic, and delinquency). Students initially in 6th-8th grades from 16 middle schools completed in-school surveys between 2008 and 2011 (Waves 1-5), and a web-based survey in 2013-2014 (Wave 6). We used discrete time survival analysis to assess predictors of initiation from Waves 1 to 5 based on students who provided NMPDU information at any of these waves (n=12,904), and regression analysis to examine high school outcomes associated with initiation based on a sample that was followed into high school, Wave 6 (n=2539). Low resistance self-efficacy, family substance use, low parental respect, and offers of other substances from peers were consistently associated with NMPDU initiation throughout middle school. Further, perceiving that more of one's peers engaged in other substance use was associated with initiation at Wave 1 only. By high school, those students who initiated NMPDU during middle school reported lower social functioning, and more suspensions and fighting, compared to students who did not initiate NMPDU during middle school. NMPDU initiation during middle school is associated with poorer social functioning and greater delinquency in high school. It is important for middle school prevention programs to address NMPDU. Such programs should focus on both family and peer influences, as well as strengthening resistance self-efficacy.


The "heterolytic hydroperoxide lyase" is an isomerase producing a short-lived fatty acid hemiacetal.
To elucidate the reaction mechanism of hydroperoxide lyase (HPL), the enzyme from guava (Psidium guajava) fruits, was incubated for 10-60 s at 0 degrees C with 13-HPOT. The products were rapidly extracted and derivatized by trimethylsilylation. Two trapping products, namely the trimethylsilyl ether/ester derivatives of the hemiacetal 12-(1'-hydroxy-3'-hexenyloxy)-9,11-dodecadienoic acid and the enol (9Z,11E)-12-hydroxy-9,11-dodecadienoic acid, were detected by gas chromatography-mass spectrometry (GC-MS) analyses. The structural assignments were supported by mass spectra recorded for (a) hydrogenated products; (b) products biosynthesized from [9,10,12,13,15,16] 13-HPOT or [(18)O(2)]13-HPOT; (c) chemically prepared reference compounds. Kinetic experiments showed that the hemiacetal and enol were both unstable and transiently appearing compounds (half-lives, ca. 20 s and 2 min, respectively). Hemiacetal and enol biosynthesized from [(18)O(2)]13-HPOT retained two and one (18)O atoms, respectively, whereas no (18)O was incorporated from [(18)O]water. The data demonstrated that: (1) the true enzymatic product formed from 13-HPOT in the presence of HPL is a short-lived hemiacetal; (2) the hemiacetal spontaneously dissociates into (3Z)-hexenal and the unstable enol form of (9Z)-12-oxo-9-dodecenoic acid; (3) the enzymatic isomerization of 13-HPOT into the hemiacetal occurs homolytically.


MR image and CT scan of a tuberculous abscess in the gluteus maximus muscle.
A 77-year-old man had rapidly increased intramuscular tuberculous abscess in his left buttock. Radiographs showed a bone defect in the left ischium. Postcontrast CT scanning revealed marginal enhancement. MR imaging showed low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. T1-weighted MR images with Gd-DTPA enhancement showed enhancement of the wall. Bone defect and marginal enhancement on postcontrast MR images and on postcontrast CT images are image character of the intramuscular tuberculous abscess.


Ubiquitin-proteasome system impairment caused by a missense cardiac myosin-binding protein C mutation and associated with cardiac dysfunction in hypertrophic cardiomyopathy.
The ubiquitin-proteasome system is responsible for the disappearance of truncated cardiac myosin-binding protein C, and the suppression of its activity contributes to cardiac dysfunction. This study investigated whether missense cardiac myosin-binding protein C gene (MYBPC3) mutation in hypertrophic cardiomyopathy (HCM) leads to destabilization of its protein, causes UPS impairment, and is associated with cardiac dysfunction. Mutations were identified in Japanese HCM patients using denaturing HPLC and sequencing. Heterologous expression was investigated in COS-7 cells as well as neonatal rat cardiac myocytes to examine protein stability and proteasome activity. The cardiac function was measured using echocardiography. Five novel MYBPC3 mutations -- E344K, DeltaK814, Delta2864-2865GC, Q998E, and T1046M -- were identified in this study. Compared with the wild type and other mutations, the E334K protein level was significantly lower, it was degraded faster, it had a higher level of polyubiquination, and increased in cells pretreated with the proteasome inhibitor MG132 (50 microM, 6 h). The electrical charge of its amino acid at position 334 influenced its stability, but E334K did not affect its phosphorylation. The E334K protein reduced cellular 20 S proteasome activity, increased the proapoptotic/antiapoptotic protein ratio, and enhanced apoptosis in transfected Cos-7 cells and neonatal rat cardiac myocytes. Patients carrying the E334K mutation presented significant left ventricular dysfunction and dilation. The conclusion is the missense MYBPC3 mutation E334K destabilizes its protein through UPS and may contribute to cardiac dysfunction in HCM through impairment of the ubiquitin-proteasome system.


Osteogenesis imperfecta in childhood: treatment strategies.
Osteogenesis imperfecta (OI) is a skeletal disorder of remarkable clinical variability characterized by bone fragility, osteopenia, variable degrees of short stature, and progressive skeletal deformities. Additional clinical manifestations such as blue sclerae, dentinogenesis imperfecta, joint laxity, and maturity onset deafness are described in the literature. OI occurs in about 1 in 20,000 births and is caused by quantitative and qualitative defects in the synthesis of collagen I. Depending on the severity of the disease, a large impact on motor development, range of joint motion, muscle strength, and functional ability may occur. Treatment strategies should primarily focus on the improvement of functional ability and the adoption of compensatory strategies, rather than merely improving range of joint motion and muscle strength. Surgical treatment of the extremities may be indicated to stabilize the long bones to optimize functional ability and walking capacity. Surgical treatment of the spine may be indicated in patients with progressive spinal deformity and in those with symptomatic basilar impression.


[Comment on articule "Bibliometric analysis of scientific publications on COVID-19 elaborated by staff of the Instituto Mexicano del Seguro Social"].
In this letter to the editor, some doubts are expressed about the methodology used in the article Bibliometric analysis of scientific publications on COVID-19 elaborated by staff of the Instituto Mexicano del Seguro Social with the purpose of clarifying them and strengthening the scientific rigor with which it was carried out the investigation. The replicability of the studies is essential for other researchers to be able to assess the quality of the study and the validity of its results, in addition to ensuring the transparency of the science.


Variation in the mutation rate across mammalian genomes.
It has been known for many years that the mutation rate varies across the genome. However, only with the advent of large genomic data sets is the full extent of this variation becoming apparent. The mutation rate varies over many different scales, from adjacent sites to whole chromosomes, with the strongest variation seen at the smallest scales. Some of these patterns have clear mechanistic bases, but much of the rate variation remains unexplained, and some of it is deeply perplexing. Variation in the mutation rate has important implications in evolutionary biology and underexplored implications for our understanding of hereditary disease and cancer.


SLCO1B1 Variants and Angiotensin Converting Enzyme Inhibitor (Enalapril)-Induced Cough: a Pharmacogenetic Study.
Clinical observations suggest that incidence of cough in Chinese taking angiotensin converting enzyme inhibitors is much higher than other racial groups. Cough is the most common adverse reaction of enalapril. We investigate whether SLCO1B1 genetic polymorphisms, previously reported to be important determinants of inter-individual variability in enalapril pharmacokinetics, are associated with the enalapril-induced cough. A cohort of 450 patients with essential hypertension taking 10 mg enalapril maleate were genotyped for the functional SLCO1B1 variants, 388A > G (Asn130Asp, rs2306283) and 521T > C (Val174Ala, rs4149056). The primary endpoint was cough, which was recorded when participants were bothered by cough and respiratory symptoms during enalapril treatment without an identifiable cause. SLCO1B1 521C allele conferred a 2-fold relative risk of enalapril-induced cough (95% confidence interval [CI] = 1.34-3.04, P = 6.2 × 10(-4)), and haplotype analysis suggested the relative risk of cough was 6.94-fold (95% CI = 1.30-37.07, P = 0.020) in SLCO1B1*15/*15 carriers. Furthermore, there was strong evidence for a gene-dose effect (percent with cough in those with 0, 1, or 2 copy of the 521C allele: 28.2%, 42.5%, and 71.4%, trend P = 6.6 × 10(-4)). Our study highlights, for the first time, SLCO1B1 variants are strongly associated with an increased risk of enalapril-induced cough. The findings will be useful to provide pharmacogenetic markers for enalapril treatment.


Vanishing twins in diamniotic dichorionic in vitro fertilization gestation in mid-second trimester.
The authors report a diamniotic dichorionic twin pregnancy after in vitro fertilization (IVF) in mid-second trimester. The dead fetuses were delivered by cesarean section at the 20th week of gestation. The authors discuss management aspects and review of the literature.


Identification of Hub Genes and Biomarkers between Hyperandrogen and Normoandrogen Polycystic Ovary Syndrome by Bioinformatics Analysis.
The common and divergent genetic mechanisms of hyperandrogen (HA) and normoandrogen (NA) polycystic ovary syndrome (PCOS) are currently unknown. This study aimed to explore the hub genes and potential mechanisms of HA and NA PCOS through bioinformatics analysis. The GSE137684 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The co-expressed genes and differentially expressed genes (DEGs) between HA and NA PCOS samples were functionally annotated by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The protein-protein interaction (PPI) network of the DEGs was constructed and visualized using STRING and Cytoscape, respectively, and the hub genes were screened using the Cytohubba plug-in. The transcription factors (TFs) of these hub genes were identified with the JASPAR database, and the hub gene-TF regulatory network was constructed. A total of 327 DEGs, including 191 upregulated and 136 downregulated genes, were identified in HA PCOS relative to NA PCOS. Ten hub genes were screened, of which MYC, CAV1, and HGF were mainly enriched in the Proteoglycans in the cancer pathway. In addition, 47 TFs were identified that were found to be involved in the regulation of hub genes. MYC, CAV1, and HGF are potential diagnostic biomarkers and therapeutic targets for HA PCOS.


Food intake assessment and quality of life in women with fibromyalgia.
To compare the food intake of women with and without fibromyalgia and verify if the food intake of patients with fibromyalgia interferes with the pain and quality of life. Study participants were women with fibromyalgia (FM) seen in Fibromyalgia Outpatient Clinic, Hospital das Clínicas/UFPR and a control group (CT) with healthy women. Data collection was conducted from March to October 2012. For the assessment of food intake we used the Food Registration and the analyzed items were total calories, carbohydrates, proteins, lipids, vitamins (A, C, B12, D and E) and minerals (folate, selenium, zinc, iron, calcium and magnesium). The software used was Avanutri Online(®). To evaluate the quality of life, the Fibromyalgia Impact Questionnaire (FIQ) and pain threshold were used. 43 patients with FM and 44 healthy women were evaluated. CT group showed a mean consumption of nutrients greater than FM group except for iron. However, only caloric intake, carbohydrates, proteins and lipids in grams and percentage of lipids, vitamin A, E, B12, folate, selenium and calcium were statistically significant. In FM group, there was a negative correlation between vitamin E and FIQ and a positive correlation between percentage of protein and pain threshold. Women with FM showed a lower qualitative and quantitative intake in comparison with CT group. Only vitamin E correlated with quality of life and percentage of protein in the diet with sensation of pain.


Influence of prenatal maternal stress, maternal plasma cortisol and cortisol in the amniotic fluid on birth outcomes and child temperament at 3 months.
This prospective, longitudinal study aimed to investigate relationships between indicators of maternal prenatal stress, infant birth outcomes and early temperament. We examined the pattern of associations and postulated pathways between physiological (cortisol plasma concentrations) and self-report indices (stress, anxiety) of maternal prenatal stress, cortisol in the amniotic fluid, birth outcomes and infant temperament at 3 months. The sample consisted of 158 women undergoing amniocentesis in the 2nd trimester of pregnancy. Questionnaire measures of maternal stress and anxiety were found to be unrelated to cortisol in plasma or amniotic fluid. Maternal cortisol was related to amniotic cortisol, which in turn was associated with lower birth weight. Birth weight predicted infant fear and distress to limitation at 3 months old. We found trend-like indirect effects of amniotic fluid on infant distress to limitation and fear via birth weight. This is one of the few studies to simultaneously assess the role of maternal and amniotic fluid cortisol on birth outcomes and infant emotional development. The results suggest that foetal cortisol may be an important predictor of infant outcomes and shed light on the mechanisms through which prenatal maternal stress affects infant psychological health.


Biofilm carriers for anaerobic ammonium oxidation: Mechanisms, applications, and roles in mainstream systems.
The anaerobic ammonium oxidation (ANAMMOX) process was proposed as the most promising nitrogen removal process. Biofilm carriers were demonstrated to effectively enhance the anaerobic ammonium oxidating bacteria (AnAOB) retention. This paper reviews the effect of carrier properties on the AnAOB biofilm development according to the biofilm development process and the application state-of-art of three major kinds of conventional carriers, organic-based, inorganic-based carriers, and gel carriers, from the view of system performance and functional microorganisms. The carrier modification methods and purpose are thoroughly summarized and classified into three categories corresponding to various carrier defects. Four important aspects of the desirable carrier for the mainstream ANAMMOX process were proposed, including providing spatial configuration, enhancing the biomass retention, reinforcing the activity, and improving the growth environment, which needs to combine the advantages of organic and inorganic materials. Eventually, the future application directions of novel carriers for the ANAMMOX-based process were also highlighted.


Control of gut differentiation and intestinal-type gastric carcinogenesis.
Gastric cancer is one of the world's most common cancers. Its carcinogenic pathway is mainly associated with Helicobacter pylori infection, subsequent inflammation and tissue regeneration. During the regeneration process, cells deviate from the normal pathway of gastric differentiation to an 'intestinal phenotype', which is thought to be precancerous and associated with the intestinal type of gastric cancer. Inappropriate activation of intestine-specific transcription factors could contribute to the occurrence of the intestinal-type cancer of the stomach.


Maladaptive Consequences of Mental Intrusions with Obsessive, Dysmorphic, Hypochondriac, and Eating-disorders Related Contents: Cross-cultural Differences.
Unwanted mental intrusions (UMIs) with contents related to Obsessive-Compulsive Disorder (OCD), Body Dysmorphic Disorder (BDD), Illness Anxiety Disorder (IAD), and Eating Disorders (EDs) are highly prevalent, independently of the cultural and/or social context. Cognitive-behavioral explanations for these disorders postulates that the escalation from common UMIs to clinically relevant symptoms depends on the maladaptive consequences (i.e., emotions, appraisals, and control strategies) of experiencing UMIs. This study examines, from a cross-cultural perspective, the cognitive-behavioral postulates of the maladaptive consequences of having UMIs. Non-clinical 1,473 participants from Europe, the Middle-East, and South America completed the Questionnaire of Unpleasant Intrusive Thoughts to assess the maladaptive consequences of experiencing highly disturbing OCD, BDD, IAD, and EDs-related UMIs. Findings revealed main effects for both the country and the consequences associated with the four UMI contents. Interaction effects between the consequences of each UMI content and the sample location were also observed. Cognitive-Behavioral models for OCD, BDD, IAD, and EDs should be implemented along with socio-cultural variables that increase the understanding of the role of these variables in the phenomenology of UMIs and their associated consequences.


Targeting Epicardial Fat in Obesity and Diabetes Pharmacotherapy.
Epicardial adipose tissue surrounds and infiltrates the heart. Epicardial fat displays unique anatomic, genetic, and biomolecular properties. People with obesity and in particular, those with abdominal obesity and associated type 2 diabetes mellitus, have an increased amount of epicardial adipose tissue (EAT). Epicardial fat works well as therapeutic target due to its fast-responding metabolism, organ fat specificity, and easy measurability. Epicardial fat responds to thiazolidinediones (TZD), glucagon-like peptide 1-receptor agonists (GLP1A), sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i), and statins. Modulating epicardial fat morphology and genetic profile with targeted pharmacological agents suggests novel strategies in the pharmacotherapy of diabetes and obesity.


POSTMORTEM INTERVAL ESTIMATION BY THE METHOD OF WAVELET ANALYSIS OF STOKES-POLARIMETRIC MAPPING DATA OF HUMAN VITREOUS BODY LAYERS.
The aim: To develop a set of forensic criteria for determining PMI on the basis of complex selective statistical data analysis of magnitude distributions of the wavelet-amplitude coefficients of VB polycrystalline films microscopic images. Materials and methods: The object of study are polycrystalline films of VB, taken from 41 cadavers of both sexes aged from 37 to 79-year with pre-known time of death coming ranged from 3 to 36 h. Measuring the coordinate allocation meanings of parameters of polarization in the points of microscopic images was carried out at the location of the standard Stokes-polarimeter. Results: The magnitudes of statistical moments of the 1st-4th orders linearly vary within 36 hours. It was revealed that the data of time changes of the asymmetry and the excess are the most sensitive to necrotic changes in the polycrystalline structure of such samples. Conclusions: The scale-selective approach provides an increase in the range of sensitivity up to 36 h and increase the accuracy of the PMI estimation up to 45 min.


Effect of Larrea divaricata Cav. extract and nordihydroguaiaretic acid upon peroxidase secretion in rat submandibulary glands.
Free radicals are involved in several diseases, including cancer, central nervous system alterations and inflammatory pathologies. Peroxidase is an oral enzyme implicated in the defence of oral cavity. It has been determined that flavonoids and lignans possess antioxidant and free radical scavenging either directly or indirectly, usually by means of increasing the secretion of free radicals scavenger enzymes. Larrea divaricata Cav. is a plant used in folk Argentine medicine for the treatment of cancer and inflammatory ailments. In this study, we have determined the effect and mechanism of action of an aqueous extract of the leaves of L. divaricata and NDGA on peroxidase secretion in female rat submandibular glands. The extract significantly increased the secretion and total peroxidase. % of secreted peroxidase (X +/- S.E.M.): extract maximum response: 150 +/- 10; % of total peroxidase (X +/- S.E.M.): extract maximum response: 1000 +/- 90. The effect of the extract on peroxidase secretion was mediated by beta1 adrenoceptors (% of secreted peroxidase: extract + atenol maximum response: 50 +/- 4 ). Meanwhile, NDGA produced a decrease in peroxidase secretion (peroxidase secreted: basal: 0.44 +/- 0.03; NDGA 2.5 x 10(-6) M: 0.20 +/- 0.02; prostaglandins E2 (PGE2) 10(-7)M: 1.32 +/- 0.5; NDGA + PGE2: 0.46 +/- 0.035), an effect that was exerted by the inhibition on prostaglandins synthesis.


Induction of apoptosis in rat myocardium under anoxic conditions.
The effect of anoxic incubation of small slices of isolated rat hearts on respiration, internucleosomal DNA fragmentation, and mitochondrial ultrastructure was investigated. Anoxic incubation for 72 h induced apoptosis accompanied by internucleosomal DNA fragmentation and changes in respiration and mitochondrial ultrastructure. The mitochondrial population was characterized by morphological heterogeneity. In a significant part of the mitochondrial population there were signs of mitochondrial swelling and appearance of electron-dense mitochondria. Anoxia also induced the appearance of an atypical (and previously unknown) population of small electron-dense mitochondria. They were characterized by unusual localization inside electron-light mitochondria. Under anoxic conditions the inner mitochondrial membrane formed electron-dense ordered structures. All changes described here reflect two opposing processes occurring in mitochondria: apoptotic destruction and compensatory processes responsible for maintenance of mitochondria.


Synthesis, biological evaluation, and pharmacokinetic study of novel liguzinediol prodrugs.
Liguzinediol (LZDO) ester prodrugs 3-5 were synthesized and evaluated in vitro and in vivo for their potential use in prolonging the half-life of the parent drug LZDO (1a) in vivo. Prodrugs 3-5 were found to display a potent positive inotropic effect on the myocardium, without the risk of arrhythmia. Prodrugs 3-5 rapidly underwent enzymatic hydrolysis to release the parent compound LZDO in 1-3 h in rat liver microsomes and rat plasma. The half-life of the parent compound was prolonged after intragastric administration of prodrug 3, which was found to be a superior prodrug candidate for increasing myocardial contractility.


Vitamin K antagonist-associated intracerebral hemorrhage: lessons from a devastating disease in the dawn of the new oral anticoagulants.
Intracerebral hemorrhage (ICH) is the most feared complication associated with vitamin K antagonists (VKAs). We performed a retrospective study on the clinicoradiologic characteristics that influence its outcome. We reviewed the clinical histories and neuroimaging studies of all patients attended at the Hospital Universitario Central de Asturias in 2010-2011 who had an ICH while being on VKA and analyzed the differential characteristics between patients with acceptable versus poor outcomes attending to 3 end points: death, poor outcome (modified Rankin Scale [mRS] score ≥ 4) at discharge, and poor outcome 3 months later. Additionally, CHA2DS2-VASc and HAS-BLED scores (validated tools for prediction of the risk of stroke and major hemorrhage, respectively, in patients with atrial fibrillation) were calculated to assess a priori risk-benefit balance for anticoagulant therapy. Eighty patients entered the sample (median age of 79 years). A priori annual risk of major bleeding surpassed ischemic stroke risk-without anticoagulation-only in 4. Fifty percent of the patients had an initial Glasgow Coma Scale (GCS) score lower than 13; in 51.3%, initial international normalized ratio was above their therapeutic range. Median hematoma size was 24.75 cc(3); relevant growth (≥33%) occurred in 29.4% of patients with a second computed tomography scan. On multivariable analysis, overall in-hospital mortality (47.5%) was related to prior antiplatelet therapy (P = .008), GCS (P = .001), and perilesional edema size (P = .036). Baseline mRS (P = .058) and National Institutes of Health Stroke Scale (NIHSS) scores (P = .008) were associated with poor outcome at discharge (77.5%). Initial NIHSS (P = .005) and glycemia (P = .038) predicted 3-month poor outcome (68.3%). VKA reversal was performed in almost all patients, which prevented assessment of its therapeutic value. VKA-associated ICH presents in a particularly vulnerable population and has a poor prognosis that may be reliably predicted by several clinicoradiologic features.


Integrated Analysis and MicroRNA Expression Profiling Identified Seven miRNAs Associated With Progression of Oral Squamous Cell Carcinoma.
MicroRNAs have been used as diagnostic and prognostic biomarkers for many cancers including oral squamous cell carcinoma (OSCC). Several studies have been shown that microRNA (miRNA) play important roles during the progression of OSCC. However, the results vary largely in different studies due to different platforms and sample sizes. In this study, we systematically evaluated a large scale of miRNA profiles from current qualified OSCC samples, and further investigated the functions of genes regulated by these key miRNAs as well as the signaling pathways through which these miRNA effect carcinogenesis. Seven key miRNAs were identified, and of which three were significantly upregulated, including hsa-miR-21, hsa-miR-31, hsa-miR-338, and four were downregulated, namely hsa-miR-125b, hsa-miR-133a, hsa-miR-133b, and hsa-miR-139. The function enrichment analysis revealed that target genes of upregulated miRNAs were associated with cellular protein metabolic process, macromolecule metabolic process, and TGF-beta pathway, while the targets of downregulated were enriched in negative regulation of macromolecule biosynthetic process and gene expression, and p53, long-term potentiation and adherens junction pathways. Transcription factor analysis revealed that there were 67 (51.1%) transcription factors influenced by both up and downregulated miRNAs. In summary, seven key miRNAs were found to play essential role in progression of OSCC, as well as the target genes and transcription factors of these miRNAs. The potential functions of these target genes identified in our study may be profitable to diagnosis and prognostic prediction of OSCC as biomarkers. J. Cell. Physiol. 232: 2178-2185, 2017. © 2016 Wiley Periodicals, Inc.


Income-related equity in inpatient care utilization and unmet needs between 2013 and 2018 in Tibet, China.
Providing equitable access to health care for all populations is an important sustainable development goal. China has made significant progress in achieving equity in healthcare utilization. However, research on equity in healthcare utilization in Tibet is sparse. This study aims to evaluate changes in income-related inequity in inpatient care utilization and unmet needs between 2013 and 2018 among the Tibetan population and identify the inequity source. Data for this cross-sectional study were obtained from the fifth and sixth waves of the National Health Services Survey in 2013 and 2018. After excluding observations with missing values for key variables, 11,092 and 10,397 respondents were included in this study, respectively. The outcome variables of interest were inpatient service utilization and unmet hospitalization needs. The concentration index and horizontal inequity index (HI) were used to assess income-related inequity. Non-linear decompositions were performed to identify the main contributors to inequity. In the decomposition method, need variables included sex, age, chronic diseases, and the EuroQol-Visual Analog Scale; non-need variables consisted of income, education, employment status, marital status, and health insurance schemes. The probability of inpatient care utilization increased from 6.40% in 2013 to 8.50% in 2018. The HI for inpatient care utilization was 0.19 (P < 0.001) in 2013, whereas it decreased to 0.07 (P < 0.001) in 2018. The contribution of income to inequity in inpatient care utilization decreased from 87.09% in 2013 to 59.79% in 2018. As for unmet inpatient care needs, although its probability increased from 0.76 to 1.48%, the percentage of reasons for financial hardship decreased from 47.62 to 28.57%. The HI for unmet hospitalization need was - 0.07 in 2013 and - 0.05 in 2018, and neither was statistically significant. The New Rural Cooperative Medical Scheme made majority contributions to promote equity in unmet hospitalization need. Moreover, the female respondents reporting low EuroQol-Visual Analog Scale scores and patients with chronic disease were not only more likely to seek for inpatient care, but also have more unmet need than the reference groups. The inequity in inpatient care utilization in Tibet narrowed from 2013 to 2018, and there was no inequity in unmet hospitalization needs in 2013 and 2018. Income and the New Rural Cooperative Medical Scheme are the main drivers of equity promotion. To promote access to inpatient care utilization and decrease the probability of unmet hospitalization need in future, policymakers should target high-need residents in Tibet to improve accessibility, availability, and acceptability.


Rabbit antithymocyte globulin induction and risk of post-transplant lymphoproliferative disease in adult and pediatric solid organ transplantation: An update.
The most modifiable risk factor for post-transplant lymphoproliferative disease (PTLD) is the type and dose of induction and maintenance immunosuppressive therapy. It is challenging to identify the contribution of a single agent such as rabbit antithymocyte globulin (rATG) in the setting of multidrug therapy. Registry analyses can be helpful but are limited by methodological restrictions and inclusion of historical patient cohorts. These are typically from eras when rATG dosing was markedly higher than current dosing (e.g. total dose 14 mg/kg versus 6 mg/kg now), accompanied by higher exposure to maintenance therapies, and often an absence of antiviral prophylaxis. The largest registry analysis to assess rATG specifically found no risk of PTLD after kidney transplantation, but conflicting results have been reported, highlighting the difficulty of interpreting this type of analysis. The relative rarity of PTLD means that individually controlled trials are underpowered to assess its occurrence, but the available data do not suggest an effect of rATG. A pooled analysis of data from studies of rATG induction in kidney and heart transplantation found the incidence of PTLD to be comparable to published reports in the overall transplant population. Data on the effect of rATG dose are inconclusive, but in patients receiving antiviral prophylaxis it does not appear to be influential. Nevertheless, it would seem reasonable to employ the lowest dose of rATG compatible with effective induction, particularly in EBV-seronegative recipients and other high-risk groups such as heart-lung transplant recipients. Overall, the risk of PTLD following rATG induction therapy with modern dosing regimens and under current management conditions appears unlikely to make an important contribution to the risk:benefit balance.


Grading System and Surgical Strategy for Temporal Bone Diffuse-Type Tenosynovial Giant Cell Tumor.
To develop a novel grading system and appropriate surgical approaches for patients with diffuse type tensosynovial giant cell tumor (D-TGCT) of the temporal bone. Retrospective cohort study. We retrospectively reviewed 31 patients with temporal bone D-TGCT between June 2012 and July 2021. All patients underwent comprehensive clinical evaluations, including clinical presentations, hearing threshold, imaging studies, surgical approaches, and prognosis. A grading system was developed based on the tumor location and adjacent neurovascular structures involvement according to imaging and intraoperative findings. In this study, grade II tumors were the most common (13/31), followed by grades I (7/31), III (7/31), and IV (4/31) tumors. Seven grade I patients received the subtemporal middle cranial fossa approach (SMCF) combined with the canal wall up mastoidectomy and tympanoplasty (CWUT). Nine grade II patients underwent SMCF combined with subtotal petrosectomy (SPTR), and four grade II patients underwent SMCF combined with CWUT. Seven grade III patients received SMCF combined with SPTR and dura mater reconstruction, and four grade IV patients underwent infratemporal fossa approach type B. Gross total resection was achieved in all patients, and the median follow-up time was 30.1 months (range, 4-96 months). Three patients (one grade II, one grade III, and one grade IV) had recurrence during follow-up, and the patient with grade III tumor had two recurrences. Gross total resection is the first-line treatment for patients with D-TGCT of the temporal bone. This novel grading system enables surgeons to select optimal surgical strategy. Long-term follow-up is mandatory postoperatively. 4 Laryngoscope, 132:1275-1284, 2022.


Low temperature-resistant superhydrophobic and elastic cellulose aerogels derived from seaweed solid waste as efficient oil traps for oil/water separation.
Aerogel has excellent application potential in adsorption, heat preservation, and other areas due to its typical advantages of low density and high porosity. However, there are several issues with the use of aerogel in oil/water separation, including weak mechanical qualities and challenges in eliminating organic contaminants at low temperature. Inspired by cellulose Iα, which has excellent performance at low temperature, this study used cellulose Iα nanofibers extracted from seaweed solid waste as the skeleton, through covalent cross-linked with ethylene imine polymer (PEI) and hydrophobic modification of 1, 4-phenyl diisocyanate (MDI), supplemented by freeze-drying technology to form three-dimensional sheet, and successfully obtained cellulose aerogels derived from seaweed solid waste (SWCA). The compression test shows that the maximum compressive stress of SWCA is 61 kPa, and the initial performance still maintains 82% after 40 cryogenic compression cycles. In addition, the contact angles of water and oil on the surface of the SWCA were 153° and 0°, respectively, and the stable hydrophobic time in simulated seawater is more than 3 h. By combining the elasticity and superhydrophobicity/superoleophilicity, the SWCA with an oil absorption capacity of up to 11-30 times its mass, might be utilized repeatedly for the separation of an oil/water mixture.


Renal Mitochondrial Response to Low Temperature in Non-Hibernating and Hibernating Species.
Therapeutic hypothermia is commonly applied to limit ischemic injury in organ transplantation, during cardiac and brain surgery and after cardiopulmonary resuscitation. In these procedures, the kidneys are particularly at risk for ischemia/reperfusion injury (IRI), likely due to their high rate of metabolism. Although hypothermia mitigates ischemic kidney injury, it is not a panacea. Residual mitochondrial failure is believed to be a key event triggering loss of cellular homeostasis, and potentially cell death. Subsequent rewarming generates large amounts of reactive oxygen species that aggravate organ injury. Recent Advances: Hibernators are able to withstand periods of profoundly reduced metabolism and body temperature ("torpor"), interspersed by brief periods of rewarming ("arousal") without signs of organ injury. Specific adaptations allow maintenance of mitochondrial homeostasis, limit oxidative stress, and protect against cell death. These adaptations consist of active suppression of mitochondrial function and upregulation of anti-oxidant enzymes and anti-apoptotic pathways. Unraveling the precise molecular mechanisms that allow hibernators to cycle through torpor and arousal without precipitating organ injury may translate into novel pharmacological approaches to limit IRI in patients. Although the precise signaling routes involved in natural hibernation are not yet fully understood, torpor-like hypothermic states with increased resistance to ischemia/reperfusion can be induced pharmacologically by 5'-adenosine monophosphate (5'-AMP), adenosine, and hydrogen sulfide (H2S) in non-hibernators. In this review, we compare the molecular effects of hypothermia in non-hibernators with natural and pharmacologically induced torpor, to delineate how safe and reversible metabolic suppression may provide resistance to renal IRI. Antioxid. Redox Signal. 27, 599-617.


Amygdalar κ-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence.
Opiates produce a strong rewarding effect, but abstinence from opiate use emerges with severe negative emotions. Depression is one of the most frequent emotion disorders associated with opiate abstinence, which is thought to be a main cause for relapse. However, neurobiological bases of such an aversive emotion processing are poorly understood. Here, we find that morphine abstinence activates κ-opioid receptors (KORs) by increasing endogenous KOR ligand dynorphin expression in the amygdala, which in turn facilitates glutamate transporter 1 (GLT1) expression by activation of p38 mitogen-activated protein kinase (MAPK). Upregulation of GLT1 expression contributes to opiate-abstinence-elicited depressive-like behaviors through modulating amygdalar glutamatergic inputs to the nucleus accumbens (NAc). Intra-amygdala injection of GLT1 inhibitor DHK or knockdown of GLT1 expression in the amygdala significantly suppresses morphine-abstinence-induced depressive-like behaviors. Pharmacological and pharmacogenetic activation of amygdala-NAc projections prevents morphine-abstinence-induced behaviors. Overall, our study provides key molecular and circuit insights into the mechanisms of depression associated with opiate abstinence.


Surgery for constipation: systematic review and practice recommendations: Results V: Sacral Nerve Stimulation.
To assess the outcomes of sacral nerve stimulation in adults with chronic constipation. Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements with a summative Oxford Centre for Evidence-Based Medicine (2009) level. Seven articles were identified, providing data on outcomes in 375 patients. Length of procedures and length of stay was not reported. Data on harms were inconsistently reported and heterogeneous, making estimates of harm tentative and imprecise. Morbidity rates ranged between 13 and 34%, with overall device removal rate between 8 and 23%. Although inconsistently reported, pooled treatment success was typically 57-87% for patients receiving permanent implants, although there was significant variation between studies. Patient selection was inconsistently documented. No conclusions could be drawn regarding particular phenotypes that responded favourably or unfavourably to sacral nerve stimulation. Evidence supporting sacral nerve stimulation is derived from poor quality studies. Three methodologically robust trials are have reported since this review and all have all urged greater caution.


Analysis of phase-shifted fiber Bragg gratings written with phase plates.
A method for obtaining phase-shifted Bragg gratings by use of phase plates is presented. A comparison of experimental and theoretical results allows us to describe the utility of such a component.


Condensation reaction of hexanucleotides containing guanine and cytosine with water soluble carbodiimide.
The condensation reactions of hexanucleotides involving guanine and cytosine in the presence of water-soluble carbodiimide (WSC) have been investigated as a model reaction of the prebiotic formation of RNA under primitive earth. The reactions formed cyclic hexanucleotides and dimers in which the product yields were dependent on the sequence.


Help Desk Answers: Are IV fluids better than oral rehydration for children with acute diarrhea and vomiting?
Intravenous fluid therapy (IVF) has a slightly lower failure rate than oral replacement therapy (ORT) in children with acute gastroenteritis, but the clinical significance is questionable. IVF takes longer to initiate than ORT and lengthens the hospital stay.


Aqueous humor dynamics in patients with diabetes mellitus.
We measured aqueous dynamic variables in subjects with diabetes mellitus and correlated them with severity of retinopathy and metabolic control to determine whether diabetes affects the anterior circulation of the eye as it affects the posterior (retinal) circulation. Sixty-one subjects with diabetes mellitus type 1 and 60 subjects with diabetes mellitus type 2 were recruited from the active practice of the Mayo Clinic. Thirty-two normal subjects, divided by age into two overlapping groups of 20 each, served as contemporaneous control subjects. The diabetic subjects were stratified into four groups according to severity of retinopathy. Aqueous humor flow was measured by clearance of topically applied fluorescein with a spectrofluorophotometer; outflow facility was measured by tonography; and intraocular pressure was measured by applanation tonometry. In type 1 diabetics, the mean intraocular pressure was slightly greater (14 +/- 3 mm Hg), compared with control subjects (12 +/- 2 mm Hg [P = .002]), while aqueous humor flow was slightly less (2.5 +/- 0.6 microliter/min), compared with control subjects (2.9 +/- 0.5 microliter/min [P = .023]). In type 2 diabetics, the intraocular pressure was 14 +/- 3 mm Hg, which did not differ from that of control subjects (14 +/- 3 mm Hg [P = .258]). Aqueous humor flow in type 2 diabetics (2.5 +/- 0.7 microliter/min) did not differ significantly from that of the control group (2.5 +/- 0.7 microliter/min [P = .961]). Tonographic facility of outflow was not significantly different in type 1 and type 2 diabetics and the control subjects. There was no significant correlation in aqueous humor flow, intraocular pressure, or tonographic facility of outflow to severity of retinopathy or hemoglobin A1c in either type 1 or type 2 diabetics. The dynamics of aqueous humor are not affected to any clinically significant extent in the early or middle stages of diabetic retinopathy. However, there is a tendency toward less aqueous humor flow in the advanced stages of retinopathy.


Observer reliability in grading nephrocalcinosis on ultrasound examinations in children.
Nephrocalcinosis is often associated with a variety of hypercalcemic conditions. Diagnostic ultrasound is often used for assessing nephrocalcinosis in children, but its reliability has not been proven. To determine the reliability of expert interpretation of sonographic films with a grading scale of severity for nephrocalcinosis. Fifty-eight ultrasonographic films of 30 children with Williams syndrome and other conditions know to be associated with nephrocalcinosis were assessed. We used a blinded randomized design to assess intra- and interobserver reliability. Grades I, II, and III nephrocalcinosis were noted in 13 %, 19 %, and 27 % of the examinations, respectively. The weighted kappa coefficient was 0.80 (standard error 0.12; 95 % confidence interval 0.68-0.92) for intraobserver agreement and 0.76 (standard error 0.13; 95 % confidence interval 0.63 to 0.89) for interobserver agreement. Reliability in assessing change from one examination to the next, with independently graded films, was fair with an unweighted kappa coefficient of 0.68 (95 % confidence interval 0.38-0.96) and 0.51 (95 % confidence interval 0.21-0.80) for intra- and interobserver reliability, respectively. The severity of nephrocalcinosis can be reliably interpreted with an ultrasonography grading scale.


Gene regulation in macrophage activation: differential regulation of genes encoding for tumor necrosis factor, interleukin-1, JE, and KC by interferon-gamma and lipopolysaccharide.
Although macrophage activation is induced in a complex manner by signals such as interferon-gamma (IFN gamma) and bacterial lipopolysaccharide (LPS) and depends on alterations in levels of specific proteins due to differences in gene expression, the complexity of gene regulation during macrophage activation in regard to multiple signals is not fully appreciated. To probe this question, we selected four model genes encoding for tumor necrosis factor (TNF), interleukin-1 (IL-1), and the immediate early genes JE and KC. After analyses of Northern blots for specific mRNA, LPS was found to enhance levels of mRNA for IL-1, TNF, JE, and KC. IFN gamma initiated heightened mRNA levels for JE but did not alter specific mRNA for IL-1, TNF, or KC. When IFN gamma and LPS were combined, additive effects on levels of specific mRNA for JE, enhancement of mRNA for TNF, suppressed mRNA for KC, and no effect on mRNA for IL-1 were observed. When transcription of these genes was assessed by nuclear "run on" experiments, LPS increased transcription of KC and TNF but not of IL-1 or JE, implying that the increased levels of mRNA for JE and IL-1 were attributable to increased stability of mRNA. Likewise, IFN gamma did not initiate transcription of JE. When IFN gamma and LPS were given together, IFN gamma enhanced the LPS-induced transcription of TNF and KC, suggesting decreased stability of mRNA for KC. A distinct pattern of regulation for each of the four genes was thus observed. Taken together, the data suggest that gene regulation in macrophage activation represents a complex response of enhanced and suppressed transcription and mRNA stability, the precise pattern of which depends on the stimuli given to the macrophages and the gene examined.


A comprehensive review on current status and future perspectives of microbial volatile fatty acids production as platform chemicals.
Volatile fatty acids (VFA), the secondary metabolite of microbial fermentation, are used in a wide range of industries for production of commercially valuable chemicals. In this review, the fermentative production of VFAs by both pure as well mixed microbial cultures is highlighted along with the strategies for enhancing the VFA production through innovations in existing approaches. Role of conventionally applied tools for the optimization of operational parameters such as pH, temperature, retention time, organic loading rate, and headspace pressure has been discussed. Furthermore, a comparative assessment of above strategies on VFA production has been done with alternate developments such as co-fermentation, substrate pre-treatment, and in situ removal from fermented broth. The review also highlights the applications of different bioreactor geometries in the optimum production of VFAs and how metagenomic tools could provide a detailed insight into the microbial communities and their functional attributes that could be subjected to metabolic engineering for the efficient production of VFAs.


Nonoperative management of traumatized spleen in children: how and why.
In the absence of the apleen, overwhelming infection is a real threat. Therefore, there is a trend to try to preserve all spleens. Recognizing this, and realizing that not every damaged spleen must be removed, a nonoperative approach has been advocated and practiced for 35 yr at the Hospital for Sick Children in Toronto. This experience is recorded herein, providing indications and methods of management. The results are considered to be very satisfactory.


(In search of) probabilistic P systems.
The aim of this paper is to (preliminarily) discuss various ways of introducing probabilities in membrane systems. We briefly present both ideas already circulated in the literature and new proposals, trying to have a systematic overview of possibilities of associating probabilities with the ingredients of a membrane system: with (localization of) single objects, with multiplicities of objects (hence with the multisets), with the rules (depending or not on the previous applied rule), with the communication targets. For a certain mode of using the probabilities associated with the evolution rules (in string-object P systems) we obtain the computational universality.


Age decreases mitochondrial motility and increases mitochondrial size in vascular smooth muscle.
Age is proposed to be associated with altered structure and function of mitochondria; however, in fully-differentiated cells, determining the structure of more than a few mitochondria at a time is challenging. In the present study, the structures of the entire mitochondrial complements of cells were resolved from a pixel-by-pixel covariance analysis of fluctuations in potentiometric fluorophore intensity during 'flickers' of mitochondrial membrane potential. Mitochondria are larger in vascular myocytes from aged rats compared to those in younger adult rats. A subpopulation of mitochondria in myocytes from aged, but not younger, animals is highly-elongated. Some mitochondria in myocytes from younger, but not aged, animals are highly-motile. Mitochondria that are motile are located more peripherally in the cell than non-motile mitochondria. Mitochondrial function, motility and architecture are each central to cell function. Age-associated mitochondrial dysfunction may contribute to vascular disease. However, mitochondrial changes in ageing remain ill-defined because of the challenges of imaging in native cells. We determined the structure of mitochondria in live native cells, demarcating boundaries of individual organelles by inducing stochastic 'flickers' of membrane potential, recorded as fluctuations in potentiometric fluorophore intensity (flicker-assisted localization microscopy; FaLM). In freshly-isolated myocytes from rat cerebral resistance arteries, FaLM showed a range of mitochondrial X-Y areas in both young adult (3 months; 0.05-6.58 μm(2) ) and aged rats (18 months; 0.05-13.4 μm(2) ). In cells from young animals, most mitochondria were small (mode area 0.051 μm(2) ) compared to aged animals (0.710 μm(2) ). Cells from older animals contained a subpopulation of highly-elongated mitochondria (5.3% were >2 μm long, 4.2% had a length:width ratio >3) that was rare in younger animals (0.15% of mitochondria >2 μm long, 0.4% had length:width ratio >3). The extent of mitochondrial motility also varied. 1/811 mitochondria observed moved slightly (∼0.5 μm) in myocytes from older animals, whereas, in the younger animals, directed and Brownian-like motility occurred regularly (215 of 1135 mitochondria moved within 10 min, up to distance of 12 μm). Mitochondria positioned closer to the cell periphery showed a greater tendency to move. In conclusion, cerebral vascular myocytes from young rats contained small, motile mitochondria. In aged rats, mitochondria were larger, immobile and could be highly-elongated. These age-associated alterations in mitochondrial behaviour may contribute to alterations in cell signalling, energy supply or the onset of proliferation.


Analysis of crystallization data in the Protein Data Bank.
The Protein Data Bank (PDB) is the largest available repository of solved protein structures and contains a wealth of information on successful crystallization. Many centres have used their own experimental data to draw conclusions about proteins and the conditions in which they crystallize. Here, data from the PDB were used to reanalyse some of these results. The most successful crystallization reagents were identified, the link between solution pH and the isoelectric point of the protein was investigated and the possibility of predicting whether a protein will crystallize was explored.


Interpretable machine-learning model for Predicting the Convalescent COVID-19 patients with pulmonary diffusing capacity impairment.
The COVID-19 patients in the convalescent stage noticeably have pulmonary diffusing capacity impairment (PDCI). The pulmonary diffusing capacity is a frequently-used indicator of the COVID-19 survivors' prognosis of pulmonary function, but the current studies focusing on prediction of the pulmonary diffusing capacity of these people are limited. The aim of this study was to develop and validate a machine learning (ML) model for predicting PDCI in the COVID-19 patients using routinely available clinical data, thus assisting the clinical diagnosis. Collected from a follow-up study from August to September 2021 of 221 hospitalized survivors of COVID-19 18 months after discharge from Wuhan, including the demographic characteristics and clinical examination, the data in this study were randomly separated into a training (80%) data set and a validation (20%) data set. Six popular machine learning models were developed to predict the pulmonary diffusing capacity of patients infected with COVID-19 in the recovery stage. The performance indicators of the model included area under the curve (AUC), Accuracy, Recall, Precision, Positive Predictive Value(PPV), Negative Predictive Value (NPV) and F1. The model with the optimum performance was defined as the optimal model, which was further employed in the interpretability analysis. The MAHAKIL method was utilized to balance the data and optimize the balance of sample distribution, while the RFECV method for feature selection was utilized to select combined features more favorable to machine learning. A total of 221 COVID-19 survivors were recruited in this study after discharge from hospitals in Wuhan. Of these participants, 117 (52.94%) were female, with a median age of 58.2 years (standard deviation (SD) = 12). After feature selection, 31 of the 37 clinical factors were finally selected for use in constructing the model. Among the six tested ML models, the best performance was accomplished in the XGBoost model, with an AUC of 0.755 and an accuracy of 78.01% after experimental verification. The SHAPELY Additive explanations (SHAP) summary analysis exhibited that hemoglobin (Hb), maximal voluntary ventilation (MVV), severity of illness, platelet (PLT), Uric Acid (UA) and blood urea nitrogen (BUN) were the top six most important factors affecting the XGBoost model decision-making. The XGBoost model reported here showed a good prognostic prediction ability for PDCI of COVID-19 survivors during the recovery period. Among the interpretation methods based on the importance of SHAP values, Hb and MVV contributed the most to the prediction of PDCI outcomes of COVID-19 survivors in the recovery period.


Effects of adenoidectomy/adenotonsillectomy on ADHD symptoms and behavioral problems in children.
In children, the most common reason of upper airway obstruction (UAO) is adenotonsillar hypertrophy. In literature, the adverse effects of UAO and obstructive sleep apnea syndrome on behavior and attention in children have been reported in several articles. However, the methods used for the evaluation of behavioral disorders have not been standardized in those studies. The aim of this study was to investigate the behavioral and attention characteristics of children before and after adenoidectomy/adenotonsillectomy using an internationally valid method. A total of 41 patients, between 6 and 11 years of age and having a medical history of UAO for at least one year for which adenotonsillectomy procedure was indicated, were enrolled in the study. The patients were evaluated for signs of attention/behavioral disorders by a child-adolescent psychiatrist and Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children: Present and Lifetime Version (K-SADS-PL) and The Turgay DSM-IV-Based Child and Adolescent Disruptive Behavioral Disorders Screening and Rating Scale (T-DSM-IV-S), before and at the 6th month following the operation. In the preoperative period, a psychiatric disorder was identified by K-SADS-PL in 41.4% (n =1 7) of patients. Of these, 11 patients had attention deficit hyperactivity disorder (ADHD), 6 had enuresis nocturna, and 2 had separation anxiety disorder. Pre- and postoperative mean scores in T-DSM-IV-S parent scale were 31.3 ± 8.5 and 20.2 ± 10.3, respectively, and this difference was statistically significant (p < 0.001). The relationship of UAO and attention/behavioral disorders should be taken into consideration by child-adolescent psychiatrists together with ENT specialists and a multidisciplinary approach is important for the treatment team.


Family history as a predictor of early menopause.
To determine the relative importance of family history as a predictor of early menopause. Case-control study. From a population-based survey of 10,606 women between 45 and 54 years of age, we selected 344 cases with early menopause (average age 42.2 years) and 344 age-matched controls who were still menstruating or who had a menopause after age 46 years. Subjects were interviewed about their medical and family history and blood was drawn for identification of women who were carriers for the classic or Duarte variant of galactosemia, a potential hereditary factor for early menopause. Logistic regression analysis was used to estimate the risk of an early menopause in women with and without a family history of early menopause. Overall 129 (37.5%) of the early menopause cases reported a family history of menopause before age 46 years in a mother, sister, aunt, or grandmother compared to 31 (9.0%) of controls yielding an odds ratio (OR) of 6.1 (95% confidence interval [CI] of 3.9 to 9.4) after adjustment for smoking history, education, parity, and body mass index. Risk for early menopause associated with family history of same was greatest: for family history in a sister, OR = 9.1 (95% CI 3.1 to 26.5); multiple relatives, OR = 12.4 (95% CI 4.4 to 34.2); and cases menopausal before age 40 years, OR = 8.4 (95% CI 2.5 to 31.2). Cases with a family history of early menopause were not more likely to have errors of galactose metabolism compared with cases without a family history or to all controls, nor did they possess Turner's stigmata such as short stature, but they were less likely to have brothers in their sibships. Although preferential recall of family history by women with early menopause could contribute to the association between family history and early menopause observed in this study, a genetic factor is also plausible including partial deletions of the X chromosome compatible with the deficiency of male siblings in cases with family history of early menopause.


Cloning and characterization of a phospholipase C-beta isoform from the sea urchin Lytechinus pictus.
Calcium is a ubiquitous intracellular signaling molecule controlling a wide array of cellular processes including fertilization and egg activation. The mechanism for triggering intracellular Ca(2+) release in sea urchin eggs during fertilization is the generation of inositol-1,4,5-trisphosphate by phospholipase C (PLC) hydrolysis of phosphatidylinositol-4,5-bisphosphate. Of the five PLC isoforms identified in mammals (beta, gamma, delta, epsilon and zeta), only PLCgamma and PLCdelta have been detected in echinoderms. Here, we provide direct evidence of the presence of a PLCbeta isoform, named suPLCbeta, within sea urchin eggs. The coding sequence was cloned from eggs of Lytechinus pictus and determined to have the greatest degree of homology and identity with the mammalian PLCbeta4. The presence of suPLCbeta within the egg was verified using a specifically generated antibody. The majority of the enzyme is localized in the non-soluble fraction, presumably the plasma membrane of the unfertilized egg. This distribution remains unchanged 1 min postfertilization. Unlike PLCbeta4, suPLCbeta is activated by G protein betagamma subunits, and this activity is Ca(2+)-dependent. In contrast to all known PLCbeta enzymes, suPLCbeta is not activated by Galphaq-GTPgammaS subunit suggesting other protein regulators may be present in sea urchin eggs.


Red cell oxygen transport in man in relation to gender and age.
P50 values, the O2-partial pressure at 50% O2-saturation of hemoglobin, 2,3-DPG, hematological parameters and the plasma concentrations of sexual hormones were determined in 135 subjects of both sexes aged from 10 to 60 years. P50 was significantly higher in sexually mature women than in men, but did not differ between sexes before puberty and after menopause. In females P50 increased with sexual maturation by about 2 mmHg (0.27 kPa). RBC, Hb and Hct remained unchanged. In males Hb-O2-affinity, RBC, Hb and Hct increased with aging. In sexually mature females 2,3-DPG was significantly higher (2 mumol/gHb) than in males, although before puberty and postmaturity no difference was found. In males, 2,3-DPG increased slightly with maturation although P50 decreased. P50 values (pH = 7.4) correlated positively with red cell 2,3-DPG only when data from all groups were pooled (r = 0.330, P less than or equal to 0.0001). Hb was negatively correlated with P50 (r = 0.221, P less than or equal to 0.01). The data suggest a sex hormone and maturation induced influence in the development of the red cell O2-transport system. Estrogens seem to favour a decrease in Hb-O2-affinity rather than an elevation in O2-transport capacity, whereas androgens do the reverse.


Investigation of The Relationship Between IL-18 (-607 C/A), IL-18 (-137 G/C) Gene Variations and Ischemic Stroke Disease Development in Thrace Region of Turkey.
Ischemic stroke is a clinical condition characterized by focal or global cerebral dysfunction resulting from inhibition of brain blood flow. Genetic factors play an important role in the pathogenesis of ischemic stroke. As a result of IL-18 (-607 C/A, -137 G/C) gene variations, it is thought that binding of transcription factors may be affected and IL-18 mRNA expression can be modulated. Therefore, the purpose of our study is to investigate the roles of IL-18 (-607 C/A), IL-18 (-137 G/C) gene variations in the development of ischemic stroke in Trakya Region of Turkey. Our study was performed with 90 ischemic stroke patients and 89 healthy controls. Genotype distributions of IL-18 (-607 C/A, -137 G/C) gene variations were determined using polymerase chain reaction (PCR) method. GC genotype and CA genotype of IL-18 (-137 G/C) and IL-18 (-607 C/A) gene variations were determined higher significantly in patent group as compared with other genotypes. However, the statistically significant difference was not determined between patients with ischemic stroke and healthy control groups in terms of IL-18 (-137 G/C) and IL-18 (-607 C/A) gene variations (p > 0,05). Allele frequencies of IL-18 (-137 G/C) and IL-18 (-607 C/A) in patient and control groups were significantly different from the Hardy-Weinberg distribution (p < .001 for all). Although these gene variations' genotype distributions were not determined as a genetic risk factor for the development of ischemic stroke, allele frequencies of IL-18 (-137 G/C) and IL-18 (-607 C/A) in patient and control groups were significantly different from the Hardy-Weinberg distribution.


Longitudinal associations of serum fatty acid composition with type 2 diabetes risk and markers of insulin secretion and sensitivity in the Finnish Diabetes Prevention Study.
To examine the longitudinal associations of serum fatty acid composition with type 2 diabetes, insulin secretion and insulin sensitivity over several years. We conducted a prospective cohort study derived from the randomized Finnish Diabetes Prevention Study. Total serum fatty acid composition was measured using gas chromatography in 407 overweight, middle-aged people with impaired glucose tolerance at baseline (1993-1998) and annually during the intervention period (1994-2000). Longitudinal associations of 20 fatty acids and three desaturase activities (Δ5 (20:4n-6/20:3n-6, D5D), Δ6 (18:3n-6/18:2n-6, D6D), stearoyl-CoA desaturase-1 (16:1n-7/16:0, SCD-1)) with type 2 diabetes incidence, and estimates of insulin sensitivity (Matsuda), secretion (ratio of insulin and glucose concentrations) and β-cell function (disposition index) by an oral glucose tolerance test were analyzed using Cox regression and linear mixed models. We validated estimated D5D and D6D using a known FADS1 gene variant, rs174550. The baseline proportions of 20:5n-3, 22:5n-3 and 22:6n-3, and D5D were associated with lower incidence of type 2 diabetes during a median follow-up of 11 years (HR per 1SD: 0.72, 0.74, 0.73, 0.78, respectively, P ≤ 0.01). These long-chain omega-3 fatty acids and D5D were associated with higher insulin sensitivity in subsequent years but not with disposition index. Saturated, monounsaturated and trans fatty acids and 18:3n-3, 18:2n-6, SCD-1 and D6D were inconsistently associated with type 2 diabetes or related traits. Serum long-chain omega-3 fatty acids and D5D predicted lower type 2 diabetes incidence in people at a high risk of diabetes attending to an intervention study; a putative mechanism behind these associations was higher insulin sensitivity.


Vitamin D deficiency is associated with chronic obstructive pulmonary disease and exacerbation of COPD.
Low Vitamin D levels have been associated with Chronic Obstructive Pulmonary Disease (COPD) and acute exacerbations. There is a paucity of data on Vitamin D and COPD, its severity and exacerbations in populations that are exposed to sunlight regularly with high levels of physical activity most of their lives. Serum levels of 25-OH-Vitamin-D were assessed in 100 COPD subjects and 100 age- and gender-matched controls from the rural community-based MUDHRA cohort in South India. Levels of <20 ng/mL were defined as Vitamin D deficiency. Smoking habits, occupation, Charlson co-morbidity index, Standard of living index(SLI), body mass index(BMI), 6-minute walking distance were examined for associations with logistic regression between controls and COPD subjects. Unconditional logistic regression was used to examine the association with exacerbation of COPD. Vitamin D deficiency was observed in 64.5% (95%CI 57.7-70.8) of the subjects in spite of regular exposure to sunlight. Subjects with COPD had higher risk of Vitamin D deficiency (Adjusted OR: 5.05; 95%CI 1.4-17.8) as compared to controls. Amongst subjects with COPD, Vitamin D deficient subjects were three times more likely to have exacerbations in the previous year (Adjusted OR:3.51; 95%CI 1.27-9.67) as compared to COPD subjects without Vitamin D deficiency. Levels of Vitamin D <20.81 ng/mL and <18.45 ng/mL had the highest levels of combined sensitivity and specificity for COPD and acute exacerbation of COPD (AECOPD) respectively. In a rural population exposed to sunlight many hours a day throughout their lives, low Vitamin D levels were associated with COPD and exacerbations of COPD.


A study of cyclic nucleotide metabolism and the histology of rat liver during 3'-methyl-4-dimethylamino-azobenzene carcinogenesis. II. Cyclic AMP metabolism.
We have studied cAMP metabolism in rat livers undergoing carcinogenesis induced by dietary 3'-methyl-4-dimethylaminoazobenzene. A correlation between the biochemical and the histological changes described in the companion paper has been made. In this study, we saw 100% incidence of cholangiocarcinoma by 10 weeks. During weeks 1--10, the biochemistry of tumor-free areas of the livers only was studied; during weeks 11-13, the increased size of the tumors made possible a biochemical study of the tumor tissue as well as the non-tumor tissue, and a comparison between the two was made. Alterations in all parameters of cAMP metabolism were seen from the earliest stages of treatemnt. Most striking were those of adenylate cyclase activity which preceded and accompanied tumor formation, and were seen in both non-tumor and tumor tissue. In the first few weeks of treatment, small acidophilic glycogen-deficient hepatocytes appeared in the periportal areas of the liver lobules. During this time, there was an increase in maximal isoproterenol stimulation of adenylate cyclase and to a lesser extent in the basal activity of the enzyme; increases in phosphodiesterase activity were seen, and were greatest in weeks 1, 2; cAMP levels were diminished in weeks 1, 2 and slightly but not significantly elevated at week 3. From week 4 onwards an even smaller glycogen-deficient cell population appeared in perilobular areas amongst the acidophilic hepatocytes, and tumors began to appear elsewhere in the livers; at this time, there were further marked increases in the basal activity and isoproterenol responsiveness of adenylate cyclase, and the appearance of increased Gpp(NH)p responsiveness of the enzyme; the increase in phosphodiesterase activities seen at week 3 (smaller than that seen in weeks 1, 2) was sustained but did not further increase; cAMP levels were now significantly elevated also, but they did not rise steadily as did the activity of adenylate cyclase. There was a marked difference between the adenylate cyclase activities in non-tumor tissue from tumor-bearing and non-tumor-bearing livers in weeks 4--10, but there was no difference between the phosphodiesterase activities or cAMP levels in these two groups. Adenylate cyclase activity was extremely high in both non-tumor tissue of tumor-bearing livers from weeks 4--10 and tumors from weeks 11--13. Although phosphodiesterase activities were most elevated in the tumors, there were extremely high cyclic AMP levels in these tissues. The difference between the cAMP levels of tumor and non-tumor tissue was striking. Our findings are discussed with respect to the two-state model of carcinogenesis...


Biological postural oscillations during facial expression of pain in virtual characters modulate early and late ERP components associated with empathy: A pilot study.
There is a surge in the use of virtual characters in cognitive sciences. However, their behavioural realism remains to be perfected in order to trigger more spontaneous and socially expected reactions in users. It was recently shown that biological postural oscillations (idle motion) were a key ingredient to enhance the empathic response to its facial pain expression. The objective of this study was to examine, using electroencephalography, whether idle motion would modulate the neural response associated with empathy when viewing a pain-expressing virtual character. Twenty healthy young adults were shown video clips of a virtual character displaying a facial expression of pain while its body was either static (Still condition) or animated with pre-recorded human postural oscillations (Idle condition). Participants rated the virtual human's facial expression of pain as significantly more intense in the Idle condition compared to the Still condition. Both the early (N2-N3) and the late (rLPP) event-related potentials (ERPs) associated with distinct dimensions of empathy, affective resonance and perspective-taking, respectively, were greater in the Idle condition compared to the Still condition. These findings confirm the potential of idle motion to increase empathy for pain expressed by virtual characters. They are discussed in line with contemporary empathy models in relation to human-machine interactions.


Increase of serum interleukin 6 and interferon γ is associated with the number of impulses in patients with supraventricular arrhythmias treated with radiofrequency catheter ablation.
Activation of the immune system plays a pathogenic role in the process of myocardial remodeling in patients with supraventricular arrhythmias. The intensity of this process is associated with the effectiveness of electrical cardioversion and radiofrequency catheter ablation (RFA). The aim of this study was to test the ability of the biochip microarray to detect immune parameters in patients with supraventricular arrhythmias undergoing RFA treatment. We used a biochip-based microarray system to determine multiple immune parameters in a group of 35 patients who had undergone RFA for atrioventricular nodal reentry tachycardia (AVNRT), atrial flutter (AFL) and atrial fibrillation (AF). Before the procedure, serum IL-6 and VEGF levels were significantly increased in patients with atrial fibrillation compared to patients with AVNRT (IL-6: 6.4±6.3 ng/L vs. 1.5±0.7 ng/L, P < 0.01; VEGF: 132.4±74 ng/L vs. 88.5±56.4 ng/L, P < 0.01). After the procedure, serum IL-6, VEGF, IFN-γ and MCP-1 levels significantly increased compared to baseline (IL-6: 5.2±4.8 ng/L vs. 2.9±2.1 ng/L, P < 0.01; VEGF: 195.8±160 ng/L vs. 119.8± 110 ng/L, P < 0.05; IFN-γ: 3.1±1.2 ng/L vs. 2.3±0.6 ng/L, P < 0.05; MCP-1: 104.1±84.5 ng/L vs. 54.5±50 ng/L, P < 0.05). Serum IL-6 and IFN-γ were associated with the number of RFA applications (IL-6: r = 0.56, n 33; IFN-γ: r = 0.47, n 33). This study showed that biochip-based microarray can be useful in the detection of immune activation in patients with arrhythmias and can detect myocardial injury after RF procedures.


Anterior intrapelvic approach and suprapectineal quadrilateral surface plate for acetabular fractures with anterior involvement: a retrospective study of 34 patients.
The purpose of the study is to evaluate the use of the suprapectineal quadrilateral surface (QLS) plates associated with the anterior intrapelvic approach (AIP) to the acetabulum in the surgical treatment of acetabular fractures with anterior involvement. We did a retrospective study of patients surgically treated with QLS plates and AIP for acetabular fractures with the involvement of the anterior column, between February 2018 and February 2020, in our Hospital. The following data were recorded: mechanism of injury, the pattern of fracture, presence of other associated injuries, the time before performing the surgery, surgical approach, position on operating table, time of surgery, intraoperative bleeding, hospitalization time, intraoperative and postoperative complications. Follow-ups were performed at 1, 3, 6, 12 months, then annually. The clinical-functional outcome was assessed with the Merle d'Aubigne Postel score (MAP) modified by Matta; while the radiological outcome with the Matta Radiological Scoring System (MRSS). A Chi-square test was utilized to examine associations between parametric variables. We included 34 patients, mean age 62.1, with an average follow-up of 20.7 months. The most frequent traumatic mechanism was road trauma. There were 15 isolated anterior columns and 19 associated patterns. There were 5 cases of associated visceral injuries, and 10 cases of other associated skeletal fractures. All patients were in the supine position. The surgical approach used was the AIP in all cases, with the addition of the first window of the ilioinguinal approach in 16 cases and of the Kocher-Langenbeck approach in 2 cases. The average time before performing the surgery was 8.5 days. The mean time of the surgery and the mean length of stay after surgery were 227.9 min and 8.2 days, respectively. There weren't cases of intra-operative complications, while there were postoperative complications in 5 patients. The MRSS was judged anatomical in 26 cases, imperfect in 7 cases and poor in 1 case. The average MAP value was 15.2. We observed a significant relationship between the radiological outcome and the clinical outcome (p < 0.05). The QLS plates in association with the AIP approach represent an effective treatment strategy for the treatment of acetabular fractures with anterior involvement.


Electromechanical stresses and the effect of pH on membrane structure.
The presence of an electric field in a membrane creates stresses which lead to a mechanical compression of the membrane material. It is shown that considerations of this effect yield results consistent with the observed differential effect of pH on the plasma membrane substructure if the central electron-lucent layer in OsO4-fixed membranes is identified with the ionic depletion in the double-fixed charge model of cell membranes.


Cannabis self-administration in the human laboratory: a scoping review of ad libitum studies.
Cannabis self-administration studies may be helpful for identifying factors that influence cannabis consumption and subjective response to cannabis. Additionally, these paradigms could be useful for testing novel pharmacotherapies for cannabis use disorder. This scoping review aims to summarize the findings from existing ad libitum cannabis self-administration studies to determine what has been learned from these studies as well as their limitations. We examined studies that specifically examined cannabis smoking, focusing on subjective response and self-administration behavior (e.g., smoking topography). A systematic search was conducted using PubMed and Embase from inception to October 22, 2022. Our search strategy identified 26 studies (total N = 662, 79% male) that met our eligibility criteria. We found that tetrahydrocannabinol (THC) concentration significantly affected subjective response to cannabis in some but not all studies. In general, cannabis self-administration tended to be most intense at the beginning of the laboratory session and decreased in later parts of the session. There was limited data on cannabis self-administration in adults older than 55. Data on external validity and test-retest reliability were also limited. Addressing these limitations in future ad libitum cannabis self-administration studies could lead to more valid and generalizable paradigms, which in turn could be used to improve our understanding of cannabis use patterns and to help guide medication development for cannabis use disorder.


Bone marrow, peripheral blood and cord blood stem cell transplantation in children: ten years' experience at Siriraj Hospital.
Stem cell transplantations were performed in 69 children at Siriraj Hospital over a ten year period. The source of stem cells was bone marrow (60), peripheral blood (3), or cord blood (6). The diseases treated included 35 thalassemias, 11 Burkitt's lymphoma, five non-Hodgkin's lymphoma, five aplastic anemia, eight acute leukemia, and one each of neuroblastoma, severe combined immunodeficiency, Wiskott-Aldrich syndrome, myelodysplastic syndrome, and pyruvate kinase deficiency. The success rate of stem cell transplantation in Thai children varied according to the underlying diseases of the patients, ranging from 50% in acute leukemia to 100% in aplastic anemia. The outcome of stem cell transplantation in 35 thalassemic children revealed 23 (79.4%) were cured, whereas three (10.3%) remain alive with disease and the other three (10.3%) died. The incidence of graft-versus-host disease was low hen compared with that of Western countries. It is concluded that bone marrow, peripheral blood and cord blood stem cell transplantation will be the treatment of choice and will be widely used in the future to cure many hematologic and malignant disorders in children.


Association of pemphigus and pemphigoid with osteoporosis and pathological fractures.
Patients with pemphigus and bullous pemphigoid (BP) have potential risk factors for osteoporosis and/or fractures. To determine whether pemphigus and BP are associated with osteoporosis and fractures in the US, a cross-sectional study of 198,102,435 adults was performed, including 4506 with pemphigus and 8864 with BP from the 2006-2012 National Emergency Department Sample, a 20% sample of emergency care visits throughout the US. Pemphigus was associated with higher odds (multivariate logistic regression; adjusted odds ratio [95% confidence intervals]) of osteopenia (2.20 [1.59-3.05]), osteoporosis (2.54 [2.16-2.98]), osteomalacia (29.70 [4.05-217.83]), and pathological fractures (2.04 [1.42-2.91]). BP was associated with osteoporosis (1.55 [1.39-1.73]) and pathological fractures (1.52 [1.22-1.88]). When compared to BP, pemphigus was associated with higher odds of osteopenia (1.59 [1.06-2.41]), osteoporosis (1.38 [1.18-1.63]), and fractures (1.26 [1.04-1.53]), particularly of the ulna and radius (3.17 [1.23-8.17]). Patients with pemphigus or BP as well as long-term systemic corticosteroid use had highest odds of osteoporosis and fractures. No data were available on treatments for pemphigus or BP. Pemphigus and BP were associated with osteopenia, osteoporosis, and pathologic fractures. Patients with PEM and BP may benefit from increased screening for osteoporosis and interventions to prevent fractures.